Noskova et al.

BMC Anesthesiology (2015) 15:38

DOI 10.1186/s12871-015-0020-1

RESEARCH ARTICLE Open Access

Neonatal effect of remifentanil in general

anaesthesia for caesarean section:
a randomized trial
Pavlina Noskova1, Jan Blaha1*, Hana Bakhouche2, Jana Kubatova1, Jitka Ulrichova1, Patricia Marusicova1,
Jan Smisek3, Antonin Parizek4, Ondrej Slanar2 and Pavel Michalek1

Abstract
Background: Remifentanil has been suggested for its short duration of action to replace standard opioids for
induction of general anaesthesia in caesarean section. While the stabilizing effect of remifentanil on maternal
circulation has been confirmed, its effect on postnatal adaptation remains unclear, as currently published studies
are not powered sufficiently to detect any clinical effect of remifentanil on the newborn.
Methods: Using a double-blinded randomized design, a total of 151 parturients undergoing caesarean delivery
under general anaesthesia were randomized into two groups 76 patients received a bolus of remifentanil prior to
induction, while 75 patients were assigned to the control group. Remifentanil 1 g/kg was administered 30 seconds
before the standard induction of general anaesthesia. The primary outcome measure was an assessment of neonatal
adaptation using the Apgar score, while secondary outcomes included the need for respiratory support after delivery
and differences in umbilical blood gas analysis (Astrup).
Results: The incidence of lower Apgar scores between 0 and 7 was significantly higher in the remifentanil group at
one minute (25% vs. 9.3% of newborns, p = 0.017); whilst at five minutes and later no Apgar score differences were
observed. There was no difference in the need for moderate (nasal CPAP) or intensive (intubation) respiratory support,
but significantly more neonates in the remifentanil group required tactile stimulation for breathing support (21% vs. 7%
of newborns, p = 0.017). There was no difference in the parameters from umbilical cord blood gas analysis between
the groups.
Conclusion: At a dose of 1 g/kg, remifentanil prior to induction of general anaesthesia increases the risk of neonatal
respiratory depression during first minutes after caesarean delivery but duration of clinical symptoms is short.
Trial registration: ClinicalTrials.gov: NCT01550640.
Keywords: Remifentanil, Neonatal effect, General anaesthesia, Caesarean delivery

Background obstetric anaesthetists [3,4]. Therefore, the ultra short-

Opioids are routinely avoided during induction to gen- acting 1-receptor agonist remifentanil has been
eral anaesthesia for caesarean section because of the po- suggested as a replacement for longer acting opioids in
tential for respiratory depression in the neonate [1,2]. parturients undergoing caesarean delivery [5-11]. Remi-
On the other hand, insufficient depth of analgesia in fentanil rapidly crosses the placenta but simultaneously
parturients until foetal delivery remains a concern for is quickly eliminated from the neonatal circulation by
degradation with nonspecific esterases in plasma and/or
redistribution [12-14]. With a half-life of 310 minutes,
* Correspondence: jan.blaha@lf1.cuni.cz

Equal contributors
remifentanil should be almost entirely eliminated from
1
Department of Anaesthesiology, Resuscitation and Intensive Medicine, 1st foetal circulation by the time of delivery [15]. How-
Faculty of Medicine, Charles University in Prague and General University ever, in obstetrics, despite promising pharmacokinet-
Hospital in Prague, U Nemocnice 2, 128 08 Praha 2, Czech Republic
Full list of author information is available at the end of the article
ics and pharmacodynamics, remifentanil is currently

2015 Noskova et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative
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unless otherwise stated.
Noskova et al. BMC Anesthesiology (2015) 15:38 Page 2 of 7

more frequently used as a systemic alternative to epidural (www.randomization.com). Each patient was allocated
labour analgesia rather than for general anaesthesia for cae- before entering the operating room. The randomization
sarean delivery [16]. was kept blinded for the patient, surgeon, and neonat-
While the stabilizing effect of remifentanil on maternal ologist. Patients in the RMF group received a bolus of
circulation has been clearly and consistently described in remifentanil 1 g/kg 30 seconds prior to induction with
several studies, including the systematic review and thiopentone; while all other preoperative, anaesthetic,
meta-analysis published by Heesen and colleagues [17], obstetric and postoperative procedures, were identical
the effect on postnatal adaptation remains unclear, as for both groups.
these studies have not been sufficiently powered. We
therefore aimed our study primarily as a comparison of General anaesthesia
postnatal adaptation of neonates after caesarean delivery Standard departmental protocol for caesarean delivery
in parturients receiving remifentanil bolus of 1 g/kg under general anaesthesia was used with metoclopra-
prior to induction of general anaesthesia with those hav- mide and ranitidine administered orally for aspiration
ing standard opioid-free induction. prevention. After preoxygenation, general anaesthesia
was induced using i.v. thiopentone 5 mg/kg followed by
Methods succinylcholine 1.25 mg/kg, and, until delivery, main-
Study design tained with sevoflurane at an expired concentration of
This prospective, randomized, controlled, and double- 0.5-0.7% in a 50% gas mixture of nitrous oxide/oxygen.
blinded study was conducted at a tertiary care university After ligation of the umbilical cord, sufentanil 0.5 g/kg
hospital with an average of 4,600 births per year, in and atracurium 0.35 mg/kg were administered for anal-
the period between March 2011 and April 2014.The gesia and muscle relaxation and sevoflurane was in-
study was approved by the Ethics Committee of the creased to 1%.
General University Hospital in Prague (MZ10-UK1LF-
Slanar) and registered at the Clinical Trials Database Obstetric management
(ClinicalTrials.gov NCT01550640). Study was conducted Pfannenstiel supra-cervical laparotomy and Geppert
in accordance with Helsinki Declaration principles. Signed uterotomy were used in all cases. Oxytocin 5 IU as a
informed consent was obtained from each participant. bolus was administered intravenously, diluted in 20 ml
Primary objective of the study was to compare new- of saline after removal of the placenta.
born postnatal adaptation in parturients undergoing
caesarean delivery under general anaesthesia with a Monitoring and evaluation
remifentanil bolus 1 g/kg administered prior to the in- Intraoperative monitoring was performed using Datex
duction of general anaesthesia with those undergoing Ohmeda S/5 TM Compact Anaesthesia Monitor (Datex-
standard induction. Secondary outcomes were require- Ohmeda Inc., USA) according to general standards for
ments for postoperative respiratory support of neonates patient monitoring during general anaesthesia. Time 0
and differences in umbilical cord blood gas analysis. was determined as the time of remifentanil administra-
tion in the RMF group or time 30 sec prior to thiopen-
Study population tone administration in the STD group. The following
Eligible patients were parturients undergoing caesarean parameters were monitored; systolic and diastolic non-
delivery under general anaesthesia. Patients were invasive blood pressure (NIBPsyst; NIBPdiast), mean
screened and enrolled in the study by an anaesthetist blood pressure (MAP), heart rate (HR), electrocardiog-
during the pre-anaesthesia visit before caesarean de- raphy (ECG) with ST segment analysis (lead II), pulse
livery. Inclusion criteria were: age of 18 45 years. oximetry (SpO2), capnography (EtCO2), % of oxygen and
Exclusion criteria included known allergy to remifentanil, volatile anaesthetic, and ventilation parameters (minute
multiple pregnancy, gestational age below the 35th week, ventilation, tidal volume, respiratory rate and maximal
estimated weight of foetus below 2500 grams, severe foetal inspiratory pressure). To evaluate the depth of anaesthesia,
hypoxia, severe maternal hypotension, and other serious continuous bispectral index analysis (BIS) was used.
foetal or maternal conditions. Discontinuation criterion Evaluation of newborn adaptation was performed
was difficult foetal delivery defined as uterine incision-to- using Apgar scores at 1, 5 and 10 minutes, simultan-
delivery interval >3 min. eously with arterial and venous umbilical cord blood gas
analysis and clinical examination. Clinical assessment
Study interventions was undertaken by an experienced neonatologist and
Parturients were randomly assigned to two study groups - acid/base balance status was evaluated directly in the
remifentanil (RMF) or standard (STD). Treatment alloca- delivery room with ABL 90 Flex (Radiometer Medical,
tion was performed using online randomization generator Denmark) blood gas analyser.
Noskova et al. BMC Anesthesiology (2015) 15:38 Page 3 of 7

Statistical analysis anaesthesia by the parturient (67 vs. 68 patients). In only

The sample size of 150 parturients was calculated to de- 9 (RMF group) and 7 (STD group) cases, respectively,
tect an overall twofold difference between the groups in the choice of general anaesthesia was based on medical
the primary outcome (Apgar scores 07) with a two- considerations - placenta praevia centralis (6 pts.),
sided 5% significance level and a power of 80%. For thrombocytopenia (3 pts.), psychosis (3 pts.), tokophobia
sample size calculation, we used data from long term de- (2 pts.), history of spinal trauma (1 pt.) and hypersensi-
partmental baseline statistics, where Apgar score of 07 tive tetany (1 pt.).
was observed in 9.5% of caesarean sections under gen- Anaesthesia and surgical baseline management charac-
eral anaesthesia. A 36-month inclusion period was antic- teristics including delivery time (induction to delivery
ipated to recruit this number of patients. interval) are shown in Table 2. No intra- or postop-
Statistical analysis was performed with the STATISTICA erative major complications were recorded during the
10 software (StatSoft, Czech Republic). All data was tested study.
for normality using Kolmogorov-Smirnov test prior to final
analysis. Numerical data from both groups was compared Neonatal outcome
using Students t-test or MannWhitney Rank Sum Test, Table 3 and Figure 2 show the characteristics of neonatal
as appropriate. For categorical variables the Fishers exact postnatal adaptation Apgar scores and the need for re-
test and chi-square test were used. All statistical tests were spiratory support. We noted a higher incidence of low
performed two-tailed and values of P < 0.05 were consid- Apgar scores between 0 and 7 in the remifentanil group
ered statistically significant. at the first minute (19 vs. 7 newborns, p = 0.017), but
after the fifth minute no difference between the groups
Results was observed. No difference between the study groups
A total of 151 parturients were included in the study, 76 was found in requirement for moderate or intensive
patients were allocated to the remifentanil group while respiratory support following delivery (p = 0.983). Tem-
another 75 were assigned to the standard group. All par- porary CPAP (continuous positive airway pressure) ven-
ticipants were in physical status class I-II according to tilation was employed in 10 newborns (5 in each group),
the American Society of Anesthesiologists. Demographic but none required intubation or admission to a neonatal
characteristics of parturients are expressed in Table 1. intensive care unit. There was however, a significant dif-
Figure 1 represents study flow diagram. ference in the need for mild breathing support using
The most frequent reason for employment of general tactile stimulation during the first 5 minutes (16 vs. 5
anaesthesia in this study was refusal of regional newborns, p = 0.017) (Table 3). No newborn required ad-
ministration of an 1-opioid receptor antagonist.
Table 4 shows umbilical cord arterial and venous
Table 1 Characteristics of parturients and newborns blood gas analysis. No difference was observed for any
Remifentanil Standard P parameter including number of pH values <7.2; such a
group (n = 76) group (n = 75) value was recorded only once (7.18, in the remifentanil
Age (years) 33.1 5.1 32.3 5.3 0.362 group).
Weight prior to pregnancy (kg) 68.1 13.1 69.8 13.4 0.473
Actual weight (kg) 82.0 13.4 81.4 14.3 0.813 Maternal haemodynamics
Height (cm) 168.9 6.8 167.6 5.8 0.233
The study groups were equal in basal haemodynamic pa-
2
rameters (blood pressure and heart rate at time 0), but
BMI (kg.m ) 24.0 4.4 24.9 5.0 0.254
they varied significantly at the time of intubation (both
Medical concomitant diseases blood pressure and heart rate) and delivery (heart rate).
Hypertension 6 (8%) 6 (8%) 0.981 The basal haemodynamic profiles are shown in Table 5.
Asthma 4 (5%) 3 (4%) 0.712
Thyreopathy 3 (4%) 3 (4%) 0.987 Depth of anaesthesia
Diabetes 3 (4%) 2 (3%) 0.660
No difference was found between the groups after in-
duction of general anaesthesia in depth of anaesthesia
Placenta praevia centralis 3 (4%) 3 (4%) 0.987
(BIS), ST-analysis, or respiratory-ventilation parameters
Other 11 (14%) 13 (17%) 0.796 (SatO2, EtCO2). The profiles of BIS values are shown in
Newborns Table 2.
Weight of newborns (g) 3162.9 467 3122.5 618 0.334
Gestational age (weeks) 38.6 1.1 38.9 1.4 0.541 Discussion
Data are presented as mean standard deviation or n (%).
Our study is not the first one to evaluate the effect
BMI = Body Mass Index. of remifentanil in parturients undergoing caesarean
Noskova et al. BMC Anesthesiology (2015) 15:38 Page 4 of 7

Figure 1 Assessment, randomization, and follow-up of the study patients.

delivery under general anaesthesia. However, to our response to intubation and surgery during caesarean
knowledge, it is the only one adequately powered to delivery, they vary in terms of its effect on neonatal
assess the effect on the incidence of respiratory de- adaptation. Yoo [18] and Ngan Kee [15] used an identi-
pression during postnatal adaptation of newborns. cal bolus of remifentanil - 1 g/kg. They highlighted,
Moreover, the other important aspect of our study is its similarly to our study, a risk of transient, neonatal re-
sample size. With 151 patients participating in the study spiratory depression. In contrast, Bouattour and col-
and 76 in the remifentanil group, this is the largest remi- leagues did not demonstrate any attenuation of neonatal
fentanil assessment in obstetric patients undergoing cae- adaptation after administration of 0.5 g/kg of remifenta-
sarean delivery. The size of our homogenous study group nil [19]. More worryingly, 14.3% of newborns in another
should be highlighted especially in comparison to the study had to be intubated for respiratory support, follow-
meta-analysis conducted and published in 2013 by a ing a pre-induction dose of remifentanil 0.5 g/kg [20].
German-Belgian team with the inclusion of 186 patients The determination of a remifentanil safe dose, not
from 5 randomized clinical trials [17]. causing adverse effect on neonate, was not even unrav-
While published studies agree on the positive effect elled by the aforementioned meta-analysis performed by
of remifentanil on reducing adverse haemodynamic Heesen et al. [17].
Noskova et al. BMC Anesthesiology (2015) 15:38 Page 5 of 7

Table 2 Data related to general anaesthesia

Remifentanil Standard P
group (n = 76) group (n = 75)
Anaesthesia prior foetal delivery
Thiopentone bolus (mg) 398 64 401 68 0.745
Sevoflurane (%) 0.57 0.2 0.58 0.3 0.586
SatO2 (%) 98.4 1.7 97.9 2.3 0.219
ETCO2 (kPa) 4.5 0.5 4.4 0.4 0.529
Induction-to-delivery interval (min) 4.0 1.4 3.9 1.2 0.884
Duration of surgery (min) 43 9.2 41 9.4 0.724
Estimated blood loss (ml) 594 196 576 148 0.648
BIS (%) Figure 2 Bar graph showing the need for management of
newborn respiratory depression. The bar graph plots the
Baseline 95.4 4.3 96.2 4.2 0.360 percentage of newborns requiring each level of respiratory
Tracheal intubation 52.4 16 52.2 12.9 0.930 stimulation or support (n = 76 in the remifentanil group and n = 75
in standard group). The black column represents the remifentanil
Delivery 57.7 13.7 55.7 12.2 0.401
group; the cross-hatched column the control group. *P = 0.017.
At 10 min after induction 58.3 10.5 55.8 12.3 0.231 CPAP = continuous positive airway pressure ventilation.
Data are presented as mean standard deviation. Sevoflurane = mean end
expiratory concentration of sevoflurane from induction to delivery; SatO2 = mean
oxygen saturation from induction to delivery; ETCO2 = mean end tidal
capnography from induction to delivery; BIS = bispectral index analysis. group required some form of respiratory support after
Baseline means time before induction to general anaesthesia. delivery, however they mostly responded only to tactile
stimulation.
In our study, we observed a significantly higher inci- The observed incidence of short-time lasting, deterio-
dence of moderate to severe aggravation of neonatal rated postpartum neonatal adaptation was quite high in
adaptation (Apgar scores 07) after remifentanil admin- the remifentanil group, although its clinical significance
istration (p =0.017). However, in all cases, neonatal re- and severity are not clear. A hypothetical explanation of
spiratory depression lasted only for several minutes different results in published studies could be the exist-
because lower Apgar scores were observed at the 1st mi- ence of genetic polymorphism of the placenta transport-
nute only. The Apgar scores were similar at 5 minutes, ing system glycoprotein P (multidrug resistance gene 1,
which is a more crucial time for subsequent neonatal
care and/or eventual transfer to neonatal intensive care
Table 4 Umbilical cord blood gas analysis
unit. In total, 28% of neonates in the remifentanil
Remifentanil Standard P value
group (n = 76) group (n = 75)
Table 3 Neonatal outcome Arterial
Remifentanil Standard P value pH 7.3 0.0 7.3 0.0 0.210
group (n = 76) group (n = 75)
pCO2 (kPa) 6.7 0.7 6.6 0.7 0.450
Apgar score
HCO3-act (mmol/l) 25.0 1.9 24.9 1.9 0.786
1-minute 8.1 2.0 8.9 1.4 0.005
HCO3-std (mmol/l) 22.2 1.9 22.0 1.3 0.567
5-minute 9.2 1.1 9.6 0.8 0.022
BE (mmol/l) 1.4 1.7 1.2 1.7 0.645
10-minute 9.8 0.5 9.8 0.4 0.198
pO2 (kPa) 2.8 0.6 2.6 0.6 0.189
Apgar score 0 -7
satO2 (%) 41.9 14.6 38.0 13.6 0.137
1-minute 19 (25.0%) 7 (9.3%) 0.017
Venous
5-minute 5 (6.6%) 2 (2.7%) 0.442
pH 7.4 0.0 7.3 0.0 0.203
10-minute 0 (0%) 0 (0%) -
pCO2 (kPa) 5.8 0.5 5.8 0.6 0.721
Need for respiratory support
HCO3-act (mmol/l) 23.5 1.6 23.4 1.9 0.848
Tactile stimulation 16 (21.1%) 5 (6.7%) 0.017
HCO3-std (mmol/l) 22.4 1.1 22.2 1.4 0.421
CPAP 5 (6.6%) 5 (6.7%) 0.983
BE (mmol/l) 1.7 1.7 1.8 1.7 0.801
Mechanical ventilation 0 (0%) 0 (0%) -
pO2 (kPa) 4.6 0.8 4.3 1.1 0.157
Administration of naloxone 0 (0%) 0 (0%) -
satO2 (%) 72.6 10.4 68.3 14.4 0.069
Data are presented as mean standard deviation or n (%).
CPAP = continuous positive airway pressure ventilation. Data are presented as mean standard deviation.
Noskova et al. BMC Anesthesiology (2015) 15:38 Page 6 of 7

Table 5 Maternal haemodynamic profiles [17]. Acid/base balance parameters in umbilical cord
Remifentanil Standard P blood correspond with the status of foetal oxygenation at
group (n = 76) group (n = 75) the time of delivery. We detected only one newborn in the
Systolic blood pressure (mmHg) remifentanil group presenting with pH <7.2, which may
Baseline 140.8 16.2 140.6 18.0 0.948 be associated with increased neonatal morbidity [28].
At intubation 145.4 23.5 164.1 26.4 <0.0001 Therefore, our assessment of remifentanil effect on neo-
natal adaptation should not have been affected by concur-
At delivery 146.6 22.5 149.9 25.4 0.444
rent foetal intrauterine hypoxia.
At 10 min after induction 125.7 17.3 122.5 17.0 0.283
We are aware of limitations of our study. Although
Heart rate (bpm) the adaptation of each newborn was evaluated by experi-
Baseline 89.4 12.8 93.1 16.9 0.187 enced neonatologist, requirements to stimulate their
At intubation 91.8 16.6 109.7 17.2 <0.0001 breathing by tactile stimulation might still be biased by
At delivery 88.9 13.7 101.3 20.1 <0.001 inter-individual differences. Another limitation may be
exclusion of deliveries indicated for acute foetal hypoxia.
At 10 min after induction 73.0 16.3 76.6 14.7 0.204
General anaesthesia is most commonly administered in
Data are presented as mean standard deviation. Baseline means time before
induction to general anaesthesia. such cases, where suppression of stress response to tra-
cheal intubation and surgical stimuli would be theoretic-
ally desirable.
MDR1) and polymorphism of -receptors and then Forming a consensus with other published trials, we
divergent transfer of remifentanil into the foetal circula- also recorded the positive effect of remifentanil on the
tion [21,22]. Another reason for relatively higher inci- suppression of cardiovascular stress response to tracheal
dence of respiratory depression in our study may intubation and surgery. A dose of remifentanil 1 g/kg
also be shorter time of foetal delivery (4.0 min given 30 seconds prior to induction of general anaesthe-
induction-to-delivery time) compared to some other sia effectively reduced a rise in both blood pressure and
centres [20,23,24]. We may hypothesize that remifen- heart rate until delivery of foetus. Whereas the haemo-
tanil with its half-life of 310 minutes was not com- dynamic monitoring wasnt the main aim of this study, it
pletely eliminated at the time of delivery. This could was not blinded for anaesthesiologist. Therefore its as-
explain why Yoo et al. [24] found no significantly sessment might be burdened by a potential bias, albeit
higher depression rate, even with a dose of 1.25 g/kg. It most likely only an insignificant. The haemodynamic
should be noted that they reported interval to delivery profile herein is given primarily within an overall de-
approximately 10 minutes, which is potentially longer scription of intraoperative course of our study.
than expected effect of remifentanil. Unlike its stabilizing effect on the cardiovascular sys-
It should be also highlighted that postnatal adaptation tem, the dose of remifentanil 1 g/kg did not affect the
of the newborn is affected by previous intrauterine foetal depth of anaesthesia. BIS values were below 60 in both
condition, concurrent administration of thiopentone and groups throughout the study. This value has been ac-
volatile anaesthetics, as well as by induction-to-delivery cepted as a threshold which should decrease the inci-
interval and technique of caesarean section. Therefore dence of awareness [29,30]. Similar results have been
we excluded parturients with expected alteration of neo- reported in other studies [18]. It is assumed that the ma-
natal respiratory function (immaturity of foetus or in jority of hypnotic effect during induction is achieved by
utero pathologies). In order to decrease bias of the study, the initial dose of thiopentone potentiated by anaesthetic
we also excluded females with multiple pregnancy (risk gases, while remifentanil in this dose has only small ef-
of low birth weight and prematurity) and newborns fol- fect on depth of anaesthesia [31].
lowing difficult delivery with uterine incision-to-delivery
interval more than 3 min [25-27]. Nevertheless, we ob- Conclusion
served 14% incidence of moderate respiratory depression We demonstrated that a pre-induction dose of remifen-
even in the standard group, with 5 newborns requiring the tanil 1 g/kg is associated with a relatively high risk of
use of CPAP. Specific reasons for this depression remain neonatal respiratory depression. However, this attenu-
unclear even after detailed analysis of individual cases (with ation was present only in the first five minutes after de-
no noted significant differences in delivery interval, gesta- livery and its clinical significance seems to be rather
tional age or weight, blood gas analysis results or maternal mild. Remifentanil is a suitable choice of co-induction
demographic, respiratory or haemodynamic parameters). agent in parturients who could be prone to excessive
In contrast to other studies, we did not find any differ- hypertension and tachycardia during induction to anaes-
ence in the umbilical cord blood gas analysis parameters, thesia. In these cases, careful postnatal care must be ap-
including Base Excess reported in Heesens meta-analysis plied if respiratory depression is observed.
Noskova et al. BMC Anesthesiology (2015) 15:38 Page 7 of 7

Abbreviations 10. Orme RM, Grange CS, Ainsworth QP, Grebenik CR. General anaesthesia
BIS: Bispectral index analysis; BMI: Body Mass Index; BP: Blood pressure; using remifentanil for caesarean section in parturients with critical aortic
CPAP: Continuous positive airway pressure; ECG: Electrocardiography; stenosis: a series of four cases. Int J Obstet Anesth. 2004;13(3):1837.
EtCO2: End-tidal capnography; IU: International unit; HR: Heart rate; 11. Scott H, Bateman C, Price M. The use of remifentanil in general anaesthesia
MAP: Mean blood pressure; NIBPsyst: Systolic non-invasive blood pressure; for caesarean section in a patient with mitral valve disease. Anaesthesia.
NIBPdiast: Diastolic non-invasive blood pressure; Sat O2: Saturation; 1998;53(7):6957.
SD: Standard deviation. 12. Ltd. GG. ULTIVA 1 MG. SPC - Summary of product characteristics. http://www.
sukl.eu/modules/medication/detail.php?kod=0017711&tab=texts&lang=2: SUKL.
Competing interests State Institute for Drug Control; 2011.
PN, JB, HB, JK, JU, JS, AP, OS and PM declare no competing interests. 13. Egan TD. Pharmacokinetics and pharmacodynamics of remifentanil: an
update in the year 2000. Curr Opin Anaesthesiol. 2000;13(4):44955.
14. Kan RE, Hughes SC, Rosen MA, Kessin C, Preston PG, Lobo EP. Intravenous
Authors contributions remifentanil: placental transfer, maternal and neonatal effects.
PN and JB contributed equally to this work. All authors have made substantive Anesthesiology. 1998;88(6):146774.
intellectual contributions to the manuscript. JB and OS designed the study. PN, 15. Ngan Kee WD, Khaw KS, Ma KC, Wong AS, Lee BB, Ng FF. Maternal and
JB and HB were responsible for conducting the study and analysing the data. neonatal effects of remifentanil at induction of general anesthesia for
PN and JB wrote the manuscript. PM revised the manuscript. JK, JU, PM, JS cesarean delivery: a randomized, double-blind, controlled trial.
and AP conducted the study and helped analyse the data. All authors have Anesthesiology. 2006;104(1):1420.
seen the original study data, reviewed the data analysis, and approved the 16. Stourac P, Suchomelova H, Stodulkova M, Huser M, Krikava I, Janku P, et al.
final manuscript. Comparison of parturient - controlled remifentanil with epidural bupivacain
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The study was supported by IGA MZCR grants no. NT11324 and NT12211. 17. Heesen M, Klohr S, Hofmann T, Rossaint R, Devroe S, Straube S, et al.
Maternal and foetal effects of remifentanil for general anaesthesia in
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