Critical Care
Vol 3 Suppl 1
The Official Journal of the Critical Care Forum
Editor: Jean-Louis Vincent
19th International Symposium
on Intensive Care and Emergency Medicine
Brussels, Congress Center, 16–19 March 1999
Organisers
Chairman: J-L Vincent
Manager: Carl Vanhaesendonck
Abstracts of Posters
With the collaboration of:
R Askenasi (Brussels, Belgium)
J Berre (Brussels, Belgium)
JM Bouton (Brussels, Belgium)
A d'Hollander (Brussels, Belgium)
R Naeije (Brussels, Belgium)
Scientific advisors
L Brochard (Créteil, France)
ED Bennett (London, United Kingdom)
TW Evans (London, United Kingdom)
MR Pinsky (Pittsburgh, USA)
PM Suter (Geneva, Switzerland)
J Takala (Kuopio, Finland)
LG Thijs (Amsterdam, The Netherlands)
E Van Der Voort (Rotterdam, The Netherlands)
March 1999
Poster abstracts
P1
1
A prospective study of the incidence of iatrogenic ocular damage in critically ill patients
C Gorman, T Rogers, J Price, A Waboso, L Flackett and N Stallard
Intensive Care Service, University Hospital of Wales, Cardiff, CF4 4XW, UK
Crit Care 1999, 3 (suppl 1):P1
Introduction: Critically ill patients requiring intensive care are at
risk of iatrogenic ocular damage. Studies have reported an incidence of eye problems of up to 40% in critically ill ventilated
patients. We conducted this study to assess the incidence of ocular
complications in our intensive care unit where all patients are
cared for according to an eye care standard.
Methods: All ventilated patients over a 2 month period were
included. Ophthalmic assessment was performed on admission
and repeated every other day during the period of ventilation. At
each assessment the average Ramsey sedation score over the previous 24 h, the presence of tracheal secretions and the presence of
P2
ventilation associated pneumonia was noted. Eye care performed
was recorded.
Results: Sixty patients were included. One patient developed
corneal exposure keratopathy. No patient developed conjunctivitis or corneal ulceration. Further advice on appropriate measures
of eye care was given in five cases (8%). Nine patients (15%) had
large amounts of respiratory secretions with positive microbiological results.
Conclusion: This study confirms that the use of an eye care standard is associated with a low incidence of ocular surface complications. The incidence of ocular complications in this group of
patients is far lower than previously described.
Intensive care unit procedures: cost savings and patient safety
NW Knudsen, MW Sebastian, RA Perez-Tamayo, WL Johanson and SN Vaslef
Duke University Medical Center, Durham, NC, USA
Crit Care 1999, 3 (suppl 1):P2
Introduction: Intensive Care Unit (ICU) management of critically
ill patients often includes the requirement for tracheostomy and
feeding access, most often a pecutaneous endoscopic gastrostomy
(PEG). Although advances in ICU airway management include
percutaneous tracheostomy, semi-open tracheostomy and conventional tracheostomy, the majority of critically ill surgical and
injured patients still receive open tracheostomy in the Operating
Room at Duke University Medical Center (DUMC). Although
percutaneous tracheostomy is performed routinely in many
medical ICU settings, in high risk surgical and trauma patients
who often have unstable cervical spine injury and tissue edema,
direct visualization of the cervical structures and trachea is imperative during tracheostomy. We have undertaken open tracheostomy and PEG in the ICU in selected patients as part of a
collaborative, mulitidisciplinary ICU patient management strategy
at DUMC. This initiative has been undertaken to address the risk
of patient transport, the inappropriate use of OR time, and the
cost to the patient as part of an effort to standardize and improve
patient care.
Methods: After informed consent, utilizing DUMC conscious
sedation protocol, full ICU monitoring, and sterile OR technique,
P3
13 tracheostomies and 8 PEG placements were performed in 13
patients in the ICU since July, 1998. There were no complications. Operating Room costs include basic room fee and charge
per minute for general surgery and anesthesia and the anesthesia
professional fee. Surgical professional fee, tracheostomy tube cost,
and gastroscope maintenance are identical and not included in the
analysis. ICU costs include gowns, gloves, drapes and tracheostomy tray. For purposes of analysis, OR tracheostomy and
OR PEG times were defined as 120 min and 60 min respectively;
although analysis of fiscal year 1997–1998 yield widely divergent
average OR times for these procedures.
Results: A table of cost comparison for individual procedure, total
to date and associated cost savings are shown below.
Procedure
OR cost
ICU cost
Cost savings
Tracheostomy (n = 13)$37 555.05
$1323.92
$36 231.13
PEG (n = 8)
$1733.44
$16 030.16
$17 763.60
Conclusion: Tracheostomy and PEG placement in the ICU in
selected patients are safe, avoid patient travel, improve OR utilization and show a significant reduction in cost.
Fiberoptic bronchoscopy of the intubated patient with life-threatening hemoptysis
H-J Düpree, J-C Lewejohann, J Gleiß, E Muhl and H-P Bruch
Medical University of Luebeck, Dept. of Surgery, Ratzeburger Allee 160, 23538 Luebeck, Germany. E-mail: JLewejohann@t-online.de
Crit Care 1999, 3 (suppl 1):P3
Introduction: Bleeding into the tracheobronchial tree is a potentially fatal occurrence for intubated patients. The subsequent
acute respiratory failure requires an effective therapy. Fiberoptic
bronchoscopy represents an easy available technique for the diagnosis and treatment of this type of hemoptysis.
Methods: We show the bronchoscopic management of endobronchial bleeding in intubated patients at our ICU. During the
period 7/97–12/97 seven consecutive patients with acute endobronchial bleeding were treated with fiberoptic bronchoscopy. All
patients received an endobronchial instillation of epinephrine and
physiological saline solution (1:10 000–100 000).
2
Critical Care 1999, Vol 3 suppl 1
Patient
Diagnosis
Interventions
SaO2 [%] before treatment
Outcome
1 (74 y/f)
Goiter, large retrosternal, sternotomy
5 in 5 h
60
survived
2 (60 y/f)
Stenosis of the left internal carotid artery
20 in 10 d
90
survived
3 (71 y/m)
Ruptured abd. aortic aneurysm
5 in 5 d
90
survived
4 (65 y/f)
Axillo-bifemoral bypass-infection
3 in 2 d
50
survived
5 (63 y/m)
Aspergilloma left lung, acute myeloic leucemia
1
70
dead
6 (60 y/f)
Lung contusion, polytrauma
6 in 3 d
65
survived
7 (77 y/f)
Acute abdominal pain, urosepsis, nephrectomy
1
85
survived
Results: Control of bleeding was achieved with 1 to 20 (m ± SEM:
5.86 ± 0.93) bronchoscopic interventions. Hemostasis was accomplished in a period of 0.5 h and 10 days. Cardiocirculatory instability was observed in five patients. One patient died because of
persistent bleeding caused by severe aspergillosis. Six patients
survived without further interventions.
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Conclusion: Endobronchial instillation of epinephrine and physiological saline solution represents an effective method in case of
lifethreatening hemoptysis in intubated and mechanical ventilated patients.
The compliance characteristics of the Portex Soft-Seal cuff improves seal against leakage of fluid in a pig
trachea model
PJ Young and MC Blunt
ICU, Queen Elizabeth Hospital, Kings Lynn, PE30 4ET, UK
Crit Care 1999, 3 (suppl 1):P4
A high volume low pressure (HVLP) cuff does not protect the
lower airway from contamination by material leaking along longitudinal folds within the cuff wall [1]. This is a major factor in the
pathogenesis of ventilator associated pneumonia [2]. The combination of shape and high compliance of the Portex Soft-Seal cuff
might eliminate the folds in the cuff walls circumferentially for a
portion of the cuff and prevent leakage. We have tested the SoftSeal cuff in a pig trachea model to establish whether protection
against leakage is better than that afforded by standard HVLP
cuffs.
Method: The Portex Soft-Seal, Mallinckrodt Hi-Lo, Sheridan Preformed and Portex Profile size 8 mm internal diameter HVLP
cuffed tracheal tubes were assessed for leakage of dye placed in
the subglottic space to the trachea in a benchtop ventilation
model and in six isolated pig tracheas. All cuffs were inflated at
30 cmH2O pressure.
Results: There was no leakage in the ventilation model or in the
pig tracheas with the Portex Soft-Seal group, but rapid leakage
occurred in all the pig tracheas for the standard HVLP cuffs.
P5
Isolated pig Simulated
trachea (n = 6)
IPPV
Simulated
Tube
tracheal
motion
suction in trachea
Mallinckrodt Hi-lo
Leak
Leak
Leak
Leak
Sheridan Preformed
Leak
Leak
Leak
Leak
Portex Profile
Leak
Leak
Leak
Leak
No leak
No leak
No leak
No leak
Portex Soft-Seal
Conclusion: This benchtop study suggests that the improved
HVLP cuff compliance characteristics and shape of the Portex
Soft-Seal cuff might be beneficial in the prevention of leakage of
fluid to the lungs known to occur with HVLP cuffs.
References
1. Seegobin RD, Van Hasselt GL: Aspiration beyond
endotracheal cuffs. Can Anaes Soc J 1986, 33:273-279.
2. Craven DE: Prevention of hospital-acquired pneumonia:
measuring effect in ounces, pounds, and tons. Ann Intern
Med 1995, 122:229-231.
Colibri coloriometric technology rapidly detects oesophagal intubations
SA Puntervoll*, E Søreide**, W Jacewicz** and E Bjeland*
*Norwegian Air Ambulance, Stavanger, Norway. **Department of Anaesthesia and Intensive Care, Rogaland University Hospital, Stavanger,
Norway
Crit Care 1999, 3 (suppl 1):P5
Introduction: Rapid verification of correct placement is extremely
important [1,2]. We have tested a new coloriometric CO2 detection indicator meant for this purpose [3].
Methods: An entdotracheal tube was placed both in the trachea
and the oesophagus in otherwise healthy patients undergoing
elective surgery under general anaesthesia. We compared the four
first ventilations of the endotracheal and oesophageal tube using
capnography and a Capno Bri indicator with four different colour
Poster abstracts
gradings. (Blue ~ 0.5%, dark green ~ 1.0%, light green ~ 3.0% and
yellow ~ 4.0%)
especially suitable in emergency situations where capnography is
not available
Results: In all patients (n = 9), the indicator confirmed correct
placement of the tube in the trachea at the first ventilation (yellow
color). The indicator also verified incorrect oesophageal placement at the first ventilation in all patients (blue color).
References
1. Sum Ping ST: Accuracy of the FEFCO2 detector in the
assessment of endotracheal tube placement. Anaest
Analg 1992, 74:415-419.
2. Sayah AJ: End-tidal CO2 measurement in the detection of
esophagus intubation during cardiac arrest. Ann Emerg
Med 1990, 19:8.
3. Singer M: Colibri: a new means of CO2 detection. ESA
Congress in Barcelona 1998.
These results were confirmed by the capnography.
Conclusion: The Colibri technology is a reliable technique for
confirmation of correct endotracheal tube placement. It may be
P6
3
Lung volume and oxygenation changes with a closed suction system (CSS) in patients undergoing volume
controlled ventilation (VCV)
M Cereda, E Colombo, F Villa, G Greco, L De Marchi and A Pesenti
Istituto di Anestesia e Rianimazione, Ospedale S. Gerardo, via Donizetti 106, Monza (MI) 20052, Italy
Crit Care 1999, 3 (suppl 1):P6
We wished to measure changes in lung volume (∆LV), airway
pressures, and oxygenation during tracheal suctioning performed
with a CSS and with an open suction system (OSS). We enrolled 7
adult patients, sedated and paralyzed, VCV ventilated by a
SERVO 900C ventilator (Siemens, Sweden) with PEEP
≥5 cmH2O and FiO2 ≥ 0.4. Keeping all remaining ventilatory settings unchanged, we set trigger sensitivity at –2 cmH2O, inspiratory time at 25%, inspiratory pause at 10%. We performed four
suctioning manouvers at 20 min intervals using alternatively a CSS
and an OSS. With both systems, we used 12 F size catheters. We
performed no pre-oxygenation manouvers. Suction was applied
for 20 s at a pressure of 100 cmH2O. We continuously recorded
signals of respiratory inductance pletismography (RIP, Respitrace
Plus, NIMS, FL), arterial oxygen saturation (O2Sat) by pulse
oxymetry, and airway pressures. We obtained ∆LV as the change in
the RIP signal measured during VCV and during suction. We
measured Respiratory Rate (RR), peak inspiratory pressure (PIP),
positive end-expiratory pressure (PEEP), and mean airway pressure (MAP) during VCV and during suction with the CSS.
P7
Results: variables are reported as mean ± DS.
VCV
CSS
OSS
–
–0.05 ± 0.13
–1.13 ± 0.27*
97.8 ± 1.8
97.3 ± 1.8
93.9 ± 4.5‡
14.9 ± 4.3
39.4 ± 6.6†
–
32.4 ± 8.7
26.2 ± 9.2†
–
PEEP (cmH2O)
10.2 ± 4.2
7.8 ± 4.2†
–
MAP (cmH2O)
15.9 ± 4.8
18.1 ± 5.3†
–
∆LV (l)
O2Sat (%)
RR (bpm)
PIP (cmH2O)
*P < 0.01 vs CSS, †P < 0.05 vs VCV, ‡P < 0.01 vs VCV
Comment: the use of the OSS resulted in discontinuation of ventilatory support with a loss in lung volume and in O2Sat. The CSS
effectively preserved lung volume and oxygenation by maintaining airway pressures during the suction manouvre. The increase in
RR observed with the CSS was due to activation of the trigger
mechanism.
Balloon laryngoscopy reduces head extension and blade leverage in patients with potential cervical spine
injury
SD Mentzelopoulos, MV Tsitsika, MP Balanika, MJ Joufi and EA Karamichali
Department of Anaesthesia, Evangelismos General Hospital, 45 Ypsilantou Street, GR-10676, Athens, Greece
Crit Care 1999, 3 (suppl 1):P7
Background: In trauma patients, rigid cervical collar placement
reduces head extension (HE) during laryngoscopy [1]. In patients
with difficult airway, upper teeth or gums may be traumatized by
excessive laryngoscope blade levering motion (LBLM) needed for
laryngeal visualization [2]. The current study aims to compare,
under stimulated spine precautions, HE and LBLM upon
maximum glottic exposure (MGE) achieved with #4 conventional
Macintosh blade (CMB) and #4 modified Macintosh blade
(MMB) carrying two 10 Foley catheters (Fig. 1).
Methods: Anaesthesia was induced in 17 male, ASA I, Mallampati
I, elective surgery patients. Spine precautions included rigid board
placement under the shoulders and occiput and a rigid collar
placement round the neck. Laryngoscopy was performed twice,
changing between MMB and CMB. Before each laryngoscopy, the
patients head was placed in the neutral position. MMB laryngoscopy technique consisted of MMB tip insertion into vallecula,
right catheter balloon inflation with 2 ml air and MMB elevation
until MGE achievement. The angles of laryngoscope handle axis
(Fig. 2 AH) and of maxillary molars occlusal surface axis (OS) relative to horizontal (angles â1 and â2 in Fig. 2) were recorded upon
MGE. Angles â1 and â2 were measured with an automatic angle
finder (Fig. 1). The difference of 90°–â2 was defined as HE angle
and the difference â1–â2 was defined as LBLM angle (angle â3 in
Fig. 2), He and LBLM angles were compared with paired t test;
P < 0.05 was considered statistically significant.
Results: MMB laryngoscopy resulted in significantly less HE and
LBLM than CMB laryngoscopy (P < 0.001). Results and summarized statistics are presented in the Table. Values are shown as
4
Critical Care 1999, Vol 3 suppl 1
Figure 1. Modified Macintosh Blade with right catheter balloon
inflated with 2 ml air and automatic angle finder.
Conventional
Macintosh
blade
Modified
Macintosh
blade
P value
8.29 ± 1.57
4.91 ± 1.42
<0.001
Angle of
10.76 ± 1.75
Laryngoscope-BladeLevering-Motion
5.53 ± 2.13
<0.001
Angle of head
extension
P8
Figure 2. Lateral neck radiograph during direct laryngoscopy. AH,
axis of handle; OS, axis of maxillary molars’ occlusal surface; â1,
angle between AH and horizontal plane; â2, angle between
occlusal surface and horizontal plane, â3, angle of laryngoscope
blade levering motion.
means ± SD, Cormack-Lehane grade of laryngoscopic view was
≤II during all laryngoscopies.
References
1. Hastings RH et al.: Airway management for trauma
patients with potential cervical spine injury. Anesth Analg
1991, 73:471-482.
2. McCoy EP, Mirakhur RK: The levering laryngoscope.
Anaesthesiology 1993, 48:516-519.
Laboratory study of new technique using a one-pass dilator for percutaneous dilatational tracheostomy
P Ciaglia and W Marx
St Elizabeth Medical Center, 2215 Genesee Street, Utica NY 13501, Masonic Medical Research Laboratory, Utica, SUNY HSC, Syracuse, NY, USA
Crit Care 1999, 3 (suppl 1):P8
Background and objectives: Percutaneous dilatational tracheostomy requires the use of several dilators of increasing size. It
would be a marked advantage to use only one dilator to achieve
the desired 36 F. This report presents preliminary animal studies
using freshly sacrificed dogs, adult pig tracheas fresh from the
slaughterhouse and live piglets.
Methods: The usual technique for percutaneous dilatational tracheostomy was first followed to insert a guidewire into the
trachea. A well-lubricated, one-pass, long, tapered dilator was
threaded over the guidewire into the trachea. With twisting, it was
P9
inserted to the 36 F level. The one-pass dilator was removed
leaving the guidewire in place and the chosen tracheostomy tube
was passed over the guidewire into the trachea using the usual
technique of percutaneous dilatational tracheostomy.
Results: A total of 50 dog cadavers and 25 slaughterhouse sheep
tracheas were successfully tracheotomized using the one-pass
dilator employing 7 and 8 mm I.D. tubes. Six live piglets were
finally used successfully. No perforations or false passengers
occurred.
Concusions: A one-pass technique was used successfully on fresh
dog cadavers and should be evaluated on human beings.
Percutaneous dilatational tracheostomy with a lightwand device
K Kokkinis, T Vrettos, K Lefkaditi, P Manolopoulou and K Zbouki
Department of Anesthesiology and Intensive Care Medicine, University Hospital of Patras, Greece
Crit Care 1999, 3 (suppl 1):P9
Percutaneous dilatational tracheostomy (PDT) is a new technique
which shares the same indications as surgical tracheostomy. We
describe our experience with the PDT in combination with tracheal transillumination.
Patient population: Elective PDT was performed in 55 critically
ill patients, mean age 54.5 ± 16 (22–72), intubation time 6.5 ± 3.2
(3–14) days.
Technique: The procedure was undertaken on the bedside using
the Griggs-Portex PDT set as has been already described [1].
Before cannulation of the trachea the trachlight device (trachlight,
Poster abstracts
Leardal Medical) was inserted into the endotracheal tube with the
tip at the end of the tube. By pulling back the endotracheal tube
with the trach-light we examined the anatomy of the trachea and
the location of the first and second tracheal rings. Besides the
proper position of the end of the tube above the first tracheal ring
was achieved. Afterwards we continued with the PDT technique.
At the end the exact tracheotomy site and the correct placement
of the tracheostomy tube was evaluated by endoscopy.
Results: The procedure lasted from 7 to 21 min (m.v. 9.5 min).
The maneuver with the trachlight device lasted between 40–80 s
Perioperative complications are listed below:
1) Hemorrhage minor: 2 patients
Hemorrhage major: 0 patients
2) Premature extubation of the translaryngeal tube: 0 patients
P10
3)
4)
5)
5
Puncture of the endotracheal tube/cuff: 0 patients
Paramedian puncture of the trachea: 0 patients
Hypoxemia: 0 patients
Conclusion: PDT is a simple bedside procedure with a low complication rate. The combination with the trachlight device gives
the opportunity for better identification of the anatomy of the
trachea as well as the correct placement of the endotracheal tube
above the first endotracheal ring. These contribute to better conditions for safe and accurate tracheal puncture and cannulation.
Reference
1. Griggs WM, Worthley Lig, Gilligan JE, Thomas PD, Myburg
JA: A simple percutaneous tracheostomy technique. Surg
Gynecology Obstetrics 1990, 170:543-545.
Percutaneous dilatational tracheostomy (PDT): a report on 103 consecutive cases of the translaryngeal
tracheostomy (TLT) technique
A Karnik and JW Freeman
Featherstone Department of Intensive Care, Queen Elizabeth University Hospital, Birmingham B15 2TH, UK
Crit Care 1999, 3 (suppl 1):P10
Introduction : We describe our experience with the TLT technique, which is a purely dilatational PDT with low inherent risks.
The technique has the additional benefit of maintained ventilation and airway protection.
Technique: The TLT consists of a reinforced tracheostomy tube,
with an integral dilator, which is pulled out between tracheal rings
following retrograde insertion through the larynx [2]. A cuffed oral
5mm-tracheal tube inserted past the proposed stoma site maintains
ventilation and airway protection. We prospectively collected data
in 103 consecutive patients, 56 males and 47 females, undergoing
this technique. The authors (JWF & AK) performed tracheostomies on all patients (16 to 88 years old). Pre-existent coagulopathy was not corrected. Indications for tracheostomy were
mainly for term ventilation (39) and weaning difficulties (44).
Results : 102 tracheostomies were performed successfully. One was
converted to a Ciaglia technique after accidental decannulation.
Mean duration of operative procedure was 13.9 min. The INR
ranged from 0.8–2.6, (mean 1.3), platelets ranged from 23–667
× 109 (mean 184 × 109). There were six transient episodes of
P11
hypoxia (SpO2<90%), three cases of hypotension, two related to
the anaesthetic technique and one following traumatic intubation.
There were four episodes of accidental decannulation and one
case of minor subcutaneous emphysema. There was one case of
moderate blood loss (100–250 ml). There was one episode of loss
of airway, in a patient who was difficult to intubate (Gr. III). We
had two cases of wound infection associated with pre-existent systemic bacteremia. Total duration of the tracheostomy ranged from
1–65 days. Total closure of the stoma took a mean of 4 days (range
2–9 days). The resultant scar was minimal.
Conclusion: This pure dilatational and bronchoscopically visualised method is easy to perform with training. It is worthy of consideration in patients with coagulation abnormalities. We feel it
offers better control over the airway than other available techniques although there is a definite risk of decannulation while
withdrawing the cannula over the obturator. The overall morbidity
of this technique is low.
References
1. Freeman et al.: Crit Care 1997, 1 (suppl 1):S44.
2. Fantoni et al.: Intensiv Care Med 1997, 23:386-392.
Independent lung ventilation using a double-lumen endobronchial tube by nasotracheal intubation
K Yasumoto and I Kagami
Department of Anesthesiology, Showa University Hospital, 1-5-8 Hatanodai Shinagawa-ku, Tokyo, Japan
Crit Care 1999, 3 (suppl 1):P11
Independent lung ventilation (ILV) is effective for the patient
who is suffering from unilateral lung disease. When we ventilate
the patients with ILV, they should be intubated with a doublelumen endobronchial tube. While ILV is continued for some time
a number of difficulties related to the management of the doublelumen endobronchial tube (DLT) arise. Movements of the patient
and routine turning of the patient threaten the DLT position and
can lead to loss of lung isolation or lobe occlusion. Nasal intubation is better suited for long-term intubation than oral intubation
because it is safer for equipment attachment. We have ventilated
six patients (Table) with ILV using the DT by nasotracheal
Case
Age and
sex
Diagnosis
Height
(cm)
WB
(kg)
DLT
size
Durat.
(h)
44
5.5
65
1
49 M
Post upper lobectomy 155.5
2
88 F
Aspiration pneumonia
145
35
5.5
120
3
59 F
Lung trauma
143
60
5.5
94
4
71 M
Aspiration pneumonia
153
59.8
6.0
100
5
85 F
Atelectasis
150
50
5.5
50
6
75 M
Atelectasis, DIC
157.8
42
6.0
25
Durat., duration.
6
Critical Care 1999, Vol 3 suppl 1
intubation for 25 to 120 h. We intubated Portex #5.5 DT for all
cases. There was no case in which DLT was required to correct its
position during ILV. Although we examined the condition inside
P12
the nose, there was no severe damage by the DLT. We concluded
that nasotracheal DLT intubation was done safely and could be
used for ILV up to 7 days.
The effect of dexamethasone on the incidence of post extubation stridor in pediatric patients
AK Kalloghlian, BM Pittappilly and NT Matthews
The Pediatric Intensive Care Unit, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354 Riyadh, Saudi Arabia
P13
Crit Care 1999, 3 (suppl 1):P12
12 h and 1 h prior to extubation for a total of 2 doses. The control
group received placebo at corresponding times.
Post extubation stridor is due to reactive subglottic laryngeal
edema at the cricoid ring. Dexamethasone has been used to
reduce the incidence of stridor in such patients. The evidence in
the literature however is not conclusive. We conducted a prospective, randomized, double blind study of dexamethasone versus
placebo to assess the efficacy of dexamethasone in reducing the
incidence of post extubation stridor in children. Fifty-one patients
without any known preexisting upper airway problems were
studied. There were 27 patients in the treatment group and 24 in
the placebo group. Both groups had similar weight, age and length
of intubation. Dexamethasone was given at a dose of 0.6 mg/kg at
There was no statistical difference in the incidence of post extubation stridor in the two groups. Ten of 24 children in the placebo
group (41.7%) and 8 of 27 (30%) in the dexamethasone group
developed stridor (P = 0.39). There were 3 patients in placebo
group and 1 in dexamethasone group that needed reintubation,
but again the difference was not statistically significant (P = 0.33).
This study, although with relatively small sample size, suggests
that routine use of dexamethasone to prevent post extubation
stridor, in children without any known upper airway abnormality,
is not warranted.
Evaluating the effect of steroids on the incidence of reintubation rates in children with
laryngotracheobronchitis
J Rajah, J Riera-Fanego, J Keeton, A Ramjee, R Bhana and H Hon
Intensive Care Unit, Chris-Hani Baragwanath Hospital, University of Witwatersrand, P O Bertsham, 2013, South Africa
Crit Care 1999, 3 (suppl 1):P13
Introduction: Postextubation stridor is a serious problem in children with an incidence of up to 33% in electively intubated children. Our aim was to determine whether steroids decreased
reintubation rates and to identify other risk factors for reintubation.
Methods: Retrospective analysis (1994–1996) of the 82 children
(72 received steroids). Steroids were categorized according to the
type used and the time of administration. Recognized risk factors
for postextubation stridor including age (<1 and >1 year) and duration of intubation (<120 and >120 h) were analyzed.
Results: There was no significant difference in either the preintubation grade or stridor (P = 0.67) in both outcome groups (reintubated 22/23 grade 3 and not-reintubated 50/59 grade 3) or in the
postextubation grade of stridor between both groups (P = 0.1).
Neither type of steroid (P = 0.32), nor time administered (P = 0.79),
nor age (P = 0.22) nor duration of intubation (P = 0.35) was found
to significantly influence reintubation rates.
Conclusion: The prophylactic use of corticosteroids in routine
elective extubations for laryngotracheobronchitis cannot be rec-
P14
Not reintubated
(n = 59)
Reintubated
(n = 23)
P value
Age (months)
19.3
12.6
0.28
Weight (kg)
9.75
8.6
0.28
Intubation (2 days)
7.6
11.1
0.04 (S)
PaO2/FiO2
232
269
0.02 (S)
ICU stay (days)
9.6
13.3
0.05 (S)
Steroids
52/59
20/23
0.88
Atelectasis
10/59
9/23
0.03 (S)
Infections
23/59
10/23
0.2
Pneumonia
29/59
9/23
0.4
Variable
ommended, based on current findings. Overall, 28% of all patients
needed to be reintubated. However, reintubation seems to be correlated best with atelectasis rather than the degree of postextubation stridor.
Advantages of a new humidification technique
G Via, M Olivei*, A Palo, S Neri, G Ragni, M Bertolini, N Fusilli, F Capra-Marzani, G Rodi, G Iotti and A Braschi
Anestesia e Rianimazione Io, *Lab. Tecn. Biomediche IRCCS S. Matteo P. le Golgi 2 27100-Pavia, Italy
Crit Care 1999, 3 (suppl 1):P14
Recently, an active HME (AHME) (Humid-Heat, Gibeck) has
been developed. The AHME combines a HME with a unit which
adds humidity and heat to the patient-side of the HME. The
supply of humidity and heat is automatically regulated, in order to
achieve 100% humidity of inspired gases at 37°C. The operation
of AHME requires only the user-set input of the patient minute
Poster abstracts
AHME
F&P
P
Minute ventilation (l/min)
11.1 ± 3.5
11.5 ± 2.4
0.64
Insp. gases temperature (°C)
36.9 ± 0.5
37.1 ± 0.2
0.33
1.9 ± 0.1
0.42
ventilation. We evaluated the potential advantages of the AHME
over a conventional active humidifier.
Methods: The study included seven mechanically ventilated
patients. In each patient, the AHME was used for 24 h and then
substituted with a conventional active humidifier (F&P) (MR730,
Fisher & Paykel) with a heated wire in the inspiratory limb, for
the next 24 h. AHME was preset to keep the temperature of
inspired gases at 37°C. The F&P was set to 37°C in the humidifier-chamber, and to 37°C at the Y piece. The AHME and the
F&P were compared in terms of: humidity and temperature
output, water consumption and condensate in the water traps.
The humidity output was evaluated on the basis of the condensate in the flex tube, which was scored from 0 (absent) to 3 (excessive).
Results: Minute ventilation did not differ during application of
AHME and of F&P. Both devices kept the set temperatures, and
provided adequate humidification, as assessed by the condensate
in the flex tube. However, when the F&P was used, there was formation of condensate in the ventilator tubings, and the water traps
needed to be emptied on average eight times (range: 6–9) per day.
P15
Condensation in the flex tube (score) 2 ± 0
No. of water traps emptying
0
8±2
–
Quantity of H2O in the water traps
0
100 ± 17
–
117 ± 29
667 ± 76
0.008
H2O consumption (ml)
7
means ± SD; Student t test.
No condensation of water was found in the ventilator tubings with
AHME. Compared with F&P, the AHME remarkably reduced the
water usage.
Conclusion: Compared to a conventional active humidifier, the
AHME provides equivalent humidification, with the advantages
of both reducing the time-expenditure for handling, and of eliminating the risk caused by water condensation in the ventilator
tubings.
Heat and moisture exchanger PALLBB22-15F can prevent ventilator-associated pneumonia (VAP) in short
term mechanically ventilated ICU patients
MY Yassin
Libanese University School of Medicine, Department of Internal Medicine, Pulmonary and Critical Care Division, Hammoud Hospital, SidonLebanon
Crit Care 1999, 3 (suppl 1):P15
Study population: Intubated ICU patients with normal CXR on
admission to the unit.
Introduction: VAP is a serious infection with a mortality rate
exceeding 50%. It also leads to an increase in the duration of the
treatment and adds to hospital costs. Bacteria, in intubated
patients, may be directly inoculated into the endotracheal tube
from the hands of medical personnel or from contaminated respiratory therapy equipment (i.e. humidifiers). We tried a heat and
moisture exchanger to substitute the conventional ventilator
humidifiers to prevent VAP in the ICU setting.
Results: VAP rates decreased in the group of HMEF dramatically
in comparison to the conventional humidification method (see
Table below).
Methods: Subjects were intubated and attached to the conventional respiratory assistance cascades in the first year of the study
(July 1992–June 1993). Retrospectively, cases of VAP were calculated prospectively, during the following year (July 1993–June
1994), subjects were intubated and attached to respiratory assistance cascades; but PALL filter, a heat and moisture exchanger,
was in-line and the machine humidifiers were bypassed. The
cases of VAP were calculated.
P16
Humidification method
Total patients in group
Cascade
PALLBB22-15F
174
284
VAP rate, incubated 1 day
5.50%
0%
VAP rate, intubated 2–4 days
24.30%
8%
VAP rate, intubated > 5 days
46.60%
26%
VAP rate, total
28.20%
12.70%
Conclusion: We concluded that heat and moisture exchanger
filters can prevent VAP in short term mechanically ventilated ICU
patients, and can halve its rate in long term durations.
A clinical evaluation of a new humidifier in long-term mechanical ventilation
M Olivei*, G Via, A Palo, S Neri, G Maggio, T Mediani, C Galbusera, M Belliato, E Haeusler, G Iotti and A Braschi
Anest. e. Rianimazione Io *Lab. Tecn. Biomediche IRCCS S. Matteo P. le Golgi 2 27100-Pavia, Italy
Crit Care 1999, 3 (suppl 1):P16
The adequacy of humidification of heat and moisture exchangers
(HMEs) during long-term mechanical ventilation is still controversial. Recently, an active HME (AHME) (Humid-Heat, Gibeck)
has been developed. This AHME combines a HME with a unit
which adds water and heat between the patient and the HME.
The AHME automatically regulates the water and heat supply.
The only user-set input for AHME is the minute ventilation (V’e)
of the patient. We evaluated the AHME efficiency for humidification during long-term mechanical ventilation.
Methods: The AHME was used for 5 days on seven patients
which were mechanically ventilated in different modes. On each
8
Critical Care 1999, Vol 3 suppl 1
day we measured the number of tracheal aspirations, the secretions characteristics, the condensate in the flex tube and in the
water traps, the airway temperature, the number of changes of the
V’e setting on AHME. A chest X-ray and a bronchoscopy were
performed on days 1, 3 and 5. We scored the secretions characteristics and the condensate in the flex tube from 0 (insufficient) to 3
(excessive), the atelectasis at chest X-ray from 0 (absent) to 2
(evident), and the bronchial occlusions at bronchoscopy from 1
(absent) to 4 (complete).
by the absence of new atelectasis and of secretions accumulation
in the bronchi. The temperature of inspired air was adequate. The
value of V’e set on the AHME was changed on average twice
(range: 0–8 times) per day, to maintain this setting close to the V’e
of the patient. No water condensate was found in the water traps.
The AHME is adequate for humidification in long-term mechanical ventilation, and eliminates the problem of condensation in the
ventilator tubings. The humidification efficiency of AHME is not
influenced by the mechanical ventilation mode, provided that the
V’e setting of AHME is kept close to the V’e of the patient.
Results and conclusion: AHME provided adequate humidification
over the 5 days, as indicated by the secretions characteristics and
Day 1
Day 2
Day 3
Day 4
Day 5
P
No. aspirations
12 ± 2
12 ± 1
12 ± 1
12 ± 2
13 ± 1
0.76
Quantity of
secretions (score)
1.6 ± 0.4
1.4 ± 0.3
1.7 ± 0.5
1.4 ± 0.2
1.8 ± 0.5
0.34
Viscosity of secretions (score)
1.1 ± 0.1
1.2 ± 0.2
1.2 ± 0.3
1.1 ± 0.1
1 ± 0.1
0.17
Condensation in the flex tube (score)
1.9 ± 2
2 ± 0.1
1.9 ± 0.2
2±0
0.69
2 ± 1.2
–
1.7 ± 0.8
–
1.7 ± 1
0.49
RX atelectasis (score)
0.3 ± 0.5
–
0.3 ± 0.5
–
0.3 ± 0.5
1
Insp. gases temperature (°C)
37 ± 0.4
36.9 ± 0.8
36.8 ± 0.5
37.2 ± 0.4
36.9 ± 0.5
0.67
Nr. of changes of V’e set on AHME
0.9 ± 1.2
2 ± 1.9
1.9 ± 1.3
1.9 ± 2.3
1.3 ± 1.6
0.66
Bronchial obstruction (score)
2±0
means ± SD. ANOVA.
P17
Comparison of conventional heated humidification to a new active heat and moisture exchanger in the ICU
RD Branson, RS Campbell, M Ottaway and JA Johannigman
University of Cincinnati, Department of Surgery
Crit Care 1999, 3 (suppl 1):P17
Background: Heated humidification (HH) is commonly used with
or without a heated wire circuit (HWC) to humidify inspired gases
during mechanical ventilation (MV). We compared HH and HH
with a HWC to a new active heat and moisture exchanger
(AHME). The AHME (Humid Heat, Gibeck, Sweden) consists of
a typical HME and a heat and water source delivered between the
patient and the HME. The volume of water delivered and heat
output are based on a set minute ventilation. A pre-set airway
temperature of 37°C is used.
Methods: Thirty patients requiring MV for >72 h were studied.
Pts received humidification via a HH, HH + HWC (Fisher &
Paykel), and AHME in random sequence for 24 h each. All
devices were set to deliver 37°C at the proximal airway. During
each period of ventilation, the following were measured; airway
temperature, min and max body temperature, number of suctioning attempts, volume of secretions, consistency of secretions,
number and volume of saline instilled, water usage, condensate,
ventilator settings, minute volume, number of circuit disconnections. Water usage was measured by weighing the water bag
before and after 24 h use. Consistency of secretions were judged
as thin, moderate, or thick as previously described (Suzukawa:
Respir Care 1989, 34:976). Condensate was measured by emptying
fluid into a graduated container and sputum volume measured by
collecting secretions in a Luken’s trap. Airway temperature was
measured at the ET tube using a rapid response thermistor. Resistance of the AHME was measured before and after use.
Results: There were no differences in any of the variables related
to humidification efficiency (secretion volume and consistency,
number of suctioning attempts, or volume of saline used). Water
usage and volume of condensate were significantly different
between devices, but delivered airway temperatures were not.
Statistical analysis was done with ANOVA. *P < 0.05, see Table.
Device
HH
Water Usage (ml) Condensate (ml) Airway Temp. (°C)
2039 ± 387
930 ± 271
36.3 ± 1.2
HH + HWC
766 ± 281
12 ± 16*
37.1 ± 1.0
AHME
135 ± 53
1 ± 3*
36.4 ± 1.7
Minute volume was similar between groups (11.6 ± 3.3 vs
11.9 ± 3.4 vs 11.8 ± 2.7 l/min) as was bias flow during flow triggering (5.8 ± 2.5 vs 5.4 ± 2.6 vs 5.9 ± 2.3). AHME resistance before and
after use was unchanged (1.66 ± 0.11 vs 2.28 ± 0.82 cm H2O/l/s).
Conclusion: In this early study, the AHME provided equivalent
humidification as HH and HH + HWC with a lower water usage.
This occurs because the HME portion of the AHME returns
~32 mgH2O/l, which only requires the active portion to add
~12 mgH2O/l to reach 44 mgH2O/l. Additionally, by placing the
AHME between the patient and ventilator circuit, continuous
flow from flow triggering systems is not humidified. No other
differences were noted. Disadvantages of the AHME include
Poster abstracts
deadspace (~70 ml), weight on the ET tube and the heat source
near the patient. Measured external temperature of the AHME
P18
9
did not exceed 38°C. Further long term studies are required to
define the role of the AHME.
A new device for 100% humidification of inspired air
A Larsson and L Svanborg
Department of Anesthesia and Intensive Care Medicine, University Hospital Lund, Sweden and Louis Gibeck AB, Upplands Väsby, Sweden
Introduction. Passive heat/moisture ex-changers (HME) which are
based on a hygroscopic condensor principle usually provide adequate humidity (up to 32 mgH2O/l air) of the inspired gas during
ventilator treatment [1,2]. However, in about 5–10% of the
patients with e.g. thick secretions [1,2] active humidifiers that can
provide 100% humidity are needed. These devices cause free
water condensation in the tubings [3] with risks of contamination
and of compromising the ventilator function. To avoid this a new
humidifier has been developed. It consists of a supply unit with a
microprocessor and a water pump, and a humidification device,
which is placed between the Y-piece and the endotracheal tube.
The humidification device is based on a hygroscopic HME, which
absorbs the expired heat and moisture and releases it to the
inspired gas. External heat and water are then added to the
patient side of the HME, so the inspired gas reaches 100% humidity at 37°C (44 mgH2O/l air). The external water is delivered via a
pump onto a porous membrane and then evaporated in the
inspired air by an electrical heater. The microprocessor controls
the water pump and the heater by an algorithm using the minute
ventilation (which is fed into the microprocessor) and the airway
temperature measured by a sensor mounted in the flex tube on
the patient side of the humidification device.
The aim of this study was to test the performance of this humidifier at different ventilator settings in a lung model.
Methods: The lung model is based on the ISO 9360 International
Standard with the exception of that the water-bath temperature is
regulated to have a constant temperature of 35.5 ± 0.5°C. The
model was ventilated with a Siemens 900 B ventilator set a minute
ventilation from 5 to 25 l/min, I:E 1:2, and a rate of 12, 15 or
20/min during 90 min. The moisture content (MC) in the inspired
air was calculated from the water delivered (WD) and the loss of
water from the lung model (WL): MC = WL– WT + (WD–WH),
P19
where WT is the water in the tubing between the device and the
lung model and WH the water trapped in the HME. WL, WT,
WD, and WH were found by weighing before and after the experiment. During the experiment no condensation was found in the
flex tube between the device and the lung model.
Results:
Inspired humidity (MC)
45
40
mg/l
Crit Care 1999, 3 (suppl 1):P18
35
30
15 BPM
25
12 BPM
20 BPM
20
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
M inute Ventilation (l/m in)
Conclusion: In a lung model, ventilated with 5–25 l/min, the new
humidifier gave an absolute humidity of 39–45 g/l, with the lower
level at the highest ventilation. Thus, the device had the intended
performance characteristics.
References
1. Branson RD, Davis Jr K, Campbell RS et al.: Humidifaction
in the Intensive Care Unit. Prospective study of a new
protocol utilizing heated humidification and a
hygroscopic condensor device. Chest 1993, 104:18001805.
2. Kollef MH, Shapiro SD, Boyd V et al.: A randomized clinical
trail comparing an extended-use hygroscopic condensor
humidifier with heated-water humidification in
mechanically ventilated patients. Chest 1998, 113:759767.
3. Craven DE, Goularte TA, Make BJ: Contaminated
condensate in mechanical ventilator circuits. Am Rev
Respir Dis 1984, 129:625-628.
Modelling the effect of ambient oxygen fraction on hypoxaemia during apnoea
JG Hardman
Department of Anaesthesia and Intensive Care, University of Nottingham, UK
Crit Care 1999, 3 (suppl 1):P19
Hypoxaemia during apnoeic oxygenation complicates tests for
brainstem death and exposes the patient’s organs to the risk of
anoxic damage. This study investigates the effect on hypoxaemia
of varying the ambient oxygen fraction during apnoea.
Methods and results: The Nottingham Physiology Simulator is a
validated simulation of advanced, iterative physiological models
[1]. The model was set up as a 70 kg adult with normal physiological values other than: pulmonary venous admixture 20%, alveolar
deadspace fraction 20% of tidal volume and functional residual
capacity 2 l. The patient’s lungs were ventilated with 100%
50
PaO2 with ambient o xygen fraction :
a) 21%
b) 50%
c) 80%
d) 100%
40
PaO2 or PaCO2 30
(kPa)
PaCO2
20
10
a
b
d
c
0
-5
0
5
10
15
20 25
30
Time (minutes)
35
40
45
50
55
60
10
Critical Care 1999, Vol 3 suppl 1
oxygen for 2 min and the patient was then apnoeic with an open
airway exposed to 21, 50, 80 or 100% oxygen. Arterial oxygen and
carbon dioxide tensions (PaO2, PaCO2) were recorded continuously until arterial oxygen saturation fell to 50%. The changes in
PaO2 and PaCO2 are shown in the figure on the previous page.
P20
Discussion: Provision of very high ambient oxygen fractions
greatly extends the safe duration of apnoea. As oxygen fraction is
increased, increasingly large effects are achieved.
Reference
1. Hardman JG, Bedforth NM, Ahmed AB, Mahajan RP,
Aitkenhead AR: Br J Anaesth 1998, 81:327-332.
Obstructive sleep apnea in acute respiratory failure
S Pivetti, F Navone, B Tartaglino, R Urbino and V Gai
Medicina d’Urgenza e P.S. Medicina, E.D., Az.Osp. ‘S. Giovanni Battista’ di Torino’, Torino, Italy
Crit Care 1999, 3 (suppl 1):P20
Study objectives: Emergency medicine deals with the diagnosis
and the prevention of potentially life-threatening events, as well
as prevention, diagnosis and treatment of acute illnesses; one of
this event is sleep apnea syndrome (SAS). The relationship
between obstructive sleep apnea (OSA) and acute respiratory
failure (ARF) is not well established.
The aim of the study was to evaluate the prevalence of OSA in
hypercapnic ARF patients and its correlations with the severity
and length of nocturnal arterial oxygen desaturation, diurnal arterial carbon dioxide (PaCO2) and oxygen (PaO2) tensions, diurnal
oxygen saturation, sudden death and BMI.
Methods: 46 patients with chronic obstructive pulmonary disorder
(COPD) (31 men and 15 women; M=68 years; range 36 to 83) with
hypercapnic ARF underwent a full night of polysomnography.
The polysomnography consisted of continuous polygraphic
recording (by Compumedic Sleep PTYLTD Abbotsford) from
surface leads for electroencephalography, electrooculography,
electromyography and ECG, and from noninvasive sensor for
P21
nasal airflow, tracheal sounds, body position, thoracic and abdominal respiratory efforts, and oxymyoglobin level. The number and
duration of nocturnal sleep apneas and hypopneas and the consequential oxygen desaturation were evaluated; sleep apnea was
defined as more than five episodes of apnea or hypopnea per hour
of sleep (apnea/hypopnea index = AHI >5). Furthermore BMI,
basal diurnal PaCO2, PaO2 and arterial oxygen saturation were also
recorded.
Results: Overnight polysomnography was successfully performed
in 39 of the 46 studied patients; 4 patients were intolerant to the
study and 3 patients were awake all the sleep time. OSA was
found in 13 of the 39 ARF patients (33.3%) and the mean AHI
was 19.3 events per hour. We found statistically significant correlations between OSA and BMI (P < 0.01; M=38), PaO2 (P < 0.001;
M=65), diurnal oxygen saturation (P < 0.001; M=86) and nocturnal
oxygen desaturation (P < 0.001; M=80).
Conclusion: The overnight polysomnography detects the possible
existence of OSA in hypercapnic ARF. We also found a statistical
significance positive correlation between OSA and hypoxemia.
Polysomnography may be indicated to exclude sleep-induced
desaturation contributing to the actual ARF, but it may also
improve therapeutic and prevention strategy.
Nasal continuous positive airway pressure: do mask pressures reliably reflect intratracheal pressures?
D Kindgen-Milles, A Gabriel, R Buhl, H Böhner and E Müller
Department of Clinical Anaesthesia, Heinrich-Heine-University, 40001 Düsseldorf, FRG
Crit Care 1999, 3 (suppl 1):P21
Introduction: Nasal continuous positive airway pressure (nCPAP)
increases intrathoracic pressure. This way, it may increase functional residual capacity, improve pulmonary oxygen transfer, and
reduce the need for endotracheal intubation in acute respiratory or
cardiac failure. However, little is known about the loss of externally applied pressure on its way from mask via pharynx into the
trachea. We studied the correlation between mask and intratracheal pressures in 8 surgical ICU-patients.
Patients and methods: In 8 postoperative patients after extubation, pressures were measured in nasal mask and trachea (via a
catheter, o.d. 0.9 mm) during nCPAP treatment with either 5 or
10 mbar positive pressure (high-flow gas source, 65 l/min, maskpressure adjusted with a PEEP-valve). From the area under the
pressure–time curves, absolute pressures, but also the percentage
of mask pressure transmitted into the trachea were calculated.
Study performed with approval of the committee of medical
ethics and informed consent; mean ± SD; t-test, P < 0.05.
Results: With the PEEP
valve set at 5 or 10 mbar,
pressures within the nasal
mask were 5.6 ± 0.8 and
9.4 ± 1.0 mbar, respectively.
Mean intratracheal pressures increased in all
patients and were significantly higher during
10 mbar mask pressure
compared to 5 mbar
(6.8 ± 0.3 vs. 2.9 ± 0.5 mbar;
P < 0.007). The relative
amount of mask pressure
transmitted into the trachea
was significantly higher
with 10 compared to 5 mbar
(P < 0.04) (Figure). With 5 mbar of nCPAP, in 50% of the subjects,
significant negative pressure swings occured during inspiration.
This was not the case with 10 mbar.
Poster abstracts
Conclusion: NCPAP is an effective noninvasive means to increase
airway pressure in postoperative patients after extubation.
However, only with mask pressures of 9–10 mbar, but not with
P22
11
5 mbar, intratracheal pressures will be maintained reliably and
continuously positive during the whole respiratory cycle.
Effects of mask–ventilator interface elements in a home noninvasive portable ventilator. Study in cold
hypercapnic patients
A Esquinas, G González, M Del Baño, P Jara, M Rodríguez, F García and A Carrillo
Intensive Care Unit, Hospital Morales Meseguer, Murcia. Spain
IPAP drops pressure from
base line/type of filter
Crit Care 1999, 3 (suppl 1):P22
Noninvasive mechanical ventilation (NIMV) in hypercapnic
COLD excacerbations with a home portable ventilator with a
single ventilatory tube has some technical considerations.
Objective: We analyze influence of elements used in the maskventilator interface in hypercapnic COLD with a NMV: To
compare differents 1). Design of filters (A, B, C, D), 2) Nonrebreathing expiratory valve: a) Swisper and b) Plateau exhalation
valve 3) Rramp inspiratory time: (0.05, 0.1, 0.5 seg) affect a predetermined level inspiratory positive pressure (IPAP) (15 cmH2O),
2) Hypercapnia (PCO2) control and 3) Subjective responses:
a) Dysnea Brog index (low: 2 to 10 high) and psychological
dependence at different stages of therapy (low 2 to high 10).
Setting: ICU.
Subjects: Twelve hypercapnic COLD stable patients.
IPAP: 15 cmH2O
PCO2/pH – type of
nonrebreathing valve
PCO2 mmHg/pH
Dysnea Borg index/ramp
inspiratory time
A
B
C
D
12 ± 3
12 ± 5
10 ± 2
8±2
Valve Swisper
Plateau exhalation
80/Ph: 7.23
70/pH: 7.35
0.05 seg
0.1 seg
0.5 seg
Dysnea Borg index
2
4
10
Psychological score
dependence/period
Acute
Post-acute
Weaning
phase
Ventilator
8
6
6
Nurse
10
8
8
Physicians
8
8
8
Material: BiPAP ST-D (Resp, Inc). Facial mask.
Results: See Table.
Conclusion: Subjective (dysnea Brog index), objective respiratory
response (hypercapnia) and level of IPAP pressure applied during
P23
NMV were influenced by a specific design of element intercalates
at mask–tube–ventilator line. A specific design of these elements
as we showed with a home portable single tube ventilator could
affect NMV efficacy in hypercapnic COLD exacerbations.
Evaluation by volunteers of respirator characteristics in modes used in non-invasive ventilation
R Rokyta, P Hora, M Nalos, J Ruzicka, M Matejovic, I Novak and V Sramek
ICU, Medical Department I, Charles Uni Hospital Plzen, Alej Svobody 80, CZ-30466 Plzen, Czech Republic
Introduction: We studied the medical personnel’s power of distinction between various types of respirators in CPAP and
CPAP+pressure support (PS) modes.
Materials and methods: Five blindfolded volunteers (2 ICU
doctors and 3 nurses) performed random evaluation (5 point scale,
1 = best) of following respirators: Elema Siemens 300 (ES300),
Adult Star 2000 (AS 2000) and Bird 8400 STi. All volunteers were
comfortably seated and instructed to breathe freely with the
Table 1. CPAP 5 cmH2O
Table 2. CPAP 5 cm H2O+PS 10 cmH2O
Crit Care 1999, 3 (suppl 1):P23
Resp
BIRD
Adult
Star
E 300
flow trig
E 300
Press tr
Resp
BIRD
Adult
Star
E 300
flow trig
E 300
press tr
Vol 1
2
1
1
1
Vol 1
2
2
2
2
Vol 2
2
2
1
2
Vol 2
4
3
1
3
Vol 3
4
3
2
2
Vol 3
2
3
3
4
Vol 4
3
1
1
1
Vol 4
4
3
3
3
Vol 5
2
1
2
2
Vol 5
2
3
1
3
Mean
2.6
1.6
1.4
1.6
Mean
2.8
2.8
2
3
SD
0.8
0.8
0.49
0.49
0.98
0.4
0.89
0.63
SD
12
P24
Critical Care 1999, Vol 3 suppl 1
respirator through the mouthpiece with the nostrils clipped. Pressure trigger was set at –1 cmH2O in all respirators and in ES 900
flow trigger was also tested. After 1 min warm-up, 1 min breathing
test was performed at the end of which volunteers were asked to
classify their satisfaction with respirator. At first, 5 cmH2O CPAP
was tested at random in all four settings (three respirators, in ES 300
for both pressure and flow triggering) and thereafter the evaluation
continued similarly with CPAP 5 cmH2O + 10 cmH2O pressure
support. Data are presented as means ± SD, Kruskal-Wallis test was
used for statistical analysis, P < 0.05 was considered significant.
When CPAP and CPAP+PS were tested together significant differences were found within the group (P < 0.05). Generally, CPAP
was better tolerated than CPAP+PS. ES 300 and AS 2000 yielded
better results than Bird respirator.
Results: Individual scores and mean values ± SD are listed in
Tables 1 and 2.
Acknowledgement: Supported by IGA grant No. 3999-3
Conclusion: ICU personnel may easily differentiate between characteristics of ICU respirators. Respirator with best characteristics
may then be used for NIV and possibly also for difficult weaning.
Noninvasive positive pressure ventilation (NPPV) in critically ill patients: preliminary experience
R Urbino, C Antro, S Pivetti, B Tartaglino, MG Gregoretti, C Bonetto and V Gai
U.O.A Medicina d’Urgenza e P.S. Medicina, Azienda Ospedaliera San Giovanni Battista di Torino, Corso Bramante 88, 10126 Torino, Italy
Crit Care 1999, 3 (suppl 1):P24
Study objective: To validate the efficacy of NPPV in patients with
hypercapnic or hypoxemic acute respiratory failure (ARF) admitted to a Medical Intensive Care Unit.
Materials and methods: Thirty-two patients (23M, 9F, mean age
66, range 25–91) received NPPV if they met the following criteria:
severe dyspnea at rest, respiratory muscle fatigue, normal mentation, normal upper airways, stable hemodynamic status and, as for
hypercapnic ARF, pH <7.35, PaCO2 >45 mmHg, respiratory rate
(RR) >25 bpm and, as for hypoxemic ARF, PaO2/FiO2 <200, RR
>30 bpm. Eighteen patients (12M, 6F, mean age 68,4, range
50–91) had hypercapnic ARF due to chronic obstructive lung
disease (COLD); 7 (6M, 1F, mean age 75, range 73–84 ) had cardiogenic hypercapnic acute pulmonary edema (cAPE); 7 (5M, 2F,
mean age 50, range 25–72) had severe pneumonia (SP), 2 with
hypercanic ARF. End-points were the following: pH >7.35, RR
<24 bpm, VT >7 ml/kg, reduced dyspnea, diminished signs of
muscle fatigue, SpO2 >90%. NPPV was considered successful if
the patient was not intubated and mechanically ventilated. NPPV
was considered unsuccessful if the patient was intubated and
P25
mechanically ventilated, became intolerant of mask or died.
BiPAP Respironics® ventilators (S/T-D 20, S/T-D 30, Vision), were
used to administer NPPV, as pressure support ventilation, by nasal
or facial masks. All patients were given standard medical therapy,
as required by the underlying disease.
Results: NPPV was successful in 14 of 18 COPD patients (77.7%),
in all 7 patients with cAPE (100%) and in 3 of 7 patients with SP
(42.8%). Failure in 4 COLD patients was due to mask intolerance
in three cases and to sudden death in one case. Four patients with
SP (three seriously immunocompromised) died. COLD patients
were ventilated for 3 to 62 h (mean 21.5 h), cAPE patients for 4 to
15 h (mean 7.4 h) and SP patients for 12 to 148 h (mean 59.7 h).
Ventilation was longer in SP patients who obtained a therapeutic
benefit (mean 112 h) than in SP patients who did not (mean 23 h).
Conclusion: With the limits of this observational study, we conclude that NPPV has been shown to be an effective support
therapy for COLD patients with acute exacerbation and for
hypercapnic severe cAPE patients. The use of NPPV in patients
with SP was less effective and warrants ulterior study to be validated, according to literature.
Noninvasive mechanical ventilation in asthma crisis: an alternative ventilatory therapy to endotracheal
intubation
A Esquinas, D González, A Carrillo, M Del Baño, M Rodríguez, F García and P Jara
Intensive Care Unit, Hospital M Meseguer, Murcia, Spain
Crit Care 1999, 3 (suppl 1):P25
Oxygen therapy by mask venturi (OMV) in asthma crisis (AC)
could not be avoided,, and urgent endotracheal intubation (ETI)
is the lifesave procedure recommended. Sometimes in a selected
population noninvasive ventilation (NMV) may avoid ETI and his
deleterious effects (barotrauma, infections, etc).
Objective: We describe our first experience in treatment of acute
respiratory insufficiency in (AC). Period of study 1995-98.
Setting: Polyvalent ICU.
Subjects: MV group n = 5, ETI group n = 12, and NMV n = 8.
Material: Ventilators: Dragger Evita 2, and BiPAP ST-D (Resp,
Inc).
Method: Inclusion criteria: Borg dysnea score: 5 ; respiratory rate:
>30 rpm, PaO2 <60 mm Hg ( FIO2 0.5%). ETI: apnoea or unstable
breathing pattern, or severe dysnea. Continuous cardiorespiratory
monitoring.
Results: Time of NMV: 5 ± 3 h levels of IPAP: 12 ± 3 EPAP
6 ± 3 cmH2O; Global respiratory rate: 38 ± 10; pH: 7.36 ± 0.02;
pCO2: 45 ± 7 mmHg paO2: 49 ± 26 mmHg. NMV intolerance
(12.5%). Complications: NMV group: skin nose lesion n = 3; ETI
group: neumothorax n = 2.
Poster abstracts
Groups
n
Success
Non-invasive
8
50%
4±2
Skin lesion
Endotracheal intubation
12
30%
12 ± 6
Neumothorax n = 2
Venturi mask
5
70%
7±3
0
Conclusion: NMV in asthma crisis refractory to (OMV) is a safe
alternative to ETI, and could be avoided in selected patients
P26
UCI stays
Complications
13
Mortality
0
20%
0
(50%). Borg Dysnea score index and respiratory rate at 3 h: 38 ± 6
to 25 ± 6 rpm in NMV group are the best early clinical predictors.
Noninvasive positive-pressure ventilation in acute respiratory distress syndrome: preliminary results
T Principi, S Pantanetti, P Carletti, E Adrario and P Pelaia
Department of Medical and Surgical Emergency, University of Ancona
Crit Care 1999, 3 (suppl 1):P26
The NIV in acute respiratory failure of a previously healthy lung
is not much widespread but much discussed. We report the first
data about four patients, who have been accepted in our ICU due
to acute respiratory failure post-trauma and treated with ventilatory support via face mask like NIV. All patients were negative to
pre-existing lung disease and got thoracic trauma with multiple
costal fractures and bony fractures. We used the mechanical ventilator Adult Star (Infrasonic, Inc., San Diego USA). All the patients
were co-operating and without neurological deficiency. The NIV
has been applied for 2 days and alternated with spontaneous ventilation through Venturi mask after 24 h.
Results: the analyzed data show an improvement of PaO2 in all
patients, already after the first hours of treatment as well as a respiratory rate reduction.
Basal
PaO2
PaCO2
1h
2h
3h
Discussion: The NIV has to be considered as a conventional ventilation’s kind also by acute hypoxemic respiratory failure. The
admission’s criteria of the patients to this kind of ventilation is
however important. In conclusion, we can affirm that the NIV has
an important advantage compared to the conventional ventilation,
that is a shorter stays in the intensive care unit, associated to a
reduction of pneumonia related to endotracheal intubation.
References
1. Antonelli M, Conti G et al.: A comparison of noninvasive
positive-pressure ventilation and conventional
mechanical ventilation in patients with acute respiratory
failure. N Engl J Med 1998, 339:429-435.
2. Meduri GU: Noninvasive positive-pressure ventilation in
patients with acute respiratory failure. Clin Chest Med
1996, 17:513-553.
6h
57.6 ± 11.1 126.9 ± 14.4a 121.7 ± 17.9a 121.7 ± 17.9a 125.4 ± 3.9a
40 ± 15.7
RR
33.7 ± 2.5
PS
/
34.3 ± 3.4
23 ± 3.6a
15
34.7 ± 3.8
20.5 ± 1a
15
34.2 ± 3.3
21 ± 1.1a
15
35.2 ± 2.8
12 h
18 h
24 h
36 h
125.4 ± 3.9a 130.7 ± 29.9a 116.2 ± 7.2a 114.7 ± 12.3a
35.4 ± 2.6
19 ± 1.1a
12
19 ± 1.1a
35.6 ± 2
36.2 ± 1.3
36.3 ± 1.6
17.7 ± 0.8a,b
19.5 ± 1a
17.7 ± 2a,b
12
12
12
12
PEEP
/
5
5
5
5
5
5
5
5
FiO2
0.5
0.4
0.4
0.4
0.3.5
0.35
0.35
0.35
0.35
Trigger
/
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
SAPS II
6±2
/
/
/
/
/
/
/
/
ANOVA One Way rep. P < 0.001. Tukey: asignificantly diff. vs. basal; bvs. 1 h.
P27
Noninvasive mechanical ventilation (NIMV) in weaning failure: could be an alternative approach?
A Esquinas, D González, A Carrillo, M Del Baño, M Rodríguez, F García and P Jara
Intensive Care Unit, Hospital Morales Meseguer, Murcia, Spain
Crit Care 1999, 3 (suppl 1):P27
Setting: Polyvalent ICU.
A trial with noninvasive ventilation (NIMV) could be a safe alternative option in some selected unweanneable patient, after a
period of invasive approach of weaning with: 1) Endotracheal tube
(ET) or 2) Traqueostomizated with a ‘T’ oxygen or Pressure
Support Ventilation (PSV) trials.
Subjects: We show a cases series where NIMV have been applied
as an alternative weaning technique in three difference clinical situations of unweanneability: 1) Post-extubation failure n = 12,
2) Decanulation in traqueostomizated n = 1, and 3) Elective extubation n = 3.
14
Critical Care 1999, Vol 3 suppl 1
Material: NIMV with BiPAP ST-D (Resp, Inc) ventilator, facial
mask.
Weaning
Success
Postextubation – NMV
n = 12
8
3
Methods: Inclusion criteria: acute respiratory insufficiency in a
period (0–48 h): respiratory rate >30 rpm, increase accessory respiratory muscular activity, hypoxemia PaO2 <60 mmHg at mask
venturi (FIO2: 0.5) after a period of ‘T’ piece or PSV and almost
four consecutive weaning failure trials. Excluded: hemodynamic
instability (SAT <90 mmHg), uncooperative patients, and excessive secretions., IPAP/EPAP cmH2O to achieve: >10 ml/Kr and
decrease in dysnea Borg score. Continuous cardiorespiratory monitoring.
Decanulation – NIMV
n=1
0
1
Extubation – NIMV
n=3
1
1
4±2
15 ± 5
2%
15 %
9
5
UCI stay
Mortality
Results
n = 16
Failure
Exclusion
1
1
2
Results: Unweanneable population n = 16. Average age: 61 ± 20,
male n = 12; APACHE II score: 21 ± 3, time of NIMV: 72 ± 12 h.
NIMV was effective in reduce dysnea Borg scores (4 to 2), gasometric alterations and avoid reintubation 8/12. Causes of exclusion: secretions 23%, hemodynamic instability 15%. Complications:
skin lesion n = 2, gastric distension n = 1.
P28
Conclusion: 1). A trial with a NMV as a weaning alternative technique is a safe alternative in selected patients with showed a persistent weaning failure. 2). Reduction in ICU stay, mortality, with
a great comfort and few complications compare to others method.
Airway pressure release ventilation (APRV) enhances cardiac performance in patients with acute lung injury
(ALI)/adult respiratory distress syndrome (ARDS)
LJ Kaplan, H Bailey and V Formosa**
Medical College of PA-Hahnemann University, Departments of Surgery, *Emergency Medicine, **Pulmonary Medicine 3300 Henry Avenue,
Philadelphia, PA 19129, USA. Tel:(215) 842-7558; Fax; (215) 843-1095; E-mail: kaplanl@wpo.auhs.edu
Crit Care 1999, 3 (suppl 1):P28
Purpose: To determine whether APRV can safely enhance hemodynamics in patients with ALI/ARDS.
Methods: Patients with ALI/ARDS were ventilated in pressure
control (PCV) with both upper and lower inflection points eliminated from the hysteresis curve; all patients had a pulmonary
artery catheter. Ventilator settings achieved a pCO2 of 35–45 torr
and a pO2 of >60 torr. Patients were then changed to APRV. Data
included: age, diagnosis, ventilator settings, hemodynamic profiles, ABG, lactate, and medications. Data (means ± SD) were
compared using a Student’s t-test; significance assumed for
P < 0.05.
Results: Mean age was 58 ± 9 years (n = 12) and mean Lung Injury
Score was 7.6 ± 2.1. Temperature (PCV 100.8+1 v APRV 100.6+1F;
P > 0.5) and PaO2/FIO2 (PCV 168 ± 24 v APRV 182 ± 18; P > 0.05)
were similar. Diagnoses were pneumonia (22%), abdominal sepsis
P29
(45%), trauma (33%), bacteremia (18%) and transfusion related
lung injury (1%). Peak airway pressures fell from 38 ± 3 (PCV) to
25 ± 3 cmH2O (APRV, P < 0.05); mean pressures fell from 18 ± 3
(PCV) to 12 ± 2 cmH2O (APRV; P > 0.05). Paralytic use (PCV 74%
v APRV 4%; P < 0.05) and sedative use significantly declined
(PCV 100% v. APRV 68%, P < 0.05). Pressor use decreased substantially (PCV 92% v ARPV 45%, P < 0.05). Lactate levels
remained unchanged (PCV 2.2 ± 0.6 v APRV 1.8 ± 0.8 mmol/l;
P > 0.05). Cardiac index rose from 3.2 ± 0.4 (PCV) to
4.6 ± 0.3 l/min/m2 BSA (APRV; P < 0.05) while DO2I increased by
36% (P < 0.05). CVP declined from 18 ± 4 (PCV) to 12 ± 5 cmH2O
(APRV; P > 0.05).
Conclusion: APRV may be used safely in patients with ALI/ARDS
and decreases the need for paralysis and sedation compared to
PCV. APRV increases cardiac performance with decreased pressor
use and CVP in patients with ALI/ARDS. Further study of ARPV
is warranted to discover its impact on resource utilization and
patient outcome.
Pulmonary function in children who were on long-term mechanical ventilation due to neonatal respiratory
disease
I Vidmar, J Primozic, S Grobovsek Opara and M Grasselli
University Medical Centre, Division for Paediatric Surgery and Intensive Care, Zaloska 7, SI-1525 Ljubljana, Slovenia
Crit Care 1999, 3 (suppl 1):P29
Context: Children with a history of neonatal respiratory disease
that required mechanical ventilation, who develop subsequent
bronchopulmonary dysplasia, often have abnormal pulmonary
function. The extent to which the neonatal respiratory disease
alone is involved is not clear.
Objective: To evaluate the association between neonatal respiratory disease without bronchopulmonary dysplasia on discharge
and pulmonary function later in childhood.
Design: Case–control study.
Setting: Ambulatory follow-up of former intensive care patients at
a university medical centre.
Poster abstracts
15
Table. Pulmonary function tests: mean ± standard deviation
Group
VC (n = 18) ml
FEV1 (n = 18) ml
DLCO (n = 18) (mmol/min)/kPa
Rt (n = 16) kPa/l/s
TGV (n = 15) ml
Cases
2835 ± 806
2236 ± 570
6.01 ± 1.31
0.45 ± 0.19
2003 ± 491
Controls
2984 ± 572
2534 ± 435
6.36 ± 1.01
0.29 ± 0.12
1958 ± 550
–149
–299*
–0.35
0.16*
45
Difference
*Significant difference (P < 0.01)
Participants: Eighteen children aged 11–15 years with a history of
neonatal respiratory disease were randomly recruited, regardless
of gestational age or cause of disease. Inclusion criteria: mechanical
ventilation for >14 days; high inspired oxygen fraction for >2 days
(FiO2 >0.4). Exclusion criteria: presence of bronchopulmonary dysplasia or other acute or chronic pulmonary disease at the time of
this investigation. Eighteen controls matched for age, sex and
height were recruited from children of the hospital staff. All were
healthy at birth and had no pulmonary disease at the time of this
investigation. All parents gave informed consent.
Pulmonary function tests: Vital capacity (VC); forced expiratory
volume in the first second (FEV1) with and without challenge by
the bronchoconstrictor methacholine; diffusing capacity (DLCO);
airway resistance (Rt) with and without methacholine challenge;
and thoracic gas volume (TGV).
P30
Main outcome measures: Variables of pulmonary function in the
cases. Differences between the cases and controls were compared
using the paired-sample t-test.
Results: Both FEV1 and Rt differed significantly (P < 0.01)
between children who had had respiratory disease as neonates
(cases) and controls. There were no significant differences in VC,
DLCO and TGV (Table).
Differences in VC and FEV1 between cases and controls after
methacholine challenge were not significant; however, this analysis is of limited value because only eight or nine matched pairs
underwent these tests.
Conclusion: A mild degree of airway obstruction is apparent in
children 11 to 15 years after neonatal respiratory disease, even in
the absence of bronchopulmonary dysplasia or other pulmonary
disease.
Does the size of the ventilator tidal volume affect the incidence of post operative pneumonia?
SK Appavu, TR Haley, A Khorasani and SR Patel
Division of Surgical Critical care, Cook County Hospital and the Department of Surgery, University of Illinois College of Medicine, Chicago, Illinois, USA
Crit Care 1999, 3 (suppl 1):P30
After major abdominal or thoracic surgery, the patient may
develop rapid shallow ventilation because of splinting, pain or
heavy sedation. This may lead to the development of post operative atelectasis and pneumonia. Hence, it seems reasonable to
expect that the administration of large tidal volumes (VT) during
post operative mechanical ventilation will prevent or decrease the
incidence of post operative pulmonary complications including
that of pneumonia. Whether or not this is true is yet to be determined. Therefore, we performed the following prospective study.
We hypothesized that large VT mechanical ventilation after major
operations resulted in a lower incidence of post operative pneumonia.
Adults admitted to the surgical intensive care unit for post operative mechanical ventilation after major abdominal or thoracic
surgery were placed on one of two VT regimens: 9 ml/kg (group 1)
or 14 ml/kg up to a maximum of 1000 ml (group 2). Patients who
were not placed on the correct VT regimen and those whose tidal
volumes were changed during the study were excluded. Standard
ICU monitoring was instituted. In addition, ventilator performance, peak inspiratory pressures, blood gases and daily chest Xrays were monitored. The incidence of post operative pneumonia
was recorded. Results were analyzed by SPSS statistical software.
Results: Forty-nine patients completed the study, 29 in group 1
and 20 in group 2. Their mean age was 52.7 years. There were 28
males and 21 females. Thirteen of 49 patients (26.5%) developed
post operative pneumonia. A comparison of the two groups is
shown below:
Age
Males
Females VT (ml) vent (h)
Pneumonia
Group 1
49
14
15
705
93
6/29 (20.7%)
Group 2
57
14
6
870
63
7/20 (35%)
Conclusion: Post operative ventilation with large tidal volumes
does not reduce the incidence of pneumonia.
16
P31
Critical Care 1999, Vol 3 suppl 1
Bronchoscopy and BAL in mechanically ventilated patients in an ICU at a university teaching hospital
R Strauss, M Sander, A Müller, M Wehler, C Ernst and EG Hahn
Department of Medicine I, University Erlangen–Nuremberg, Krankenhausstr. 12, D-91054 Erlangen/Germany. Tel: 0049-9131-8533885
Fax: 8536909; E-mail: richard.strauss@med1.med.uni-erlangen.de
Crit Care 1999, 3 (suppl 1):P31
Introduction: Bronchoscopy is an important diagnostic and therapeutic tool in modern intensive care medicine. In ventilated
patients it can lead to hemodynamic instability and can compromise the gas exchange .
Method: We evaluated in a prospective study from 3/1997 to
9/1998 indications, complications and side effects of bronchoscopy
in a 12 bed medical ICU. The vital signs of the patients were
monitored continuously by ECG, invasive blood pressure and
SaO2 measurement. A BGA was performed 5 min before and
5/30/120 min after the examination.
Results: One hundred and fifty-one bronchoscopies were performed in 103 patients (63 male, median age 60 years, median
APACHE II-Score 27.5). The indications were bacteriological
examinations in 113/151 (75%), respiratory toilet in 29/151 (19%),
oxygenation problems in 11/151 (7%). Less common indications
were atelectasis, intubation and biopsy. A BAL was performed in
111/151 (74%) cases. The median PaO2/FiO2-ratio (PFR) was 292
mmHg 5 min before bronchoscopy and 254/182/193 mmHg
5/30/120 min afterwards. In the subgroup with BAL the median
PFR was 295 mmHg 5 min before, 5/30/120 min after examination
261/181/194 mmHg. The PFR was in the critical range <80 mmHg
before bronchoscopy in 5/151 (3%) and 5/30/120 min after the
examination in 5/151 (3%), 9/151 (6%) and 7/151 (5%) cases. In
P32
patients with BAL the corresponding figures were 2/111 before
and 3/111, 6/111, 4/111 after bronchoscopy. A decrease of the PFR
between the beginning and 30 min after finishing bronchoscopy
by more than 50 mmHg was observed in 59/151 (39%) cases for all
patients, in 50/111 (45%) for the BAL subgroup. During 5/151
(3%) procedures serious complications were observed. An increase
of the blood pressure (215/120 mmHg max.) after local application
of noradrenalin and a high peak pressure during ventilation (>45
Torr) did not need therapy. A tachyarrhythmia absoluta was
treated by cardioversion. A decrease of systolic arterial blood pressure (min. 67 mmHg) during sedation, could be stabilised by
volume substitution and dopamine infusion. Bundle-branch block
like ventricular complexes were observed on the ECG monitor in
one case, which were accompanied by a blood pressure decrease.
After an interruption the ECG showed sinus rhythm and the
hemodynamic stabilised again. In a 24 h period after bronchoscopy
the patient died because of an acute myocardial infarction.
Conclusion: Bronchoscopy is a safe procedure in critical ill
mechanically ventilated patients. Even in patients with BAL, in
the most cases only a slight decrease of the PFR could be
observed. The lowest PFRs were observed 30 min after bronchoscopy, 90 min later the PFR was almost back to the starting
level. Critical PaO2 values were only seen in rare cases. Complications could be handled in all cases. The death of one patient in a
24 h range after bronchoscopy was probably caused by the underlying disease and is to be seen only in temporal coincidence.
Clinical presentation and prognostic factors in fat embolism syndrome
GD Puri, VK Arya and P Chari
Department of Anaesthesiology and Intensive Care, Post Graduate Institute of Medical Education and Research, Sector 12, Chandigarh, 160012
Crit Care 1999, 3 (suppl 1):P32
Fat embolism occurs in most of the patients following long bone
fractures but 1–5% of these present clinically as fat embolism syndrome. The recorded data of 64 patients having uncomplicated
long bone fractures without head and chest injuries admitted to
our ICU with diagnosis of FES over a period of 3 years was evaluated to determine factors effecting management and prognosis.
Forty-two patients belonged to subacute and 29 to fulminant FES
group depending upon their clinical status at the time of ICU
admission.
Majority of FES patient had fracture femur and presented with
respiratory distress as initial symptom. Lung injury score was
1.34 ± 0.64 in subacute and 3.36 ± 0.44 in fulminant group
(P < 0.01). Patients with fulminant FES had more number of
abnormal laboratory parameters. Eighteen patients (43%) in subacute and all patients in fulminant group required ventilation.
There was significant delay from FES presentation to ICU admission for subacute FES patients requiring ventilatory support than
the patients improving with conservative therapy alone (P < 0.05).
One patient in subacute (2.3%) and 10 patients in fulminant FES
group (45.5%) died. The compliance of respiratory system (Crs) at
the start of intermittent positive pressure ventilation was significantly less in fulminant as compared to subacute FES patients
(P < 0.05). Most of the ventilated patients had initial improvement
in Crs with ventilation but only those patients who made continuous improvement in Crs beyond 48 h of ventilation ultimately
maintained oxygenation and survived in both the groups. We conclude that early ICU admission and supportive therapy is important determinant of morbidity in FES. Patients with more number
of abnormal laboratory parameters and those in whom Crs and
oygenation index does not improve even after 48 h of adequate
ventilatory support are unlikely to improve by conventional ventilatory support alone and need to be shifted to other modalities of
maintaining oxygenation.
Poster abstracts
P33
17
Acute respiratory distress syndrome in a University Hospital ICU in Japan
H Yukioka and K Nakatani*
Division of Critical Care Medicine and *Department of Anesthesiology and Intensive Care Medicine, Osaka City University Medical School, 1-5-7
Asahi-machi, Abeno-ku, Osaka 545-8586, Japan
Crit Care 1999, 3 (suppl 1):P33
Objective: To determine prognostic factors for and the outcome of
acute respiratory distress syndrome (ARDS) in our ICU.
Method: The American–European consensus conference definition [1] was used for ARDS diagnosis. Thirty-three (2.1%) of 1588
patients admitted to the ICU met the criteria for ARDS. Mechanical ventilation with PEEP was performed for all patients with
ARDS. Steroid pulse therapy (60%), nitric oxide inhalation (21%),
surfactant replacement (9%), and neutrophil elastase inhibitor
administration (24%) were also used. For determination of prognostic factors of ARDS, mean pulmonary arterial pressure (mPAP),
pulmonary vascular resistance (PVR), and multiple organ dysfunction score (MODS) [2] excluding the Glasgow Coma Score were
measured and compared with outcome.
Results: There were 22 men and 11 women aged 61 ± 12 years.
The mortality rate of ARDS was 73%. Sepsis was the main cause
P34
of ARDS accounting for 73% of cases. All ARDS patients with
septic shock (n = 9) and with sterile shock [3] (n = 4) died. The
patients with shock had higher MODS compared to those without
shock with mortality rate 55%. There were no significant differences in mPAP and PVR between survivor and nonsurvivors.
ARDS patients who had high MODS, especially those with low
PaO2/FIO2 and high pressure-adjusted heart rate, 5 days after the
onset of ARDS had a poor prognosis.
Conclusion: Shock and MODS, but not pulmonary hypertension,
are important as prognostic factors for ARDS.
References
1. Bernard GR et al.: Am J Respir Crit Care Med 1994,
149:818.
2. Marshall JC et al.: Crit Care Med 1995, 23:1638.
3. Muckart DJJ et al.: Crit Care Med 1997, 25:1789.
High-frequency oscillatory ventilation (HFOV) in bronchiolitis patients
ELIM Duval*, AJ van Vught*, PLJM Leroy*† and RJBJ Gemke*
*Ped. Int. Care Unit, Wilhelmina Kinderziekenhuis,PO Box 18009, 3501 CA Utrecht, The Netherlands and †Department of Pediatrics, University
Hospital Ghent, Belgium
Crit Care 1999, 3 (suppl 1):P34
HFOV is currently considered to be contraindicated in obstructive
airway disease with prolonged time constants due to the risk of
dynamic airtrapping. This could give rise to circulatory and ventilatory compromise and barotrauma. Nevertheless, bronchiolitis
patients are sometimes put on HFOV after deterioration on CMV.
In distinct to current opinion, we showed that small airway disease
can safely and successfully be managed with HFOV. Ventilatory
strategy should be directed to open up the small airways and keep
them open with sufficiently high mean airway pressures (‘the
open airway strategy’ similar to the ‘open lung strategy’ in diffuse
alveolar disease). Permissive hypercapnia may be used to reduce
pressure swings as much as possible, leading to less shear stress on
lung tissue, without influencing airway recruitment. Further
dynamic airtrapping can be prevented with the use of longer expiratory than inspiratory times and with prevention of spontaneous
breathing. An increasing OI at 48 h may be an indicator of failure
of HFOV and alternative treatments should be considered. NO
might be such an option to avoid ECMO.
We report 9 patients with RSV bronchiolitis and pulmonary
overdistention (small airway disease) successfully treated with
HFOV after deterioration on CMV. Although marked hyperinflation was present in all our patients prior to transition, no airleaks
developed during HFOV. In one patient the oxygenation index
(OI) increased after start of HFOV. Nitric oxide was added and
oxygenation improved immediately. All patients survived without
residual lung disease.
References
Arnold JH, Truog RD, Thompson JE, Falcker JC: High-frequency
oscillatory ventilation in pediatric respiratory failure. Crit
Care Med 1993, 21:272-278.
Thompson MW, Bates JN, Klein JM: Treatment of respiratory
failure in an infant with bronchopulmonary dysplasia with
respiratory syncytial virus using inhaled nitric oxide and
high frequency ventilation. Acta Paediatr 1995, 84:100-102.
Respiratory syncytial virus (RSV) is nowadays the leading cause of
bronchiolitis and viral pneumonia in children. Although the course
is often benign, some children need prolonged hospitalisation and
mechanical ventilation or even ECMO if conventional mechanical
ventilation (CMV) fails.
P35
The importance of prone position ventilation in ARDS for the improvement of oxygenation index
J-C Lewejohann, H-J Düpree, J Gleiß, S Lewejohann, E Muhl and H-P Bruch
Med. Univ. of Luebeck, Dept. of Surgery, Ratzeburger Allee 160, 23538 Luebeck, Germany. E-mail: JLewejohann@t-online.de
Crit Care 1999, 3 (suppl 1):P35
Introduction: In acute respiratory distress syndrome (ARDS)
change from supine (SP) to prone position can improve gas
exchange by recruiting alveoli situated in dorsal dependent
regions and by alteration of ventilation/perfusion ratio. The aim of
this study was to investigate the effect of prone position (PP) after
application of high fractional inspired oxygen (hFiO2), inverse
ratio ventilation (IRV), positive end exspiratory pressure (PEEP)
18
Critical Care 1999, Vol 3 suppl 1
as well as kinetic therapy (KT) and hemofiltration (HF) did not
lead to a breakthrough in treatment of severe ARDS.
Methods: We studied 22 consecutive patients with severe ARDS
(mean age 64 ± 11.16 [SE] years) in a clinical follow-up design. All
patients received hFiO2, IRV and PEEP before starting prone
position, while 15 obtained HF (Prisma®, Hospal) and 3 KT
(Rotorest®). Prone position was commenced 82 h median time
(range 6 to 417 h) after onset of severe ARDS at a mean PaO2/FiO2
ratio of 98.02 ± 6.11 (SEM) mmHg. We compared individual oxygenation index (PaO2/FiO2) before and after start of prone position with linear regression analysis (Excel® regression-procedure;
SPSS® T-test).
Results: In the stage of supine position neither treatment with
hFiO2, IRV, PEEP nor HF and KT led to an improvement of oxygenation index. After starting prone position ventilation 20 of 22
patients showed a significant increase of the oxygenation index
(responder: Y[SP] = [–46.11 ± 3.41] × X + [194.03 ± 3.78];
P36
Y[PP] = [25.00 ± 3.05] × X + [170.36 ± 2.68]; [mean ± SEM]; P < 0.05),
while 2 patients showed no improvement of oxygenation index
(slope of regression SP/PP: 42.96/–22.70 and –11.63/–19.33). Renal
failure of these two non-responders was not treated by HF.
Improvement of oxygenation index was independent of duration
in supine before the begin prone position (range 6 to 417 h). In
one patient PP was started actually after 417 h of treatment at our
Intensive Care Unit.
Conclusion: Starting prone position seems to mark a U-turn for
oxygenation for the majority of patients with severe ARDS, while
application of high fractional inspired oxygen, inverse ratio ventilation, positive end exspiratory pressure as well as kinetic therapy
and hemofiltration do not necessarily improve oxygenation. The
timing of this non invasive technique primarily depends on the
decision to turn the patient from supine to prone. We recommend
prone position in ARDS as soon as possible to reduce lung injury
and complications resulting of mechanical ventilation.
The effect of the pulmonary time constant on the cough peak flow rate at two different inflation pressures: a
bench test model
JS Wills and RP Mahajan
University Department of Anaesthesia and Intensive Care, Queen’s Medical Centre, Nottingham NG7 2UH, UK
P37
Crit Care 1999, 3 (suppl 1):P36
Time constant (ms) 420
1078
1850
2800
Supramaximal flow is characteristic of the cough manoeuvre and is
thought to be the result of dynamic compression of collapsible
airways. We investigated the effect of changing the pulmonary
time constant on the peak flow rate produced by an in vitro cough
manoeuvre. We used a prototype artificial cough generator and a
simplified lung-airway model. The model consisted of a compliant
bag with a resistor (internal diameter 3 mm to 7 mm) that emptied
through a collapsible tube. The resulting range of emptying time
constants (420 to 2800 ms) included those found in vivo (500 to
2000 ms). The lung-airway model was inflated to one of two pressures (31 cmH2O or 55 cmH2O) and then compressed within a
glass container to a pressure of 45 cmH2O. A mechanically-operated glottis opened rapidly and the resultant flow was measured
by a pneumotachograph. The cough peak flow rate (CPFR) was
CPFR l/min
Inflation to
31 cmH2O
419
SD 44.6
185
SD 25.3
108.7
SD 17.1
67.6
SD11.7
CPFR l/min
Inflation to
45 cmH2O
544
SD 70.8
353
SD 56.6
225
SD 29.4
112
SD 29.0
recorded for 20 cough manoeuvres for each configuration and the
values of the mean and standard deviation are shown in the Table.
The results from this bench-test model suggest that the pulmonary time constant has a profound effect on the magnitude of
the cough peak flow rate.
Computer simulation: a guideline in ventilator setting in severe lung disease
L Uttman, S Sigurdsson and B Jonson
Departments of Clinical Physiology and Anaesthesiology, University Hospital, Lund, Sweden
Crit Care 1999, 3 (suppl 1):P37
Mechanics and gas exchange can in be studied with a computercontrolled ventilator. The physiological profile obtained describes
the Pel/V diagram, inspiratory and expiratory resistance versus
volume and the expired volume of CO2 versus tidal volume. When
setting PEEP, frequency, I:E ratio, and minute ventilation or inspiratory pressure the physician needs to assimilate the information of
the physiological profile and all clinical information to assure an
adequate gas exchange at a non-traumatic ventilation. In
ALI/ARDS harm can be caused both by ventilation at too low lung
volumes and by ventilation at high volumes. In COPD the task is
to ventilate at the lowest possible volume and airway pressure.
The complexity of the physiology and ventilator settings makes it
impossible to figure out what is the ideal pattern of ventilation in
order to reach the immediate therapeutic goals defined by the
physician. However, on the basis of an adequate mathematical
physiological profile, a computer can by simulation prognosticate
what would be the consequences of alternative modes of ventilation. Through repeated simulations the physician can search a
mode of ventilation that leads to his goals.
Computer simulation can be used to: a) increase the understanding of various patterns of ventilation in disease. b) predict the consequences of alternative settings in a particular patient.
In left diagram the total pressure in the ventilator (Pvent), the tracheal pressure (Ptr) and the alveolar, i.e. the elastic pressure, Pel,
Poster abstracts
Current ventilator setting
19
Alternative ventilator setting
P, cm H2O
80
Ptr
Pvent
Pel
60
40
20
0
0
500
1000
0
V, ml
is shown for a patient with critical obstructive lung disease. Under
current setting (volume control 10 l/min, Ti = 25%, Tpause = 10%,
RR = 16, PEEP = 4 cmH2O) the PaCO2 of 9.2 kPa was deemed
P38
500
V, ml
1000
acceptable. The pressures were, however, very high. By repeated
simulations it was possible to identify a setting which dramatically
would reduce the pressures without changing PaCO2.
Clinical evaluation of a new closed loop ventilation mode: adaptive supportive ventilation (ASV)
RS Campbell, RP Sinamban, JA Johannigman, FA Luchette, SB Frame, KDavis Jr and RD Branson
University of Cincinnati College of Medicine, Cincinnati, OH 45267-0558, USA
Conventional
ASV
Crit Care 1999, 3 (suppl 1):P38
Table 1.
Introduction: ASV (Galileo, Hamilton Medical, Inc.) is a mode of
mechanical ventilation (MV) with a closed loop algorithm to
determine and adjust ventilator settings. ASV may adjust mandatory breath rate, I:E ratio, and inspiratory pressure of mandatory
breaths. Target minute ventilation (VE) is determined by ideal
body weight (IBW) and clinician selected Percent Vent (% Min
Vol). Galileo assesses the pt by measuring dynamic compliance
and expiratory time constant. With IBW and %Min Vol settings,
optimal settings for rate, Ti, VT, and VE are determined. We compared MV with ASV to MV with physician determined vent settings during the initiation of MV.
Rate (bpm)
10.1 ± 2
14.4 ± 3
VT (ml)
863 ± 133
690 ± 121
Methods: Ninteen post-operative pts requiring MV were studied.
Vent settings by physician were noted and each pt was placed on
those settings or ASV randomly. IBW was determined from standardized tables and %MinVol was set to 100%. PEEP and FiO2
were determined by staff and held constant. ABG’s and cardiopulmonary variables (f, VT, VE, Ti, PIP, Paw, HR, MAP, and VCO2)
were measured and recorded after 30 min on each mode. Data
were compared using student’s t-test.
VE (l/min)
9.5 ± 2
9.6 ± 2
PIP (cmH2O)
31.9 ± 9
25.2 ± 8
Paw (cmH2O)
11.5 ± 2.4
12.0 ± 2.8
1.5 ± 0.5
1.43 ± 0.3
TI (s)
Table 2.
Discussion/conclusion: Upon initiation of mechanical ventilation,
the precise VE requirement of the pt may not be known. Clini-
ASV
PH
7.39 ± 0.06
7.40 ± 0.07
PaCO2 (mmHg)
38.6 ± 5
37.6 ± 5
106.1 ± 33
100.0 ± 31
SaO2 (%)
PaO2 (mmHg)
99.3 ± 1
99.1 ± 1
VD/VT (%)
51.3 ± 6
57.4 ± 8
VCO2 (ml/min)
265 ± 56
262 ± 48
Conventional
ASV
Table 3.
Results: 19 pts (14 male) were studied. Initial ‘test breaths’ during
ASV were well tolerated. Mean IBW was 88.8 Kg. Mean age was
54.3 years. Table 1 reveals set and measured ventilator parameters
for both study periods. PIP and VT were lower during ASV. Respiratory rate was higher during ASV. VE, TI, and Paw were unchanged
between study periods. Mean values for PEEP and FiO2 were 7.3
and 0.48, respectively. Table 2 reveals ABG measurements, CO2
production, and VD/VT ratio. There were no clinically relevant differences in ABG’s or VCO2 between study periods. VD/VT was
lower during ASV. No pt suffered any adverse events from
derangements in ventilation or acid-base balance. One pt with
ARDS receiving 17 cmH2O PEEP was hypoxemic during ASV
(PaO2 57.2). Table 3 reveals heart rate and mean arterial pressure
during each study period. There were no clinical changes to any
measured vital sign between the two study periods.
Conventional
HR
89 ± 16
87 ± 16
MAP
72 ± 19
73 ± 15
cians use rough estimates and clinical experience to determine VE,
respiratory rate, VT, and Ti. Determination of vent settings made
by the machine have been suggested (Intern Care Med 1996,
22:199). Our results suggest that ASV as startup mode of ventilation is acceptable and comparable to physician determined ventilator settings. Gas exchange during ASV is equivalent to physician
determined ventilation. VT during ASV is more consistent with
‘lung protective’ strategy (7.8 ml/kg) than was conventional VT
(9.7 ml/kg). Mechanical ventilation with ASV is more efficient as
evidenced by lower VD/VT and may be safer as a result of lower VT
and PIP.
20
P39
Critical Care 1999, Vol 3 suppl 1
Relationship of body mass index (BMI), lactate and intra-abdominal pressure (IAP) to subsequent mortality
in ICU patients
MLNG Malbrain
Department of Intensive Care, Ste-Anne St-Remi Hospital, Boulevard Jules Graindor 66, 1070 Brussels, Belgium
IAP≥12 (n = 71) IAP<12 (n = 334) P-value
Crit Care 1999, 3 (suppl 1):P39
Introduction: Excess body weight increases the risk of death from
any cause and from cardiovascular disease in adults [1]. In the
majority of population studies, the relationship of BMI to mortality is a U-shaped curve, with increased risk in the lowest and
highest percentiles of the distribution. In acutely ill patients
however BMI below the 15th percentile remains an independent
predictor of mortality whereas a high BMI (>85th percentile) was
not significantly related to risk of mortality [2]. We wanted to
study in a prospective clinical trial the relationship between IAP
and lactate and BMI and their relationship to subsequent mortality in ICU patients. The results of an interim analysis are presented in this abstract.
IAP (mmHg)
15.8 ± 3.6
BMI
26.3 ± 5
Results: The percentage of female patients was 55.3, age 66 ± 17.4,
MODScore 3.4 ± 3.3, APACHE-II score 16.4 ± 6.2, SAPS-II score 35.1
± 17.5, BMI 25.1 ± 4.8, IAP 8.3 ± 4.7 mmHg, lactate 3.3 ± 4.2 mEq/l,
ICU-stay 6.3 ± 9.5 and hospital stay 22.4 ± 22.9 days. Raised IAP
was present in 71 patients (17.5%). The incidence of IAP ≥ 12 and
the mean IAP values were higher in patients who underwent
emergency surgery: 39.4% (mean 11.5 ± 5.3) versus 19.8%
(8.6 ± 4.9) in medical versus 6.1% (6.9 ± 3.5) in scheduled surgical
patients. The ICU and hospital mortality were respectively 18%
and 27.2%. The IAP was significantly higher in patients who died
in the ICU: 13.2 ± 5.2 versus 7 ± 3.6 (P < 0.0001) as well as in
patients who died in the hospital: 11.5 ± 5.3 versus 6.9 ± 3.6
(P < 0.0001). The Table lists the parameters studied in patients
with high and normal IAP. The ICU and hospital mortality was
significantly higher in patients with high IAP; respectively 64.8%
versus 8.1% (P < 0.0001, OR 20.9, 95% CI 11.2–39) and 70.4%
versus 18% (P < 0.0001, OR 10.9, 95% CI 6.1–19.5). With a cut-off
at 12 IAP had 64.8% sensitivity, 78.6% specificity, 75.8% accuracy,
38.7% positive predictive value and 91.3% negative predictive
value for ICU mortality. There was a poor but significant correlation between BMI and IAP: BMI = 0.2106 × IAP + 23.268
P40
<0.0001
0.15
Lactate (mEq/l)
6.7 ± 6.3
2.4 ± 2.9
<0.0001
MODS
6.9 ± 3.5
2.6 ± 2.7
<0.0001
SAPS-II
52.4 ± 16.1
31.3 ± 15.4
<0.0001
APACHE-II
23.3 ± 9
14.3 ± 7.8
<0.0001
Age (years)
69.1 ± 11.9
65.3 ± 18.3
NS
ICU-stay (days)
16.2 ± 15.2
4.2 ± 5.9
<0.0001
21.5 ± 22.7
0.06
Hospital stay (days)
Methods: Over a 12 month period 405 patients, hospitalised in a
seven bed mixed ICU, were screened for increased IAP
>12 mmHg (normal 0–5 mmHg) with the standardised intravesical
pressure recording method. Data collected within the first 24 h of
ICU admission were: age, gender, MODScore, APACHE-II and
SAPS-II score and BMI. Maximal IAP and lactate levels were
recorded within the first 72 h. Study endpoints were: duration of
ICU and hospital stay, ICU and hospital mortality and cost of ICU
and hospital stay. Statistical analysis was done with Fisher exact
and two-tailed unpaired Student’s t-test, values are mean ± SD.
6.4 ± 2.6
24.8 ± 4.7
27 ± 23.3
ICU cost (US$)
11980 ± 10230
2651 ± 3490
<0.0001
Hospital cost (US$)
15600 ± 11590
8388 ± 8226
<0.0001
(R2 = 0.0413, P < 0.0001) and between lactate and IAP; lactate =
0.4851 × IAP–0.3885 (R2 = 0.2847, P < 0.0001). There was a trend
towards lower ICU mortality with higher BMI but none of this
reached statistical significance: 25.8% in the first, 15% in the
second, 16.3% in the third, and 16.2% in the fourth BMI quartile. In
patients within the first BMI quartile (<22) ICU mortality was significantly higher when compared to the total group of other BMI
quartiles: 25.8% versus 15.8% (P = 0.04, OR 1.9, 95% CI 1.1–3.3).
Conclusion: The interim results of an ongoing prospective clinical
trial show that increased IAP can be expected in about 17.5% of
cases. It seems to be a predictor of mortality and causes a considerable extra-cost and prolonged ICU-stay. High IAP does not correlate well with high BMI or lactate. There is no U-shaped
(concave) mortality curve associated with BMI, on the contrary,
patients with higher BMI had lower mortality compared to
patients within the first BMI quartile, and this is in accordance
with the results from others [2]. We suggest that IAP should be
used as part of routine monitoring in the ICU and that future
studies examining variables predictive of ICU-mortality should
include IAP and BMI.
References
1. Stevens J et al.: N Engl J Med 1998, 338:1-7.
2. Galanos AN et al.: Crit Care Med 1997, 25:1962-1968.
The search for optimal PEEP in acute lung injury (ALI): correlation between intra-abdominal pressure (IAP)
and the lower inflection point (Pflex). Results of a pilot study
MLNG Malbrain
Department of Intensive Care, Ste-Anne St-Remi Hospital, Boulevard Jules Graindor 66, 1070 Brussels, Belgium
Crit Care 1999, 3 (suppl 1):P40
Introduction: It is well known that IAPs above 15–20 mmHg
increase peak and plateau alveolar pressures. The rise in pressure
on the diaphragm causes a pattern of restrictive lung disease with
a drop in functional residual capacity and all other lung volumes.
Finally this results in diminished chest wall compliance causing
difficult ventilation and weaning. The respiratory system can be
Poster abstracts
21
divided into the chest wall and the lung. Since the diaphragm is
coupled to the abdominal wall any increase in IAP may therefore
affect chest wall and lung compliance [1]. By calculation of static
V–P curves it has been shown in animal and human studies that
abdominal and subsequently chest wall compliance goes up after
abdominal decompression and this correlates well with the
volume recruited [1]. Recent studies looking at compliance in
primary and secondary ARDS found that the latter presents with
preserved lung but decreased chest wall compliance and PEEP
allows to recruit lung units markedly [1,2]. In a previous study we
found that in patients with secondary ARDS and raised IAP,
PEEP-adjustment for IAP calculated at zero PEEP (ZEEP)
resulted in significant better oxygenation at the expense of a significant increase in peak and plateau alveolar pressures but
without the risk for early barotrauma [3]. In this pilot study we
wanted to sort out if there is a correlation between IAP and Pflex.
Methods: Over a 2 month period 115 measurements were performed in 11 patients. The IAP was calculated at ZEEP with the
standardised intravesicle pressure recording method and Pflex
with the super-syringe method. The M/F ratio was 6/5, age
67.1 ± 9.4, MODScore 6.5 ± 3.3, APACHE-II score 25.2 ± 8.5,
SAPS-II score 54.4 ± 15.7, ICU-stay 11.3 ± 6.3 days. The number
of measurements in each patient was 10.5 ± 7.5. There were three
patients with primary and three with secondary ARDS, and three
patients had secondary ALI according to the definitions given by
the American–European consensus conference. Calculation of correlation was done with the Prism GraphPad™ software (version
2.00 October 31 1995), values are mean ± SD.
Results: The values for IAP (mmHg), IAP (cmH2O) and Pflex
(cmH2O) were 14.9 ± 6.8, 19.4 ± 8.9 and 13.3 ± 5.5, respectively for
the whole group of patients; 15.8 ± 7.6, 20.6 ± 9.8 and 13.2 ± 6.0,
respectively in secondary ALI/ARDS and 12.6 ± 3.4, 16.4 ± 4.4 and
13.6 ± 3.9 respectively in primary ARDS. There was a very good
correlation between IAP (cmH2O) and Pflex (cmH2O) for the
whole group of patients (Fig. 1): Pflex = 0.552 × IAP + 2.5146
(R2 = 0.808, P < 0.0001) and this correlation was even better in the
patients with secondary ALI/ARDS; Pflex = 0.5745 × IAP + 1.3227
(R2 = 0.888, P < 0.0001). As suspected the correlation was worse in
P41
patients with primary
(R2 = 0.7428, P < 0.0001).
ARDS:
Pflex = 0.7622 × IAP + 1.1624
Conclusion: We found a very good correlation between IAP and
Pflex. Calculation of IAP can easily be done at the bedside of
every ICU patient who has a Foley catheter in place. We propose
this simple strategy for determination of best PEEP in ALI
instead of the more time consuming, not generally accepted and
not without risk calculation of Pflex with the super syringe
method. Before being used for clinical purposes, the results of this
pilot study need to be validated in a multicentre trial.
References
1. Ranieri VM, et al.: Am J Respir Crit Care Med 1997;
156:1082-1091.
2. Gattinoni L, et al.: Am J Respir Crit Care Med 1998; 158:
3-11.
3. Malbrain MLNG: Int Care Med 1998; 24:S125.
Determination of the best volume of perfluorocarbone to ensure partial liquid ventilation in the pig with
ARDS
JM Constantin, G Gindre, JD Segrell-Therre, JE Bazin and P Schoeffler
Département d’Anesthésie-Réanimation; G.H Saint Jacques ; 63000 Clermont-Ferrand, France
Crit Care 1999, 3 (suppl 1):P41
Introduction: Partial liquid ventilation consists of filling the residual functional capacity with perfluorocarbon (PFC), while providing tidal volume by conventional ventilation. Several studies have
shown that smaller volumes of PFC allow significant improvement in ventilation parameters during experimental ARDS. To
date no study has compared several small volumes of PFC. The
purpose of this study was to make a comparison with the
minimum doses of PFC in a pig model presenting ARDS.
Method: 16 pigs, average weight 24 ± 5 kg, under general anesthesia and myorelaxation were prepared with installation of a central
venous catheter and an arterial catheter with continuous oxygen
saturation monitoring The animals were then ventilated (Evita 4,
Dräger) with intermittent positive pressure ventilation (FiO2:1) in
order to obtain PaCO2 at 35 ± 1 mmHg. At this point ARDS was
induced by intravenous injection over half an hour of 0.3 ml/kg
oleic acid. ARDS was confirmed by a PaO2/FiO2 <150 taken over
two successive arterial samples. A pressure–volume curve was
established and used to identify the lower inflection point (LIP)
and the level of the ‘best PEEP’. The animals were then split into
four groups of four, with a control group being given continuous
positive pressure ventilation (CPPV) without PFC. The second
group was administered 5 ml/kg intra tracheal perfluorocarbon
(Rimar 101, Mitsubishi Milano) then given CPPV ventilation. The
third group was administered 10 ml/kg PFC and the last group 15
ml/kg. In all four groups CPPV ventilation was maintained with
the ‘best PEEP’. Arterial pressure, central venous pressure, heart
rate, SaO2 and PETCO2 were recorded continuously. Blood gases
and ventilation parameters: peak inspiratory pressure, tidal
volume and pulmonary compliance were recorded every 15 min.
The three groups were compared using an ANOVA, a Friedman
test and a Mann and Whitney U-test (P < 0.05 significant).
22
Critical Care 1999, Vol 3 suppl 1
EVOLUTION OF LUNG COMPLIANCCE
700
600
60
500
Group 1
Group 2
50
400
300
Groupe
30
Group 4
20
200
100
x
x x
x
5 ML
x
x
TEMOIN
40
10 ML
15 ML
10
x
0
0
T0
T1
T2
T3
T4
T5
T6
T7
T8
TIME
Time 1= 15 min
Figure 2. Evolution of lung compliance.
Figure 1. Evolution of the PaO2 in the four groups. x: times when
the pigs died.
Results: In the control group lung compliance and PaO2 continued
to drop for all the animals; in PLV groups, lung compliance
decrease after administration of PFC. After a few minutes, the
compliance increase significatly. In the 5 ml/kg group lung compliance and PaO2 rose to an average of 354 ± 197 mmHg and 15.4. In
the 10 and 15 ml/kg group PaO2 was restored to its initial level of
448 ± 74 and 445 ± 86 mmHg. Lung compliance increase to satifactorys values (21.4 ± 3.1; 21.48 ± 2.4). All the animals in the control
P42
group died in a mean time of 109 ± 25 min, the animals in the
5 ml/kg group survived on average 158 ± 17 min, the animals in the
10 ml/kg and 15 ml/kg groups survived for the whole 3 h the experiment lasted (P < 0.05).
Discussion: It would thus appear that in pigs a dose of 5 ml/kg PFC
enables satisfactory ventilation parameters to be restored, but the
level remains lower than that obtained with 10 ml/kg. The fact that
a low dose does not have long-lasting effects might be due to faster
evaporation of the product and a drop in its efficiency. There is no
beneficial effect with larger dose than 10 ml/kg.
Cardiorespiratory effects of inhaled nitric oxide during acute hypercapnia with and without correction of
blood pH in acute respiratory failure in piglets
G Zobel, S Rödl, B Urlesberger, M Bermoser, W Schwinger, D Dacar and I Knez
Departments of Pediatrics, Neonatology and Cardiac Surgery, University of Graz, Austria
Crit Care 1999, 3 (suppl 1):P42
Objective: To evaluate the effects of inhaled nitric oxide on gas
exchange and hemodynamic data during acute hypercapnia with
uncorrected and corrected blood-pH.
Design: Prospective, randomized, experimental study.
Setting: University research laboratory.
Subjects: Ten piglets weighing 9 to 13 kg.
Interventions: After induction of anesthesia, tracheostomy and
controlled mechanical ventilation animals were instrumented with
two central venous catheters, a pulmonary artery and two arterial
catheters, and an ultrasonic flow probe around the pulmonary
artery. Acute respiratory failure was induced by the infusion of
oleic acid (0.08 ml/kg) and repeated lung lavages with 0.9% NaCl
(20 ml/kg). The protocol consisted of randomly assigned periods
with different PaCO2 levels (Normocapnia = PaCO2 40 torr,
Hypercapnia I = PaCO2 65 torr, Hypercapnia Ic = PaCO2 65 torrpH corrected, Hypercapnia II = PaCO2 85 torr, Hypercapnia Iic =
Hypercapnia 85 torr-pH corrected). Tidal volume was reduced to
BL
NC
21.8 ± 1.4
28.1 ± 0.6
PAP (torr)NO-10
19 ± 1.1
25.8 ± 1.2
27 ± 3**
MAP (torr)NO-0
83 ± 1.7
79.3 ± 2.9
72.6 ± 2.5
MAP (torr)NO-10
82 ± 1.8
81 ± 2.4
CO (l/min)NO-0
2.6 ± 0.39
PAP (torr)NO-0
HC-I
32 ± 1.7
HC-Ic
HC-II
29.2 ± 1.2
35.1 ± 1.8
30.8 ± 1.6#
26 ± 1
HC-IIc
28.5 ± 1.1**
26.3 ± 1.3*
78.4 ± 3.7
74.2 ± 3.0
76.7 ± 4.1
79 ± 3.8
82 ± 5
74 ± 4
77 ± 4
1.9 ± 0.19
1.72 ± 0.15
1.77 ± 0.1
1.90 ± 0.17
1.90 ± 0.2
CO(l/min)NO-10
2.5 ± 0.4
2.0 ± 0.2
1.77 ± 0.11
1.72 ± 0.14
1.91 ± 0.16
2.16 ± 0.21
PVR (dyne.s.cm–5)NO-0
362 ± 53
684 ± 85
928 ± 157
694 ± 97
956 ± 142
823 ± 197
PVR (dyne.s.cm–5)NO-10
275 ± 41
582 ± 99
642 ± 69*
611 ± 123
685 ± 124*
469 ± 107*
PaO2/FiO2 (torr)NO-0
454 ± 37
98 ± 12
101 ± 5.2
109 ± 12
PaO2/FiO2 (torr)NO-10
469 ± 35
148 ± 11**
151 ± 13**
146 ± 17*
95 ± 5
154 ± 25**
106 ± 13
148 ± 21*
*P < 0.05 vs iNO 10ppm, **P < 0.01 vs iNO 10ppm, #P < 0.05 vs pH-correction, BL, baseline; NC, normocapnia; HC-I, hypercapnia 65 torr; HCII, hypercapnia 85 torr; C, pH-correction
Poster abstracts
induce hypercapnia, inspiratory time was prolonged to achieve
constant mean airway pressures (Paw). Tham infusion was used to
correct pH. At each PaCO2-period the animals were ventilated
with and without inhaled nitric oxide (10 ppm).
Measurements and results: Continuous hemodynamic monitoring
included right atrial, mean pulmonary artery and mean systemic
arterial pressures, and continuous flow recording at the pulmonary
artery. In addition, airway pressures, tidal volumes, lung compliance and airway resistance, arterial and mixed venous blood gases
were measured. Data were obtained with and without inhalation
P43
23
of nitric oxide at baseline, normocapnia and 2 levels of hypercapnia with and without pH correction and are given in the Table.
Conclusion: Acute hypercapnia resulted in a significant increase in
pulmonary artery pressure and pulmonary vascular resistance
without significantly influencing oxygenation and cardiac output.
pH-correction at hypercapnic episodes decreased pulmonary
artery pressure and pulmonary vascular resistance associated with
a slight increase in cardiac output and oxygenation. Inhaled nitric
oxide significantly reduced pulmonary hypertension induced by
acute hypercapnia and significantly improved oxygenation during
normocapnia and acute hypercapnia with and without acidosis.
Cardiorespiratory effects of inhaled nitric oxide and moderate hypercapnia in an experimental model of
single ventricle
G Zobel, D Dacar, I Knez, S Rödl, Y Salaymeh, A Knez and E Gradnitzer
Departments of Pediatrics and Cardiac Surgery, University of Graz, Austria
Crit Care 1999, 3 (suppl 1):P43
Objective: To evaluate the effects of inhaled nitric oxide and
moderate hypercapnia on hemodynamics and gas exchange in an
experimental model of single ventricle.
protocol consisted of randomly assigned periods with different
PaCO2 levels (Normocapnia = PaCO2 40 torr, Hypercapnia I =
PaCO2 50 torr, Hypercapnia II = PaCO2 60 torr,) and a period of
inhaling nitric oxide (10 ppm) at normocapnia. Tidal volume was
reduced to induce hypercapnia, inspiratory time and PEEP were
adjusted to achieve constant mean airway pressures (Paw).
Design: Prospective, randomized, experimental study.
Setting: University research laboratory.
Subjects: Nine piglets weighing 10 to 14 kg.
Interventions: After induction of anesthesia, tracheostomy and
controlled mechanical ventilation animals were instrumented with
two central venous catheters and two arterial catheters. After a
midline sternotomy the animals were placed on cardiopulmonary
bypass and subjected to atrial septectomy, patch closure of the tricuspid valve, and creation of a 4 mm systemic to pulmonary arterial shunt. Before weaning from cardiopulmonary bypass
ultrasonic flow probes were placed around the pulmonary artery
and the descending aorta. In addition a pulmonary artery catheter
was inserted into the pulmonary artery via the right ventricle. The
BL
RAP (mmHg)
8.9 ± 0.9
PAP (mmHg)
MAP (mmHg)
Conclusion: The creation of this experimental model of single
ventricle resulted in a significant decrease in oxygen saturations
and mean arterial pressure. Moderate hypercapnia resulted only in
minimal changes in pulmonary artery pressure, pulmonary vascular resistance, and oxygen saturations. Inhaled nitric oxide
decreased pulmonary artery pressure and resistance associated a
slight increase in oxygen saturations.
NC
NC-iNO
10.6 ± 1.5
10.7 ± 1.4
11 ± 1.4
23.1 ± 1.8
20.4 ± 1.5
23.6 ± 1.8
25.2 ± 2.1*
HC-II
11.3 ± 1.5
51.5 ± 3.4#
48.6 ± 3#
46.4 ± 3.3#
0.94 ± 0.1
1.17 ± 0.1
0.89 ± 0.1*
0.98 ± 0.1
CO (l/min)
1.95 ± 0.1
1.89 ± 0.1
1.81 ± 0.1
1.63 ± 0.1
1514 ± 246
1661 ± 188*
(dyne.s.cm–5)
53 ± 3.7#
HC-I
Qp/Qs
PVR
88 ± 5.9
Measurements and results: Continuous hemodynamic monitoring
included right atrial, mean pulmonary artery and mean systemic
arterial pressures, and continuous flow recordings at the pulmonary artery and the descending aorta. In addition, arterial and
central venous blood gases were measured. Data were obtained at
baseline, normocapnia with and without NO-inhalation and 2
levels of hypercapnia and are given in the Table.
1504 ± 331
967 ± 148
SaO2 (%)
99.6 ± 0.1
77 ± 3.6#
79.7 ± 2.3#
74 ± 4.4#
74 ± 3.4#
SvO2 (%)
89 ± 1.2
45 ± 3.5#
47 ± 2.4#
42 ± 3.2#
40 ± 2.1#*
RAP, right atrial pressure; PAP, pulmonary artery pressure; MAP, mean arterial pressure; Qp, pulmonary artery flow; Qs, systemic flow; PVR,
pulmonary vascular resistance; BL, baseline; NC, normocapnia; HC-I, hypercapnia 50 torr; HC-II, hypercapnia 60 torr; iNO, inhaled nitric oxide
*P < 0.05 vs NC-iNO, #P < 0.01 vs BL
24
P44
Critical Care 1999, Vol 3 suppl 1
Impact of inhaled nitric oxide on pulmonary capillary pressure in ARDS patients
V Sramek, R Rokyta, I Novak, M Nalos, P Hora, J Ruzicka and M Matejovic
ICU, Medical Dpt I, Charles Uni Hospital Plzen, Alej Svobody 80, CZ-30466 Plzen, Czech Republic. Tel: +420-19-710 3 165;
Fax: +420-19-522 566; E-mail: sramek@fnplzen.cz
Crit Care 1999, 3 (suppl 1):P44
Introduction: Inhaled nitric oxide (NO) causes selective pulmonary vasodilation. In experiment, pulmonary arteries were
shown to be primary site of NO effect. Our aim was to study the
effect of inhaled NO on pulmonary vasculature in ARDS patients.
Materials and methods: Inhaled NO was tested in 8 ARDS
patients (PaO2/FiO2 = 71 ± 26 mmHg, LIS >2.5). One hour test of
20 ppm NO was performed and in 3 patients NO was additionally
increased to 40 ppm with the primary aim to improve oxygenation.
Positive pressure response was defined as a decrease of mean pulmonary artery pressure (mPAP) >2 mmHg. Pressure curves during
pulmonary artery occlusion were recorded in duplicate before and
with NO and the more representative one was used for pulmonary
capillary pressure (PCP) estimation [1]. Positive response in oxygenation was defined as PaO2/FiO2 increase >20%. Statistics: nonparametrical Wilcoxon test for two related samples and simple
correlation when appropriate. Data are presented as means ± SD.
P< 0.05 was considered significant.
Results: In 1 patient a marked decrease in mPAP was measured
(15 mmHg), in other 4 patients the drop was marginal
Conclusion: When effective in lowering pulmonary pressures,
inhaled NO seems to act primarily on the arterial component of
transpulmonal vascular resistance.
Acknowledgement: Supported by IGA grant No. 3999-3
Reference
1. Cope DK, et al.: Measurement of effective pulmonary
capillary pressure using the pressure profile after
pulmonary artery occlusion. Crit Care Med 1986,
14:16-22.
Correlation of lung mechanics with saturated phosphatidylcholine ratios and surfactant protein A in
bronchoalveolar lavage fluid from infants with RSV induced respiratory failure
SM Tibby, M Hatherill, SM Wright, AD Postle, KB Reid and IA Murdoch
Department of Pediatric Intensive Care, Guy’s Hospital, London SE1 9RT, UK
Crit Care 1999, 3 (suppl 1):P45
400
0.7
0.6
Methods: Nineteen infants were studied, median age 7 weeks
(range 3–25 weeks), median weight 4 kg (range 2–6 kg). BALs
were taken within 24 h of commencing mechanical ventilation.
BAL surfactant phospholipid composition was detected by electrospray ionization mass spectrometry, and SPA levels by enzymelinked immunosorbent assay. Static respiratory system compliance
and resistance were measured using the single breath occlusion
technique with a commercially available device (PEDS® 4.1,
Medical Associated Services, USA).
0.5
resistance
Aim: Infants with respiratory syncytial virus (RSV) induced respiratory failure have been shown to be deficient in surfactant, both
in quantity and ability to reduce surface tension. Theoretical evidence suggests that surfactant may have a role in maintaining
patency of small airways, which has implications for RSV bronchiolitis. In addition, a minimum ratio of surfactant protein A (SPA)
to fully saturated dipalmitoylphosphatidylcholine (DPPC) must
be present for surfactant to be fully functional. We wished to
investigate the relationship between (a) lung mechanics and
SPA/DPPC ratios, and (b) lung mechanics and the ratio of DPPC
to the monounsaturated palmitoyloleoylphosphatidylcholine
(POPC) in bronchoalveolar lavage (BAL) fluid from ventilated
RSV positive infants.
compliance
P45
(3–4 mmHg). Three patients did not respond to NO inhalation by
any significant change in mPAP. In five responders PCP and
PCWP pressure did not change before and after the NO test (25.0
± 4.5 and 24.2 ± 5.3 mmHg for PCP; P = 0.18 and 18.0 ± 3.3 and
17.8 ± 3.9 mmHg for PCWP; P = 0.59). Transpulmonary pressure
difference (dPAP–PCWP) decreased significantly (14.6 ± 1.4 and
11.0 ± 3.7 mmHg, respectively; P = 0.04) which corresponded with
trend to decrease the arterial component of the transpulmonary
pressure difference (dPAP–PCP) (7.6 ± 3.0 and 4.5 ± 2.6 mmHg,
respectively; P = 0.11 i.e. decrease in 4 cases).
0.4
0.3
0.2
r = 0.53
0.1
p = 0.02
300
200
100
0
r = -0.50
p = 0.03
0
0
2
dppc/popc
4
0
2
dppc/popc
4
Results: The median (interquartile range) values for compliance
were 0.36 (0.31–0.47) ml/cmH2O/kg, and resistance 234 (184–277)
cmH2O/l/s. The DPPC/POPC ratio correlated significantly with
both compliance and resistance (see Figure). There was no correlation (neither linear nor exponential) between SPA/DPPC ratio
and lung mechanics (compliance: r = 0.1, resistance r = 0.24).
Conclusion: Surfactant containing higher ratios of saturated phosphatidylcholine has a role in maintaining compliance and small
airway patency in RSV infected infants. Although a certain
minimal level of SPA is necessary for surfactant function, additional benefit is not seen with increasing SPA/DPPC ratios. These
findings have implications for exogenous surfactant supplementation in this disease.
Poster abstracts
P46
25
Experimental study on prevention of simulated high altitude ALI by tetramethylpyrazine in dogs
F Liangui and G Xianjian
Scientific Research Division, The Third Military Medical University, ChongQing, 400038, P.R. China. Tel: (8623) 68752126;
E-mail: jshaw@public.cta.cq.cn
Crit Care 1999, 3 (suppl 1):P46
Twenty-one hybird dogs were randomly divided into acute lung
injury (ALI) treated and control groups at simulated high altitude
environment of 4000 m. All animals were sacrificed after 6 h. The
tetramethylpyrazine (TMP) treated group showed that the WBC
count was significantly higher at 15 min after fat tissue extract was
given (P < 0.05), the edema of both capillary endothelial cells and
alveolar epithelial cells was less serious, the number of leukocytes
accumulated in the lungs was less. The increase in production of
P47
leukotriene B (LTB) by polymorphonuclear neutrophil (PMN),
alveolar macrophage (AM), and the activity of platelet-activating
factor (PAF) by PMN were partially inhibited (P < 0.01). Although
the ratio of the pulmonary extravascular water volume/blood free
dry lung weight (PEWV/BFDL) of TMP group was significantly
elevated as compared with that of control group, no significant difference was seen (P > 0.05). However, the level of PaO2, the PMN
and AM count, and the albumin level of the BALF in both groups
had no significant difference. These results demonstrated that the
early treatment with TMP could inhibit the decrease in the WBC
count, and reduce the accumulation of leukocytes in the lungs.
Effects of C1-inhibitor and rSP-C surfactant on oxygenation and histology in rats with lavage-induced acute
lung injury
B Vangerow*, D Häfner, P-G Germann†, G Marx* and H Rueckoldt*
*Dept. of Anesthesiology, Hannover Medical School, 30625 Hannover, Germany. Tel: +49-172-4211038; †Institute of Pathology and Toxicology,
‡Dept. of Respiratory Pharmacology, Byk Gulden, 78403 Konstanz, Germany
Crit Care 1999, 3 (suppl 1):P47
Introduction : The acute respiratory distress syndrome (ARDS) is
characterized by diffuse injury to the endothelial and epithelial
surfaces of the lung leading to severe respiratory failure. Alterations in the surfactant system and activation of the contact
system of coagulation are major contributors to the pathophysiology of ARDS. C1-inhibitor (C1-INH) is the main inhibitor of
contact activation and the only known inhibitor of classical
pathway complement activation. The aim of this study was to
investigate the effects of C1-inhibitor administration and rSP-C
surfactant application on oxygenation and lung histology in an
ARDS-model.
Methods: Thirty-six male Sprague Dawley rats were subjected to
repetitive lung lavage with isotonic saline solution. Three experimental groups and two control groups were studied: Group 1 and
2 served as controls without any treatment. Animals of group 1
were sacrificed 60 min after the last lavage procedure (p.l.).
Animals of group 3–5 received 200 U/kg body weight (b.w.) C1INH (Centeon, Germany) intravenously (group 3), 25 mg/kg b.w.
rSP-C Surfactant (Byk Gulden, Germany) intratracheally (group
4) or both (group 5) at 60 min p.l. Blood gases were determined
P48
120, 150, 180 and 210 min p.l. All animals of group 2–5 were sacrificed at 210 min p.l. and the lungs were excised for histological
examination. Hyaline membrane formation, distribution and
severity of intraalveolar neutrophil (PMN) accumulation and the
severity of intraalveolar and perivascular hemorrhage were graded
semiquantitatively using a scale from 0 to 4+.
Results: At 210 min p.l. pO2 values of group 4 (456 ± 74 mmHg)
and group 5 (387 ± 155 mmHg) were significantly higher than in
group 3 (120 ± 103 mmHg) or in controls (63 ± 12 mmHg). Hyaline
membrane formation was significantly reduced in group 4 and 5.
The grading for PMN infiltration was significantly lower in
animals who received C1-INH (group 3 = 2.0, group 5 = 2.3) than
in controls (group 2 = 2.7) or in animals treated with surfactant
only (group 4 = 3.3). The severity of intraalveolar hemorrhage and
edema were significantly reduced in group 3 and highest in
group 4.
Conclusion: Surfactant application was effective in improving pO2
which was related to the reduction of hyaline membrane formation. C1-INH administration had no significant effect on pO2 and
hyaline membrane formation but was effective in reducing PMN
infiltration, intraalveolar hemorrhage and edema formation.
Inhibition of pulmonary microvascular chemokine production by human Laktoferrin and
Phosphatidylethanolamine
GC Beck, BA Yard, FJ van der Woude and K van Ackern
Institute for Anaesthesiology, Faculty of Clinical Medicine Mannheim, Theodor Kutzer Ufer 1-3, 68165 Mannheim, Germany
Crit Care 1999, 3 (suppl 1):P48
Chemokines, a large family of structurally related chemotactic
cytokines, are essential for the migration of leukocytes during
inflammatory processes. The release of neutrophil attractant
chemokines such as MCP-1, Groα, ENA-78, GCP-2 and NAP-2 as
well as fractalkine by lung microvascular endothelial cells
(LMVEC) is dramatically increased upon stimulation with LPS.
The present study was performed to investigate, whether human
Lactoferrin (hLf) or Phospholipase A2-inhibitor Phosphatidylethanolamine (PE) can intervene with the release of these
chemokines by LMVEC under LPS stimulation.
LMVEC were pretreated with hLf for various time intervals prior
to stimulation with LPS or with LPS in the presence of hLf. In
other experiments, cell impermeable PE, Cyclooxygenase-
26
Critical Care 1999, Vol 3 suppl 1
inhibitors (CoI) (indomethacine, acetyl-salicylic acid) and a
platelet activating factor (PAF)-antagonist, were added to LPS
stimulated LMVEC. Chemokine release was measured by ELISA
and detection of chemokine mRNA by means of RT-PCR.
HLf added to LMVEC at the time of stimulation did not influence chemokine production. However, when hLf was added prior
to LPS stimulation, a significant inhibition of MCP-1 (P < 0.001)
and ENA-78 (P < 0.01) but not of Groα production was observed.
In order to investigate if LPS induced chemokine production was
dependent on PAF, Arachidonic acid (AA) or its metabolites,
LMVEC were treated with PE, CoI and PAF-antagonist either
P49
after or at the time of LPS stimulation. Treatment of LMVEC
with PE completely inhibited the LPS induced chemokine production of MCP-1, ENA-78 and Groα in a time and dose dependent fashion. This was still observed, when LMVEC were
pretreated with LPS. CoI and PAF-antagonist could partly reduce
LPS induced chemokine production. Furthermore mRNA expression of ENA-78, Groα, GCP-2 and fractalkine was decreased after
LPS stimulation in the presence of PE. Our data demonstrate,
that hLf and PE are potent agents to counteract LPS induced
chemokine produktion by LMVEC. These findings may have
clinical implications in the treatment of acute lung injury during
sepsis.
Lipid peroxidation, antioxidant status and selenium levels in patients requiring prolonged ventilatory support
V Cerny, P Zivny*, P Dostal and R Parizkova
Department of Anesthesiology and Intensive Care, *Dept. of Biochemistry, Charles University, Faculty of Medicine, 50005 Hradec Králové,
Czech Republic
Crit Care 1999, 3 (suppl 1):P49
Introduction: Recently free oxygen radicals have been implicated
as possible mediators of respiratory muscle dysfunction, particularly diaphragm fatigue. The aim of the study was to evaluate lipid
peroxidation, antioxidant status and selenium levels in patients
with sepsis requiring ventilatory support and during weaning.
Methods: After institutional approval 40 critically ill patients were
prospectively studied during ventilatory support and weaning,
three patients due to death were excluded. All patients were
weaned according to standard weaning protocol. Blood samples
were drawn daily and collected until analysis. Malondialdehyde
(MDA) serum levels, total glutathion (GSH), glutathion-peroxidase (GPX) and superoxid-dismutase (SOD) activity in erythrocytes and serum selenium levels were estimated at the time of
admission to ICU (T1), on the last day of full ventilatory support
(T2), on the day when weaning was started (T3) and on the first
day of spontaneous ventilation (T4). After successful weaning
patients were divided in two groups according to the length of
weaning (W): group S (W ≤ 3 days, n = 15), group L (W > 3 days,
n = 22). t-test or Mann Whitney Rank Sum test were used for statistical analysis (SigmaStat, Jandel Co., USA), values are expressed
as mean (SD) or median (25%–75% percentiles), P < 0.05 was considered statistically significant.
P50
Results: Summarized selenium values (µmol/l) were 0.63 (0.28) in
Group S and 0.57 (0.16) in Group L.
T1
MDA – S
0.72
(0.55–1)
MDA – L
1.14
(0.94–1.89)*
GPX – S
31.5 (8.2)
T2
T3
0.94
0.89
(0.72–1.39) (0.82–1.25)
T4
1.02
(0.82–1.2)
1.07
0.96
0.94
(0.67–1.43) (0.74–1.32) (0.67–1.31)
39 (8.0)
34.9 (8.6)
39.1 (7.8)
GPX – L
34.6 (10.2)
35.5 (4.2)
27.2 (11)
31.3 (6.2)**
SOD – S
1320 (279)
1320 (310)
1090 (256)
1270 (350)
SOD – L
1270 (439)
1120 (107) 1360 (107)*** 1290 (275)
MDA pg/ml – median (25–75%), GPX U/g Hb – mean (SD), SOD
%inhib – mean (SD), * P = 0.006, **P = 0.009, ***P = 0.013
Discussion: Prolonged ventilatory support and weaning longer
than 3 days were associated with higher MDA levels and lower
GPX levels, also selenium levels were insignificantly lower in
patients with prolonged ventilatory support. The clinical importance of these findings needs to be further studied.
Acknowledgement: Supported by grant IGA MZ CR 3674-3
Primary endogenous pneumonia in severe burn patients
L Lorente, MA de la Cal, E Cerdá, P Garcia and M Sánchez
Intensive Care Unit, Hospital Universitario de Getafe, Madrid, Spain
Crit Care 1999, 3 (suppl 1):P50
The study has been approved by the Institutional Board for Clinical Research
Objective: To determine primary endogenous pneumonia effect
on severe burn patient mortality and to establish the associated
factors with primary endogenous pneumonia.
Patients: All patients of ≥14 years admitted between January 1995
and January 1996 with a total body surface burn area of ≥20%.
Exclusion criteria included immunosuppression, pregnancy, and
length of stay less than 5 days or admission ≥48 h following burn
trauma.
Intervention: Collection of data on surveillance samples from throat
and rectum on admission and afterwards twice weekly, and primary
endogenous pneumonia during the intensive care unit stay.
Design: Prospective observational.
Setting: A six-bed burn intensive care unit.
Statistical analysis: The variables potentially related to mortality
were age, sex, total body surface burn area, full-thickness burn
Poster abstracts
area, inhalation injury, primary endogenous pneumonia, bloodstream infection, burn wound infection and urinary tract infection.
Comparison between groups was performed using Wilcoxon test
or Fisher’s exact test when appropriate.
P51
27
Results: Thirty-one patients fulfilled the criteria of analysis. Mean
age was 43 years (36–50), total body surface burn area 43%
(36–50), full-thickness burn area 24% (17–31). Inhalation injury
was identified on 13 patients. Mean stay was 28 days (21–35).
Mortality was 29% (nine patients).
In the univariate and multivariate analysis the factors associated
(P < 0.05) with mortality were primary endogenous pneumonia
and full-thickness burn area. The risk factors associated (P < 0.05)
with primary endogenous pneumonia were full-thickness burn
area and inhalation injury. Increasing the number of cases (56
patients), both variables were statistically significant in the univariate analysis, but were not statistically significant in the multivariate analysis. At present we are continuing the study to know
the factors associated with morbidity and mortality in severe burn
patients.
Fourteen patients developed 19 pneumonias: 12 primary endogenous, six secondary endogenous and one exogenous. The
causative microorganisms were 14 Staphylococcus aureus, three
Haemophilus influenzae, two Streptococcus pneumoniae, one
Pseudomona aeruginosa and one Acinetobacter spp.
Conclusion: Half the patients developed a pneumonia (63%
primary endogenous pneumonia). The isolated pathogens were
predominantly Staphylococcus aureus. Primary endogenous pneumonia in severe burn patients may be associated with mortality,
but is necessary collecting more cases to show it.
Outbreak of nosocomial infection/colonisation caused by Stenotrophomonas maltophilia with mucoid
phenotype
I Palabiyikoglu, M Tulunay, I Asik, M Oral, M Unsal and S Gungor
Ankara University Medical Faculty, Department of Anaesthesiology & Reanimation, Ibni-Sina Hastanesi, 06100 Samanpazarý Ankara, Turkey
Crit Care 1999, 3 (suppl 1):P51
The Gram-negative bacillus Stenotrophomonas maltophilia (SM) has
emerged as an important pathogen associated with significant
case/fatality ratio [1,2]. SM is a potentially dangerous organism
because of its resistance to many antibiotics. We present here an
outbreak of mucoid phenotype SM pneumonia (four cases) and
respiratory tract colonisation (three cases). Our review of literature
revealed only one case report of pneumonia characterised as
mucoid phenotype [2]. The outbreak was caused following admission of a 65-year-old male patient with respiratory distress, fever,
leukocytosis (24000/µl) in the ICU. Chest X-ray showed an infiltrative shadow in the right lower lobe and bilateral pleural effusion was detected on CT. Sputum cultures obtained before
admission to ICU and subsequent days yielded mucoid phenotype SM. Treatment with ticarcilline plus clavulonic acid to which
the isolates was susceptible was initiated. One-day later chest X-
P52
ray showed diffuse bilateral pneumonic infiltrates and the
patient’s condition rapidly deteriorated. Ciprofloxacine was added
to the treatment. Subsequent SM isolates rapidly developed
antimicrobial resistance to antibiotics. Four patients in the ICU
were lost with SM pneumonia within 7–10 days. SM isolates were
identified by standard Analytical Profile Index procedure (API
20E and API 20 NE). A significant number of both infected and
colonised patients had severe systemic diseases and tracheotomy,
they were mechanically ventilated and receiving broad spectrum
antibiotics before isolation of SM. SM is emerging as an important
nosocomial pathogen in critically ill ICU patients and should no
longer be regarded as a harmless bacillus in ICU.
References
1. J Clin Microbiol 1986, 24:52-55.
2. J Clin Microbiol 1994, 32:2856-2857.
Selective decontamination of the digestive tract influences the acquisition of Helicobacter pylori among
intensive care nurses
PHJ van der Voort, RWM van deer Hulst*, DF Zandstra, AAM Geraedts†, J Kesecioglu‡ and GNJ Tytgat§
Department of Intensive Care and †Gastroenterology, Onze Lieve Vruwe Gasthuis, PO Box 95500, 1090 HM Amsterdam, Department of *Internal
Medicine and Gastroenterology, Kennemer Gasthuis, Haarlem, ‡Department of Intensive Care and §Gastroenterology, Academic Medical Centre,
Amsterdam, The Netherlands
Crit Care 1999, 3 (suppl 1):P52
Introduction: H. pylori prevalence is increased in health care
workers and in intensive care nurses. Exposure to H. pylori by
gastric secretions and faeces are the main sources of transmission
of H. pylori infection to health care workers. The routine use of
selective decontamination of the digestive tract (SDD) at an
intensive care unit suppresses H. pylori in critically ill patients. It
was questioned whether as a consequence, a decreased exposure
of H. pylori to intensive care nurses would lead to a lower prevalence of H. pylori infection in these nurses.
Methods: The H. pylori infection prevalence of intensive care
nurses from a unit using SDD routinely (group I) was compared to
that of intensive care nurses from a unit not using SDD (group II).
Health care workers from other departments where no SDD was
used (group III) served as a control group. Both the intensive care
nurses and controls were included on a voluntary basis. Persons
using proton pump inhibitors were excluded. H. pylori was detected
by Laser Assisted Ratio Analyser-13C-urea breath test (UBT).
Results: Three UBTs were unable to be processed in group I
(n = 64), five in group II (n = 55) and five in group III (n = 50). The
prevalence of H. pylori infection was 11% (7/61) in group I and
25.5% (14/50) in group II (P = 0.027, Pearson Chi-Square). In group
III the prevalence of H. pylori infection was 16% (8/45) which is
not significantly different from both group I and II. The mean age
in the three groups was 35.9, 37.8 and 36.6 years respectively (NS).
28
Critical Care 1999, Vol 3 suppl 1
Conclusion: The prevalence of H. pylori infection among intensive
care nurses is lower in nurses from units using SDD compared to
the ones from a unit not using SDD. Acquisition of H. pylori by
P53
transmission from critically ill patients appears to be diminished
once SDD is used.
Factors predicting the etiologic pathogens in intensive care patients with early-onset pneumonia
H Carsauw, C Suetens and B Jans
Scientific Institute of Public Health - Louis Pasteur, J. Wytsmanstreet 14, 1050 Brussels, Belgium
Crit Care 1999, 3 (suppl 1):P53
Objective: National surveillance data of nosocomial infections in
Intensive Care Units (ICUs) in Belgium show that in early-onset
pneumonia cases (i.e. within 48 h after ICU-admission) microbiology results are more likely to be lacking than in late-onset pneumonia cases. The aim was to examine whether the etiologic
pathogen in ICU-patients with early-onset pneumonia could be
predicted by specific patient characteristics.
Material and methods: Data provided by the ICUs participating in
the national surveillance programme for nososcomial infections in
ICUs between January 1996 and June 1998 were examined. For
the most frequently isolated pathogens in early-onset pneumonia,
associated patient characteristics at admission were identified.
Independence of association was verified by multivariate analysis
using logistic regression.
Results: Seventy hospitals reported 472 cases of early-onset pneumonia, 366 (77.5%) of which were microbiologically documented.
The most frequently isolated pathogens were S. aureus (17.2%),
E. coli (13.7%), P. aeruginosa (13.4%) and S. pneumoniae (12.8%). In
P54
univariate analysis, S. aureus infection was associated with a high
Simplified Acute Physiology Score (SAPS II) (55 or more: OR 4.0,
P < 0.001; P for trend = 0.001), P. aeruginosa infection with prolonged prior hospital stay (1–7 days: OR 2.9, P = 0.02; >7 days: OR
4.3, P < 0.001; P for trend = 0.002). Factors associated with S. pneumoniae infection were younger age (<70 years: OR 2.2, P = 0.01),
community origin (OR 4.8, P < 0.0001), no use of antibiotics in the
last 48 h (OR 3.4, P < 0.001) and no prior surgery in the 30 days
preceding diagnosis of pneumonia (OR 3.1, P = 0.002). No patient
characteristics were found to be predictive for infection with E.
coli. After multivariate analysis, S. aureus and P. aeruginosa infection remained significantly associated with respectively a high
SAPS II score and prolonged prior hospital stay. For S. pneumoniae
infection, only community origin and no use of antibiotics in the
last 48 h remained independently associated.
Conclusion: Empirical antimicrobial treatment for early-onset
pneumonia in Belgian ICUs is common. Patient characteristics at
admission, such as duration of prior hospital stay, prior antibiotic
use and patient severity score, are important factors in predicting
the most probable etiologic pathogen and may be helpful in decision-making with regard to empirical antimicrobial therapy for
early-onset pneumonia in ICUs.
Nosocomial infection: main cause in development of septic complications in surgical postoperative patients
E Gyurov, M Milanov and S Milanov
Emergency Medicine Institute ‘Pirogov’ General ICU 21 ‘TotlebeN’, 1606, Sofia, Bulgaria. E-mail marga@sps-elsys.com
Crit Care 1999, 3 (suppl 1):P54
Introduction: In this first attempt to prove the main cause of
septic complications in postoperative ICU patients in Bulgaria’s
biggest hospital (more than 1000 beds) we analyzed all patient
admitted in general ICU during 5 year period (1993–1997).
Methods: We provided a standard bacterial monitoring of all body
media (tracheal tubes, urinary tract, blood, central venous lines,
sputum and surgical wounds). According to bacterial growth we
divided patients into three groups. The Group 1 included patiens
without any bacterial growth. Group 2 included patients with
nosocomial infection. Group 3 included patients with secondary
surgical endogenous infections.
Results: Of all patients during these 5 years, we include those 913
(62.9%) who stayed for more than 72 h in ICU. Group 1 included
256 patients(28%). From Group 2 we obtained following positive
cultures: 457 from tracheal tubes (88.8%), 376 from urinary tract
(41.9%), 282 from blood (47.2%), 164 from central venous lines
(15%) and 66 from sputum (8.8%). The dominating pathogens in
cultures were: from tracheal tubes: Acinetobacter spp. (27.4%);
from blood: Acinetobacter spp. (21%), Serratia spp. (16.4%), S. epidermidis (21%); from urine: till 5 day E. coli (18%), Acinetobacter
spp. and Citrobacter spp. (13.8%); and after 5 days: Candida spp.
(25%) and Pseudomonas aeruginosa and S. aureus. In Group 3 we
obtained samples from surgical wounds and drainage tubes. The
dominating pathogens were the same as in other body media
(Acinetobacter spp., Serratia spp.).
Conclusion: The nosocomial infection remains the main cause of
septic complications in postoperative ICU patients and its emergence in ICU further rises There is also increase in secondary
endogenous surgical infection. We noted P. aeruginosa moved to
third-second place as a cause of nosocomial infection. The importance of Gram-positive flora nearly equalised that of Gram-negative in ICU.
Poster abstracts
P55
29
Nosocomial pneumonia and bacteremia in intensive care: results from the Belgian national surveillance,
1996–1998
C Suetens, B Jans, H Carsauw and O Ronveaux
Scientific Institute of Public Health – Louis Pasteur, Department of Epidemiology, Brussels, Belgium
Crit Care 1999, 3 (suppl 1):P55
episodes), Staphylococcus aureus (17.7%), Escherichia coli (12.6%),
Candida spp. (12.1%) and Enterobacter spp. (9.5%).
In 1996 the Scientific Institute of Public Health – Louis Pasteur
(IPH), in collaboration with the Belgian Society of Intensive Medicine and Emergency Medicine, started a multicentre surveillance
of intensive care units (ICU) acquired pneumonias and bacteremia. From January 1996 to June 1998, 60% of Belgian acutecare hospitals (n = 101) participated during at least one
surveillance period (3 months), and 64% of those participated
more than one period. A total of 31 374 patients were included for
the analysis.
Bacteremia was reported in 2.4% of the patients. Five percent of
bacteremia occurred within the first 48 h. Forty percent (n = 301)
were secondary to another infection site and 55% (1.3% of the
patients and 2.3 BSIs per 1000 patient-days) matched the CDC
case definition of laboratory-confirmed primary bacteremia. The
device-adjusted primary bacteremia rate was 3.1/1000 catheterdays and varied between 1.5 in coronary surgery to 4.8 in patients
with multiple trauma and 6.0 in neurosurgical patients. The five
predominant micro-organisms in primary bacteremia were Staphylococcus epidermidis (in 33.3% of the episodes), Staphylococcus aureus
(12.8%), Enterococcus faecalis (7.1%), Pseudomonas aeruginosa (6.1%)
and Enterobacter aerogenes (5.7%).
In 4.7% (95% CI 4.5–5.0) of the patients a pneumonia with onset
later than 48 h of ICU stay and matching CDC criteria for nosocomial pneumonia was registered. In 89% of those at least one ventilation-day had preceded the onset of the infection (RR 10.4%;
8.9–12.2). The number of ventilator-associated pneumonias per
1000 ventilation-days was 19.0/1000 ventilation-days, varying from
11.9 in coronary surgery patients to more than 25 in patients
having undergone neurosurgery, non-cardiac thoracic surgery, vascular surgery and transplantation. The predominant micro-organisms were Pseudomonas aeruginosa (recovered in 18.0% of the
P56
The frequent participation to the national surveillance led to an
important national database that allows to study the risk factors of
ICU-acquired infections, to identify areas for prevention and to
improve the inter-ICU comparability of infection rates according
to the risk profile of the different ICU populations. International
comparisons remain a delicate matter by lack of internationally
standardised surveillance methods.
Protected specimen brush bronchoscopically directed versus unprotected tracheal aspirate in patients with
ventilator associated pneumonia
S Morra, C Laudi, F Nespoli, M Ferrario, M Latino, MT Cecini, J Hernandez, A DiTeodoro and C Sturla*
Dept. of Anesthesia and Intensive Care, S. Abate Hospital, Via Pastori 4, 21013, Gallarate Italy; *Biochemistry laboratory , S. Abate Hospital
Crit Care 1999, 3 (suppl 1):P56
Objectives: Bacterial resistance to antimicrobial treatment is actually one of the most debated issue in medical field. Therefore, it is
important to dispose a diagnostic procedure to allow an aimed
antimicrobial treatment. Unprotected tracheal aspirate (UTA) is
the most widely used sampling technique to assess pulmonary
infection even though known to have a high sensivity and a low
specificity [1]. Protected specimen brush bronchoscopically
directed (PSB) is a procedure that purpose a higher specificity [2].
The aim of the study is to compare both methods for the diagnosis
of pneumonia in ICU.
Materials and methods: 70 consecutive patients admitted to an 8bed general ICU over a period of 18 months, intubated and
mechanically ventilated [3]. When patients met clinical and radiological criteria for suspicion of pneumonia both UTA and PSB
were performed.
Results: Data collected from the two methods pointed out significative differences.
PSB vs UTA revealed complete negativeness or growth of different microorganisms in 29 patients (41.5%); this result had statistically significance (P < 0.01).
Above all it is to underline that microorganism most frequently
represented in UTA and not detected by PSB were in sequence:
Candida spp, Pseudomonas aeruginosas, Staphylococcus aureus. No
complications were reported during the procedures.
Antimicrobial therapy based on PSB data was started, leading to a
good clinical response and favourable outcome.
Conclusion: PSB is a reliable and safe method useful to investigate pulmonary infections. High specificity of the technique
allows to aim antibiotic therapy, so reducing the risk of inducing
resistance to molecule still effective with a consequent optimization of expenses. UTA and corrispective PSB were both negative
in X case (y%) VPN = 1. In consideration of UTA elevated vpn,
this method could represent a first diagnostic step followed in case
of positiveness by PSB
References
1. Baselski VS, El-Torky M, Coalson JJ, Griffin JP: The
standardization of criteria for processing and interpreting
laboratory specimens in patients with suspected ventilatorassociated pneumonia. Chest 1992, 102:571S-579S.
2. Jourdain B, Novara A, Joly-Guillou, et al.: Role of
quantitative cultures of endotracheal aspirates in the
diagnosis of nosocomial pneumonia. Am J Respir Crit
Care Med 1995, 152:241-246.
3. Pingleton SK, Fagon JY, Leeper KV: Patient selection for
clinical investigation of ventilator-associated pneumonia.
Criteria for evaluating diagnostic techniques. Chest 1992,
102 (Suppl 1): 553S-556S.
30
P57
Critical Care 1999, Vol 3 suppl 1
Incidence and pathogenesis on severe burns patients infection
L Lorente, E Cerdá, MA de la Cal, M Sánchez and P Garcia
Intensive Care Unit, Hospital Universitario de Getafe, Madrid, Spain
Crit Care 1999, 3 (suppl 1):P57
Twenty-two patients developed 59 infections: 28 primary endogenous, 27 secondary endogenous and four exogenous.
The study has been approved by the Institutional Board for Clinical Research
Fourteen patients developed 19 pneumonias: 12 primary endogenous, six secondary endogenous and one exogenous. The
causative microorganisms were: 14 Staphylococcus aureus, three
Haemophilus influenzae, two Streptococcus pneumoniae, one
Pseudomona aeruginosa and one Acinetobacter spp. Eight patients
had nine urinary tract infections: eight primary endogenous and
one secondary endogenous. The pathogens were: six Escherichia
coli, three Streptococcus faecalis and one Serratia.
Objective: To know infection incidence, pathogenesis and
microorganisms on severe burns patients.
Design: Prospective observational.
Setting: A six-bed burn intensive care unit.
Patients: All patients of ≥14 years admitted between January 1995
and January 1996 with a total body surface burn area of ≥20%.
Exclusion criteria included immunosuppression, pregnancy and
length of stay less than 5 days or admission ≥48 h following burn
trauma.
Intervention: Collection of data on surveillance samples from
throat and rectum on admission and afterwards twice weekly, and
infections during the intensive care unit stay. The infections were
diagnosed according to the CDC criteria.
Results: Thirty-one patients fulfilled the criteria of analysis. Mean
age was 43 years (36–50), total body surface burn area 43%
(36–50), full-thickness burn area 24% (17–31). Inhalation injury
was identified on 13 patients. Mean stay was 28 days (21–35).
Mortality was 29% (nine patients).
P58
Nine patients developed 10 burn wound infections: one primary
endogenous, eight secondary endogenous and one exogenous.
The causative microorganisms were: six Staphylococcus aureus,
three Pseudomona aeruginosa, one Escherichia coli, one Acinetobacter
spp, one Proteus and one Klebsiella.
Fourteen patients had 21 bloodstream infections: seven primary
endogenous, 12 secondary endogenous and two exogenous. The
pathogens were: nine Staphylococcus aureus, four coagulase-negative staphylococcus, two Streptococcus faecalis, one Streptococcus
faecium, three Escherichia coli, two Pseudmona aeruginosa, and one
Candida spp.
Conclusion: Burns patients infections are similar to trauma
patients, with 50% primary endogenous infections. The isolated
pathogens were predominantly gram positive coccus, except in
urinary tract infections.
Evaluation of the infections due to central venous catheters in intensive care unit patients
L Ýyilikçi, C Eyigör, A Atay, Ü Evliya, N Koroðlu, M Çelik and A Günerli
Dokuz Eylül University School of Medicine, Department of Anaesthesiology, Ýzmir, Turkey
Crit Care 1999, 3 (suppl 1):P58
Introduction: Central venous catheters (CVC) are responsible for a
part of the infections seen in intensive care units (ICU). In our ICU
routinely we use CVC for fluid and drug administration as well as
CVP measurement. On the ather hand, infection, one of the most
important complications of CVC must always be thought. Infections
due to CVC are attributed to colonization of microorganisms at the
tip of CVC and then their migration to the circulation. In our study ,
we planned to determine the colonization ratio of microorganisms at
the tip of CVC and analyse the agents of infection.
Method: We evaluated the data obtained from 40 CVC that we
could send to the laboratory in a year. The insetion sites of CVC
were V. basilica (n = 25), V. subclavia (n = 5), V. jugularis interna
(n = 4) and V. femoralis (n = 6). CVC were inserted under sterile
condition by using sterile gloves and surgical drapes. The duration
of catheterization was 8.4 ± 5.1 days (2–23 days). Central venous
pressure measurements and fluid administrations were made by
the nurses under sterile conditions. Fluid administration sets were
changed two times a week. Cannulation sites were cleaned with
povidone-iodine (Betadine®) every day and sterile deesings
(Tegaderm®) were applied. Approximately 2 cm to the tip of each
with drawn CVC is sended to the laboratory of microbiology in a
sterile tube for culture-antibiogram analysis.
Findings: We determined an agent of infection in 6 of 40 catheters
tips that we evaluated (1%5). The agents were: Acinetobacter spp.
(n = 2), Coagulase (–) staphylococci (n = 2), Fungi (n = 1),
Oxacilline resistant Staphylococci aureus (n = 1). We determined
no agent of infection in the others 34 catheters.
Discussion: Infection rate was less compared to previous reports
and was similar to the results of the study by Nahidh et al. in
which povidine iodine was used in the control group. Then we
concluded that the ratio of infections due to colonization at the tip
of CVC may be decreased by daily care of catheters made under
sterile conditions.
References
1. Chest 1996; 109:1030-1032.
2. Türk Anaesthesiology and Reanimation Congrees XXVII.
1993:145.
Poster abstracts
P59
31
A.V.A.: a novel approach to venous access
PR Lichtenthal and A De Wolf
Department of Anesthesiology, Northwestern University, 303 E. Superior Street, Room 360, Chicago, IL 60611, USA
Crit Care 1999, 3 (suppl 1):P59
Introduction: Central venous access is an integral part of patient
care. The dilemma was whether to insert an introducer or multilumen catheter for access. However, the Advanced Venous Access
device (A.V.A.) from Baxter now offers the option of a single
device to accomplish multiple functions with one stick. The
object of this study was to compare maximal flow rates of this new
device with other introducers utilizing the Haemonetics Rapid
Infusion System (R.I.S.) and the more traditional pressurized I.V.
system
Test methods: Devices tested with the traditional system were:
Baxter A.V.A., which incorporates a 9F PA access with one distal
(D) and two proximal lumens (P1&P2); Arrow 9F; Argon 9F. The
test system has been described previously. Devices tested with
the RIS were the Baxter A.V.A. and the Arrow 9F introducer.
Fluids measure were saline and a blood/plasma mixture. The RIS
was set up in a manner to continually infuse fluids through the
device using a cut-off pressure of 300 mmHg to judge maximum
flow. Devices were tested with PA catheters (7.5F & 8F). Results
for the A.V.A. are shown in various configurations: AVA(1)=D+P1;
AVA(2)=P1+P2; AVA(3)=D+P1+P2 (Fig. 1).
P60
Results: In the traditional I.V. system, the A.V.A. delivered higher
flows than all other introducers. Figure 1 below shows flow rate
results for the RIS system.
Discussion: In all categories, the Advanced venous Access device
delivered higher flows than the other introducers. Therefore, the
A.V.A. device offers a new dimension in central access for trauma,
critical care, and high blood loss surgeries (i.e. liver transplants). It
now gives us the ability to monitor the circulation and infuse
fluids with fewer venous punctures.
Biochemical and haematologic predictors of fungemia in previous colonised ICU patients
A Bártola, R Milheiro, E Lafuente, C Gonçalves, J Fernandes, J Leão, A Sousa, M Martins and A Vieira
Intensive Care Unit, Hospital Senhora da Oliveira, 4800 Guimarães, Portugal
Crit Care 1999, 3 (suppl 1):P60
Introduction: In last years the nosocomial ICU fungal infections
are assuming a greater impact with increasing morbidity, mortality
and cost. A better outcome is correlated with an earlier treatment.
Objectives: The aim of the study was to assess the accuracy of
simple not expensive biochemical and haematologic parameters to
predict the change of fungal colonisation to a status of fungemia.
Materials and methods: Three-year retrospective study with 806
ICU medical and surgical non-neutropenic patients. The study
group consisted of 90 patients with fungal documentation, 37
patients were excluded for insufficient data. We considered two
groups.
Group 1 – colonisation 73 patients (fungal documentation in biological products except blood)
Group 2 – fungemia 17 patients (at least one positive blood
culture)
Group I
24 h
Age
SAPS II
48 h
Group II
72 h
54.87 ± 13.43
40.87 ± 12.58
40.87 ± 13.43
110.06 ± 98.2
154.4 ± 130.13
Lactate dehyd.
735.74 ± 575.52
705.4 ± 598.8
Leukocytes
Platelets
pH
48 h
63 ± 13.78
Alkaline phosph. 120.6 ± 110.91
772.5 ± 591.6
24 h
117.5 ± 73.86
773 ± 335.6
13.7 ± 6.3
13.28 ± 6.37
12.9 ± 5.71
13.85 ± 4.86
195.26 ± 139.8
183.6 ± 140
195.2 ± 150.3
332.4 ± 193.3
136.5 ± 70.6
650 ± 311.3
14 ± 5.24
317.2 ± 188.3
72 h
178.27 ± 87
717.13 ± 370.9
12.55 ± 5.78
288.1 ± 171
7.4 ± 0.11
7.42 ± 0.09
7.42 ± 0.1
7.4 ± 0.09
7.4 ± 0.07
7.42 ± 0.08
Bicarbonate
28.87 ± 9.56
30 ± 8.92
31.6 ± 9.2
26.6 ± 7.28
26 ± 6.07
27.77 ± 7.26
Blood lactate
33.6 ± 20.5
33.35 ± 21.7
28.5 ± 20.83
27.23 ± 8.4
24.42 ± 8
27.66 ± 12.11
32
Critical Care 1999, Vol 3 suppl 1
Age, SAPSII in first 24 h, alkaline phosphatase, lactate dehydrogenase, blood lactate, pH, bicarbonate, leukocytes, and platelets
were evaluated in all patients the 3 days preceding fungal documentation. We compared biochemical and haematologic results in
group 1 and group 2 trying to identify a different profile and evaluated the predictive value of the different parameters. Results are
presented as media and standard deviation. We applied t student
test comparing the two groups and we considered a P < 0.05 to be
significant.
P61
Results: (See Table). We found significant statistical difference
with bicarbonate, and platelet count when comparing the two
groups. We also observed an increasing blood level on alkaline
phosphate in fungemic patients.
Conclusion: In our study, variations on bicarbonate, platelet count
and alkaline phosphatase are predictive of fungemia in previous
colonised patients. However, further observations, analyses, are
needed and perhaps involving larger patient numbers to evaluate
the clinical utility of these findings.
Fluconazole prophylaxis of systemic candida infection in non-neutropenic critically ill patients: a prospective
randomized study
R Parizkova, P Dostal and V Cerny
Department of Anesthesiology and Intensive Care, Charles University, Faculty of Medicine, 500 05 Hradec Kralove, Czech Republic
Crit Care 1999, 3 (suppl 1):P61
Introduction: Systemic candida infection has been associated with
increased morbidity and mortality in patients requiring intensive
care. Fluconazole (F) is the preferred therapy in Candida albicans
infection. The aim of the study was to evaluate effect of daily prophylactic fluconazole administration on the incidence of systemic
candida infection.
Results: Selected results are presented in the Table.
Group F
Group C
APACHE II
23.6 (3.8)
22.6 (4.7)
ICU stay (days)
17.6 (8.9)
11.5 (4.1)
Hospital stay (days)
Ventilatory days
Methods: After institutional approval 38 critically ill patients were
prospectively studied. In 18 patients (group F) presumptive fluconazole therapy after admission was started in daily dose 100 mg
intravenously until discharge or evidence of systemic candida
infection, which was treated using standard dosage. Control group
(C) consisted of 20 patients. Apache II, candida colonization,
selected risk factors for candidemia (central venous and urinary
catheters, parenteral nutrition, corticosteroids therapy, broad-spectrum antibiotics, H2-receptor antagonists), length of ICU and hospital stay, ventilatory days, incidence of candida albicans and non
albicans candida species were recorded. The cultures from
nasopharynx, trachea, urine, stool and blood stream were taken.
Values are expressed as a mean (SD), t-test, Mann Whitney Rank
Sum test, z-test were used for statistical analysis, P < 0.05 was considered significant.
P62
Candida colonization
Candida albicans
Non albicans species
21 (9)
15.7 (6.2)
17.6 (11.9)
11.9 (4.9)
27%
33%
10 (66%)
13 (81%)
5 (33%)
3 (19%)
Conclusion: There were no significant differences in incidence of
candida colonization and proportion of albicans v. non albicans
species between both groups. Hospital and ICU stay and length of
ventilatory support were nonsignificantly longer in group F. Clinical usefulness of early fluconazole prophylaxis needs to be further
evaluated.
Nosocomial candidemia in an Italian tertiary care hospital
R Luzzati, G Todeschini*, G Amalfitano†, F Soldani, M Franchini*, L Lazzarini, A Grassi*, G Perona* and E Concia
Malattie Infettive, *Ematologia, †Microbiologia, Università ed Azienda Ospedaliera di Verona, 37126 Verona, Italy
Crit Care 1999, 3 (suppl 1):P62
In a retrospective ongoing study, the incidence of nosocomial candidemia among patients (pts) admitted to a tertiary-care teaching
hospital (bed capacity 2400; 78 beds for intensive care units,
ICUs) was evaluated together with causative pathogens, potential
risk factors, antifungal treatment, and crude mortality. During the
primary study period (November 1991–October 1994) there were
136 episodes of candidemia occurring in 136 pts (median age 62
years, range 4–96). The overall incidence of candidemia was 11.3
episodes per 10 000 hospital admissions. The underlying diseases
were the following: solid or hematological malignancies (43 pts),
major abdominal surgery (30 pts), cardiovascular diseases (18 pts),
trauma (17 pts), other diseases (28 pts). At the onset of candidemia
67 pts (49%) were located in ICUs, 48 and 21 pts respectively in
surgical and medical wards. C. albicans (83 strains) accounted for
53% of all blood culture Candida isolates. Fifty-three pts (39%)
received adequate antifungal treatment: 16 pts amphotericin-B
and 37 pts fluconazole. The overall crude mortality was 54%. The
number of positive fungal blood cultures (1 culture versus >1
culture) did not influence crude mortality (54% versus 63%). In
addition, the mortality of pts infected by C. albicans (55%) was
similar to that of pts infected by C. non-albicans species (45%).
The mortality of pts located in ICUs (79%) was significantly
higher (P < 0.001) than that of pts in surgical (29%) and medical
wards (33%). Finally, the mortality of pts who did not receive adequate antifungal therapy (70%) was significantly higher (P < 0.001)
than that of treated pts (30%). In conclusion, the incidence of
nosocomial candidemia was high during the primary phase of the
study; most of our pts with candidemia had severe underlying diseases and were hospitalized in ICUs. The number of fungal positive blood cultures did not influence the crude mortality,
confirming that a single bood culture shuld not be dismissed as
benign transient candidemia. On the contrary, about two-third of
our pts did not receive an adequate antifungal treatment and the
majority of them died.
Poster abstracts
P63
33
Herpes simplex and intensive care medicine: an underestimated problem?
K Camps*, PG Jorens†, HE Demey†, H Coen‡, SR Pattyn*, H Goossens* and M Ieven*
From the Depts of *Microbiology, †Intensive Care Medicine and ‡Radiology, University Hospital of Antwerp, Wilrijkstraat 10, B-2650 Edegem, Belgium
Crit Care 1999, 3 (suppl 1):P63
Herpes Simplex Virus (HSV) infection may cause different disorders in patients hospitalized in intensive care. Bronchoalveolar
lavage (BAL) is a procedure performed almost as a routine in
patients with unexplained respiratory insufficiency in our department. During the last 10 years, HSV has been isolated frequently
from the respiratory tract at our 30 beds intensive care unit. The
objectives of this retrospective study were to define risk factors of
the population in whom HSV virus was isolated.
The study concerned patients with an isolation of HSV from
either bronchial aspiration (BA) or BAL in the past 5 years
(1992–1997). HSV was isolated by culture on shell vials and identified by immunofluorescence after staining with monoclonal antibodies or by the conventional culture and cytopathogenic effect
on Vero-cells. From the 64 cases observed, 47 HSV isolations originated from BA, 13 from BAL (of which 9 with simultaneously
negative BA) and 4 from both BA and BAL. The mean age of the
patients was 62 years (range from 16 to 82). Only 50% of the
patients had fever at the time of the investigation. The majority of
P64
the patients (94.9%) was intubated before the isolation. The role
of immunosuppression, previously recognized as a risk factor for
herpes infection, was not confirmed in this study: only 20.4% had
received either corticosteroids or immunosuppressive agents.
Striking is that 73.4% had undergone a surgical procedure before
the isolation, mainly coronary bypass grafting or other thoracic
operations. Daily chest X-rays from 2 days before till 2 days after
virus isolation were reviewed blindly by the same radiologist.
There was no pathognomonic image at the chest X-ray: a localized
infiltrate resembling pneumonia, diffuse alveolar infiltrates or an
interstitial pattern were observed and 14% of the chest X-rays
were even defined as normal. Lung injury was severe: almost 60%
had a PaO2/FiO2 less than 200. 28 patients received aciclovir
therapy once herpes was isolated, without an effect on the
outcome: 48.4% of all patients and 42.8% of those receiving aciclovir therapy (28) died.
Isolation of HSV in respiratory samples from critically ill patients
is therefore more frequent than previously known. Whether these
isolates contribute to illness and its evolution remains to be determined.
Preliminary validation of new prognostic scoring system in patients with invasive meningococcal disease
E Kasal, I Chytra, V Štruncová* and M Bílek†
Dept. of Anaesthesiology and Intensive Care, *Dept. of Infectious Diseases, †Center of the Quality of Care, Charles University Hospital Pilsen, Dr.Beneše
13, 305 99 Pilsen, Czech Republic. Tel.+Fax: 420 19 277531. E-mail: Kasal@fnplzen.cz
Crit Care 1999, 3 (suppl 1):P64
Introduction: Invasive meningococcal disease (IMD) caused by an
invasive strain of Neisseria meningitidis group C:2a:P1,2,P1,5 and
lately by an invasive strain group B:2a:P1,2 as well appeared in the
Czech republic in 1993 and completely changed severity of the
disease. Incidence and severity of the disease in the West
Bohemian region is the highest in our country. We have published
preliminary results of our several studies of prediction factors of
this disease. Haemocoagulopathy seemed to be of great and reliable prediction value. Fibrinogen, Quick, platelets and AT III.
were found as the most reliable factors in patients treated in the
interdisciplinary ICU.
Purpose of the study: Prospectively to develop and preliminarily
validate a model for the probability of hospital death in patients
with meningococcal invasive disease.
Methods: Defined continuous variables (fibrinogen, Quick,
platelets and AT III) and categorical variable (survival) were collected. A preliminary model was developed on the base of 82
patients data. Logistic regression was used for the development of
the model, which was evaluated by the receiver operating characteristic (ROC) analysis. The mortality rate preliminary validation
as the outcome was studied.
Studied group characteristics: Unlike previous studies we studied
now the group of patients with IMD treated in the whole West
Bohemian region. Six patients from total number of 88 patients
were excluded from the study due to incomplete data (n = 82).
Age-median
12 years
Male:female ratio
39:43
Niklasson-median
3
Mortality rate
14.6% (12)
Fibrinogen-median
Quick-median
Platelets-median
AT III-median
2.6 g/l
50%
139 × 1012/l
60.5%
Results:
(1) Logistic regression model has validity coefficient = 0.469:
P(Death=1)= 1/(1+EXP(Σβ0 + βiXi))
(2) Receiver operating characteristic for logistic model – ROC
report: (see Table overleaf).
Set up of optimal value of P(Death=1) by logistic regression
model was based on minimal number of the false death predictions (C) along with maximum correct death predictions (A),
(D=survival prediction, B=false death prediction). We looked up
in ROC report the value of P(Death=1) with maximum ratio
between sensitivity and false positivity. The value P(Death=1)
≥0.256 increased the percentage of correctly classified patients on
the level of 91.46%. The area under the ROC curve is 0.869. By
the substitution to the next equation enables simply calculate the
preliminary validated prediction. Result ≥0.256 means the prediction of the death probability 91.46%.
P(Death=1)= 1/(1+EXP(1.200–0.020×TROMBO–0.448×
QUICK–0.592×ATIII+0.228×FBG))
Reference
1. Kasal E et al.: Acta Anaest Scand 1997, 41 (Suppl 111):354.
34
Critical Care 1999, Vol 3 suppl 1
Response: DEATH
P65
Sens.
False+ Spec.
X: LOG MODEL
A
B
C
D
A/A+C
C/A+C
B/B+D
D/B+C
Cum Area
2.198709E-04
12
69
0
1
1.0000
0.0000
0.9857
0.0143
0.014286
8.559445E-02
11
21
1
49
0.9167
0.0833
0.3000
0.7000
0.671429
.170969
10
8
2
62
0.8333
0.1667
0.1143
0.8857
0.833929
.2563436
10
5
2
65
0.8333
0.1667
0.0714
0.9286
0.869643
.3417182
7
4
5
66
0.5833
0.4167
0.0571
0.9429
0.879762
.4270928
7
4
5
66
0.5833
0.4167
0.0571
0.9429
0.879762
.5124674
4
3
8
67
0.3333
0.6667
0.0429
0.9571
0.886310
.597842
2
3
10
67
0.1667
0.8333
0.0429
0.9571
0.886310
.6832166
2
3
10
67
0.1667
0.8333
0.0429
0.9571
0.886310
A novel explanation for profound shock in meningococcal sepsis
PC Holland, SW Hancock, D Thompson and SW Evans
Department of Paediatrics and Child Health, The Clarendon Wing, Belmont Grove, LS2 9NS, UK. Tel: 0113 3922840;
E-mail: philiph@ulth.northy.nhs.uk
Crit Care 1999, 3 (suppl 1):P65
Background: A principle feature of Gram negative sepsis is the
rapid onset of profound shock. The failure of anti-endotoxin antibodies to produce significant improvement in outcome [1] and the
profound hypocalcaemia we have observed in meningococcal
sepsis led us to re-evaluate the possible aetiologies of shock in
Gram negative infection.
Objective: To test the hypothesis that Gram negative organisms
directly or indirectly may be capable of proteolytic breakdown of
albumin thus explaining in part the aetiology of shock and
hypocalcaemia seen in severe Gram negative sepsis.
Methods: Urine was collected from patients with severe meningococcal sepsis (11) and from controls including patients admitted to
intensive care (2) and patients with known proteinuria (4). The
urine was dialysed and subjected to polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting with a sheep antihuman albumin antibody.
Albumin was incubated with lipopolysaccharide (LPS) derived
from various Gram negative organisms and the incubates were
subjected to SDS-PAGE to ascertain the presence of albumin
degradation products. Albumin was also incubated with
P66
homogenates of cultured Neisseria meningitidis and again the incubates were subjected to SDS-PAGE.
Results: Multiple albumin fragments were detected in urine collected from patients with meningococcal sepsis. In vitro incubation of human albumin with crude LPS derived from gram
negative organisms and subsequent SDS-PAGE also showed
cleavage of albumin into multiple fragments. Similar in vitro
studies with homogenates of N. meningitidis failed to show evidence of breakdown. No albumin cleavage products were
detected in the urine of control patients.
Conclusion: This study suggests that in meningococcal sepsis
there is release into the circulation of protease(s) which cleave
albumin. We were not able to distinguish whether the protease
action was of exogenous or endogenous origin. This may have profound significance for the treatment of meningococcal sepsis.
Reference
1. The HA-1A Sepsis Study Group: Treatment of gram
negative bacteraemia and septic shock with HA-1A
human monoclonal antibody against endotoxin: a
randomised, double blind placebo-controlled trial. N Engl
J Med 1991, 324:429-436.
Continuous infusion versus intermittent administration of meropenem in critically ill patients: a pilot study
F Thalhammer, F Traunmüller, M Frass, UM Hollenstein, GJ Locker, T Staudinger and H Burgmann
Department of Internal Medicine I, Div. of Infectious Diseases, Waehringer Guertel 18 - 20, A-1090 Vienna, Austria.
E-mail: florian.thalhammer@akh-wien.ac.at
Crit Care 1999, 3 (suppl 1):P66
This prospective crossover study compares the pharmacokinetics
of meropenem administered by continuous infusion with intermittent administration in critically ill patients. Fifteen patients were
randomized to receive meropenem either as a 2 g iv loading dose
followed by a 3 g continuous infusion (CI) over 24 h or as intermit-
tent administration (IA) of 2 g iv every 8 h (q8h). Each regimen
was performed over a period of 2 days followed by a cross over to
the alternative regimen for the same time. Pharmacokinetic
parameters (mean ± SD) of CI included following: concentration at
steady state (CSS) was 11.9 ± 5.0 mg/l, area under the curve (AUC)
was 117.5 ± 12.9 mg/l/h. Maximum and minimum serum concentration of meropenem (Cmax, Cmin) and total meropenem clearance
Poster abstracts
(Cltot) for IA were 110.1 ± 6.9 mg/l, 8.5 ± 1.0 mg/l and 9.4 ± 1.2 l/h,
respectively. The AUC during IA regimen was larger than the
AUC during CI (P < 0.001). In both treatment groups meropenem
serum concentrations remained above the minimal inhibitory concentration for the most important bacterial strains all the time. We
P67
35
conclude that CI of meropenem is equivalent to the IA regimen
and is therefore suitable for treating critically ill patients. Additionally, a CI regimen can save costs of antibiotic therapy as bactericidal serum levels can be achieved with only 50% of the amount
of drug used for IA.
Clearance of meropenem during continuous renal replacement therapy in critically ill patients
F Thalhammer, P Schenk, H Burgmann, UM Hollenstein, K Ratheiser and S Breyer
Department of Internal Medicine I, Div. of Infectious Diseases, Waehringer Guertel 18 - 20, A-1090 Vienna, Austria.
E-mail: florian.thalhammer@akh-wien.ac.at
Crit Care 1999, 3 (suppl 1):P67
Meropenem is a new carbapenem antibiotic with a broad spectrum
of activity against Gram-positive and Gram-negative strains including β-lactamase producers. Thus, it is particularly useful in intensive care patients (pts) with septic complications due to unknown
pathogens. The present study was conducted to evaluate the pharmacokinetic properties of meropenem in nine critically ill patients
treated by continuous venovenous hemofiltration (CVVH).
All pts received one single dose of 1 g meropenem intravenously.
High-flux polysulfone membranes (Diafilter-30, Amicon, Ireland)
were used as dialyzer. Meropenem serum concentrations as well as
filtrate aliquots were determined by high-performance liquid
chromatography.
P68
Peak serum concentrations were 28.1 ± 2.7 µg/ml, trough levels
6.6 ± 1.5 µg/ml after 6 h CVVH. The post-to-pre hemodialysis ratio
was 0.24 ± 0.06, total removal was 35.8 ± 10.1% and the mean difference of meropenem concentration between arterial and venous
line was 23.4 ± 4.9%. The calculated pharmacokinetic parameters
were: half-life 2.3 ± 0.4 h, elimination constant 0.31 ± 0.05 h–1,
AUC 118.0 ± 15.8 mg/l/h and the clearance during CVVH was
49.7 ± 8.3 ml/h. No side effects were seen.
The calculated total daily meropenem requirements in these
patients with acute renal failure and CVVH was 2482 ± 321 mg.
Based upon these data we conclude that patients with severe
infections on CVVH can be treated effectively with 1 g
meropenem every 8 h.
Meropenem clearance by continuous haemofiltration: a comparison of in vivo and in vitro data
LJ Giles, Z Johnson*, GJ Phillips*, JG Davies*, CJ Olliff* and A McLuckie
Directorate of Intensive Care, Guy’s Hospital, St Thomas’ Street, London, SE1 9RT, UK and *School of Pharmacy and Biomolecular Sciences,
University of Brighton, Brighton, BN2 4GJ, UK
Crit Care 1999, 3 (suppl 1):P68
Often a new drug is licensed for use in the critically ill before its
pharmacokinetic profile has been fully described. In particular
information relating to the amount removed by continuous renal
replacement therapies, such as haemofiltration, is sparse. This
relates to the difficulties associated with patient recruitment and
standardisation for in vivo studies. This study describes the
removal of meropenem, a broad spectrum antibiotic, by an in vitro
model of haemofiltration and compares the data with that
obtained in a previous in vivo investigation [1]. The in vitro model
incorporated a polyacrylonitrile membrane (Hospal, Multiflow 60)
employing a blood pump (Hospal BSM22SC) to circulate carrier
fluid (3.5% human albumin solution in Tyrode Ringer) around an
extracorporeal circuit. Ultrafiltration rates were manipulated using
a peristaltic pump attached to the ultrafiltration line. Pre-membrane, post-membrane and ultrafiltration samples were collected
from the model at timed intervals, employing three different UFR
rates. Meropenem concentrations were measured by HPLC and
used to calculate the drugs’ sieving coefficient (S) and filter clearance (FCL), using standard equations [2]. The results were then
compared to values obtained from a previous in vivo study [1]
employing a similar membrane (Hospal, Multiflow 100). A mean
(± SD) S value of 0.99 ± 0.07 (n = 13) was calculated for the in vitro
model for al UFR rates used which compared favourably with a
mean ( ± SD) S of 0.95 ± 0.03 reported during the in vivo study,
involving four patients. A significant linear correlation was seen
between UFR and FCL for both in vitro and in vivo data (r = 0.98,
P < 0.05 and r = 0.90, P < 0.05, respectively). The results of this
study suggest that the in vitro model is capable of providing accurate meropenem filter clearance data. Although further validation
of this model using a range of drugs is required, this preliminary
work suggests that, in the absence of in vivo pharmacokinetic
information, extracorporeal drug clearance determined using an in
vitro model could be used to aid prescribing in patients receiving
haemofiltration.
References
1. Giles TJ, Barber AC, Creed G, Beale RJ, McLuckie A:
Pharmacokinetics of meropenem in intensive care
patients receiving continuous veno-venous
haemofiltration or haemodiafiltration. Crit Care Med (in
press).
2. Bickley SK: Drug dosing during continuous arteriovenous
hemofiltration. Clin Pharm 1988; 7:198–206.
36
P69
Critical Care 1999, Vol 3 suppl 1
Is a single daily dose the correct way to administer ceftriaxone in intensive care patients?
GM Joynt, J Lipman, CD Gomersall, RJ Young, E Wong and T Gin
Department of Anaesthesia and Intensive Care, Chinese University of Hong Kong and Royal Brisbane Hospital, Brisbane
Crit Care 1999, 3 (suppl 1):P69
1000
Plasma ceftriaxone
concentration (mg/l)
Introduction: The bactericidal activity of β-lactam antibiotics on
gram-negative bacilli is related to the time that concentrations of
antibiotic in tissues and plasma exceed a certain threshold. The
effect is maximal and constant at relatively low concentrations
(four times the MIC of the organism). The dosing regime should
maintain these serum levels for the entire dosing interval, as there
is no significant post-antibiotic effect. Pharmacokinetic data from
healthy patients may not be adequate in the critically ill.
100
Objectives: To determine if the current recommended regimen
for ceftriaxone maintains adequate serum concentrations for antibacterial efficacy in critically ill patients.
Methods: We administered ceftriaxone in the maximum recommended dose (2 g daily IV) to 10 intensive care patients without
renal or hepatic failure. Plasma samples were taken at timed intervals over 24 h with a further trough sample taken on day 4. Ceftriaxone concentrations were measured by high performance liquid
chromatography and analysis performed with Kinetica™ (Simed
SA, Creteil, France).
Results: The pharmacokinetics were different to reported data in
healthy subjects. Vd (20.5 l vs 11.1 l) and Cl were increased (2.4 l/h
vs 1.24 l/h), resulting in a similar, but slightly prolonged T1/2 (7.2 h
vs 6.1 h). However, there was large inter-patient variability in drug
P70
Figure 1. Plasma ceftriaxone concentration time curves.
Hatched line at 8 µg/ml. Note three patients with suboptimal levels for 20–40% of the dosing interval.
10
1
0
200
400
600
800
1000
1200
1400
1600
Time (minutes)
concentrations (Fig. 1), and four patients had plasma ceftriaxone
concentrations less than the desired four times MIC (8 µg/ml) of
common gram-negative organisms found in ICUs. On day 4,
trough ceftriaxone concentrations were <8 µg/ml in four patients.
There was no clinical predictor of which patients would have low
plasma concentrations.
Conclusion: Because of large inter-patient variability in critically
ill patients, the recommended dosing regimen for ceftriaxone may
result in sub-optimal tissue concentrations and loss of bactericidal
efficacy in some patients. This may be overcome by more frequent boluses or possibly by continuous infusion.
Pruritus: a clinical sign we can use to detect the vasodilating effect of vancomycin
M Bertolissi and F Bassi
Department of Anesthesia and ICU 2° Azienda Ospedaliera 33100 Udine, Italy
Crit Care 1999, 3 (suppl 1):P70
We observed that the administration of vancomycin (V) is sometimes accompanied by pruritus, a clinical sign which appears a few
minutes after the beginning of V infusion and lasts soon after V
administration has been stopped. Generally it is not associated
with a cutaneous rash. The aim of this study was to evaluate the
hemodynamic behaviour which follows the appearance of pruritus.
phylactic reactions. After ECG, radial artery cannula and pulmonary
artery catheter were put in place, vancomycin (15 mg/kg) was administered by a syringe pump, at a constant rate, over 30 min. The hemodynamic data were collected before the administration of V (time 1),
15 min (time 2) and 30 min (time 3) after the beginning of V infusion,
and 15 min after the administration of V has been stopped (time 4).
The patients were divided into two groups: group A who had pruritus
during V infusion, and group B who did not. Statistical analysis was
performed by ANOVA test, significant for P < 0.05.
Method: We studied 45 patients undergoing elective coronary
surgery. The inclusion criteria consisted of stable hemodynamics
without i.v. cardiovascular drugs, normovolemia and no history of ana-
Results: Group A included 17 patients, group B 28 patients. In
patients of group A SVRI decreased significantly, CI increased
Times
2
1
3
4
MSP
(mmHg)
A
B
85 ± 17
88 ± 18
81 ± 21
88 ± 20
81 ± 18
88 ± 21
84 ± 17
92 ± 20
SVRI
(dynes.s.cm–5.m2)
A
B
2808 ± 577
2654 ± 968
2533 ± 507
2780 ± 1091
2351 ± 602*
2568 ± 889
2559 ± 539
2813 ± 786
CI
(l/min/m2)
A
B
2.34 ± 0.5
2.67 ± 0.6
2.42 ± 0.5
2.56 ± 0.5
2.64 ± 0.5*
2.74 ± 0.6
2.5 ± 0.4
2.58 ± 0.5
HR
(beats/min)
A
B
60 ± 11
65 ± 11
59 ± 11
63 ± 12
60 ± 9
64 ± 12
58 ± 8
62 ± 11
MSP, mean systemic pressure; SVRI, systemic vascular resistance index; CI, cardiac index; HR, heart rate. *P < 0.05 versus time 1.
Poster abstracts
significantly and no change was observed in MAP and HR at time
3 if compared with time 1. In patients of group B the hemodynamic data did not change significantly at the four times of the
study (Table). No patient showed a cutaneous rash throughout the
study.
Discussion: The analysis of our data points out that in patients
who showed pruritus during the administration of vancomycin,
SVRI went down. This vasodilating effect was offset by the
increase in CI. As a result MSP was well maintained. Certainly
this compensation was possible because the patients studied were
P71
37
normovolemic. But we would like to know what would happen if
pruritus appears in patients with hypovolemia? Probably the compensatory mechanism would not be so effective and hypotension
could occur. We conclude that pruritus which follows the administration of vancomycin can be considered an alarm-bell indicating a
condition of peripheral vasodilatation, and must lead us to evaluate the patient in order to detect the hypovolemic state and to
compensate for it before continuing the infusion of vancomycin.
Reference
Wihelm MP: Vancomycin. Mayo Clin Proc 1991, 66:1165-1170.
Acute peritonitis leads to early remote microvascular dysfunction
R Gill, K Donais*, JJ Ryan* and CG Ellis*
Shackleton Department of Anesthetics, SUHT, Tremona Rd, Southampton, SO16 6YD, UK and *Department of Medical Biophysics, UWO, London,
Ontario, Canada N6A 5C1
Crit Care 1999, 3 (suppl 1):P71
Introduction: Remote organ injury, as evidenced by loss of functional capillaries and impaired microvascular function, has been
demonstrated in a resuscitated normotensive 24-h chronic model
of intra-abdominal sepsis [1,2]. Our objective has been to develop
an acute intra-abdominal model of sepsis which can be used to
observe the temporal evolution of this remote microvascular dysfunction.
Methods: Twenty-eight male Sprague Dawley rats were randomised to either sham (SH) laparotomy or modified caecal ligation and perforation (CLP) and divided into three experimental
groups. Haemodynamic variables were monitored for 4-h post
laparotomy in all animals. Group A (n = 8) provided microbiological and haematological data prior to and 4-h post laparotomy.
Group B (n = 10) provided blood lactate data at 4-h post laparotomy. Group C (n = 10) proceeded to intravital microscopy of the
hind limb to asses the effect of acute normotensive sepsis at 1 and
4-h on capillary blood flow in a remote organ.
Conclusion: In this acute model of sepsis remote organ damage
occurs early and is equivalent to that seen at 24 h. Therapies
aimed at MODS prevention need to be commenced at the first
possible opportunity.
References
1. Lam C, et al.: Microvascular perfusion is impaired in the
rat model of normotensive sepsis. J Clin Invest 1994,
94:2077-2083.
2. Gill R, et al.: Oxygen delivery and extraction in the septic
microcirculation. Respir Crit Care Med 1995, 151:A324.
SH 1 h
CLP 1 h
P value by group
SH 4 h
CLP 4 h
P value by group
WBC’s
×109/l
9 ± 1.72
n=4
8.1 ± 1.15
n=4
0.5
6.2 ± 1.83
n=4
2.8 ± 0.18
n=4
0.008
Lactate
mmol/l
–
–
–
1.4 ± 0.4
n=5
2.5 ± 0.7
n=5
0.027
2.5 ± 0.6
n=5
3.4 ± 1.02
n=5
0.3
2.78 ± 0.6
n=5
6.6 ± 1.03
n=5
0.028
CDstop
caps/mm
P72
Results: Data are reported as mean ± SEM. Blood and haemodyanmic data were compared between groups and by time using
ANOVA (SPSS v8.0). Capillary density measurements were analyzed using Repeated Measures ANOVA (SPSS v8.0). Blood cultures from all CLP animals were positive for a combination of E.
coli, Proteus and Bacteroides. There were no differences in haemodynamics or arterial blood gases between CLP or SH animals at different time points. However, there were significant differences in
white blood cell count (WBC’s), blood lactate and stopped capillary
flow (CD stop) density measurements between the groups (Table).
β inhibit nitric oxide synthesis and prevent septic shock?
Does transforming growth factor-β
S Endo, T Kasai, Y Yamada, Y Inoue, S Taniguchi, K Inada*, K Ikeda† and T Ikeda†
Critical Care and Emergency Center, Iwate Medical University, 19-1 Uchimaru, Morioka 020-8505, Japan. *Department of Bacteriology, Iwate
Medical University, 19-1 Uchimaru, Morioka 020-8505, Japan. †Division of Critical Care Medicine Hachioji Medical Center of Tokyo Medical
University, 1163 Tatemachi, Hachioji, Tokyo 193-8639, Japan
Crit Care 1999, 3 (suppl 1):P72
Objective: We measured nitrite/nitrate (NOx) levels and
transforming growth factor beta (TGF-β) levels in septic shock,
and assessed these factors during the onset of shock.
Patients: Twenty-two patients with sepsis not complicated by
shock and 23 patients with septic shock.
Measurements and main results: NOx levels were significantly
higher in the septic shock group than in the sepsis-alone group.
38
Critical Care 1999, Vol 3 suppl 1
NOx levels were significantly higher in the group that died than
in the group that survived. TGF-β levels were significantly
higher in the sepsis-alone group than in the septic shock group.
TGF-β levels were significantly higher in the group that survived than in the group that died. Twenty-one (80.8 %) of the 26
patients with NOx levels of 92.9 µmol/l or more (mean + standard deviation in the sepsis group without shock) had sepsis
complicated by shock, as opposed to only 2 (10.5%) of the 19
patients with NOx levels below 92.9 µmol/l, and the rate of
occurrence of shock as a complication of sepsis was significantly
higher when the NOx level was 92.9 µmol/l or more. Two
(12.5%) of the 16 patients with TGF-β levels of 19.3 ng/ml or
P73
more (mean + standard deviation in the septic shock group) had
sepsis complicated by shock, versus 21 (72.4%) of the 29 patients
with TGF-β levels below 19.3 ng/ml, and the rate of occurrence
of shock as a complication was significantly higher among the
patients with TGF-β levels below 19.3 ng/ml. There was a significant negative correlation between NOx levels and TGF-β
levels.
Conclusion: NO is involved in the pathogenesis of septic shock.
TGF-β appears to inhibit NO production, and may act to prevent
septic shock.
Albumin clearance in the endotoxemic rat after administration of Nω-nitro-L-arginine methyl ester (L-NAME)
K Metcalf and B Lisander
Dept of Anaesthesia and Intensive Care, University hospital, 581 85 Linköping, Sweden
Crit Care 1999, 3 (suppl 1):P73
Introduction: Endotoxin (LPS) is a powerful activator of the
inducible nitric oxide (NO) synthase. Whereas NO seems to be
one factor behind the decreased responsiveness of the circulation
to adrenergic stimulation in septic shock, the role of NO in
increased vascular permeability is less clear. In a former study [1]
we have shown that although NO production increased after LPS
there was no increased extravasation of albumin in a wide variety
of rat tissues examined; on the contrary clearance was decreased in
the entire gastrointestinal tract. In this study tissue extravasation
was examined after administration of the nitric oxide synthase
inhibitor L-NAME.
Methods: Anaesthetised Wistar rats were given E. coli lipopolysaccharide (LPS) 3 mg/kg i.v. and were studied for 5 h. Mean arterial
pressure (MAP) and heart rate (HR) were recorded. As an indicator of NO production methemoglobin (metHb) was measured in
the beginning and end of experiments. 2 h after LPS a bolus of
L-NAME 100 mg/kg, or saline, was given i.v. The tissue clearance
of albumin was studied over the last 2 h of the experiment by
means of a double isotope method [2].
P74
Results: In response to LPS all rats had a drop in MAP. After
administration of L-NAME (n = 7) MAP increased significantly as
compared to controls (n = 8). MetHb increased during experiments
in controls but not in NAME-treated rats. Tissue plasma clearance
for albumin increased in the NAME-group in skin, skeletal
muscle and heart and decreased in testes as compared to controls.
Discussion: We have shown an increased production of NO after
LPS and the dose of L-NAME administered abolished this. No
differences in gastrointestinal albumin clearance were detected
between groups, however in heart, skeletal muscle and skin
albumin extravasation was increased. We conclude that this is
most likely due to changes in regional hemodynamics with locally
increased capillary pressures leading to increased albumin filtration in certain tissues only. In the majority of tissues no differences were found.
References
1. Metcalf K, Sundqvist T, Lisander B: Acta Anaesthesiol Scand
1998, 42:966-973.
2. Åkerström G, Lisander B: Acta Anaesthesiol Scand 1991,
35:257-261.
Loss of erythrocyte deformability during systemic sepsis is prevented by nitric oxide synthase inhibition
RM Bateman, JE Jagger, MD Sharpe* and CG Ellis
Depts. of Medical Biophysics and *Anaesthesia (Program in Critical Medicine), The University of Western Ontario, London Ontario,
Canada, N6A 5C1
Crit Care 1999, 3 (suppl 1):P74
Introduction: ‘Rigid’ red cells in sepsis are thought to play a role
in multiorgan failure by plugging the microvasculature and compromising oxygen delivery. During sepsis endogenous nitric oxide
(NO) production is increased. What effect this has on erythrocyte
deformability (RBCd) is unclear. We report the effects on RBCd
and capillary blood flow when NO overproduction was prevented
in septic rats.
Methods: Acute sepsis was induced in Sprague-Dawley rats via
cecal ligation and perforation (CLP). At 2 h post CLP, aminoguanidine (AG), a selective inducible nitric oxide synthase
inhibitor was infused (i.v. 60 mg/kg/h) to maintain baseline NOx
levels. Capillary blood flow in the EDL skeletal muscle was
filmed using intravital video microscopy. Plasma NOx
(NO2–/NO3–) levels were measured by chemiluminescence and
deformability was assessed by membrane displacement, using the
micropipette aspiration technique.
Results: At 6 h, an increase in plasma NOx of 260% ± 46 SEM in
CLP animals was associated with a 12% ± 1.6 SEM loss in red cell
deformability and a twofold increase in stopped flow capillaries
(P < 0.05, relative to Sham). Infusion of AG prevented the
increase in NOx, the loss of deformability and the increase in
stopped capillary flow, (P < 0.05). In sham rats, AG augmented
RBCd (P < 0.05), but had no effect on stopped flow.
Conclusion: Eliminating nitric oxide overproduction in septic rats
was associated with preventing 1) the loss of red cell deformability
and 2) the increase in stopped capillary blood flow, resulting in the
maintenance of the microvascular circulation.
Poster abstracts
P75
39
Nitric oxide synthase activities in white blood cells of septic patients
M Hersch, JA Scott, G Cepinskas, M Ostermann, S Mehta, DG McCormack and WJ Sibbald
The A.C. Burton Vascular Biology Laboratory, University of Western Ontario, London Health Sciences Centre, London, Canada
Crit Care 1999, 3 (suppl 1):P75
Introduction: The bulk of data that links inducible nitric oxide
synthase (iNOS) activity to the pathophysiology of sepsis originates in animal studies. However, the role of iNOS in human
sepsis is controversial. Therefore, we measured in this pilot study
iNOS activity in inflammatory cells from septic ICU patients compared to normal controls.
Methods: Blood samples from 5 ICU patients with clinically and
bacteriologically documented sepsis, and from four healthy volunteers were centrifuged to separate the plasma/buffy coat. The
buffy coat was layered onto Histopaque 1077 and centrifuged at
400 g to finally isolate white blood cells (WBCs). Constitutive
(cNOS) and iNOS activities were analyzed in WBCs by the [3H]
L-arginine-L-citrulline assay and measured in Units (pmol L-cit-
P76
rulline evolved/min/mg protein). The metabolic end-products of
nitric oxide (nitrite/nitrate; NOx–) were also determined in plasma
from these subjects by chemiluminescence.
Results: Plasma NOx– levels were elevated in septic compared to
control subjects (208 ± 107 vs 26 ± 7 µmol/l, respectively).WBCs from
septic patients exhibited low cNOS activities (0.1 ± 0.1 vs 1.0 ± 0.6
Units for controls). iNOS activity from the septic WBCs was elevated, compared to controls (3.1 ± 1.8 vs 0.5 ± 0.3 Units, respectively).
Conclusion: This pilot data suggests, that consistent with the
plasma accumulation of nitric oxide metabolites, inflammatory
cells of septic humans produce high levels of iNOS compared to
healthy controls while cNOS production is suppressed. These
findings support the theory that iNOS has an important role in the
pathogenesis of human sepsis.
PLA2 antagonists suppress inducible nitric oxide synthase and inducible cyclooxygenase in
lipopolysaccharide-induced Raw264.7 cells
S-H Baek, S-S Yun, H-W Chang*, J-Y Kwak†, J-H Kim and K-B Kwun
College of Medicine, *College of Pharmacy , Yeungnam University, Taegu, 705-717, South Korea, †College of Medicine, Dong-A University, Pusan,
South Korea
Crit Care 1999, 3 (suppl 1):P76
Phospholipase A2 (PLA2) regulates eicosanoids and platelet activating factor production and plays an important role in regulating
critical mediators in inflammatory diseases. PLA2 activity is significantly enhanced during sepsis and multiple organ failure and
therefore offers an intriguing target in developing anti-inflammatory drugs. We have identified several kinds of biflavonoids with
inhibition of PLA2 activity, which are isolated from plant sources,
as potential putative anti-inflammatory and anti-septic agents.
Two of them (bilobetin and ginkgetin) potently inhibit several
kinds of type II 14 kDa PLA2 but exhibits a weaker inhibition of
type I 14 kDa PLA2 using 2-linol-[1-14C]PE as substrate. These
inhibitors have been tested for their ability to inhibit the production of TNF-α and the formation of two enzymes, inducible NO
synthase (iNOS) and inducible cyclooxygenase (COX-2) using
P77
LPS-stimulated Raw264.7 macrophages as assay systems. In the
Raw264.7 cells, bacterial LPS induced the protein of COX-2 and
iNOS as well as TNF-α release. The inhibitors consistently inhibited the production of TNF-α in a dose-dependent manner. The
inhibitory effect of TNF-α was observed at concentrations similar
to those related by PLA2. Moreover, treatment of cells with bilobetin and ginkgetin inhibited nitrite production, one of the stable
end products of NO production measured in culture supernatants.
The inhibition of NO products is caused by decreased iNOS
protein levels as assessed by immunoblotting using a specific antiiNOS antibody. The inhibitors treatment also reduce the expression of COX-2 protein level to about 80% in LPS-stimulated cells,
which coincided with reduction of the iNOS protein. These
results suggest that inhibition of PLA2 and subsequent metabolism of arachidonic acid by COX-2 contribute to LPS-induced
NOS pathway including TNF-α in Raw264.7 cells and these two
inhibitors may develop as useful agents for anti-inflammation.
Fusidin down-regulates the production of IL-6 in septic patients: a pilot study
P Toft, E Tønnesen and K Bendtzen
Department of Anaesthesia and Intensive Care, Aarhus University Hospital, DK-8000, Aarhus C, Institute for Inflammation Research, National
University Hospital, DK-2200 Copenhagen N, Denmark
Crit Care 1999, 3 (suppl 1):P77
Septic shock is characterized by pathophysiological derangements
in the function of multiple organs. Many of the manifestations of
shock have been related to high levels of circulating cytokines.
Fusidic acid is an antiotic with a tetracyclic structure. Its chief
clinical use is in the treatment of staphylococcal infections. It has
been proposed, that the acid form as well as the sodium salt of the
drug (Fusidin) possess antiinflammatory properties.
Aim: The present pilot study was carried out to test the hypothesis that fusidin downregulates the production of pro- and antiinflammatory cytokines in septic patients. The study was
approved by the Regional Ethical Committee and informed
consent was obtained from each patient or a close relative.
Material and methods: Five consecutive septic patients received
fusidin 500 mg × 3 i.v. for 1 day. Blood samples were drawn two
times before fusidin administration, six times during the 24 h
where fusidin was given and 24 h after the last dose. The pro-
40
Critical Care 1999, Vol 3 suppl 1
inflammatory cytokines IL-1a, IL-1b, TNFα and IL-6 and the
antiinflammatory cytokines IL-10 were analysed using ELISA.
Results: Three females and two males were included. age 21–72
years (range). APACHE II score 13–24 (range). Two patients died
in the ICU. No clinical or biochemical side effects were seen in
relation to fusidin administration.
The proinflammatory cytokines IL-1b, TNFα and IL-6 and the
antiinflammatory cytokine IL-10 were detectable in peripheral
blood in al patients while IL-1a was undetectable. Treatment with
P78
fusidin was associated with a decline in plasma concentrations of
IL-6 from 183 (78–293) to 116 (67–406) pg/ml 12 h later (median
values with range) (P < 0.05). No changes occurred in the other
cytokine levels. The measured cytokines were characterized by
large interindividual variations.
Discussion: The results from this pilot study provide further in
vivo evidence for the antiinflammatory properties of fusidin.
Fusidin may be useful in the management of the systemic inflammatory response in septic patients.
α after stimulation with proinflammatory cytokines
Human vascular endothelial cells produce TNF-α
V Ranta, A Orpana*, O Carpén†, U Turpeinen*, O Ylikorkala and L Viinikka*
Departments of Obstetrics and Gynecology, *Clinical Chemistry, and †Pathology, Helsinki University Central Hospital, Haartmaninkatu 2, 00290
Helsinki, Finland. Tel: +358-0-4711; Fax: +358-9-471 4801; E-mail: varpu.ranta@pp.fimnet.fi
Crit Care 1999, 3 (suppl 1):P78
Vascular endothelial cells are one of the main targets of tumor
necrosis factor α (TNF-α) action. We studied whether these cells
are capable of producing TNF-α after stimulation with proinflammatory cytokines and bacterial lipopolysaccharide (LPS).
Human umbilical vein endothelial cells (HUVECs) were incubated with interferon-γ (IFNγ) interleukin β (IL-β), and LPS, or
their different combinations for 2–48 h. TNF-α was measured by
time-resolved immunofluorometric assay. Unstimulated HUVECs
did not produce detectable amounts of TNF-α but IFNγ IL-β
P79
and LPS in combination induced TNF-α production in a timedependent manner. Immunofluorescent staining confirmed that
the TNF-α was synthesized by endothelial cells. IFNγ IL-β or
LPS alone did not induce TNF-α production, whereas IFNγ and
IL-β in combination induced TNF-α production, which was
further increased with LPS. TNF-α messenger-RNA expression
was detected with RT-PCR in stimulated, but not in unstimulated
HUVECs.
Human vascular endothelial cells are capable of producing TNFα after proinflammatory cytokine stimulation, and may therefore
contribute to the increased amount of TNF-α found in states like
cachexia and septic shock.
Cytokine plasma levels during weaning in critically ill patients with sepsis
V Cerny, P Zivny*, P Dostal and R Parizkova
Department of Anesthesiology and Intensive Care, *Dept. of Biochemistry, Charles University, Faculty of Medicine, 50005 Hradec Králové,
Czech Republic
Crit Care 1999, 3 (suppl 1):P79
Introduction: Poor muscle functions play a pivotal role in developing ventilator dependency after long term ventilatory support and
studies have shown that sepsis may be associated with decreased
muscle contractility. The aim of the study was to evaluate plasma
levels of TNF alpha, IL-8 and sIL-2R during ventilatory support
and weaning.
Methods: After institutional approval 40 critically ill patients were
prospectively studied during ventilatory support and weaning,
three patients due to death were excluded. All patients were
weaned according to standard weaning protocol. Blood samples
were drawn daily and collected until analysis. Apache II score,
organ failure score (Goris), sepis organ failure assessment score
(SOFA), ventilatory days and ‘weaning’ days were recorded. After
successful weaning patients were divided in two groups according
to the length of weaning (W): group S (W ≤3 days, n = 15), group L
(W >3 days, n = 22). TNFα, IL-8 and sIL-2R serum levels were
selected and measured at the time of admission (T1), on the last
day of full ventilatory support (T2), on the day when weaning was
started (T3) and on the first day of spontaneous ventilation (T4).
Values are expressed as a mean ± SD (or median and 25th and 75th
percentiles), t-test or Mann Whitney Rank Sum test were used for
statistical analysis (SigmaStat, Jandel Co., USA), P < 0.05 was considered statistically significant.
Results: Total ventilatory and weaning days were 9.6 ± 4.8 resp.
1.7 ± 0.7 in group S and 24.6 ± 11.3 resp. 9.0 ± 3.7 in group L. Selected
results (TNFα and IL-8 in pg/ml) are presented in the Table:
T1
T2
T3
T4
Group S – TNFα
11.6(5.6)
7.72 (7.7)
4.39 (6.1)
0
Group L – TNFα
10.1 (8)
10.8 (5.8)
6.7 (6.0)
6.8 (6.0)*
Group S – IL-8
63.7 (38–81)
35.9 (0–66)
0 (0–30)
0 (0–0)
Group L – IL-8
45.7 (34–67)
62.7 (42–102)**
42.7 (26–56)***
30.5 (0–43)§
TNF – mean (SD), IL-8 – median (25%–75%), *P = 0.002, **P = 0.021, ***P = 0.011, §P = 0.001
Poster abstracts
Discussion: Serum TNFα and IL-8 levels were significantly
higher and persisting in patients with prolonged ventilatory
support. This suggests that these mediators may also be involved
41
in ventilatory failure leading to difficult weaning after long term
mechanical ventilation.
Aknowledgement: Supported by grant IGA MZ CR 3674-3
P80
Cytokines and sepsis
S Marum, JP Ribeiro, E Arranhado*, H Lage*, C Gil, L Mota and MR Silva
Unidade de Cuidados Intensivos, *Lab. de Imunologia/S. Nefrologia, Hospital de Curry Cabral, U.C.I., Rua da Beneficiência, Nº 8, 1050, Lisboa,
Portugal
Crit Care 1999, 3 (suppl 1):P80
Introduction: Being sepsis a clinical syndrome with a very high
mortality rate, this led us to the effort of monitoring some
cytokines as potential diagnostic and prognostic serum markers.
Methods: In 1998 a prospective study was initiated, consisting at
the moment in 24 patients, with diagnostic criteria for SIRS (Systemic Inflammatory Response Syndrome), sepsis and/or MODS
(Multiple Organ Dysfunction Syndrome). The soluble serum
cytokines – TNFα, IL-1β, IL-6, IL-8 and TGF-1β – were measured by a solid phase immunoassay method (RD Systems –
CITOMED PORTUGAL) based on a previously established protocol. The blood samples were immediately separated in aliquots
(3/cytokine) and frozen in sterile tubes at minus 70°C. Every
sample of all the patients were simultaneously analysed for each
cytokine, duplicated and performed by the same technician,
having as references the maximum values of a healthy population.
P81
Results: Amongst the 24 patients studied, 16 presented IL-6
>300 pg/ml. High concentrations of IL-8 and TNFα were also
observed, but these were not uniformly coincident with the
former. Two of these patients survived, being those in whom we
were able to interfere with the cytokine profile. The 7 patients
with SIRS, presented relatively low concentrations of cytokines,
having one of them died. TNFα and IL-8, sometimes in very high
concentrations, do not correlate with any particular organic dysfunction. IL-1β and TGF-1β always presented low values, close to
the detection limits, in all of the patients.
Discussion: The high concentrations of IL-6 (the ‘black smoke’?),
revealed a homogenous correlation with the clinical severity, thus
making it a useful diagnostic and prognostic serum marker. The
rapid knowledge of the cytokine profile is important for intervention in the mechanisms, which lead to multiple organ failure. The
relation of some cytokines with particular organ dysfunction, such
as ARDS and cardiac failure, as well as the influence of presently
known and future anti-cytokine strategies, remains to be evaluated.
The perioperative course of C1-esterase-inhibitor: evidence for an early deficiency
M Cobas Meyer, G Marx, B Vangerow, J Heine, M Leuwer, S Piepenbrock and H Rueckoldt
Dept. of Anaesthesiology, Hannover Medical School, D-30625 Hannover, Germany. Fax: +44-511-532-3642
Crit Care 1999, 3 (suppl 1):P81
Mean ± sd
Objective: Since the extent of complement- and contact-activation and a low functional index of their main inactivator C1esterase-inhibitor (C1-INH) are related to outcome in sepsis, a
relative deficiency of C1-INH might contribute to the development of fatal complications. At present few data on the periperative course of C1-INH plasma levels have been published. In our
study the early perioperative course of C1-INH in relation to the
acute phase protein interleukin-6 (IL-6) was investigated in order
to assess one possible important aspect of the balance between
anti- and proinflammatory mediators.
C1-Inh, functional (%)
105 ± 20
92 ± 20
102 ± 24.7
C1-Inh, antigenic (mg/l)
105 ± 29
87 ± 18
98 ± 28
326 ± 380
192 ± 133
Methods: In 19 consecutive patients undergoing elective oropharynx tumorresection functional C1-INH was measured by chromogenic substrate assay Berichrom® C1-Inactivator, the total
quantity by single radial imunodiffusion assay NOR-Partigen®
and cytokine IL-6 levels by MEDGENIX IL-6-45MIN-EASIA.
Samples were taken before operation (t1), on ICU admission (t2)
and on the first postoperative day (t3).
Results: The mean operation time was 9 h (range: 4:05 to 14:40 h)
and all patients showed an uncomplicated ICU course up to 86 h.
IL-6 (pg/ml)
t1
52 ± 84
t2
t3
IL-6 levels increased from t1 to t2 (P < 0.01), whereas C1-INH
functional levels declined tendencially and antigenic levels
dropped (P = 0.024). Levels of C1-INH at t3 returned to preoperative values and IL-6 declined.
Conclusion: As expected (postoperative agression syndrome) IL-6
increased significantly. Surprisingly, plasma levels of the antiinflammatory acute phase protein C1-INH remained normal or
even declined. On the first postoperative day C1-INH and IL-6
levels tended to return to preoperative values. This was associated
with uncomplicated clinical course. We suggest, that this short
period of disproportion between pro- and anti-inflammatory mediators may increase the ‘second hit’ risk, if it is longer lasting.
42
P82
Critical Care 1999, Vol 3 suppl 1
Changes in serum cytokine levels during induced whole body hyperthermia
O Ahlers, T Boehnke, T Kerner, M Deja, D Keh, J Löffel*, B Hildebrandt*, H Riess*, P Wust P†, D Pappert and H Gerlach
Abteilung für Anästhesiologie und operative Intensivmedizin (GD: Prof. Dr. KJ Falke), *Abteilung für Hämatologie/Onkologie (GD: Prof. Dr. D.
Huhn), †Strahlenklinik und -poliklinik (GD: Prof. Dr. Dr. h.c. R. Felix), Charité, Campus Virchow Klinikum, Humboldt-Universität, 13691 Berlin,
Deutschland
Crit Care 1999, 3 (suppl 1):P82
Results: We found a reversible, significant decrease (P = 0.017) of
IL-2 at 42°C (Fig. 1), whereas the levels of IL-4 and IFN-γ
decreased slightly (data not shown). In contrast, IL-6 showed a
sustained increase (P = 0.008) during and after therapy which
returned to baseline after 20 h (Fig. 2).
50
40
40
30
IL-6 [pg/ml]
IL-2 [pg/ml]
Background: Recent data from our laboratory demonstrated a significant decrease in the number of circulating T helper cells and
monocytes as well as in the expression of IL-2 receptors on T cells
during induced whole body hyperthermia [1,2]. The aim of
further investigations was to analyze the influence of these effects
on the function of TH1 cells, TH2 cells and monocytes. Therefore, we measured the levels of IL-2, IL-4, IL-6 and IFN-γ in the
blood of cancer-patients, undergoing whole body hyperthermia of
42°C. This is used as part of so called ‘systemische KrebsMehrschritt-Therapie’ (sKMT) in our clinic.
Methods: Cytokine levels of 9 patients were measured by an
ELISA technique. Blood samples were obtained before beginning
of therapy at 37°C, at 40°C, at the end of the plateau of 42°C, at
37°C again, as well as after 20 h (on the next morning). Time
between the first four investigations was about 2 h. Cytokine
levels were compared by using a Wilcoxon rank sum test.
30
20
10
20
10
0 (37°C) 2 (40°C) 4 (42°C) 6 (37°C) 20 (37°C)
Timepoints (h)
0
0 (37°C) 2 (40°C) 4 (42°C) 6 (37°C) 20 (37°C)
Timepoints (h)
Figure 1–2. IL-2 (Fig. 1) and IL-6 levels (Fig. 2) during induced whole body hyperthermia. Data are presented as mean-values with SEM.
Conclusion: Despite a similar decrease in the number of both circulating T helper cells and monocytes, there seems to be a different change in the function of these cells during whole body
hyperthermia up to 42°C. IL-2, which is postulated to be mainly
produced in TH1 cells, decreased significantly; IL-4 and IFN-γ,
mainly produced in TH2 cells, decreased slightly and IL-6, one of
the main products of monocytes, showed a significant increase.
Further investigations are necessary to verify these results.
P83
Acknowledgement: Supported by: Deutsche Krebshilfe,
Deutsche Forschungsgemeinschaft (SFB 331, GraKo 273)
References
1. Critical Care 1998, 2 (Suppl. 1):2.
2. BMA 1998, 80 (Suppl. 1):A301.
Influence of mild hypothermia on cytokine gene expression in the culture of human mononuclear cells
S Rußwurm, W Meissner, I Stonans, M Wiederhold, E Stonane* and K Reinhart
Clinics of Anesthesiology and Intensive Care and *Institute of Clinical Immunology, Friedrich-Schiller-University Jena, 07740 Jena, Germany
Crit Care 1999, 3 (suppl 1):P83
Introduction: Clinical studies demonstrated that moderate
hypothermia may improve neurological outcome after severe head
injury. On the other hand hypothermia is associated with
increased incidence of infection complications. Recent studies
suggest that mild hypothermia directly impaires natural host
defenses – leukocyte mobility, phagocytosis and reactive oxygen
species production and antibody production.
Methods: In order to investigate influence of mild hypothermia on
cytokine gene expression human peripheral blood mononuclear
cells (PBMC) were cultivated at normothermic (37°C) and
hypothermic (33°C) conditions (n = 3). Additionaly parallel cultures were stimulated with phytohaemagglutinin (PHA). Multiple
cytokine mRNA expression in the cultures of PBMC was esti-
mated using reverse transcriptase-polymerase chain reaction
(RT-PCR).
Results: Our findings demonstrated that moderate hypothermia
(33°C) did not alter the basic levels of IFN-γ, TNF-α, IL-1α, IL-2
and IL-10 mRNA expression in PBMC, but significantly inhibited
increase in IL-2 mRNA expression caused by PHA stimulation.
Conclusion: These data strongly suggest that cytokine expression
in stimulated human leukocytes can be affected by hypothermia.
IL-2 is one of the key cytokines of immune response. It is known
to stimulate growth and differentiation of T cells, B cells, NK
cells, LAK cells, monocytes and macrophages. Hence, inhibition
of IL-2 mRNA expression in PHA-stimulated PBMC by
hypothermia can partially explain increased risk of infections in
hypothermic patients.
Poster abstracts
P84
43
Influence of temperature during cardiac operations on myocardial apoptosis
M Qing, JF Vazquez-Jimenez, B Klosterhalfen, M Sigler, BJ Messmer, G von Bernuth and M-C Seghaye
Dept of Pediatric Cardiology, Aachen University of Technology, Aachen, Germany
Crit Care 1999, 3 (suppl 1):P84
Objectives: To investigate the influence of temperature (T°)
during cardiopulmonary bypass (CPB) on induction of myocardial
apoptosis.
Methods: Eighteen pigs were assigned to a T° group during CPB:
37°, 28° and 20°C, respectively (n = 6 each). Duration of CPB was
120 min and aortic clamping 60. Cardioplegia was achieved with a
single dose of Bretschneider solution (4°C; 30 ml/kg). TNF-α was
determined by a pig specific ELISA. Six hours post-CPB, tissue
probes of the heart were taken for standard- and immunohistochemistry examinations. Apoptotic cells were detected by an in
situ apoptosis detection kit (TUNEL).
P85
Results: TNF-α production during and after CPB was significantly higher in group 37°C than in group 20°C. There was no
TNFα production in group 28°C. Histological examination
showed that the most important myocardial tissue damage in
terms of intertitial edema, leukostasis and necrosis was seen in
group 37°C followed by group 20°C while the least important
damage was present in group 28°C. There was significantly lesser
degree of apoptosis of myocardial cells in group 37°C than in both
hypothermic groups.
Conclusion: Hypothermia during CPB induces a reduction of the
systemic release of TNFα production and also of myocardial
tissue damage. This could be due to increased apoptosis seen in
the animals operated on in hypothermia. Apoptosis during cardiac
operations could be in part responsible for the protective role of
hypothermia.
Intestinal ischemia and reperfusion: beneficial effects of a platelet activating factor antagonist
R Andersson, Z Sun, X Wang, Å Lasson and A Börjesson
Department of Surgery, Lund University Hospital, S-221 85 Lund, Sweden
Crit Care 1999, 3 (suppl 1):P85
levels of interleukines-1 and 6, plasma protease inhibitors and
intestinal endothelial and epithelial permeability were assesed.
Gut barrier dysfunction in conditions associated with intestinal
ischemia and reperfusion (I/R) might contribute to the further
development of multiple organ dysfunction. The present study
evaluates the effects of platelet activating factor (PAF) antagonist
in intestinal I/R injury.
Results: Intestinal I/R resulted in intestinal barrier dysfunction
with pronounced plasma leakage to the intestinal lumen. A
protely plasma activity was evident. MPO content significantly
increased as did levels of interleukines. Treatment with the PAF
inhibitor partly, though not fully, restored the changes caused by
I/R.
Methods: Intestinal ischemia was induced by clamping of the
superior mesenteric artery for 40 min followed by 12 h reperfusion.
15 min after the end of ischemia, the rats received intraperitoneal
injections of saline or the PAF antagonist lexipafant (5 mg/kg),
repeated after 6 h in the groups subjected to 12 h reperfusion.
Myeloperoxidase (MPO) content in the small intestine, serum
P86
Conclusion: PAF seems involved in the release of cytokines and
consumption of protease inhibitors following intestinal I/R and
the associated impairment of intestinal barrier integrity. Treatment with a PAF antagonist was effective in restoring changes
caused by I/R, though not reaching normal levels.
Platelets and platelet-activating factor acetylhydrolase in septic patients
S Rußwurm, B Dohrn, M Oberhoffer, A Meier-Hellmann, S Krause*, W Lösche* and K Reinhart
Clinic of Anaesthesiology and Intensive Care and *Centre for Vascular Biology and Medicine/Erfurt, Friedrich-Schiller-University of Jena, D-07743
Jena, Germany
Crit Care 1999, 3 (suppl 1):P86
Introduction: Platelet-activating factor (PAF) and its inactivating
enzyme PAF-acetyl-hydrolase (PAF-AH) are implicated in the
development of sepsis and its sequela septic shock. It has been
shown that the administration of rPAF-AH has a beneficial effect
on the outcome of sepsis in animals as well as in humans.
Methods: We measured PAF-AH activity daily in 2586 plasma
samples that were obtained from 240 patients admitted to our
intensive care unit. Patients were screened daily for sepsis according to ACCP/SCCM criteria, and PAF-AH activities were analysed
in relation to severity of sepsis and to whole blood platelet count
as an indicator of platelet activation and consumption.
Results: PAF-AH activity was positively correlated to the severity
of disease, but was proved to be a poor sepsis marker, when compared to others, such as neopterin, TNFα, procalcitonin etc. In
patients with septic shock a low PAF-AH activity
(<2.00 µmol/ml/h) could indicate a high mortality risk. Only 4
patients met these criteria, but all died. Platelet count was highest
in patients with uncomplicateted sepsis, but dropped dramatically
in septic shock. The overall correlation between PAF-AH and
platelet count was relatively poor (r = 0.266), but remarkable differences were observed between patients with PAF-AH activities
<2.00 or >5.00 µmol/ml/h, resp.: 125 (70/112) × 108/ml versus 280
(206/388) × 108/ml; P < 0.0001.
44
Critical Care 1999, Vol 3 suppl 1
No infection
PAF-AH*
(µmol/ml/h)
SIRS
Sepsis
Septic shock
2.41
(1.76/3.24)
2.81
2.90
3.31
(2.06/3.67) (2.32/4.26) (2.12/4.49)
platelet count*
1.69
(1.01/2.78)
(108/ml)
2.20
2.46
1.05
(1.31/3.53) (1.37/3.51) (0.54/127)
Conclusion: Our data provide further evidence that PAF-AH has a
beneficial effect in sepsis and that it can prevent platelet activation and sequestration which is known to contribute to multiple
organ failure.
*Data are given as median with 25th and 75th percentiles.
P87
Hypertonicity induces shedding of L-selectin: a role for p38 activation
S Rizoli, O Rotstein and A Kapus
University of Toronto, 200 Elizabeth St. EN9-232, Toronto-Ontario, Canada, M5G2C4
Crit Care 1999, 3 (suppl 1):P87
Hemorrhagic shock predisposes to adult respiratory distress syndrome, which frequently results in prolonged ICU stay and carries
a 50% mortality. We have previously shown that resuscitation with
hypertonic saline (NaCl 7.5%) attenuates the post-hemorrhage
lung injury by preventing neutrophil (PMN) sequestration. This
beneficial effect was due to multiple effects on PMN function and
included shedding of the PMN adhesion molecule L-selectin.
The aim of the present study was to investigate the signalling
pathway underlying this immunological effect. Isolated human
PMN were treated with either iso (290 mOsm) or hypertonic
(500 mOsm) medium, for up to 2 h. Hypertonicity induced extensive tyrosine phosphorylation in multiple bands. The broad-spectrum inhibitor genistein, abrogated this effect and concomitantly
prevented the hypertonic (HT) shedding of L-selectin (graph). In
order to characterize the tyrosine kinases involved in this process,
we investigated which kinases were phosphorylated upon shrinkage, and then whether pharmacological inhibition prevented
shedding. We found that the non-receptor tyrosine kinases Syk,
Pyk-2 and the Src-family kinase Hck were strongly phosphorylated upon shrinkage. However, PP1, a Src-family inhibitor, prevented their phosphorylation but not the HT shedding of
L-selectin, suggesting that this effect is independent of Src activation. Next, we found that the p38 was activated upon hypertonic
shrinkage in a genistein sensitive but PP1 insensitive way.
Moreover, the inhibition of p38 activation by SB203580 significantly reduced the HT shedding suggesting that p38 is involved
in this process (graph). The LPS- and FMLP-induced shedding of
L-selectin was also abrogated by SB203580. THUS: Hypertonicity
P88
100
*
*
80
*
60
% Lselectin
40
20
0
ISO
HT genist SB
p38 kinase assay
ISO
HT
genist
PP1
induces a unique pattern of tyrosine phosphorylation in human
neutrophils, involving a variety of kinases, most Src-dependent.
However, the hypertonic shedding of L-selectin seems to be selectively coupled to p38 activation. In fact, p38 appears to be a
central mediator of L-selectin shedding induced by various
stimuli. Hypertonicity-induced, p38-mediated L-selectin shedding appears to have an important role in the beneficial immune
modulatory effect of hypertonicity, preventing neutrophil lung
sequestration and cell-mediated tissue damage.
No correlation between serum levels of intercellular adhesion molecules (s-ICAM) and acute renal
dysfunction following coronary-artery bypass grafting (CABG)
J van Zwienen, A Voets, S van Leeuwen, T Hendriks, C Doelman, K Miedema, P van der Starre, M Haalebos, H Bilo
and W van Rooijen-Butjin
Afdeling Intensive Care, LUMC, Postbus 9600, 2300 RC Leiden, Nederland
Crit Care 1999, 3 (suppl 1):P88
Introduction: Acute renal dysfunction is a common postoperative
complication of CABG. Extracorporeal circulation induces an
inflammatory response, causing the release of adhesion molecules
by endothelial cells and leukocytes. These adhesion molecules
are incriminated in the pathophysiology of renal dysfunction, but
their relative importance is unknown. We investigated the relationship between levels of s-ICAM and renal dysfunction following CABG.
Methods and materials: Eighteen consecutive patients undergoing
elective, uncomplicated CABG were included. Exclusion criteria
were: preoperative creatinine clearance <50 ml/min, age >80 years,
hypotension >1 h (MAP <60 mmHg), and congestive heart failure
(NYHA III-IV). s-ICAMs were measured by RIA (in ng/ml); (a)
10 min prior to anaesthesia, (b) 2 min after aortic clamp release, (c)
at admission to ICU, (d) 4, (e) 8, (f) 12, and (g) 16 h postoperatively, and corrected for haemodilution. Serum creatinine levels
(sCr) were measured (a) 10 min prior to anaesthesia, (b) the first,
and (c) third postoperative day, and corrected for haemodilution;
Poster abstracts
renal dysfunction was defined as a rise in sCr of >25% over baseline value. Mean levels of s-ICAM of the group of patients with
(group I) and without (group III) postoperative renal dysfunction
are compared at each time interval. Statistical analysis is performed by Student’s t-test.
Results: Postoperative renal dysfunction is observed in eight
patients. A comparison of mean s-ICAM (in ng/ml) of both groups
is in the Table, differences are not statistically significant.
P89
45
n
A
B
C
D
E
F
G
Group I
8
67.4
53.8
43.9
60.1
81.2
70.8
91.5
Group II
10
68.3
45.8
43.6
54.1
73.4
67.0
84.9
0.71
0.44
0.82
0.77
0.47
0.72
0.94
P value
Conclusion: These results do not support a (major) role for s-ICAM
in the pathophysiology of acute renal dysfunction following CABG.
Procalcitonin is released by human monocytes
S Russwurm, M Wiederhold, I Stonans, M Oberhoffer and K Reinhart
Clinics of Anesthesiology and Intensive Care, Friedrich-Schiller-University Jena, D-07740 Jena, Germany
Crit Care 1999, 3 (suppl 1):P89
Introduction: Procalcitonin (PCT), the precursor of calcitonin, was
recently forwarded as a diagnostic marker of systemic bacterial
infection and sepsis. Previously we have demonstrated that PCT
is expressed in human peripheral blood mononuclear cells
(PBMC). Aim of this study was to estimate wether PCT could be
released by monocytes in culture medium.
Methods: PBMC were prepared from heparinized venous blood
samples from healthy volunteers and septic patients (according to
ACCP/SCCM consensus conference criteria) by density gradient
centrifugation. Monocytes were obtained by differential adhesion
to plastic surface and cultivated for 12 h with or without 10 µg/ml
P90
lipopolysaccharide E. coli B4. Supernatants were analyzed for
PCT content by commercially available Lumitest® kit
(B.R.A.H.M.S, Berlin).
Results: In contrast to monocytes from septic patients, monocytes
from healthy volunteers did not release PCT at detectable levels
(<0.1 ng/ml) under control conditions. LPS-stimulation lead to
readily detectable levels of PCT both in the supernatants of
healthy and septic patient monocyte cultures. In comparison to
monocytes from healty volunteers monocytes from septic patients
released significantly more PCT after LPS stimulation
Conclusion: Our data demonstrate for the first time that PCT can
be released by human monocytes. Furthermore LPS, a key mediator of septic sequelae, can significantly increase the PCT release.
Intracellular distribution pattern of procalcitonin in human monocytes and HepG2 cells
S Rußwurm, M Wiederhold, I Stonans, M Oberhoffer and K Reinhart
Clinics of Anesthesiology and Intensive Care, Friedrich-Schiller-University Jena, D-07740 Jena, Germany
Crit Care 1999, 3 (suppl 1):P90
Introduction: Procalcitonin (PCT), the precursor of calcitonin, was
recently forwarded as a diagnostic marker of systemic bacterial
infection and sepsis. Previously we have demonstrated that PCT
is expressed in human peripheral blood mononuclear cells
(PBMC). Preliminary experiments indicated a PCT expression in
HepG2 cells, too. Because of several homologies with cytoskeletal
elements of PCT amino acids sequence we investigated the basal
expression and distribution pattern of PCT in human monocytes
and HepG2 hepatoma cells.
Methods: PBMC were prepared from heparinized venous blood
samples from healthy volunteers by density gradient centrifugation. Monocytes were obtained by differential adhesion to plastic
surface and cultivated up to 24 h. HepG2 human hepatoma cells
were incubated under standard conditions. For the experiments
cell lysates were used or cellular proteins were divided in cyto-
P91
plasmatic, microtubular, nuclear-microfilamentous, and resulting
pellet fraction. These protein fractions were analyzed by Western
blot using monoclonal anti-calcitonin or anti-katakalcin
(Lumitest®, B.R.A.H.M.S, Berlin) or polyclonal anti-human calcitonin (Natutec, Frankfurt/M.) antibodies. For secondary immunofluorescence cells were fixed and incubated with the same
antibodies used in western blotting.
Results: As verified by Western blotting and secondary immunofluorescence human monocytes and HepG2 hepatoma cells
express PCT in association with cytoskeleton. The content of
PCT seems to be higher in monocytes than in HepG2 cells. No
PCT was found in cytoplasmic fraction.
Conclusion: We demonstrated for the first time an association of
PCT with cytoskeletal components. Because of the high content
of PCT in human monocytes it could be speculated that PCT has
some intracellular physiological function outside systemic inflammation that have not been yet determined.
Downregulation of procalcitonin in mechanicaly ventilated patients
J Gleiß, HJ Düpree, JC Lewejohann, S Lewejohann and H-P Bruch
Medical University Lübeck, Department of Surgery, Ratzeburger Allee 160, 23538 Lübeck, Germany. Tel: 0451/5002001; Fax: 0451/5002026;
E-mail: JLewejohann @t-online.de
Crit Care 1999, 3 (suppl 1):P91
Introduction: Procalcitonin (PCT) has recently attracted attention
as a possible marker of the systemic inflammatory response to
46
Critical Care 1999, Vol 3 suppl 1
infection. Downregulation of PCT in healthy human subjects
after repetitive injection of endotoxin has been published. This
effect was not investigated in critical ill patients so far.
Methods: We obtained serum levels of Procalcitonin (PCT) in 14
consecutive patients with long term mechanical ventilation
(30–150 days (65.0 ± 2.6 [Mean ± SEM])). All patients experienced
at least two severe systemic infections. Conventional markers of
infection (C-reactive proteine, fibrinogen, white blood cell count
and body temperature) as well as microbiological screening was
performed simultaneously.
Results: A marked rise of PCT over 2.0 ng/ml could be observed
in 7 patients (group 1) in response to severe infection. On admission on ICU these patients presented PCT serum levels between
0.24 and 25.4 ng/ml (6.8 ± 1.3 [Mean ± SEM]). The remaining 7
P92
patients (group 2) had PCT levels between 1.1 and 147.6 ng/ml
(17.5 ± 7.4 [Mean ± SEM]) on admission. Recurrent microbiologically and clinically proved severe infections were not accompanied
by increased levels of PCT. The mortality in group 1 was significantly lower than in the second group (43% vs. 100%) [P < 0.05,
Chi-Square-Test].
Conclusions: Our data suggest a downregulation of PCT levels in
critically ill patients. Lacking rise of PCT serum levels with recurrent severe infections seems to be associated with high mortality.
The predictive value of PCT for severe infections might be
impaired by this mechanism. Further studies are required to
verify these findings and to explain the potential reasons for
failure of PCT in detection of recurrent infections of some
patients in ICU.
Procalcitonin is a good marker for the diagnosis of infection and the severity of illness in patients with SIRS
S Endo, T Kasai, S Koike, Y Yamada, Y Inoue, S Taniguchi, K Inada*, K Ikeda† and T Ikeda†
Critical Care and Emergency Center, Iwate Medical University, 19-1 Uchimaru, Morioka 020-8505, Japan. *Dept. of Bacteriology, Iwate Medical
University, 19-1 Uchimaru, Morioka 020-8505, Japan. †Div. of Critical Care Medicine Hachioji Medical Center of Tokyo Medical University, 1163
Tatemachi, Hachioji, Tokyo 193-8639, Japan
Crit Care 1999, 3 (suppl 1):P92
To understand the presence or absence of bacterial infection in
patients with systemic inflammatory response syndrome (SIRS),
the level of procalcitonin (PCT), a precursor of calcitonin, was
determined. Subjects consisted of 14 SIRS patients without complication by bacterial infection, 14 SIRS patients complicated by
sepsis, and 14 SIRS patients complicated by severe sepsis and
septic shock. PCT levels in SIRS patients with sepsis
(2.9 ± 2.3 ng/ml) were significantly higher than those in SIRS
patients without complication by infection (0.7 ± 1.1 ng/ml).
P93
However, there were no significant differences in the levels of Creactive protein (CRP), interleukin 6 (IL-6) or tumor necrosis
factor-α (TNF-α) between the two groups. PCT levels in SIRS
patients with severe sepsis and septic shock (172.2 ± 276.3 ng/ml)
were significantly higher than those in SIRS patients with sepsis.
Levels of CRP, IL-6 and TNF-α were also significantly higher in
the patients with sepsis compared to those in patients with local
infection. Significant correlations were observed between the
levels of PCT and those of CRP, IL-6 and TNF-α in SIRS
patients. It was suggested that to measure the levels of procalcitonin in patients with SIRS is useful to diagnose the infection and
severity of illness.
Increased procalcitonin serum levels as predictive parameter of multiple organ failure and outcome in acute
pancreatitis patients
SMA Lobo, RF Meirelles Jr, P Lupino, MD Pires, ML Kuga and G Beolchi
Faculdade de Medicina de S.J.R.P., São Paulo, Brazil
Crit Care 1999, 3 (suppl 1):P93
Introduction: A high serum level of procalcitonin (PCT), an
inflammatory mediator precursor of human calcitonin, has been
detected in patients with inflammatory conditions from bacterial
infection. The formation and release of PCT seems to be a selective induced response to bacterial inflammation or sepsis and it is
sustained during a prolonged period of time compared with other
inflammatory mediators. In relation to this, PCT could be an
important parameter to evaluate patients with AP as systemic
involvement and infectious complications that influence the
antibiotic use, CT scan indication, invasive hemodynamic monitoring, and surgical intervention are frequently.
Patients and methods: A prospective study was undertaken in
patients with diagnosis of AP. The clinical classification was made
according to the Symposium of Atlanta and radiological findings
by Balthazar’s criteria. The presence of infection and multiple
organ failure (MOF) were evaluated in a daily basis until hospital
discharge or death. These findings were correlated with PCT
serum levels that were determined by monoclonal antibodies
(Lumitest; B.R.A.H.M.S. Diagnóstica; Germany). Kruskal-Wallis
and Mann-Whitney tests were used for statistical analysis.
Results: Ten patients presented with mild AP and three with
severe AP that had their PCT level measured in the first 48 h from
admission were enrolled. Only the severe AP patients developed
infection conditions and MOF. The PCT serum levels in mild and
severe AP patients in admission were 0.65 ± 0.29 ng/ml (0.34 ng/ml
to 1.45 ng/ml) and 13.68 ± 12.23 ng/ml (2.5 ng/ml to 26.58 ng/ml),
respectively. The PCT serum levels were higher in severe AP
patients (P = 0.09), when infectious conditions (P = 0.08) and
MOD (P = 0.003) were present. All patients that died had high
PCT serum levels (P = 0.008).
Conclusion: Increased serum PCT levels may be a predictive
parameter of infection and MOF development during AP and correlated with high mortality rate.
Poster abstracts
P94
47
Serum procalcitonin levels in bacterial and viral meningitis
S Schwarz, M Bertram, S Schwab, K Andrassy* and W Hacke
Department of Neurology, University of Heidelberg, INF 400, 69120 Heidelberg, Germany and *Department of Nephrology, University of Heidelberg,
Bergheimerstr. 56a, 69115, Heidelberg, Germany
Crit Care 1999, 3 (suppl 1):P94
Background and objectives: Serum procalcitonin (PCT) levels
increase in invasive bacterial, but not in viral infections. In
patients with meningitis, the initial differential diagnosis of bacterial or viral infection is frequently difficult. The aim of this study
was to test the hypothesis that serum procalcitonin levels are elevated in patients with bacterial meningitis and remain within
normal limits in viral meningitis.
Patients and methods: We prospectively evaluated 30 patients (13
men and 17 women, mean age 52 years), with acute bacterial
(n = 16) or viral (n = 14) meningitis. Upon admission, cerebrospinal
fluid (CSF), serum PCT, C-reactive protein (CRP), white blood
cell (WBC) count, and lactate were analysed. Blood and CSF cultures, CFS Gram stains and serological studies were performed.
Sepsis was categorised according to the Society of Critical Care
Medicine consensus criteria. Outcome was assessed upon discharge using the Glasgow Outcome Scale.
Results: Patients with viral meningitis were younger and had a
shorter hospital stay. Fourteen of 16 patients with bacterial, but
only five of 14 patients with viral meningitis were in a septic condition upon admission. Upon discharge, 12 patients were without
any symptoms, nine patients were moderately, and nine severely
P95
disabled. No patient died.
Upon admission, PCT,
CRP, white blood cell and
CSF leukocyte counts, CSF
protein and lactate were
higher, and the serum/CSF
ratio was lower in patients
with bacterial meningitis as
compared with viral meningitis (P < 0.001). PCT was
the parameter with the
highest specificity (100%)
for bacterial infections but
was false-negative in five
patients
with
bacterial
meningitis (a sensitivity of
69%).
Conclusion: Our results
indicate that PCT is a useful additional parameter to differentiate
bacterial from viral meningitis. In patients with viral meningitis
and even if viral sepsis is present, PCT levels do not increase.
Elevated PCT levels indicate a bacterial origin with high specificity.
Procalcitonin for early diagnosis and differentiation of SIRS, sepsis, severe sepsis and septic shock
FM Brunkhorst, K Wegscheider*, ZF Forycki and R Brunkhorst*
Krankenhaus Neukölln, Abt. Internistische Intensivmedizin und Kardiologie, Rudowerstr. 48, 12351, Berlin, Germany and *Universität Hamburg,
Abt. Biometrie and Statistik, Germany, Medizinische Hochschule Hannover, Abt. Nephrologie, Hannover, Germany
Crit Care 1999, 3 (suppl 1):P95
Objective: To determine the value of procalcitonin (PCT) in the
early diagnosis (and differentiation) of patients with SIRS, sepsis,
severe sepsis and septic shock in comparison to C-reactive protein
(CRP), white blood cell and thrombocyte count, and APACHE-II
score (AP-II).
Design: Prospective cohort study including all consecutive
patients admitted to the ICU with the suspected diagnosis of
infection over a 7-month period.
Patients and methods: One-hundred and eight-five patients were
included, 17 patients with SIRS, 61 with sepsis, 68 with severe
sepsis, and 39 patients with septic shock. CRP, cell counts, AP-II
and PCT were evaluated on the first day after onset of inflammatory symptoms.
P96
Results: PCT values were highest in patients with septic shock
(12.89 ± 4.39 ng/ml; P < 0.05 versus patients with severe sepsis).
Patients with severe sepsis had significantly higher PCT levels
compared to patients with sepsis or SIRS (6.91 ± 3.87 ng/ml versus
0.53 ± 2.9 ng/ml; P < 0.001 and 0.41 ± 3.04 ng/ml; P < 0.001, respectively). AP-II scores did not differ significantly between sepsis,
severe sepsis and SIRS (19.26 ± 1.62, 16.09 ± 2.06 and 17.42 ± 1.72
points, respectively), but was significantly higher in patients with
septic shock (29.27 ± 1.35, P < 0.001 versus patients with severe
sepsis). Neither CRP, cell counts nor the degree of fever showed
significant differences between sepsis and severe sepsis. White
blood cell count and platelet count differed significantly between
severe sepsis and septic shock.
Conclusion: In contrast to AP-II, PCT appears to be a useful early
marker to discriminate between sepsis and severe sepsis.
Influence of extracorporeal circulation on the kinetics of procalcitonin
A-H Kiessling, F Isgro, K-H Tran, Nagel and W Saggau
Heartcenter Ludwigshafen, Clinic for Cardiac Surgery, Bremserstr.73, 67063 Ludwigshafen, Germany
Crit Care 1999, 3 (suppl 1):P96
Subject of the study: There are a number of clinical and laboratory
parameters available for diagnosis of infections. The informative
value postoperatively on the start and course of an infection is,
however, considerably reduced. Extracorporeal circulation provokes a systemic immunological reaction, which shows changes of
all parameters measurable at present. Procalcitonin is a new
48
Critical Care 1999, Vol 3 suppl 1
marker for bacterial and viral infections. The aim of this study was
to evaluate the kinetics of procalcitonin after cardiac surgery using
extracorporeal circulation. In a second phase patients were examined who had a demonstrated postoperative infection. Procalcitonin values should be correlated with the occurrence, course and
intensity of the infection.
Materials and Methods: 39 patients (mean age 66.4 years, 32 men)
with uncomplicated course after ACVB operation were enrolled in
a phase I study. Samples were collected preoperative, in the 1st,
6th and 12th postoperative hours and then every 24 h up to and
including the 5th day. In phase 2, 20 patients (mean age 68.2
years, 10 men) were examined in whom a demonstrable infection
was found postoperatively after cardiac surgery.
Results: Procalcitonin rises significantly within the first 24 h after
extracorporeal circulation. The serum levels measured, however,
P97
are still within the normal range for healthy patients. Standard
infection parameters which are used routinely in clinical situations
show, in contrast, clearly significantly false positive values from
the start of the 6th postoperative hour onwards. The serum values
obtained in phase 2 showed that in some patients (8/20) there was
a significant procalcitonin rise before the occurrence of a clinically
manifest infection. In 3 patients there was no increase in the
serum level, even in the course of the infection.
Conclusion: Procalcitonin is a new parameter that is not influenced by extracorporeal circulation which can be used for the
diagnosis of an early postoperative infection.
A closed system with reduced blood/air activation was used in all
patients. It must be determined in further studies what influence
different perfusion techniques have on the kinetics of procalcitonin.
Delayed neutrophil apoptosis in sepsis is associated with reduced Caspase-3 activity
R Taneja, Y Li, J Parodo and JC Marshall
The Toronto Hospital, Toronto, Ontario, Canada
Crit Care 1999, 3 (suppl 1):P97
and activity was determined spectrophotometrically using a specific substrate (DEVD-AMC).
Apoptosis or programmed cell death is effected through a family
of proteases called caspases. Mature neutrophils undergo spontaneous apoptosis mediated in part by the proapoptotic enzyme
caspase-3. Since circulating neutrophils from patients with sepsis
show delayed apoptosis, we evaluated caspase-3 activity in experimental and clinical sepsis.
Results: Caspase-3 activity was reduced by exposure to LPS and
in sepsis patients (results follow, mean ± SEM). Apoptosis was
stimulated by PDTC in all groups.
Methods: Neutrophils from septic patients and normal controls
were treated with pyrrolidine dithiocarbamate (PDTC), an
inhibitor of NFκB with or without preincubation with LPS. Apoptosis was assessed as propidium iodide uptake by flow cytometry
at 24 h. Caspase-3 expression was determined by western blots
Incubation of neutrophils with PDTC in a separate group of 4 of 6
patients with similar organ dysfunction scores demonstrated no
increase in CPP32 expression at 4 h of in vitro culture.
Conclusion: Caspase-3 activity is reduced in clinical and experimental sepsis. Modulation of effector caspase activity may represent a novel approach to hasten the resolution of an inflammatory
response.
Control
Unstim.
Apoptosis(%)
Caspase-3 activity
35 ± 4.1
17.2 ± 6
LPS
PDTC
Resting
Sepsis
PDTC
Unstim.
61.9 ± 6.7**
15 ± 4.9
59.6 ± 6.2**
4.2 ± 1.7
13.5 ± 2.5
8.8 ± 1.9*
16.5 ± 3.5
6.6 ± 0.8*
PDTC
24.5 ± 4.4**
9 ± 0.9
*P < 0.05(vs. control);** P < 0.05 (vs. no PDTC)
P98
Pan-peritonitis due to intestinal perforation, and efficacy of direct hemoperfusion with polymyxin B
immobilized fiber (PMX-20R)
T Ikeda
Division of Emergency and Critical Care Medicine, Hachioji Medical Center, Tokyo Medical University
Crit Care 1999, 3 (suppl 1):P98
We used PMX-20R in the treatment of 20 septic shock patients
who developed complicated multiple organ failure caused by
intestinal perforation. Extracorporeal circulation was performed
for 120 min with blood flow of 80–120 ml/min. In this treatment,
we assessed the changes of the patient’s hemodynamics and the
levels of cytokine levels (TNF-α, IL-6, IL-1ra and IL-10), soluble
ICAM-1, thrombomodurin, NOx and PAI-1 during and after
hemoperfusion using PMX-20R. Before the treatment, the mean
APACHE-2 score of the 20 patients was 24.3, mean septic severity
score was 46.9, and Goris score was 4.7. Mean arterial BP and
LVSWI after the treatment increased significantly compared to
the values in similar patients who did not receive this treatment,
while our patients showed slight decrease in platelet counts. The
values of the endospecy test (the new PCA method) apparently
declined at the end of PMX treatment. The two inflammatory
cytokines, TNF-α and IL-6, and the anti-inflammatory cytokines,
Poster abstracts
IL-1ra and IL-10, decreased immediately after PMX and at 24 h
after completing PMX. On the other hand, the levels of ICAM-1,
thrombomodurin, NOx did not decline. PAI-1 decreased remarkably at the end of PMX treatment and 24 h after PMX. As a result,
15 of the 20 patients had good prognosis and 5 had a poor progno-
P99
49
sis. Therefore, hemoperfusion with PMX-20R could be a useful
therapeutic measure for patients with septic shock caused by
intestinal perforation, and it is recommended that this treatment
shold be begun as quickly as possible after emergency surgical
treatment.
Antithrombin III (AT III) prevents increased permeability and leukocyte adhesion in response to endotoxin
(LPS) in the microcirculation of rat mesentery
B Leithäuser, J Schumacher, S Lendemans, S Schmidtke, H Tillmanns and FR Matthias
Medical Clinic I, Dept. of Cardiology, Angiology, Justus-Liebig-University, Klinikstrasse 36, 35385 Giessen, Germany
Crit Care 1999, 3 (suppl 1):P99
Background: Clinical trials with substitution of AT III in patients
with sepsis showed a trend towards reduction of mortality and a
positive effect on development and course of multiple organ
failure. The mode of action is under discussion. Recent experimental studies suggest a possible effect on microvascular permeability and endothelial leukocyte adhesion.
Methods: By means of intravital microscopy we investigated the
effect of substitution of AT III on LPS-induced microvascular
leakage and leukocyte adhesion in the rat mesentery. Male CD
rats (300–400 g bw) were used. The animals were infused with
0.5 mg/kg LPS (E. coli O55:B5) over 80 min. Vascular leakage was
detected with FITC-marked rat serum albumin by fluorescence
microscopy and evaluated by grey value analysis with a computer
assisted image processing system. Light microscopy was used to
evaluate the adherence of leukocytes to the vessel wall of postcapillary venules. Two treated groups received 500 U/kg AT III either
20 min prior (pretreatment) or 20 min after (posttreament) the
beginning of LPS-infusion. Groups of animals not infused with
LPS (sham), and infused with LPS ± placebo (albumin), served as
controls. The observation period was 3 h after the beginning of
LPS infusion.
Results: Infusion of LPS led to a significant increase in microvascluar permeability and leukocyte adherence compared to unstimulated controls. Both effects were reduced to the level of
unstimulated controls by substitution of AT III. No significant differences were found between the pretreated or the posttreated
group. Treatment with placebo and LPS showed no difference
compared to the untreated LPS group.
Conclusion: Substitution of AT III, even when it is given after the
inflammatory stimulus, ameliorates vascular leakage and leukocyte adhesion to the vessel wall as a consequence of LPS infusion.
Thus, AT III could improve the microcirculation in the course of a
generalised inflammatory reaction.
P100 Immunomodulation of AT III in septic disease
U Leonhardt, I Lehmann*, U Sack* and L Engelmann
University Leipzig, Medical Clinic I, Department of Intensive Care, *Institute of Immunology, Philipp-Rosenthal-Str. 27, 04103 Leipzig, Germany
Crit Care 1999, 3 (suppl 1):P100
Introduction: Antithrombin III is a physiological inhibitor of
thrombin, a central procoagulatory factor with pleiotropic activities. Decompensated disseminated intravascular coagulation in
septic patients is associated with a rapid consumption of AT III.
Therefore the anti-inflammatory effects of AT III is a main point
of interest in the pathway of sepsis. To determine whether AT III
concentration has beneficial effects on the severity of immunological function in sepsis, the present study investigated the association between AT III and the DR-expression on monocytes.
Methods: AT III concentration, IL-6 and TNF-a were measured
by standard methods in 18 patients with sepsis. Levels of DR
expression on monocytes are analysed flow cytometrically. The
severity of the disease was assessed at the APACHE II-score. The
substitution of antithrombin III (100 IE/h) was performed in
patients with AT III-level <80%.
Results: There was a significant correlation between AT III and
DR-expression on monocytes (P < 0.002). The substitution of AT
III in a standard dose was associated with higher level of DRexpression on monocytes. Also the AT III level shows a linear correlation to IL-6 and TNF-α (P < 0.05; P < 0.03).
Conclusion: The results indicate that the AT III level is not only a
marker of the disseminated intravascular coagulation in septic
patients. Also there is a relationship to the process of inflammation. Higher levels of AT III were associated with a higher amount
of DR-expression. Thus, the study confirmed the effect of AT III
on the immunomodulation.
P101 Effect of antithrombin III (AT) on lipopolysaccharide (LPS)-induced production of tissue factor and
interleukin-6 (IL-6) by human umbilical vein endothelial cells (HUVECs), mononuclear cells (MNCs) and
whole blood
PJ Souter, S Poole, J Römisch* and E Gray
NIBSC, Potters Bar, UK, *Centeon Pharma GmbH, 35002 Marburg, Germany
Crit Care 1999, 3 (suppl 1):P101
During disseminated intravascular coagulation (DIC), the extrinsic tissue factor (TF)-dependent pathway has been implicated as
the dominant route to thrombin generation and the production of
IL-6 has been shown to correlate positively with the severity of
sepsis-induced DIC. Pharmacological doses of AT have been
shown to reduce mortality and morbidity in patients with DIC and
50
Critical Care 1999, Vol 3 suppl 1
there is increasing evidence to suggest that AT possesses antiinflammatory properties in addition to its anticoagulant properties.
In the present study, we have investigated the effect of AT on
LPS-induced TF and IL-6 production in three different in vitro
systems. Citrated whole blood, HUVECs and MNCs were stimulated with LPS for 4–6 h in the presence or absence of AT. TF
activity was estimated by a TF-dependent clotting or chromogenic assay and IL-6 was measured by ELISA. Our results
show a dose-dependent inhibition of TF and IL-6 production by
AT, EC50 – ~36 and 20–35 iu/ml respectively in MNCs and
HUVECs, but ~14 and <10 iu/ml in whole blood. Immuopurifica-
tion experiments confirmed that the inhibitory activity was attributable to the AT and not to components that may have co-purified
with the clinical product. In addition, up to 40 µM of hirudin, a
specific thrombin inhibitor, did not inhibit the production of TF
and IL-6 in either of the three cell systems, suggesting that the
observed inhibition by AT was not due solely to the inhibition of
thrombin. Our investigation has shown that, apart from the inhibition of thrombin and other activated clotting factors, AT may also
down-regulate the cellular expression of proinflammatory
cytokines. Consequently, AT concentrates may have value in the
treatment of sepsis-induced DIC.
P102 tPA–PAI (tissue plasminogen activator–plasminogen activator inhibitor-1 complex) can be a predictive
marker of multiple organ dysfunction syndrome in seriously ill acute patients with glucose intolerance —
analysis under strict blood glucose control by artificial pancreas
M Hoshino, Y Haraguchi*, M Sakai, H Saegusa, K Hayashi, N Horita and H Ohsawa
Department of Intensive and Critical Care Medicine, Tokyo Police Hospital, Fujimi 2-10-41 Chiyoda-ku, Tokyo 102 8161, Japan
and *Tokyo Disaster Medical Center
Crit Care 1999, 3 (suppl 1):P102
Background and purpose: Recently close relationships between
multiple organ dysfunction syndrome (MODS) and coagulopathy,
particularly hypercoagulability, have been reported in seriously ill
acute patients. However, there are few studies suggesting which
parameters related to coagulopathy are most intensively correlated
with MODS, and whether the coagulopathy has a role of the cause
of MODS or is only the result of it.
The purpose of this report is to (1) study whether PAI-1 related
markers including tPA–PAI are parameters related to coagulopathy
closely related to MODS, and (2) analyse whether the coagulopathy
indicated by the elevation of the PAI-1 related markers is the cause
of MODS in seriously ill acute septic patients with glucose intolerance. Patients under strict blood glucose control by artificial pancreas
(AP) were selected in order to sample reliable PAI-1 values because
fluctuation of blood glucose and serum fat levels are believed to
influence the blood levels of PAI-1 related parameters. AP used was
STG-22, manufactured by NIKKISOH corporation in Japan.
Materials: Nine severe septic patients with glucose intolerance
without NIDDM, aged 27–83 years were investigated. Primary diseases were, four patients with hepatobiliary diseases, two with gangrene of lower extremities, two with ARDS, and one with burn.
Analyzed items were (1) regarding to the MODS: MOF score (calculated from the MOF criteria of Japanese Association for Critical
Care Medicine), (2) regarding to glucose intolerance: M value
(mg/kg per min, measured by the euglycemic hyperinsulinemic
glucose clamp method with AP. The clamped blood glucose level
was 80 mg/dl with the insulin infusion rate of 3.36 mU/kg per
min), as reported in the literature, (3) regarding coagulopathy: (i)
DIC (disseminated intravascular coagulation) score calculated
from the DIC criteria of the Ministry of Health and Welfare of
Japan, (ii) PAI-1 related markers (PAI-1 activity, PAI-1 antigen,
and tPA–PAI), (iii) platelet count (PLT), (iv) fibrinogen (Fb), (v)
FDP, (vi) prothrombin time ratio (PT), (vii) TAT, (viii) D-dimer,
(ix) PIC, (x) antithrombin-III (AT-III), (xi) protein-C activity
(PC), (xii) protein-S activity (PS), (4) thrombomodulin (TM) as a
parameter of endothelial cell injury, and (5) serum fat (free fatty
acid, triglyceride, cholesterol).
Results: (1) Mean value of the daily mean blood glucose levels
(BSm), and M values measured within a few days after admission
were 165 ± 42 mg/dl (n = 35) and 7.4 ± 3.6 mg/kg per min (n = 8),
respectively. (2) MOF score was correlated with DIC score (correlation coefficient: 0.86, n = 111), PLT (–0.60, n = 115), tPA–PAI
(0.57, n = 37), TAT (0.49, n = 25), and D-dimer (0.46, n = 25), (3)
DIC score was correlated with PLT (–0.75, n = 111) and TPA–PAI
(0.49, n = 35). (4) tPA–PAI was correlated with PLT (–0.54, n = 38),
PC (–0.54, n = 24), TAT (0.53, n = 24) and Fg (–0.52, n = 35). (5)
TM was correlated with tPA–PAI (0.62, n = 33). (6) There were no
definite relationships between tPA–PAI and BSm, blood insulin
concentration, and serum fat levels. (7) The marked change of
tPA–PAI levels apparently preceded those of MOF score in three
out of eight patients and were parallel to them in four out of eight.
Interpretation and conclusions: Several important relationships
between tPA–PAI and DIC, hypercoagulability, endothelial cell
injury, and MODS became evident. These analyses were thought
to be possible because strict blood glucose control was performed
by using AP. The degree of MODS correlated with that of DIC
and/or hypercoagulability. Among parameters related to coagulopathy, tPA–PAI was not only a sensitive marker of DIC and
hypercoabulability, but also correlated well with the severity of
MODS and the endothelial cell injury. Moreover, hypercoagulable
state indicated by the elevation of tPA-PAI was thought to be one
of the causes of MODS, and treatment for the hypercoabulability
may be justified as an important method.
P103 Inhibition of endotoxin-induced leukocyte/endothelial cell interaction by antithrombin III
JN Hoffmann, B Vollmar*, D Inthorn, FW Schildberg and MD Menger*
Department of Surgery, Klinikum Großhadern, Ludwig-Maximilians-University Munich, 81377 München and *Department of Clinical and
Experimental Surgery, University of Homburg/Saar, 66421 Homburg, Germany
Crit Care 1999, 3 (suppl 1):P103
Antithrombin III (AT III) is an important inhibitor of thrombin
activity, as well as of many other proteases of the coagulation
system. AT III administration showed beneficial effects on
Poster abstracts
septic multiple organ dysfunction in clinical and experimental
studies. This study investigates the AT III effect on
leukocyte/endothelial cell interaction and microvascular perfusion. In the skin fold preparation of the hamster severe endotoxinemia was induced by repeated administration of endotoxin
(LPS, 2 mg/kg), at t0 = 0 h and t3 = 48 h. AT III (250 U/kg) was
substituted intravenously at t0, t2 = 24 h, and t3 (n = 6 animals, AT
III group). In control animals (n = 5, controls) LPS was given
without AT III substitution. By intravital fluorescence
microscopy (FITC dextrane, rhodamine 6G) venular leukocyte
adherence was determined at t0, t1 = 8 h, t2, t3, t4 = 56 h, and t5 =
72 h. Functional capillary density (FCD) served as a measure of
51
capillary perfusion. AT III resulted in a significant modulation of
LPS-induced leukocyte adherence and in a modulation of the
LPS-induced depression in FCD (P < 0.01, MANOVA). Thus,
the number of sticking leukocytes after induction of endotoxinemia was significantly lower in the AT III group compared with
control animals (AT III: t1 = 182 ± 35 cells/mm2, t2 = 176 ± 21, t3 =
210 ± 51, t4 = 243 ± 48, t5 = 144 ± 29; control: t1 = 630 ± 105, t2 =
465 ± 113, t3 = 404 ± 50, t4 = 542 ± 93, t5 = 356 ± 102; P < 0.05). AT
III downregulated LPS-induced leukocyte/endothelial cell
interaction and prevented the depression in FCD which served
as a measure of capillary perfusion. Both mechanisms may
explain beneficial AT III effects in patients with severe sepsis.
P104 Effects of hydrocortisone stress-dose therapy in septic shock (part I): influence on hemodynamic stability
and plasma nitrite/nitrate levels
D Keh, S Weber-Carstens, T Böhnke, C Schulz, M Pettersson, O Ahlers, S Bercker, A Berg, G Risse*, M Nordman*, K Falke
and H Gerlach
Clinic of Anaesthesiology and Intensive Care Medicine, Charité, Campus Virchow Clinic, Humboldt University, 13691-Berlin, Germany
*Hospital-Pharmacy, Charité, Campus Virchow Clinic
Crit Care 1999, 3 (suppl 1):P104
A renaissance of the ‘glucocorticoid discussion’ emerged during
the last years with reports of ‘stress dose’ or ‘low-dose’ hydrocortisone (HC) replacement therapy in patients with septic shock,
assuming relative adrenal insufficiency, improving hemodynamic
stability, modulating the inflammatory response, and probably
improving outcome [1,2]. Here we present results from an interim
analysis for the first 20 patients enrolled in a double blinded, randomized, placebo controlled, cross-over study to investigate the
effects of HC infusion on 40 patients in septic shock [3] who
needed norepinephrine (NE) for hemodynamic support. Patients
were randomized to receive either HC 10 mg/h after an initial
bolus of 100 mg, or placebo (PL). After 3 days, the medication was
switched, i.e. patients who had HC for the first 3 days received PL
for another 3 days, and vice versa. Plasma nitrite/nitrate (Griess
reaction) was measured before the study and daily for 6 days,
hemodynamic monitoring was performed before and every 8 h
throughout the study period. No differences between the two
group were found for age, sex, cause of sepsis, and severity of
illness at time of study entry established by SAPS II and SOFA.
HC treatment allowed marked reduction of NE infusion within
48 h after study began (Fig. 1). Systemic vascular resistance (SVR)
increased with HC infusion but remained unchanged in the PLgroup during the first study period (Fig. 2). When HC was
switched to the other group, SVR decreased despite increased NE
requirement in patients who received HC before, whereas in the
other group SVR increased and NE could be reduced. Mean arterial blood pressure, but not cardiac index, paralleled changes of
SVR. Plasma nitrite/nitrate decreased with HC infusion, indicating suppression of endogenous nitric oxide (NO) production
(Fig. 3). Interestingly, rebound phenomenon after cessation of HC
was not accompanied by increased nitrite/nitrate concentrations.
Conclusions: In patients with septic shock, stress-dose HC infusion improves hemodynamic stability, reduces NE requirement
and increases SVR. Improvement of SVR may be due to HCinduced suppression of inducible NO synthases (iNOS) and/or
suppression of the synthesis of iNOS stimulating cytokines. Cessation of HC infusion induces rebound effects which seem to be
NO-independent.
Figures 1–3. Norepinephrine administration (1), systemic vascular
resistance (SVR) (2), and plasma nitrite/nitrate concentrations (3)
in patients with septic shock who received stress-dose hydrocortisone (HC) therapy (see text). Day 0: values before study. Triangles,
HC during day 1–3; squares, HC during day 4–6. Note that the
medication was switched on day 3. Data are presented as
mean ± SEM, n = 10 for each data point.
References
1. Bollaert PE, et al.: Crit Care Med 1998; 26:645–650.
2. Briegel J, et al.: Clin Invest 1994; 72:782–787.
3. Bone RC, et al.: Crit Care Med 1992; 20:864–874.
52
Critical Care 1999, Vol 3 suppl 1
P105 Effects of stress-dose hydrocortisone therapy in septic shock (part II): soluble E-selectin and interleukin-6.
Preliminary results of a double blinded, randomized, placebo-controlled cross-over study
S Bercker, O Ahlers, D Keh, M Pettersson, C Schulz, T Böhnke, S Weber-Carstens, A Berg, G Risse*, M Nordmann*, K Falke
and H Gerlach
Clinic for Anesthesiology and Intensive Care Medicine, Charité, Campus Virchow Clinic, Humboldt University, 13691 Berlin, Germany, *HospitalPharmacy, Charité, Campus Virchow Clinic
Crit Care 1999, 3 (suppl 1):P105
Background: E-selectin is a member of the selectin family, i.e. a
transmembrane molecule which is essential for the adherence and
extravasation of leukocytes. E-selectin is expressed by activated
endothelial cells and interacts with circulating neutrophiles. IL-6
is a proinflammatory cytokine, produced by various cell types.
Both markers are elevated in the blood of patients with septic
shock; E-selectin possibly plays a role in permeability alterations
and organ damage, IL-6 is a predictor of outcome and severity.
Stress-dose hydrocortisone improves the clinical situation of
patients in septic shock. In vivo studies could show that corticosteroids inhibit the endothelial expression of adhesion molecules
including E-selectin.
Results: We found a decrease in IL-6 and E-selectin levels under
application of hydrocortisone compared to the placebo group as
well as to the primary values. After switching to placebo, values
increased again.
Conclusion: We could show that stress-dose hydrocortisone given
to patients in septic shock markedly decreases soluble E-selectin
and IL-6 levels. In addition to the hemodynamic effects of this
therapy, there also seems to be an immunmodulating and antiinflammatory effect, which might be organ protective.
14 0 0
1 00
12 0 0
90
E -S electin [ng/m l]
IL -6 [p g /m l]
Methods: As a part of a double blind controlled cross-over study
with stress dose hydrocortisone (10 mg/h) E-selectin and IL-6
levels were monitored for six days in 20 patients with septic
shock. For the first 3 days patients received either hydrocortisone
or placebo as a continuous intravenous infusion, for the next
3 days medication was switched. Blood was taken before starting
and then once every day. Both IL-6 and E-selectin were measured
by an ELISA technique.
10 0 0
800
600
400
200
80
70
60
50
Hydro cortisone
40
day 1- 3
30
0
20
0
1
2
3
4
5
6
Day
day 4- 6
0
1
2
3
4
5
6
D ay
Figures 1–2. IL6 (Fig.1) and E-selectin levels (Fig.2) in septic shock patients, who received hydrocortisone therapy (see text). Day 0: before
study. Data are presented as mean-values with SEM; n = 10 for each data point.
P106 Effects of stress-dose hydrocortisone therapy in septic shock (part III): monocyte HLA-DR expression and
blood interferon-γγ concentration. Preliminary results of a double blinded, randomized, placebo-controlled
cross-over study
T Böhnke, C Schulz, D Keh, M Pettersson, S Weber-Carstens, O Ahlers, S Bercker, A Berg, G Risse*, M Nordmann*, K Falke and H Gerlach
Clinic of Anaesthesiology and Intensive Care Medicine, Charité, Campus Virchow Clinic, Humboldt University, 13691 Berlin, Germany, *Hospital
Pharmacy, Charité, Campus Virchow Clinic
Crit Care 1999, 3 (suppl 1):P106
Background: Immunoparalysis, defined as a decreased level of
human leukocyte antigen (HLA)-DR receptor expression on
monocytes, correlates with the severity of septic shock and
outcome [1].
Hydrocortisone (HC) alters the immune response at almost all
levels and is considered to suppress HLA-DR expression on
monocytes. IFN-γ as a potent activator of mononuclear phagocytes increases the ability of monocytes to express HLA-DR in
vitro and in vivo. One of the aims of our study was to analyze
immunosuppressive effects of HC stress-dose therapy in septic
shock patients. Here we present results of an interim analysis of
the first 20 patients enrolled in the study.
Methods: The study was designed as a double blinded, randomized, cross-over , placebo-controlled trial in 40 patients. Patients
who fulfilled the criteria for septic shock according to the Consensus Conference on Sepsis and Organ Failure [2] received a dose of
10 mg/h hydrocortisone after an initial loading dose of 100 mg, or
placebo for 3 days. After 3 days, patients from the HC-group
switched to the placebo-group and vice versa. Blood samples were
obtained before the study and daily for a period of 6 days. A whole
53
120
80
IFN-gamma [pg/ml]
H L A -D R po s . M o no c y te s ( % )
Poster abstracts
70
60
50
40
100
80
60
H y d r o c o r t is o n e
40
da y 1 - 3
20
30
0
1
2
3
4
5
6
da y 4 - 6
0
1
2
3
4
5
6
D ay
D ay
Figures 1–2. Monocyte HLA-DR expression (Fig. 1) and IFN-gamma concentration (Fig. 2) in septic shock patients who received hydrocortisone therapy (see text). Day 0: before study. Data are presented as mean-values with SEM; n = 10 for each data point.
blood flow-cytometry analysis was performed to analyze monocyte
HLA-DR antigen expression. Plasma IFN-γ levels were measured
by an enzyme-linked immunoassay.
Results: There were no striking differences in monocyte HLADR expression between patients who received HC or placebo
(Fig. 1). However, compared to baseline values, a transient
decrease of HLA-DR expression was observed in the group which
received HC early. INF-γ increased in both groups after start of
the study, but returned to baseline in the placebo-group on day 3
(Fig. 2). In the follow-up, INF-γ did not further increase in the
placebo-group but noticeably in the HC-group.
Conclusion: Stress-dose HC treatment did not induce
immunoparalysis in patients with septic shock during the study
period. HLA-DR expression remained almost constant over the
period of the trial which we postulate to be due to HC-induced
increase of INF-γ synthesis.
References
1. Hershman MJ et al.: Injury 19:263-266.
2. Bone RC et al.: Crit Care Med 1992, 20:864-874.
P107 Sex dimorphism and sepsis: a novel approach
KH Staubach, J Schröder*, F Stüber and P Zabel†
Dept. of Surgery, University of Lübeck and *Kiel, †Forschungszentrum Borstel, Ratzeburger Allee 160, 23538 Lübeck, Germany
Crit Care 1999, 3 (suppl 1):P107
Experimentally it was recently well established that gender differences lead to an increased susceptibility to sepsis in males.
In a prospective clinical study gender differences were evaluated
in patients of a surgical ICU in terms of survival, sex hormones
and cytokine response. Fifty-two critically ill patients (19 females
and 33 males) were included in this study – there was no difference in the characteristics of patients concerning the age, cause of
sepsis and severity of their disease.
Mean age was 55.4 years for females and 53.1 for males. APACHE
II score was 17.3 for females and 18.5 for males at entry of the
study, MOD-score 9.9 versus 10.8 respectively. Biactivity of TNF
and Il-6 were measured for 14 days, as well as Il-10 (ELISA), total
testosteron and 17β-estradiol (RIA).
Though clinical assessment did not reveal any difference, prognosis and outcome of sepsis was significantly different in males and
females: MOD-score was always similar in both groups, however,
hospital mortality was significantly different with 70% (23/33) in
male and 26% (5/19) in female patients (P < 0.01, log-rank test).
Evaluation of cytokine response revealed significantly elevated
TNF levels on day 10 in males (P < 0.05 Mann-Whitney U-test)
while no difference was found for Il-6 levels. Females, however,
displayed enhanced Il-10 levels compared to males from day 1 to
day 10 which reached significant levels of P < 0.05 on day 3 and
day 5. Total testosterone levels were below the normal range for
males and estradiol levels were initially increased both in men and
postmenopausal women with higher levels for women.
Sex dismorphism, as shown, with a significant better prognosis
and outcome of sepsis in women should be considered as a novel
therapeutic approach (testosterone receptor blockade) in sepsis.
P108 The impact of eligibility criteria on enrollment in ICU sepsis clinical trials
D Foster, M Steinberg, D Cook, J Granton and J Marshall
The Toronto Hospital, 200 Elizabeth St. Toronto, Canada M5G 2C4 Tel: 416.340.4770; Fax: 416.340.3632; E-mail:dmfoster1@compuserve.com
Crit Care 1999, 3 (suppl 1):P108
Introduction: Although clinical trials of novel mediator-targeted
compounds in sepsis employ similar entry criteria, exclusion criteria
are variable. We evaluated the impact of variability in such criteria
on recruitment of patients into one of three multi-center studies.
54
Critical Care 1999, Vol 3 suppl 1
Method: We have previously developed a screen log for monitoring eligibility and enrollment of patients into multiple clinical
trials. All patients admitted to the Medical-Surgical Intensive Care
Unit of a large Canadian University affiliated teaching hospital
were screened for study eligibility into one of three multi-center
sepsis trials. The screen log defines patients who meet inclusion
criteria as eligible. Reasons for non-enrollment are divided as
follows: 1, study specific exclusion criteria; 2, hopeless prognosis;
and 3, enrolled in another trial. Truly eligible patients were those
who did not meet above criteria 1–3 and were not enrolled
because informed consent could not be obtained or because the
window of eligibility was missed by study personnel. Recruitment
efficiency was calculated as the proportion of patients enrolled of
those who were truly eligible.
Results: During the 23-month period of screening, 559 patients
were admitted with sepsis or presumed sepsis. The inclusion criteria were met for 273/559 (48.8%) patients in least one of these
three sepsis studies. Only 37/559 (6.6%) were enrolled into a
sepsis trial. The Table contains the number of eligible, excluded
(with reasons for exclusion) and enrolled patients screened for
entry into the three trials.
Eligible (% sepsis)
Study A
(phase III)
Study B
(phase III)
Study C
(phase II)
117 (20.9)
40 (7.1)
116 (20.7)
30 (75.0)
[19]
[8]
[5]
108 (93.1)
[88]
[17]
[3] [3]
10 (25)
8 (6.8)
Excluded (% of eligible) 85 (72.6)
met study specific excl. [48]
hopeless prognosis
[32]
other study
Truly eligible (% eligible)
Enrolled
Recruitment efficiency
32 (27.3)
27
6
4
84%
60%
50%
Conclusion: Within an institution that actively participates in
sepsis clinical trials, only a minority of patients with sepsis are
treated in the context of a trial. The impact of study-specific
exclusion criteria is to create very different study populations.
Such differences may account in part for the discordant results
seen in Phase II and Phase III trials and raise important questions
regarding the external validity of conclusions from trials with low
inclusion or recruitment efficiencies.
P109 Antiarrhythmic effect of interleukin-1 (IL-1) in conjunction with contractile depression
F Schlegel, K Werdan and U Müller-Werdan
Department of Medicine III, Universität Halle-Wittenberg, Ernst-Grube-Strasse 40, D-06097 Halle, Germany. Tel: +49-345-557-4545,
Fax: +49-345-557-4546, E-mail: ursula.mueller-werdan@medizin.uni-halle.de
Crit Care 1999, 3 (suppl 1):P109
While IL-1 is known to be cardiodepressant via the induction of
an inducible nitric oxide synthase (iNOS) and enhanced production of nitric oxide (NO), conflicting results have been reported
regarding its potential to induce or suppress arrhythmias. Here we
report a potent antiarrhythmic effect of IL-1β in conjunction with
an enhanced release of NO.
Methods: Neonatal rat cardiomyocytes (CM) were incubated for
24 h in the absence or presence of IL-1β (100 U/ml) in serum-free
medium. Thereafter, the production of NO was assessed by a NOsensitive microelectrode and the Griess reaction. For testing contractile performance, cells were electrically triggered at constant
pace and monitored continously.
Results: Il-1β (24 h) resulted in a significant increase in the contents of NO, nitrite and lactate (indicative of altered energy
metabolism) in the culture supernatants, which was suppressed by
simultaneous administration of dexamethasone (Dex.) (0.1 µM).
The cardiodepressant IL-1β effect was documented by a lacking
response in pulsation amplitude to the isoproterenol-challenge
(control: n = 20, 148% ± 20 versus IL-1β: n = 27, 103% ± 3*,
P < 0.05), which was preserved by co-incubation with Dex. (control:
n = 21, 131% ± 10 versus IL-1β: n = 27, 130% ± 8). Arrhythmias were
regularly elicited in controls upon α-adrenoceptor-stimulation
(16/17), even if the duration of the electrical pulse was increased to
keep the cells in pace. In contrast, recordings of IL-1β-treated CM
(n = 11) did not display beating irregularity. If, however, Dex. was
added to the incubation medium, arrhythmias occurred both in the
groups without IL-1β (9/11) and with IL-1β (9/10).
Conclusion: A potentially beneficial antiarrhythmic effect of
IL-1β may go along with its cardiodepressant action in vivo.
P110 Decreased beating rate variability of cultured cardiomyocytes by endotoxin
H Schmidt, U Müller-Werdan and K Werdan
Department of Medicine III, Universität Halle-Wittenberg, Ernst-Grube-Strasse 40, D-06097 Halle, Germany. Tel: +49-345-557-4545,
Fax: +49-345-557-4546; E-mail: ursula.mueller-werdan@medizin.uni-halle.de
Crit Care 1999, 3 (suppl 1):P110
A decreased heart rate variability is a marker of autonomic dysfunction and indicates poor prognosis in critically ill patients. In
healthy volunteers, such a decreased heart rate variability can be
reversibly induced by i.v. administration of endotoxin (Crit Care
Med 24:1117-1124). It is unknown if this effect is due to a direct
impact of endotoxin on the heart, or if secondary release products
are responsible herefore. Using isolated, spontaneously contracting neonatal rat cardiomyocytes (CM) we investigated if endotoxin narrows beating rate variability directly.
Methods: CM from three independent preparations were cultured
in serum-free medium with endotoxin (1 µg/ml, 24 h, inducing
inducible nitric oxide synthase and stimulating interleukin-6 production) or without additive. 100 consecutive contractions per cell
Poster abstracts
were analysed (photo-optical system), per preparation 18 control
cells and 18 cells in endotoxin-containing medium.
Parameter
n
Control
Endotoxin
Mean of intervals (ms)
1800
987
852
Results: There was a significant (*P < 0.05) decrease in beating
rate variability in endotoxin-treated CM (Table: data from one
preparation, parameters equivalent to the measures of heart rate
variability in patients).
Standard error of means (ms)
1800
50
39
Median of means (ms)
1800
1025
961
Mean of pNN50
1800
38.9%
21.7%*
Conclusion: Endotoxinemia (e.g. by intestinal translocation) could
in vivo directly contribute to autonomic dysfunction
Median of pNN50
1800
40.0%
15.8%
55
P111 Proinflammatory impact of norepinephrine in cardiomyocytes: increased interleukin-6 production, which is
suppressed by carvedilol
U Müller-Werdan, J Jacoby, H Loppnow and K Werdan
Department of Medicine III, Universität Halle-Wittenberg, Ernst-Grube-Strasse 40, D-06097 Halle, Germany. Tel: +49-345-557-4545;
Fax: +49-345-557-4546; E-mail: ursula.mueller-werdan@medizin.uni-halle.de
Crit Care 1999, 3 (suppl 1):P111
In severe heart failure elevated plasma/serum levels of both norepinephrine and proinflammatory cytokines have been reported.
Several hypotheses have been proposed to explain, why and how
cytokine release is triggered in heart failure, one possible player
being the neurohumoral dysbalance, while other studies suggest an
overspill of cytokines from the failing heart itself. Here we report
that norepinephrine in vitro stimulates the release of interleukin-6
(IL-6) from cardiomyocytes (CM), in keeping with a previously
unrecognized direct proinflammatory effect of norepinephrine on
CM.
Methods: Spontaneously beating neonatal rat CM were incubated
for 8–24 h in serum-free medium supplemented with norepineph-
rine (0.1–1 µM) or without additive, in the absence or presence of
carvedilol (10 µM). In some experiments, an inhibitor of phosphodiesterase was simultaneously added. The adrenergic response
was documented by monitoring beating rate. Inflammation was
assessed by measuring the IL-6 (bioassay) content of culture
supernatants.
Results: In numerous experiments, norepinephrine weakly, but
reproducible enhanced IL-6 release from cultured CM, resulting
in about a doubling of the IL-6 content of culture supernatants
after 24 h. The IL-6 release was more pronounced by simultaneous administration of an inhibitor of phosphodiesterase, but suppressed in the presence of carvedilol.
Conclusion: The release of proinflammatory cytokines in heart
failure may be directly linked to the enhanced sympathetic tone.
P112 Impact of cardiopulmonary-bypass assisted surgery on markers of monocyte function
K Neuhaus, U Müller-Werdan, D Riemann, C Lautenschläger, H-WL Ziegler-Heitbrock*, H-R Zerkowski†, J Langner and K Werdan
Universität Halle-Wittenberg, D-06097 Halle, Germany, Tel.: +49-345-557-4545, Fax: +49-345-557-4546,
E-mail: ursula.mueller-werdan@ medizin.uni-halle.de. *University of Munich, Germany, †University of Basel, Switzerland
Crit Care 1999, 3 (suppl 1):P112
HLA-DR
Day 0
Day 1
Day 5
An APACHE-II-score ≥24 on the 1 po day is a prospectively validated parameter to identify cardiac surgery patients with an escalating ‘post pump’ systemic inflammatory response syndrome at
high risk of multiple organ dysfunction syndrome. We investigated the impact of cardiopulmonary bypass-assisted cardiac
surgery on monocyte markers in a prospectively conducted study
for up to 5 days (group 1: APACHE II ≥24, group 2: APACHE II
<24), compared to septic non-surgical patients (Elebute sepsis
score ≥12, APACHE II score ≥24).
Group 1 1060 ± 505 (n = 24) 403 ± 186 (n = 24) 500 ± 298 (n = 23)
Group 2 1099 ± 525 (n = 5) 380 ± 158 (n = 5) 472 ± 182 (n = 2)
Group 3
483 ± 360 (n = 8) 332 ± 130 (n = 7)
CD 86
(costimulatory)
Day 0
Day 1
Day 5
Group 1 380 ± 325 (n = 24) 353 ± 520 (n = 24) 392 ± 439 (n = 23)
Group 2
630 ± 773 (n = 5)
287 ± 205 (n = 5)
405 ± 98 (n = 2)
Results: HLA-DR: significant fall from day 0 to day 1 (P < 0.05;
generalised linear model), but no significant difference between
groups 1 and 2; CD 86: no significant differences.
Group 3
Mean channel fluorescence (FACS®) ± SD, corrected by isotype
control:
Conclusion: The expression of HLA-DR and CD86 on monocytes
does not allow for an early risk stratification after cardiac surgery.
618 ± 746 (n = 8) 243 ± 175 (n = 7)
56
Critical Care 1999, Vol 3 suppl 1
P113 Cardiac surgery induces increased production of interleukin-10 and lactoferrin
B Adamik*, J Kübler-Kielb†, A Wlaszczyk*†, G Durek*, M Zimecki† and A Kübler*
*Department of Anaesthesiology and Intensive Therapy, Wroclaw University of Medicine, Chalubinskiego 1a, 50-368 Wroclaw, Poland; †Institute of
Immunology and Experimental Therapy, Weigla 12, 53-114 Wroclaw, Poland
Crit Care 1999, 3 (suppl 1):P113
(3) and 48 (4) h after the end of ECC. All measurements were
done in duplicate using ELISA techniques.
Objective of the study: The interaction of blood with nonphysiologic surfaces during cardiac operations with extracorporeal circulation activates leukocytes and endothelial cells with the release
of various systemic inflammatory mediators. The balance of proand anti-inflammatory factors is important in the limitation of
SIRS development. In this study we turned out our attention to
interleukin-10 and lactoferrin (LF) which role in the regulation of
immune response has already been established.
Results: We observed low plasma level of both IL-10 and LF
before the operation and significantly increased during the operations. Postoperatively the concentration of both mediators
decreased to the baseline level.
Study design: Prospective, clinical study approved by the local
Ethical Committee.
Patients: We assessed 24 patients subjected to coronary artery
bypass graft (CABG) operations. ECC time was 90–115 min and
AC time was 70–80 min.
Methods: IL-10 and LF level was measured before the operation
after induction of anaesthesia (1), during surgery (2) and then 24
Time of sampling
IL-10 (pg/ml)
Lactoferrin (ng/ml)
Before the operation
54.2 ± 58.6
297.3 ± 296.7
During ECC
97.3 ± 84.7
1228.8 ± 842.5
24 h after operation
60.0 ± 31.0
315.5 ± 338.8
48 h after operation
39.8 ± 23.6
259.2 ± 213.8
Conclusion: Extracorporeal circulation is associated with the excessive release of IL-10 and lactoferrin and the kinetic of production of
these both factors is very similar. This may suggest that they participate in the limitation of the inflammatory process during ECC.
P114 Cardiopulmonary bypass contributes to less than half of interleukin-6 release post cardiac surgery
R Prondzinsky, A Knüpfer, I Stabenow, F Redling*, D Lehmann†, J Radke†, H-R Zerkowski‡, H Loppnow and K Werdan
Chair of Cardiac Intensive Care at the Department of Internal Medicine III, *Chair of Cardiac Surgery, †Institute of Anesthesiology, Klinikum
Kröllwitz, Martin-Luther University Halle-Wittenberg, Ernst-Grube-Str. 40, D-06097 Halle, Germany; ‡ present address: University of Basel
Crit Care 1999, 3 (suppl 1):P114
Introduction: IL-6 is an important marker for impairment of left
ventricular function. Former studies have shown a significant
release of IL-6 during coronary artery bypass grafting (CABG).
The contribution of cardiopulmonary bypass (CPB) for IL-6release and potential effects on decrease of the left ventricular
function after CABG is still unknown. Therefore we examined
three different types of revascularisation procedures which
allowed us to estimate the CPB induced IL-6 release in CABG.
Methods: 121 patients with coronary artery disease undergoing
coronary revascularisation were examined in following groups: 1)
Elective PTCA without CPB (n = 70), 2) CPB-supported PTCA
(n = 8), 3) CPB-supported coronary artery bypass grafting (CPBCABG; n = 41).
Results: 1) The IL-6 plasma levels increased in all three groups to
a significantly different degree with maximal IL-6 levels between
3 and 24 h after intervention. 2) The levels of the three collectives
were significantly different at 3, 6, and 24 h (Table). 3) The corre-
IL-6 levels in three different groups of revascularisation procedure
PTCA
CPB-PTCA
CPB-CABG
3h
9.5 ± 17.3*†
218.1 ± 158.7*
501.1 ± 305.0
6h
10.8 ± 14.0*‡
192.5 ± 112.0*
508.5 ± 264.5
24 h
14.3 ± 18.2*§
128.6 ± 137.7*
428.6 ± 269.2
*P < 0.001, versus CPB-CABG; †P = 0.01 versus CPB-PTCA;
‡P = 0.008 versus CPB-PTCA; §P = 0.163 versus CPB-PTCA
lation of IL-6 peak levels and duration of CPB was stronger in
CPB-supported PTCA than in CPB-CABG.
Conclusion: The prolonged duration of the CPB may contribute
to the development of a systemic inflammatory response syndrome (SIRS). Reduction of bypass duration or elimination of
CPB, like it is performed in minimally invasive coronary bypass
grafting, may be beneficial for patients and may further reduce the
risk of SIRS.
α are elevated in plasma of patients undergoing
P115 sCD14, IL-6 and TNF-receptors, but not IL-1, IL-8 or TNF-α
high risk coronary angioplasty with cardiopulmonary support
R Prondzinsky, A Knüpfer, I Stabenow, F Redling*, D Lehmann†, J Radke†, H-R Zerkowski‡, H Loppnow and K Werdan
Chair of Cardiac Intensive Care at the Department of Internal Medicine III, *Chair of Cardiac Surgery, †Institute of Anesthesiology, Klinikum
Kröllwitz, Martin-Luther University Halle-Wittenberg, Ernst-Grube-Str. 40, D-06097 Halle, Germany; ‡present address: University of Basel
Crit Care 1999, 3 (suppl 1):P115
Introduction: The cardiopulmonary bypass (CPB) is discussed as a
potential trigger of cytokine release. Here we determined a not
Poster abstracts
investigated spectrum of pro- and antiinflammatory cytokines in
high risk patients undergoing CPB-PTCA.
Methods: Patients with coronary artery disease (n = 3) with a high
risk of coronary intervention according to the ‘National registry for
supported angioplasty, 1994’ undergoing CPB-supported PTCA
were examined. Interleukin 1α (IL-1α), IL-1β, IL-1 receptor
antagonist (IL-1ra), Tumor-necrosis-factor-α (TNF-α), soluble
TNF-Receptors (TNF-R-p55; TNF-R-p75), IL-6, IL-8, IL-10
and soluble CD14 (sCD14) levels were measured in specific commercially available ELISA-Tests.
Results: We detected no significant levels of IL-1α, IL-1β, IL-8
and TNF-α during CPB support. IL-1ra levels were increased.
IL-6 levels increased measurable starting 30 min after begin of
CPB with peak values of 20–60 pg/ml between 3 and 12 h. One
patient showed significant levels of IL-10, this patient expressed
57
the lowest level and shortest kinetic of IL-6 production and more
pronounced TNFα-receptor levels, although TNF-receptor levels
increased in all patients. sCD14 raised continously in all 3 patients
to a maximum of 7 ng/ml followed by a plateau for more than
5 days.
Conclusion: In this study we compared the cytokine levels of
patients undergoing high risk coronary angioplasty with CPBsupport. There were no findings to show a significant relation of
IL-1α, IL-1β, IL-8 and TNF-α to the inflammatory response after
CPB-PTCA – this might be a sign for other mechanisms than systemic activation of monocytes by endotoxin may be involved. IL6 as a marker of the degree of systemic inflammatory reaction
increased significantly. We suggest, the mayor source of this
increase of IL-6 levels is the CPB-support. IL-6 release might be
inhibited by IL-10 production.
P116 tPA-lysis leads to reduced levels of sL-selectin in patients with acute myocardial infarction
H Reschreiter, T Kerner, O Ahlers, M Möckel*, F Klefisch*, M Riehle*, U Frei*, KJ Falke and H Gerlach
Department of Anesthesiology and Intensive Care, Charité Campus Virchow, Humboldt-University, Berlin and *Department of Nephrology and
Intensive Care, Charité Campus Virchow, Humboldt- University, Berlin, Germany
Background: Thrombolysis is still the standard therapy for
patients with acute myo-cardial infarction (AMI). Studies have
demonstrated, that an inflammatory process is induced by the
reopening of the occluded coronary artery. Adhesion of leukocytes
to endothelial cells is the initial event in an inflammatory response
and is mediated by expression of several adhesion molecules (e.g.
selectins), leading to a reperfusion injury.
Methods: 30 patients with AMI underwent treatment with tPA
(n = 10), streptokinase (n = 10) or PTCA (n = 10) within 6 h, respectively. Blood samples were taken immediately prior and 1, 2, 4, 8,
12 and 24 h after treatment, as well as from 10 healthy donors. The
serum levels of soluble L-selectin were measured with a commercially available EIA (R&D Europe). Statistic was performed by
the Mann-Whitney-U-Test.
Results: Patients treated with tPA had significantly reduced levels
of sL-selectin (P = 0.003) compared to healthy donors and to
patients treated with streptokinase or PTCA (P = 0.03), respec-
Mean±SE L-selectin (ng/ml)
Crit Care 1999, 3 (suppl 1):P116
1400
1200
1000
Therapy
l tPA lysis
¨ SK lysis
∆ PTCA
* Healthy
donors
800
600
400
Healthy
donors
0
1
2
4
8
12
24
Time (h) after beginning of therapy
tively. Clinically, tPA-treated patients tended to have more complications and a higher reocclusion-rate, and more additional interventions were necessary.
Conclusion: The reduced circulating sL-selectin levels probably
reflect an inflammatory process and could be a sign of a panendothelial activation in the occluded and then reperfused myocardial area.
α production and myocardial cell
P117 Catheterization of cardiac lymph trunk for evaluation of myocardial TNFα
damage during cardiac operations
JF Vazquez-Jimenez, Ma Qing, OJ Liakopoulos, RG Grabitz, G von Bernuth, BJ Messmer and MC Seghaye
Department of Thoracic and Cardiovascular Surgery and Paediatric Cardiology, RWTH Aachen, Pauwelsstr.30, 52057 Aachen, Germany
Crit Care 1999, 3 (suppl 1):P117
Objectives: To test the hypothesis that the myocardium is a site of
TNFα production and that cardiac lymph is more sensitive than
venous blood from the coronary sinus (CS) to investigate myocardial cell damage related to cardiac operations in an experimental
model.
Methods: In 14 young pigs the efferent cardiac lymph trunk and
CS were cannulated before conventional cardiopulmonary bypass
(CPB); lymph and blood were collected for perioperative TNFα
and troponin I (TnI) measurement.
Results: TNFα was in similar range in cardiac lymph and in CS
before, during and after CPB. There was no significant myocardial
TNFα production related to CPB. TnI concentrations were significantly higher in cardiac lymph than in CS during and after
CPB. A significant elevation of TnI related to CPB occurred in
both cardiac lymph and CS, lymphatic concentrations reaching
100 times venous ones.
58
Critical Care 1999, Vol 3 suppl 1
Conclusion: Our results exclude the myocardium as a major source
of TNFα and indicate myocardial cell damage with loss of important contractile cell proteins during CPB.
The significantly higher TnI concentrations in cardiac lymph
(draining the myocardial interstitium) than in CS imply that determinations of plasmatic concentrations of TnI in the CS leads to
strong underestimation of myocardial cell damage related to
cardiac operations.
P118 Predictors of outcome after primary PTCA for acute myocardial infarction complicated by cardiogenic shock
I Krakau, H Lapp, K Emmerich, G Haltern and H Gülker
Department of Cardiology, Wuppertal Heart Center, University of Witten/Herdecke, Germany
Crit Care 1999, 3 (suppl 1):P118
Direct coronary angioplasty of the infarct related artery is well
accepted as one of most important therapeutic options for cardiogenic shock (CS) complicating acute myocardial infarction (AMI).
However, in-hospital still remains high. The aim of the following
study was to analyse which clinical and procedural factors were
associated with high or low in-hospital mortality when primary
PTCA is applied systematically to all patients with CS within 12 h
of symptom-onset. Patient chararcteristics: n = 78, age 60 ± 14
years, male 67%, primary venticular fibrillation, mechanical ventillation 59%, total branch block 24%.
Procedural data: Single-vessel-disease 41%, ejection fraction
(acute biplane) 0.51 ± 0.16, infarct-related artery: LAD 38%, LCX
8%, RCA 54%; intra-aortic-balloon-pumping 17%, coronary stents
28%, successful angioplasty 87% (TIMI 3, residual stenosis
<50%), in-hospital mortality (0–30 days) 49%. The most important
predictors for a high in-hospital mortality rate were: acute ejection
fraction <40% (P = 0.0035), unsuccessful PTCA (P < 0.05) and
patient age >75 years (P < 0.05). A high in-hospital mortality rate
was also seen in patients requiring mechanical ventillation. Mortality did not depend on the infarct location (inferior versus anterior), patient sex, ventricullar fibrillation or total branch block
prior to intervention, single- or multi-vessel-disease. Furthermore
mortality was independent of the time between onset of symptoms and PTCA and was also not affected by the employment of
coronary stents or intra-aortic balloon conterpulsation.
Conclusion: Systematic primary-PTCA results in a lower in-hospital mortality rate when compared to conservative therapy of AMI
with CS. However, mortality remains extremely high if angioplasty is unsuccesful. But even if myocardial perfusion is able to
be re-established, patients initially requiring mechanical ventillation or with a low acute ejection-fraction as well as the very elderly
>75 years of age maintain a poor prognosis.
P119 The storage-lesion in murine red blood cells: comparison to stored human red blood cells and applications
for an animal model of transfusion efficacy
JE Jagger, I Chin-Yee, CG Ellis and M d’Almeida
Vascular Biology Program, London Health Sciences Centre, and the Department of Medical Biophysics, University of Western Ontario, London,
Ontario, Canada, N6A 5C1
Crit Care 1999, 3 (suppl 1):P119
Introduction: Under storage conditions, red blood cells (RBCs)
undergo significant biochemical and biomechanical changes that
compromise their ability to unload oxygen to the tissues. The clinical benefit of RBC transfusions are, therefore, less than anticipated and may lead to tissue injury rather than improvement. The
development of an animal model is an important step in characterizing the loss of effective oxygen availability and assessing the
efficacy of transfusion therapy. The aim of this study was to determine when stored rat RBCs develop a storage-lesion similar to
human RBCs near the end of their shelf life.
Methods: Human and rat RBCs were collected in CPDA-1,
packed and stored at 4°C for 29 days according to Red Cross standards. ATP and 2,3 DPG concentrations were assessed in rat and
human RBCs during the storage. Biomechanical changes were
assessed by assaying RBC membrane deformability (RBCd) using
the micropipet aspiration technique. Stored RBCs were treated
with a rejuvenation solution to determine the effect on biochemical and biomechanical function.
Results: The storage-induced decline in ATP and 2,3 DPG in
human RBCs were consistent with the literature. These changes,
however, occurred more rapidly in rat RBCs; ATP levels after 7
days of storage declined to the same extent as human RBCs after
4 weeks (40% decrease). DPG levels in rat and human RBCs fell
by 60% and 90% after 7 days of storage. By day 7 of storage the
mean membrane deformability had dropped 45% (P < 0.001).
RBCs exposed to the rejuvenation protocol at day 7 had ATP
levels returned to baseline while the mean RBCd showed almost
complete recovery to baseline levels. Significantly, 12% of the
population of rejuvenated cells still showed compromised membrane deformability (i.e. membrane displacement less than 80% of
baseline).
Conclusion: The biochemical data from this study suggest that rat
RBCs stored for 7 days develop a storage-lesion similar to that of
human RBCs stored for 29 days. Rejuvenation of RBCs improves
RBCd and may be related to improved ATP levels. Using rat
RBCs stored for 7 days gives researchers a valuable tool to assess
blood storage and the consequences on transfusion efficacy and
tissue oxygen availability.
Poster abstracts
59
P120 Systemic inflammation promotes erythrocyte sequestration
O Eichelbrönner, M Christ, AG Mattar, I Chin-Yee, C Martin and WJ Sibbald
A.C. Burton Vascular Biology Laboratory, LHSC, 375 South Street, N6A 4G5, London, Canada
Crit Care 1999, 3 (suppl 1):P120
Introduction: Changes in red blood cell (RBC) flexibility and
membrane surface properties affect their circulatory clearance.
Glutaraldehyde (GLUT) stiffened RBC are cleared by about 70%
within 30 min after transfusion [1]. Recently, we have shown that
endotoxin (ETX) increases RBC adhesion to human vascular
endothelial cells [2]. In this study we investigated the effects of
endotoxin and cecal ligation and perforation induced sepsis (CLP)
on RBC survival and sequestration in healthy and septic rats.
Methods: Groups: Rats were randomized to six groups. Groups
H/N, H/E and H/S were healthy rats (H) receiving naive (N),
endotoxin treated (E) or septic (S) RBC. Groups S/N, S/E and S/S
were septic rats (24 h CLP)(S) receiving naive (N), endotoxin
treated (E) or septic (S) RBC. RBC solutions: Blood was harvested
from healthy or septic (24 h after CLP) donor rats. ETX treated
RBC were prepared by incubating whole rat blood with ETX
(75 µg/ml). RBC and plasma were separated by centrifugation
(15 min, 1000 g). After washing with phosphate buffered saline,
RBCs were labeled with 51Chromium (51Cr) and resuspended in
plasma to the experimental animal’s hematocrit. Infusion of
labeled RBC solution was performed by an isovolemic and simultaneous exchange transfusion. Blood samples were taken after the
exchange transfusion every 5 min for 30 min and in 60 min intervals over 4 h for 51Cr measurements. Organs were harvested for
tissue 51Cr measurements. Cardiac output, body temperature
(TEMP), mean arterial (MAP) and central venous pressure (CVP)
were measured before and 4 h after exchange transfusion.
Results: Infusion of naive, ETX-treated or septic RBC did not
affect cardiac index, TEMP, CVP or MAP in healthy (H/N, H/E,
H/S) or septic rats (S/N, S/E, S/S). The amount of radiolabeled
RBC in the circulation remained unchanged for the first 30 min in
all groups. After 60 min, however, intravascular survival of septic
and ETX treated RBC started to fall in healthy rats and was significantly lower than survival of naive RBC at 240 min. In septic
rats, not only the E and S-RBC but also the naive RBC were
cleared by 15% at 240 min. In healthy animals, sequestration of
transfused S- and E-RBC in liver and spleen was higher than
sequestration of N-RBC. In septic animals, no difference in
sequestration was found between N-, E-, and S-RBC. In skeletal
muscle, lungs, intestine, femur, diaphragm and skin, sequestration
was not different between healthy or septic recipients nor
between the different groups of transfused RBC.
Conclusion: Both ETX and sepsis induced alterations of the RBC
membrane increase RBC clearance. However, the kinetics of
ETX treated or septic RBCs clearance are completely different
from the kinetics of RBC stiffened by GLUT. The majority of the
injured and cleared RBC are entrapped in liver and spleen while
other organ systems play only a minor role. Furthermore, RBC
sequestration also appears to depend on the host’s inflammatory
state indicating RBC-host interactions in the microcirculation
going beyond changes in RBC deformability.
References
1. Simchon S, Kung-Ming J, Chien S: Influence of reduced red
cell deformability on regional blood flow. Am J Physiol
1987, 253:H898-H903.
2. Eichelbrönner O, Sielenkämper, Cepinskas G, Sibbald WJ,
Chin-Yee I: Endotoxin promotes adhesion of human
erythrocytes to human vascular endothelial cells under
conditions of flow (in review process).
P121 Oxygen-ozone treatment improves p50 std value in patients with peripheral vascular disease
R Giunta, C Luongo, C Vicario, A Sammartino, MA Marfella, G Esposito, A Coppola, B Lettieri and L Coppola
Istituto di Anestesia, Analgesia, Rianimazione e Terapia Intensiva, II Università degli Studi di Napoli, Piazza Miraglia 1, 80100 Napoli, Italy
p50 std (mmHg) 2,3 DPG (mmol/l)
Crit Care 1999, 3 (suppl 1):P121
In our previous study [1] we demonstrated that the ozonized autohemotransfusion increases erythrocyte filterability and reduces
plasma and total blood viscosity, thus supporting the theory that
the ozone-induced improvement of peripheral vascular disorders
(PVD) might be related to its influence on the hemorheologic
properties of blood.
Given that oxygen delivery to tissues is dependent on its affinity
for hemoglobin, in the present study we evaluated the effect of
oxygen-ozone treatment on hemoglobin oxygen affinity in 15
patients suffering from PVD (clinical stage IV according to
Fontaine).
Before and 30 min after slow reinfusion of 150 ml of autologous
venous blood exposed in a glass box to an O2–O3 mixture (3.6 mg
of total ozone erogation with a Multiossigen Medical 93 Multi
Tech Milano, Italy) we evaluated hemoglobin oxygen affinity
using p50 STD value. This value is defined as oxygen tension in
mmHg at 50% oxygen saturation, at pH 7.4, at 37°C and at pCO2
Treatment
Before
(ozonized
After
autohemotransfusion)
Control test
Before
(non-ozonized After
autohemotransfusion)
28 ± 0.9
2.5 ± 0.2
32 ± 1.1
2.5 ± 0.3
27.5 ± 1.0
2.5 ± 0.3
28.1 ± 1.1
2.4 ± 0.5
15 Patients paired Student t-test P < 0.005.
40 ± 2 mmHg and is calculated according to the formula:
p50 std = antilog [log p02 (log s02/2.7) – 0.4 (7.4-pH)].
The value of 2,3 diphsophoglycerate (2,3 DPG), an important regulator of oxygen unloading were also evaluated before and after
ozone treatment. Control studies in the same patients were done
in other occasions and random order to test the influence of blood
manipulation (non-ozonized autotransfusion). The results (Table)
show that after ozone treatment, p50 value increased (P < 0.005),
60
Critical Care 1999, Vol 3 suppl 1
whereas plasma value of 2,3 DPG did not significantly change. No
significant changes were induced by control tests (non-ozonized
autohemotransfusions).
These results strengthen the conclusions of our previous ‘in vitro’
study [2] proving that the ozone treatment shifts to right the
oxygen hemoglobin dissociation, ultimately resulting in improved
tissue oxygenation.
References
1. Coppola L, et al.: Oxygen-ozone therapy and
hemorheological parameter in peripheral chronic arterial
occlusive diseases. Tromobosi e Aterosclerosi 1992;
3:83-89.
2. Coppola L, et al.: Influence of ozone and hemoglobin
oxygen affinity in type-2 diabetic patients with peripheral
vascular disease. In-vitro study. Diabete & Metabolismo
1995; 21:252-255.
P122 Sudden cardiac failure following treatment of metabolic alkalosis with hydrochloric acid
J Gleiß, HJ Düpree, JC Lewejohann, S Lewejohann, S Knorr and H-P Bruch
Medical University Lübeck, Department of Surgery, Ratzeburger Allee 160, 23538 Lübeck, Germany. Tel: 0451/5002001; Fax: 0451/5002026;
E-mail: JLewejohann@t-online.de
Crit Care 1999, 3 (suppl 1):P122
Introduction: Severe metabolic alkalosis is a common problem in ICU
due to high gastric reflux, diuretic drugs or parenteral nutrition. The
mortality is considerable. Therapy of severe metabolic alkalosis with
hydrochloric acid is widely accepted and described as save and effective.
Patients: We report five unexplained cases of acute cardiac arrest on our
ICU in 1998 following infusion of hydrochloric acid in mechanically
ventilated patients with severe metabolic alkalosis. Treatment with
HCl (0.2 N, 10–15 ml/h) was commenced at pH 7.55 and BE
+10 mmol/l. All patients suddenly showed a marked fall of oxygen saturation followed by bradycardia, hypotension and cardiac arrest 30 to
140min after onset of HCl-infusion. CPR and high dose adrenalin (up
to 5mg in bolus) showed no effect. Oxygenation could not be
improved by FiO2 1.0. No patient survived the incident. The clinical
aspect suggested a fulminant pulmonary embolism as the most likely
cause of death. Autopsy was performed in three patients. The cause of
death remains unclear. A fulminant pulmonary embolism could be
excluded in these patients.
Age
Underlying disease
Postop.
day
HCl
infusion Infusionperiod
rate
Pat. 1
71
Peritonitis
3
140 min 15 ml/h
Pat. 2
63
Chest wall abscess
15
50 min 15 ml/h
Pat. 3
58
Perforated gastric ulcer
11
70 min 20 ml/h
Pat. 4
50
Empyema of pleural cavity
4
40 min 20 ml/h
Pat. 5
73
Peritonitis
2
30 min 10 ml/h
Conclusions: The therapy of severe metabolic alkalosis with HCl is
suggested to be linked with potentially lethal complications. The
observed and reported cases of death should be considered before
application of HCl in treatment of severe metabolic alkalosis. Further
studies are requested to analyze the reasons for sudden cardiac failure
during HCl-infusion.
P123 Effects of epidural and halothane anaesthesia on vasoconstrictive properties of cell-free haemoglobin
HG Bone, R Waurick, UR Jahn, M Booke, J Meyer and H Van Aken
Dept. of Anaesthesiology, University of Münster, Albert-Schweitzer-Str. 33, 48129 Münster, Germany. Tel:+49(0)2518347258; Fax:+49(0)25188704;
E-mail: bone@uni-muenster.de
Crit Care 1999, 3 (suppl 1):P123
8
Cardiac Index
Methods: Sheep were assigned to three different groups: a) 6 not
anaesthetised sheep, b) 6 sheep with a halothane anaesthesia (2.0
Vol. % in oxygen), c) 6 sheep had an thoracic epidural anaesthesia
with bupivacaine. After a stabilisation period all 18 animals
received an i.v. bolus of 100 mg Pyridoxalated Haemoglobin Polyoxyethylene Conjugate/kg.
Results: The vasoconstrictive effects of a HBOC were similar in
awake sheep and in sheep with epidural anaesthesia. Anaesthesia
7
CI (l/min/m 2 )
Introduction: In the moment haemoglobin based oxygen carries
(HBOC) are under clinical investigation. Only few studies looked
for the interactions between anaesthetic drugs and HBOC. The
effects of HBOC during regional anaesthesia have never been
analysed. Therefore, we investigated the hemodynamic changes
after HBOC infusion during different kinds of anaesthesia.
*
*
6
*
*
90
120
5
4
3
Bl
5
15
Awake
Epidural
30
Minutes
60
Halothane
* = p< 0,05 vs. Bl
Poster abstracts
120
MAP (mmHg)
with halothane reduced the effects on mean arterial pressure and
cardiac index but did not abolish the pulmonary vasoconstriction.
Mean arterial pressure
110
*
100
*
*
*
90
*
*
*
*
*
61
Conclusion: The selection of the anaesthesia method may alter
hemodynamic side effects of HBOC.
*
80
70
PAP (mmHg )
25
Pulmonary artery pressure
20
*
*
*
*
*
*
*
15
Awake
10
Epidural
Bl
5
15
30
Minutes
Halothane
* = p< 0,05 vs. Bl
60
90
120
P124 ‘Wet’ and ‘dry’ lungs: a useful sonographic distinction
G. Soldati and M Rossi
Emergency Department, General Hospital, Lucca, 55100 Lucca, Italy
Crit Care 1999, 3 (suppl 1):P124
Pulmonary edema develops when the movement of liquid from
the blood to the interstitium exceed the return of the liquid to the
blood. The diagnosis of this interstitial expansion is based on
chest X-ray and the basic clinical signs appear when the pulmonary compliance is reduced (aspecific dyspnea), a large mismatch exists between ventilation and perfusion or with the onset
of alveolar flooding (moist and fine crepitant rales, wheezes or
extreme breathlessness). The detection of an interstitial edema is
a crucial step in the diagnostic procedure in a dyspneic patient and
the intensivist or the emergency physician must make daily therapeutic decisions on the basis of a bedside clinical examination,
often difficult, and chest X-ray, wich is known to be often technically deficient.
Methods and patients: During a 4-month period, 83 patients (49
males and 34 females, mean age 74 years) admitted to our
Emegency Room (ER) were included in a prospective
study.They showed dyspnea (>25 breaths/min) and/or discomfort
and signs of augmented work of breath (inspiratory retraction of
the intercostal spaces and supraclavicular fossa) or orthopnea.
Immediately after the clinical examination, all patients underwent chest sonography. Longitudinal scans of the anterior, lateral
and posterolateral (or posterior in the sitting patient) chest wall
were taken using a Toshiba SSA250A portable unit equipped
with a 3.75 MHz convex transducer. We particularly studied the
respiratory motion of the pleuropulmonary surface (gliding sign)
and the comet tail artifacts arising from the lung surface. These
artifacts are roughly vertical narrow based projections spreading
up to the edge of the screen and appear when there is a marked
difference in acoustic impedance between subpleural septa thick-
ened by edema and the alveolar air (alveolar-interstitial syndrome). Chest radiographs of all patients performed during the
same period of ER evaluation were interpreted by radiologists
unaware the sonography findings and classified on the basis of
widely accepted criteria. Once the diagnosis of wet lungs was
sonographically confirmed, the patients were considered for
hearth failure treatment (diuretics and vasodilators) in absence of
other diagnostic possibilities or particulary controindications,
while the patients with dry lungs underwent advanced diagnostic
work up. Finally we evaluated the effect of the diuretic therapy
(in 3 h), the correlations between radiologic and sonographic patterns and the usefulness of ultrasonography in the diagnostic
approach to the critically ill patients.
Results: All patients were successfully and quickly (<5 min)
analysed using ultrasound (feasibility 100%). Twenty-nine subjects (34%) showed ‘wet lungs’ with diffuse bilateral comet tail
artifacts. Of these, 21 (72%) had associated pleural effusions (bilateral in 13 cases), with water levels (WL) between 1 and 8 cm.
Chest X ray discovered congestion or edema in 30 pts. (flow inversion, enlarged/iperdense ila: 5 pts. blurred ila, perivascular/peribronchial cuffs, Kerley B lines: 13 pts.; patchy alveolar edema: 7
pts. and confluent alveolar edema: 5 pts.), 29 of them exibiting
diffuse artifacts. Pleural effusions were shown radiologically in 13
subjects with eight missed diagnoses (effusions with WL <2 cm).
One discordant case was noted (sonographic false negative) but
none of 51 patients with normal X rays had significant comet tail
artifacts. Sonographic imaging led to a change in the initial diagnosis (hearth failure) in 11 pts. (13% of the whole group studied), six
with COPD, three with pulmonary embolism and one with important anemia, these subjects showed normal chest X rays and sonographic ‘dry lungs’; one patient had the diagnosis changed from
COPD to hearth failure.
62
Critical Care 1999, Vol 3 suppl 1
Conclusion: We think that echography offers a new method for
the diagnosis of alveolar-interstitial syndrome at bedside and may
provide vital informations when a radiograph is not readily available or undesiderable. Moreover it may be valuable for
differentating cardiogenic pulmonary edema from decompensated
COPD or pulmonary embolism showing, in our experience, a sensibility of 96% and a specificity near to 100% for diagnosing ‘wet
lungs’.
References
Lichtenstein D, Meziere G, Biderman P et al.: The comet tail
artifact, an ultrasound sign of alveolar-interstitial
syndrome. Am J Respir Crit Care Med 1997, 156:16401646.
Yu CJ, Yang PC, Chang DB, Luh KT: Diagnostic and therapeutic
use of chest sonography: value in critically ill patients.
AJR Am J Roentgenol 1992, 159:695-701.
P125 A comparison between impedance plethysmography and thermodilution for the measurement of cardiac
output in pre-operative haemodynamic optimization
RM Venn, C Bradshaw, R Cusack, PE Belcher, HMA Morris, LK Estcourt, A Rhodes and ED Bennett
Dept of Intensive Care, St George’s Hospital, London, SW17 0QT, UK. Fax: 0181 7679748
Crit Care 1999, 3 (suppl 1):P125
Introduction: New developments in Impedance Plethysmography
(IP) (IQ, Renaissance Technology, PA, USA) have been reported
to allow accurate measurement of cardiac output in patients on the
intensive care unit.
Methods: Ten patients on the ICU admitted pre-operatively for
haemodynamic optimization were prospectively studied. Each
patient had measurement of cardiac output by a thermodilution
right heart catheter technique and also by IP. Data sets were
obtained during the procedure of haemodynamic optimization.
Data was analyzed using regression analysis for the differences
between cardiac output measurements between the two techniques, depending on both the patient and the absolute level of
cardiac output.
Results: Ten patients were analyzed with a total of 51 pairs of
cardiac output measurements. Thermodilution cardiac outputs
were obtained between 4.1 l/min and 10.5 l/min. Regression analysis revealed a significant difference between cardiac output measurements for the two techniques (P < 0.0001). Differences existed
when the data was analyzed between patients and also when
looking at different measurements for individual patients.
Discussion: IP would be ideal non-invasive tool for the measurement of cardiac output in ICU patients. This study suggests,
however, that there are major differences between the cardiac
outputs obtained from thermodilution and IP for pre-operative
patients on the ICU.
P126 Hemodynamic monitoring by double indicator dilution technique in patients after orthotopic heart
transplantation
T Seebauer, O Goedje, M Peyerl and B Reichart
Department of Cardiac Surgery, Grosshadern University Hospital, Ludwig-Maximilians-University, 81377 Munich, Germany
Crit Care 1999, 3 (suppl 1):P126
Background: Cardiac index (CI) and preload monitoring by pulmonary artery catheter (PAC) is increasingly confronted with criticism. We evaluated the less invasive arterial double indicator
dilution method (TDD) as an alternative. Preload with this technique is determinated by measuring intrathoracic blood volume
index (ITBVI) and global enddiastolic volume index (GEDVI)
instead of filling pressures CVP and PCWP. As there is no clinical
experience in patients with denervated hearts, we investigated
this monitoring method in patients after heart transplantation.
Methods: Forty patients (34 male, 54.4 ± 8.5 years) were studied
with the TDD and PAC methods. Measurements were performed
at the ICU at 3, 6, 12, 24, 36, 48 and 72 h postoperatively. Based on
Frank-Starling law, ITBVI, GEDVI, CVP, and PCWP have been
investigated on their usefulness as preload indicators and for this
purpose correlated with stroke volume index (SVI).
Results: No difference between femoral and pulmonary artery CI
were found (r = 0.98, bias 0.35 l/min/m2). Changes of CVP
(r = –0.23) and PCWP (r = –0.06) did not correlate significantly to
changes in SVI. ITBVI (r = 0.55) and GEDVI (r = 0.63) showed
significant correlations. Equally directed changes of SVI with
GEDVI and ITBVI occurred in 70.3% and 66.9% respectively, of
SVI with CVP and PCWP in 41.1% and 41.9%.
Conclusion: CVP and PCWP are not as reliable preload parameters as ITBVI and GEDVI. The latter even in denervated hearts
show good correlations to SVI. They can be obtained less invasively and therefore should be the method of choice.
P127 The cardiac chemoreflex sensitivity (cCRS) and the influence of respiration
BH Schmidt, H Opitz, M Rauchhaus* and K Werdan
University Halle, Department of Medicine III/Cardiac Intensive Car, 06097 Hale, Germany, Institute of Physiology, University Halle,
06097, Halle Germany, and *NHLI, London, SW3 6LY, UK
Crit Care 1999, 3 (suppl 1):P127
Introduction: Assessment of cCRS may be a predictor of serious
arrhythmic events after survived sudden cardiac death.
However, chemoreceptor (CR) stimulation produces not only
cardiovascular but also respiratory responses. The aim of this
study was to correct the respiratory influence on apparent values
of cCRS.
Poster abstracts
Methods: The cCRS was assessed in 47 healthy volunteers during
free breathing (FB). Twenty subjects underwent further monitoring during controlled breathing (CB, fixed minute ventilation).
Peripheral arterial CTs were stimulated by 5 min of hypoxia (10%
O2 in N2). Cardiac CRS was calculated as ∆heart rate
interval/∆pO2. We developed a mathematical model to reduce the
respiratory influence on cCRS, and calculated a respiration independent second cCTS value using this correction. The corrected
cCRS was compared with cCRS values experimentally obtained
during CB.
Results: Cardiac chemoreflex sensitivity under free and controlled
breathing
pCCS (ms/mmHg)
63
CB
FB
FB (corrected
values)
1.53 ± 0.32
3.64 ± 0.81*
0.89 ± 0.91 NS
*P < 0.05 versus controlled breathing (CB), NS, not significant versus
CB.
Conclusions: Our results suggest that ventilation causes a major
disturbance in the measurement of cardiac chemoreflex sensitivity. We argue that this disturbance should be minimised to obtain
correct values of cardiac chemoreflex sensitivity for predicting
serious arrhythmic events.
P128 Do we need a basis bolus concept for sedoanalgesia of mechanically ventilated patients in ICU?
J-C Lewejohann, H-J Düpree, J Gleiß, S Lewejohann, E Muhl and H-P Bruch
Med. Univ. of Luebeck, Dept. of Surgery, Ratzeburger Allee 160, 23538 Luebeck, Germany. E-mail: JLewejohann@t-online.de
Crit Care 1999, 3 (suppl 1):P128
Introduction: Tolerance for mechanical ventilation is generally
achieved by continuous application of analgesics and sedatives.
Their effect is usually controlled by physical examination. The
dosage in daily routine occasionally is not adapted to the patients
needs in the circardian course. Evidence exists that classical neurological and hemodynamic parameters do not always reflect the
level of sedoanalgesia. Neuromonitoring with heart-rate-variability (HRV) is a new opportunity to evaluate the patients neurological status. HRV is a window for usually invisible central autonomic
regulation. This phenomenon is caused by oscillation in the interval between consecutive heart beats. It represents a quantitative
marker of autonomic activity. Currently monitoring of autonomic
nervous system is no routine tool for mechanically ventilated
patients. Our study presents first results of continous neuromonitoring of autonomic nervous system with heart-rate-variability in
the setting of an intensive care unit.
Methods: We studied 10 mechanically ventilated patients (5 male,
5 female) without any cardiovascular diseases in case history who
received analgesics (Fentanyl®) and sedatives (Dormicum®) continuously. Heart-rate-variability was recorded with a flash-memory
recorder, the analysis of HRV was performed by a special software
(both elamedical, Munich). We investigated over a period of 24h
in each case.
Results: The investigations show considerable variations regarding to the level of HRV parameters in the circadian course. During
night time frequency domain parameters of HRV go down (total
power: 85.88 ± 19.10 ms2), while they increase during daytime
(170.66 ± 57.29 ms2) with a considerable variation. Nursing and
medical manipulations as well as the doctor’s round at bedside in
the morning time lead to a conspicuous increase of total power
[mean ± SEM]:
Frequency
domain
Total power (ms2)
1 h before
doctor’s round
During doctor’s
round
1 h after
doctor’s round
46.10 ± 11.55 193.20 ± 54.50
62.50 ± 20.82
Low freq. (ms2)
5.40 ± 1.54
14.30 ± 4.23
(ms2)
8.30 ± 3.15
31.50 ± 15.76
High freq.
7.30 ± 3.13
10.50 ± 3.70
Conclusion: Continuous monitoring of the autonomic nervous
system with heart-rate-variability is a new approach to demonstrate the status of the patients sedoanalgesics. It shows considerable variations of autonomic activity in the circadian course.
Especially during manipulations at the patients bedside a dysbalance of central autonomic activity seems to appear. A basis-bolusadministration of sedoanalgesia seems to be a useful concept to
compensate the undesirable and obvious dysbalance of central
autonomic activity under stress situations like doctor’s round at
the bedside of mechanically ventilated patients with sedoanalgesics.
P129 Multigated radionuclide blood pool scans (MUGA) for preoperative assessment of patients undergoing
orthotopic liver transplantation (OLT)
L Nel, A Watts, D Potter, M Buxton-Thomas*, J O’Grady† and N Heaton†
Depts. of Anaesthesia, *Nuclear Medicine and †Institute of Liver Studies, King’s College Hospital, London, UK
Crit Care 1999, 3 (suppl 1):P129
Introduction: OLT is a major cardiovascular stress both intra- and
postoperatively. The ideal preoperative cardiac screening test for
patients with end-stage liver disease (ESLD) has not been determined [1]. We evaluated the value of MUGA in predicting perioperative morbidity and mortality in patients undergoing OLT.
Methods: After IRB approval we retrospectively examined the
medical records of 170 ESLD patients who had MUGA scans prior
to OLT from January 1994–April 1998. Morbidity was defined as
reperfusion syndrome (fall in MAP >33%), requirement for intraor postoperative inotropes, myocardial infarction (AMI), need for
haemodiafiltration or ICU stay >5 days. Mortality was restricted to
30 days. MUGA scans were defined as normal if ejection fraction
(EF) was >55% [2]. Analysis of results was by Chi-squared test.
64
Critical Care 1999, Vol 3 suppl 1
Results: There were 127 patients in group A (EF >55%) and 37
patients in group B (EF <55%). Six patients were excluded
because of incomplete data. No patients had AMI. Two patients
in group A died and there were no deaths in group B.
Conclusion: For patients undergoing OLT, MUGA is not a useful
screening test for predicting perioperative morbidity and mortality. Based upon these findings we have revised our method of preoperative cardiac assessment of patients presenting for OLT.
Event
Group A (No. (%))
Group B (No. (%)) P value
Reperfusion
67 (53)
23 (65)
0.28
Inotropes (intra)
42 (33)
16 (43)
0.27
Inotropes (post)
20 (16)
9 (24)
0.24
CVVHD
11 (9)
3 (8)
0.6
49 (38)
16 (43)
0.21
ICU stay >5 days
References
1. Liver Transplant Surg 1998, 4:253-257.
2. Br Heart J 1994, 71:33.
P130 Lithium dilution cardiac output (LiDCO) measurement using peripheral venous injection of lithium chloride
MM Jonas, FE Kelly*, NWF Linton*, RAF Linton*, TK O’Brien* and DM Band*
Department of Intensive Care, Southampton General Hospital, Tremona Rd., Southampton SO16 6YD and *The Rayne Institute, St Thomas’
Hospital, London SE1 7EH, UK
Peripheral venous injection
Crit Care 1999, 3 (suppl 1):P130
Patient
No.
Central venous injection
Mean LiDCO (l/min)
SEM
Mean LiDCO (l/min)
SEM
1
7.55
0.40
7.24
0.33
2
12.22
0.15
12.47
0.41
3
5.23
0.12
5.12
0.21
4
7.23
0.08
7.16
0.18
There are many patients who have arterial cannulae and peripheral, rather than central, venous access in whom cardiac output
measurements would greatly assist management.
5
4.98
0.18
5.24
0.14
6
7.37
0.14
7.74
0.14
7
4.90
0.10
4.54
0.12
We have therefore explored the feasibility of measuring cardiac
output using a peripheral rather than central venous injection of
lithium chloride.
8
5.06
0.05
5.02
0.03
9
5.63
0.20
6.04
0.21
10
9.32
0.22
10.08
0.29
Background: We have previously described a simple indicator
dilution method of measuring cardiac output in which lithium
chloride is injected via a central venous catheter and its plasma
concentration-time curve measured in arterial blood using a
lithium selective electrode [1]. This technique has the advantage
of requiring only central venous and arterial cannulation and
therefore avoids pulmonary artery catheterisation.
Methods: Ten stable patients with peripheral (antecubital vein),
central venous and arterial cannulae on a General Intensive Care
Unit were studied. For each patient, 10 consecutive LiDCO
measurements of cardiac output were made at 5-min intervals.
The injections of lithium chloride were given alternately via the
peripheral and central venous cannulae and the cardiac outputs
calculated from the arterial plasma concentration-time curves. For
each patient the average of the five LiDCO measurements
obtained using peripheral venous injection was compared with the
average of the five LiDCO measurements obtained using the
central venous route.
Results: There was good agreement between the two methods
(r2 = 0.98) and the results are summarised in the Table.
Conclusion: This study shows that LiDCO can be measured using
peripheral or central venous injections of lithium chloride. Safe,
quick and reliable cardiac output measurements can therefore be
obtained in patients with arterial and antecubital venous access.
Reference
1. Critical Care Medicine 1997, 25:1796-1800.
P131 PiCCO monitoring during anesthesia
G Della Rocca, L Pompei, C Coccia, MG Costa, F Ruberto and F Pugliese
Istituto di Anestesiologia e Rianimazione, Dir. Prof A. Gasparetto, University of Rome ‘La Sapienza’,Via del Policlinico n°155-00161 Rome, Italy
Crit Care 1999, 3 (suppl 1):P131
Introduction: The Pulse Contour Cardiac Output (PiCCO) is an
innovative technology that monitors the cardiac preload volume
through the global end diastolic volume (GEDV) and gives an
extimation of the intrathoracic blood volume, an indicator of circulating volume and of the extravascular lung water (EVLWI), which
is considered to be a good extimator of interstitial lung edema.
Poster abstracts
Moreover PiCCO, through a ‘beat to beat’ analysis of the arterial
pressure wave, measures continuous cardiac output. The aim of this
study is to evaluate the new volumetric hemodynamic monitoring
during major surgery and during liver and lung transplantation (Tx).
Methods: After approval from ethical committee 41 patients
undergoing lung transplantation (11), liver transplantation (10),
thoracic surgery (10) and major abdominal surgery (10) were
included in the study. In all pts were placed a Swan-Ganz catheter
(IntelliCath-Baxter, Irvine CA-USA, connected to Vigilance
Monitor-Baxter) and a 4 F fiberoptic-thermistor catheter was
inserted into the femoral or brachial artery (Pulsion PiCCO-Medizintechnik, Munchen). Hemodynamic volumetric data were collected in different phases: during lung Tx (MV = after induction
of anesthesia; CL1 = after the first pulmonary artery clamping;
REP1 =after the reperfusion of the first lung; CL2 = after the
second pulmonary artery clamping; REP2 = after the reperfusion
of the second lung; Fin = end of surgery); during liver Tx (A =
Phases
CI
Thoracic
(l/min/m2) Abdominal
Liver Tx
(Lung Tx)
mAP
(mmHg)
A (MV)
2.4 ± 0.3
2.7 ± 0.7
3±1
(3.2 ± 0.7)
Thoracic
Abdominal
Liver Tx
(Lung Tx)
68 ± 7
67 ± 6
82 ± 12
(74 ± 9)
Thoracic
Abdominal
Liver Tx
(Lung Tx)
23 ± 5
20 ± 4
17 ± 3
(31 ± 10)
Thoracic
Abdominal
Liver Tx
(Lung Tx)
11 ± 6
6±1
9±2
(9 ± 2)
Thoracic
Abdominal
Liver Tx
(Lung Tx)
14 ± 3
12 ± 2
12 ± 3
(17 ± 9)
GEDVI
(ml/m2)
Thoracic
Abdominal
Liver Tx
(Lung Tx)
904 ± 214
1165 ± 236
773 ± 180
(711 ± 201)
EVLWI
(ml/kg)
Thoracic
Abdominal
Liver Tx
(Lung Tx)
7±3
6±2
8±3
(9 ± 4)
mPA
(mmHg)
CVP
(mmHg)
PAWP
(mmHg)
(CL1)
B (REP1)
(4 ± 1)
3.7 ± 0.6
3.3 ± 0.5
3±1
(5.1 ± 1)
(77 ± 11)
74 ± 14
92 ± 6
81 ± 16
(83 ± 17)
(43 ± 10)
21 ± 4
20 ± 5
19 ± 4
(34 ± 8)
(15 ± 5)
8±2
15 ± 3
12 ± 4*
(18 ± 5)
(25 ± 8*)
14 ± 2
12 ± 3
14 ± 4
(22 ± 9)
(657 ± 228)
1045 ± 142
1124 ± 145
763 ± 173
(650 ± 95)
(11 ± 6)
7±3
4±1
12 ± 9
(18 ± 8*)
65
after induction of anesthesia; B = anephatic phase; C = end of
surgery); during thoracic (A = after induction of anesthesia; B =
during surgery in one lung ventilation; C = end of surgery) and
abdominal surgery (A = after induction of anesthesia; B =during
surgery; C = end of surgery).
Results: See Table.
Discussion: Other authors reported GEDV modifications correlated to cardiac index rather than standard cardiac filling pressures
such as CVP and PAWP, so that GEDV is considered a ‘pure’
volume indicator. EVLWI can be considered a potential indicator
of lung damage and pulmonary function, and it is hypothesized to
be a better endpoint than PAWP during fluid management.
In conclusion monitoring EVLWI, as pulmonary edema indicator
and GEDV, as cardiac preload value, lead our diagnostic and terapeutic management during major surgical procedures.
(CL2)
(3.6 ± 1)
(88 ± 11)
(42 ± 14)
(18 ± 6)
(26 ± 6)
(647 ± 118)
(23 ± 21)
(REP2)
C (FIN)
(4 ± 1)
4.7 ± 1.8
3.5 ± 1.2
4±1
(3.4 ± 1)
(100 ± 15)
89 ± 23
88 ± 21
84 ± 13
(82 ± 6*)
(27 ± 7*)
25 ± 4
23 ± 3
22 ± 4
(23 ± 5)
(15 ± 4)
10 ± 4
10 ± 2
11 ± 3
(13 ± 6)
(17 ± 4)
15 ± 7
14 ± 2
15 ± 4
(15 ± 4)
(818 ± 112)
1350 ± 427
1208 ± 322
945 ± 137
(789 ± 104)
(21 ± 12)
11 ± 2
4±1
12 ± 10
17 ± 8
*P < 0.05.
P132 Measurement of aortal blood flow in supranormal cardiac output
T Kerner, M Deja, O Ahlers, E Grosse, H Lohbrunner, J Löffel*, H Riess*, P Wust† and H Gerlach
Abteilung für Anaesthesiologie und operative Intensivmedizin (GD: Prof. Dr. KJ Falke), *Abteilung für Hämatologie/Onkologie
(GD: Prof. Dr. D Huhn), †Strahlenklinik und -poliklinik (GD: Prof. Dr. Dr.h.c. R. Felix), Charité Campus Virchow-Klinikum der
Humboldt-Universität zu Berlin, Deutschland
Crit Care 1999, 3 (suppl 1):P132
Introduction: In order to minimize complications of invasive techniques for measurement of cardiac output, non-invasive methods
will be of growing importance in anesthesiology and intensive
care. The validity of non-invasive measurements has frequently
been questioned. In our study the validity of non-invasive measurements was assessed in supranormal cardiac output.
Critical Care 1999, Vol 3 suppl 1
Methods: In 12 patients, who underwent whole body hyperthermia (WBH) in general anesthesia, aortal blood flow was measured
using an esophageal Doppler probe (DYNEMO 3000, Sometec,
France). Measurements were performed at 37°C, 40°C, 42°C and
39°C body core temperature. At the same time cardiac output was
determined by the invasive thermodilution method using a pulmonary artery catheter (Swan-Ganz-Catheter) as well an arterial
catheter (PULSION COLD®). Blood flow in the descending aorta
is assumed to represent approximately 70% of total cardiac output,
accordingly 70% of the value measured with the invasive technique was compared to the non-invasive measurement. For
cardiac output measured by Doppler ultrasound median values
were evaluated over a period of 5 min. Statistics were performed
using the Mann-Whitney-U-Test.
*
12
11
ABF / 70 % CO [l/min]
66
*
10
9
8
7
6
Swan-Ganz-Catheter
Doppler-Ultrasound
5
37°C
40°C
42°C
39°C
Temperature
Figure. ABF and 70% CO during WBH.
Results: There were no significant differences between values
obtained with the two different invasive techniques. Values measured with Doppler ultrasound were significantly lower at 40°C
(P = 0.04) and 42°C (P = 0.01) compared to invasive measurements,
despite a growing tendency with rising temperature (see Figure).
Conclusion: Under conditions with increasing supranormal cardiac
output measurements with Doppler ultrasound do show a tendency, but absolute values are significantly underestimated with
an increasing difference towards growing values.
P133 Trends of volemic indicators in a group of critically ill patients
CG Ruggieri, P Passarello, M Pettoni Possenti, G Rambelli, F Ruggeri, M Sanseverino and M Nastasi
Dept of Surgery, Section of Anaesthesia and Intensive Care Hospital ‘G Ceccarini’, Via F.lli Cervi 49, 47838 Riccione (RN), Italy
Crit Care 1999, 3 (suppl 1):P133
Introduction: The aim of this prospective non intervention study
is to analyse the clinical utility of traditional preload indicators, as
central venous pressure (CVP, mmHg) or pulmonary capillary
wedge pressure (PCWP, mmHg), and the meaning of a pure
volume indicator, as intrathoracic blood volume (ITBV, ml/m2 BS).
Material and methods: Eighty-four medical or surgical patients
were studied (mean age 51, SD 17; mean SAPS II (1st day) 56, SD
9). After 6 h of ICU stay, a 7.5 F pulmonary artery catheter and a
4 F femoral artery catheter, with thermistor and fiberoptics were
inserted and connected to ‘COLD System’, an integrated monitoring system which uses the double indicator technique for
studying blood volumes. All patients were in CMV (PEEP
<8 cmH2O); haemodynamic management was realized in order to
optimize cardiac output (CO, l/min/m2 BS) and systemic oxygen
delivery. Infusion of crystalloids and colloids was guided by measurements of CVP and PCWP. All data were recorded at the beginning of the study (T0) and after 6 (T1), 12 (T2), 24 (T3) and 36
(T4) h. Statistical analysis of data was performed using Manova
Test, considering the significant differences in the times of study
between group A (38 pts., ITBV in T0 <1 l/m2 BS) and group B
(46 pts., ITBV in T0 >1 l/m2 BS) and analysing the variance of
repeated measures. Levels of P < 0.05 were accepted.
Result and conclusions: The Table shows the trends of parameters
in the times of study (data are expressed as mean and (SD); A vs
B, $P < 0.0001; *P < 0.05; T vs T0, §P < 0.05).
When preload is the main determinant of CO, CVP and PCWP
may be misleading in management of volemia in mechanically
ventilated patients, on the contrary ITBV may be useful to optimize central filling and haemodynamic conditions.
Time 0
Time 1
Time 2
Time 3
Time 4
CO
A 4 (1.5)*
B 5.1 (1.7)
4.6 (1.8 )*§
5 (1.7)
4.8 (1.9)§
5.1 (1.8)
4.6 (1.6)§
5.2 (2.1)
4.8 (1.6)§
4.9 (1.6)
CVP
A 7.9 (5.2)
B 8.3 (4.6)
7.5 (4.1)
7.9 (3.6)
7.5 (4.2)
8.1 (3.3)
8 (4)
8 (4.2)
8 (4.7)
8.4 (4)
PCWP
A 11.5 (5.2)*
B 14.9 (6.8)
11.1 (4.3)*
14.2 (6)
12.2 (3.6)
13.9 (5.4)
12.2 (4.3)
13.9 (6.4)
13.1 (4.5)
15.7 (7.3)
ITBV$
A 804 (129)
B 1285 (237)
922 (238)§
1234 (248)
1023 (305)§
1314 (285)
928 (205)§
1321 (384)
985 (323)§
1269 (288)
Poster abstracts
67
P134 Usefulness of intrathoracic blood volume in the early phase of hemodynamic instability of patients with
sepsis or septic shock
SG Sakka, A Meier-Hellmann and K Reinhart
Department of Anesthesiology and Intensive Care Medicine, Friedrich-Schiller-University of Jena, Bachstr. 18, D-07740, Germany.
Tel: +49-3641-933041; Fax: +49-3641-933256; E-mail: sakka@anae1.med.uni-jena.de
Crit Care 1999, 3 (suppl 1):P134
40
Methods : We analysed 581 hemodynamic profiles in 57 septic
patients (60 ± 15 years, SAPS II 53 ± 15, SOFA 15 ± 3) who received
a 7.5 F pulmonary artery catheter and a 4 F flexible aortic catheter.
Hemodynamic profiles were at least 15 min apart, the maximum
time period was 24 h (8.25 ± 5.30 h).
(r = 0.07). Increases in SI (n = 265) were more often associated with
increases in ITBVI (n = 189, 71.3%) than in PCWP (n = 122,
46.0%). Decreases in SI (n = 256) were associated with decreases
in ITBVI in 176 (68.8 %) and for PCWP in 119 cases (46.5%).
Results : In all second profiles, changes in stroke index were
accompanied by changes in ITBVI (r = 0.67) and not PCWP
20
0
-1000
-20
0
1000
∆SI [ml/m²]
Introduction: Previous studies in cardiac surgical and ARDS
patients suggested that the intrathoracic blood volume index
(ITBVI) is a more reliable indicator of cardiac preload than the
pulmonary capillary wedge pressure (PCWP). Since these studies
were under controlled conditions, we analysed the value of both
preload variables with respect to stroke index (SI) in patients with
sepsis and septic shock under actual ICU conditions of frequent
changes in ventilation, volume loading and catecholamine treatment.
∆SI [ml/m²]
40
20
0
-10
-20
-40
∆ITBVI [ml/m²]
0
10
-40
∆PCWP [mmHg]
Conclusion : In the early phase of hemodynamic stabilisation of
patients with sepsis or septic shock, ITBVI is a more reliable indicator of cardiac preload than the PCWP.
P135 Assessment of intrathoracic blood volume and extravascular lung water by single transpulmonary
thermodilution
SG Sakka, A Meier-Hellmann and K Reinhart
Department of Anesthesiology and Intensive Care Medicine, Friedrich-Schiller University of Jena, Bachstr. 18, D-07740, Germany
Crit Care 1999, 3 (suppl 1):P135
Introduction: The transpulmonary double-indicator dilution technique enables to measure the intrathoracic blood volume (ITBV)
and extravascular lung water (EVLW). Since this technique is relatively time consuming and expensive, we studied whether the
global end-diastolic volume (GEDV) which can be derived only
from single indicator dilution (thermodilution) allows the estimation of intrathoracic blood volume.
Methods: In a heterogeneous population of 57 critically ill patients
(56 ± 15 years) we found by structural regression analysis a correlation of ITBV=(1.25×GEDV)–28.4 [ml]. We then applied this equation on the first double-indicator measurements in 209 other patients
(52 ± 19 years) with sepsis (n = 98), ARDS (n = 31), head injury
(n = 38), hemorrhagic shock (n = 19), intracranial hemorrhage (n = 19),
brain infarction (n = 3), and heart failure (n = 1). Each patient
received a 4 F flexible aortic catheter with an integrated thermistor
and fiberoptic. Bolus injections used cooled (0–4°C) indocyanine
green dissolved in glucose 5% in a concentration of 2 mg/ml.
Results: By using the equation mentioned above, thermodilution
ITBV (ITBV*) and correlated ITBV*=(1.06×ITBV)–124.3 [ml],
r = 0.98, P < 0.0001. For thermodilution EVLW (EVLW*) linear
regression analysis showed EVLW*=(0.83×EVLW)+133.9 [ml]
(r = 0.96, P < 0.0001).
Conclusion: At least for patients on a surgical intensive care unit,
single transpulmonary thermodilution is sufficiently accurate for
the estimation of intrathoracic blood volume and extravascular
lung water.
P136 Diagnostic determinants for capillary leakage syndrome (CLS) in septic shock patients
G Marx, C Burczyk, M Cobas Meyer, B Vangerow, N Maassen*, KF Gratz†, M Leuwer and H Rueckoldt
Department of Anaesthesiology, *Physiology, and †Nuclear Medicine, Hannover Medical School, D-30625 Hannover, Germany.
Fax: +44-511-532-3642; E-mail:marx.gernot@mh-hannover.de
Crit Care 1999, 3 (suppl 1):P136
Objectives: CLS is a frequent complication in sepsis characterized
by loss of intravasal fluids leading to generalized edema and
hypotension. Despite the importance there are still no standardized diagnostic criteria available for CLS. The aim of this study
was to evaluate diagnostic determinants for CLS.
68
Critical Care 1999, Vol 3 suppl 1
Design: Prospective clinical study.
Methods: The study was performed in 4 patients with septic
shock (SOFA-Score = 12 ± 2), multiple organ failure and CLS compared to 4 control patients. CLS was judged clinically by generalized edema, positive fluid balance and weight gain. Plasma
volume by indocyanin green (PVICG), red blood cell volume by
tagged chromium-51 (RBC:51Cr), extracellular fluid volume
(ECF) calculated by inulin space technique and colloid osmotic
pressure (COP) were measured before (T0 = 0 min) and after (T1
= 90 min) administration of 300 ml of albumin 20%. Measurement
of total body water (TBV) and the phase angle (phi, degrees), a
global parameter of the body composition were performed using
bioelectrical impedance analysis (BIA).
Results: PVICG was measured in CLS patients with 45.9 ± 14.6 ml/kg/
total body weight (BW) and in controls with 67.8 ± 15.2 ml/kg/BW.
The RBC:51Cr averaged 20.2 ± 1.3 ml/kg/BW in CLS patients and in
the controls 24.4 ± 3.7 ml/kg/BW. ECF was expanded in CLS
patients compared to controls (45.1 ± 8.5%BW vs. 29.5 ± 6.7%BW;
P < 0.05). Increase of COP level at T2 in CLS patients was smaller
than in the control patients (1.1 ± 0.4 mmHg vs. 2.4 ± 1.0 mmHg;
P < 0.05). Phi was low in CLS patients (2.1 ± 0.8° vs. 4.8 ± 1.2°;
P < 0.05) and TBV was elevated compared to controls (76.5 ± 12.0 kg
vs. 55.7 ± 3.8 kg; P < 0.05).
Conclusion: These results suggest that measurements of phi and
TBV using BIA combined with a difference of COP levels before
and after administration of albumin are promising approaches to
discriminate CLS from non-CLS patients at the bed-side.
P137 Evaluation of the use of bioelectrical impedance analysis in assessing the hydration and fluid balance of
infants with bronchiolitis requiring intensive care
N Hansard, G Gaillard, P Holland, JG Truscott*, B Oldroyd* and JA Evans*
Department of Paediatrics and Child Health, Clarendon Wing, Belmont Grove,The General Infirmary at Leeds, Leeds LS2 9NS
and *Department of Medical Physics, University of Leeds, UK. Tel: (0113) 3922840; E-mail philiph@ulth.northy.nhs.uk
Crit Care 1999, 3 (suppl 1):P137
Objective: To examine whether regular bioelectrical impedance
(Z) measurements in babies with bronchiolitis detects daily
changes in fluid status and if it may be used as a guide to hydration when compared to age matched well babies.
Methods: Bioelectrical impedance was measured using a Xitron
4000B machine, with electrodes placed 6 cm apart on the dorsal
surface of the hand and foot. In babies with bronchiolitis measurements were made as soon as possible after admission and every
24 h until discharge. Data on fluid balance over the previous 24 h
were recorded at each measurement period.
Results: There was a clear linear relationship between impedance
(ohms) plotted against body mass index (r = 0.95, P < 0.0001) in the
control babies. Using control data for BMI and Z, an equation was
developed using linear regression to predict Z from BMI values.
This equation was used (Z=19.04BMI + 114.6) to predict values
for Zexpected in the babies with bronchiolitis on admission. These
values were compared with those at admission (Z1), where using
paired t-test a significant difference existed (P < 0.0008) and at discharge (Z2) where there was no significant difference. There was
no significant relationship between changes in body impedance
and changes in fluid balance (both positive or negative) although
impedance changed appropriately in association with fluid boluses
or with diuretics.
Conclusion: Regular impedance measurements give a guide to the
state of hydration of babies requiring intensive care and help
determine whether the baby is adequately hydrated or not. There
is a poor relationship between measured changes in fluid balance
and changes in impedance and it may not be used to calculate
absolute values of fluid required.
P138 External cardiac pressures and the left ventricular pressure–volume relationship
MF Haney, G Johansson, S Häggmark and B Biber
Department of Anesthaesia and Intensive Care, Umeå University Hospital, 901 85 Umeå, Sweden
Crit Care 1999, 3 (suppl 1):P138
Introduction: Wide variations in external cardiac pressures are
known to occur in clinical situations and can have significant
effects on cardiac performance [1,2]. We designed an experimental situation where external cardiac pressure conditions were controlled and adjusted to physiological extremes to mimic clinically
relevant situations, while cardiac performance was assessed using
left ventricular pressure–volume relationships (LVPVR) which are
relatively preload and afterload independent.
Methods: Healthy adult pigs (n = 4) were anesthetized, received
central vascular catheters, a pericardial catheter, and bilateral
pleura drains. Left ventricular volume was assessed by the conductance technique [3]. External cardiac pressures were manipulated: pneumothorax (20 ml/kg air injected in the pleura), and
pericardial infusion (mean pressure of +6 mmHg). End sytolic
elastance (Ees), preload recruitable stroke work (PRSW), preloadadjusted maximal power (PWRmax/EDV2) [4].
Results: During pericardial infusion, where the end-systolic pressure was low and limited in beat-to-beat decrement during the
preload reduction, only elastance increased while the other
derived systolic parameters decreased. During pleura insufflation,
all the systolic function parameters increased.
Discussion: These data suggest that relatively load-independent
means are needed to assess cardiac function in the setting of
extreme extracardiac pressure. LVPVR provides beat-to-beat
insight into heart function at wide ranges of loading conditions.
Further work is warranted to validate clinically applicable means
to implement this type of assessment, as well as to further develop
reference methodology for experimental and clinical heart volume
assessment.
Poster abstracts
Pleural intervention
Control
Pericardial infusion
Insufflation
Control
±6 mmHg
EDV (ml)
85 + 10
54 + 4
86 + 13
62 + 11
EDP (mmHg)
13 + 2
12 + 0.2
13 + 1
13 + 1
ESV (ml)
42 + 6
22 + 3
47 + 7
33 + 6
ESP (mmHg)
90 + 3
70 + 14
88 + 3
47 + 5
Pericardial pressure (mmHg)
0.8 ± 1.3
5.1 ± 1.8
-0.6 ± 1.1
6.4 ± 0.7
dP/dt max (ms)
1557 + 152
1581 + 453
1622 + 260
809 + 63
Ees (mmHg/ml)
1.24 + 0.2
1.72 + 0.3
1.25 + 0.2
2.26 + 0.9
PRSW (mmHg ml/ml)
50 + 4.1
60.1 + 11.3
51.6 + 4.4
43.6 + 6.2
PWRmax/EDV2 (dE/dt)
3.1 + 0.8
6.6 + 2.0
3.0 + 0.8
2.5 + 0.6
References
1. Cardiovasc Res 1990, 24:633-640.
2. J Emerg Med 1997, 15:147-153.
3.
4.
Circulation 1984, 70:812-823.
Circulation 1991, 84:1698-1708.
P139 Computer simulation of the left ventricular pressure–volume relationship (LVPVR)
G Mion, P Koulmann and Y LeGulluche
D.A.R., HIA Val de Grâce, BP 302-F-00446 Armées
Crit Care 1999, 3 (suppl 1):P139
Background: The concept of time-varying elastance developed by
Suga and Sagawa in the 1970s integrates on the same graph all the
components of LV function: contractility (Ees, slope of ESPVR
[1]), preload (Ved), afterload (slope Ea ~ HR.SVR), matching of
LV with arterial system (graphical analysis of SV) and LV efficiency [2]. A computer simulation makes it a remarkable didactic
tool.
Methods: Input data: volume (V); compliance of capacitive vessels
(Cv); venous resistance at the entry of LV(Rv); LV compliance
(CLV); (Ees); zero-volume intercept (Vd); systemic resistances
(SVR); heart rate (HR). Output data: Ved = (MSP.CLV) –
(MSP.CLV–Ves) × e(–t/Rv.CLV) with loading time (t) = (60/HR)–0.2
and mean systemic pressure (MSP)=V/Cv; Ped=e(0.33/CLV)(Ved–Vd)–1;
Ea=HR.SVR;
Ves=(Ea.Ved+Ees.Vd)/(Ees+Ea);
SV=Ved–Ves
PES=Ea.SV; LVEF=SV/Ved; CO=HR.SV; Pressure–volume area
PVA=EW+PE; external work EW (SV.(Pes–Ptd/2); Potential
energy PE=1/2(Ves–Vd).Pes; MVO2=2.5× APV+0.3 × Ees+1; 1
mmHg ~ 1.333 × 10–4 J; mechanical efficiency ME=EW/MVO2.
Results: The computer calculates output values according to input
data and simultaneously modifies the classic graph on the screen.
Discussion: The software simulates realistically the altering of
preload (Ved) and afterload (Ea, HR, SVR), contractility (Ves, Vd)
and the corresponding modifications of ME. LVF and ME evolve
according to theoretic and experimental expectations, i.e. ME =
0.28 to Ved = 250 ml; ME max to Ea/Ees = 0.5.
Figure 1. Results for V = 5500; Cv = 660; Rv = 0.03; CLV = 20;
Ees = 3; Vd = 10; SVR = 20; HR = 75; Ea = 1.5; Ea/Ees = 0.5;
Ved = 123; Ves = 48; LSV = 75; Ped = 5; Pes = 113; CO = 5.6;
EF = 0.61; WE = 1.1; PVA = 1.4; MVO2 = 5.4; ME = 0.21.
References
1. Suga H, Sagawa K, Shoukas A: Circ Res 1973; 32:314322.
2. Suga H, Goto Y, Kawaguchi O, et al.: Bas Res Cardiol
1993; 88 (suppl 2):43-65.
69
70
Critical Care 1999, Vol 3 suppl 1
P140 Prospective, randomized trial of the effect of supranormal oxygen delivery on morbidity and mortality in high
risk surgical patients
SMA Lobo, PS Fialho, AA Borim, SLA Brienze, VG Castilho, CA Polachini and JC Palchetti
Faculdade de Medicina de S.J.R.P., São Paulo, Brazil
Crit Care 1999, 3 (suppl 1):P140
Introduction: This prospective, controlled study was undertaken to
evaluate the response to therapy aimed at achieving supranormal
cardiac and oxygen transport values (cardiac index >4.5 l/min/m2,
oxygen delivery >600 l/min/m2, and oxygen consumption
>170 l/min/m2) in patients older than 60 or with previous severe cardiorespiratory illnesses, who have undergone elective extensive
ablative surgery planned for carcinoma or abdominal aortic aneurism.
Method: Thirty-seven consecutive high risk patients who underwent major surgery were randomized. The postoperative hemodynamic and oxygen transport variables and outcomes in 18 patients
(control group ) treated to maintain normal hemodynamic values
were compared with 19 patients (protocol group) treated to maintain supranormal values. Therapy in both groups consisted of
volume expansion, vasopressors, and when necessary, dobutamine
(3–30 µg/kg/min), to reach their target values, during the surgery
and 24-h postoperative period.
Results: We interrupted the study as a significative difference in
mortality rate was seen. The mortality rate in control group (50%)
was significantly higher (P < 0.05) when compared with protocol
group (15.7%). The incidence of clinical and infectious complications was higher in control group (P < 0.05) and organ dysfunction
evaluated by SOFA score occurred more frequently in non-achievers.
Conclusions: Patients with a previous cardiorespiratory illness or
older patients submitted to extensive surgery had a reduction in
morbidity and mortality with the use of supranormal values as
therapeutic goals during and after the surgical trauma.
P141 Are supranormal values of DO2 defined well?
R Kula and M Májek*
Dept. of Anaesth. & Int.Care, University Hospital, Ostrava, Czech Republic and *Dept. of Anaesth. & Int.Care, Derer’s Hospital, Bratislava,
Slovak Republic
Methods: There were included 36 high-risk surgical patients in
the prospective research (age 53 ± 15 years, 28 male and 8 female,
58% extensive ablative surgery for carcinoma). PA catheter and
arterial catheter were inserted 12 h before surgery in the average.
The target of therapeutical approach was to reach DO2I
>600 ml/min/m2 within 12 h from the end of surgery in every
patient and then to keep these values during following 36 h.
Haemodynamic measurements and laboratory analyses of blood
samples, including arterial lactate, were analysed during the first
48 h after an interval of 6 h. While the data were analysed, we were
comparing the dynamics of changes of DO2 and arterial lactate in
the peri-perative period in relation to the real achievement of the
therapeutical target (DO2I >600 ml/min/m2 within 12 h after the
end of surgery) and the survival rate of the patients.
Results: The 28-day mortality was in the whole group of patients
31% (11/36). We achieved therapeutical target in 22 patients
nonsurvivors
1000
750
750
500
500
250
250
DO2I
Introduction: The physiological assumption of oxygen debt elimination is a spontaneous or therapeutically induced increase of
DO2 in relation to the values of DO2 recorded before the occurrence that led to the oxygen debt formation. The target of this
research was to analyse the relation between post-operative
achievement of DO2I >600 ml/min/m2 and the dynamics of
changes of DO2 during the perioperative period and in that way to
give an answer to the question if the achievement of so called
‘supranormal values’ of DO2 is equal to the physiological principle
of oxygen debt elimination.
survivors
1000
0
Post-oper.
Pre
Post-oper.
P < 0.05 in relation to pre-operative value
NS in relation to pre-operative value
Figure 1. Perioperative oxygen
delivery.
nonsurvivors
8
8
6
6
4
4
2
2
0
0
Pre
survivors
Lactate
Crit Care 1999, 3 (suppl 1):P141
0
Post-oper.
Post-oper.
P < 0.05 in relation to average value during
fiirst 24 h after surgery
Figure 2. Postoperative arterial
lactate.
(61%). The mortality was 23% (5/22) in this group which was not
statistically lower compared to the group of patients where the
target was not achieved (43%, 6/14). When we compared the
dynamics of changes of DO2 and arterial lactate during the perioperative period in relation to the real achievement of the therapeutical target and surviving of patients, we found out in group of
patients which achieved target the results which are demonstrated
on the following figures. The results which were found out in
group of patients which did not achieve target were the same.
Conclusion: Regardless of post-operative achievement of DO2I
>600 ml/min/m2, in survived patients there was observed that they
were achieving statistically higher values of DO2 in comparison
with pre-operative values of DO2 and this process was accompanied by a decrease of arterial lactate level. We suppose that supranormal values of DO2 should be define in relation to the
pre-operative (i.e.normal) values of DO2 and not in relation to the
‘magic number’ 600 ml/min/m2.
Poster abstracts
71
P142 Correlation between three methods of calculating oxygen extraction ratio (OER)
B Prasad, S Giles and F Gao Smith
Intensive Care Unit, Birmingham Heartlands Hospital, Birmingham, UK. Fax: +44 0121 685 5545; E-mail: jefg.smith@virgin.net
Crit Care 1999, 3 (suppl 1):P142
Regression Plot
Y = 4.08665 + 1.03373X
R-Sq = 0.795
Introduction: OER can be calculated using OER =
(SaO2–SvO2)/SaO2. SaO2 and SvO2 can be measured by blood gas
analysis or by continuous non-blood sampling display. The aim of
this study was to compare the three methods of calculating OER.
50
OER3
Methods: Sixty-five sets of measurements from 16 patients were
studied. Arterial and continuous cardiac output with SvO2
(SvO2–CCO, Baxter) catheters were inserted. Simultaneous blood
samples were taken for arterial and mixed venous blood gas measurements using co-oximetry. Continuous SaO2 from pulse oxymetry (SpO2) was recorded. OER was calculated using three methods
for each set of measurements: Conventional blood sampling
method: OER1 = (SaO2–SvO2)/SaO2; Partial blood sampling
method: OER2 = (SaO2–SvO2-CCO)/SaO2; Non-blood sampling
method: OER3 = (SpO2–SvO2-CCO)/SpO2. Simple linear regression with 95% confidence intervals was applied to test the correlation between the three methods.
60
40
30
20
Regression
95% CI
10
10
20
30
40
50
OER1
Regression Plot
Y = 3.15348 + 1.06154X
R-Sq = 0.770
Results: There was a significant positive correlation (P < 0.001)
between the three methods.
60
50
OER2
Regression Plot
– 0 2
Y = –5.1E + 1.00241X
R-Sq = 0.991
40
30
60
20
OER3
50
Regression
95% CI
10
10
40
20
30
40
50
OER1
30
Regression
95% CI
20
20
30
40
50
60
OER2
Discussion: These three methods can be used to calculate OER.
However, the conventional method (OER1) appears to have more
variability than OER2 and OER3. OER3 (SpO2 and SvO2–CCO),
in contrast, is the simplest and most accurate method for continuous monitoring of OER in intensive care management.
P143 Relationship between oxygen extraction (OER) and age in septic patients
M Piagnerelli, E Carlier, S Jamart, K Zouaoui Boudjeltia* and P Lejeune
Department of Intensive Care and *Experimental Medicine Laboratory, CHU A, Vesale, 6110 Montigny-le-Tilleul, Belgium
Crit Care 1999, 3 (suppl 1):P143
Introduction: A pathologic dependency between oxygen consumption (VO2) and oxygen transport (DO2) is characteristic of
septic patients. Septic state appears to be associated with a defect
in oxygen extraction (OER = VO2/DO2), causes possible cellular
hypoxia, mitochondrial dysfunction and development of multiple
organ failure. We studied the relationship between the mean OER
and age in septic patients in a 12-bed ICU.
Methods: We investigated 53 septic patients (age range 20–93
years), invasively monitored in a descriptive study. DO2, VO2 and
OR were obtained in each patient in triplicate during the first 24 h
of sepsis diagnosis. Cardiac output (CO) was determined during
thermodilution. Lactate concentrations were obtained in 46/53
patients (86%) and were elevated in 39%.
Results: We obtained a significant increase of the mean OER
(r = 0.30; P = 0.027, two-tailed) in elderly septic patients. We noted
also a significant decrease of DO2 (P < 0.0001) and VO2 (P = 0.004)
in relation with age. No significant modifications were demonstrated with venous saturation of O2 (SvO2, P = 0.16), arterial saturation of O2 (SaO2; P = 0.7), hemoglobin concentration ([Hb],
P = 0.56) and CO (P = 0.2)] in relation with age.
72
Critical Care 1999, Vol 3 suppl 1
Conclusion: In this descriptive study, mean OER increases in
elderly septic patients. These results are probably explained by
the decrease of DO2 and VO2 in relation with age.
P144 Cardiac index estimation using central venous oxygen saturation (Scv O2) in critical illness
C Ladakis, P Myrianthefs, V Lappas, G Filndisis, A Damianos, S Pactitis and G Baltopoulos
Athens University School of Nursing Intensive Care Unit at ‘Agioi Anargyroi’ Cancer Hospital of Kifissia, Nea Kifissia 14564, Greece.
Department of Intensive Care Unit of ‘IASO’ Maternity Hospital at Athens, Marousi 15123, Greece
Crit Care 1999, 3 (suppl 1):P144
Background: The use of PA catheter is associated with increased
costs and risks to the patients. Central venous (superior vena cava)
oxygen saturation obtained by a less risky and costly manner can
be used to estimate Sv O2 with great accuracy up to 92% according
to our results.
Objective : The aim of this study was to find whether estimated
values of Sv O2 can estimate with accuracy cardiac index using
Fick method in comparison with thermodilution in critically ill
patients.
Material and methods: Sixty-one critically ill patients were
catheterized (Opticath PA Catheter P7110 Abbot) upon their
admission and the values of Sv O2, Scv O2 and CI were simultaneously measured.
Results: The value of Sv O2 was 68.6% ± 1.1 (X ± SEM) , the value
of Scv O2 was 69.4% ± 1.1, pearson correlation coefficient was
r = 0.95 and r2 = 0.89 with standard error 3.01. The power model of
regression analysis which has the expression Sv O2 = b0 (Scv O2)b1
[in our patients Sv O2 = 1.1612 (Scv O2)0.9617] was found to better
describe the relation between the two variables with value of
r2 = 0.92. That means we can estimate the value of Sv O2 from the
value of Scv O2 with accuracy 92%. We used estimated values of
Sv O2 with power model in Fick equation to estimate CI values
and we correlated the estimated CI values with thermodilution CI
values. Thermodilution CI values were 3.93 ± 0.17 (range =
1.85–9.3) and Fick method CI values were 3.88 ± 0.18 (range =
1.3–9.76). Pearson correlation coefficient between them was
r = 0.86 and r2 = 0.73 with high significance (P < 0.001).
Discussion–conclusion: Scv O2 can be used as a mirror of Sv O2 for
the initial evaluation of critically ill patients with value of r = 0.95
and r2 = 0.89. These results are in accordance with other authors
[1,2]. However, some others found that there is poor correlation
and questioned the usefulness of Scv O2 measurement [3]. Power
model of regression analysis which has the expression Sv O2 =
1.1612 (Scv O2)0.9617 can estimate the value of Sv O2 from the value
of Scv O2 with accuracy 92% (r2 = 0.92). The use of estimated
(with power model) value of Sv O2 in Fick equation can estimate
the value of CI with accuracy 86% in comparison with thermodilution (value of r = 0.86).
References
1. Goldman RH, Braniff B, Harrison DC, Spivac AP: The use of
central venous oxygen saturation measurement in a
coronary care unit. Ann Intern Med 1968, 68:1280-1287.
2. Reinhart K, Rudolph T, Bredle DL, Hannemann L, Cain SM:
Comparison of central-venous to mixed-venous oxygen
saturation during changes in oxygen supply/demand.
Chest 1989, 95:1216-1221.
3. Vincent J-L: Does central venous oxygen saturation
accurately reflects mixed venous oxygen saturation?
Nothing is simple, unfortunately. Intensive Care Med
1992, 18:386-387.
P145 AKBR (arterial ketone body ratio) associates with lactate in the lactic acidosis
A Yaguchi, A Amenomori and T Suzuki
Tokyo Women’s Medical University, Department of Emergency and Critical Care Medicine, 8-1 Kawadacho, Shinjuku-ku, Tokyo 162-8666, Japan
Crit Care 1999, 3 (suppl 1):P145
Introduction: Lactate anion is a normal product of anaerobic glycolysis of mitochondria. Lactic acidosis, the serum lactate concentration in increased and metabolic acidemia, relates to the
prognosis of Multiple Organ Dysfunction Syndrome (MODS).
While the AKBR reflects the glycolysis function of liver mitochondria, we hypothesized similar relationships between the
blood concentrations of lactate and the AKBR in lactic acidosis
because when the function of mitochondria is low, aerobic glycolysis in the Krebs cycle is disordered and hyperlactemia is caused.
Methods: We studied 20 MODS patients in our ICU. We surveyed
their blood concentrations of lactate and AKBR and analyzed arterial blood gas when they were in a state of shock. Then we studied
the correlation between the lactate concentrations and AKBR in
lactic acidosis and non-acidosis. The correlation coefficient was
Poster abstracts
73
found by regressional analysis each in lactic acidosis and non-lactic
acidosis.
patients, the blood levels of lactate had no relation with the
AKBR.
Results: Among 20 MODS patients, in 10 lactic acidosis patients
who were all type A lactic acidosis the blood levels of lactate and
the AKBR were interrelated. The correlation coefficient was 0.75
and that showed the blood levels of lactate correlated closely with
the AKBR in lactic acidosis. When the AKBR was low, the blood
level of lactate rose, but in the other 10 non-lactic acidosis
Conclusion: We conclude that the AKBR has a strong relation to
the concentration of lactate in lactic acidosis, but in non-lactic acidosis there was no relation. This study clinically proves that in
lactic acidosis the blood concentration of lactate reflects the
AKBR which is shown by the malfunction of liver mitochondria.
Now right at the bed side, we can survey lactate concentrations
easier and at a lower cost than the AKBR.
P146 Blood lactate: an excellent prognostic indicator in high-risk surgical patients
AF Meregalli, UL Sant’Anna, ES Oliveira and G Friedman
Central ICU of Santa Casa Hospital – Rua Fernando Machado 455/503. Porto Alegre–Brazil-90010-321. Tel/Fax: 55513116649;
E-mail: gfried@portoweb.com.br
Crit Care 1999, 3 (suppl 1):P146
Objectives: To evaluate the prognostic value of blood lactate
levels in high-risk surgical patients.
Methods: Forty-four consecutive patients admitted to a general
ICU for high-risk non-cardiac post-operative care. We recorded
blood lactate levels, mean arterial pressure (MAP), heart rate (HR)
and PaO2/FIO2 ratio at admission, 12, 24 and 48 h. We also
recorded SAPS II score, surgery duration, number of complications, length of ICU and hospital stay for all patients.
Results: 39 patients survived, and 34 had no complications during
their stay in the ICU. The survivors had blood lactate levels lower
than the non-survivors at 12 (1.67 ± 0.8 vs 3.16 ± 1.7; P = 0.004) and
24 h (1.5 ± 0.7 vs 2.3 ± 0.6; P = 0.05) but not at the admission. The
blood lactate levels decreased in the survivors (P = 0.002) but not
in the non-survivors. Blood lactate levels was lower among noncomplicated patients (none complication) at admission (2.12 ± 0.85
vs 3.21 ± 2; P = 0.01); 12 h (1.63 ± 0.8 vs 2.5 ± 1.6; P = 0.02) and 24 h
(1.36 ± 0.47 vs 2.1 ± 0.9; P = 0.004). Blood lactate levels decreased
in the non-complicated patients (P = 0.004) but not in the complicated patients. All others variables were not statistically different
between groups. The length of ICU stay was greater in the nonsurvivors (P < 0.0001) but not the hospital stay.
Conclusion: Blood lactate level was the best prognostic indicator
in our population when compared to other variables often used at
bedside, including SAPS II score.
P147 Outcome of early hyperlactataemia in critically ill children
M Hatherill, A McIntyre, M Wattie and IA Murdoch
Paediatric Intensive Care Unit, Guy’s Hospital, St Thomas’ Street, London SE1 9RT, UK
Crit Care 1999, 3 (suppl 1):P147
Objective: To examine the relationships between hyperlactataemia, acidosis, organ failure, and mortality in children admitted to intensive care.
Design: Prospective observational study. Children with lactate
levels >2 mmol/l within 24 h of admission were enrolled. Post-
operative patients and those with inherited metabolic disease
were excluded. The Paediatric Risk of Mortality (PRISM) score,
Multiorgan System Failure (MOSF) score, length of ICU stay, and
outcome were recorded. Data were collected for pH, base deficit
(BE), and lactate (mmol/l) on admission, at 12 and 24 h. Data are
reported as median (range). Fifty children aged 20.3 months
(0.1–191) were enrolled. Data were analysed by the MannWhitney, Fisher’s Exact, Kruskal-Wallis tests, and the Chi-squared
test for trend.
74
Critical Care 1999, Vol 3 suppl 1
Results: Median PRISM score was 19 (4–49), median MOSF score
2 (0–5), and observed mortality 32/50 (64%). Median duration of
ICU stay was 6 days (2–32) in survivors, and median time until
death 3 days (0–13) in nonsurvivors. Eleven nonsurvivors (34%)
died within 24 h.
Admission lactate did not increase with increasing MOSF score
(P = 0.5). However mortality increased with increasing MOSF
score (P = 0.005).
Conclusion: Early hyperlactataemia is associated with a high mortality in critically ill children. Organ failure and peak lactate levels
may distinguish nonsurvivors in this group.
Survivors
(n = 18)
Nonsurvivors
(n = 32)
P
Age (months)
19 (0.1–184)
21 (0.1–191)
0.5
MOSF score
2 (0–4)
3 (1–5)
Admission pH
7.32 (6.8–7.6)
7.3 (7.0–7.7)
0.6
Admission BE
–7.5 (–14 to 5)
Parameter
0.005
–8 (–30 to 3)
0.45
Admission lactate (mmol/l) 3.8 (0.9–8.5)
4.6 (1.2–22)
0.27
Peak lactate (mmol/l)
6.8 (2.3–22)
0.02
5.0 (2.0–9.3)
P148 Artificial colloids influence survival rate of human monocytes
N Deschner, S Rieg, H Häberle and H-J Dieterich
Department of Anaesthesiology, University of Tübingen; Hoppe Seyler Str. 3, 72076 Tübingen, Germany
Crit Care 1999, 3 (suppl 1):P148
performed. Slope values were tested with Students’t-test against
0. Significance was assumed for P < 0.05.
Introduction: Monocytes are within the first line of an organisms
immune defense. However in the course of sepsis they undergo
apoptotic cell death [1,2]. It is unclear whether this serves to
protect the organism from a hyperreactive inflammatory response
or is a sign for immune dysfunction.
The artificial colloids hydroxyethylstarch (HES), dextran (DEX)
and gelatine (GEL) are essential in perioperative volume replacement as well as in the treatment of trauma, shock and sepsis. In
this study we investigated whether artificial colloids influence survival or apoptosis of human monocytes in vitro.
Methods: Monocytes were isolated from buffy coats of healthy
donors by gradient centrifugation and adherence to plastic culture
dishes. They were incubated for 8 h with HES, DEX and GEL at
10 to 40 mg/ml. Staurosporine was added to induce cell death.
Alive, apoptotic and necrotic cells were identified by Annexin
V/Propidium Iodide staining and 10 000 cells were analysed by
flow cytometry. Presence of apoptotic cell death was confirmed by
electron microscopy, TUNEL, and cell death detection ELISA.
Regression analysis of colloid concentration against cell status was
Results: All artificial colloids reduced the fraction of viable cells in
a concentration dependent manner. This effect was significant
with DEX. Apoptotic cells, which were calculated as a fraction of
dead cells were reduced with DEX more than with HES, but
increased significantly with GEL.
Incubation with staurosporine reduced cell viability and increased
the fraction of apoptotic cells. Neither colloid nor concentration
had additional influence. Only the results for HES are shown.
Conclusion: DEX, HES, and GEL promote monocyte death in
vitro. This effect is concentration dependent, but most obvious
beyond concentrations found in clinical practice. Cell viability is
reduced most by DEX, whereas GEL seems to delay the course
of cell death, as apoptotic cells undergo secondary necrosis in
vitro. Staurosporine induced cell death is not blocked.
References
1. Baran J et al.: Infect Immun 1996, 64:4242-4248.
2. Ayala A et al.: J Trauma 1996, 40:568-574.
Concentration of colloids (mg/ml)
Culture medium
Colloid added
Status of monocytes
Standard
HES
Staurosporine
400 nM added
0
10
20
40
Alive
% apototic/dead
58.15
17.63
53.33
17.35
50.35
16.77
45.25
15.23
GEL
Alive
% apototic/dead
58.15
17.63
53.8
23.96
52.58
25.53
52.48
26.6
DEX
Alive
% apototic/dead
58.15
17.63
53.25
17.24
51.86
16.45
43.93
12.2
HES
Alive
% apototic/dead
31.15
34.39
31.05
34.27
32.81
33.75
29.29
33.64
P149 Determination of the clearance factor for TSE agents during the manufacturing process of polygeline
S Peano, G Reiner*, M Carbonatto, L Bodenbender*, P Boland* and KJ Abel*
LCG-RBM, Istituto di Ricerche Biomediche ‘A. Marxer’, S.p.A., 10015 Colleretto Giacosa (TO), Italy, *Hoechst Marion Roussel Deutschland GmbH,
D-35001 Marburg, Germany
Crit Care 1999, 3 (suppl 1):P149
Polygeline (a polymer prepared from heat-hydrolyzed gelatine) is
a plasma substitute used by infusion as a 3.5% solution in the
Poster abstracts
management of hypovolaemic shock. TSEs (transmissible spongiform encephalopathies) are a group of fatal neurodegenerative
(CNS) diseases affecting humans (e.g. Kuru, CJD) and animals
(e.g. ovine scrapie, bovine BSE), all caused by a common class of
agents, Prions. The link between TSEs and polygeline lies in its
precursor, the gelatine which derives from bovine bones; bones
may be at risk due to adjacent CNS (skull and vertebrae) contamination. In this experiment the main steps of the manufacturing
process of polygeline were validated in order to see if the process
is able to reduce the risk of iatrogenic transmission of the infectious agent, if present. It is the first time that results of a validation study on a gelatine-derived product have been published.
Three steps of the process were validated separately: in step 1,
gelatine was subjected to three alternative autoclaving schedules
(1A: 121°C for 1.5 h; 1B: 121°C for 3 h; 1C: 133°C for 40 min). Step
2 was the crosslinking and distillation phase, and Step 3 the final
sterilization at 121°C for 45 min. The hamster-adapted 263K strain
of scrapie was used as the TSE model. The infective spike was
75
added to each material before being processed and titrated in
hamsters. Each assay was performed in duplicate, and animals
were monitored for 1 year. The initial hamster-titrated infectivity
of the spike resulted in 109.0 LD50/2 ml. From the preliminary
results of the experiment, only based on symptomatology (histological results of all brains expected till February 1999), the
average step-clearance of infectivity (mean of two replicates) was
(LD50/2 ml): 106.0 (1A), 106.9 (1B) and ≥107.4 (1C), 102.4 (2) and
104.6 (3). It is clear that heating the gelatine (step 1) was very effective in reducing the infectivity of TSE agents. Taking also into
account that the initial experimental contamination level adopted
was extremely high, that raw materials used in the real production
are carefully selected from a BSE-free country (USA) and exclude
the skull and spinal cord, that the starting material - gelatine - is
already produced by BSE-reducing procedures, and that steps 2
and 3 also contribute to lowering the infectivity, if any, it may be
concluded that the polygeline manufacturing process is capable of
inactivating BSE agents to a very high extent.
P150 Persistent pruritus after hydroxyethyl starch (HES) infusions in critically ill patients
C Sharland, A Huggett and M Nielsen
General Intensive Care Unit, Southampton University NHS Hospitals Trust, Tremona Rd, Southampton, SO16 6YD, UK. Tel: 01703 794216;
Fax: 01703 796119
Crit Care 1999, 3 (suppl 1):P150
Introduction: It was noticed that severe persistent pruritus was a
common complaint in patients attending our nurse-led ICU follow
up clinic. Pruritus is a known adverse effect after hydroxyethyl
starch (HES) infusions [1]. We therefore undertook this retrospective study to clarify any association between pruritus and HES
infusions.
Method: Questionnaires were sent to all surviving patients who,
over a 6 month period, had been on ICU for greater than 24 h
(n = 100). The 19 questions covered a wide range of areas including general well-being, quality of life, mood and memories of
intensive care. Two questions asked about itching. Respondents
complaining of pruritus and non respondents were telephoned.
Standardised questions were asked to identify incidence, severity,
duration, triggering or relieving factors and the parts of body
affected. For patients, the volume of HES received in the ICU
was identified from ICU charts. Statistical analysis was by MannWhitney U test, with significance determined by P < 0.05.
Results: Details were obtained from 73 patients. 34% had experienced pruritus since their discharge from ICU. Of these 44% had
severe persistent pruritus, which had not resolved with conventional treatments. In patients with pruritus, the total volume of
HES infused ranged from 0–27350 ml, (median 2000 ml), infused
over a mode of 2 days. The ‘non pruritus’ group, total HES
volume ranged from 0–13350 ml, (median 500 ml), infused over a
mode of 1 day. There was a significant relationship between the
volume of HES and the occurrence of pruritus (P = 0.003).
Conclusion: This retrospective study shows that HES infusions
may be associated with persistent pruritus. This may seem a trivial
problem after a life-threatening illness, but our experience suggests that it significantly detracts from quality of life in survivors.
Reference
1. Speight EL, MacSween RM, Stevens A: Persistent itching
due to etherified starch plasma expander. BMJ 1997,
314:1466-1467.
P151 Volume replacement after cardiac surgery: a comparative study between hydroxyethylstarch (6%, 70/0.5),
gelatin (3.5%) and Ringer’s solution
N Huebner, K-F Klotz*, F Woroszylski†, J Darup†, H-J Krebber†, P Schmucker* and U Christmann
Department of Anesthesiology, Schuechtermann Klinik, Bad Rothenfelde, Germany, Ulmenalle 11, 49214 Bad Rothenfelde, Germany,
*Department of Anesthesiology, Medizinische Universität zu Lübeck, Germany and †Department of Cardiac Surgery and Anesthesiology, CardioClinic,
Hamburg, Germany
Crit Care 1999, 3 (suppl 1):P151
Introduction: During hypothermic cardiopulmonary bypass (CPB)
patients often experience vasoconstriction and later their peripheral circulations gradually dilate over a period of several hours.
The redistribution of circulation produces hypovolemia for which
volume loading is necessary. Our aim was to compare 6% hydroxyethylstarch (70/0.5), 3.5% polygelin and Ringer’s solution when
used for volume restoration during the first 6 h after CPB. We
were especially interested in hemodynamic stability, plasma viscosity, bleeding, volume uptake and oxygenation index
(PaO2/FiO2).
Methods: Ninety adult patients undergoing cardiac surgery and
CPB were randomized before surgery to one of three fluid regimens. The groups were comparable with respect to age, sex, heart
function and pre-existing diseases. Hemodynamic function,
plasma viscosity, mediastinal blood loss, and volume uptake were
76
Critical Care 1999, Vol 3 suppl 1
measured after 30 min, 60 min postoperatively and then every
hour during the first 6 h after surgery. The oxygenation index was
measured 1, 3 and 6 h after surgery. A P value <0.05 was considered significant.
Results: There were no significant intergroup differences in any of
the hemodynamic variables MAP, CVP and HR. There was no significant difference among the three groups in the plasma viscosity
after surgery. Mediastinal blood flow increased significantly in the
HES group 2–6 h after surgery (P < 0.05) compared with the geline
and Ringer’s group. The two colloid groups needed significantly
less fluid compared with the Ringer’s group (P < 0.05). There were
no differences in diuresis. There were no significant intergroup
differences in the oxygenation index. The need for postoperative
ventilatory support did not vary between the three groups.
Conclusion: This randomized comparison of two colloid and a
Ringer’s solution fluid regimens after cardiac surgery shows that
there is no difference in hemodynamic stability, plasma viscosity,
oxygenation index and duration of intubation. The HES group
has a significantly higher blood loss. The Ringer’s group has a significant higher volume uptake. The colloid-free regimen did not
affect the pulmonary function.
The colloid-free Ringer’s solution regimen is clinically fully
acceptable and economically more favourable than the two colloid
fluid regimens studied.
P152 Extracellular fluid variations during a fluid challenge: a comparison of normal saline (NS) and hydroxyethyl
starch (HES) in stressed patients
P Singer, A Kogan, V Zolotarski, E Grozovski and J Cohen
General Intensive Care, Rabin Medical Center, Campus Beilinson, Petah Tikva, Israel
Crit Care 1999, 3 (suppl 1):P152
The controversy regarding the use of crystaloids or colloids for
fluid resuscitation of critically ill patients continues. Fluid remaining in the vascular compartment would have an obvious advantage. We used bioimpedance, a technique allowing assessment of
body cell mass and extracellular water, to compare NS and HES, a
relatively new colloid.
Methods: Twenty-two critically ill patients requiring a fluid challenge were randomized to receive either 500 ml of NS or 500 ml of
HES 10% (Fresenius, Germany). Vital signs (heart rate, systolic
blood pressure, central venous pressure (CVP) and urine output)
were noted before and immediately after the challenge. Bioimpedance changes, using a tetra-polar system working on 800
microamperes and 50 Khz (BIA-109), Ackern) were measured
before and after the fluid challenge. Body cell mass (BCM) and
extracellular water (ECW) were then derived. Results are
expressed as the mean ± SD.
Results: Ten patients (mean age 57 ± 18.6 years) received HES
10% and twelve (mean age 56.9 ± 13.9 years) received NS. There
were no significant differences between the two groups regarding
pre- and post-challenge hemodynamic parameters, in particular
change in CVP. Bioimpedance measurements before and after
fluid challenge were as follows:
NS group (n = 12)
Before
BCM (kg)
43.0 ± 11.4
ECW (%)
55 ± 10.3
After
HS 10% group (n = 10)
Before
After
43.3 ± 10.7
30.7 ± 14.5 31.1 ± 16.1
56.3 ± 10.6*
63.0 ± 5.3
63.9 ± 6.4
*P < 0.03 versus before value
Conclusion: We showed that there is an increase in extracellular
water in critically patients receiving a fluid challenge with normal
saline but not with HES. This could indicate a beneficial effect of
HES on extravascular extravasation of water in stressed patients.
P153 HES 130/0.4, a new HES specification: tissue storage after multiple infusions in rats
F Bepperling, J Opitz and J Leuschner*
FRESENIUS AG, D-61346 Bad Homburg, *LPT Laboratory of Pharmacology and Toxicology, D-21147 Hamburg, Germany
Crit Care 1999, 3 (suppl 1):P153
Hydroxyethyl starches (HES) are widely used in volume replacement therapy. One point of concern is tissue storage after repetetive dosing [1]. A controlled, multi-dose study was performed in
48 female rats. Daily infusions of 14C radio-labelled HES 130/0.4
or HES 200/0.5 (0.7 g/kg bw) were administered on 18 consecutive
days. HES tissue storage was measured 3, 10, 24 and 52 days after
the last administration in the total body, carcass, liver, spleen,
kidney and lymph nodes.
Significantly reduced HES storage (P < 0.01) was observed in the
HES 130/0.4 group in total body, carcass and liver compared to the
HES 200/0.5 group, while no differences were found in spleen,
kidney and lymph nodes. These results clearly demonstrate significant differences of HES tissue storage between two HES specifications after repetetive administration of clinically relevant
dosages. Even if the clinical relevance of tissue storage remains
under debate the reduction in the HES 130 group per se seems
advantageous. (See overleaf for Table.)
Reference
1. Ginz et al.: Excessive tissue storage of colloids in the
reticuloendothelial system. Anaesthesist 1998, 47:330334.
Poster abstracts
77
Radioactivity per organ expressed as percentage of the administered total HES dosage (mean)
Days after the last administration
3
Organ
n
Total
10
24
52
HES 130
HES 200
HES 130
HES 200
HES 130
HES 200
HES 130
HES 200
8
8
8
8
4
4
4
4
4.32*
7.72
2.04*
3.97
1.38*
2.86
0.65 *
2.45
Carcass
3.03*
6.02
1.56*
3.29
1.09 *
2.33
0.49 *
2.03
Liver
1.09*
1.44
0.37*
0.56
0.24 *
0.45
0.05
0.26
Spleen
0.07
0.12
0.05
0.06
0.03
0.04
0.03
0.06
Kidney
0.11
0.13
0.05
0.05
0.02
0.02
0.02
0.02
Lymph node
0.02
0.01
0.01
0.01
0.00
0.03
0.06
0.08
*P < 0.01 (student’s t-test)
P154 HES 130/0.4, a new HES specification: pharmacokinetics after multiple infusions of 10% solutions in healthy
volunteers
F Bepperling, J Opitz, J Waitzinger*, G Pabst*, M Müller* and JF Baron†
FRESENIUS AG, D-61343 Bad Homburg, *L.A.B. GmbH & Co, D-89231 Neu-Ulm, Germany, †Hôpital Broussais, Départment d’AnesthésieRéanimation, F-75014 Paris, France
Crit Care 1999, 3 (suppl 1):P154
Both the peak plasma HES concentration and the time course of
the plasma concentrations were similar on Day 1 and Day 10 of
treatment. There was a marginal increase in the plasma HES concentration 24 h after the infusion, from approximately 0.23 mg/ml
on Day 1 to approximately 0.48 mg/ml on Day 10. HES was eliminated from the plasma rapidly, with α- and β-half-lives of some 1.2
h to 1.4 h and 21.9 h, respectively. The β-half-life on Day 1 could
not be determined with sufficient reliability since the next infusion was given only 24 h later. Although the baseline-corrected
AUC0–∞ on Day 1 is thus likely to have been underestimated, the
geometric mean of 32.8 h·mg/ml was in fairly close agreement with
the result of 35.7 h·mg/ml determined for the AUC0–∞ on Day 10.
The results for the urinary recovery of 69% on Day 1 and of 70%
on Day 10 agreed very well. It was demonstrated that no clinically
9
Plasma Concentrations [mg\mL]
An open, one-way, multiple-dose study was performed in twelve
(12) healthy male volunteers. Daily infusions of 500 ml of HES
(130/0.4) 10% solution were administered within 30 minutes on 10
consecutive days. The plasma and urine HES concentrations were
determined repeatedly in the course of the study, up to 72 h after
the final infusion.
8
7
6
5
On Day 1
On Day 10
4
3
2
1
0
0 1 2
4
6
Time after HES infusion [h]
8
12
24
Fig.1 Plasma Levels of HES After Infusion of 500 mL HES
(130/0.4) on day 1 and day 10 (mean +/- SD) n = 12
relevant accumulation of HES occurred in plasma after multipledose administrations of 10 times 500 ml of 10% HES (130/0.4)
solutions.
P155 Effect of hypertonic dextran on intestinal mucosal perfusion during porcine endotoxin shock
Y Oi, A Åneman, M Dahlqvist, M Svensson*, S Ewert* and H Haljamäe
Department of Anesthesiology and Intensive Care, Sahlgren’s University Hospital, S- 413 85 Göteborg, Sweden, *Dept of Physiology, Göteborg
University, S-413 45, Göteborg, Sweden
Crit Care 1999, 3 (suppl 1):P155
Introduction: Mucosal hypoperfusion during sepsis might impair
the epithelial barrier function leading to translocation of luminal
bacterial products and further aggravation of the septic state. Supporting perfusion of the intestinal mucosa could ameliorate barrier
dysfunction. The microcirculatory effects of hypertonic vs isotonic
colloid volume resuscitation during sepsis have with respect to
mucosal perfusion been sparsely reported.
78
Critical Care 1999, Vol 3 suppl 1
Aim: To evaluate the effects of hypertonic vs. isotonic colloid
volume resuscitation to maintain mucosal perfusion during
porcine endotoxemia.
Interventions: Fasted, anesthetised, mechanically ventilated pigs
(30.6 ± 2.0 kg, mean ± SEM) received infusion of LPS (EC
seropype 0111: B4) during 2 h to establish septic shock and were
then observed for another 90 min. After 1 h of LPS infusion,
animals were randomized to resuscitation (4 ml/kg for 10 min) with
isotonic dextran (Macrodex®, ISO, n = 6) or hypertonic dextran
(RescueFlow®, HYPER, n = 6).
Measurements and main results: Mean arterial pressure (MAP),
cardiac output (CO), portal venous blood flow (QPV), mucosal
perfusion by laser-Doppler flowmetry (LDF) and tonocapnometry
(giving regional prCO2 and the pCO2 gap from paCO2) were
assessed. Statistical analyses were made by ANOVA. §P < 0.05 vs.
60 min. *P < 0.05 vs. ISO.
LPS-infusion resulted in hypodynamic shock after 60 min with no
intergroup differences. Resuscitation with HYPER improved the
mesenteric and specifically the mucosal circulation, whereas ISO
was ineffective in this respect. HYPER also tended to improve
CO while this effect failed to gain statistical significance
(P = 0.11).
Conclusion: Volume resuscitation with hypertonic colloid proved
superior to isotonic colloids to support intestinal and in particular
mucosal perfusion during hypodynamic septic shock. The results
indicate that hypertonic colloids might be of special value to
support mucosal perfusion and thereby possibly barrier function in
sepsis.
Baseline
60 min
120 min
180 min
210 min
MAP
HYPER
ISO
96 ± 10
109 ± 4
54 ± 7
56 ± 7
43 ± 3§
45 ± 9§
44 ± 5
35 ± 10§
38 ± 6§
35 ± 9§
CO
HYPER
ISO
4.6 ± 0.5
44.8 ± 0.4
3.2 ± 0.4
3.0 ± 0.3
3.5 ± 0.4
3.2 ± 0.4
3.4 ± 0.5
2.1 ± 0.4
2.8 ± 0.7
1.3 ± 0.5
QPV
HYPER
ISO
958 ± 49
946 ± 76
916 ± 147
882 ± 145
1143 ± 326§
1082 ± 248§
1152 ± 164§
698 ± 146
972 ± 258*
283 ± 152
LDF
HYPER
ISO
268 ± 48
248 ± 18
220 ± 25
177 ± 14
255 ± 41
185 ± 34
234 ± 28
153 ± 25
194 ± 12*
103 ± 18§
TONO
HYPER
ISO
1.6 ± 0.6
1.4 ± 0.6
2.9 ± 1.1
2.6 ± 0.6
2.9 ± 0.9
3.5 ± 1.3
3.9 ± 1.0
5.5 ± 1.0§
4.1 ± 0.9*
8.3 ± 0.5§
P156 Splanchnic microcirculation after resuscitation with hypertonic saline in a porcine model of cardiac
tamponade
M Dahlqvist, A Åneman and H Haljamiäe
Department of Anaesthesiology and Intensive Care, Sahlgren’s University Hospital, 413-45 Gothenburg, Sweden
Crit Care 1999, 3 (suppl 1):P156
Background: The beneficial effects of hypertonic saline (HS) for
resuscitation in hypovolemic shock have long been known, it has
also been reports on positive effects of HS on microcirculation in
different organ systems. HS is known to increased cardiac output,
reduce afterload and blood viscosity, it is also known to improve
capillary blood flow by endothelial deswelling. However, there is
very few data on the effects of HS on microcirculation in low
cardiac output stakes.
Aim: The aim of this study was to investigate the effects of HS on
splanchnic microcirculation in a model of cardiac tamponade with
subsequent disturbances in splanchnic microcirculatory flow.
Materials and methods: The study design was randomised and
crossover. Seven pigs of both sexes, weighing 27–35 kg were
included in the study. After induction of anaesthesia all animals
were tracheotomized. Central hemodynamics, portal venous blood
flow and gastric, hepatic and renal microcirculation were measured simultaneously. Microcirculation was measured with LaserDoppler technique. Cardiac tamponade was established with
infusion of dextran in the pericardium. After stabilization of the
tamponade the animals were resuscitated with either HS or
Ringer’s acetate (4 ml/kg) during 20 min. Changes of perfusion
were evaluated with ANOVA and paired comparisons were made
by Wilcoxon* P < 0.05 HS versus R–Ac.
Results: There was a significant increase in portal venous flow in
the HS group, there was also a significant increase in microcirculatory flow in gastric mucosa, hepatic and renal surface microcirculation in the HS group. Those changes were not present in the R-Ac
group. Values in Table are absolute changes by volume resuscitation during cardiac tamponade.
CO
(l/min)
Gastric
(PU)*
Liver
(PU)*
Kidney
(PU)*
v.Porta
(ml/min)*
HS
+0.28
+19.4
+48
+5.9
+71
R–Ac
+0.22
–2.8
+2
–8.6
+7
Conclusion: We conclude that HS is beneficial for microcirculation
in this model of cardiac tamponade and associated disturbances
microcirculatory flow in the splanchnic system. The increase of
microcirculatory flow could prevent initialization of inflammatory
processes and bacterial translocation and thereby prevent initiation of multi organ failure.
Poster abstracts
79
P157 A randomised controlled trial of low-dose dopamine in postoperatively ventilated patients in the ICU: renal
effects and the influence on outcome
K Schulze, J Unger, R Uebelen, L Verner, A Bornscheuer and S Piepenbrock
Dept. of Anaesthesiology, Medical School Hannover, Carl-Neuberg-Str.1, D-30625 Hannover, Germany. Tel.: 0049 511 532-2345; Fax: 0049 511 532-3642
Crit Care 1999, 3 (suppl 1):P157
Background: Despite the widespread use of low-dose dopamine in
the ICU, there are only a few conflicting studies on its (protective)
renal effects, some of them with contradictory results [1,2]. Consequently, we investigated renal effects as well as morbidity and
mortality rates in patients being ventilated postoperatively in our
ICU.
Patients and methods: Three hundred and forty-seven urology
and abdominal surgery patients were randomised into two groups:
A) no dopamine (n = 174) and B) dopamine at 2 µg/kg/min for the
duration of intensive care treatment (n = 173). Creatinine and urea
were determined at admission in our ICU (day 1) and the next day
at 7 a.m. (day 2) together with hourly diuresis. Complications,
length of stay and outcome from ICU treatment were recorded.
The study was approved by the local Ethics Committee and
informed consent was obtained from the patient prior to admission for surgery. Paired and unpaired Student’s t-tests, Fisher’s
Exact Test and Chi square tests were used for statistical analysis.
Creatinine (µmol/l)
Urea (mmol/l)
+1.9 ± 37.1
–1.1 ± 40.1
n.s.
+0.03 ± 1.2
–0.1 ± 1.7
n.s.
Group A
Group B
Significance
Results: The individual differences for creatinine and urea
(day 2–day 1) (mean ± S.D.) are shown in the table: (Complications: Group A) 38 pts. (22%), B) 38 pts. (21.8%) [n.s.]).
Conclusion: In our study, dopamine caused a significant diuresis
without significant changes in creatinine or urea levels. Low-dose
dopamine was not associated with a higher incidence of adverse
cardio-circulatory reactions. We observed no protective effect on
the incidence of ARF and our results indicate that low-dose
dopamine may be associated with unfavourable outcomes, in
particular higher mortality.
References
1. Flancbaum L, Choban PS, Dasta JF: Quantitative effects of
low-dose dopamine on urine output in oliguric surgical
intensive care unit patients. Crit Care Med 1994, 22:61-66.
2. Baldwin L, Henderson A, Hickman P: Effect of
postoperative low-dose dopamine on renal function after
elective major vascular surgery. Ann Intern Med 1994,
75:744-747.
Diuresis (ml/kg/h) Cardio-circulatory events Acute renal failure (ARF) Mortality
2.2 ± 1.2
3.1 ± 1.3
P < 0.001
13 pts. (7.5%)
10 pts. (5.8%)
n.s.
None
5 pts. (2.9%)
P < 0.05
None
7 pts. (4.0%)
P = 0.007
P158 Effect of a dopexamine induced increase in cardiac output on splanchnic hemodynamics in septic shock
P Kiefer, I Tugtekin, M Putzke, H Bracht, G Geldner, J Vogt, M Weiß, H Wiedeck, M Georgieff and P Radermacher
Universitätsklinik für Anästhesiologie, Universität Ulm, 89070 Ulm, Deutschland
Crit Care 1999, 3 (suppl 1):P158
Objective: In patients after cardiac surgery dopexamine is known
to increase both global and hepato splanchnic blood flow. Sepsis
per se and the infusion of noradrenaline may alter the response to
the onset of dopexamine. Therefore we determined the changes in
global and regional hemodynamics in patients with septic shock.
Patients/methods: Twelve patients with septic shock were
studied. All patients had a cardiac index (CI) ≥3 l/min/m2 and
needed noradrenaline ≥ 0.04 µg/kg×min–1 to maintain mean arterial pressure (MAP ≥60 mmHg). In addition to routine systemic
hemodynamics and gas exchange we inserted a balloon-tipped
Swan Ganz catheter into a hepatic vein to determine splanchnic
Median/range
CI (l/min/m2)
Qspl (l/min/m2)
HVOP (mmHg)
HVP (mmHg)
CVP (mmHg)
SVRi (mmHg/l*min–1)
SPLRi (mmHg/l*min–1)
Qspl/CI (%)
blood flow (Qspl), hepatic venous pressure (HVP) and the hepatic
venous occlusion pressure (HVOP) as an estimate of portal venous
pressure. Splanchnic blood flow was measured using the steadystate indocyanine green (ICG) infusion technique. Measurements
were done before, during and after dopexamine infusion. Data
were always obtained after at least 90 min of hemodynamic
steady-state. Dopexamine was titrated (1–4 µg/kg×min–1) to obtain
a 30% increase in CI.
Results: See Table.
Conclusion: The dopexamine induced increase in Qspl paralleled
that of CI. A preferential effect on splanchnic circulation could not
be detected. The increase in Qspl was due to a decreased prehepatic resistance.
Baseline
Dopexamine
Baseline
3.7 (7.6–3.1)
0.86 (1.42–0.24)
15 (18–8)
12 (17–7)
11 (15–6)
17 (21–6)
76 (268–36)
21 (40–7)
4.9 (10.3–3.9)#
0.96 (2.23–0.25)#
16 (25–8)
12 (16–5)
10 (14–3)
14 (16–5)#
65 (296–29)#
19 (53–5)#
4.2 (7.6–3.1)*
0.94 (1.63–0.23)*
16 (26–8)
12 (15–6)
11 (15–4)
16 (21–8)*
70 (284–40)
20 (47–6)
Statistics Friedman-test; Wilcoxon test; #P < 0.05 versus baseline; *P < 0.05 versus dopexamine
80
Critical Care 1999, Vol 3 suppl 1
P159 Effect of dopexamine on CO2-gradients and splanchnic energy balance in septic shock
P Kiefer, I Tugtekin, M Putzke, H Brahct, G Geldner, J Vogt, M Weiß, H Wiedeck, M Georgieff and P Radermacher
Universitätsklinik für Anästhesiologie, Universität Ulm, D-89070 Ulm, Germany
Crit Care 1999, 3 (suppl 1):P159
Objective: Septic shock is characterized by enhanced hepatosplanchnic blood flow resulting from increased metabolic activity.
This hypermetabolism may lead to mismatch of regional O2
supply and demand reflected by increased CO2-gradients and
lactate/pyruvate ratios. In patients after cardiac surgery dopexamine is known to increase splanchnic perfusion. Therefore, we
studied the effect of dopexamine on regional CO2-gradients and
energy balance in patients with septic shock.
vein to measure splanchnic blood flow (Qspl) using primed continuous infusion of indocyanine green (ICG) dye. Moreover, we
assessed splanchnic lactate uptake (Fick principle), hepatic
venous lactate/pyruvate ratio as well as PCO2 (PCO2hv), splanchnic O2 delivery (DO2spl) and consumption (VO2spl). The gastric
mucosal PCO2 (PCO2gm) was determined via a nasogastric tube.
Measurements were done before, during and after dopexamine
infusion. Data were obtained after 90 min of hemodynamic
steady-state. Dopexamine was titrated (1–4 µg/kg×min–1) to obtain
a 30% increase in CI.
Results: See Table.
Patients and methods: Twelve patients with septic shock were
studied. Cardiac index (CI) was ≥3 l/min/m2 and noradrenaline
≥0.04 µg/kg×min–1 was infused to maintain mean arterial pressure
(MAP) ≥60 mmHg. In addition to routine systemic hemodynamics
and gas exchange we inserted a Swan Ganz catheter into a hepatic
Median/range
Conclusion: The unpredictable changes in the metabolic state and
regional PCO2 gradients after a dopexamine-induced increase in
DO2spl, underscores the independent response of hepatosplanchnic perfusion and metabolism to therapeutic interventions.
Baseline
Dopexamine
Baseline
116 (211–39)
130 (323–38)#
120 (233–34)
66 (88–17)
62 (142–14)
61 (113–16)
239 (876–358)
425 (1448–590)
345 (2040 to –578)
27 (61–20)
30 (185–22)
42 (75–21)
PCO2gm–PCO2art (kPa)
2.8 (5.2–0.0)
2.2 (4.2 to –0.3)
2.8 (4.5–0.3)
PCO2mv–PCO2art (kPa)
0.9 (1.5–0.1)
0.6 (1–0.1)
0.8 (1.3–0.3)
PCO2hv–PCO2art (kPa)
1.2 (2.3–0.3)
0.8 (1.7 to –0.1)
1.1 (1.8–0.5)
DO2 index spl (l/min/m2)
VO2 index spl
(l/min/m2)
Lactate utilisation
(µmol/m2/min)
Lactate/pyruvate ratio
Statistics: Friedman-test; Wilcoxon-test; #P < 0.05 versus baseline
P160 Dopeamine does not improve intestinal mucosal perfusion measured by scanning laser Doppler flowmetry
NH Boyle, PC Roberts, A McLuckie, L Giles, RJ Beale and RC Mason
Departments of Surgery and Intensive Care, 2nd floor, New Guy’s House, Guy’s Hospital, St Thomas Street, London, SE1 9RT, UK
Crit Care 1999, 3 (suppl 1):P160
Background: There is conflicting evidence that dopexamine
hydrochloride exerts a selective vasodilating effect upon the gastrointestinal mucosa. Whilst some human studies conducted in
the critically ill and in high risk surgical patients have suggested
that dopexamine may cause an increase in tonometrically measured gastric intra-mucosal pH (pHi) and an improvement in clinical outcome, this has not been confirmed in other randomised
trials. Furthermore, there is no data with regard to dopexamine’s
influence upon small bowel perfusion. Laser Doppler flowmetry
has been used to measure gastrointestinal mucosal blood flow, and
the recent advent of scanning laser Doppler flowmetry appears to
overcome some of the limitations of the single point method. This
study employed this new technique to assess the effect of dopexamine on ileostomy mucosal blood flow.
Method: The study was prospective and double-blind. Fourteen
patients with ileostomies were randomised into treatment (n = 7)
and placebo groups (n = 7). The stomas were exposed to the air
for a period of 20 min whilst the laser Doppler scanner (Moore
Instruments, Axminster, Devon, UK) was positioned above the
patient at a distance of 32 cm. A laser scan was then made, and
the stoma outlined on the photographic image. This equated to
over 2500 individual perfusion measurements on the corresponding perfusion image, allowing calculation of mean perfusion
units (PUs) within the stomal mucosa. Heart rate and mean arterial pressure were recorded. An intravenous infusion of either
dopexamine (2 µg/kg/min) or of a placebo was then commenced
and after 30 min the recordings were repeated. The infusion was
then stopped and a final set of recordings made after 30 min. The
results were analysed using the Mann–Whitney test for non-parametric data.
Pre infusion
Mean PUs (SD)
Mucosal perfusion
Intra infusion
Post infusion
Dopexamine
Control
Dopexamine
Control
Dopexamine
Control
357 (165)
432 (210)
342 (170)
448 (185)
315 (165)
315 (180)
Poster abstracts
Results: There were no significant changes in systemic arterial in
either group during the study. However, in the dopexamine group
there was a significant increase in mean (SD) heart rate from 80
(14) to 94 (7) beats per minute during the infusion and a subsequent fall to 83 (12) beats per minute after its cessation (in both
cases P < 0.05). There was no significant change in mucosal perfusion measured using the scanning laser Doppler during dopexamine or placebo infusion (in all cases P > 0.05).
81
Conclusion: This study is the first to directly measure the influence of dopexamine hydrochloride on ilea mucosal perfusion. The
scanning laser Doppler flowmeter produced easily interpreted
images of the stomas. Dopexamine caused no demonstrable
increase in ileostomy blood flow, and this finding suggests that
any improvement in outcome caused by the drug in the critically
ill may be caused by an alternative mode of action.
P161 Dopexamine does not improve jejunal or gastric tube mucosal perfusion following oesophageal resection
NH Boyle, PC Roberts, A McLuckie, WJ Owen, RJ Beale and RC Mason
Departments of Surgery and Intensive Care, 2nd Floor, New Guy’s House, Guy’s Hospital, St Thomas’ Street, London, SE1 9RT, UK
Crit Care 1999, 3 (suppl 1):P161
nected to separate ‘Tonocap’ analysers (Datex, Helsinki, Finland).
24 h following surgery all the patients were sedated, ventilated
and cardiovascularly stable. Three measurements of heart rate,
mean arterial pressure, central venous pressure as well as gastric
and jejunal pHi were made at 30 min intervals prior to the commencement of an intravenous infusion of either dopexamine
(2 µg/kg/min) or of a placebo. Four further sets of measurements
were made at 30 min intervals during the infusion, and after 2 h it
was stopped and three measurements over the next 90 min were
made. The results were analysed using the Mann–Whitney test
for non-parametric data.
Background: There is conflicting evidence that dopexamine
hydrochloride exerts a selective vasodilating effect upon the gastrointestinal mucosa. Whilst some human studies conducted in
the critically ill and in high risk surgical patients have suggested
that dopexamine may cause an increase in tonometrically measured gastric intra-mucosal pH (pHi) and an improvement in clinical outcome, this has not been confirmed in our randomised trials.
Furthermore, there are no previously published reports of the
effect of dopexamine on human small bowel mucosal perfusion.
An increase in splanchnic perfusion in general or gastric mucosal
perfusion in particular following oesophageal resection may potentially reduce the incidence of anastomotic leaks and strictures as
these complications are thought to be caused by hypoperfusion
and consequent tissue hypoxia at the gastric end of the oesophagogastric anastomosis. This study assessed the effect of dopexamine on gastric tube and jejunal mucosa pHi measured
tonometrically following oesophagectomy.
Results: There were no significant changes in systemic arterial or
central venous pressure in either group during the study.
However, in the dopexamine group there was a significant
increase in mean (SD) heart rate from 85 (12) to 104 (10) beats per
minute during the infusion and a subsequent fall to 94 (10) beats
per minute after its cessation (in both cases P < 0.005). There were
no significant changes in either gastric or jejunal pHi during
dopexamine or placebo infusion (in all cases P > 0.05).
Methods: Twelve patients undergoing oesophageal resection for
carcinoma and reconstitution of gastrointestinal continuity using a
gastric tube were randomised into dopexamine and control
groups. During surgery tonometer balloons (Tonometric Division,
Instrumentarium Division, Helsinki, Finland) were placed 5 cm
distal to the anastomosis within the stomach and 10 cm during the
duodeno-jejunal flexure within the jejunum. These were con-
Conclusion: Dopexamine hydrochloride does not increase gastric
tube pHi following oesophagectomy. Furthermore there is no evidence from this study that dopexamine is capable of influencing
jejunal mucosal perfusion, and its potential role not only in protecting gastrointestinal anastomoses but also in reducing mortality
due to MODS by directly influencing splanchnic perfusion is not
supported by the findings of this study.
Pre infusion
Intra infusion
Post infusion
Mean pHi (SD)
Dopexamine
Control
Dopexamine
Control
Dopexamine
Control
Gastric pHi
7.21 (0.09)
7.23 (0.07)
7.18 (0.08)
7.24 (0.08)
7.21 (0.06)
7.24 (0.05)
Jejunal pHi
7.26 (0.08)
7.25 (0.06)
7.26 (0.07)
7.26 (0.06)
7.26 (0.09)
7.25 (0.05)
P162 Cytokines and endotoxin generation and the effects of dopexamine in patients undergoing abdominal aortic
reconstruction (AAR)
HI Rashid, N van Heerden*, PR Taylor† and RA Edmondson
Departments of Vascular Surgery and *Intensive Care, University Hospital Lewisham, Lewisham High Street, London SE13 6LL
and †Guy’s Hospital, St.Thomas’Street, London SE1 9RT, UK
Crit Care 1999, 3 (suppl 1):P162
causes endotoxin and cytokines release, initiating the systemic
inflammatory response and multiorgan dysfunction syndrome.
Hypothesis: Colonic ischaemia may increase morbidity and mortality following AAR. Animal studies suggest ischaemic colon
Aim of study: (1) Study the effects of temporary ischaemia, caused
by aortic cross clamping (AXC); (2) confirm ischaemic colon as
82
Critical Care 1999, Vol 3 suppl 1
source of endotoxin and cytokine release in humans; (3) investigate any modification of the degree of ischaemia and cytokine and
endotoxin generation with dopexamine hydrochloride.
tive correlation with IMV pH (r = –0.49 and –0.47 respectively).
Patients with IMV pH <7.3 had higher levels of endotoxin
(P = 0.04).
Study design: Placebo-controlled prospective trial, 15 patients
undergoing AAR randomised to receive dopexamine hydrochloride (n = 8) or normal saline (n = 7). Inferior mesenteric vein (IMV)
sampled for IL-6, TNF-α, endotoxin, pH, PCO2 and PO2 prior to
AXC and 30 min postreperfusion. Peripheral systemic cytokines
and endotoxin measured 24 h preoperatively and postoperatively.
Hepatic and renal functions studied perioperatively.
Dopexamine (1 µg/kg/min) produced an improvement in colonic
pH without statistical significance between groups. Dopexamine
produced statistical difference in postoperative creatinine clearance (P = 0.02), serum albumin (P = 0.02) and INR (P = 0.05).
Results: A statistically significant rise occurred in IMV IL-6
(P = 0.001) between pre-clamping and postreperfusion but not in
TNF-α and endotoxin. IL-6 and endotoxin levels showed nega-
Conclusion: Results confirm hypoperfused colon generates
cytokines which, with endotoxin, are related to the IMV pH. Pharmacological modification of this response was not statistically significant. Dopexamine could improve renal and hepatic functions
during AAR.
P163 Dopexamine reduces the incidence of colonic ischaemia following aortic surgery: a randomized placebo
controlled study
MS Baguneid, M Bukhari, PE Fulford, M Howe*, G Bigley*, RFT McMahon*, J Eddleston† and MG Walker
Dept of Vascular Surgery, *Dept of Pathological Sciences, †Dept of Anaesthesia, Manchester Royal Infirmary and Medical School, Oxford Rd,
Manchester M13 9WL, UK. Tel: +44 161 276 4525; Fax: +44 161 276 8014; E-mail docmo@zen.co.uk
Crit Care 1999, 3 (suppl 1):P163
Background: Mechanisms involved in the development of colonic
ischaemia following aortic surgery are not fully understood and
there are conflicting reports regarding predisposing factors.
Dopexamine hydrochloride, a synthetic catecholamine with both
dopaminergic and β2 agonist properties, has been demonstrated to
have anti-inflammatory properties.
Aims: To evaluate the effect of dopexamine hydrochloride on the
incidence of colonic ischaemia following aortic surgery
Methods: Thirty patients, mean age 65.1 years (range 46–84),
undergoing elective infrarenal aortic surgery were randomized to
receive a peri-operative infusion of either dopexamine at
2 µg/kg/min (n = 12) or 0.9% saline placebo (n = 18). All patients
underwent colonoscopy and biopsy following induction of anaesthesia and at one week post-operatively. Sections were stained
with haematoxylin and eosin, mast cell tryptase (MCT), myeloper-
oxidase (MPO) and both the inducible (iNOS) and endothelial
(eNOS) isoforms of nitric oxide synthase. Sections were analysed
blind and independently by two histopathologists. Patient and
operative related data were collected and stored separately.
Results: Colonic ischaemia was noted in 9 (30%) patients based on
microscopic findings. Endoscopy alone had a sensitivity of 55.5%.
There was a significantly lower incidence of colonic ischaemia in
patients receiving dopexamine compared to placebo (P < 0.05).
One death resulted from colonic infarction in the placebo group
11 days post-operatively. There was increased MPO and MCT
expression in patients with histological evidence of ischaemia
(P < 0.05). iNOS staining within the vascular (P = 0.001) and
lamina propria (P < 0.05) components of the mucosa was also significantly greater. No association was found with eNOS.
Conclusions: Peri-operative dopexamine infusion confers a degree
of protection to colonic mucosa following aortic surgery, possibly
through an anti-inflammatory effect.
P164 Endothelin-1 (ET-1) blockade improves mesenteric perfusion in a porcine low cardiac output model
D Burgener, M Svensson†, Y Oi‡, P Jolliet§, S Strasser, A Hadengue and A Aneman‡
Division of Gastroenterology and Hepatology, §Division of Medical Intensive Care University Hospital, 1211 Geneva 14, Switzerland;
†Department of Physiology, ‡Department of Anesthesiology and Intensive Care, Sahlgrenska University Hospital, S-41385, Göteborg, Sweden
Crit Care 1999, 3 (suppl 1):P164
Background: Various vasomediators regulate the hemodynamic
response to acute circulatory failure, including endothelin-1 (ET-1)
which is one of the most potent vasoconstrictors known. Mesenteric
vasoconstriction reduces the perfusion and oxygenation of the gut
mucosa, compromising mucosal barrier integrity. A growing body of
evidence links mucosal barrier dysfunction with the development
of multiple organ failure (MOF). Improving gut perfusion could
preserve mucosal barrier integrity and thus reduce the risk of MOF.
Aim: To investigate if the combined ETA-ETB blocker Ro 610612 improves gut microcirculation and micro-oxygenation during
acute circulatory failure.
Materials and methods: Seven fasted, anesthetised (pentobarbital), mechanically ventilated pigs (30–34 kg) were instrumented to
measure cardiac output (CO), portal venous blood flow (QPV;
Transonic Systems Inc.), jejunal mucosal microcirculation by laser
Doppler flowmetry (LDF, Perimed AB), jejunal tonocapnometry
(giving arterial to regional PCO2 gap, Tonocap, Datex Instruments) and jejuna mucosal micro-oxygenation (tPO2, Licox,
GMS). A pericardial drainage catheter was inserted to establish
cardiac tamponade by infusing dextran (reducing QPV to 2/3 of
baseline). Measurements were made at baseline (BL), after 90 min
of cardiac tamponade (T90) and 90 min following the administration of Ro 61-0612 (at 1 mg/kg/h) during tamponade (T90RO).
Statistical analyses were made by ANOVA and Fischer’s PLSD. A
P value < 0.05 was considered statistically significant.
Poster abstracts
Results: Cardiac tamponade significantly decreased CO, MAP,
QPV, LDF, while the pCO2 gap increased as compared to baseline
(BL). The change in tPO2 failed to gain statistical significance
(P = 0.08). Administration of Ro 61-0612 increased QPV, LDF,
tPO2 and decreased PCO2 gap, as compared to T90.
CO (l/min)
QPV (ml/min)
MAP (mmHg)
BL
2.97 ± 0.2
721 ± 65
84 ± 6
T90
1.55 ± 0.1*
470 ± 40*
T90RO
1.98 ± 0.2
758 ± 92**
83
Conclusion: ET-1 blockade in acute circulatory failure improved
mesenteric perfusion illustrating the importance of ET-1 induced
mesenteric vasoconstriction. Importantly ET-1 blockade restored
mucosal blood flow and oxygenation which might be particularly
significant considering the implications for maintenance of
mucosal barrier integrity.
LDF (PU)
PCO2 gap (kPa)
tPO2 (kPa)
175 ± 14
2.0 ± 0.4
14.6 ± 2.1
47 ± 5*
127 ± 15*
3.9 ± 0.3*
11.5 ± 1.8
44 ± 5
147 ± 16**
2.2 ± 0.2**
17.0 ± 2**
Values are expressed as mean ± SEM. *Significant versus BL. **Significant versus T90
P165 Monitoring initial volume therapy after coronary bypass surgery by gastric tonometry
H Vogelsang, T Uhlig, H Heinze and P Schmucker
Clinic of Anesthesiology, University of Luebeck, Ratzeburger Allee 160, D-23538 Luebeck, Germany. Tel: 0049-451-500 2765;
Fax: 0049-451-500 3407
Crit Care 1999, 3 (suppl 1):P165
Introduction: Gastric tonometry is a very sensitive, non-invasive
method to detect hypovolemia in critical care patients. Several
studies document the predictive value of tonometry for patients’
outcome. Especially a widened arterial to gastric-intramucosal
PCO2 difference (aiDCO2) warns of complications. This study
demonstrates the use of tonometry as a monitoring device for
actual aspects of volume status and tissue oxygenation in patients
after cardiac surgery.
Methods: After IRB approval we studied 24 patients admitted to
the ICU after aorto-coronary bypass surgery. In addition to standard monitoring each patient received a nasogastric tube (TRIP,
NGS catheter; Tonometrics, Helsinki, Finland), a fiberoptic pulmonary artery catheter (CCO catheter for Vigilance monitor;
Baxter Healthcare Corp., Irvine, USA) and a polarographic
intramyocardial oxygen catheter (Licox; Kiel, Germany). Documentation of standard parameters followed every 15 resp. 60 min.
intra- and postoperative until extubation. Retrospectively patients
were devided into two groups (2×12) by the amount of postoperative colloid volume replacement: Group 1: <750 ml colloids during
the first 3 postoperative hours; Group 2: >1000 ml colloids during
the first 3 postoperative hours. Statistics were done by using
Mann-Whitney-U and Friedman-test.
Results: There were no significant differences between group 1
and 2 with regard to age, ejection fraction, duration of extracorporal circulation, number of bypasses, arterial or mixed venous blood
gas analyses, arterial or pulmonary arterial hemodynamics, lactate,
heart rate and central venous pressure. Regional oxygenation
differed significantly between the groups. Group 1 (<750 ml/3 h)
showed a small aiDCO2 during the first 5 postoperative hours.
Afterwards
splanchnicus
perfusion
impaired
(aiDCO2
>20 mmHg). In group 2 (>1000 ml/3 h) an initially higher aiDCO2
was lowered by volume therapy. Group 2 developed a significantly
lower postoperative increase in intramyocardial oxygen then group
1. More than 5 h after extracorporal circulation there was a significantly increasing need of epinephrine in group 2 and cardiac index
was lower in group 2 without reaching significance.
Conclusion: Volume replacement after coronary bypass surgery
should be monitored by gastric tonometry since hemodynamic
parameters are less sensitive. High volume replacement without
need (aiDCO2 <20 mmHg) can improve splanchnicus perfusion
but might impair myocardial oxygenation and myocardial function.
P166 Evaluation of intestinal perfusion monitoring techniques
A Aneman, D Burgener*, M Svensson†, Y Oi and A Hadengue*
*Division of Gastroenterology and Hepatology, University Hospital 1211 Geneva 14, Switzerland. †Department of Physiology and Department of
Anesthesiology and Intensive care, Sahlgrenska University Hospital S-41385 Göteborg, Sweden
Crit Care 1999, 3 (suppl 1):P166
Introduction: Persistent hypoperfusion of the intestinal mucosa is
considered important for the development of systemic complications during critical illness. The mucosal circulation is however
not readily accessible to quantitative measurements of perfusion.
Measurements of systemic perfusion are often extrapolated clinically to reflect regional perfusion, including the gastrointestinal
organs. This extrapolation may introduce errors in the evaluation
of hemodynamic status. Furthermore, the complex variable of perfusion involves movement of blood and erythrocytes as well as the
exchange of carbon dioxide and oxygen.
Aims: To investigate the relationship between clinically available techniques of measuring mucosal perfusion in relation to
mesenteric and central blood flow during acute circulatory
failure.
Materials and method: Thirteen fasted, anesthetized (pentobarbital) mechanically ventilated, normovolemic pigs (28-35 kg) were
instrumented to monitor cardiac output (CO), portal blood flow
(QPV, Transonic Systems), jejunal, mucosal laser-Doppler
flowmetry (LDF, Perimed AB), jejunal CO2-tonometry (TONO,
Tonocap, Datex Instr) and jejunal, mucosal oxygen tension (tO2,
Licox, GMS). Acute reduction of CO by 40% from baseline was
84
Critical Care 1999, Vol 3 suppl 1
established by intrapericardial infusion of dextran and maintained
for 90 minutes. Correlations between monitored variables were
analyzed by ANOVA and linear regression (*P < 0.05) and differences were analyzed by Wilcoxon’s test (§P < 0.05).
Results: The best regressions coefficients were found between
variables relating to measurements of movement of volume (QPV)
or erythrocytes (LDF). Second to best regressions were obtained
for TONO (measuring the exchange of CO2). Notably, tPO2
(measuring the exchange of O2) did not correlate to variables of
flow or CO2 exchange.
Conclusion: In the setting of acute circulatory failure in pigs,
cardiac output approximates mesenteric as well as intestinal
mucosal perfusion. Importantly, the mucosal oxygen tension
CO
QPV
TONO
LDF
CO
–
QPV
–
TONO
LDF
tPO2
0.81*
0.45*
0.53*
0.28 ns
–
0.34*
0.57*
0.15 ns
–
–
–
0.41*
0.05 ns
–
–
–
–
0.31 ns
might vary independent from flow, which probably reflects the
complexity of the counter current circulation within the mucosa.
Oxygenation, being the pivotal variable determining tissue function, is thus not assessed even by techniques specifically directed
towards the mucosal circulation.
P167 Jejunal mucosal NO production and substrate dependency during mesenteric hypoperfusion in pigs
J Snygg, A Åneman, A Pettersson and L Fändriks
Department of Anaesthesiology and Intensive Care, Sahlgrens University Hospital, Eastern hospital, S-416 85 Göteborg, Sweden.
Tel: +46 31 343 40 00; Fax: +46 31 343 44 90; E-mail: snygg@clavicula.mednet.gu.se
Crit Care 1999, 3 (suppl 1):P167
and mucosal perfusion was measured by laserdoppler flowmetry.
Regional oxygen consumption was calculated from blood samples.
Background and aims: Intestinal NO production has been attributed a central role in the maintenance of the intestinal mucosal
barrier. Hypofunction of this barrier has been suggested to be one
important factor behind the initiation of the multiple organ dysfunction syndrome. Jejunal NO formation, as we previously have
reported, has been shown to be impaired during mucosal hypoperfusion [1]. This study was undertaken to investigate if the impaired
jejunal NO levels could be due to restricted mucosal availability of
NO-synthase substrates, i.e. oxygen and/or L-arginine.
Results: Cardiac tamponade reduced jejunal NO formation (–52%),
mesenteric oxygen delivery (–75%), oxygen consumption (–39%)
and mucosal laser doppler flow (–43%). Oxygenation of the jejunal
intraluminal perfusate completely restored the intestinal NO levels
within 30 min. Presence of L-arginine was without effect.
Methods: Chloralose-anesthetized pigs (n = 18) were prepared for
jejunal intraluminal perfusion with 150 mM NaCl or 3 mM L-arginine solution and then subjected to cardiac tamponade. Jejunal
mucosal NO formation was measured with a tonometric technique. Mesenteric blood flow was measured as portal blood flow
References
1. Åneman A, Snygg J, Pettersson A, Johansson B, Holm M,
Fändriks L: Detecting gastrointestinal hypoperfusion
during cardiac tamponade in pigs: A role for nitric oxide
tonometry? Crit Care Med 1998, 26:1251-1257.
Conclusion: The study indicates that oxygen rather than L-arginine is the rate limiting factor for mucosal NO production during
reduced splanchnic perfusion.
P168 In-vitro evaluation of the neonatal tonometer
K Thorburn, P Roberts, M Hatherill and I Murdoch
Paediatric ICU, Guy’s Hospital, London SE1 9RT, UK
Crit Care 1999, 3 (suppl 1):P168
Objectives: A Neonatal Tonometer (5 French) using saline capnometry has been developed. We compared these tonometers invitro, using 0.9% saline (NS) and phosphate buffered saline (PBS)
as the CO2 vehicle, along with a Tonocap (14 F) against a set of
known PCO2’s in a saline solution.
Method: A sealed equilibration chamber containing 0.9% Saline
was maintained at 37°C and the dissolved CO2 was kept at constant pCO2’s of 2.5, 5, 7.5, 10 kPa using a Paratrend 7 probe (Biomedical Sensors). Two Neonatal Gastric tonometers
(Tonometrics) were positioned in the chamber along with a
Tonocap monitor (Datex). NS was the CO2 vehicle in the first
tonometer, PBS (pH 6.0) in the second, and recirculating gas
tonometry in the Tonocap. 20 consecutive measurements were
taken, each after 60 min equilibration periods, from each of the
tonometers at pCO2’s of 2.5, 5, 7.5, 10 kPa and processed in the IL
BGE blood gas analyser. Data was analysed by linear regression
and Bland-Altman plots.
Results: The Figure overleaf shows the known pCO2 against the
mean pCO2 (95% CI ) for Tonocap (Tcp), PBS and NS. The calculated Tonometer pCO2 (TpCO2) is derived from the linear regression equation.
Conclusion: Recirculating gas tonometry is undoubtedly the best
mode of tonometry. Whilst we await its development for neonates
either NS or PBS may be used. We suggest that correction factors
specific to each unit’s blood gas analyser should be calculated
before appropriate comparison can be made between the arterial
pCO2 and the Neonatal tonometer’s pCO2.
Poster abstracts
85
TpCO2 = (Tonocap+0.13)/0.97
R2 = 0.99
12
pCO2 (tonometer) kP
10
Tcp
8
TpCO2 = (PBS–0.74)/0.70
R2 = 0.97
PBS
6
TpCO2 = (NS–0.16)/0.53
R2 = 0.98
NS
4
Bias + precision:
2
1. Tonocap: –0.31 kPa ± 0.25 kPa
0
2. PBS: –1.13 kPa ± 1.13 kPa
0
2
4
6
8
10
12
pCO2(Paratrend) kPa
3. NS: –2.80 kPa ± 2.64 kPa
P169 Automated gas tonometric measurement of gastric tube carbon dioxide gap following oesophageal
resection predicts post-operative complications
NH Boyle, PC Roberts, A McLuckie, WJ Owen, RJ Beale and RC Mason
Departments of Surgery and Intensive Care, 2nd Floor, New Guy’s House, Guy’s Hospital, St Thomas’ Street, London, SE1 9RT, UK
Crit Care 1999, 3 (suppl 1):P169
Background: Gastric mucosal perfusion can be assessed tonometrically by measuring the gastric intra-mucosal pH (pHi) and its ability
to predict outcome in the critically ill and following major surgery
has been demonstrated by several previous studies. It has been suggested that the CO2 gap (tonometer pCO2) may provide a more sensitive measurement of mucosal hypoxia than pHi. Post-operative
anastomotic leak and stricture following oesophageal resection and
restoration of gastrointestinal continuity with a pro-peristaltic gastric
tube has a multi-factorial aetiology. However, gastroplasty involves
division of short gastric, left gastric and left gastroepiploic vessels
and the consequent hypoperfusion and tissue hypoxia at the gastric
end of the oesophago-gastric anastomosis is thought to be the most
important causative factor. This study employed the new technique
of automated gas tonometry to measure both gastric CO2 gap and
pHi following oesophagectomy to test the predictive ability of the
technique for anastomotic complications.
Method: Gastric tonometers (Tonometric Division, Instrumentarium Division Helsinki, Finland) were placed in the gastric tube of
30 consecutive patients undergoing oesophageal resection and
pro-peristaltic tubular gastroplasty based upon the right gastroepiploic and right gastric arteries. These were connected to a
‘Tonocap’ analyzer (Datex-Engstrom Division, Instrumentarium
Corporation, Helsinki, Finland) which automatically samples gas
from the tonometer balloon and measures the CO2 concentration
within it. In conjunction with simultaneously taken arterial blood
samples the gastric CO2 gap and pHi were calculated at 12 hourly
intervals up to 48 h post-operatively. Those patients who survived
were followed for 3 months and all post-operative complications
recorded. Statistical comparison was made using the
Mann–Whitney test for non-parametric data.
Results: Eleven patients suffered an anastomotic leak or benign
stricture post-operatively, whilst five others suffered a life threatening complication not related to the anastomosis, of whom two
survived. Because of balloon failure or re-operation within 48 h of
initial surgery data was not available for one patient from each of
the complication and no complication groups. Mean (SD) CO2 gap
and pHi over the first 48 post-operative hours were 1.7 kPa (0.8)
and 7.26 (0.06) in the no complication group and 3.5 kPa (1.4) and
7.18 (0.09) in the complication group, respectively. The difference
in CO2 gap between the two groups was more significant than in
pHi (P < 0.005 and P < 0.05). A mean CO2 gap of 2.5 kPa or above
had a sensitivity of 82% and a specificity of 70% for predicting
anastomotic complications. The CO2 gap was a better predictor of
outcome than the pHi (<7.22 for predicting complications), with
areas under their respective ROC curves of 0.847 and 0.684.
Conclusion: Gastric tube CO2 gap and pHi are easily measured
post-operatively using recirculating gas tonometry. Mean CO2 gap
was higher and pHi lower over the first 48 h following surgery in
those patients in whom an anastomotic complication subsequently
developed than in those in whom it did not. The CO2 gap proved
to be a better predictor of complications than the pHi. These findings confirm the suggestion that the CO2 gap may be a more
useful clinical tool than the pHi and that measures to improve
gastric tube CO2 gap post-operatively might reduce the incidence
of anastomotic failure.
P170 Enteral nutrition via a jejunostomy decreases both jejunal and gastric tube intra-mucosal pH following
oesophagectomy
NH Boyle, PC Roberts, A McLuckie, WJ Owen, RJ Beale and RC Mason
Department of Surgery and Intensive Care, 2nd Floor, New Guy’s House, Guy’s Hospital, St Thomas’ Street, London, SE1 9RT, UK
Crit Care 1999, 3 (suppl 1):P170
Background: Many animal and human studies have demonstrated
that gastrointestinal intra-mucosal pH (pHi) which is usually
measured using a gastric tonometer is partly dependent upon
86
Critical Care 1999, Vol 3 suppl 1
mucosal perfusion, and that its measurement can predict for poor
outcome in the critically ill. There is increasing evidence that not
only in this group of patients but also following upper gastrointestinal surgery that the early introduction of enteral nutrition may
reduce morbidity and mortality and increase enteric mucosal
tissue perfusion. Theoretically this effect may be especially desirable following oesophagectomy and oesophagogastric anastomosis
as gastric blood flow is compromised following gastroplasty.
However, the measurement of gastric pHi using the tonometric
method is thought to be confounded during infusion of enteral
feed by the release of carbon dioxide from the feed itself following enzymic digestion. This study assessed the effect of a standard
enteral feed upon both gastric and jejunal pHi measured using gas
tonometry when delivered via a feeding jejunostomy.
Method: Nineteen patients undergoing oesophageal resection for
carcinoma and reconstitution of gastrointestinal continuity using a
gastric tube were studied. During surgery tonometer balloons
(Tonometric division, Instrumentarium Division, Helsinki,
Finland) were placed 5 cm distal to the anastomosis within the
stomach and 10 cm from the duodeno-jejunal flexure within the
jejunum. The jejunal tonometer was placed alongside a standard
8 F Foley feeding jejunostomy tube. The tonometers were connected to separate ‘Tonocap’ analysers (Datex, Helsinki, Finland).
Five days following surgery all the patients had left the intensive
care unit and had returned to the surgical ward and were being fed
(Fresubin Standard, Fresenius Ltd, Runcorn, Cheshire, UK) via
the jejunostomy tube (mean rate 108 ml/h). The feed was stopped
for a minimum of 6 h and then both jejunal and gastric pHi was
measured using a simultaneously taken arterial blood gas sample.
The feed was then recommenced and after 2 h the measurements
were repeated. The results were analysed using the
Mann–Whitney test for non-parametric data.
Results: Prior to the commencement of feeding mean (SD) jejunal
and gastric pHi were 7.44 (0.06) and 7.37 (0.08) respectively. Following 2 h of enteral nutrition jejunal and gastric pHi had fallen to
7.26 (0.09) and gastric pHi to 7.29 (0.12). These falls were both
significant (P < 0.005 and P < 0.05, respectively).
Conclusion: Standard enteral nutrition delivered via a feeding
jejunostomy appears to cause a fall in tonometrically measured
jejunal pHi. That this may at least in part reflect a fall in mucosal
blood flow rather than have been caused by the release of carbon
dioxide from the feed is supported by the finding that gastric pHi
also falls despite the fact that no feed was introduced into the
stomach. That an enteric reflex may be responsible for this
finding seems likely although its significance with regard to its
effect upon anastomotic perfusion remains unknown.
P171 In vitro evaluation of a fast response, modified pH-Glass electrode designed for continuous measurement of
the pCO2 in the gastric lumen
J Fuchs, DH von Kleist, J Hann and M Karaus
Otto-von-Guericke-University Hospital, Dept. of Anesthesiology and Intensive Care Medicine, Leipziger Str. 44, 39120 Magdeburg, Germany
Crit Care 1999, 3 (suppl 1):P171
Introduction: The intramucosal pH (pHi) is a sensitive and early
parameter of various shock states. Its prognostic and therapeutic
value has been demonstrated. Tonometry relies on the measurement of intragastric pCO2 via a nasogastric probe and the arterial
bicarbonate. There are several shortcomings of the tonometric
method (e.g. handling and measurement errors, and the need for a
long equilibration time (30–90 min)). Therefore, we evaluated a
modified pH-glass electrode for fast and continuous pCO2-monitoring in the stomach.
Methods: Our in vitro measurements were performed using a
special designed pH-metry glass electrode with an outer diameter
of 4.5 mm (GK2801C;Radiometer) covered with a thin gas permeable teflon membrane. Thus, CO2 may easily diffuse through the
membrane and induces changes of the pH of an interspersed electrolyte solution. At first, the membrane and the membrane
covered electrode were tested for chemical and mechanical stability in aggressive and acidic fluids. Secondly, the precision of two
one-point calibrated electrodes to measure the pCO2 in the range
of 20 to 250 mmHg was tested. For each of five given pCO2-levels
a set of five measurements was done. Thirdly, the response time
of two electrodes to reach 90% of the maximum (t90) was tested by
exposing the electrodes rapidly to two different solutions with a
pCO2 of 28.9 and 85.9 mmHg, respectively.
Results: The teflon membrane has proved to be stable against
0.1N hydrochloric acid, gastric and biliary secretions adjusted to
pH 1, and mechanical irritations. In acidic fluids a linear relationship between the measured pCO2 and the defined pCO2 for both
electrodes was observed. The slope of the regression line was
y=24.43x+7.64 (r = 0.99, n = 25) and 27.57x+4.64 (r = 0.99, n = 25)
respectively. The deviation from the line of identity was only
caused by the one point calibration. The reponse time t90 of the
electrode was 19.5 ± 1.38 s and 25.5 ± 2.42 s (± SD), respectively.
Conclusion: This teflon membrane covered modified pH-glass
electrode offers a fast, real time, and continuous measurement of
the pCO2 in the acidic environment of the gastric lumen.
P172 Investigation into the effects of enteral feeding on gastric tonometry monitoring using the saline technique
and the Tonocap
P Charlton, H Jeffrey, B Barrie and M Vucevic
Academic Unit of Anaesthesia, The General Infirmary at Leeds, Great George Street, Leeds, LS1 3EX, UK
Crit Care 1999, 3 (suppl 1):P172
Aims of study: A prospective study of gastric PrCO2 in ventilated
neurosurgical patients when given enteral feed comparing two
techniques: time corrected saline (TCS) tonometry and air
tonometry (Tonocap).
Poster abstracts
87
Methods: After Ethical committee approval and patient assent,
two tonometric catheters were inserted into patients who after an
overnight fast, were given 30 ml per hour of water for 4 h and following a 1 h rest, 30 ml per hour of enteral feed for 4 h. All patients
received iv ranitidine. The PrCO2 was measured hourly using
both techniques.
Results: Eight neurosurgical intensive care patients were studied
(mean age 52 years, SD 15.3 years). All patients were stable and
had no significant changes in cardiovascular or blood gas parameters during the study.
There was a significant difference between the TCS and Tonocap
PrCO2: 4.84 (± 2.78) kPa compared to 6.74 (± 4.46) (r2 = 0.36).
Bland–Altman analysis showed the mean bias between TCS and
Tonocap PrCO2 and –1.85 kPa with a precision of ± 3.49 kPa.
There was no significant difference between the effects of
feeding with the two techniques.
Conclusion: Enteral feeding has no effect on PrCO2 in neurosurgical patients. Saline tonometry under reads compared to the
Tonocap similar to that of general intensive care patients.
P173 Does enteral feeding potentially alter the PCO2 gap and pHi?
GPS Bawa, TJ Morgan* and B Venkatesh
Intensive Care Facility, Royal Brisbane Hospital, Brisbane, Australia; *Tel: 07 3253 1529; Fax: 07 3253 3542;
E-mail morgant@health.qld.gov.au
Crit Care 1999, 3 (suppl 1):P173
Introduction: Measurement of pHi or the mucosal–arterial PCO2
gap is advocated to detect splanchnic ischaemia and covert shock.
Nasogastric feeding may significantly affect these measurements.
We used a previously described animal model [1] to evaluate the
effect of enteral feeds on the luminal PCO2 response to intermittent splanchnic ischaemia.
Results: See Table. Feeds significantly elevated the mean baseline luminal PCO2, and delayed and blunted the PCO2 increases
(∆PCO2) in response to transient ischaemia.
Control
Feed
Methods: Adult male Wistar rats (285–425 g) were anaesthetised
with sodium pentobarbitone 60 mg/kg i.p. and ventilated with
100% oxygen and isoflurane via tracheostomy to a PaCO2 of
30–40 torr. Distal aortic pressure was monitored continuously. A
sensor (Paratrend 7, Diametrix Medical Inc., Bucks, UK) was
inserted into the ileal lumen to record PCO2 measurements every
2 s. Four rats received no feeds (controls) whilst in another four
rats an ileal cannula was inserted and feed (Nutrison, Nutricia,
Zoetermeer, Holland) infused at 3 ml/h. In each rat, five twominute episodes of aortic hypotension were induced to a mean
pressure of 30 mmHg by intermittent elevation of a silk sling
placed around the proximal aorta.
Baseline
PCO2
(torr)
Time to
onset of
response (s)
Time to
peak response
(sec)
Peak
∆PCO2
(torr)
55 ± 4
47 ± 15
180 ± 12
28 ± 8
51 ± 18
196 ± 16*
23 ± 4*
67 ± 9*
Data are mean ± SD. *P < 0.05
Conclusion: Assuming no differences in PaCO2 in both groups,
the data suggest that enteral feeding increases the baseline
mucosal–arterial PCO2 gap and reduces baseline pHi. It may also
impair the detection of splanchnic ischaemia by delaying and
blunting the responses of these indices to reduced mucosal perfusion.
Reference
Morgan TJ, Venkatesh B, Endre ZH: Crit Care Med 1997,
25:1575-1578.
P174 Enteral feed delays response times of a tissue PCO2 sensor
GPS Bawa, B Venkatesh and TJ Morgan
Intensive Care Facility, Royal Brisbane Hospital, Brisbane, Australia
Crit Care 1999, 3 (suppl 1):P174
Introduction: Real time assessment of gut luminal PCO2 is possible with rapidly responsive tissue CO2 sensors [1]. The impact of
the presence of feeds in the gut on the rapidity of response of the
sensor to a change in mucosal CO2 tension has not been evaluated.
Methods: The speed of onset of response and the 90% response
time of a commonly used tissue gas sensor the Paratrend 7 (Diametrics Medical, UK) to a change in ambient CO2 tension were
compared in normal saline (control) and an enteral feed solution
(Nutrison, Nutricia, Zoetermeer, Holland). Probe onset and 90%
response times were determined for a step up and step down
change in CO2 tensions in saline and feed solutions by bubbling
the following three pairs of gases A) 2% CO2 and 10% CO2 B) 10%
88
Critical Care 1999, Vol 3 suppl 1
CO2 and 5% CO2 and C) 5% CO2 and 2% CO2 through these solutions maintained at 37°C in a bubble tonometer. After calibration,
the sensor was equilibrated in saline bubbled with the first gas of
each pair. After equilibration the second gas of each pair was
bubbled through the solution. This was repeated for a total of six
equilibrations between each pair of gases. The experiment was
then repeated with the feed solution.
Results: See Table
Onset time (s)
Saline
Feed
90% response time (s)
Saline
Feed
Step up
39 ± 9
65 ± 10*
188 ± 25
307 ± 42*
Step down
30 ± 6
52 ± 9*
191 ± 18
297 ± 20*
Overall
34 ± 8
59 ± 11*
189 ± 21
302 ± 32*
The data are presented as mean ± SD (*P < 0.001)
Conclusion: The presence of enteric feed significantly slows down
the onset time and response time of the sensor to a change in
ambient CO2 tension. Altered viscosity and CO2 binding by the
feed are possible mechanisms for the altered response of the sensor.
The reduction in response time may impact on the ability of tissue
CO2 sensors to provide accurate real time data in clinical practice.
Reference
1. Morgan TJ, Venkatesh B, Endre ZH: Crit Care Med 1997,
25:1575-1578.
P175 Splanchnic and haemodynamic data as prognostic indexes in MODS patients
CG Ruggieri, F Cecchini, G Donati, A Morigi*, S Montanari, M Sanseverino, S Spedicato*, M Nastasi and G Martinelli*
Dept of Surgery - Section of Anaesthesia and Intensive Care Hospital ‘G Ceccarini’, Via F.lli Cervi 49, 47838 Riccione (RN), Italy
and *Dept of Surgery, Intensive Care and Transplantations, University of Bologna, Italy
Crit Care 1999, 3 (suppl 1):P175
Introduction: The aim of this prospective non intervention study
is to evaluate if the analysis of some perfusional indexes, as gastric
intramucosal pH (pHi, U) and plasma disappearance rate of indocyanine green (PDR dye, %/min), may be useful for prognostic
evaluation in patients with MODS.
Material and methods: Eighty-four medical or surgical patients,
with MODS ( mean age 51, SD 17; mean SAPS II (1st day) 56, SD
9), were studied. After 6 h of ICU stay, a gastric tonometer, a 7.5
pulmonary artery catheter and a 4 F femoral artery catheter were
inserted. The vascular catheters were connected to ‘COLD
System’, an integrated monitoring system which uses the double
indicator technique and studies hepatic perfusion, by analysis of
PDR. All patients were in CMV and received ranitidine. The
haemodynamic management was realized in order to optimize
cardiac output (CO, l/min/m2 BS) and systemic oxygen delivery
(DO2, ml/min/m2 BS). All data were recorded at the beginning of
the study (T0) and after 6 (T1), 12 (T2), 24 (T3) and 36 (T4)
hours. Statistical analysis of data was performed using Manova
Test, considering the significant differences in the times of study
between survivors (S) and non-survivors (NS) and analysing the
variance of repeated measures. Levels of P < 0.05 were accepted.
Results and conclusions: 40 (47.6%) patients died. Some data are
shown in the Table (as mean and (SD); S vs NS: *P < 0.0001;
$P < 0.005; T vs T0: §P < 0.05).
In this group of patients, a precocious splanchnic hypoperfusion
seems to be the main prognostic factor. In NS group, gastric intramucosal acidosis is present in the early period of study and it is
possible to notice a continuous worsening of liver perfusion.
According to this point of view, perfusional parameters may give
more prognostic informations than systemic data.
Time 0
Time 1
Time 2
Time 3
Time 4
CO
S 4.5 (1.5)
NS 4.7 (1.9)
5 (1.6)
4.6 (1.9)
(1.6)
4.9 (2.1)
(1.6)
5 (2.3)
5 (1.5)
4.6 (1.7)
DO2
S 656 (202)
NS 631 (273)
723 (219)
628 (274)
713 (186)
670 (288)
672 (199)
679 (351)
697 (207)
614 (228)
PHi*
S 7.45 (0.07)
NS 7.32 (0.1)
7.41 (0.09)
7.29 (0.21)
7.39 (0.14)
7.25 (0.24)§
7.40 (0.13)
7.24 (0.19)§
7.41 (0.1)
7.25 (0.18)§
PDR$
S 13.3 (6)
NS 9.2 (6.1)
13.1 (7.2)
8.9 (5.5)
13.4 (6.2)
8.7 (4.8)
13.3 (6.3)
8.5 (4.2)
13.8 (6.8)
8.6 (5.7)
P176 Major abdominal surgery and complications: is air gastric tonometry predictive of outcome?
B Dubau, V Hernandez, F Mary, S Malbert, A Botton, S Winnock and P Maurette
Département d’Anesthésie Réanimation III, Hôpital Saint André, 1 rue Jean Burget 33075 Bordeaux Cedex, France
Crit Care 1999, 3 (suppl 1):P176
Introduction: Gut mucosal ischemia can initiate a systemic inflammatory response sometimes leading to multiple organ failure. The
adequacy of splanchnic perfusion during major abdominal surgery
Poster abstracts
can be evaluated by an easy, non invasive, new method : gastric air
tonometry. Air tonometry is an important technical advance which
eliminates errors involved in saline tonometry.
The aim of our study was to investigate wether there was a relationship between a perioperative tonometric parameter and clinical outcome.
Methods: 27 patients, ASA 1–3, admitted for major abdominal
surgery (hepatectomy, pancreatoduodenectomy, colorectal resection) were prospectively studied between March 98 and October
98. After induction of anesthesia, intramucosal PCO2 (PrCO2) was
measured by a gastric tonometer placed in the stomach and then
connected to a TONOCAP® (Tonometrics-Datex-Engstrom).
PCO2 gap was measured immediately after tracheal intubation
and until discharge of the SICU at H24 postoperatively. Post operative complications were recorded during the entire hospital stay.
Statistical analysis used FISCHER’s Exact Test.
Complications
No complication
Gap ≥15
15
1
Gap <15
4
7
89
Results: 19 out of 27 patients suffered complications (bleeding,
SIRS, sepsis, MOF, pancreatitis, wound infection, hepatic failure,
anastomotic leakage) leading to death for two of them. Fifteen out
of these 19 patients had a PCO gap >15 mmHg during surgery.
The FISCHER’s Exact Test (P < 0.002) was conclusive for both
group. According to these results, PCO2 gap can predict complications with a sensibility of 78.5% and a specificity of 88%.
Conclusion: During abdominal surgery, the assessment of splanchnic perfusion can be easily achieved with air tometry ; a PCO2 gap
>15 mmHg seems to be predictive of postoperative complications.
P177 Hemodynamic changes and cytokine trends during abdominal stop-flow
A Donati, R Coltrinari, G Mercuri, P Carletti, G Conti, S Loggi, S Falcetta, P Pelaia and P Pietropaoli*
Institute of Medical and Surgical Emergency, University of Ancona and *Institute of Anesthesiology and Intensive Care,
University ‘La Sapienza’, Rome, Italy
Crit Care 1999, 3 (suppl 1):P177
Background: The stop-flow is a therapeutic technique to treat local
splanchnic malignant neoplasm, especially of the liver. The rational
of this technique is to reach and maintain high concentration of
antiblastic drugs in the site of the tumor. This is made positioning
two intravascular devices to stop both the arterial in-flow and the
venous out-flow of the site where the tumor is localized. In this way
a decreased vascular flow with consequent hypoxia is created to
increase the efficacy of some antiblastic drugs. The aim of this work
is to verify the hemodynamic changes due to the splanchnic
hypoxia and the trend of TNFa, interleukin 1B, 6 and 8.
Material and methods: We have examined three patients: two with
metastasis from carcinoma of colon-rectum and another with not
operable carcinoma of pancreas. Before the stop-flow a pulmonary
catheter to measure the cardiac output on-line (Vigilance, Baxter),
a gastric tonometer and a radial artery were positioned. After the
induction of anesthesia (fentanyl, thiopental, vecuronium) a
venous device in vein cava and an arterial device in aorta artery,
both with a balloon in the top, were positioned just under
diaphragma muscle and inflated. In this way the aortic and caval
flows were interrupted for 20 min and in this time antiblastic
drugs were administred in the hypoxic and isolated splanchnich
area. After 20 min the baloons were deflated, splanchnic area was
revasculated and a dyalisis started to eliminate as soon as possible
the drugs. At 5 times (after the induction of anesthesia, after 10’,
20’ of stop flow and after 15’ and 40’ of the end of stop-flow) all
hemodynamic and oxyphoretic parameters, pHi and blood lactate
were measured and sierum to detect cytokine TNFa, Il-1B, Il-6,
Il-8, was stored at –60°C.
Results: In all three patients there was an increase of more 100%
and a decrease of systemic vascular resistance after the stop flow
and these changes were still present after 40 min from the revascularisation. At the same time blood lactate increased and pHi
decreases below 7.32. Among the cytokines only Il-6 showed an
increase of more 100% after the stop-flow, while the others had no
significant movements.
Discussion: Decreasing tissue perfusion causes hypoxia and then
acidosis that provokes a cellular damn, increasing of cellular permeability with loss of barrier function of gut mucosa. This induces
the liberation of some substances, such as endotoxins, which start
the inflammatory cascade of TNFa, Il-1, Il-6, Il-8. Moreover,
another way to induce the formation of toxic substances, in the
presence of ischemia followed by riperfusion, is the activation of
purine metabolism with activation of xantine-oxydase (XO) and
consequent production of the anion superoxydodismutasis, that,
in the presence of iron (Fenton reaction) causes the formation of
ossidryl ion, very dangerous for the organism. The hemodynamic
response of these two cases (high CO, low SVR, pHa, pHi and
increased blood lactate) and the increasing of Il-6 are not explanable only in terms of hypoxia and it could be supposed that these
changes probably are due to a septic state, caused by the substances liberated from the hypoxic splanchnic tissue. This experimental model could be useful in the comprehension of
physiopathology of hypoxia and perhaps of septic shock and, in
some way in the experimentation of new drugs against the effects
of hypoxia.
References
1. Pohlen U, Berger G, Jung M, Buhur HJ: Concentration of
intra-aortic 5-FU administration in Hypoxia–an animal
experiment study of abdominal stop-flow perfusion in the
rabbit. Langenbecks Arch Chir Suppl Kongressbd 1997,
114:137-140.
2. Roversi R, Cavallo G, Ricci S, Rossi G et al.: Antiblastic
Hjpoxic sstop-flow perfusion in the treatment of liver
metastasis:preliminary results. G Radiol Med (Torino )
1997, 93:410-417.
3. Ricci S, Rossi G, Roversi R,Cavallo G et al.: Antiblastic
locoregional perfusion with control of the aorto-caval
flow: techique of percutaneous access. G Radiol Med
(Torino) 1997, 93:246–252.
4. Akagi Y, Hiraki M, Isomoto H et al.: Hepatic arterial
chemoterapy for liver metastases from colorectal cancer.
Kurume Med J 1996, 43:41-47.
90
Critical Care 1999, Vol 3 suppl 1
P178 Continuous assessment of colonic perfusion during abdominal aortic reconstruction using a modified
Paratrend 7™
HI Rashid, N van Heerden*, PR Taylor† and RA Edmondson
Departments of Vascular Surgery and *Intensive Care, University Hospital Lewisham, Lewisham High Street, London, SE13 6LH, †Guy’s Hospital,
St Thomas’ Street, London, SE1 9RT, UK
Crit Care 1999, 3 (suppl 1):P178
Background: Colonic ischaemia may initiate multiple organ dysfunction syndrome following abdominal aortic reconstruction.
Most methods available to detect colonic hypoperfusion are not
ideal for continuous intraoperative and postoperative monitoring.
Objective: Prospective evaluation of the use of a modified intraarterial fiberoptic probe (Paratrend 7™) for continuous perioperative monitoring of colonic luminal pH, PCO2 and PO2 in patients
undergoing abdominal aortic reconstruction.
Study design: Fourteen consecutive patients scheduled for
infrarenal abdominal aortic reconstruction were recruited. Preoperative bowel preparation was partially performed in the first six
patients and completely performed in the last eight patients.
Under general anaesthetic, a modified Paratrend 7™ probe was
inserted transanally to the rectosigmoid junction. Continuous
intraoperative analysis was compared to intermittent intraoperative inferior mesenteric vein (IMV) sampling for pH, PCO2 and PO2
was observed on aortic cross clamping and declamping. The 95%
limits of agreement with IMV pH, in patients with complete
bowel preparation were 0.16 and –0.1 for the calculated intramucosal pH and 0.72 and –0.48 for the luminal pH. The estimated
bias for the calculated pHi was –0.03. Results were directly
affected by the condition of bowel preparation
Conclusion: The modified Paratrend 7™ effectively detects
changes in colonic perfusion during abdominal aortic reconstruction. However, complete bowel preparation is essential and modifications may be required to increase its precision.
P179 Effect of endotoxemia on hepatic portal and sinusoidal blood flow in rats
A Secchi, M Ortanderl, MM Gebhard, E Martin and H Schmidt H
Department of Anaesthesiology, University of Heidelberg, INF 110, 69120 Heidelberg, Germany. Tel: +49 6221- 566355
0 min
Crit Care 1999, 3 (suppl 1):P179
A decrease of liver blood flow leads to a dysfunction of hepatocytes and Kupffer-cells with subsequent local and systemic liberation of proinflammatory mediators [1] that may maintain SIRS and
may lead to MODS [2]. There is only limited knowledge about
the hepatic micro- and macrocirculation during sepsis or endotoxemia. Therefore, aim of our study was to investigate alterations in
hepatic portal (PBF) and sinusoidal blood flow (SBF) during
endotoxemia.
Cardiac output
(ml/min)
Control (n = 10) 127 ± 12
LPS (n = 10)
124 ± 20
Portal blood flow Control (n = 10)
(ml/min)
LPS (n = 10)
60 min
120 min
150 ± 14
143 ± 30
135 ± 24
131 ± 22
22 ± 4
15 ± 4*
22 ± 3
16 ± 3*
24 ± 4
23 ± 3
Sinusoidal blood Control (n = 10) 37.3 ± 9.2 37.1 ± 8.5 36.3 ± 7.1
flow (10³ µm³/s) LPS (n = 10)
39.4 ± 8.1 27.0 ± 5.6* 22.5 ± 3.7*
Data are expressed as mean ± SD. * P < 0.01 vs. control
In male Wistar rats endotoxemia was induced by continuous infusion of 2 mg/kg/h lipopolysaccharides (LPS) from E. coli 026:B6
immediately after baseline measurements (LPS group; n = 10).
The control group (n = 10) received an equivalent volume of
Ringer’s solution. MAP, HR, CO, PBF and SBF were measured at
baseline, and 60 min, and 120 min after induction of endotoxemia.
PBF was measured using a laser-doppler flow probe that was positioned around the portal vein. SBF was detected by in vivo
videomicroscopy of the left liver lobe. Statistical analysis was performed using Mann-Whitney’s U-test.
Our results demonstrate that during early endotoxemia hepatic
macro- and microcirculatory perfusion is significantly decreased
despite unchanged MAP and CO. This early reduction of hepatic
perfusion might be caused by an increased hepatic vessel resistance as a consequence of liberation of vasoconstrictive mediators
(e.g. endothelin) or/and by a decrease in intestinal perfusion.
MAP and CO remained at baseline values in both groups. In the
LPS-group HR significantly increased. During endotoxemia PBF
and SBF significantly decreased (Table).
Reference
1. Gimson: Intensive Care Med 1987, 13:162.
2. Michie: Br J Surg 1989, 76:670.
P180 Multiple organ disfunction, surgical techniques and prognostic markers in acute pancreatitis
MV de la Torre-Prados, A Poullet-Brea, A Soler-García, A García-Alcántara, C Reina-Artacho and JM Molina
Servicio de Medicina Intensiva, H U Virgen de la Victoria, 29010-Málaga, Spain
Crit Care 1999, 3 (suppl 1):P180
Introduction: Multiple organ dysfunction (MOD) is the leading
cause of morbidity and mortality in patients admitted to an intensive care unit (ICU).
Poster abstracts
Objective: To study the relationship between MOD and mortality
in severe acute pancreatitis (SAP) together with bacterial infections, surgical techniques as well as clinical and biological markers.
Material and method: A prospective study of clinical results and
laboratory testing and image techniques made in 100 patients
treated in the ICU over 6 years, from 1991–96.
91
Results: See Table.
Conclusion: MOD score higher than 2 is related to serious pancreatitis. It is important to preserve different organ functions together
with nosocomial vigilance with the support of biological markers
just to indicate specifif antibiotherapy if sepsis is present, and
surgery in early phase as a last resort.
Survival
Yes
No
Variables
n
Average
SD
n
Average
SD
P*
Age
72
61.7
13.8
28
69.8
11.3
0.005
RCP 48 h
34
25.7
22,4
10
68
43
0.05
S. Calcium 48 h
67
7.6
1.4
24
5.7
1.4
0.000
Albumin 1 Week
34
2.1
1.5
13
1.6
1.1
ns
N. Dysfunction Organ
68
0.98
0.71
27
3.1
1.03
0.000
MOD Score#
68
2
1.5
26
7.8
3.2
0.000
N. Bacteria Inf. Abdom.
26
1.3
0.98
15
2.9
1.9
0.04
N. Surgery
52
0.8
0.4
22
1.3
0.86
0.01
Days onset surgery
40
12
4.7
18
3.6
2.1
0.003
n
%
N Group
n
%
N Group
P**
Biliar etiology
46
66
72
15
60
28
ns
Sepsis
18
27
69
14
64
24
0.008
Marsupialization***
9
22
40
7
38
18
0.002
*t Test. **Chi Square. N., number; RCP, reactive C protein, S., serum. ***Included if is biliar colechistectomy. #Crit Care Med 1995; 10:16381652.
P181 Outcome prediction for patients with chronic liver disease requiring medical intensive care
M Wehler, R Strauß, J Kokoska, A Müller, M Meyer*, U Reulbach* and EG Hahn
Department of Medicine I and *Institute of Medical Statistics and Documentation, University Erlangen-Nuremberg, 91023 Erlangen, Germany
Crit Care 1999, 3 (suppl 1):P181
Introduction: To determine the outcome and prognostic factors of
patients with cirrhosis of the liver requiring medical intensive care
Patients and methods: All patients with chronic liver disease and
cirrhosis admitted to the medical ICU between 7/95 and 6/97 were
enrolled in the study. Prospectively the reason for ICU admission,
acute diagnoses, presence of co-morbid illness, stage of liver
disease, number and length of organ failures, daily APACHE II
and TISS classification and outcome were documented. Laboratory values were drawn retrospectively from the charts. Patients
with multiple ICU treatments were reviewed only for the initial
admission. Contingency tables were analysed using χ2 test, continuous variables were compared using Mann–Whitney U test.
Results: One hundred and two patients met the study criteria;
mean age was 51 ± 12 (± SD) years, median 50, range 28–78 years,
67% were male. Mean ICU length of stay was 8.6 ± 14.7 days.
Mean APACHE II score (first 24 h) was 20 ± 11, range 5–48. Mean
TISS score (first 24 h) was 30 ± 14, range 0–69. ICU mortality was
38%, a significant association was seen between ICU mortality and
the following variables: sepsis (P = 0.000001), pneumonia
(P = 0.00027), elevated serum lactate (P = 0.00003) and CRP
(P = 0.00001) on admission, respirator, renal replacement or catecholamine therapy (all P = 0.00001), Child–Pugh (P = 0.19) and
APACHE II score (P = 0.00001) within the first 24 h. No significant
association was noted between ICU mortality and age (P = 0.89),
length of stay (P = 0.12), gastrointestinal bleeding (P = 0.15), spontaneous bacterial peritonitis (P = 0.31), and the etiology of liver
disease (alcohol, viral, both combined, others P = 0.68).
Conclusion: Among critically ill patients with cirrhosis of the liver
ICU mortality was 38%, in comparison, the mortality for all ICU
admissions in this period of time was 23%. APACHE II score and
variables describing single or multiple organ dysfunction and pulmonary infection are excellent predictors of mortality.
92
Critical Care 1999, Vol 3 suppl 1
P182 Outcome of chronic liver disease in a specialist liver intensive therapy unit
A Verma, M Phillips and J Wendon
Institute of Liver Studies, King’s College Hospital, London SE5, UK
Crit Care 1999, 3 (suppl 1):P182
Background: Decompensated chronic liver disease (CLD) is associated with high morbidity and mortality. Intensive therapy unit
(ITU) admission in this clinical setting consumes significant
resources and remains of unproven benefit.
Methods: We examined the records of all patients with chronic
liver disease who were admitted to the Liver ITU at King’s
College Hospital between 1/9/97 and 30/9/98.
Results: One hundred and nine patients were admitted with CLD
(M:F 70:39, median age 47 years, range 18–72, aetiology: alcoholic
liver disease (ALD) 67%, viral hepatitis 12%, ALD+viral hepatitis
9%, other CLD 12%). Fifty-four (50%) patients survived (including two who underwent liver transplantation) and 55 died. There
was no difference in age between survivors and non-survivors
(P = 0.5208, unpaired t-test). Seventy-eight patients (72%) were
ventilated, of whom 51 (65%) died. Forty-six patients (42%) were
treated with renal support, of whom 42 (91%) died. Of the 4 survivors from the renal supported group 2 underwent liver transplantation. 44 patients (40%) needed both ventilation and renal
support, of whom 40 (91%) died.
Conclusion: Patients with decompensated CLD needing ITU
care have a high mortality. Single organ support in the form of
mechanical ventilation is a reasonable use of resources as there is a
good chance of recovery. The need for renal support is a bad prognostic indicator. Unless there is an acute reversible component to
renal failure or liver transplantation is contemplated, the use of
renal support in this patient group may not be a good use of
resources.
P183 Association between interleukin-10 (IL-10) gene promoter polymorphisms and outcome in acetaminophen
induced acute liver failure requiring admission to a liver intensive care unit
N Jackson, S Cookson, W Bernal, J Wendon and P Donaldson
Institute of Liver Studies, Kings College Hospital, Denmark Hill, London SE5 8RX, UK. Tel: 0041 171 346 3406
Crit Care 1999, 3 (suppl 1):P183
Background: The outcome of severe hepatic necrosis following
acetaminophen overdose is unpredictable and may have up to a
90% mortality. IL-10 is an anti-inflammatory cytokine which plays
a pivotal role in inflammation and potentially in multiorgan
failure. Elevated plasma levels of IL-10 are found in patients with
acute liver failure. Polymorphisms in the promoter region of the
IL-10 gene have recently been described comprising three single
base-pair substitutions at positions (–1082, –819, –592) resulting in
three common three haplotypes GCC, ACC and ATA. The
GCC/GCC genotype is associated with higher IL-10 production,
and ATA haplotype with lower production.
Patients and methods: 96 patients with severe acetaminophen
hepatotoxicity requiring intensive care were studied. IL-10 gene
polymorphisms were determined by sequence-specific oligonucleotide probing using a standard PCR based technique. Haplotype frequencies were compared with those of 71 racially and
geographically matched controls.
Results: See Table.
Patients (no)
No. haplotypes
GCC
ATA
ACC
Controls (71)
142
47%
25%
28%
All patients (96)
192
56%
19%
25%
Survivors (60)
120
57%
20%
23%
Non survivors/Tx (36) 72
54%
18%
28%
ARDS (25)
50
56%
20%
24%
ARF (47)
94
61%
18%
21%
Hypotensive/
vasopressors (32)
64
56%
20%
24%
ARF, acute renal failure: creatinine > 300 µmol/l and/or oliguria
requiring haemofiltration; ARDS, acute respiratory distress syndrome:
PaO2 (kPa)/FiO2 <20, PEEP >5 cmH2O; Tx, liver transplant. Haplotype
frequencies were compared using χ2 test with Yates correction.
Conclusion: There is no significant association between outcome
or incidence of multiorgan failure in patients with acetaminophen
induced acute liver failure and these three common IL-10 gene
promoter haplotypes.
P184 A reproducible rabbit model of acetaminophen induced acute hepatic failure (AHF) and multi-organ failure
(MOF)
TM Rahman, C Selden and HJ Hodgson
Dept. of Gastroenterology, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Rd, London, UK
Crit Care 1999, 3 (suppl 1):P184
Background: Acetaminophen overdose is the commonest cause of
AHF in the UK. Patients may require liver transplantation and
intensive care for support for MOF. Acetaminophen (APAP)
metabolism is catalysed by cytochrome P450 (CYP450). This
leads to formation of the toxic metabolite N-acetyl-p-benzoquinnone (NAPQI). NAPQI detoxification requires glutathione. Both
prior CYP450 induction and glutathione depletion exacerbate
hepatic damage.
Poster abstracts
Aim: To develop a reproducible rabbit model of AHF and MOF
paralleling, clinical, biochemical and histological patterns of
human disease.
Method: CYP450 was induced in New Zealand White Rabbits
(n = 8) using 20-methylcholanthrene (80 mg/kg i.p.) dissolved in
corn oil. The glutathione synthetase inhibitor buthionine
sulphoxime (2 mmol/kg i.v.) was administered just prior to APAP
administration, (500 mg/kg s.c.) 4-hourly for 24 h.
AST (24–40 iu/l)
NH3 (<75 N-µg/dl)
24 h
36 h
6470 ± 1310
4321 ± 750
148 ± 22
164 ± 12
Lactate (0.6–1.8 mm/l)
8.1 ± 1.3
11.1 ± 1.0
PT (10–12 s)
8.2 ± 0.97
Creatinine (60–100 µmol/l)
214 ± 31
93
11 ± 0.44
312 ± 52
Clinical observations were recorded and arterial blood sampled
over 48 h.
Results: Clinical: Grade I-III encephalopathy (modified from Zimmerman et al.) occurred at 8–12, 12–18, 18–36 h, respectively. Mortality was 75% at 48 h, preceded by a short period of grade IV
encephalopathy.
Biochemistry: Expressed as mean values ± s(n–1)
Histology: Liver: Centrilobular necrosis was prominent on the
surface of the liver at 24 h, with extensive severe coagulative
necrosis at 48 h. Kidney: Acute tubular necrosis at 24 h.
Conclusion: Preliminary data suggests that we have developed a
reproducible rabbit model of AHF and associated MOF, however,
further characterisation is required.
P185 Monitoring in liver transplantation
P Lamsch, R Schwarz, M Werner, M Wenzke and J Hauss
Department for Abdominal, Transplant and Vascular Surgery, University of Leipzig, Germany
Gram+ sepsis
Gram– sepsis
Fungal infection
PCT
↑↑
↑↑
↑
IL-6
↑
↑
↑(↑)
IL-8
↑
↑
(↑)
TNF alpha
↑
↑
↑↑↑↑
↑↑↑
(↑)
↑↑↑↑
Crit Care 1999, 3 (suppl 1):P185
Introduction: Despite the overall acceptable results obtained in
liver transplantation during the last 15 years infection and the
appropriate management of the immunosuppressive treatment
remains a major issue in the follow-up and outcome after liver
transplantation.
s-IL-2R
Patients and methods: One hundred liver transplants with a 1 year
survival rate of 81% were performed at the university of Leipzig
since December 1993. Patients were monitored beside the routine
laboratory parameters by Procalcitonin (PCT), soluble IL-2-receptor (s-IL2-R) TNF alpha, Interleukin 6 (IL-6) and Interleukin 8
(IL-8). The postoperative complications were differentiated
whether a gram– or + sepsis or a fungal infection occurred.
Results: See Table.
Conclusion: These qualitatively summarized results indicate the
potential role of an advanced monitoring for the differentiation of
infectious complications. Elevated PCT, IL-6 and s-IL-2 R levels
are found in severe bacterial infections, whereas very high levels
of TNF alpha and s-IL-2 R seem to be more specific for fungal
infections. These findings may be a useful guide for the initiation
of a specific diagnostic work up, for the induction of an adequate
treatment and/or for an appropriate modification of the immunosuppressive treatment.
P186 Rare fatal complications of acute fatty liver of pregnancy
TM Rahman, M Phillips and J Wendon
Dept. of Gastroenterology, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Rd, London W12 ONN.
Institute of Liver Studies, King’s College Hospital, Denmark Hill, London SE5, UK
Crit Care 1999, 3 (suppl 1):P186
Background: Acute fatty liver of pregnancy (AFLP) and the syndrome of haemolysis, elevated liver enzyme levels, and low
platelet count (HELLP) are rare but major disorders of the third
trimester of pregnancy and are maybe related to pre-eclampsia.
Mortality of 9–24% has been reported and complications include
pulmonary oedema, adult respiratory distress syndrome, abruptio
placentae, disseminated intravascular coagulation, ruptured liver
haematomas, and acute renal failure increasing mortality to
50–90%. Multi-organ failure may result requiring full intensive
care support. Perinatal mortality is equally high, ranging from 79
to 367 per 1000 live births, and neonatal complications correlate
with the severity of maternal disease. Most presentations of AFLP
and HELLP require monitoring and supportive care, however,
early recognition of rarely associated complications and their
appropriate treatment is of paramount importance to the survival
of the mother and child.
Case reports: We report five patients referred to the Liver Intensive Care Unit (LITU) with mild AFLP in 3 years. Their disease
progressed rapidly to acute hepatic failure with associated multi-
94
Critical Care 1999, Vol 3 suppl 1
organ failure(1 ± 2 days post admission to LITU). Patients (age
26.4 ± 5.2 years) presented in the third trimester of pregnancy
(33 ± 3 weeks) with proteinuria, hypertension (systolic 186 ± 27.1,
diastolic 103 ± 10.1 mmHg), and deranged liver function consistent
with AFLP and evidence in four patients of HELLP syndrome.
Maternal deterioration and foetal distress required emergency
caesarean section. Following uncomplicated caesarean section,
reduced conscious level (Grade I–II encephalopathy) was associated with severe hypovolaemic shock (systolic 60 ± 5 diastolic
40 ± 7 mmHg). Haematological investigations demonstrated a fall
in haemoglobin (8.6 ± 1.4 g/dl), worsening thrombocytopaenia
(platelets 42 ± 20 ×109/l), rising coagulopathy (prothrombin time
23.2 ± 5.6 s),and disseminated intravascular coagulopathy. Biochemical investigations revealed, metabolic acidosis (pH
7.09 ± 0.15), hyperlactataemia (10.16 ± 4.5 mmol/l), severe transaminitis (AST 4050 ± 599 iu/l), increasing total bilirubin
(194 ± 75 µmol/l) and oligo-anuric renal failure (creatinine
353 ± 156 µmol/l). Patients were resuscitated, intubated and
mechanically ventilated. Intra-cranial transducers were inserted to
monitor intracranial pressure. Vaso-active agents were used to
maintain haemodynamic stability and continuos venous-venous
haemofiltration initiated. Intravenous N-acetylcysteine, antibiotics
and anti-fungals were commenced. Ultrasound, helical computer
tomography and angiography confirmed extensive subcapsular
haematomas suggestive of liver rupture in three patients, massive
hepatic necrosis in the fourth patient and abnormal aorto-portal
shunting suggestive of veno-occlusive disease in the fifth patient.
Patients were listed for liver transplantation.
Of the five, patient one did not survive long enough for transplantation, however, the others successfully received liver transplants
(7.4 ± 6 days post caesarean section). Unfortunately patient two
developed hepatic artery thrombosis and was re-transplanted, but
died soon after.
The other three patients remain alive and well. Patients have
been investigated for pro-thrombotic disorders, evidence of which
is not present.
Conclusion: We describe potentially fatal complications in five
patients initially presenting with mild AFLP and or HELLP associated with pre-eclampsia with a mortality of greater than 90%.
These rare complications include hepatic rupture, hepatic infarction and necrosis and veno-occlusive disease. Clinical suspicion
must be high if there is evidence of hypotension, altered conscious state, metabolic acidosis, hyperlactataemia and deranged
liver function. The early recognition of the changing clinical
parameters of disease, multidisciplinary support, and specialist
intensive care is required for the survival of this rare group of
patients and their children.
P187 Treatment of acute hepatic failure and encephalopathy with extracorporeal ex vivo pig-liver perfusion in the
critical care unit
MC DaSilva, M Gupta, MJ Holman, HC Yang, RL Conter and RN Cooney
Department of Surgery, Section of Transplantation, and Critical Care at the PennState College of Medicine, The Milton S. Hershey Medical Center,
Hershey, Pennsylvania, 17033, USA
Crit Care 1999, 3 (suppl 1):P187
Patients with fulminant hepatic failure have a higher mortality
rate after orthotopic liver transplantation than patients with
chronic liver disease. Due to the shortage of cadaveric livers for
transplantation, the concept of perfusion through a liver outside
the body has recently been reintroduced in the clinical setting.
terminated when the oxygen extraction and bile production
decreased, and the total bilirubin level went back up. During the
period of ex vivo perfusion the patient moved all four extremities
spontaneously within 30 min of perfusion, serum total bilirubin,
and the serum ammonia level decreased by 50% and 60% respectively. The patient eventually developed sepsis and the therapy
was discontinued.
We describe a venovenous perfusion circuit with two Biomed
pumps and one oxygenator connected to the patient’s venous
system via two hemodialysis catheters. The circuit provided adequate flow during ex vivo pig-liver perfusion in a critically ill
patient with a stage 5 coma. The procedure lasted 4.5 h and was
Conclusion: For patients with acute hepatic failure and
encephalopathy associated with cerebral edema in whom cadaveric liver transplantation is not an immediate option, extracorporeal ex vivo pig-liver perfusion is a reasonable alternative in the
critical care setting.
P188 Increased prevalence of Helicobacter pylori infection in critically ill patients with stress ulceration
PHJ van der Voort, RWM van der Hulst*, DF Zandstra, AAM Geraedts†, A van der Ende‡ and GNJ Tytgat§
Department of Intensive care and †Gastroenterology, Onze Lieve Vrouwe Gasthuis, PO box 95500, 1090 HM Amsterdam,
Department of *Internal Medicine and Gastroenterology, Kennemer Gasthuis, Haarlem, §Department of Gastroenterology and ‡Microbiology,
Academic Medical Centre, Amsterdam, The Netherlands
Crit Care 1999, 3 (suppl 1):P188
Introduction: H. pylori is known for its causative role in gastric and
duodenal ulcer disease. However, it is unknown whether H. pylori
plays a role in the formation of stress ulceration in critically ill
patients. Therefore we studied the presence of H. pylori infection
in critically ill patients on admission to the intensive care and the
relation to gastric and duodenal mucosal injury.
Methods: Inclusion criteria were admittance to the intensive care
unit for emergency reasons and the need for mechanical ventilation. H. pylori was detected by the Laser Assisted Ratio analyser13C-urea breath test (UBT). Upper gastro-intestinal endoscopy
was performed in all patients by the same endoscopist who was
blinded for the results of the H. pylori test. Breath test and
endoscopy were performed within 6 h after admission. Gastric and
duodena mucosal injury were assessed according to the so called
Brown scoring system [1]; grade 0, normal mucosa; grade 1, 1 to 5
Poster abstracts
95
erosions or submucosal hemorrhages; grade 2, 6 to 20 erosions or
hemorrhages; grade 3, more than 20 erosions or hemorrhages.
cantly associated with mucosal injury gradation 2 or 3 (P = 0.003,
Pearson Chi-square, odds ratio 8.4 and relative risk 4.2).
Results: Fifty consecutive patients were included. In seven
patients the UBT was unable to be processed (n = 6) or endoscopy
was inadequate (n = 1). Of 43 eligible patients 21 were H. pylori
positive and 22 were H. pylori negative. Of 28 patients who had a
mucosa injury grade 0 or 1 nine were H. pylori positive (32%) and
mean APACHE II score was 25.6. Of 15 patients who had a
mucosal injury score 2 or 3, 12 were H. pylori positive (80%) and
mean APACHE II score was 25.5. H. pylori infection was signifi-
Conclusion: The severity of gastric and duodenal mucosal injury
in critically ill patients during mechanical ventilation is significantly related to the presence of H. pylori infection.
Reference
1. Brown TH, Davidson PF, Larson GM: Acute gastritis
occurring within 24 hours of severe head injury.
Gastrointest Endosc 1989; 35:37-40.
P189 Effects of spinal sympathicolysis on gastrointestinal motility in critically ill patients
P Wegermann and M Tryba
Department of Anesthesia, Intensive Care Medicine and Pain Therapy, City Hospital Kassel, Germany
Crit Care 1999, 3 (suppl 1):P189
In surgical ICU patients many causes provide a gastrointestinal
atony, i.e. shock, systemic analgesia + sedation. Due to this atony,
early enteral nutrition and a normal function of the gut is often
prevented. Translocation, ileus or endotoxine transmission and
their complications are pretended. Most of the seriously injured
polytrauma patients and those after major abdominal surgery are
concerned. Even intensive and prolonged conservative efforts for
stimulation of gastrointestinal motility (i.e. laxatives, contrast
agent, metoclopramid, neostigmin, ceruletid, enteroclysis, erythromycin, systemic sympathicolytics) are not always successful. In
the last 2 years, we performed in unsuccessful cases after excluding all contraindications a central neuraxial block with local anesthetics as an ultima ratio approach.
Methods: Spinal sympathicolysis was performed if critically ill
ICU patients in spite of prolonged and repeated conservative
efforts did not defecate within 6 days. After the decision conservative efforts were continued for 24 h. If the patients did not defecate, we carried out spinal or epidural anesthesia. Sepsis, coma and
coagulation abnormalities were contraindications. In presence of
leucocytosis without septic symptoms, the local anesthetic (3 ml
bupivacaine 0.25%) + 0.5 mg morphine was injected intrathecally.
In other cases we placed a lumbar epidural catheter with an initial
dose of 10 ml bupivacaine 0.25% + 3 mg morphine. If necessary,
the dose was repeated within 12 h.
Results: We report about 26 patients, which were treated with
spinal sympathicolysis, in 10 cases as single shot spinal anesthesia
and in 16 cases as epidural anesthesia. In all patients gastrointestinal motility improved significantly within the first 12 h. Twelve
(46%) patients defecated within 12 h and 9 (35%) within 24 h.
Four of the remaining patients, all with epidural anesthesia,
defecated during the second day after the beginning of the sympathicolysis. One patient with intrathecal single shot sympathicolysis without defecation within 48 h received a second intrathecal
treatment with success. As an accompanying and important sideeffect, in most patients systemic analgesia and sedation could be
reduced significantly and weaning could be initiated. None of the
26 patients had an untoward effect.
Conclusion: In our patients spinal sympathicolysis was a successful
method to stimulate gastrointestinal motility in critically ill ICU
patients. Regarding to the possible complications of a prolonged
intestinal atony (translocation, ileus operation, endotoxine transmission) and after trying all conservative efforts spinal sympathicolysis
can be considered as an acceptable approach in spite of the possible
untoward effects. By the good results we now more often decide for
this method because of the good effects and side-effects.
P190 Gastro-intestinal bleeding in 1211 ventilated trauma patients: a multivariate analysis of the risk factors
L Petit, A Leger, F Masson, JF Cochard, C Pinaquy and P Erny
Service de Réanimation Chirurgicale et Post Traumatique, Hôpital Pellegrin 33076, Bordeaux Cedex, France
Crit Care 1999, 3 (suppl 1):P190
Aim: Anti-acid therapies are described as potential risk factors for
acquired pneumonia in ICU patients. The aim of this prospective
study is to assess the incidence and risk factors of gastro-intestinal
bleeding (GIB) in a level 1 trauma ICU, in order to better define
the populations of patients likely to benefit from such a preventive treatment.
Methods: 5 year prospective study (May 1st 1993, April 30th 1998).
All trauma patients admitted to ICU and ventilated for more than
2 days were included. All patients were submitted to the same
diagnostic and therapeutic procedures. None of them received
systematic anti-acid therapies except in the case of documented
history of GIB. GIB patients (confirmed by endoscopy) were compared to all others patients (GIB–).
Results: 1211 patients (age*: 38.6 ± 19.3 years, ISS**: 31 (24–41),
GCS**: 7 (3–15), Coma (GCS = 8): 52%, SAPS II**: 30 (19–37),
96
Critical Care 1999, Vol 3 suppl 1
Table 1
n
AIS Head**
Coma**
ARF
UGIT
Septic shock
SDRA
GIB +
28
2(0–5)
32%
32%
57%
25%
21%
GIB –
1183
5 (2–5)
52%
6%
9%
8%
5%
–
<0.001
0.05
<0.001
<0.001
0.005
0.003
P
AIS head, Abbreviated injury score, Coma: GCS = 8, ARF: Acute renal failure, UGIT: unavailability of the gastro intestinal tract, *mean, standard
deviation, **median, centils 25–75
Table 2
Coefficient
Odds ratio
Confidence limits
P
2.366
10.65
5.53–25.00
<0.001
Acute renal failure
1.18
3.253
1.24–8.49
0.01
Spinal cord injury
1.288
3.624
1.23–10.68
0.02
UGIT
ventilation: 13.5 ± 11 days) were included. The incidence of GIB
is 2.3% (n = 28). Table 1 summarizes the only significant risk
factors after univariate analysis, Table 2 the final model after stepwise logistic regression.
Conclusion: Unavailability of the gastro-intestinal tract, acute
renal failure and spinal cord injury are important risk factors for
GIB. These results emphasize the importance of early enteral
feeding which certainly represents the best prevention from the
occurrence of GIB.
All patients were successfully treated (medical treatment: 22, surgical treatment: 6) and the occurrence of GIB resulted in no additional mortality.
P191 Emergency treatment of hemorrhagic gastric and duodenal ulcer
S Tsamis, E Pikoulis, C Theos, D Banos and P Koulouvaris
Second Department of Surgery, ASCLEPEION Voulas, Vasileos Pavlou 1, 16673 Voula , Athens, Greece
Crit Care 1999, 3 (suppl 1):P191
Introduction: Hemorrhage is one of the most common serious
complication of gastric and duodenal ulcer even so, the knowledge
and the usage of new anti-ulcer drugs (H2-receptor antagonists
and inhibitors of the proton-pump enzyme such as omeprazole)
and the success of therapy of Helicobacter pylori infection of gastric
and duodenal mucosa, have changed the role of surgical treatment
of ulcer disease.
Our aim is to describe the evaluation of bleeding peptic ulcer, the
indications for surgical treatment and the type of operative procedure or method that it has to be performed.
Patients and methods: From 1987–1992 we had in our clinic 416
patients with severe gastric-duodenal hemorrhage (312 males and
104 females). The average age of the patients was 63 years (range:
20–85 yrs). Analytically we had: 251 (60.3%) patients with duodenal ulcer, 72 (17.3%) with gastric ulcer, 58 (13.9%) with gastric
cancer, 27 (96.5%) patients had acute hemorrhagic gastritis and 4
(1%) patients had gastric benign tumors.
Results: In 84 patients we could not manage to control the bleeding (severe hemorrhage) by conservative methods (transfusions of
blood, anti-ulcer medication) or/and by using the method of
endoscopy. These patients have been operated. The surgical procedures that have been undertaken were: vagotomy and pyloroplasty 43 (51.1%), vagotomy and gastrojejunostomy 23 (27.5%)
and gastrectomy 18 (21.4%).
From these patients 78 have cured and 6 died because of the high
severity of the bleeding in association with their old age (age >80
years) and their general health status (2 of them had coronary
disease and another one was diabetic with respiratory deficiency).
Conclusions: Bleeding as complication of peptic ulcer remains up
today very serious factor that increases the morbidity and the mortality. The aim is to avoid operating on all patients who would
recover on medical treatment, but to operate on all patients who if
treated medically would bleed again to a dangerous extent. Furthermore, if surgical treatment is undertaken, it should be performed at the optimal time and the safest operative procedure
should be used, by a highly skilled surgeon. The age and general
condition of the patient are important factors to consider. The
amount of hemorrhage and the rate of hemorrhage are of prognostic significance.
Poster abstracts
97
P192 Probiotics in critical illness
B Klarin, M-L Johansson*, A Larsson and B Jeppsson†
Dept of Anaesthesiology & Intensive Care, University Hospital, S-221 85 Lund, Sweden; *Probi AB, Ideon, S-223 70 Lund, Sweden;
†Dept of Surgery, University Hospital Malmö, Sweden
Crit Care 1999, 3 (suppl 1):P192
Introduction: Critically ill patients are commonly treated with
broadspectrum antibiotics. This brings about a major impact on
the delicate microbiological balance in the gut, often causing diarrhoea and overgrowth of resistant pathogens and fungi.
Results: Four of the control patients were colonised with L p 299v
on admission, but at the second biopsy they were all negative. Of
eight treated patients none had positive cultures for L p 299v on
admission but from the second sample and through their ICU-stay
three of them had the bacteria adhered to the mucosa confirmed
by cultures from homogenised biopsies.
Many potentially pathogenic bacteria adhere to enterocytes via a
mannose-specific adhesin. This mechanism has also been found in
Lactobacillus plantarum 299v (L p 299v) both in the jejunum in the
rectum. It is when bacteria are adhered to the mucosa that they
interact with the enterocytes, both in negative and positive fashions.
Bacterial analyses revealed a reduction of sulphite-reducing
clostridia in the treatment group. In treated patients lactobacilli
increased while they remained at the original level in controls.
Given in fermented oatmeal soup to healthy subjects, L p 299v
was detected even 11 days after termination of intake.
Discussion: The initially positive biopsies in four of the control
patients were probably due to that these patients had ingested
L p 299v through the commercial L p 299v-containing ‘Proviva’,
which is sold in almost all grocery-shops in southern Sweden. The
use of antibiotics leads to a level of L p 299v below the limit of
detection in those that were colonised from the beginning.
In patients with persisting Clostridium difficile infections this fermented oatmeal soup containing L p 299v has also been effective
in normalising gutflora and function.
Objectives: The prime objective was to study if L p 299v could
survive and colonise on the mucosa in the intestine of patients
treated in an ICU. Stool consistency and frequency were among
other parameters studied.
Method and materials: In a randomised prospective trial 8 patients
received 200 ml daily for 3 days and then 100 ml of an oatmeal soup
containing 109 cfu/ml of L P 299v through out their stay in the ICU.
Enteral nutrition as well as the oatmeal soup was started within 24 h
after admission to the ICU. Control-patients (7) were treated in the
same fashion except for the fermented oatmeal soup. The rectal
mucosa was biopsied after admission and then twice a week. Biopsies were analysed blindly for bacterial content and species.
Diarrhoea was less frequent in treated patients.
In the treatment group the L p 299v adhered to the mucosa in 3/8
patients although they as well were treated with antibiotics. It
seems that repeated administration is essential if the bacteria
should remain in sufficient numbers adhered to the mucosa. Our
study shows that antibiotic treated patients in an ICU environment can benefit from probiotics. Less diarrhoea means less
impact on the gutflora.
By the repeated administration of the oatmeal soup fermented
with L p 299v it is concluded that the bacteria can adhere to the
gut mucosa in antibiotic treated critically ill patients. Further
studies with larger numbers of patients are needed to evaluate
other effects.
P193 A simple and safe bedside method of transpyloric feeding tube placement in critically ill patients
R Stögbauer and C Hermann
Department of Anesthesiology and Intensive Care Medicine, Bethanien Hospital Moers, Bethanienstr. 21, 47441 Moers, Germany.
Tel: 0049-2841-2002275: Fax: 0049-2841-2002291
Crit Care 1999, 3 (suppl 1):P193
Background Early enteral nutrition is an accepted gold standard
in the treatment of critically ill patients. The major limiting factor
is depressed gastric motility. However, while small bowel function
usually remains intact, the placement of postpyloric feeding tubes
increases the number of patients absorbing a sufficient volume of
enteral nutrition early in their ICU course. To eliminate the need
of invasive and expensive interventions, many bedside techniques
have been proposed. Recently one effective way has been
described in critically ill children [1]. We modified this method
and used it in 27 adult patients.
Methods: Thirty-one postpyloric feeding tubes were placed blindly
in 27 consecutive ventilated postsurgical ICU patients using a
bedside protocol. The feeding tube was considered to be postpyloric when following the insufflation of 20 ml of air an amount less
then 5 ml could be reaspirated. The explanation is the immediat
collapse of the narrow small intestine lumen, when air is reaspirated. The tube position was confirmed by abdominal radiography .
Results: In all 31 cases the enteral feeding tube was placed successfully. The average placement time was 14 min. Nineteen tubes
(61.2 %) were positioned in the duodenum and 12 tubes (38.8%) in
the jejunum. The inability to reaspirate insufflated air correctly
predicted transpyloric position in all cases. Initially the administration of enteral feeding was in 100% successfully possible. After 2
days of continous enteral nutrition, we observed duodeno-gastric
reflux in one patient. No further complications occured.
Conclusion: A simple bedside placement protocol enables the
positioning of postpyloric feeding tubes in adult ventilated critically ill patients. The inability to aspirate insufflated air from the
tube confirmed the correct position in every case. This approach
leads to a cost effective and early initiation of enteral feeding in
the critical care setting without requiring extensive methods.
References
1. Crit Care Med 1997, 25:2055-2059.
98
Critical Care 1999, Vol 3 suppl 1
P194 Peritoneal ventilation in volume controlled hemorrhagic shock: outcome model in rats
J Barr, S Prueckner*, P Safar*, S Thisherman*, J Stezoski* and G Eshel
Pediatric Intensive Care Unit, Assaf Harofeh Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Zerifin 70300, Israel.
*Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine 3434 Fifth Avenue, Pittsburgh PA 15260, USA
Crit Care 1999, 3 (suppl 1):P194
Introduction: Peritoneal ventilation was studied few years ago
[1,2] to be a successful auxiliary extrapulmonary method for
improving oxygenation and CO2 elimination in laboratory animals
with experimental ARDS. Bowel ischemia during hemorrhagic
shock is known to cause, after initial fluid resuscitation, late hazardous remote effects with multiple organ system failure and high
mortality rate [3].
Hypothesis: In severe volume controlled hemorrhagic shock, peritoneal ventilation with oxygen would: 1) improve local oxygenation of the abdominal viscera, preventing later multiple organ
failure, and 2) increase survival rate.
Methods: (Figure) The study included three groups (10 rats each),
using light anesthesia (N2O/O2 and Halothane) during preparation
and the first 120 min of the study. Group I = PEV-O2 (Peritoneal
ventilation with 100% oxygen), Group II = PEV-RA (PEV with
room-air), Group III (control, no PEV). In groups I & II, a 14 F
catheter was surgically introduced into the peritoneal cavity,
before hemorrhagic shock (HS). Phase I – HS: All rats underwent
blood withdrawal of 3 ml/100 g body weight within 15 min,
causing HS lasting up to 60 min. Starting at 15 min, Group I & II
were terated by peritoneal ventilation (oxygen vs. room-air), rate =
40/min, tidal volume = 6 ml, until the end of resuscitation phase.
Phase II - Resuscitation - lasted 60 min (from 60 to 120 min), at the
beginning of which 3–4 ml of blood transfusion increased MAP to
>80 mmHg within 2–3 min. The rest of the blood was transfused
over the next 15 min. Phase III - observation – lasted 7 days. Surviving rats were scarified (high dose halothane). Necropsy of abdominal organs was performed in all rats.
Results: Survival to 7 days was achieved by 10 of 10 rats in PEVO2 Group I, 9 of 10 in PEV-RA Group II, and 5 of 10 rats in the
90
Preparation
Conclusion: Peritoneal ventilation with oxygen during and after
hemorrhagic shock, seems to help to preserve viability of the
intestine and may significantly decrease morbidity and mortality.
Acknowledgement: The study was supported by the US Navy
MRDC-ONR)
References
1. Barr J et al.: Peritoneal ventilation: an animal model of
extrapulmonary ventilation in experimental adult
respiratory distress syndrome. Pediatr Res 1994, 35:682684.
2. Barr J et al.: Peritoneal ventilation in rabbits:
augmentation of gas exchange with cisapride. Thorax
1996, 51:82-86.
3. Chang TW: Improvement of survival from hemorrhagic
shock by enterectomy in rats: finding to implicate the role
of the gut for irreversibility of hemorrhagic shock. J
Trauma 1997; 42:223-30.
HS Phase I
80
Resuscitation
Phase II
Blood
Withdrawal
70
60
MAP
Control Group III. Survival rate in the PEV-O2 group (100% survival) was significantly higher than that of the control group, but
not significantly higher than that of the PEV-RA group. The survival rate of the PEV-RA group (90%) was not significantly higher
than that of the control group (50%). Morbidity evaluation of all
rats during the observation phase, as reflected by their daily neurological deficit scores, showed significant difference between all
groups. Necropsy examination of the rats who died during the
observation phase showed marked, diffuse pathology of abdominal organs, mainly gut perforations and necrosis. Necropsy of the
rats who survived the 7 days of observation, showed marked
macroscopic abnormalities in all survivors of the Control Group
III, moderate changes in most of the rats of the PEV-RA Group II,
and normal examination in all 10 rats of the PEV-O2 Group I.
Observation Phase III
7 Days
50
(mmHg)
40
Peritoneal
Ventilation
30
20
10
0
-45
-30
-15
0
15
30
45
60
75
90
105
120
Time (min)
Figure. Peritoneal ventilation: study design.
P195 The Paracetamol Absorption Test (PAT): an obligatory addition to the enteral nutrition algorithm?
J Cohen, A Aharon and P Singer
General Intensive Care Unit, Rabin Medical Center, Campus Beilinson, Petah Tikva, Israel
Crit Care 1999, 3 (suppl 1):P195
Enteral nutrition (EN) is beneficial for critically ill patients. The
simplest and most convenient way of providing EN is via a nasogastric (NG) tube. Feeding is often stopped because of increased
Poster abstracts
99
paracetamol through the NG tube was >600 mg/min/l. Results of
the test were obtained within 4 h and EN was resumed in those
patients with a normal result.
volumes of NG aspirate, thought to reflect inadequate intestinal
function. However, this has been shown to be an unreliable indicator of gastric function. We assessed whether the PAT (absorption of paracetamol in the small intestine depends on the rate of
gastric emptying) could provide more reliable information in
patients with a large NG rest.
Results: See Table; expressed as median ± SD. EN was successfully restarted in all group 2 patients
Methods: We studied 14 consecutive patients receiving continuous EN via NG tubes who had large gastric residues (>120 ml or
2× the hourly rate) on routine aspiration. EN was stopped and
gastric emptying using the PAT was assessed immediately thereafter. The test was considered normal if the area under the concentration curve from 0–60 min (AUC60) after giving 1 g of
Conclusions: This study showed that 6/14 patients (43%) with an
abnormal NG aspirate had a normal PAT; these patients continued
to receive EN without untoward effects. We suggest that the PAT
be performed in all patients receiving EN with a large NG aspirate; if the test was normal, EN should be continued; if the test is
abnormal, use of prokinetic agents should be considered.
Total group
Group 1 (AUC60 <600)
Group 2 (AUC60 >600)
14
8
6
AUC60 (ml/min/l)
314.25 ± 356.81
118.12 ± 123.14
NG aspirate (ml)
245 ± 247.11
Number
350 ± 296.9
711 ± 174.96
180 ± 55.50
P value
(Gp 1 versus 2)
<0.001
0.109
P196 Enteral versus parenteral nutrition: no difference in the incidence of fungal infections in critically-ill patients
on mechanical ventilation with selective digestive decontamination
J Garbino, P Pichna, D Lew, D Pittet and J-A Romand
Division of Infectious Diseases, University Hospital of Geneva, Geneva 1211, Switzerland
Crit Care 1999, 3 (suppl 1):P196
Background: Infections are an important cause of morbidity and
mortality in patients in the intensive care units (ICUs). Fungal
infections have increased substantially over recent years and fungi
have become one of the important pathogens in intensive care
patients. This study was undertaken to test the hypothesis that
the incidence of fungal infections is lower in critically-ill patients
under mechanical ventilation receiving enteral rather than parenteral nutrition.
Methods: By using a prospectively-built database, we analyzed
retrospectively the charts of 110 critically-ill, intubated patients
hospitalized in surgical and medical ICUs and receiving selective
digestive decontamination (SDD). SDD is the prophylactic use of
topical, nonabsorbable antibiotics to reduce the incidence of respiratory tract infections in critically-ill patients. It is known that this
therapy significantly reduces the incidence, but not the mortality
rate of pneumonia in ICU patients. In this study the SDD for all
patients comprised of a PNV solution (polymyxin B, neomycin,
vancomycin) at a dosage of 15 ml administered six times daily.
Seventy-nine patients received enteral nutrition and 31 patients
parenteral nutrition.
Those patients without contraindications, and expected to be
intubated for more than 72 h, received enteral nutrition which was
started within 24 h after intubation. Patients with contraindications for enteral nutrition received parenteral nutrition which was
discontinued when the criteria for enteral nutrition were met. We
compared the incidence of fungal infections in both subgroups of
patients, i.e., enteral versus parenteral nutrition.
Results: The two subgroups were similar with regard to their
APACHE II score, in age, sex distribution and comorbidities at
the time of study entry. The rate of fungal infection was seen to
be higher in the parenteral nutrition group, 5 out of 29, as compared to 7 out of 71 in the enteral nutrition group. However, this
difference was not considered to be statistically significant.
Conclusion: No significant difference is observed between enteral
vs. parenteral nutrition in the incidence of fungal infections in
critically-ill patients receiving SDD.
P197 Hyperglycemia predispose to catheter-related sepsis in diabetic patients receiving Total Parenteral Nutrition
V Alivizatos, S Scarpetas, D Delidimitri and P Athanasopoulos
Department of Surgery and Nutrition Unit, ‘St. Andrew’ General Hospital, Patras, Greece
Crit Care 1999, 3 (suppl 1):P197
Hyperglycemia is encountered during nutritional support in diabetics and in patients with stress-related glucose intolerance. Aim
of this study is to determine the incidence of central venous
catheter-related sepsis (CRS) and its relationship with the serum
glucose levels in diabetic patients treated with Total Parenteral
Nutrition (TPN).
Methods: Medical records of 123 surgical patients (median age
68.1 years) treated with TPN in our Department between
1/1/1990 and 31/12/1997 were reviewed. They received TPN for a
median duration of 14.3 days (range 2–65) by the method of ‘allin-one’. Out of these, 27 patients were diabetics. Two units of
regular insulin were added in the TPN-bag for each 20 g of
glucose contained, in each diabetic patient. The nutrient admixture was volumetrically delivered over 24 h through a subclavian
100
Critical Care 1999, Vol 3 suppl 1
vein catheter. The parameters measured were lenght of TPN
therapy, serum glucose levels (measured every 6 h) during the
nutritional support, and the incidence of CRS which was defined
by local or systemic signs of sepsis, positive culture of the catheter
tip, concurrent positive blood cultures and defervescence of the
clinical signs of sepsis following catheter removal. Data analysis
was done using the Fisher’s exact test. Values P < 0.05 were considered statistically significant.
Results: There was no difference to the lenght of TPN therapy
between diabetics and non diabetics. In 20 diabetics the serum
glucose levels remained <200 mg/dl, and in 7 were constantly high
(>200 mg/dl) in all measurements during TPN administration.
Eleven out of the 96 non diabetics (11.4%) and 3 out of the 20
‘euglycemic’ diabetics (15%) presented CRS, but this difference
was not significant (P = 0.8); however, CRS was presented in 5 out
of the 7 diabetics whom serum glucose levels were >200 mg/dl
during TPN therapy (P = 0.01).
Conclusion: The results of out study suggest that CRS is serious
risk in diabetics receiving TPN if good control of glycemia is not
maintained; in adverse, the incidence of CRS doesn’t seem to be
significantly increased in well-controlled diabetics.
P198 Dysregulation of glucose metabolism in enterally fed patients with acute pancreatitis
P Tesinsky, T Staudinger*, Z Rusavy, H Kordova, Z Jankovec and R Karova
Department of Internal Medicine 1, University Hospital, Plzen, Czech Republic; *Depertment of Internal Medicine 1, University Hospital, AKH,
Vienna, Austria
Crit Care 1999, 3 (suppl 1):P198
Introduction: Dysregulation of glucose metabolism is one of
Ranson’s criteria for prognostic scoring in acute pancreatitis. Aim
of this study was to evaluate the impact of gastric and jejunal
access of enteral nutrition on glucose metabolism in patients with
mild and severe acute pancreatitis.
Patients and methods: Eighty-two non-diabetic patients admitted
to a medical ward for acute pancreatitis entered the study. All
patients were treated with total parenteral nutrition, and subsequently with total enteral nutrition administered into the
jejunum. The jejunal tube was placed into the stomach at the end
of the study period. Glycaemia was monitored 48 h after onset of
acute pancreatitis (G1), on the last day of jejunal nutrition (G2)
and on day 2 of gastric nutrition (G3).
Results: In patients with mild acute pancreatitis (n = 56), G1 was
above the normal range in 10 patients (17.9%), G2 in 2 patients
(3.6%), and G3 in 3 patients (5.4%).
In patients with severe acute pancreatitis (n = 26), G1 was above
the normal range in 22 patients (84.6%), G2 in 5 patients (19.2%),
G3 in 5 patients (19.2%). Secondary diabetes mellitus was present
in 3 patients of this group (11.5%). No significant difference of
serum insulin levels was found between both groups.
Conclusion: Dysregulation of glucose metabolism in mild acute
pancreatitis is transient and usually does not require therapeutic
intervention. Hyperglycaemia in severe acute pancreatitis is clinically relevant and manifestation of secondary diabetes mellitus is
frequent. Type of enteral nutrition does not represent a significant
impact on glucose metabolism.
P199 Energy consumption rate of critically ill patients: a prognostic factor?
S Hentsch, E Kollig, M Kemen and V Zumtobel
Surgical Department, Ruhr-University Bochum/Germany; St.-Josef-Hospital 44791 Bochum, Gudrunstr. 56, Germany
Crit Care 1999, 3 (suppl 1):P199
Introduction: Energy consumption of critically ill patients is
increased in relation to basic metabolic rate due to post aggression
metabolism. The aim of the present study is to assess the effect of
various energy consumption rates in critically ill patients referring
to the outcome of these patients.
Materials and methods: 40 critically ill patients on a surgical intensive care unit were included in a prospective clinical trial (6
female and 34 male patients). The following criteria for these
patients were fixed: mechanical ventilation for at least 3 days, clinical criteria of MODS or SIRS, APACHE-II-score >10, TISS-score
>20, total parenteral nutrition for at least 6 days, FiO2 >40%,
informed consent. The basic metabolic rate was calculated daily
(Harris-Benedict). Current metabolic rate was measured by indirect calorimetry using a Deltatrac II( Datex-Engström) in the res-
piratory mode. Data aquisition (oxygen consumption VO2 and
CO2 production VCO2) was performed in 6-h periods over average
5.7 days. Energy consumption was determinated by calculation of
respiratory quotient. We compared the energy consumption rates
with the patients outcome during the trial (14 days).
Results: 30 patients survived the first 14 days, 10 patients died
due to multi organ failure. The mean calculated basal metabolic
rate in the group of survivors was 1662 kcal/24 h, the measured
energy consumption was 2109 kcal/24 h. The mean increase was
26.9% in relation to basal rate. Non-survivors had a basal rate of
1653 kcal/24 h, a measured rate of 2097 kcal/24 h. That is a mean
increase of 25.4%. The increase in both groups was statistically
not significant (t-test, P < 0.05). Energy consumption rates of critically ill patients show no significant differences between survivors
and non-survivors during 2 weeks. Deviations of energy consumtion in these patients could not use as a prognostic factor.
Poster abstracts
101
P200 Alterations of metabolic and hemodynamic parameters during whole body hyperthermia on the ICU
A Nierhaus, C Meissner, S Hegewisch*, J Panse* and J Schulte am Esch
Dept of Anaesthesiology and *Dept of Oncology, University Hospital Eppendorf, D-20246 Hamburg, Germany. Tel:+49404717-2450; Fax:-5372;
E-mail: nierhaus@uke.uni-hamburg.de
Crit Care 1999, 3 (suppl 1):P200
Introduction: Whole body hyperthermia (WBH) has received
renewed interest for the treatment of metastatic cancer [1]. Using
a radiant heat device for induction and maintenance of WBH has
been shown to have little toxicity [2]. However, the acute
cardiovascular and metabolic changes during the treatment are
pronounced [3].
156 ± 21 ml/min to 303± 33 ml/min. The values remained elevated
after the patients had returned to baseline core temperature.
Lactate plasma concentrations did not change significantly. Plasma
levels of noradrenaline changed from 156 ± 140 µg/l after induction
of anaesthesia to 699 ± 302 µg/l during plateau, adrenaline levels
increased slightly from 40 ± 48 µg/l to 67 ± 64 µg/l. Arrhythmia,
myocardial ischemia or left ventricular failure were not observed.
Pulmonary and renal function remained undisturbed.
Methods: After informed consent, in 12 ASA II patients with
metastatic malignant disease who were eligible for WBH hemodynamic, metabolic parameters, lactate and catecholamine plasma
concentrations were studied over a 24 h period. The heating
device was a RHS-7500, Enthermics Medical Systems, Inc.,
Menomonee Falls, WI, USA. Target temperature was 41.8°C, time
at target was 60 min. Anaesthesia was total intravenous anaesthesia
by TCI using propofol (4–6 µg/kg/min). Patients were intubated
and mechanically ventilated with an FiO2 of 0.4 after induction
with sufentanil (0.3–0.4 µg/kg), propofol and rocuronium
(0.8 mg/kg). Measurements were taken at baseline, during
heating, at plateau, after reaching baseline temperature and at 24 h
post plateau. Hemodynamic data consisted of HR, MAP, CVP,
PAP, PCWP, CI, SVR. Metabolic data were obtained by indirect
calorimetry (Puritan Bennett 7250 Metabolic Monitor, PuritanBennett-Hoyer GmbH, Bremen, Germany) and consisted of VO2,
VCO2, RQ and energy expenditure (EE).
Discussion: During WBH, the changes of cardiovascular and
metabolic parameters are severe but in our patients did not compromise cardiac, pulmonary or renal function. However, great care
must be taken to exclude patients with cardiorespiratory pathology. Elevation of the body temperature to 41.8°C was accompanied by a fourfold rise in plasma noradrenaline, reflecting high
sympathetic nerve activity. Plasma adrenaline remained almost
unchanged during plateau. The pronounced heat-induced hypermetabolism and the endocrine response to heating were not abolished by general anaesthesia and were present throughout the
observation period. Lactate levels did not rise significantly, suggesting that metabolism remained aerobic. To compensate for the
massive loss of peripheral vasomotor tone, aggressive fluid
replacement guided by invasive monitoring is recommended for
management of patients undergoing WBH. Further studies will
determine what type of anaesthetic management should be preferred.
Results: During heating and plateau at 41.8°C an increase of
cardiac index from baseline of up to 140% could be observed,
which was due to a decrease of SVR and MAP. HR increased to
138 ± 27 bpm. CVP, PCWP and PAP did not change significantly.
VO2 increased from 176 ± 23 ml/min to 372 ± 62 ml/min, EE from
1232 ± 51 kcal/day to 2214 ± 62 kcal/day and VCO2 from
References
1. Kapp DS: Int J Hyperthermia 1994, 10:355-359.
2. Robins HI: Cancer Res 1985, 45:3937-3944.
3. Kim YD et al.: Am J Physiol 1979, 237:H570-H574.
4. Gautherie M: Whole Body Hyperthermia: biological and
clinical aspects, 1992:48.
P201 GH and cortisol secretion in patients with burn on day 7 after thermal injury
D Bollero, L Gianotti*, F Broglio*, F Lanfranco*, A Bertagna*, M Stella, G Magliacani and E Ghigo*
Division of Plastic Surgery, Burn Unit, CTO Hospital, Turin;*Division of Endocrinology, Department of Internal Medicine, University of Turin, Italy
Crit Care 1999, 3 (suppl 1):P201
Objectives: Hormonal and nutritional changes occur in burns
patients, in whom low IGF-I and high cortisol levels are commonly
reported during the first 2 weeks after the burn event. However, conflicting data about GH secretion are still present. In fact, high GH
levels have been reported by some but not by other authors. Aim of
this study was to define growth hormone (GH) and cortisol (F) secretion during a 12-h period on day 7 after a major burn in man.
Methods: In 5 patients with major burn injury (BURN, age, mean ±
SEM: 35.5 ± 5.4 years; BMI: 27.1 ± 2.3 kg/m2; burn area: 36.5 ± 5.5%;
ROI score: 0.3 ± 0.1) serum GH and cortisol levels were evaluated
every 20 min from 7.00 am to 7.00 pm on day 7 after burn unit (BU)
admission, during parenteral and/or enteral nutrition and dopamine
infusion (5–10 µg/kg/min). The same hormonal evaluation was performed in six normal fed adult subjects (NS, age: 30.2 ± 2.5 years;
BMI: 22.3 ± 2.6 kg/m2). IGF-I levels were also evaluated at 7.00 am
on day 7 after BU admission in BURN and basally in NS.
102
Critical Care 1999, Vol 3 suppl 1
Results: On day 7 after BU admission, IGF-I levels in BURN
were lower than in NS (90.5 ± 12.3 vs 210.6 ± 12.8 µg/l, P < 0.05).
On the contrary, mean serum GH levels in BURN (solid circles)
were higher than in NS (open circles) (mean GH levels: 2.8 ± 1.5
vs 0.4 ± 0.1 µg/l, P < 0.001; AUC: 85.7 ± 41.9 vs 21.7 ± 6.7 µg/l/h,
P < 0.001). Particularly, GH secretion in BURN was normally pulsatile with elevated baseline GH levels. Also mean F levels
BURN were elevated and higher than in NS (mean F levels:
241.7 ± 39.9 vs 84.4 ± 17.1 µg/l, P < 0.001; AUC: 15093.3 ± 3112.4 vs
5048.6 ± 1030.8 µg/l/h, P < 0.001), with high levels even in the late
afternoon and loss of circadian rhythm.
Conclusion: Our data show that in burns patients on day 7 after BU
admission, GH as well as cortisol secretion are markedly higher
while IGF-I levels are clearly lower than in NS. These findings
confirm the existence of peripheral GH resistance in critical illness
together with adrenal axis hyperactivity. Peripheral GH resistance
and hypercortisolism could likely contribute to impair recovery
from the catabolic state in the early phase after thermal injury.
Acknowledgement: This study has been supported by Fondazione Piemontese per gli Studi e le Ricerche sulle Ustioni and
Fondazione SMEM, Italy
P202 Magnetic stimulation of the phrenic nerves to assess diaphragm strength on the Intensive Care Unit
AC Watson, ML Harris, N Hart, M Green and J Moxham
Kings College and the Royal Brompton Hospitals, Fulham Road, London, SW3 6NP, UK
Crit Care 1999, 3 (suppl 1):P202
Traditional methods of assessing respiratory muscle strength in
the critically ill rely on some degree of co-operation from the
patient, and are of limited use. We performed bilateral magnetic
stimulation of the phrenic nerves, using two 43 mm magnetic coils
placed anteriorly on the neck [1]. The transdiaphragmatic pressure change (TwPdi) was recorded using oesophageal and gastric
balloon catheters in the conventional manner. Twitch endotracheal tube pressure (TwPett) was also recorded, which reflects
twitch oesophageal pressure (TwPoes). The pressure readings,
Poes, Pgas and Pett were displayed and recorded on a computer
together with the calculated value for Pdi (Pgas–Poes).
mean TwPett was 70 cmH2O (range 0.0–26.3). The mean difference between TwPett and TwPoes was 0.4 cmH2O, and the correlation of the means of TwPett to TwPoes was 0.93.
Diaphragm contractility can be assessed in the sedated ICU
patient, by magnetic stimulation of the phrenic nerves. This technique is non-volitional and is reasonably well tolerated. Our data
shows that diaphragm conctractility in the critically ill patient is
considerably less than in the laboratory based control subject [1].
Also, we report a good correlation between TwPoes and TwPett,
leading to the possibility of further simplification of the technique.
Acknowledgement: Funded by the Wellcome Trust
Twenty critically ill patients were studied (12 male, eight female),
with a mean age of 59 years. Average length of ICU stay prior to
the study was 27 days. The mean TwPdi was 9.5 cmH2O (range
1.0–29.3), mean TwPocs was 6.6 cmH2O (range 0.5–22.9), and
Reference
1. Mills GH et al.: Am J Respir Crit Care Med 1996;
154:1099-1105.
P203 Assessment of adductor pollicis muscle function in critically ill patients
ML Harris, YM Luo, SJ Clark*, JA Wendon* and J Moxham
Departments of Respiratory Medicine and Liver Studies*, Guy’s, King’s & St Thomas’s School of Medicine, Kings College Hospital, London, UK
Crit Care 1999, 3 (suppl 1):P203
Skeletal muscle wasting is a recognised finding in the critically ill,
but few data exist concerning the strength of peripheral skeletal
muscles in patients on the Intensive Care Unit (ICU). This may be
because previously available techniques involved measurement of
force during a maximal voluntary contraction (MVC) and on ICU
this type of test may be unreliable since it is effort dependent. We
therefore used a novel, non-volitional technique, supramaximal
magnetic stimulation of the ulnar nerve (Harris et al.: AJRCCM
1998, 157:A359), to measure adductor pollicis twitch tension (Tw
AP) in 14 patients (10M 4F), mean age 44 (range 24–73) years, with
a range of diagnoses. Severity of illness was scored within 24 h of
admission to ICU and median (95% CI) Apache II score was 19.5
(14–28). Median length of stay (95% CI) (at the time of testing)
was 11 (5–17) days. Fourteen healthy volunteers (10M 4F) mean
age 44 (21–78) years, served as controls. Median (95% CI) Tw AP
in the patients was 3.6 (23–5.9) N and in the controls 7.9 (5.3–9.9)
N (P < 0.01, Mann Whitney U Test). Our data show that patients
with critical illness are weaker than ambulant controls. The reasons
for the observed differences in strength are likely to be multifactorial; further studies are therefore warranted to elucidate the specific
causes of this weakness and the relationship between skeletal
muscle weakness and failure to wean from mechanical ventilation.
Acknowledgement: NHS Executive Grant No RDF 028
P204 Skeletal muscle strength in critically ill patients
ML Harris, C-H Hamnegard*, MI Polkey and J Moxham
Departments of Respiratory Medicine, Guys, King’s & St Thomas’s School of Medicine, Kings College Hospital, London, UK
& *Sahlgrenska University Hospital, Gothenburg, Sweden
Crit Care 1999, 3 (suppl 1):P204
Measurement of peripheral muscle strength in the Intensive Care
Unit (ICU) has been seldom documented. The purpose of the
study was to determine whether quadriceps twitch tension (Tw Q)
could be measured in a range of critically ill patients in the ICU
using a novel non-volitional technique, supramaximal magnetic
stimulation of the femoral nerve (Polkey et al.: Muscle Nerve 1996,
Poster abstracts
19:549-555) and to determine the magnitude of weakness. Measurements were made in 20 patients (12M 8F), mean age 59 (range
24–81) years, with varying diagnoses. Median (95% CI) length of
stay (at the time of testing) was 18 (7–29) days. 20 healthy elderly
volunteers (12M 8F), mean age 59 (range 25–80) served as controls.
Median (95% CI) Tw Q in the patients was 3.5 (2.6–5) kg compared with 9.5 (7.8–11.7) kg in controls (P < 0.01, Mann Whitney U
Test) and weakness was not correlated with length of ICU stay.
103
The data demonstrate that profound quadriceps weakness can
occur in critically ill patients. This weakness may influence mobilisation and rehabilitation. It is likely that other skeletal muscles are
similarly affected, including the muscles of respiration. If so, this
would in part, determine weaning outcome.
Acknowledgement: Supported by NHS Executive Grant No RDF
028
P205 Ultrasonographic quantification of muscular mass thickness in patients of intensive care unit
M Moukas, AN Chalazonitis*, K Soulpi, G Tsimitselis*, C Mandragos, A Kalopisi, C Katsenos, M Patrani, N Batakis* and PK Behrakis
Intensive Care Unit and *Radiological Department, Hellenic Red Cross Hospital. 1, Erythrou Stavrou str. 11526 Athens, Greece.
Tel: +301-6910147, Fax: +301-6910263; E-mail: red-rad@ath.forthnet.gr
Crit Care 1999, 3 (suppl 1):P205
Purpose: The aim of this study is to assess the degree of change of
upper-arm skeletal muscle thickness in patients of Intensive Care
Unit (ICU) and to propose a new method for quantifying this change.
Methods: The thickness of upper-arm biceps was measured twice
in 16 female patients (mean age 61.63 ± 8 years) and in 27 male
patients (mean age 50.7 ± 9 years) during an ultrasonographic scan
by the same ultrasonographer. A 10 MHz frequency, linear high
resolution transducer was held longitudinal to the biceps muscle
in the place of maximum thickness. All subjects were patients of
ICU (13 with multi trauma, 4 with brain injuries, 11 with cerebral
sroke, 8 with respiratory insufficiency, 3 with tetraparesis C3–C4
fracture, 3 with hypoxemic engephalopathy and 1 with septic
shock) hospitalized for 18.88 ± 3 days. Throughout hospitalization
all patients were in parenteral nutritional support with
1800–2400 Kcal/day intake and were also under physical therapy
for 60 min/day. Creatine phosphokinase (CPK), Aldolase (Ald) and
Albumin (Alb) levels were recorded twice. First measurement was
done when patients entered the study and second when they left
ICU. Ultrasonographic scans were performed at the same periods
of time. Ten of our patients were not under muscle relaxant or
drug depression muscle treatment, meanwhile all the others were
under muscle relaxant treatment for 4 ± 2 days and under drug
depression muscle treatment for 7 ± 3 days.
Results: During the period of our study CPK levels decreased
from 2301.26 U/l (mean value, with maximum level 20 000 U/l and
minimum level 20 U/l) to 251.21 U/l (mean value, with maximum
level 850 U/l and minimum level 30 U/l), Ald levels decreased
from 10.39 U/l (mean value, with maximum level 21.15 U/l and
minimum level 3.5 U/l) to 7.59 U/l (mean value, with maximum
level 18.6 U/l and minimum level 3 U/l), Alb levels decreased from
33.07 g/l (mean value, with maximum level 41.15 g/l and minimum
level 26 g/l) to 29.56 g/l (mean value, with maximum level 35 g/l
and minimum level 24 g/l). Fifteen patients showed an increase of
2.714 g/l of the Albumin levels and 28 other patients showed a
decrease of 7 g/l of the Albumin levels. Muscle thickness
decreased from 2.51 cm (mean value, with maximum level 3.75 cm
and minimum level 1.48 cm) to 2 cm (mean value, with maximum
level 2.19 cm and minimum level 1.19 cm)
Conclusion: We conclude that long term ICU hospitalization is
associated with a gradual decline (0.03 cm/day) in muscular mass.
This decline is not CPK, Ald, Alb or physical therapy-dependent.
P206 The influence of aldosterone and angiotensin II on the diuretic effects of atrial natriuretic peptide in the
isolated perfused rat kidney
M Heringlake, KF Wagner, J Schumacher, H Pagel* and P Schmucker
Medizinische Universität zu Lübeck, Klinik für Anaesthesiologie und *Institut für Physiologie Ratzeburger Allee 160,D-23538 Lübeck, Germany;
Tel/Fax: +49 (0)451 500/3477
Crit Care 1999, 3 (suppl 1):P206
Background: The diuretic effects of atrial natriuretic peptide
(ANP-99-126) are reduced in patients with advanced cirrhosis of
the liver and severe myocardial dysfunction. These patients also
often display an increased acitivity of the renin–angiotensin–
aldosterone system (RAAS) resulting in high plasma concentrations of aldosterone (ALD) and angiotensin II (AII).
Objective: To study the effects of ANP in isolated perfused rat
kidneys after pretreatment with AII or ALD to determine which
hormone causes ANP unresponsiveness in this setting.
Materials and methods: Three groups of kidneys were perfused
for 3 h with a constant perfusion pressure of 100 mmHg.: a control
group (n = 5), a AII/ANP group (n = 6; 0.1 nmol/l AII in the second
hour; 3.25 nmol/l hANP in the third hour) and an ALD/ANP
group (n = 4; 27.7 nmol/l ALD in the second hour; 3.25 nmol/l
hANP in the third hour). We determined urine flow (VU), urinary
excretion of sodium (VNaU) and potassium ( VKU), inulin-clearance (GFR) and renal vascular resistance RVR.
Results: AII/ANP group: treatment with AII decreased VU,
VNaU,VKU and GFR and increased RVR. ANP restored renal
function to control levels (VNaU, VKU, GFR) or above (VU, RVR).
ALD/ANP group: treatment with ALD induced an increase of VKU.
Subsequent treatment with ANP further increased VKU and
slightly decreased RVR. No effects on GFR, VU or VNaU were
observed.
Conclusion: Our findings suggest that blunted ANP effects during
increased RAAS-activity are mainly determined by ALD. Interestingly, this is not only due to a blunted increase of sodium excretion (tubular mechanism) but also due to a blunted increase of
glomerular filtration rate (altered glomerular vascular reactivity).
104
Critical Care 1999, Vol 3 suppl 1
P207 Urinary excretion of urodilatin is increased during pressure natriuresis in the isolated perfused rat kidney
M Heringlake, KF Wagner, J Schumacher, H Pagel and P Schmucker
Medizinische Universität zu Lübeck, Klinik für Anaesthesiologie und *Institut für Physiologie, Ratzeburger Allee 160, D-23538 Lübeck, Germany.
Tel/Fax: +49 (0)451 500/3477
Crit Care 1999, 3 (suppl 1):P207
Background: Treatment with urodilatin (URO; ANP-95-126), a
kidney derived natriuretic peptide, may be beneficial in patients
with incipient acute renal failure after cardiac surgery [1]. The
findings about mechanisms regulating endogenous production
and renal excretion of URO are controversial. Recent evidence
suggests that urinary excretion of urodilatin (VUROU) is increased
in patients after uncomplicated cardiac surgery and positively correlated with blood pressure [2].
taken every 30 min. The concentration of urodilatin in urine and
perfusate were determined by a radioimmuno-assay for rat-urodilatin (rURO: Immundiagnostik, Bensheim, Germany) not crossreacting with rBNP, rCNP,rCDD/ANP-99-126 or hURO.
Results: Mean VU, VNaU, VKU and VUROU were significantly
higher with a perfusion pressure of 120 mmHg than with
80 mmHg (all: P < 0.05); PURO did not change significantly.
Objective: To determine the effects of different perfusion pressures on urine flow (VU), urinary excretion of sodium (VNaU),
potassium (VKU) and urodilatin (VUROU) and the concentration of
urodilatin in the perfusate (PURO) in isolated perfused rat kidneys.
Conclusion: Our data suggest that renal perfusion pressure and
consequently mean arterial blood pressure are determinants of
VUROU. Additionally, our data underline the importance of perfusion pressure for adequate renal function; this may be especially
relevant for patients at risk to develop acute renal failure after
cardiac surgery.
Materials and methods: Kidneys from Sprague-Dawley rats were
perfused for 180 min with constant perfusion pressures (80 mmHg
(n = 4); 120 mmHg (n = 4)) in a closed circuit system. Samples were
References
1. Meyer et al.: Clin Exp Pharm Physiol 1997, 24.
2. Sehested et al.: J Thoracic Cardiovasc Surg 1997, 114.
P208 Urine output in the first twelve hours after cardiopulmonary bypass does not predict the development of
renal impairment
SM Ali and GR McAnulty
St George’s Hospital Cardiothoracic Unit ITU/HDU, London, UK
Hourly urine output is one of the foremost indices which are monitored in patients who have undergone cardiac surgery. Traditionally, a urine output of less than 0.5 ml/kg/h triggers intervention
[1]. However, renal failure may supervene in patients who have
seemingly adequate renal function according to conventional
monitoring. In this pilot study we analysed urine output and alterations in serum creatinine in 31 consecutive patients in the first
12 h following coronary artery bypass and valvular surgery. We
found that an ‘adequate’ urine output alone is an unreliable predictor of subsequent renal impairment (indicated by a rise in 24 h
post-operative serum creatinine by more than 50%). Six patients
demonstrated such a rise in serum creatinine despite their producing urine outputs of greater than or equal to an average of
0.5 ml/kg/h. Of these, five subsequently required renal replacement therapy. This finding may have implications for the monitoring of cardiac patients who return to low-dependency patient care
areas within 12 h of surgery.
% difference post - pre-op serum creatinine
(negative values recorded as zero)
Crit Care 1999, 3 (suppl 1):P208
Regression Plot
140
120
100
80
60
40
20
0
0
5
10
15
20
25
30
35
40
-1
Urine Output over first 12 hours (ml kg )
References
1. Corso P, Eager MD. Postoperative care of the adult cardiac
surgical patient. In: Shoemaker WC, et al. Eds. Textbook of
Critical Care 3rd edn. Philadelphia: Saunders, 1995; 604-617.
P209 Homeostatic indications for the administration of diuretics
M Balik and A Kazda*
Department of Anaesthesia and Intensive Care, 3rd Med. Faculty, University Hospital Kralovske Vinohrady, Srobarova, 50, Prague 10, Czech
Republic, *Department of Clinical Biochemistry, Postgrad. Medical School, Faculty Policlinic, Karovo nám. 32, Prague 2, 120 00, Czech Republic
Crit Care 1999, 3 (suppl 1):P209
The authors monitored the effects of the different diuretics upon
the natrium and water homeostasis and acid–base balance. The
aim of the study was to clarify the exact mechanisms of their
action and possible ways of monitoring of their homeostatic
effects. The effects of furosemide (18 patients), hydrochlorothiazide (eight patients), spironolactone (14 patients), acetazolamide
(10 patients), amiloride (four patients) and manitol (eight patients)
were monitored in critically ill patients using computer pro-
Poster abstracts
gramme utilizing 17 routinely monitored input values and calculating creatinine clearance, tubular resorbtion , excretion fractions of
sodium, potassium, water and osmotically active substances, clearance of the osmotically active substances, clearance of solute free
water, electrolyte clearance, electrolyte free water clearance, urine
outputs of sodium, potassium and urea, urea concentration index
and serum and urine anion gaps. The development of parameters
typical for each diuretic was evaluated using Student’s t-test comparing the values before and during the treatment with the agent.
Main results: The natriuresis caused by furosemide is less important
than the disturbing of the kidney concentrating ability. It is indi-
105
cated in hyponatremia. Any of the evaluated parameters except
serum potassium levels were not typical for the treatment with
spironolactone. Hydrochlorothiazide reduces adverse effects of
furosemide upon the kidney concentrating ability. It is useful in
hypernatremia especially in the secondary nephrogenic diabetes
insipidus and it is indicated in the secondary renal tubular acidosis.
Amiloride was proved as the ideal therapy of chloride resistant metabolic alkalosis and hypokalemia. In comparison to acetazolamide it is
potassium sparing drug and it seems to be less natriuretic. The indication for the use of acetazolamide is metabolic acidosis with the
need for quick correction. Hyponatremia and hypoosmolality were
not proven as the homeostatic indications for manitol.
P210 The effect of intraoperative Lasix on sodium excretion following cardiac surgery
A Durward, S Haq, D Anderson and IA Murdoch
Paediatric Intensive Care, Guy’s Hospital, London, SE1 9RT, UK
Crit Care 1999, 3 (suppl 1):P210
Objective: To determine the effect of intra-operative Lasix on
sodium excretion (NaEx) in children following cardiac surgery
after cardiopulmonary bypass (CPB).
Methods: Thirty-six children (median age 5.9 months, range
0.06–182 months) underwent corrective cardiac surgery for congenital heart disease (CHD). The patients were divided into two
groups, Group A (n = 12) received 1 mg/kg of intravenous Lasix at
the end of the surgical operation, Group B did not receive Lasix
and acted as the control group. Urine samples were collected over
the 1st (t = 0) and 16th (t = 16) postoperative hour and sent with
paired blood samples for electrolyte measurements. Sodium
excretion (NaEx) and urine volume (ml/kg/h) was compared
between the two groups at t = 0 and t = 16 using the MannWhitney test. NaEx was calculated by multiplying urine volume
by urine Na concentration and expressed as mmoles/kg/h.
Results: There were no significant differences in age, weight, preoperative renal function, CPB times or underlying heart disease
(cyanotic vs acynotic) between the two groups.
NaEx and urine volume were significantly greater at t = 0 in the
group that received Lasix (P = 0.013 and P = 0.001 respectively).
These differences were no longer present at the 16th postoperative
Figure. NaEx plotted against urine volume at t = 0 and t = 16.
Blocks indicate median values, whiskers indicate 95%CI.
hour (P = 0.67 and P = 0.38 respectively). In both groups sodium
excretion correlated with urine volume (r = 0.98).
Conclusion: Although intraoperative Lasix transiently increases
sodium excretion and therefore urine volumes in the immediate
post operative period it does not appear to offer any advantage by
the 16th postoperative hour, a time when renal water and sodium
conservation is maximal.
P211 Treatment and prognosis of patients with nontraumatic rhabdomyolysis
D Siebenlist, K Kötter and S Gernert
Department of Internal Medicine and Department of Neurology, Leopoldina - Hospital, 97422 Schweinfurt, Germany
Crit Care 1999, 3 (suppl 1):P211
Introduction: Nontraumatic rhabdomyolysis is not frequent in an
internal-neurological ICU and there are few reports of aetiology,
clinical course, therapy and outcome of patients with severe rhabdomyolysis. We analyzed our patients with nontraumatic rhabdomyolysis to evaluate therapeutic strategies and prognostic
parameters.
Methods: In a retrospective study we analyzed the hospital reports
of patients with nontraumatic rhabdomyolysis admitted to our
internal-neurological ICU during a 12-year period (1986–1997).
Results: Thirty-four patients were admitted during the study
period (incidence 1: 416). The average age of the patients was
35.2 years (27 male, 7 female patients). The most frequent causes
for nontraumatic rhabdomyolysis were drug intoxication (35.3%),
strenuous exercise (26.5%), infections (17.6%) and seizures
(11.7%). The average level of creatine phosphokinase (CK) was
16234 U/l. All patients were treated by intravenous fluids for
volume repletion and by alkalinization of the urine, dialysis was
required in six patients (17.6%) for control of uremic symptoms.
Seven patients (20.5%) were treated by plasma exchange to
reduce rapidly excessive CK-levels in order to prevent acute renal
failure. Two patients died in septic MOF after drug-induced rhabdomyolysis and delayed hospital admission (mortality 5.9%). After
106
Critical Care 1999, Vol 3 suppl 1
ICU-stay three patients showed peripheroneural lesions, all other
patients (85.3%) recovered without sequelae.
Conclusion: Nontraumatic rhabdomyolysis has a good prognosis if
the patients are admitted early to the hospital for treatment. Plasma
exchange seems to be an effective therapy to prevent acute renal
failure. Septic MOF after rhabdomyolysis has a poor prognosis.
P212 High-volume continuous veno-venous haemofiltration in hyper-acute liver failure: a pilot study
W Bernal, T Wong and J Wendon
Institute of Liver Studies, Kings College Hospital, Denmark Hill, London SE5 9RS, UK
Crit Care 1999, 3 (suppl 1):P212
Background: Once defined clinical criteria are fulfilled in hyperacute liver failure (ALF) mortality without liver transplantation
(OLT) approaches 90%. Patients’ clinical condition may deteriorate
whilst awaiting a graft, such that transplantation becomes impossible due to the rapid progression of multiple organ failure. There is
need for therapies that may stabilise the patient and thus provide a
‘bridge to transplantation’. Animal studies suggest that high-volume
continuous veno-venous haemofiltration (HVF) in septic shock is
associated with improvements in haemodynamic stability and a
reduction in the requirement for vasopressor support. We report
findings of a pilot study of HVF in patients with ALF.
Patients and methods: Eight patients fulfilling transplantation criteria with acetaminophen induced ALF were studied. Median age
was 28 years (range 19–51), INR 4.6 (1.9–15), pH 7.23 (7.1–7.42),
lactate 9.4 mmol/l (6.7–17) and APACHE II 24 (22–34). Six
patients (75%) were receiving vasopressor support with noradrena-
line at 0.29 µg/kg/min (0.03–0.5) and all were in anuric renal
failure. Five patients were already established on conventional
veno-venous filtration. HVF (Baxter system) was commenced 2
days (1–4) after admission using buffer-free dialysate at 4000 ml/h
(3500-6000) with concurrent NaHCO3 infusion and filter surface
area 1.25 m2 for a median of 34 h (22–72).
Results: HVF resulted in a rapid correction of pH and significant
reductions in both serum lactate and base deficit within 24 h.
Mean arterial pressure was increased after 6 and 12 h of HVF
(P < 0.13) without corresponding increases in vasopressor support
(Figure). After 24 h of HVF four (50%) patients required noradrenaline at 1.45 µg/kg/min (0.025–0.4). Two patients underwent
OLT and survived, and 1 patient survived without transplantation.
Conclusions: HVF effectively corrects acidosis in patients with
ALF and is associated with improvements in haemodynamic stability. Its use in the support of patients awaiting transplantation
deserves further investigation.
P213 Continuous hemodiafiltration with bicarbonate- and lactate-buffered replacement fluids in septic shock
J-C Lewejohann, H-J Düpree, J Gleiß, S Lewejohann, E Muhl and H-P Bruch
Med. Univ. of Luebeck, Dept. of Surgery, Ratzeburger Allee 160, 23538 Luebeck, Germany. E-mail: JLewejohann@t-online.de
Crit Care 1999, 3 (suppl 1):P213
Introduction. Acid–base imbalances are an important aspect while
using continuous renal replacement techniques in critically ill
patients. The quality of replacement fluid needs to be considered
regarding to the acid–base requirements especially in septic
patients. Commonly used replacement fluids contain lactate as
buffer. Whereas lactate has to enter the Cori- or Citrate-Cycle to
become effective as a buffer, bicarbonate can act immediately.
The metabolism of lactate in addition is depending on the
impaired liver function of patients with septic shock and represents an oxygen consuming process.
Methods: We investigated the metabolic effects of lactate- and
bicarbonate-buffered hemofiltration substitution fluids in a clinical
follow-up design in 13 patients (mean age 67 ± 9 years [± SD]) with
acute renal failure during septic shock. All patients received continous veno-venous hemodiafiltration (CVVHDF, Prisma® Hospal).
Seven patients have been treated with bicarbonate- (Schiwa CombiPac®, Schiwa) and 6 patients with conventional lactate-buffered
Poster abstracts
replacement fluid (Biosol®, Hospal). We evaluated individual course
of pH, HCO3–, BE and lactate levels within the first 5 days after
start of CVVHDF by linear regression analysis (Excel® regression-procedure). The slopes of the regression equations for bicarbonate- and
lactate-buffered hemodiafiltration were compared by t-test (SPSS®).
Results: The use of bicarbonate replacement fluids for CVVHDF
leads to a significant improvement of acid-base balance in the
course of acute renal failure in septic shock. Linear regression
Bicarbonate-buffered (n = 7)
107
equations for bicarbonate- and lactate CVVHDF are shown in the
folllowing table (mean ± SEM):
Discussion: Lactate buffered CVVHDF leads to the removal of
large amounts of endogenous bicarbonate per day (600–1.000 mmol).
Its impact on the acid–base balance in septic shock is considerable. The approach with bicarbonate replacement flluid for the
treatment of acute renal failure in septic shock seems to be advantageous to normalize an impaired acid–base balance.
Lactate-buffered (n = 6)
P
pH
Y = [0.039 ± 0.002] × X + [7.254 ± 0.006]
Y = [–0.004 ± 0.001] × X + [7.431 ± 0.005]
< 0.05
HCO3–
Y = [1.369 ± 0.035] × X + [18.627 ± 0.177]
Y = [0.585 ± 0.032] × X + [26.658 ± 0.107]
< 0.05
BE
Y = [1.951 ± 0.025] × X + [-8.129 ± 0.084]
Y = [0.012 ± 0.051] × X + [4.399 ± 0.168]
< 0.05
Lactate
Y = [0.354 ± 0.074] × X + [4.800 ± 0.245]
Y = [0.202 ± 0.008] × X + [3.940 ± 0.025]
n.s.
P214 Changes in C-type natriuretic peptide (CNP) levels in the plasma and cerebrospinal fluid of the patients with
subarachnoid hemorrhage
K Ikeda, T Ikeda, J Ikea, T Onizuka, H Terashi and N Ishii*
Division of Critical Care and Emergency Medicine, *Department of Anesthesiology, Hachiouji Medical Center of Tokyo Medical University, Japan
Crit Care 1999, 3 (suppl 1):P214
Objectives: This study was conducted to clarify the role of C-type
natriuretic peptide (CNP) in the plasma and cerebrospinal fluid
(CSF) in patients with subarachnoid hemorrhage (SAH).
Subjects and methods: The subjects were 10 patients with subarachnoid hemorrhage, who were admitted to our ICU, and
received clipping operation within 48 h after the disease onset.
Patients who had heart or renal diseases were excluded from this
study. CNP levels in the plasma and CSF were measured at 6.00
on days 1, 3, and 7 of hospital admission by radioimmunoassay
(RIA). As a control, CNP levels in CSF were measured in patients
who received spinal anesthesia for orthopedic surgery. Differences
between the measured levels on Day 1 and that on Day 3 or Day 7
were analyzed with Student’s t test, and values less than 0.05 were
considered statistically significant.
Results: Plasma CNP levels in the subject and control patients
were within normal range, and there were no significant group differences. Mean CNP levels ± SD in the CSF was 13.1 ± 2.4 pg/ml
in the controls and 15.5 ± 2.8 pg/ml on Day 1 in the subjects and
there were also no significant group differences. However, CNP
levels in the CSF of our subjects was significantly different
between Day 1 (15.5 ± 2.8) and Day 7 (10.6 ± 3.6) (P < 0.05).
Discussion: CNP levels is known to be highest in the brain, and
that is thought to regulate the local cerebral blood flow, because
some studies demonstrated that CNP induced relaxation of cerebral arterioles through cGMP in rat brain. Our findings show that
CNP in the CSF acts as an inhibitor of vasospasm on Day 1, and 3
because CNP levels in the CSF decreased significantly on Day 7.
Conclusion: Any specific role of CNP was not indicated from our
findings, but we presume that CNP in the CSF could function as
a vasodilator when vasospasm occurs in the brain.
P215 Prevention of infective complications of penetrating injuries to the head
LX Lei, Z Ling and LX Hua*
Department of Neurosurgery, ZhuHai Citizen Hospital, China; *Department of Neurosurgery, ZhongShan Citizen Hospital, China
Crit Care 1999, 3 (suppl 1):P215
Infective complications often occur after craniocerebral wounds
caused by explosive fragments. These dangerous sequelae are, in
our experience, the chief cause of delayed death after injury. Initial
contamination. The presence of retained bone and metal fragments acting as a nidus for micro growth,and disturbances in cerebrospinal fluid (CSF) circulation, especially when the ventricular
system is involved, are challenging problems in the management of
missile wounds of the brain. The analysis covers 53 penetrating
craniocerebral wounds, treated in ZhuHai and ZhoungShan in the
period from 1988 to 1996. In 35 cases the head injuries were produced by explosive fragments and in the remaining 18 cases by
low-velocity bullets. We have analysed the significance of these
factors in cases undergoing operation within 24 h, the incidence of
infection was 12.6%. Rising to 29.3%when delay in execess of 72 h
after injury was unavoidable. We formed the opinion that the risk
of infection was not significantly increased by failure to remove
small inaccessible bone chips. The most formidable complication
was CSF leakage which often resulted in infections of the central
nervous system. This implies that successfully addressing the risk
of infection is, potentially, the most powerful method of improving
outcome from penetrating injuries to injuries to brain.
References
Hagan RE: Early complications following penetrating wounds
of the brain. J Neurosurg 1971, 34:132-141.
Meirowsky AM, Caveness WF, Dillon JD: Cerebrospinal fluid
fistulas complicating missile wounds of the brain.
J Neurosurg 1981, 54:44-48.
Ascroft PB, Pulvertaft RJV: Bacteriology of head wounds. Br J
Surg War Surg 1947, Suppl 1:183-186.
108
Critical Care 1999, Vol 3 suppl 1
P216 Should endovascular therapy for cerebral vasospasm coincide with hypervolemic-hypertensive therapy (HT)
in aneurysmal subarachnoid hemorrhage (SAH)?
P Liopyris, EFM Wijdicks*, ML De Ruyter and KL Thielen†
Mayo Foundation, Departments of Critical Care, *Neurology and †Interventional Radiology, St Mary’s Hospital, 200 1st st. SW, Rochester MN
55905, USA
Crit Care 1999, 3 (suppl 1):P216
Introduction: In patients suffering from SAH, cerebral vasospasm
is a major cause of morbidity and mortality from multifocal cerebral
infarction. Hypervolemic-hypertensive therapy is considered the
cornerstone of the medical management and generally the first line
approach. The therapeutic role of intra-arterial infusion of papaverine and balloon angioplasty has been established as an alternative
therapy. The timing of neuroradiological intervention is unknown.
Methods: We retrospectively analyzed the charts of 537 patients
with SAH, admitted in our institution between January
1987–December 1997. Of those, 156 (29%) received HT therapy,
for clinically neurologic deficits attributable to cerebral
vasospasm, after surgical aneurysm repair. Symptomatic
vasospasm was defined as decrease in the level of consciousness or
the appearance of new focal neurologic signs. Clinical and angio-
graphic improvement, after HT alone, or in combination with
neuroradiological intervention was studied.
Results: Of the 156 patients, 92 (58%) showed neurologic improvement with HT alone. Of the remaining 64 patients (42%), 37 (57%)
underwent intra-arterial papaverine infusion and/or balloon angioplasty, as an adjunct treatment, after failure of medical therapy. 30
patients (81%) improved clinically, whereas 34 patients (89%) had
angiographic amelioration alone. Twenty-seven patients (17%) failed
medical therapy but did not receive intervention due to early death.
Conclusion: Our results indicate that endovascular therapy for
symptomatic vasospasm contributes to significant clinical improvement. Medical therapy fails in almost half of the patients, of which
a large proportion can additionally benefit from neuroradiological
intervention. These results underscore the need for future studies
on timing of both therapeutic modalities for cerebral vasospasm.
P217 Application of near infrared spectroscopy in the ICU for follow-up of patients with subdural haematomas
C Lott, B Richter and HJ Hennes
Department of Anesthesiology, Johannes Gutenberg - University; 55131 Mainz; Germany. Tel: +49 6131 172267; Fax: +49 6131 173440;
E-mail: lott@mail.uni-mainz.de
Crit Care 1999, 3 (suppl 1):P217
Background: Secondary haemorrhage is an important cause of
brain injury following initial therapy of subdural haematoma
(SDH). Early identification and treatment of secondary haemorrhage improve neurologic outcome. Nearinfrared light at a wavelength of 760 nm shows a high absorption for haemoglobin. In a
previous study we were able to show the potential of Near
Infrared Spectroscopy (NIRS) as a noninvasive tool to detect
intracranial haemorrhage. Aim of our study was to analyse the
capabilities of NIRS for follow-up of SDH patients.
Methods: We prospectively studied 21 patients with the CT diagnosis of SDH using NIRS (RunMan™, NIM Inc.). The difference
in absorbance of light (∆OD) at a wavelength of 760 nm between
both hemispheres was measured at three different measuring
points. The first measurement was performed upon hospital
admission. Measurements were repeated on day 1, 2, 3 and at discharge. Additional measurements were performed in case the
patients’ neurological conditions had changed.
Results: 17 patients showed unilateral SDH at admission, 16 of
these were correctly identified by NIRS; four patients showed
bilateral SDH at admission. All patients received neurosurgical
treatment. At day 1 after surgery NIRS measurements identified 3
patients with complete drainage of the haematoma, 4 patients
were identified at day 2 and 5 patients were identified at day
three. At discharge there were no pathologic NIRS findings in 13
patients, indicating the complete resorption of the haematoma.
CT scans at discharge proved these findings. In 8 patients we
found pathologic NIRS values at discharge, indicating an incomplete resorption of the haematomas. CT scans prior to discharge
demonstrated residual SDH in all of these 8 patients.
Conclusion: Our results showed that repeated NIRS measurements in patients with SDH help to document the clinical course
after surgical treatment. As a non-invasive, easily transportable
diagnostic device, the RunMan™ helps to avoid time delay in
diagnosis of secondary haemorrhage and facilitate early treatment,
thus possibly saving time and reducing secondary injury as well as
treatment costs.
P218 Correlation of transcranial doppler (TCD) parameters with intracranial pressure (ICP)
A Vakalos, D Matamis, I Rodini and D Rigos
I.C.U. G. Papanikolaou Hospital Thessaloniki Greece, Thessaloniki, Exohi - Greece 570 10. Fax: 003031- 350937
Crit Care 1999, 3 (suppl 1):P218
Introduction: Intracranial Pressure (ICP) is an important factor in
providing adequate cerebral blood flow and oxygen delivery to the
brain. The use of ICP monitoring techniques has a lot of surgical
risk factors, it is expensive, and is not readily available. On the
other hand, transcranial doppler ultrasonography (TCD), is a non
invasive bedside technique, which measures the velocities of the
great cerebral arteries and may detect cerebral ischemia. The aim
of our study was to test the hypothesis that, in head trauma
patients, a correlation exists between ICP and TCD findings.
Poster abstracts
109
Methods: 59 patients (37 ± 19 years) with severe head trauma
(Glasgow coma scale below 8) were included in our study. We
assessed ICP and jugular bulb venous oxygen saturation (SjvO2).
All patients were under mechanical ventilation and ICP measurements were carried out using an intracerebral or intraventricular
catheter. Intracerebral hypertension management was based on
CPP and SjvO2 findings. During the first three crucial ICU days,
multiple TCD examinations (total 108) were performed. Simultaneous measurements of ICP, CPP, SjvO2, as well as TCD values
were recorded. The TCD parameters used were: Maximum velocity (Vmax), minimum velocity (Vmin), time average mean velocity
(tamV), and pulsatility index (PI). [PI =(Vmax–Vmin)/tamV]. The
findings obtained from TCD were compared with ICP using the
multiple regression analysis method.
Conclusion: Pulsatility index (PI) can predict the elevation of ICP.
However, this is not applicable in all cases. At a prior study [1], we
found that the reduction of CPP was demonstrated by the PI
index in 50% (R2 = 0.50) and we suggested that this was due to
factors which can influence the pulsatile arterial waveform
(impaired vascular contractility, tachycardia, etc.). At this study we
found that the elevation of ICP is demonstrated by the PI index
in only 10% (R2 = 0.10). We suggest that this is due to the suppression of the cerebral autoregulation at head trauma patients.
Results: In our study, the best correlation was demonstrated
between ICP and the PI index as well as Vmin. The correlation of
PI with ICP was exponential (P = 0.028), while the correlation of
Vmin with CPP was a linear regression (P = 0.022). Using the mul-
Reference
1. 11th Annual Congress Of The European Society Of Intensive
Care Medicine. Stockholm , Sweden 6–9 September 1998.
tiple regression method, the elevation of ICP was demonstrated
by the PI index in only 10 per cent (R2 = 0.10934). With this same
method, Vmin was unable to provide more information.
P219 Transcranial Doppler sonography and cerebrovascular CO2-reactivity during whole body hyperthermia
C Meissner-Kuck, A Nierhaus, P Brauer, S Hegewisch-Becker*, J Panse*, A Meyer and J Schulte am Esch
Dept of Anaesthesiology and *Dept of Oncology/Haematology, University Hospital Eppendorf, D-20246 Hamburg, Germany.
Tel: +49 40 4717 2450; Fax +49 40 4717 5372; E-mail: nierhaus@uke.uni-hamburg.de
Crit Care 1999, 3 (suppl 1):P219
Introduction: Disturbance of neurologic function is common in
heat stroke patients. Loss of thermoregulatory response is associated with high mortality due to progressive brain edema.
However, during whole body hyperthermia (WBH) for the treatment of metastatic cancer temperatures of above 41.8°C are intentionally applied [1]. Monitoring cerebral blood flow velocity
therefore is a non-invasive method that may be useful in the
detection of acute and potentially harmful alterations of the cerebral circulation.
Methods: After informed consent, in 10 ASA II patients with
metastatic malignant disease who were eligible for WBH mean
blood flow velocity (Vm) of the M1-segment of the middle cerebral artery was studied using a 2 MHz pulsed TCD device (TC
2–64, EME) with the probe fixed to the temporal window. The
heating device was a RHS-7500 (Enthermics Medical Systems,
USA). Target temperature was 41.8°C, time at target was 60 min.
Anaesthesia was total intravenous anaesthesia by TCI using
propofol (4–6 µg/kg/min). Patients were intubated and ventilated
with an FiO2 of 0.4 after induction with sufentanil (0.3–0.4 µg/kg),
propofol and rocuronium (0.8 mg/kg). After induction of anaesthesia, three sequential measurements for Vm and Gosling’s
pulsatility index (PI) (systolic-diastolic/mean blood flow velocity)
were taken during normo- and hypercapnia at baseline and at
plateau and were averaged for each point of measurement. A two
channel EEG was continuously recorded above the prefrontal
cortex (Aspect Monitor A1000, Aspect Medical Systems). EEG
data were processed online to yield bispectral index (BIS) values
throughout the course of anaesthesia.
Results: During baseline, Vm at normocapnia (PaCO2
40.1 ± 0.99 mmHg) was 39.26 ± 11.81 cm/s. At hypercapnia (PaCO2
47.4 ± 2.08 mmHg), Vm was 55 ± 20.84 cm/s. CO2 reactivity
(∆Vm/∆PaCO2) was 2.39 ± 0.9 cm/s/mmHg. During hyperthermia,
Vm at normocapnia was 54.07 ± 21.19 cm/s, and almost doubled to
106.07 ± 40.43 cm/s at hypercapnia. CO2 reactivity increased to
6.11 cm/s/mmHg. The PI under normocapnia significantly
increased from 1.05 ± 0.2 (normothermia) to 1.49 ± 0.3 (hyperthermia). BIS readings remained below 35 during anaesthesia. During
heating and plateau at 41.8°C an increase of cardiac index from
baseline of up to 140% could be observed, which was due to a significant decrease of SVR and MAP. HR increased to 138± 27 bpm.
None of the patients showed general or focal signs of CNS toxicity
at 24 h after the treatment.
Discussion: During WBH under general anaesthesia a profound
increase of cerebral blood flow velocity can be observed. This is
partially due to the changes of systemic hemodynamic parameters,
especially to increases of heart rate and cardiac index and to the
decrease of MAP [2]. EEG data suggest that the observed effect is
of primarily vascular origin and not due to increased CMRO2,
although cerebral metabolism was not measured. Under WBH
cerebrovascular reactivity was preserved and showed a marked
positive dependency on baseline flow, as described previously [3].
Hyperventilation only slightly decreased Vm during hyperthermia, suggesting that patients with intracranial space-occupying
lesions should be excluded from WBH treatment.
References
1. Kapp DS: Int J Hyperthermia 1994, 10:355-359.
2. Matta BF et al.: Br J Anaesth 1995, 74:296-300.
3. Ackermann RH et al.: Neurology 1973, 23:21-26.
110
Critical Care 1999, Vol 3 suppl 1
P220 Serum sodium is inversely proportional to intracranial pressure in acute liver failure
N Murphy and J Wendon
Liver Intensive Care Unit, King’s College Hospital, Denmark Hill, London SE5 9RS, UK
Crit Care 1999, 3 (suppl 1):P220
ICP vs Serum sodium
Objectives: Is there a correlation between serum sodium and
intracranial pressure (ICP) in patients with acute liver failure.
38
36
95% CI
34
32
30
28
Mean ICP mmHg
Methods: All patients with ICP monitors inserted for suspected
intracranial hypertension since 1991 treated on the liver unit of
King’s College London were identified. Indications for ICP monitoring included pupillary abnormalities, low jugular venous saturation and abnormal posturing. Eighty-two of the149 ICU charts were
available for data collection. ICP, charted hourly, was averaged for
every 6 h. Serum sodium, measured approximately 4 hourly was
paired with the averaged ICP for the entire period of monitoring.
Paired data was placed into four groups. Serum sodium less than
120, serum sodium less than 130, less than 140 and less than 160.
26
24
22
20
18
16
14
Results: See Table and Figure.
12
Serum Na
Number
Mean ICP
SD
95% CI
Group 1
≤120
36
28.2
16.0
5.4
Group 2
≤130
177
24.9
14.3
2.1
Group 3
≤140
402
19.1
11.5
1.1
Group 4
>141
388
17
13.5
1.3
10
115
120
125
130
135
140
145
150
155
Serum sodium mmol/l
Conclusion: From the data examined there is a significant inverse
correlation between serum sodium and intracranial pressure in
acute liver failure. The sole use of electrolyte free fluids should be
avoided in these patients.
P221 Gastric injuries: a rare surgical event due to blunt abdominal trauma
E Pikoulis, S Delis*, N Psalidas, A Kokiniotis, F Karlis, P Dascalakis, G Koukoulides, K Derlopas* and S Mantonakis
Second Department of Surgery, General Hospital ‘ASCLEPEION’ Voulas, Athens, Greece, Vas. Pavlou 1, Str. Voula, 16673, Athens, Greece.
*Department of Surgery, General Hospital Korinthos, Korinthos, Greece
Crit Care 1999, 3 (suppl 1):P221
Background/aims: Gastric rupture from blunt abdominal trauma is
rare occurrence. The purpose of this paper was to evaluate the results
of surgical treatment of patients with blunt trauma to the stomach.
Materials and methods: In a retrospective review of hospitals records
of two trauma-admitting hospitals, 10 patients were identified. The
main cause of blunt gastric injury was motor vehicle accident.
Results: All patients presenting usually with clinical signs warranting early laparotomy. There were six full-thickness, and two
partial thickness gastric injuries located in the anterior wall in
eight cases. All injuries could be managed with simple surgical
techniques without resections. Two patients exsanguinated on the
operating table from associated injuries. All but one of the survivors had postoperative complications with a mean hospital
length of stay of 18.4 ± 7.6 (range 10–30) days.
Conclusion: Blunt gastric injury is usually diagnosed at laparotomy
for associated injuries but occasionally may be suspected from
specific clinical findings. In most cases the injury is on the anterior
wall. Simple repair is usually sufficient and the prognosis depends
on the severity of the associated injuries.
P222 Protein S100 as a marker for cerebral outcome after cardiopulmonary resuscitation
A Müller, R Strauß, M Wehler, G Wiest, H Parsch* and EG Hahn
Medical Department I and Laboratory of Medical Clinics*, Friedrich-Alexander-University Erlangen-Nuremberg, Germany, Krankenhausstr. 12,
D-91054 Erlangen, Germany. Tel. 0049-9131-8533969; Fax 0049-9131-8536012; E-mail: andreas.mueller@med1.med.uni-erlangen.de
Crit Care 1999, 3 (suppl 1):P222
Introduction : S100 is a CNS-specific protein, derived from the
cytosol of glial cells, that can be detected in peripheral blood after
structural brain damage. We prospectively examined the prognostic value of S100-levels after cardiopulmonary resuscitaton (CPR).
Patients and methods: In 17 consecutive patients admitted to a
medical intensive care unit (ICU) after primary successfull cardiopulmonary resuscitation blood specimens were collected during
the 7 days following CPR in a certain scheme, starting 1 h after the
onset of CPR. On admission pH, base excess, serum lactate, time
from cardiac arrest until onset of CPR, duration of CPR and dose of
Poster abstracts
111
catecholamines used were recorded. Blood samples were centrifugated and sera stored at –20°C. Levels of protein S100 were measured using a commercial immunoluminometric assay (Sangtec
100®, Byk Sangtec Diagnostica, Dietzenbach, Germany) according
to the guidelines of the manufacturer. Reference level was
<0.3 µg/l. Cerebral recovery was evaluated by the five-point cerebral performance category (CPC) on ICU demisson [1].
vated levels (0.1–0.7 µg/l) were found, returning to normal within
a few hours. In category C the highest S100 values (8.8/12.1 µg/l)
of surviving patients were found, in contrast to category D with
moderate elevated levels (1.7–5.4 µg/l). Patients who died had
S100 values of 4.7–15.4 µg/l. No correlation was seen between pH,
base excess, serum lactate on admission, catecholamine dosis
needed during CPR and neurological outcome.
Results : Mean age was 66 yrs, median 67, range 35–78 years, 9/17
(65%) were male. 14/17 (82%) survived and were evaluated by the
CPC. 5/13 (38%) met Category 1 criteria (conscious and
alert/normal function), 2 met CPC 2 (conscious and alert/moderate
disability, 2 met CPC 3 (conscious with severe disability), 4 met
CPC 4 (comatose), 1 met CPC 5 (brain death). In 16/17 patients
an elevated S100 was measured with a mean value of 5.13 µg/l,
range 0.5–15.4, median 3.8 µg/l, with a maximum 1 h after CPR in
13/16 patients. In all patients of category 1 normal or slightly ele-
Conclusion : S100 seems to be a sensitive marker of cerebral injury
due to diffuse hypoxia after CPR. Normal S100 values excluded
severe cerebral damage. Normal or slightly elevated levels of S100
(≤0.7 µg/l) are correlated with good neurological outcome, but high
S100 values do not necessarily predict an unfavourable prognosis.
References
1. Brain Resuscitation Clinical Trial II Study Group: N Engl J
Med 1991, 324:1225-1231.
P223 Serum S100 as a marker of cerebral injury in acute liver failure (ALF) and during orthotopic liver
transplantation (OLT)
S Leonard, ADJ Watts, K Parmar*, J Wendon† and B Hunt*
Dept. of Anaesthesia and †Liver Failure Unit King’s College Hospital and *Dept. of Haematology, St Thomas Hospital, London, UK
Crit Care 1999, 3 (suppl 1):P223
Introduction: Encephalopathy and irreversible cerebral injury may
occur in ALF. S100 is a CNS-specific protein that is a marker of
cerebral injury [1,2]. We investigated S100 protein in patients with
ALF who underwent OLT.
Methods: After IRB approval blood samples were taken in 10
patients age 20–51 years with ALF. Blood was taken before OLT
(A), during the anhepatic phase (B), 30 min after reperfusion (C),
and on days 1 (D) and 4 (E) post-OLT. The blood was centrifuged
and serum stored at –70°C. S100 was analysed using an immunoluminometric assay.
Results: Serum S100 (X ± SEM) was elevated prior to OLT
(normal <0.12 µg/l). By day 4 post-OLT S100 had fallen in all
patients except one. This patient subsequently died.
Conclusion: Serum S100 is elevated in ALF and encephalopathy.
We observed a rise in S100 during OLT in these patients. The role
of S100 as a marker of neuronal injury in ALF and OLT warrants
further investigation.
2
S100
(ug/l)
1
0
A
B
C
D
E
Reference
1. Stroke 1997, 28:1956-1960.
2. Ann Clin Biochem 1997, 34:546-550.
P224 S100: a potential marker of cerebral trauma
M Simenacz and M Vucevic
Academic Unit of Anaesthesia, The General Infirmary at Leeds, Great George Street, Leeds, LS1 3EX, UK
Crit Care 1999, 3 (suppl 1):P224
Introduction: Head injuries are associated with a high level of
morbidity and mortality. The aim of this study was to examine if
S100, a calcium binding protein localised in astroglial cells of the
central nervous system, can be used as a marker of head injury and
to predict survival outcomes from severe head injury.
Methods: After informed consent and local ethics approval, 12
severe head injured patients (GCS ≤8) were included. All patients
were treated according to standardised head injury protocols.
Serial serum samples were taken over a period of 48 h together
with various other physiologic measurements. Plasma concentrations of S100 were analysed using a radioimmunometric assay —
Sangtec®S100IMRA.
Results: The mean S100 in patients who survived was 1.1 µg/l and
in those who died 0.79 µg/l. Six of the 12 patients in the study
died.
112
Critical Care 1999, Vol 3 suppl 1
Conclusion: Plasma S100 concentrations increase in severe head
injuries. The reference value is less than 0.2 µg/l and this was
exceeded in both patients who survived and those who died.
Serum S100 levels could not be correlated with mortality.
Serum S100 (µg/l) after severe head injury
Time after admission (h)
S100 (µg/l)
0
2
6
12
24
48
72
Mean
0.417
0.5
1.25
1.06
2.49
0.7
0.35
Std deviation
0.59
0.74
2.68
1.72
6.54
1.16
0.64
12
12
12
12
12
12
6
No. of patients
P225 The effect of tracheostomy and vasoconstrictor therapy on outcome in neurosurgical patients requiring
intensive care
M Pugh, K Bresland and M Vucevic
Academic Unit of Anaesthesia, Leeds General Infirmary, Leeds, LS1 3EX, UK
1990
1996
P value
86
129
–
Mean age (years)
31.2
43.4
<0.001
Median GCS
8.4
8.7
NS
Crit Care 1999, 3 (suppl 1):P225
Aims of study: A retrospective review of the treatment and
outcome of neurosurgical patients admitted to the ICU in the
years 1990 and 1996 to assess the effect of the introduction of the
routine use of percutaneous tracheostomy and vasoconstrictor
therapy.
Total patients admitted
Days on ICU
4.2
3.4
NS
Results: See Table.
Tracheostomies performed (%)
26
44
<0.001
Days until tracheostomy
6.0
3.0
<0.001
Use of vasoconstriction (%)
16
38
<0.001
Mortality (%)
30
55
NS
Discussion: The use of tracheostomies and vasoconstrictors has
increased during this period of study. Tracheostomy has no effect
on mortality whereas vasoconstrictor usage appears to result in an
increase in mortality.
Logistic regression on mortality (odds ratio):
Tracheostomy
Exp (B) = 0.76
95% CI (0.40–1.46)
Vasoconstrictor
Exp (B) = 5.46
95% CI (2.87–10.41)
P226 Effects of continuous flow insufflation of oxygen on arterial gazometry during cardiopulmonary resuscitation
L Bargues, JP Ducourau, P Morizet, G Boussignac and JM Saïssy
Service Anesthésie-Réanimation, HIA BEGIN, Saint Mandé, France
Crit Care 1999, 3 (suppl 1):P226
Introduction: During experimental cardiac arrrest, precordial compression associated to the unique use for ventilation of constant
flow insufflation of air at the distal end of a modified endotracheal
tube provided the same ventilatory results but better hemodynamic effects than manual ventilation [1]. Because of these results
and the simplicity of the technique, a study concerning humans
beings and using oxygen during cardiopulmonary resuscitation
(CPR) has been realized.
Methods: After ethic committee approval, adult out-of-hospital
cardiac arrests (shocked arrests excluded) were randomized in two
groups: control group (C) treated by conventional CPR with active
compression-decompression (ACD) and manual ventilation after
intubation, Constant Flow Insufflation group (CFI-CPR) treated
with ACD and flow rate of 15 l/min through small capillaries of
Boussignac tube (Vygon, Ecouen, France). CPR continued for 30
min at the most. As soon as spontaneous circulation returned
(SCR), arterial gazometry was made and all patients were mechanically ventilated. Statistical analysis was performed by χ2 and
Mann-Whitney tests. A P < 0.05 was considered statistically significant. Results were expressed as mean ± SD.
Results: Thirty patients were included in C group, 34 in CFI-CPR
group. There were no differences in mean age (65 ± 3 vs 62 ± 3
years) or delayed CPR activation (6 ± 2 vs 7 ± 3 min). SCR was
observed in 8 patients of C group after 13 ± 6 min and in 6 patients
of CFI-CPR group after 14 ± 6 min (NS). The results of arterial
gazometries for both group are shown in the Table.
Poster abstracts
PaO2
(mmHg)
CFI-CPR 6.86 ± 0.08 103 ± 18
237 ± 80
18.2 ± 2.4 95 ± 3
Control
155 ± 37
14.2 ± 1.5 92 ± 3
6.88 ± 0.05
81 ± 10
HCO3–
(mmol/l)
SaO2
(%)
PaCO2
(mmHg)
PH
Arterial gazometry, no statistically differences
113
Conclusion: Comparable values of arterial gazometry were
observed after CFI-CPR or standard CPR. This easier technique
is as efficient as manual ventilation in terms of oxygenation during
the early phase of cardiac arrest. Further studies are required to
determine if CFI-CPR improve prognosis.
Reference
1. Brochard et al.: Am J Respi Crit Care Med 1996, 154:13231329.
P227 Airway management during cardiopulmonary resuscitation (CPR) by training nurses
V Dörges, H Ocker, C Sauer and P Schmucker
Department of Anaesthesiology, University Hospital of Lübeck, Ratzeburger Allee 160, D-23562 Lübeck, Germany. Tel: +49 451/500-4057;
Fax: +49 4509/71068; E-mail: v.doerges@t-online.de
Crit Care 1999, 3 (suppl 1):P227
A experimental model of a patient was designed to grade the
success of ventilation using the Guedel airway/face mask
(GA/FM), Laryngeal mask (LM) or Combitube (CT) in CPR. It
consisted of a manikin head, training lung (Dräger®: compliance
50 ml/cmH2O, resistance 16 cmH2O/l/sec), lower esophagial
sphincter pressure (LESP) 7 cmH2O and a simulated stomach [1].
Sixteen training nurses were shown the correct use of each device.
The volunteers than used each device for a 2-min ventilation. For
a successful ventilation a tidal lung volume of >200 mls had to be
achieved within 180 s. Peak pressures in the esophagus, lung and
gastric 2-min volumes were recorded. Each volunteer was graded
from 1 (excellent) to 4 (bad), on the success of airway insertion,
quality of the seal and visible adequacy of ventilation. The volunteers could deliver an adequate tidal lung volume with the
GA/FM in 7–102 s (median: 24 s); LM in 18–92 s (median: 37 s),
and 46–180 s (median: 74 s) with the CT. In the GA/FM group
there were three failures, and two in the CT group. Analysis of the
success of airway insertion, sealing and adequacy of ventilation
shows a significant advantage with the LM or CT (P < 0.0001)
against the GA/FM. There was no difference between the LM
and CT. The 2-min lung volume delivered with the GA/FM ranged
from 4.2–13.4 l (mean: 8.0 l), with peak LESP of 9–27 cmH2O
(mean: 16.4 cmH2O) causing a gastric inflation of 2.5–13.6 l (mean:
6.6 l). The 2-min lung volume with the LM was 11.7–44.1 l (mean:
25 l), peak LESP of 0–22 cmH2O (mean: 7.9 cmH2O) and gastric
inflation of 0–6.2 l (mean: 1.4 l). For the CT the 2-minute lung
volume ranged from 12.3–41.5 l (mean: 27 l), peak LESP of 0 and
without gastric inflation. Our results show the significant risk of
gastric distension when using the GA/FM. Adequate lung ventilation of >5 l/min delivered with the GA/FM could be achieved only
by 4 volunteers. The LM might provide the best alternative for
airway management during CPR by nursing staff with a 100%
success rate on adequacy of ventilation. A training program on the
LM might further reduce the risk of gastric inflation.
Reference
1. Bowman FP et al.: Lower esophagial sphincter pressure
during prolonged cardiac arrest and resuscitation. Ann
Emerg Med 1995; 26:216-219.
P228 Does emergency transportation induce a stress-response in probationers
V Doerges, S Dix, H Ocker, A Kühl and P Schmucker
Department of Anaesthesiology, University Hospital of Lübeck, Ratzeburger Allee 160, D-23562 Lübeck, Germany
Crit Care 1999, 3 (suppl 1):P228
Introduction: Common opinion is that emergency transportation is
a stressful event for patients. The question is if simulated emergency transportation might be a useful model to measure the
levels of stress-responsive with a high ecological validity.
Methods: After approval by the local ethical committee 32 male
probationers (age 18–40) were randomized into two groups
(‘strain’, ‘control’). The following values were taken: plasma-hormones (epinephrine E, norepinephrine NE, cortisol C) and CVSvalues (BP, MAP, HR). The ‘strain’-group was carried downstairs
from a third floor flat and taken into an ambulance for an emergency transport. Blood samples were taken in the flat after informing the probationer (A), at the ground-floor (B) and at the end of a
15 min emergency transportation under defined conditions (C).
The CVS-values were recorded continuously . The ‘control’group had to sit on a chair for 5 min and afterwards to lay on a
stretcher for 15 min. The blood samples were done at equivalent
times. The results were evaluated by a two-factor variance analysis with repetition of the values for the factor measuring time.
Results: Our study shows that a simulated emergency transportation induces stress. Differences in stress-responses depending on
the period of the simulated emergency transport were found. The
increase of E, NE, C and HR during the transport of the probationer down the stairs was significant (P < 0.001); no significant
alterations could be shown in the ‘control’ group. The emergency
transport in the ambulance appears to be clearly less of a strain to
the patient. This was shown by a significant decrease of HR, E
and NE levels (P < 0.001) compared to the downstairs part.
Conclusion: More attention should be focused on the period of
emergency transport from on-scene to the ambulance to influence
positively the most stressing event. Further studies concerning
sedation before transportation appear to be necessary.
114
Critical Care 1999, Vol 3 suppl 1
P229 Road traffic accident related morbidity and mortality as seen in an emergency department
E Pikoulis, F Karlis*, C Theos†, P Koulouvaris, A Geranios*, S Kiose‡, A Tsamatropoulos† and S Mantonakis
Second Department of Surgery, *Department of Intensive Care, †First Orthopedic Department, ASCLEPEION Voulas, Vasileos Pavlou 1,
16673,Voula, Athens, Greece. ‡Department of Hygiene and Epidemiology, University of Athens Medical School, Greece
Crit Care 1999, 3 (suppl 1):P229
Introduction: Trauma remains the leading cause of death in the
first four decades of life. Trauma-related costs is accounted for by
accident injuries and the resultant disabilities, lost wages, medical
expenses, insurance administration costs and most importantly
loss of life become a great national issue in Greece. The purpose
of this study is to report in epidemiological manner certain official
information regarding prenosocomial events of all traffic accidents
in the Southern area of Athens (1 000 000 inhabitants) within a
year. The records were a co-operative and cross-matched result
from the following services involved : The Department of Surgery
and Intensive Care, ‘ASCLEPEION’ Hospital of Voulas, Athens
and Department of Hygiene and Epidemiology, Athens University Medical School.
Patients and methods: From January 1997 to January 1998, 3211
trauma victims were to 1300 traffic accidents. 2173/3211 (67.7%)
were males and 1038/3211 (32.3%) females. The mean age of
victims was 39 years (range 14–90 years). In more than 70% of the
cases the cause of accident was reported as being ‘human error’
regarding the driver of vehicle.
Results: The two most common incidents of the casualties were
collision and deviation. 57/3211 (1.8%) victims died either immediately or during transportation to our hospital. From the victims
43 (75.44%) were males and 14 (24.56%) females. The mean age
of victims was 54 years (range 12–82 years). The most frequent
fatal accident time were the hours between 14:00–24:00 (28
victims = 49.12%). April and July were the most fatal months (8
victims each = 14%).The primary use of Abbreviated Injury
Scoring system (A.I.S.) on those who reached the Hospital alive
classified 518 cases (16.13%) as having mild injuries and 2693
cases (83.87%) as having medium and/or severe injuries.
Morbidity and mortality among the population of Greece were
33238 and 2139 respectively within the above period.
Conclusion: Nevertheless newspapers, radio and TV pay more
attention to the narcotic and other causes victims than that of the
car accidents which is the main reason of deaths among the young.
We can conclude that the suitable prehospitalized care of the
injured victims and the rapid assessment and resuscitation at the
Trauma Centers are the cornerstones of the current treatment and
improve the outcome of the injured significantly.
P230 Sports activity after severe polytrauma: results of a prospective study
RJ Stiletto, P Nowacki* and M Baacke
Department of Trauma Surgery/ICU, Philipps-University Marburg, Badinger Str. 35033 Marburg/Lahn, Germany,
*Department of Sports Medicine, Justus Liebig University Gießen, Germany
Crit Care 1999, 3 (suppl 1):P230
Table 1
Background: There is only a small body of literature dealing with
the problem of sports activity after survived severe polytrauma.
Having in mind that most of these patients are in the age group
between 18 to 40 years, sports activity after survived polytrauma is
a decisive factor of their quality of life.
Status of
sports activity
Materials and method: In a prospective trial we evaluated the
sports activity and sports performance of a group of 50 polytrauma
patients (ISS >15) after a minimum time of 6 months following
their discharge from hospital. The characteristics of the group
were as follows (mean values): age 28.5 years, follow-up time 18
months, sex: male 40, female 10 patients. The ISS was 50. Cause
of injury was in 96% a MVA, in 4% a fall from great height. The
APACHE II on the first day was 17. The patients’ time on respirator was 7 days. The stay on ICU was 11, and the stay in hospital 26
days. The sports activity and performance were evaluated according to a standardized score in all patients who practiced sports
before the trauma. In addition, a performance test with spiroergometry and serum lactate samples could be performed in seven
cases.
Results: During the 6 months after discharge from hospital four
patients died. The sports status of these patients could not be
evaluated. Forty-six patients (92%) were available for further evaluation. The pre- and post-traumatic status of their sports is listed
in Table 1. Sports performance and participation levels in differ-
Group 1
(sports)
Group II
(no sports)
Pre-trauma
36 = 78.2%
10 = 21.7%
Post-trauma
25 = 54.34%
21 = 45.6%
Group
changes
1 = 2.1%
Table 2
Activity
level I
Activity
level II
Activity
level III
Activity
level IV
Pre-trauma
0%
0%
3%
97%
Post-trauma
0%
42%
37%
21%
ence activities were evaluated in the 36 patients who practised
sport before the trauma. The results are listed in Table 2.
Conclusion: According to our results a decrease in activity and performance levels is obvious in the post trauma patient group. More
than 70% of the patients practising sports before the trauma had to
reduce their activity level. 23.86% had to quit their former activities. However, more than 50% of the patients were able to practice
sports after their trauma.
Poster abstracts
115
P231 Discomfort, awareness and recall of patients in the intensive care: still a problem?
IG Swaiss
ICU, King Hussein Medical Centre, PO Box 1115, Amman 11821, Jordan
Crit Care 1999, 3 (suppl 1):P231
Introduction: During surgery, anaesthetists take extra care to
prevent awareness of any patient who is having any kind of operation done, mainly under general anaesthesia either by using
inhalational or intravenous medications, but patients in the ICU,
mainly those on ventilatory support, with intubation and sedation,
pass through a lot of psychological stress and frustration, which
most of the times is not documented in the genera intensive care,
and has never been done in our unit.
Aim of this study: In this study at our general ICU, we tried to
have a proper assessment of this problem in order to avoid it in the
future, and to get a proper consensus regarding its existence and
solution.
Methods: Seventy patients between the ages 20–60 years, were
interviewed 1 day after discharge from the ICU, about their
memory of events during their stay. Patients with head injury,
CNS infection or those who were disoriented at the time of interview were excluded from the study. The remaining 55 patients
were oriented to place and time.
Intravenous opiates (morphine, pethidine) were used for analgesia
as required, while sedation was achieved using midazolam and
morphine infusions in appropriate doses as decided by the attending doctors and nurses.
Questions asked were generally about patients’ memory of events
and about their distressing experiences regarding pain, anxiety,
dreams, fear, noises, causes of discomfort and others which will be
displayed in the results section.
The same questions were repeated 5 days later.
Results: The sample of patients were representative of our regular
ICU admissions in their age group, APACHE II score and duration of stay.
The most distressing and commonest experiences recalled were:
anxiety (68%), discomfort from endo-tube (60%), fear (54%), pain
(52%), discomfort from N/G tube (48%), difficulty in communicating (33%), dreams and hallucinations (31%), discomfort from
physiotherapy (24%), noise (15%), insomnia (13%), thirst (10%),
some of these like anxiety, fear, dreams, hallucinations and insomnia had continued since discharge in 6% of patients. None of the
studied experiences correlated with age, sex, or with the
APACHE II score. On interviewing the patients 5 days later, there
were no significant changes in their responses.
Conclusion: Our sedation and analgesia in the ICU is not enough
to prevent unpleasant experiences, mainly those related to patient
awareness.
More work is still needed, i.e. using sedation scores to improve
our sedation and analgesia in the ICU.
P232 Sedation of patients in intensive care units by midazolam (MDZ): clinical and biological evaluation
D Chatellier, C Poisson, L Tronchon, D Thévenin, H Robert, P Odou, C Barthélémy and M Luyckx
Réanimation Médicale Polyvalente Centre Hospitalier du Docteur Schaffner 99, route de la Bassée 62307 Lens, France
Aim: To assess if the clinical scoring of sedation (Ramsay scale),
the administered dose of MDZ, the serum levels of MDZ from
the beginning to the end of sedation are related to clinical parameters (body area), biological data (creatinine clearance, liver
enzymes, protidemia), and pharmacokinetic parameters (elimination half-life T1/2).
Patients and methods: The study was conducted with 31 patients
(70 ± 10 year-old ; IGS II = 41 ± 14). The objective was to reach a
score of sedation of 2 up to 4. Sedation of patients was initiated
with an intravenous bolus of MDZ (B = 0.1 mg/kg) and maintained
with MDZ at the rate (H1 = 0.08 mg/kg/h). If needed, the dose of
MDZ was gradually increased: H2 = 1/2B + 1,5H1 ; H3 = 1/2B + 2H1
(if H3 was insufficient, sufentanil was added (0.17 µg/kg/h and
0.34 µg/kg/h)). Waking up of patients was monitored by the beginning of respiratory weaning. Liver enzymes, protidemia and creatinine clearance are evaluated every day and 24 h after the end of
sedation.The serum levels of MDZ and its metabolites were
measured by HPLC and RRA every 8 h during the first day; then
every 24 h, before and after each change of posology and finally
every 4 h after the end of sedation for 24 h. The correlations
between the different parameters monitored were evaluated by a
Pearson’s test.
Results: No correlation between time to awakening (22 ± 21h) and
duration of sedation (96 ± 57 h) or clinical parameters or biological
data was observed. In a similar way, score of sedation, posology
and serum levels of MDZ were not correlated. The pharmacokinetic parameters of MDZ were : T1/2 = 11.77 ± 4.8 h, clearance =
8.6 ± 4 l/h, Vd = 149 ± 98 l, concentration at steady state =
1008.7 ± 395 ng/ml. The unique parameter modulating the time to
awakening was T1/2 of benzodiazepinique total activity (T1/2 =
12 ± 4.96 h) with 7 patients.
Conclusion: The clinical evaluation of sedation is sufficient to
adjust the dose of MDZ required for sedation and efficient awake
in intensive care units.
Time to awakening (h)
Crit Care 1999, 3 (suppl 1):P232
25
20
15
10
5
0
R2 = 0,5828
0
10
20
T1/2 benzodiazepinique
total activity (h)
116
Critical Care 1999, Vol 3 suppl 1
P233 Cardiovascular effects of dexmedotomidine for ITU sedation: UK results of a multi-centre study (St George’s,
University College, St Thomas’s and Bristol Royal Infirmary Hospitals)
CJ Bradshaw, RM Venn, R Spencer, D Brealey, E Caudwell, M Singer, D Treacher, SM Willatts and RM Grounds
St George’s Hospital, Blackshaw Road, London, SW17 0QT, UK
Methods: One-hundred and nineteen post-operative patients who
required sedation and ventilation for at least 6 h on the ITU were
enrolled. Ninety-eight completed the randomised, placebocontrolled, double-blind study (81 cardiac and 17 general surgical)
in four centres in the UK, but all patient data was used in the
safety analysis. Within 1 h of return from theatre, the study drug
was started with a loading dose of 1 µg/kg for 10 min, followed by a
maintenance infusion of 0.2–0.7 µg/kg/h to maintain a Ramsay
sedation score of ≥3 and was continued for 6 h after extubation
(maximum duration 24 h). Rescue sedation and analgesia was provided with midazolam and morphine respectively. Heart rate, systolic, diastolic pressures and central venous pressures were
recorded at 10 min intervals for the first 30 min and then hourly.
midine infusion rate was 0.35 µg/kg/h whilst intubated and
0.15 µg/kg/h after extubation (range 0–0.7 µg/kg/h). Data was collated for the initial 6 h of the infusion and for the period pre- and
post-extubation ± 4 h, hence, allowing for the variation in the duration of intubation in the data analysis. Once adequately sedated the
patients receiving dexmedetomidine achieved greater cardiovascular stability as compared to the placebo group, with a significantly
lower and less variable heart rate (P = 0.0001), this was clearly
demonstrated in the period around extubation when mean heart
rate in the dexmedetomidine group was 75 (SEM ± 2.0), versus 92
(± 2.9) in the placebo group. Diastolic blood pressure showed a
similar trend with a reduction of 5 mmHg in the dexmedetomidine
group, but no sustained significant differences in systolic arterial
pressure or central venous pressures. Of the 66 patients who
received dexmedetomidine, 16 had transient episodes of hypotension (MAP <60 or >30% reduction from pre-infusion BP) and/or
bradycardia (HR <50), mainly during the loading dose, of which
three patients required temporary interruption of the infusion and
three others required termination of the infusion.
Results: Patient demographics were comparable as were Ramsay
sedation scores between the two groups. The average dexmedeto-
Summary: Dexmedetomidine may improve cardiovascular stability.
Crit Care 1999, 3 (suppl 1):P233
Introduction: A multi-centre study examining the safety and efficacy
of the novel sedative agent dexmedetomidine, a highly selective
alpha-2 agonist, possessing analgesic and sympatholytic properties.
P234 Ovarian hyperstimulation syndrome (OHSS) at a maternity hospital
V Lappas, P Myrianthefs, C Ladakis, S Pactitis, A Carousou, J Stamatiou and G Baltopoulos
Athens University School of Nursing Intensive Care Unit at ‘Agioi Anargyroi’ Cancer Hospital of Kifissia, Nea Kifissia 14564, Greece,
Department of Intensive Care Unit of ‘IASO’ Maternity Hospital at Athens, Marousi 15123, Greece
Crit Care 1999, 3 (suppl 1):P234
Table 1. Signs and symptoms on admission
Background: Ovarian hyperstimulation syndrome (OHSS) is a
clinically important entity due to assisted conception which occurs
in about 1–10% of in vitro fertilization (IVF) cycles with serious
complications such as deep vein thrombosis, hypovolaemia, haemorrhage, respiratory distress and hepato-renal failure.
Generalized edema
100%
Ascites
100%
Weight gain
100%
Chest discomfort
71%
Objective: The aim of this study was to describe our experience
with OHSS at ‘IASO’ Maternity Hospital.
Thirst sensation
71%
Nausea-vomiting
71%
Materials and methods: The last year seven patients with age
30 ± 2.4 (X ± SEM) were admitted in our ICU due to severe
ovarian hyperstimulation syndrome complications.
Hydrothorax
71%
Abdominal distension or pain
43%
Anxiety
28%
Results: Signs and symptoms (Table 1) and labs (Table 2) were
due to third space fluid shift (increased capillary permeability)
with evidence of hypovolaemia, haemoconcentration and dehydration.
Ultrasound examination of the abdomen showed ascites, pelvic
fluid and enlarged ovaries (in our patients >11 cm in diameter) in
all patients and chest X-ray revealed hydrothorax in five patients
(71%). Ovarian hyperstimulation syndrome clinical feature is due
to exaggerated ovarian response characterized by marked elevation of serum oestradiol levels and the presence of a large number
of follicles (>20).
Management and outcome: All patients had bed rest, fluid
input–output control, adequate fluid intake, high protein oral
intake, human albumin solutions iv and LMWH sc (nadroparin
Table 2. Labs on admission and discharge
Laboratory
examination
Admission
(X ± SEM)
Discharge
(X ± SEM)
Ht (%)
45 ± 1.97
33 ± 1.67
133 ± 1.02
138 ± 1.29
42 ± 4.6
32 ± 1.8
Na+
(mmol/l)
Urea (mg/dl)
Alb (g/dl)
2.8 ± 0.12
4.25 ± 0.31
WBC × 103/µl
16.4 ± 1.35
10.7 ± 1.54
Oestradiol (pg/dl)
4735 ± 1658
Poster abstracts
calcium 3000 iu). Two patients had paracentesis of hydrothorax
because of dyspnea or discomfort. Hospital and ICU stay was
8 ± 3.3 and 5 ± 1.9 days, respectively. All patients recovered
without developing any life threatening complications and were
discharged in good condition.
Conclusions and discussion: Ovarian hyperstimulation syndrome
is a serious clinical condition [1] which may be complicated by life
threatening events in up to 0.5–2% [1,2]. Early recognition and
117
management until normalization of oestradiol serum levels
provide good outcome with mortality rate 0.0025% [1].
Reference
1. Brindsen PR, Wada I, Tan SL, Balen A, Jacobs HS:
Diagnosis, prevention and management of ovarian
hyperstimulation syndrome. Br J Obstet Gynaecol 1995;
102:767-772.
2. Schenker JG, Weinstein D: Ovarian hyperstimulation
syndrome: a current survey. Fertil Steril 1978; 30:255-268.
P235 Anticoagulation: hitting the target after cardiac surgery
CD Booth and CL Nelson
Pharmacy Department, Leeds General Infirmary, Leeds, UK. E-mail: cdb@ulth.northy.nhs.uk
Crit Care 1999, 3 (suppl 1):P235
Introduction: A pharmacy led anticoagulant service has recently
been introduced to dose and monitor warfarin in all cardiothoracic
inpatients at the Leeds General Infirmary. This abstract presents
an audit of locally produced guidelines for the induction of warfarin in cardiothoracic patients.
Aim: To improve the anticoagulant process for cardiothoracic
patients by using the experience of clinical pharmacists to
produce guidelines for induction of warfarin.
Results: An audit was undertaken and data was collected on 89
patients. Sixty patients (67%) received a warfarin loading dose
according to the local guidelines. Fifteen (71%) of the 21 patients
with mechanical valves had an acceptable INR on day four. Only
one patient (5%) had a high INR, and 5 (24%) had a low INR. Of
the 39 ‘low risk’ patients (tissue valves, coronary endarterectomies
and A.F), 21 (54%) were within the acceptable range on day 4
whilst four (10%) were high and 14 (36%) were low.
In a group of 29 patients where guidelines were not followed
(dosing decisions were made by junior surgeons), only 8 patients
(28%) had an acceptable INR on day four, 16 (55%) had a low
INR and 5 (17%) had a high INR.
Discussion: This study has shown that the locally developed
guidelines can be used to safely initiate warfarin in cardiothoracic
patients immediately following cardiac surgery. In the future we
intend to undertake an analysis to produce maintenance dose
guidelines which are specific to cardiothoracic patients. A combination of these two guidelines should optimise the dosing of warfarin in cardiothoracic patients and contribute to an overall
improvement in their care.
P236 A prospective study of thrombocytopenia and prognosis in intensive care
A De Weerdt, S Vanderschueren, M Malbrain*, D Vankersschaever, E Frans, A Wilmer and H Bobbaers
Department of General Internal Medicine, Medical Intensive Care Unit, University hospitals, Herestraat 49 3000 Leuven, Belgium and
*Department of Intensive Care, Ste-Anne St-Remi Hospital, Boulevard Jules Graindor 66, 1070 Brussels, Belgium
Crit Care 1999, 3 (suppl 1):P236
Introduction: To study the incidence and prognosis of thrombocytopenia in an adult critically ill population, 329 patients consecutively admitted during a 5-month period to the medical intensive
care unit (ICU) of a university hospital (212 patients) and a
medical-surgical ICU of a regional hospital (117 patients), were
prospectively surveyed. The primary outcome measure was ICU
mortality.
Results: One hundred and thirty-six patients (41.3%) had at least
one platelet count < 150×109/l. These patients displayed a higher
APACHE (Acute Physiology and Chronic Health Evaluation) II,
SAPS II (new Simplified Acute Physiology Score) and MODS
(Multiple Organ Dysfunction Score) at admission, longer ICU stay
(8 versus 5 days median (interquartile range)) and a higher mortality rate (crude odds ratio, OR = 5.0, 95% confidence interval, CI
2.7–9.1) than those who never developed thrombocytopenia
(P < 0.0005 for all comparisons). Bleeding incidence rose from 4.1%
in non-thrombocytopenic patients to 21.4% in patients with
minimal platelet counts between 101 and 149×109/l (P = 0.0002),
and to 51.9% in patients with minimal platelet counts <100×109/l
(P < 0.0001). 19.5% of the study population died in the ICU following the index admission. Eighteen of 193 patients (9.3%) who
never became thrombocytopenic died, versus 31 of 89 patients who
were thrombocytopenic at admission (OR = 5.2, 95% CI 2.7–9.8,
P < 0.0001) and versus 15 of 47 patients (31.9%) who developed
thrombocytopenia later on during ICU stay (OR = 4.6, 95% CI
2.1–10.0, P = 0.0002). In addition we found that a drop in platelet
count to ≤50% of admission was associated with higher death rates
(OR = 6.0, 95% CI 3.0–12.0, P < 0.0001). In a linear regression
analysis, adjusting for admission APACHE II, SAPS II and MODS,
admission thrombocytosis and the occurrence of bleeding, nadir
thrombocytosis remained significantly related to ICU mortality.
Conclusion: Thrombocytopenia is a simple and readily available
risk marker for ICU mortality, independent of and complementary
to established severity of disease indices. Both a low nadir thrombocytosis and a significant fall of platelet count predict a poor vital
outcome in adult ICU patients.
118
Critical Care 1999, Vol 3 suppl 1
P237 Platelet function and inflammatory markers in septic patients
U Leonhardt, F Zeiger, M Koksch and L Engelmann
University Leipzig, Department of Internal Medicine I, Philipp-Rosenthall-Str. 27, 04103 Leipzig, Germany
Crit Care 1999, 3 (suppl 1):P237
Background: In septic patients disseminated intravascular coagulation is a severe complication whereby an altered platelet function appears contributory. Clinical outcome depends on an early
diagnosis and sufficient therapy. In the present study the association of platelet function to inflammatory markers indicating
disease severity was investigated.
Methods: Inflammatory markers C-reactive protein, procalcitonin,
interleukin-6 and interleukin-10 were measured using standard
methods in 18 patients fulfilling clinical, inflammatory and hemodynamic criteria of sepsis. Platelet activation marker P-selectin
was flow cytometrically analysed ex vivo and after stimulation
using 5 µmol/l ADP and 10 µmol/l TRAP-6.
Results: Flow cytometrically measured platelet function was
tightly associated with inflammatory markers. Pre-activation of
platelets in the circulation was significantly correlated to plasma
levels of procalcitonin (P < 0.023), whereas in vitro induced reagibility after ADP- and TRAP-6 stimulation correlated well with the
plasma concentration of the C-reactive protein (P < 0.001;
P < 0.012). Furthermore, a close relation of IL-6, but not of IL-10,
plasma levels to TRAP-6 stimulated P-selectin expression was
observed (P < 0.033).
Conclusion: Platelet function was demonstrated to be tightly associated with the inflammation process in septic patients. Whether
this finding may be a useful marker for disease severity and the
development of a disseminated intravascular coagulation should
be clarified in prospective studies.
P238 Retrospective study of patients with haematological malignancies admitted in an intensive care unit
F Faria, P Alves, E Gonçalves*, A Martins, L Viterbo*, F Viseu* and A Aguiar
Intensive Care Unit and *Onco-haematology Unit, Instituto Português de Oncologia, Porto, Portugal
Crit Care 1999, 3 (suppl 1):P238
Introduction: The development of aggressive schemes of
chemotherapy predisposes haematological patients to various lifethreatening complications. The admission of neutropenic patients
into an intensive care unit (ICU) is still controversial mainly if
they have multiple organ dysfunction (MOD) and /or if mechanical ventilation is required.
Objective: Analyses from patients with haematological malignancies admitted in a medico-surgery ICU of an oncology hospital.
Patients and methods: Retrospective observational study on
patients with haematological malignancies admitted in ICU from
October/96 to October/98, coming from Paediatric Department
(PD), Onco-Haematological Unit (OHU) and Bone Marrow Transplantation Unit (BMTU). We analysed the patient data, namely
the underlying malignancy, the reason for admission, the type and
number of organ dysfunction (including neutropenia and requirement of mechanical ventilation), the time in ICU, acute physiology, age, chronic health evaluation (APACHE II) and
sepsis-related organ failure assessment (SOFA).
Results: Between October/96 and October/98, 46 onco-haematological patients were admitted in the UCI (56 inpatients) with
ages from 9 months to 70 years old, 23 female/23 male: 6 came
from PD (13%), 29 from OHU (63%) and 11 from BMTU (24%).
Underlying haematological malignancy: Non Hodgkin Lymphoma
(34%), Acute Myeloid Leukaemia (21%), Chronic Myeloid
Leukaemia (15%), Hodgkin Disease (15%), Acute Lymphoid
leukaemia (11%), Multiple myeloma (4%). Six of the 46 patients
were excluded because of the short time in ICU (≤12 h). Six
patients were readmitted. The mean time of stay was 8.2 days.
The reasons for ICU admission were: acute respiratory failure
(54%), multi-organ dysfunction (MOD; 14%), post-surgery (14%),
septic shock (8%), tumour lysis syndrome (6%), hypovolemic
shock (2%) and neurological dysfunction (2%). The ICU mortality
was 52.5%, being 76% of them neutropenic patients with MOD
and requiring invasive ventilation. 89% of the patients coming
from BMTU died.
Conclusion: The main risk factors to dead in an ICU are the
number of organ dysfunction at admission, the requirement of
invasive ventilation, BMT, APACHE II ≥20 and SOFA ≥15.
P239 Prognostic value of the bone marrow in severe sepsis/septic shock
R Milheiro, E Lafuente, A Bártolo, A Sousa, C Gonçalves, J Fernandes, M Martins, J Leão, F Santos and P Carvalho
Intensive Care Unit, Hospital de Senhora de Oliveira, 4810 Guimarães, Portugal
Crit Care 1999, 3 (suppl 1):P239
Introduction: Peripheral haematological changes are one of the
sepsis diagnosis criteria. However, there are only a few studies
concerning the effects of severe sepsis/septic shock in bone
marrow of the adult patient.
Objectives: Characterise the bone marrow haematological changes
in severe sepsis/septic shock patients and to evaluate the prognos-
tic value of the marrow cell differential count (myeloid, lymphoreticular, erythroid series).
Materials and methods: Prospective study of 29 patients with the
diagnosis of severe sepsis/septic shock of different etiologies. Age,
SAPS II in the first 24 h, organ dysfunctions according to SOFA,
organ failure according to Knaus and the final outcome were considered in the present study.
Poster abstracts
Dead (n = 17)
Alive (n = 12)
67 ± 11.1
68 ± 11.1
119
P
The bone marrow of each patient was studied and a differential
count considering the myeloid, lymphoreticular and erythroid
series was made. The patients were separated according to final
outcome (dead and alive) and the bone marrow differential counts
were compared between the two groups applying t Student test.
Myeloid series (%)
Erythroid series (%)
Results: See Table.
Age
Conclusion: In the present study significant statistical correlation
was found between lymphoreticular count and mortality. We can
conclude that bone marrow evaluation has had a prognostic value
in this patient group.
SAPS II
55.7 ± 12.9
62.8 ± 16.6
0.24
SOFA
13.9 ± 2.6
10.9 ± 2.2
0.003
OSF
3.1 ± 1.3
1.9 ± 0.8
0.004
Lymphoreticular series (%) 10.6 ± 4.5
0.81
15.98 ± 6.22
0.018
21.7 ± 11.7
15.1 ± 7.7
0.06
52.6 ± 18.4
50.6 ± 21.1
0.79
Mortality rate 58.86%
P240 Monitoring of plasma lipid peroxide level after abdominal aortic reconstruction in humans
MS Ryszka, P Guzik*, T Zujewski*, K Rzetecka*, M Kempa*, A Wykrêtowicz*, B Sawarzyñska-Ryszka, R Szulc and H Wysocki*
Institute of Anaesthesiology and Intensive Therapy, University School of Medical Sciences, Poznañ, Poland; *Division of Cardiology, Intensive Therapy,
University School of Medical Sciences, Poznañ, Poland
Crit Care 1999, 3 (suppl 1):P240
Aortic reconstructive surgery is associated with post-ischemic
reperfusion and oxidative stress. It is expected that oxidative
stress should be self-limiting during healing process in the postoperative period. Lipid hydroperoxides (LHP) are one of oxidative
stress markers therefore we evaluated changes in LHP level in the
course of uncomplicated healing in patients who underwent
abdominal aortic reconstruction. Ten male patients, aged 56–74
years (mean 65.5 ± 6.01) with abdominal aortic aneurysm or aortoiliac occlusive disease were submitted to aortic grafting operation.
LHP concentration was measured in blood samples collected via
central line prior to (P), at the end of (E) and 1 h, 24 h, 48 h and
72 h after surgery. The results are presented as mean ± SEM.
*Nonparametric one-way ANOVA–Kruskal–Wallis test
LHP concentration was significantly increased at the end of
surgery and started to decrease just after 1 h later reaching the
initial level within 48 h. The obtained results indicate limitation of
the oxidative stress in the course of uncomplicated healing. The
results also suggest that LHP level can be used for monitoring of
oxidative stress activity in humans.
P241 Deep leg veign thrombosis in multiply injured patients: an underestimated problem? Results of a prospective
clinical study with 50 patients
RJ Stiletto, K Giannadakis and R Leppek*
Department of Trauma Surgery/ICU and *Department of Radiology Philipps-University Marburg, Baldinger Str. 35033 Marburg/Lahn, Germany
Crit Care 1999, 3 (suppl 1):P241
Introduction: Too little is still known about the incidence rate of
thromboembolic complications in polytrauma patients after ICU
treatment, as only a small amount of data is available on this topic.
The majority of the studies published to date that have been performed to assess the incidence rate of thrombosis in multiply
injured patients only refer to the clinical symptoms of a venous
thrombosis. A systematic screening-examination for the assessment of the incidence rate of thromboembolic complications in
the above-mentioned patient collective has not yet gained acceptance as a routine method in clinical practice.
Material and method: Between January 1996 and December 1997,
50 polytrauma patients were included in a prospective clinical
study. Including criteria were: an initial ISS-score >16, a stay on
the ICU of at least 72 h and a time on the respirator of at least 72 h.
All patients were examined for a deep veign thrombosis by using a
standardized protocol and by means of a colour-coded duplex
(ccd) sonography. In cases in which the clinical or/and sonographic
examination yielded results of a suspected veign thrombosis, a
phlebography was performed. In cases of a suspected pulmonary
embolism a pulmonary angiography was performed. The colourcoded duplex sonography was used before the patients were
mobilized or transfered to an other ward (generally after 15 days).
Results: If not indicated otherwise numbers are given as median.
The age of the 38 male and 12 female patients was 38.6 years.
The severity of trauma was characterized by an ISS-score of 39.5
points. Eight patients died of a multiorgan-failure during their
stay on the ICU. The autopsy findings reveal that no patient died
of the of a veign thrombosis or a pulmonary embolism. Of the
120
Critical Care 1999, Vol 3 suppl 1
remaining 42 patients, 8 patients (19%) showed deep leg veign
thrombosis in the ccd. In three of these patients (7%) also a pulmonary embolism occurred.
Conclusion: Having in mind the results of our study the incidence
rate of thromboembolic complications in polytrauma patients
seems to be much higher as expected in comparison to the published results of other authors.
P242 Obstructive shock in pulmonary embolism: thrombolytic therapy and survival
S Pivetti, E Aluffi, L Bonino, S Valpreda, R Urbino, B Tartaglino, F Navone, C Antro and V Gai
Medicina d’Urgenza e P.S. Medicina, E.D., Az. Osp. ‘ S. Giovanni Battista’ diTorino, Torino, Italy
Crit Care 1999, 3 (suppl 1):P242
Study objectives: Shock due to massive pulmonary embolism (PE)
shows a variable prevalence in literature, without general agreement
about thrombolytic therapy effectiveness. Objective of the study was
to appreciate prevalence and main clinical features of obstructive
shock (OS) in patients with PE admitted to our departement, and to
evaluate thrombolytic therapy effectiveness (BAPE regimen).
Methods and results: 236 PE cases were treated from March 95
until June 98 ; 24/236 suffered OS (10.2%, 14 F, 10 M, mean age 69
years). In 91.6% of OS we found one risk factor, at least, and in 62%
two or more risk factors. 3/24 patients presented with cardiac arrest,
7/24 showed RBBB and 5/24 S1Q3T3 pattern on EKG, 9/24 showed
a normal EKG. Echocardiography, performed in 66% of patients,
detected in all cases an enlarged and hypokinetic right ventricle;
venous duplex ultrasound, performed in 70% of cases, detected DVT
in 70.5%; perfusion radionuclide lung scan, performed in 70.5% of
cases, showed a high probability pattern in 94%. D-dimer was
altered in all cases; ABG analysis showed hypoxemia in all cases.
13/24 patients with OS were given thrombolysis according to
BAPE regimen (rTPA 0.6 mg/kg over 15 min); 11/24 patients with
OS were not given thombolysis because of absolute contraindications. Thrombolytic therapy decision-making rested on clinical
data, on echocardiography in 38% of case and on echocardiography
and lung scan in 61% of cases. Intra-hospital overall death-rate was
37.5% (9/24 patients); all 13 patients given thrombolysis were
alive at discharge, whereas, 9/11 (81.8%) patients not given thrombolysis died in the hospital.
Conclusion: We found OS in 10.2 % of PE cases; 13 patients given
thrombolysis all were alive and showed stable hemodynamic
parameters at discharge, whereas 9/11 patients not thrombolysis
given died during hospital stay. This outlines the need of an expeditious clinical and instrumental diagnosis as a tool of decisionmaking, especially about thrombolytic therapy. Moreover, we
found a 100% sensibility of D-dimer, hypoxemia as detected by
ABG analysis, echocardiography and perfusion radionuclide lung
scan.
P243 Aortic valve replacement with ‘stentless’ versus mechanical prosthesis: what difference in postoperative ICU
course?
F Guarracino, D De Cosmo, D Penzo, M Tedesco, A Bossi and R De Stefani
Department of Cardiothoracic Anaesthesia and ICU, Umberto I Hospital, Via Circonvallazione 50, 30171 Mestre (VE), Italy
Crit Care 1999, 3 (suppl 1):P243
Introduction: Aortic valve prosthesis determine a transvalvular
gradient (∆p) with changes in aortic flow that can affect left ventricular geometry and function, implanted prosthesis and aortic
route. In order to improve prognosis a new prosthesis has been
proposed , the so called ‘stentless valve’ (SV), whose main characteristic is the absence of the supporting ring. Aim of our study was
to evaluate if such valve could influence early postoperative
course in ICU.
Methods: Forty patients, age 67 ± 11 and EF 56 ± 14, undergoing
aortic valve replacement were enrolled. Nineteen patients, 12
with aortic stenosis (AoS) and seven with insufficiency (AoI)
underwent SV implantation (group S); 21 patients, 13 with AoS
and eight with AoI, received mechanical valve (group M). Anaesthesia with remifentanil and propofol, moderate hypothermia
(30°C) and anterograde blood cardioplegia were used. In all cases
mechanical ventilation (MV) and intubation time, need for
inotropic support and blood loss were registered during ICU stay.
Results: No differences were found in duration of MV (125 ± 30 min
in group S versus 136 ± 12 min in group M, P > 0.05) and intubation
(3 h in group S versus 3.4 h in group M, P > 0.05) in patients with
aortic stenosis. In patients with AoI MV and intubation time was
shorter in group S (respectively 140 ± 25 min versus 155 ± 18 min in
group M, P < 0.05; 3.9 h versus 4.5 h in group M, P < 0.05). No differences were observed in blood loss between two groups, nor in
dopamine dosage (5.4 µg/kg/min versus 6.6 µg/kg/min, P < 0.05).
Discussion: Our results show no differences in early postoperative
outcome in patients with AoS when treated with mechanical or
SV. Vice versa SV seems to improve ICU course of patients with
AoI, with regard to duration of MV and intubation. Other studies
with echocardiography are necessary to clear if these differences
can be due to a lower aortic transvalvular gradient of SV.
P244 High risk patients in major thoracic surgery
G Della Rocca, F Ruberto, F Pugliese, L Pompei, C Coccia, MG Costa and P Di Marco
Istituto di Anestesiologia e Rianimazione, Dir Prof A. Gasparetto, University of Rome ‘La Sapienza’ Via del Policlinico n°155-00161 Rome, Italy
Crit Care 1999, 3 (suppl 1):P244
Lung resections are correlated to high mortality (4–6%) and
morbidity (20–40%) that can increase in high risk patients.
Objectives of this study is to analyze preoperative risk factors,
in a group of high risk patients undergoing thoracotomy for
lung cancer and to assess the relationship with postoperative
complications.
Poster abstracts
Methods: From January 1996 to December 1997 43 patients,
undergone pulmonary resection for lung cancer, were considered at
high risk and enrolled in this study according to one or more of the
following including criteria: age older than 70 years; previous cardiovascular disease; poor pulmonary function (FEV1 <65% predicted values, PaO2 <65 mmHg or PaCO2 >42 mmHg); chronic
systemic disease. Patients clinical data are reported in the Table.
Anesthetic technique was the same for all patients. All the patients
were monitored with EKG, pulse oxymetry (Nellcor N200), invasive arterial pressure, pulmonary artery catheter when necessary
and in-end expiratory gas analysis. Preoperatively an epidural
catheter was inserted in T6-T11 space. Anesthesia was maintained
with isoflurane 0.5% vecuronium and fentanyl combined with
epidural analgesia (bupivacaine 0.5% and fentanyl). A continuous
infusion through the epidural catheter of morphine 20 mg in 250 ml
normal saline 0.9% at 5 ml/h was used for postoperative pain relief.
Surgical procedures included: 33 lobectomy, 4 bilobectomy, 3
sleeve resections, 2 pneumonectomy. Relationship among different
preoperative risk factors and postoperative complications were performed with χ2 test and corrected with Fisher’s exact test.
Results: Mean age was 69 yrs (range 50–83 years). All patients
were extubated in the operative room at the end of surgical procedures.
Complications occurred in 25.5% of patients (11/43): 3 arrhythmias, 2 myocardial infarctions, 2 pulmonary edema, 2 acute renal
failures, 2 pulmonary complications (prolonged air leakage)
(Table). The perioperative mortality rate was 4.6% (2/43). The
mean length of staying in hospital was 11 days for all patients, 12.5
for respiratory group, 9.6 for cardiac group, 10.9 for age group.
Conclusion: In our experience lung resections in high risk patients
have low mortality and morbidity. Therefore, age over 70 years
121
Table. Preoperative risk factors and perioperative
complications
Risk factors
No. patients
Complications
Age
9
Cardiovascular
4
1 MI
Respiratory
8
3 arrhythmia,
1 PE, 1 resp
Age + cardiovascular
8
1 MI (died), 1 resp
Age + respiratory
4
Age + other
1
Age + cardiovascular + other
1
2 RF (1died)
Age + respiratory + other
1
1 PE
Age + cardiovascular + respiratory
+ other
2
Age + cardiovascular + respiratory
2
Cardiovascular + other
2
Respiratory + cardiovascular
1
MI, myocardial infarction; PE, pulmonary edema; RF, renal failure
alone has no longer to be considered a limiting factor in patients
undergoing surgery for lung cancer. High risk patients need a very
careful preoperative evaluation of cardiovascular and pulmonary
function in order to avoid perioperative complications and to
reduce the morbidity. An appropiate surgical and anesthetic technique, and postoperative pain relief improves outcome in high risk
patients.
P245 Outcome of systemic rheumatic disease patients admitted in intensive care unit
B Bouffandeau, B de Cagny, V Jounieau, F Tinturier, Y Domart, PY Lallement, H Gayet and A Fournier
Unité de Réanimation Néphrologie, hôpital sud - 80054 Amiens, France
Crit Care 1999, 3 (suppl 1):P245
Survival (%)
100
Objective: The aim of this study was the determination of short
and longterm outcomes and prognostic factors for patients with
systemic rheumatic diseases (SRD) admitted to intensive care
units (ICU) in a retrospective case series study of SRD patients
admitted in six French ICU in community and teaching hospital
between January 1992 and July 1996.
non
80
Mechanical Ventilation
60
40
20
Main results: A total of 60 SRD patients were included with diagnostic of infection (40%), acute exacerbation of SRD (16.7%),
iatrogenic complication (16.7%), cardiovascular complication
(15%), and miscellaneous (11.7%). The death rate in intensive
care units was 26.7% (16/60). Multivariate analysis (Cox model)
identified two factor predicting poor MICU outcome: age above
65 years (relative risk [RR], 3.3; 95% confidence interval [CI],
1.9–5.8) and Tran organ failure indices (RR, 2.2; 95% CI, 1.7–2.8).
The mean overall survival time after admission to ICU was 18.8
months. The 1-year survival rate was 61.1%, and the 2-years
58.8%. Multivariate analysis (Cox model) identified two factors
predicting poor long term outcome: age above 65 years (RR 4.0;
95% CI 2.7–6.0), and need of mechanical ventilation (RR, 6.5;
95% CI, 4.2–10.1) (Fig).
0
0
10
20
30
40
50
Time (months)
60
70
80
Figure. Survival of patients with SRD in intensive care unit, influence of mechanical ventilation.
Conclusion: We conclude that this SRD patients should be admitted to the ICU on the same basis as other patients. In this population neither the diagnostic of the underlying disease, nor the use
of immunosuppresive therapy did influence the short and long
outcome. Long-term survival depended only on the age and the
need of mechanical ventilation.
122
Critical Care 1999, Vol 3 suppl 1
P246 Abdominal sepsis in the surgical intensive care unit: a follow up study on quality of life, morbidity and
mortality
P Haraldsen and R Andersson
Department of Surgery, Lund University Hospital, S-221 85 Lund, Sweden
Crit Care 1999, 3 (suppl 1):P246
Surgical intensive care consumes considerable facilities and the
associated costs are high. The present study aimed at evaluating
longterm outcome of patients treated due to abdominal sepsis in
the surgical intensive care unit from January 1983 to December
1995 by a follow-up from June to August 1997 of patients surviving the hospital stay. The patients were interviewed by telephone
and also completed a ‘quality-of-life’ form. Out of 210 patients
(mean age 65 years) 151 survived the hospital stay. At follow-up,
another 45 patients were deceased, 41 patients were not reached
and another 17 patients declined to participate. Thus, the followup included 48 patients. At discharge from hospital, 54% of the
patients returned directly home and 67% returned to their regular
work after a median sick-leave of 10 weeks. When comparing a
quality-of-life score, an impairment of median scores (P < 0.01)
was found, although the patients subjectively appreciated quality
of life not to have changed significantly. 49% claimed full recovery. Hospital mortality was 28% attributable to multiple organ dysfunction and total mortality over the time period was 50% and
rarely associated with abdominal sepsis. Thus, recovery following
abdominal sepsis treated in the surgical intensive care unit is good
and motivates efforts performed during the acute phase.
P247 Time and type of admission to a surgical intensive care unit
MW Sebastian, WJ Fulkerson and NW Knudsen
Duke University Medical Center, Durham, NC, USA
Crit Care 1999, 3 (suppl 1):P247
Introduction: Duke University Medical Center (DUMC) is a tertiary care hospital with a Level 1 (USA) Trauma Center Designation. Increasing level of patient acuteness, high census levels,
decreasing resident staffing and financial concerns have led to
intensive care unit (ICU) organization and staffing changes. ICU
care is being redefined at DUMC via pursuit of a multidisciplinary
approach to the treatment of critically ill patients. As part of this
initiative, analysis of Surgical Intensive Care Unit (SICU) admissions was performed for January through March 1998. This analysis showed that 45% of admissions occurred when there was no
attending in house. To fulfill the missions of patient care, education, research, cost-containment, optimal bed utilization and
appropriate reimbursement for services, we instituted around-theclock board-certified intensivist coverage in the SICU. Continuing analysis of admission distribution confirms that half of
admissions occur at night and breakdown of type of admission
indicates that these admissions are the patients most requiring
active resuscitation and supervision of resident management.
Methods: To determine time and type of SICU admissions we
retrospectively reviewed the SICU database from July through
November 1998. Time of arrival was divided into 12-h blocks
beginning at 6 AM and 6 PM. Patients were divided into four categories: postoperative, direct admission, trauma and floor transfer.
Results: There are approximately 115 admissions per month to
this 16 bed ICU for a total of 575 admissions for the study period.
From 6 PM to 6 AM, 276 (48%) admissions occurred encompassing
88% of trauma patients and 79% of floor transfers. The time distribution was constant for each month and the incidence of postoperative, direct admission, and floor transfer was also constant from
month to month, while the incidence of trauma admissions was
higher in July and August.
Admission
6 am–6 pm
6 pm–6 am
Total
Postoperative
261 (70%)
114 (30%)
375 (65.2%)
Direct admission
12 (48%)
13 (52%)
25 (4.4%)
Trauma
13 (12%)
99 (88%)
112 (19.5%)
Floor transfer
13 (21%)
50 (79%)
63 (10.9%)
299 (52%)
276 (48%)
575 (100%)
Total
Conclusion: Fifty percent of admissions to the DUMC SICU
occur during off-hours when traditionally there has been no
attending level in-house supervision. The high percentage of
trauma and floor transfers during off-hours validates this reorganization of ICU staffing and around-the-clock supervision.
P248 Preliminary data: PIM and Prism in infants and children post cardiac surgery in a UK PICU
GD Jones, M Hatherill and IA Murdoch
Paediatric ICU, Guys Hospital, London SE1 9RT, UK. Tel: 0171 955 2564; Fax 0171 955 2563
Crit Care 1999, 3 (suppl 1):P248
Objective: To describe the predictive and calibration capabilities of
PIM and PRISM in infants and children following cardiac surgery.
Design: Between December 1997 and November 1998, 250 consecutive infants and children were studied. No child died in
theatre. There were; 53 patients <1 month, 75 from 1 month–1
year and 122 >1 year. Median age 11.43 months (range 0.02–229).
Survivors were defined by ICU discharge.
Results: Crude mortality was 6% (15/250) all deaths occurred in
children <1 year old. Median age of death (range) was 0.33 months
(0.02–11.83). Median time (range) to death was 53 h (2–264).
Poster abstracts
123
Table. Observed vs (predicted) deaths and area under the ROC curve for PRISM and PIM
Mortality%
PRISM
No.
Mean risk
PIM
No.
Mean risk
<1
1–4.99
5–14.99
15–29.99
>30
Total
ROC
0 (0.42)
0 (2.8)
5 (3.22)
4 (3.96)
6 (5.78)
15 (16.1)
0.93
73
113
33
19
12
250
(0.88-0.97)
0.58
2.52
9.78
20.88
48.22
0 (0.24)
3 (3.79)
4 (1.99)
4 (4.64)
4 (3.19)
15 (13.8)
0.87
250
(0.77-0.99)
30
177
22
22
8
0.79
2.14
8.68
21.08
39.8
Calibration using the Hosmer-Lemeshow goodness of fit test,
showed a χ2 16.15, df 8, significance 0.04 for PRISM and χ2 17.05,
df 8, significance 0.03 for PIM. Using a cut off at P = 0.5, sensitivity
and specificity for PRISM was 98.3% and 33.3%, and 99.2% and
26.7% for PIM.
compares favourably with the original work by Shann et al. [1]
(0.87 vs 0.83). Therefore we would concur with their conclusion
that PIM is accurate enough to describe the risk of mortality in
groups of children, and has the added advantage of needing less
data collection than PRISM.
Conclusion: Neither PRISM, nor the new scoring system PIM are
well calibrated for predicting individual mortality. However,
despite the small numbers, the area under the ROC plot for PIM
Reference
1. Shann et al.: Intensive Care Med 1997; 23:201-207.
P249 Does intensive care improve outcome?
CD Gomersall, PY Tan, GM Joynt, TA Buckley and E Wong
Department of Anaesthesia & Intensive Care, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.
Tel. 44 171 886 1248; Fax. 44 171 886 6360; E-mail. charles@gomersal.surfaid.org
Crit Care 1999, 3 (suppl 1):P249
Introduction: ‘Does intensive care improve outcome?’ is a question of fundamental importance. It is unlikely to ever be answered
conclusively, because of ethical constraints on performing a controlled study of two groups randomised to ICU admission or no
ICU admission. It is possible however, to assess ICU admission as
an independent predictor of survival when considered alongside
other possible predictors.
Method: Prospective cohort study of all adult patients referred for
emergency admission to the only adult ICU of a university hospital during a 3-month period. Because of the limited number of
alternative ICU beds patients refused admission are not transferred to an ICU in another hospital. Exclusion criteria were:
direct ICU transfers from other hospitals, patients referred when
the ICU was full, patients with acute burn injury and cardiac
surgery patients. (The latter two groups were excluded from the
original MPM II derivation and validation sets). MPM II0 score
was calculated for each patient and the following data were collected: sex, referring specialty, APACHE II diagnostic weighting,
admission or refusal of admission to ICU and hospital survival.
MPM II0 consists of 14 physiological and diagnostic variables and
is the only severity scoring system available at ICU admission.
Logistic regression analysis using a forward stepwise conditional
method was performed using SPSS for Windows. Variables
included as possible predictors of survival were sex, MPM II0,
APACHE II diagnostic weighting, ICU admission, and interactions between admission and MPM II0, and admission and
APACHE II weighting.
Results: Three hundred and eighty-three patients were studied of
whom 229 were admitted. Low MPM II0, low APACHE II diagnostic weighting and admission to ICU were found to be independent predictors of hospital survival with a hospital survival
odds ratio for ICU admission/ refusal of 2.41 (95% CI: 1.48–3.93).
Discussion: This result demonstrates that admission to ICU is an
independent predictor of survival when compared with available
likely predictors. It is unlikely that the association between admission and survival is due to selective admission of those patients
more likely to survive as the association was independent of severity of illness, type of illness and sex. Our results therefore strongly
support a positive answer to the question ‘Does admission to ICU
improve outcome?’.
P250 Comparison of the APACHE II, MEES and GCS in patients with nontraumatic coma for prediction of mortality
S Grmec, S Piberl and V Gasparovic*
EMS, PHU Maribor, Ul. Talcev 9, Maribor 2000 Slovenia, *Division of Intensive Care Medicine, University Hospital Centre Zagreb, Kispaticeva 12,
1000 Zagreb, Croatia
Crit Care 1999, 3 (suppl 1):P250
Introduction: Due to the numerous prehospital descriptive scoring
system it is uncertain whether they are efficient in the description
124
Critical Care 1999, Vol 3 suppl 1
of how serious illness are and furthermore whether they can have
prognostic role in the estimation of the illness outcome (what is
their validity in connection with the prognostic scoring system
APACHE II).
Methods: In prehospital setting were collected from each patient
postintervention values of the MEES and GCS. The APACHE II
score were recorded on the day of admission to hospital. This
study was undertaken over a 2 year period (January 1996 to
October 1998) and included 286 consecutive patients hospitalized for nontraumatic coma. Patients less than 16 years old were
not included. There were 168 men and 118 women. Their age
varied from 16 to 87 years with a mean 51.8 ± 16.9. Sensitivity,
specificity and correct prediction outcome measured by the χ2method in four severity scores. The Youden Index was also
obtained. The best cutoff point in each scoring system was determined by the Youden index. The difference in Youden index was
calculated by Z score. A P value <0.05 was chosen to reject the
null hypothesis. For each score receiver operating characteristi-
cally curve (ROC) were obtained. The difference in ROC was
calculated by Z score.
Results: For prediction of mortality, the best cutoff points are 19
for APACHE II; 18 for MEES and 5 for GCS. The Youden index
has best cutoff point at 0.63 for APACHE II, 0.61 for MEES and
0.65 for GCS. Correct predictions outcome (%) was for APACHE II
79.9 ± 1.6; for MEES 78.3 ± 1.9 and for GCS 81.9 ± 1.5. The area
under ROC is 0.86 ± 0.02 in the APACHE II; 0.85 ± 0.06 in the
MEES and 0.88 ± 0.03 in the GCS. There was no statistical differences among APACHE II, MEES and GCS in terms of correct prediction outcome. Youden index and the area under ROC (P < 0.05).
Conclusion: APACHE II is not much better than prehospital
descriptive scoring system (MEES and GCS). APACHE II and
MEES may not replace the role of GCS in the prediction mortality in nontraumatic coma. For the assessment of mortality the
GCS score provides the best indicator for these patients (simplicity, less time-consuming and effective information, especially in
an emergency situation).
P251 Application of prognostic score to patients following cardiac arrest
MV de la Torre-Prados, A García-Alcántara A, A Poullet-Brea, C Reina-Artacho and A Soler-García
Servicio Medicina Intensiva HU Virgen de la Victoria, 29016-Málaga, Spain
Results: Average age was 61.8 ± 14.9 years (29–84), with sex distribution of 59.4% male and 40.5% female.
Crit Care 1999, 3 (suppl 1):P251
Introduction: The use of prognostic scores in continuous form
may help in decision-making in the post-resuscitation phase following cardiac arrest.
Objective: To evaluate the clinical efficacy of a prognostic score
[1] on intrahospital mortality of patients suffering extrahospital
cardiac arrest.
Material and method: A 6 month prospective study carried out on
37 patients in the Emergency Unit of a 650 bed hospital (attending to a total of 74 000 patients per year). A score of 0–6 based on
cardiac rhythm at time of arrest was applied (cardiac rhythm different to ventricular tachicardia without pulse or ventricular fibrillation = 3). Glasgow score at the time of admission (4 or 5 = 1 and 3
= 2) and type of cardiopulmonary resuscitation received up to
arrival of Emergency Assistance (no first aid from qualified personnel at time of arrest = 1).
Conclusion: 1 The application of this score may prove useful in
clinical practice to evaluate the continuity of life-support. 2 Neurological assessment is the most valuable clinical variable for prognosis in the follow-up phase. 3 As in other studies, age is not a
determining factor in intrahospital mortality following cardiac
arrest. 4 Median arterial pressure shows a difference of some 20
points between the surviving and non surviving groups. 5 Mortality among males is significantily greater than females after receiving CPR. 6 The type of assistance received prior to arrival of
health services is of significant value in the survival chain.
Reference
1.
Lancet 1995, 346:417-421.
Survival
Variables
Yes
No
No
%
No
%
Total no
P*
3
27
19
73
22
0.009
6
5
0
75
26
2
14
10
25
74
100
8
19
10
0.002
No
Average
SD
No
Average
SD
P**
MAP
11
84.4
19.9
20
65.5
30.1
0.07
Age
11
62.9
11.8
26
61.3
15.1
ns
Score
11
2,4
1.5
26
4.3
1.5
0.001
Males
Score:
1–2
3–4
5–6
MAP, Median arterial pressure hospital admisssion. *Significant difference between groups, Chi Square. **t test.
Poster abstracts
125
P252 Outcome of children with near drowning requiring treatment in PICU
D Gionis, M Moustaki, Z Beka, A Tsoutsou, E Ourani and J Papadatos
‘P&A Kyriakou’ Children’s Hospital, PICU
Crit Care 1999, 3 (suppl 1):P252
A number of near drowned children needed admission to a PICU
due to the severity of their condition. The aim of this review is to
illustrate the epidemiology, the clinical features, the management
and the outcome of near drowned children admitted to our PICU.
For this purpose, we reviewed the charts of near drowned children
admitted to our unit during the last 11 years. The study population consisted of 11 children (7 boys and 4 girls) aged 2.5–12.5
years (mean age 7.2 years, SD4,1, SE1.3). At the same period a
five-fold number of near drowned children were hospitalized in
pediatric wards. The submersion site, among our patients, was sea
in 6 cases, a swimming pool in 3, a pond in 2 cases. Ten children
were transferred from district hospitals where they had initially
received advanced life support. 6/10 children were transferred
intubated. 4/10 children were in cardiac arrest after the accident,
3/4 had been given basic life support at the accident site and sub-
sequently 2 of them were intubated on their arrival at the nearest
district hospital. 1/4 was intubated in the nearest hospital where
he was transferred with brain death without having received
appropriate basic life support for about 30 min. 2/3 children who
initially were apnoeic and comatose, required intubation. The
remaining 4 children had respiratory distress and irregular respiration but only one needed intubation. 8/11 patients have clinical
and roentgenographic features of pulmonary oedema. The intubated children remained on mechanical ventilation from 12–36 h.
Convulsions occurred in 3 children. In 1/11 patients there were
signs of high intracranial pressure with good response to mannitol
administration. 10/11 patients survived and discharged from hospital after 3–6 days of hospitalization overall. The patient who was
admitted with brain death, never recovered. All survived children
had no neurological sequalae on their follow up 2–5 years later.
Our results emphasize that even the most severe cases of near
drowning have a favorable outcome, provided that the victims are
given basic life support at the accident site.
P253 Prognosis related to organ dysfunction in intensive care unit
PS Martins and S Blecher
Hospital Santa Marcelina, São Paulo, Brazil
Crit Care 1999, 3 (suppl 1):P253
Objective: To develop a model for assessing severity of organ dysfunction (OD) among patients on the first 24 h of Intensive Care
Unit (ICU) stay, using a score to determine the probability of ICU
mortality.
Design: Prospective cohort study.
Setting: General medical and surgical ICU in a tertiary teaching
hospital in City of São Paulo, Brazil.
Patients: Three hundred and seventy-eight consecutive, unselected patients over the period from March to October of 1996:
developmental sample. Three hundred patients over the period
from February to June of 1997: validation sample.
Outcome measure: Patients vital status at ICU discharge. None
intervention was considered.
Statistical analysis: APACHE II score was calculated for all
patients. A Lowess Regression model, using the variables that
demonstrated P ≤ 0.10 in the univariate analysis was made to iden-
GLASGOW Coma Scale
Mean blood
pressure (MBP)
Heart rate (HR)
(A–a) DO2
Creatinine (ARF)
Hematocrit
Chronic disease
ARF, Acute renal failure
0
1
15–14
MBP >70
and
HR <140
13–9
MBP <70
and
HR ≤120
<200
até 1.4
≥30
não
200–349
1.5–1.9
<30
tify the level of severity of each variable. The variables were then
entered into a multiple logistic regression analysis resulting in a
probability of ICU mortality equation. The Goodness-of-fit test
was used to evaluate model calibration; discrimination was evaluated using area under the receiver operating characteristic curve
(ROC), in the developmental and validation samples.
Main results: OD was considered in five systems: neurologic, pulmonary, renal, cardiovascular and hematologic, plus the presence
of chronic disease. The points were assigned from 1 to 4 according
to the levels of severity (Table). The results showed good calibration (P = 0.96; C = 2.33; dF = 8 and P = 0.90; C = 3.01; dF = 10)
respectively in the developmental and validation samples, and
good discrimination (ROC curve of 0.81 and 0.82, respectively).
Conclusion: Cardiovascular dysfunction was the most severe organ
dysfunction, followed by pulmonary, renal and neurologic dysfunction. Hematologic dysfunction and the presence of chronic
disease were less severe. This model can be used as end point in
epidemiologic studies of organ dysfunction in our ICU when the
points are summed according to the horizontal lines (severity
within an organ system), or as a predictor of death when the points
are summed vertically, once the β is the same for all variables.
2
3
4
≤8
HR ≥140
or
MBP <70 and
HR >120
350–549
2.0–3.4
≤20
sim
MBP <50
≥550
≥3.5
126
Critical Care 1999, Vol 3 suppl 1
P254 Characteristics of patients with sepsis and multiple organ failure in the UK
L Shaikh, H Stuart, A Rhodes and RW Chang for the RIP Users Group
Dept of Intensive Care, St George’s Hospital, London, SW17 0QT, UK. Fax 0181 7679748
Crit Care 1999, 3 (suppl 1):P254
All severe sepsis and multiple organ failure patients
Total
Introduction: This study examined the characteristics and ICU
outcome of patients admitted with severe sepsis and compared
them with patients who develop severe sepsis after admission to
the ICU.
n (%)
2790
Mean age (SD)
Method: The Riyadh Intensive Care Program (RIP) database
1989–1996 contains 28 094 complete demographic data, daily
APACHE II and TISS scores from 21 UK ICUs. 2790 patients retrospectively satisfied the criteria of severe sepsis and multiple
organ failure.
Survivors
Non-survivors
P
1162 (41.6%) 1628 (58.4%)
60.2 (16.7)
58.5 (17.7)
61.5 (15.9) <0.001
Admission Apache 21.5 (7.6)
II (SD)
19.1(7.1)
23.2 (7.5) <0.001
Apache II on 1st
day of sepsis (SD)
22.6 (7.5)
19.7 (6.9)
24.7 (7.2) <0.001
No organ
failures (SD)
2.3 (0.6)
2.2 (0.5)
2.4 (0.7)
<0.001
Differences between those admitted with and those that
developed sepsis
Results: See Table.
Conclusion: The timing of development of severe sepsis and multiple organ failure appears to be an important factor for outcome
with a significantly higher mortality among those admitted with
sepsis. The admission APACHE II score and the score on the day
of development of sepsis were lower among those who developed
sepsis. This may be attributable to these patients already being in
the ICU environment and thus receiving closer monitoring and
more timely intervention. This finding may be of importance in
the design of future trials to evaluate new treatment modalities.
Admitted with
Developed
n (%)
P
782 (28%)
2008 (72%)
491 (62.8%)
1137 (56.6)
Mean age (SD)
59 (17.3)
60.7 (16.5)
0.01
Admission Apache II (SD)
25.8 (7.2)
19.8 (7.0)
<0.001
Day of sepsis Apache II(SD) 25.8 (7.2)
21.4 (7.2)
<0.001
No organ failure (SD)
2.3 (0.7)
<0.001
Mortality (%)
2.5 (0.7)
0.003
P255 Important factors for the modelling and design of clinical trials for severe sepsis and multiple organ failure
L Shaikh, H Stuart, A Rhodes and RW Chang for the RIP Users Group
Dept of Intensive Care, St George’s Hospital, London, SW17 0QT, UK. Fax 0181 7679748
Crit Care 1999, 3 (suppl 1):P255
failure. This study was done to determine the factors that have to
be controlled for in future design of clinical trials in sepsis.
Introduction: No large, well-controlled, trial has been able to
demonstrate a statistically significant and reproducible benefit of
experimental treatment in severe sepsis and multiple organ
Method: 2790 patients from the RIP database satisfied the criteria
of severe sepsis and multiple organ failure. Logistic regression
Outcome
Number of organ failures
≤2
≥4
3
APACHE II Score
[3–17]
[17–28]
[28–65]
Treating centre
1,7,19
2,3,11,13,18,20
4,5,6,9,14,15,17,21
APACHE II Score
[3–14]
[14–23]
8,10,12,16
Developed
APACHE II Score
[23–65]
[3–14]
[14–17]
APACHE II Score
[3–14]
Admitted
[14–19]
[19–65]
[17–25]
[25–32]
[32–65]
Poster abstracts
analysis was carried out to determine the factors that influenced
ICU outcome. The CHAID model of an expert system
AnswerTree (SPSS, UK) was also used to derive decision rules
that govern the outcome of these patients.
Results: Of the eight independent variables entered into the logistic regression analysis four in order of importance were selected:
APACHE II score on the day of development of sepsis, treating
centre, number of organ failures, age. The area under ROC was
127
0.75. The level and branches of the decision rules by the expert
system is shown in the Figure on the previous page. The difference in outcome for all the nodes is P < 0.0001
Conclusion: As the area under the curve of the ROC = 0.75, one is
unlikely to use logistical regression analysis to risk stratify patients
for future trials of severe sepsis; however, expert systems can
delineate statistical significance and patterns which influence
outcome in a complex trial population.
P256 Does SOFA and TISS scores correlate in long term ICU patients?
I Novak, P Hora, M Bilek, M Suchy, R Rokyta and V Sramek
ICU, Medical Dpt I, Charles Uni Hospital Plzen, Alej Svobody 80, CZ-30466 Plzen, Czech Republic. Tel: +420-19-710 3 165;
Fax: +420-19-522 566; E-mail: sramek@fnplzen.cz
Crit Care 1999, 3 (suppl 1):P256
Introduction: SOFA score is a useful tool for monitoring of organ
function in ICU patients [1]. TISS score is used for measuring of
workload in intensive care [2]. We studied if there is any link
between SOFA and TISS scores in long term ICU patients (i.e.
patients staying in the ICU >3 days).
Materials and methods: Daily SOFA and TISS scores of ICU
patients admitted between July and November 1998 who stayed
in the ICU >3 days were retrieved from data collection system. An
experienced ICU doctor has collected SOFA scores into this
system daily. Pooled scores for the whole group, for ICU survivals
(S) and nonsurvivals (NS) separately and the scores on the first
day of ICU stay were analysed.
Results: Sixty-two patients (i.e. 42% out of total admissions; age
60.0 ± 14.7 years) fulfilled the inclusion criteria and stayed in the
ICU for the mean of 11.9 ± 10.8 days). ICU mortality was 30.6%
(19 patients). Significant correlation was found for pooled SOFA
and TISS scores (r2 = 0.52, P < 0.0001) and it was more pronounced
in survivals (S) than in nonsurvivals (NS) (r2 = 0.52, P < 0.0001 and
r2 = 0.19, P < 0.0001, respectively). Significant link between the
two scores was already present on the first day of ICU stay
(r2 = 0.54, P < 0.0001).
Conclusion: In long term ICU patients a significant correlation is
present between organ failures (scored by SOFA) and workload
(measured by TISS). This link is already present on the day of
admission and later on is more pronounced in survivals possibly
because in NS the care is more often witheld or withdrawn.
References
1. Vincent JL et al.: Use of the SOFA score to assess the
incidence of organ dysfunction/failure in the intensive
care units: Results of a multicenter, prospective study.
Crit Care Med 1998, 26:1793-1800.
2. Dickie H et al.: Relationship between TISS and ICU cost.
Intensive Care Med 1998, 24:1009-1017.
P257 Daily SOFA scoring for ICU patients?
P Hora, M Bilek, M Suchy, R Rokyta, I Novak and V Sramek
ICU, Medical Dpt I, Charles Uni Hospital Plzen, Alej Svobody 80, CZ-30466 Plzen, Czech Republic. Tel: +420-19-710 3 165;
Fax: +420-19-522 566; E-mail: sramek@fnplzen.cz
Crit Care 1999, 3 (suppl 1):P257
Introduction: SOFA might be a useful tool for monitoring of organ
function in ICU patients [1]. We evaluated optimal frequency of
SOFA acquisition in long term ICU patients (i.e. patients staying
in the ICU >3 days).
Materials and methods: Daily SOFA scores of ICU patients admitted between July and November 1998 who stayed in the ICU >3
days were retrieved from the data collection system. An experienced ICU doctor has collected SOFA scores into this system
daily. Original daily SOFA score flow charts and adapted (simplified) SOFA score flow charts (SOFA on days 1, 4, 7, 10, 14, 21, 24,
28 etc.; i.e. values of unlisted days expressed as trends between
data collection days) were compared for individuals and the whole
group of patients. Data are presented as means ± SD; P < 0.05 was
considered significant.
Results: Sixty-two patients (i.e. 42% out of total admissions; age
60.0 ± 14.7 years) fulfilled the inclusion criteria and stayed in the
ICU for the mean of 11.9 ± 10.8 days. ICU mortality was 30.6% (19
patients). Original and adapted data did show equal values for the
whole group of patients (MANOVA group by time effect 0.98 at
Day 4, 62 patients and 1.00 at Day 7, 36 patients). Out of total 736
ICU days, in 374 there was theoretical possibility of data difference (adapted SOFA scores). Significant difference (defined as
∆SOFA >2) between original and adapted values was found in 64
cases (17.1%) In 30 cases adapted values were higher then original
ones.
Conclusion: SOFA score collected 2–3 times a week describes sufficiently characteristics of long term ICU patients. Significant
individual data might be lost when SOFA score is not collected on
daily basis.
References
Vincent JL et al.: Use of the SOFA score to assess the
incidence of organ dysfunction/failure in the intensive
care units: Results of a multicenter, prospective study.
Crit Care Med 1998, 26:1793-1800.
128
Critical Care 1999, Vol 3 suppl 1
P258 Evaluation of the SOFA (Sepsis-related Organ Failure Assessment) Score in 303 consecutive patients of a
medical intensive care unit
U Janssens, C Graf, J Graf and P Hanrath
Medical Clinic I, University Hospital of RWTH Aachen, Pauwelsstraße 30, D-52057 Aachen, Germany
Crit Care 1999, 3 (suppl 1):P258
Objectives: The SOFA (sepsis-related organ failure assessment)
score describes quantitatively the degree of organ dysfunction.
Although primarily not designed to predict outcome any assessment of morbidity must be related to mortality to some degree.
We therefore investigated whether an increasing SOFA score is
associated with a higher hospital mortality in patients (pts) of a
medical intensive care unit (ICU).
Methods: All consecutive pts who stayed >24 h in ICU were
included in this prospective study between 11/97 and 2/98. SOFA
score and SAPS II were determined after 24 h. Discrimination
power of the scores for survivors (S) and non-survivors (NS) [hospital mortality] was assessed by the area under the Receiver Operating Characteristic (AUROC) curve.
Results: 303 pts (216 male [71.3%], 62 ± 12 years, length of ICU
stay 3.7 ± 4.7 days, SOFA 2.5 ± 2.9, SAPS II 26 ± 12.6) were studied.
Hospital mortality was 14.5%. SOFA score for NS was significantly
higher than for S (5.9 ± 3.7 vs. 1.9 ± 2.3, P < 0.05). The AUROC was
0.82 ± 0.04 for the SOFA score and 0.77 ± 0.04 for SAPS II.
Figure. Mortality (%) versus SOFA score.
Conclusion: SOFA score discriminates well between S and NS
24 h after admission. Respiration, liver and coagulation showed an
increasing mortality rate with a higher SOFA score for each organ.
Although the SOFA score was primarily designed for use in septic
patients it may be also applied for pts of a medical intensive care
unit.
P259 Statistical modeling of prognostic indices
J Livianu, S Blecher, JMC Orlando and JO Proença
Hospital Municipal Jabaquara-Rua Francisco Paula Ribeiro 562, São Paulo, Brazil
Crit Care 1999, 3 (suppl 1):P259
Introduction: Severity scoring models can provide accurate
outcome prediction but their performance is very influenced by
variations in patient case-mix. Therefore, none of the usual
scoring systems (APACHE II, SAPS II and MPM 24) fitted to this
ICU: they had good discriminatory power but poor calibration.
Logistic regression analysis of their variables was performed to
identify the most predictive association to ICU mortality.
Methods: Data of 823 consecutive patients (pts) admitted to the
ICU were prospectively collected. Pts who stayed less than 24 h at
the ICU or were burn or had less than 16 years old were excluded.
For pts with several admissions, only the first ICU admission was
considered. The remaining 709 pts were divided in two groups:
418 (59%) pts constituted the development set and 291 (41%) pts
became the validation set. After calculating the scoring indices,
their variables and respective weights were separately analysed.
Variables with P value <0.05 at univariate analysis were included
as independent variables at logistic regression and vital status at
ICU discharge was considered as dependent variable.
Results: There were 67% male and 33% female pts; median age
was 46 years old, postoperative care took up 330 (46.7%) cases, of
which 275 (83%) were emergency surgery. Trauma was the admission cause for 200 (28%) pts. ICU mortality rate was 25.1% and
Points assigned as
β
P
OR
Age
SII
0.0266
0.000
1.1187
Neurologic
Glasgow coma scale
AII
0.3325
0.000
1.3945
Cardiovascular
Heart rate
Vasoactive drugs
AII
M24
0.3802
0.7928
0.017
0.019
1.4627
2.2095
Respiratory
Oxygenation
AII
0.2997
0.005
1.3494
Infectious
Temperature
WBC count
Infection present
AII
SII
M24
0.4433
0.2571
0.7692
0.022
0.014
0.013
1.5579
1.3120
2.1582
Urinary
Serum creatinine
Urine output
AII
SII
0.1852
0.1310
0.003
0.041
1.2034
1.1400
Variables
APACHE II, AII; SAPS II, SII; MPM 24, M24, OR, odds ratio
Poster abstracts
hospital mortality 33.7%. APACHE II was 16.7 ± 8.4 and SAPS II
was 33.5 ± 16.5. Through statistical modeling, an hibrid model was
generated, with variables and points from the three indices. With
this model, the prediction obtained was: development set with
discrimination ROC = 0.89 and calibration goodness-of-fit C = 1.68
and validation set with ROC = 0.84 and goodness-of-fit C = 7.72.
129
Conclusion: Hemodynamic instability, infection, impaired renal
function, respiratory failure and coma were the best predictors of
death. Early identification of patients at major risk may allow
treatment with more resources and interventions, in order to
improve survival. Furthermore, this study shows that suitable statistical management may be useful to customize and enhance the
prognostic accuracy of the currently available scoring systems.
P260 The determination of the duration of the nursing activities in the intensive care unit and the therapeutic
intervention scoring sysem (TISS)
N Kýlýçaslan and G Kocaman
Dokuz Eylül University School of Medicine, Ýzmir, Turkey
Crit Care 1999, 3 (suppl 1):P260
The purpose of this study was to calculate nurse/patient radio by
using TISS-28, and to assess time allocation to nursing activities in
the intensive care unit. In this study the TISS scores of 416
patients were calculated in the intensive care unit 10 weeks long
using the TISS-28 form. In order to determine the duration of the
nursing care activities due to nursing care categories the work
sampling method was used. A sampling matrix for 10 weeks was
created and the nursing care activities were observed 7 days a
week for two day shifts (08.00–16.00). The data collection instruments were, the ‘TISS-28’ and ‘Work sampling form for intensive
care unit nursing activities’. The TISS-28 point for ICU was 40.41
for day shift. One TISS-28 point equals 11.88 min of the 480 min
in each shift. Related literature shows that nursing care activity for
one day makes 40–50 TISS score. The percentage of nursing time
spent on nursing activities in the ICU was calculated by using
work sampling. Results indicated that 44.25 % of nurses time was
spent in activities in TISS-28; 12.87% in activities not in TISS-28;
25.8% in indirect patient care, 6.21% in organnizational activites,
10.64% in personnel activities and 0.15% in other activities. It is
shown that category one represents TISS-28 and that the increase
in TISS score results in the increase in nursing care activity duration. These result show that the TISS-28 can be useful to determine the patient/nurse ratio in intensive care units.
References
Miranda DR, Rijk AD, Schaufeli W: Simplified Therapeutic
Intervention Scoring System: The TISS-28 items: results
from a multicenter study. Critical Care Medicine 1996,
24:64-72.
Cullen DJ, Cývetta JM; Briggs BA: Therapeutic Intervention
Scoring System: a method for guantitative comparison of
patient care. Crit Care Med 1974, 2:57.
Hendrickson G, Doddato T, Kovner C: How do nurses use their
time? JONA 1990, 20:3.
Urden DL, Roode JL: Work sampling (a decision-making tool
for determining resources and work redesigning). JONA
1997, 27:34-41.
P261 Fast-track intensive care procedure after cardiac surgery in the 9th decade
N Huebner, W Rees*, M Boeckelmann, S Rittel*, H Warnecke* and U Christmann
Dept. Anesthesiology, *Dept. Cardiac Surgery, Schuechtermann Klinik, Ulmenallee 11, 49214 Bad Rothenfelde, Germany
Crit Care 1999, 3 (suppl 1):P261
Objective: Outcome with fast track intensive care medicine after
cardiac surgery in patients older than 80 years.
Methods: Between 7/96 and 7/97, 86 cardiac operations (3.7%)
have been performed in patients older than 80 years out of an
overall number of 2349 cardiac operations. Preoperative NYHA
Status was III in 36.1% and IV in 46.5% of the old patients. LVEF
was 49%, LVEDP 16 mmHg. Additional desaeses were: diab. mell.
23.3%, renal insufficiency 11.6%, cerebral stroke 10.5% and
myocardial infarction 37.2%. Performed cardiac operations have
been: CABG (61.6%), AVR (23.3%), CABG and AVR (12.8%),
MVR (1.2%), CABG and MVR (1.2%) and REDO operations
(4.6%). Mean time on ECC was 84 min and overall operation time
was 169 min (mean). Anesthesia was conducted as balanced anesthesia with early extubation as a main aim.
Results: Patients were extubated 6 h ( median ) after surgery, shortest duration of ventilation was 30 min. Mean stay on ICU was 2.6
days and mean time of hospitalisation was 9.4 days. 30-day-mortality was 3.4% in the old patients and 2.2% in the overall population.
Conclusion: Fast-track procedure after cardiac surgery in the octanarian is feasible with even better results and without any additional risk than conventional intensive care procedure.
P262 Prognosis and functional capacity a year after a myocardial infarction on elderly 80-year-old patients
L Lorente, M Martin, R Medina, JJ Valencia, J Mujika and A Jimenez
Intensive Care Unit, Clinica La Colina, Santa Cruz de Tenerife, Spain
Crit Care 1999, 3 (suppl 1):P262
Objective: To evaluate prognosis and functional capacity a year
after a myocardial infarction (MI) in elderly 80-year-old patients.
130
Critical Care 1999, Vol 3 suppl 1
To analyse differences between sex, localization and developed or
no Q wave.
Design: Retrospective analysis.
Patients: All patients of ≥80 years admitted between 1.1.94 and
31.10.97 with a myocardial infarction.
Evaluation of evolution curve: The study was done through telephonic interview. We analysed mortality at the reception (REC), 1,
3, 6, 9 and 12 months (M). Was used a daily activity scale (DAS)
with five factors (walking, dressing, bathing, cleaning and eating)
with a punctuation from 0 to 2 every activity (0 = total dependence,
1 = partial dependence and 2 = independence), with a range 0 to 10.
Statistical analysis: The statistical significance of the variables was
tested by Fisher’s test of t Student test. Values less than 0.05 were
considered statistically significant.
Results: We included 112 patients, 54 (48.21%) male and 58
female. The localization of the myocardial infarction was anterior
(Anter) in 71 cases (63.39%) and inferior (Infer) in 41, and 87
patients (77.67%) developed Q wave. At the reception 41
(36.60%) patients dead and 16 patients dead at the following 12
months (accumulated mortality at year = 50.89%). Q wave and
anterior myocardial infarction had more mortality, with P < 0.001
and P < 0.05 respectively. At year, the survivors had a mean DAS
8.72 ± 1.89. It was higher in non-Q wave (P < 0.05) and males
(P < 0.05).
The evolution is shown in the Table.
Conclusion: Though the mortality between elderly 80 years old
patients with myocardial infarction is high, they have an acceptable functional capacity (more in males and non-Q-wave myocardial infarction).
Patients with MI
Exitus REC
Exitus 1° M
Exitus 3° M
Exitus 6° M
Exitus 9° M
Exitus 12° M
DAS at year
112
41
47
49
51
56
57
8.72 ± 1.89
With Q
87
39
45
47
48
52
52
8.33 ± 1.88
Non-Q
25
2
2
2
3
4
5
9.36 ± 1.72
Anter.
71
30
34
36
37
39
40
8.57 ± 2.03
Infer.
41
11
13
13
14
17
17
9.01 ± 1.54
Female
58
24
26
26
28
31
31
8.13 ± 2.09
Male
54
17
21
23
23
25
26
9.35 ± 1.39
Total
P263 Very old patients (older than 85 years) at a medical ICU: indications, interventions, outcome
J Reiger and G Grimm
IInd Medical Department General Hospital, A-9020 Klagenfurt, St. Veiterstrasse 47, Austria
Crit Care 1999, 3 (suppl 1):P263
Objective: The part of elderly people in the population has been
increasing during the last decades. In 1995, 16% of the MiddleEuropean population have been older than 65 years, up to the year
2010 there should be an increase up to 22%. German investigations have shown, that a 1/3 of the population older than 65 years
are suffering from 3–4 chronic diseases, 98% of the population
older than 80 years from one chronic disease.
Through those facts the number of old patients admitted to ICUs is
increasing. Aim of following paper was to objective the treatment and
outcome of very old patients (over 85 years) at a medical ICU of a
general hospital over an 18-month period (1997-01-01 to 1998-06-30).
Results and outcome: 899 patients had been admitted to the ICU
during the study period, 48 (5.3%) older than 85 years. At admis-
sion the APACHE II-score ranked between 19 and 32. Indications
had been mainly cardial (27), metabolic (8), gastrointestinal (6),
outside CPR (5) and acute respiratory failure (2). 11 patients had
been mechanical ventilated (1–8 days, mean 2.7 days), 6 patients
received a cardiac pacemaker, 5 underwent endoscopical interventions, 4 thrombolysis (AMI, 100 mg Alteplase ‘front loaded’), 2
patients PTCA/IABP and one female patient ACBG.
Duration of stay had been 3.8 days (overall 3.9 days), mortality
27.7% (overall 14.8%).
Conclusion: Comorbidity and mortality had been higher in
patients older than 85 years compared to all patients. 6 month after
the ICU stay 24 patients (68.5%) were still alive. With good
quality of life. Despite higher mortality very old patients benefit
from ICU stay and interventions.
P264 Quality control with autopsy on a medical intensive care unit
J Roosen, E Frans, A Wilmer, S Vanderschueren and H Bobbaers
Department of Medical Intensive Care, U.Z. Gasthuisberg, Leuven, Belgium
Crit Care 1999, 3 (suppl 1):P264
Postmortem examination is considered as the golden standard for
the evaluation of clinical diagnosis. However due to several
reasons (costs, permission of family members), few medical
Poster abstracts
centers continue to perform autopsy as a means of quality control.
From 1995 to 1996, we performed an autopsy study in a medical
intensive care unit of a university hospital: 93% of the 140
deceased patients in our medical ICU underwent an autopsy, 100
consecutive patient files were studied.
The clinical diagnosis were made by internists, specialized in
intensive medicine; the diagnosis on autopsy were made by a
pathologist. According to the criteria of Goldman[1], the clinical
and autopsy findings were categorized into major and minor diagnoses. A missed diagnosis on clinical grounds was classified as a
class I error (if detected before death, this would probably have
caused a therapeutic change with possible altered outcome) or as a
class II error (if known before death, this diagnosis would not have
led to a change in therapy).
In 16% of the patients, a class I missed diagnosis was detected
(cardiac tamponade, myocardial infarction, fungal pneumonia); in
9%, a class II missed diagnosis was detected (most frequently
tumors). Sometimes the diagnosis was missed due to a combination of severe, acute problems (e.g. development of cardiac tam-
131
ponade after insertion of a venous catheter during hemorraghic
shock), or due to a lack of sensitive and specific investigational
methods (fungal pneumonia is frequently suspected in immunocompromised patients, but is often difficult to confirm), or due to
logistic transportation problems in the hemodynamically unstable
patient (e.g. retroperitoneal hemorrhage is not always detectable
on bedside echography; for diagnosis, CAT-scan is needed).
Conclusion: Even in the era of increasing diagnostic possibilities,
due to improved medical technologies in the ICU, postmortem
examination still remains useful in detecting unexpected diagnoses, missed in the premortem clinical evaluation. Our observations suggested the need for constant alertness and an aggressive
investigational planning in patients with unexplained shock or
pulmonary infiltrates.
Reference
1. Goldman L, Sayson R, Robbins S et al.: The value of the
autopsy in three medical eras. N Engl J Med 1983;
308:1000-1005.
P265 Quality of life before and after medical intensive care
M Wehler, R Strauß, A Bost, A Geise, A Müller, M Meyer* and EG Hahn
Department of Medicine I and *Institute of Medical Statistics and Documentation, University of Erlangen-Nuremberg, 91023 Erlangen, Germany
Crit Care 1999, 3 (suppl 1):P265
Introduction: We prospectively analysed changes in the quality of
life (QOL) in patients before and 6 months after admission to a
medical intensive care unit (ICU).
Patients and methods: All patients admitted to the ICU were eligible for inclusion. Patients <18 years and those who died or were
discharged within 24 h of admission were excluded, QOL measures were collected during interview during the first 24 h of ICU
stay and 6 months after admission using a questionnaire especially
designed for ICU patients developed by the Spanish Group for
Epidemiological Analysis of Critical Care Patients [1]. Baseline
QOL referred to the 2 months prior to admission and were compared with measures at 6 months using Wilcoxon matched-pairs
test, P < 0.05 was considered statistically significant.
Results: During the first 12 months of the study period 326
patients met the study criteria; mean age was 58 ± 17 (± SD) years,
median 60, range 19–95 years, 55% were male. Mean ICU length
of stay was 10.4 ± 15.1 days, range 2–127 days. Mean APACHE II
score was 23 ± 10, range 0–51. Mean TISS score after 24 h was
33 ± 14, range 0–69. Mortality rates were: ICU 24%, hospital 6%,
9% within the following 6 months after hospital discharge. Up to
now 147 patients completed the questionnaire after 6 months, six
patients (1.8%) were lost to follow-up. Relative to baseline a significant worsening was noted in the subscale of normal daily activities (P = 0.013). No significant changes were seen in total QOL
score (P = 0.25) an the subscales of physiologic basic activities
(P = 0.06) and emotional state (P = 0.09). No correlation existed
between APACHE II scores and QOL (r = 033).
Conclusion: Six months after ICU treatment patients had a significant decrease in the level of their daily activities. Basic physiologic
activities and emotional status are not significantly altered. 90% of
the long-term survivors were living at home and all previously
occupied patients were able to return to their previous profession.
Reference
1 Fernandez RR, et al.: Intens Care Med 1996; 22:1034-1042.
P266 Withdrawal of intensive care in the patient’s home
P Williams and S Mann
ICU, Middlemore Hospital, Otahuhu, Auckland, New Zealand
Crit Care 1999, 3 (suppl 1):P266
Death should be managed as vigorously as life saving. Historically
intensive therapy is withdrawn in the intensive care unit, but we
would like to present four cases where intensive care treatment
was withdrawn at home. The staff of the Intensive Care Unit at
Middlemore Hospital have taken four patients home, on ventilatory and inotropic support, and withdrawn care when the patient
was settled in their home, surrounded by family. This is felt to aid
in the grieving process, and in many cases is culturally desirable.
The cases thus far are subarachnoid haemorrhage, massive
intracerbral bleed and intractable septic shock. From our experience we recommend that certain selection criteria are observed.
There is a need for the patient and family to live locally, support is
required from the local general practitioner and district nursing
service, and a clear explanation of the whole process must be
understood by all family members prior to leaving the intensive
care unit. A palliation plan must be commenced prior to leaving
the intensive care unit.
We see this as a practical option in selected intensive care
patients.
132
Critical Care 1999, Vol 3 suppl 1
P267 Results of an ethical questionnaire distributed to members of the Australian and New Zealand Intensive Care
Society
RJ McRae
Dept Anaesthesia & Pain Management, The Alfred, Commercial Road, PRAHRAN, VIC, Australia, 3181. Tel: 613 9276 2851; Fax: 613 9276 2813;
E-mail: r.mcrae@alfred.org.au
Crit Care 1999, 3 (suppl 1):P267
Three hundred and sixty-seven (67%) of questionnaires on ethical
issues distributed to members of the Australian and New Zealand
Intensive Care Society were returned and included for analysis.
The questionnaire was similar to a questionnaire that had been
distributed to members of the European Society of Intensive Care
Medicine, but adapted and augmented for local use, and provides
a useful comparison of how issues are considered in Australasia.
Intensive Care beds are a limited resource, and availability
restricts admissions. Nonetheless, 76% of respondents admitted
patients with a poor prognosis for survival. There was high (82%)
concordance of what was felt should be done and what was done
in clinical scenarios. Respondents considered that they provided
high information to patients, including in the event of iatrogenic
complication. In terms of end-of-life decisions, 35% of respondents wrote that they would involve the family in discussions (not
an option available for selection): this appeared to be a pragmatic
approach to dealing with relatives. Withdrawal of treatment was
considered to be different to withholding treatment by 43% of
respondents. 34% of respondents would change a do-not-resuscitate order that had been previously instituted. 15% of respondents
considered that an Ethics Consultant would assist in their practice, with 95% supporting the inclusion of ethics teaching during
medical training.
P268 Withholding and withdrawing life support: national French prospective study
E Ferrand, R Robert, P Ingrand and the LATAREA group
Service de Réanimation Médicale CHU, Poitiers 86021 Poitiers cedex, France
Crit Care 1999, 3 (suppl 1):P268
Material and methods: 113 French ICU participated to the study.
The following data were collected for all the admitted ICU
patients during a 2-month study period: age, sex, SAPS II, main
diagnostic, previous chronic disease. In patients for whom WH or
WD were indicated, additional data were recorded. The reasons to
withheld or withdraw treatments and the type of WH or WD life
support treatments were recorded.
were older and had higher SAPS 2 than the remaining patients.
Decisions of withhold or withdraw were more frequent in patients
with previous chronic diseases or cardiac arrest before admission
in ICU. Futility and the poor expected quality of life were the
most frequently cited reason for WH or WD. Decision to not ventilate the patient was the most frequently reported withheld treatment (n = 214; 15%). Vasopressors were either not started or
limited in their dosage in 196 patients (14%). The most frequently
withdrawn life support treatment were vasopressors (19%). Extrarenal epuration was discontinued in 67 patients (7%). Lowering
FiO2 to 21% was indicated in 155 patients (14.5%), discontinued
ventilation was ordered in 101 patients (9.4%) and extubation was
performed only in 34 patients (3.1%). Withdrawal of hydration was
rarely performed (n = 16 ; 1.5%). 1176 out of the 7309 (16.1%)
included patients died. 628 out 1176 died (53%) after support was
withheld or withdrawn. Most of the time WH or WD was decided
by the medical team. A unique M.D. was involved in the decision
in 37 (12%) of cases. Paramedic (nurses) opinions was taken in
account for the decision in 482 (59.7%). Family was involved in
the process in less than 50%.
Results: Treatments were withheld or withdrawn in 807 out 7309
(11%). WH and WD were indicated in 336 patients (4.6%) and 471
patients (6.4%) respectively. ICU patients undergoing WH or WD
Comments: The reality and the frequency of WH and WD life
support treatments have been demonstrated in this large study
involving an important number of French ICU.
Introduction: Controversies still exists regarding indications of
WH and WD, ethical similarity or difference between WH and
WD, the way to withhold or to withdraw treatments and what
should be the family implications in these decisions
Aim of the study: To evaluate the reality of withholding and withdrawing life support (WH and WD), the type of withheld and withdrawn treatments and the conditions leading to decisions to WH or
WD.