RENAL FAILURE

Vol. 25, No. 5, pp. 855–862, 2003

CLINICAL STUDY

Continuous Renal Replacement Therapy (CRRT) or

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Intermittent Hemodialysis (IHD)—What Is the

Procedure of Choice in Critically Ill Patients?

Vladimir Gašparović,* Ina Filipović-Grčić, Marijan Merkler,

and Zoran Pišl

Department of Emergency and Intensive Care Medicine,

Zagreb, Croatia
For personal use only.

ABSTRACT

Although at present there is no prospective randomized study which could show

significantly better survival of patients on continuous procedures, the majority of
intensivists advocate this technique of renal function replacement due to generally
accepted opinion that it has less effect on circulation of already hemodynamically
unstable patients. In our prospective randomized study with 104 patients, we also
did not observe any difference in 28 days survival, in total survival, as well as in
circulatory instability between two treatment modalities. Even in subgroup of 80
patients with sepsis and septic shock there were no difference in survival. Sepsis
was the underlying disorder in 52 and septic shock in 28 patients out of 104
patients analyzed in this study
Our prospective randomized study did not show a statistically significant dif-
ference between the two methods of renal replacement therapy. Survival rates
were not affected and neither was the occurrence of hemodynamic instability.
We believe that both methods are complementary; IHD for faster elimination
of electrolytes and waste products elimination, CRRT for regulation of higher
calories requirements and for hemodynamically unstable patients. The expecta-
tions that one method is superior to the other in the term of better survival have

*Correspondence: Dr. Vladimir Gašparović, Internal Klinik, Rebro, 10 000 Zagreb,

Kišpatićeva 12, Croatia; E-mail: vgasparovic111948@yahoo.com.

855

DOI: 10.1081/JDI-120024300 0886-022X (Print); 1525-6049 (Online)

Copyright & 2003 by Marcel Dekker, Inc. www.dekker.com
 856 Gašparović et al.

not been corroborated by the current data available in the literature. The choice
of the method should be individualized. ARF, which is an integral part of MOF,
is a problem frequently encountered in critically ill patient treated in the ICU, but
outcome of these patients depends closely on the control of basic event.
Evaluation of each of the supportive procedures is therefore hindered by the
fact that the underlying disease has the crucial effect on survival and the type
of supportive procedure less so.

Key Words: Continuous renal replacement therapy (CRRT); Intermittent

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hemodialysis (IHD); Acute renal failure (ARF).

INTRODUCTION

Acute renal failure as a rule is only a part of the problem in patients with
multiple organ failure. All supportive procedures are in the function of maintenance
of impaired organ function, and they mostly aid in overcoming acute disorders in
critically ill. The most important condition for a favorable outcome is control of the
For personal use only.

underlying disease, mainly sepsis.[1,2] In the light of this knowledge the place of
intermittent hemodialysis procedures should be viewed, compared to continuous
hemofiltration procedures and their effect on the survival of critically ill.

PATIENTS AND METHODS

Eighteen months ago we started a prospective randomized study on patients

with acute renal failure, always in conjunction with multiple organ failure with the
aim to evaluate the place, role, and problems inherent in the mentioned extra-
corporeal procedures. The study included 104 patients hospitalized in general
surgical, cardiac surgical, and medical intensive care units. Table l presents different
etiology of ARF/MOF in our study. Tables 2–5 present other results of this study.

Table 1. Etiology of multiple organ failure and extracorporeal procedure (ECP).

Dg IHD CRRT Totals

Sepsis 23 29 52
Septic shock 14 14 28
Sy. renopulmonale 4 1 5
Febris hemorrhagica 4 3 7
Rhabdomyolysis 3 2 5
Cardiomyopathia ishemica 4 3 7
All groups 52 52 104

Most of our patients with multiple organ failure (MOF) had sepsis and septic
shock as a etiologic event.
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CRRT and IHD

Table 2. Severity scores in patients with mof on ihd/crrt (mean
SD).

ECP APACHE II0 MARSHAL0 SOFA0 APACHE II1 MARSHAL1 SOFA1 APACHE II2 MARSHAL2 SOFA2

IHD(N) 20.3  8.4 (52) 8.8±4.0 (52) 9.8±4.7 (52) 16.6  6.6 (48) 7.7  5.1 (48) 8.4  4.7 (48) 16.3  7.3 (44) 7.3  3.8 (44) 7.8  4.2 (44)
CRRT(N) 21.9  8.8 (52) 10.1±3.7 (52) 11.0±3.9 (52) 19.1  7.9 (46) 9.1  3.6 (46) 9.9  3.8 (46) 18.6  8.0 (43) 8.8  3.9 (43) 9.7  4.1 (43)
P NS NS NS NS NS NS NS NS NS
ECP APACHE II3 MARSHAL3 SOFA3 APACHE II7 MARSHAL7 SOFA7 APACHE II14 MARSHAL14 SOFA14
IHD(N) 16.4  7.5 (44) 7.1±3.8 (44) 7.7±4.6 (44) 15.5  8.2 (35) 6.1  3.9 (35) 6.6  4.3 (35) 13.9  7.7 (24) 5.4  3.7 (24) 5.9  4.1 (24)
CRRT(N) 18.3  8.2 (39) 8.1±3.7 (39) 9.3±7.2 (39) 18.2  8.5 (31) 7.3  4.1 (31) 8.5  4.6 (31) 14.7  6.9 (19) 6.0  4.1 (19) 7.3  4.7 (19)
P NS NS NS NS NS NS NS NS NS
ECP APACHE II21 MARSHAL21 SOFA21
IHD(N) 13.0  6.4 (17) 5.1±3.2 (17) 5.4±3.2 (17)
CRRT(N) 12.7  8.7 (15) 5.2±4.4 (15) 6.4±5.1 (15)
P NS NS NS

In our randomized prospective study there were no differences in scoring (APACHE II, MARSHAL, SOFA) between two groups on extra-
corporeal procedure (ECP).
857
 858 Gašparović et al.

Table 3. Survival depends on extracorporeal procedure.

ECP Survivors Dead Total

IHD 21 31 52
CRRT 15 37 52
36 68 104

P ¼ NS.
There was no difference in total survival rate between two groups.
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Table 4. Blood pressure instability (>10 mmHg) depends on procedure.

ECP N Rank sum p

HD 52 2505.0
HF 52 2955.0
Total 104 NS

There was no difference in total number of blood pressure drops between

two groups.
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Table 5. Survival of hemofiltration patients depends on exchanged

volume.

ECP Survivors Dead Total

HF low 9 22 31
HF high 6 15 21
15 37 52
p NS

There was no difference in total survival rate between two groups.

Acute renal failure is defined as a clinical syndrome characterized by a threefold

increase in creatinine, hyperkalemia with serum potassium over 5.5 mmol/L, base
deficit BE > 6, or at least two of these parameters. Multiple organ failure is a
clinical syndrome of organ systems failure requiring appropriate replacement of
the function (artificial ventilation in respiratory failure, vasoactive therapy in hypo-
tension). Intermittent hemodialysis (IHD) was defined as a procedure lasting 3–4 h
with blood flow rate 200–250 mL/min and dialysate flow rate 500 mL/min, using
biocompatible polysulfone membrane with surface area 1.4–1.6 m2. Hemodialysis
was performed every day, most frequently without heparin utilization.
By means of continuous renal replacement therapy—continuous venovenous
hemofiltration (CVVH) 18 mL/kg/h were replaced in the first 33 patients (low
volume hemofiltration), and subsequently 35 mL/kg/h (high volume hemofiltration).
The membrane employed for CVVH was of polysulfone. Systemic heparin was used
in case of problems with premature clotting in the extracorporeal procedure.
 CRRT and IHD 859

Standard biochemical and hematologic parameters were followed daily.

Severity of an organ function failure was defined with three different scoring
systems: APACHE II, Marshall score, and SOFA score.[3–5] Mean values for patients
were marked with the index 0 for the day of admission, 1 for 24 h later, 2 for 48 h
later, 3 for 72 h later, 7 for a week later, 14 for two weeks later, and 21 for three
weeks later. The tables show the results of the prospective randomized study.

RESULTS
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All results are presented in Tables 1–5.

DISCUSSION

Multiple organ failure is a clinical syndrome burdened with a high mortality

rate. It is well known that a higher number of failing organs result in an increased
death rate. One organ failure results in the death rate of 25–30%, two organs
50–60%, three organs 80% or more, and four organs 100%. As pointed out in the
introduction, evaluation of the role of a supportive procedure is hindered by the fact
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that the principal indicator of the outcome is the underlying disease itself. Since
sepsis is the most frequent cause of multiple organ failure in surgical as well
as medical intensive care, only control over sepsis allows evaluation of the
procedure of extracorporeal circulation. In current literature there is no prospective
randomized study, which showed better patient survival on continuous in relation
to intermittent procedures. Although at present there is no prospective randomized
study which could show significantly better survival of patients on continuous
procedures, the majority of intensivists advocate this technique of renal function
replacement due to generally accepted opinion that it has less effect on circulation
of already hemodynamically unstable patients.[6–8] In oral communications it is not
infrequent to hear that this procedure is ‘‘probably better.’’ In order to answer the
question what is the procedure of choice in critically ill patients, one must eliminate
certain forms of intermittent hemodialysis, which by themselves carry frequent
problems during extracorporeal circulation. Since the machines with controlled
ultrafiltration and bicarbonate dialysate imply smaller incidence of complications,
only these devices can be considered comparable with continuous hemofiltration.
Meta-analysis of a number of studies, which compared biocompatible to bioin-
compatible membranes gave advantage to biocompatible membrane, we used
machines with controlled ultrafiltration, bicarbonate dialysate solution, and
biocompatible polysulfone membrane in our study. It is indisputable that hemo-
dialysis can affect hyperkalemia and volume excess faster, and it solves more rapidly
the acute threat of electrolyte and water derangements. Weekly dose of hemodialysis
in chronic renal failure is defined, mainly by the quotient Kt/V>1.2. The required
dose of extracorporeal elimination in acute renal failure is not defined well enough,
however it does not essentially differ from the said quotient. The length of inter-
mittent procedure is also not well defined. It mostly lasts 3–4 h, but some used
prolonged intermittent dialysis lasting 9 h and did not obtain different survival
 860 Gašparović et al.

compared to continuous procedures. It has been well established that cytokines

affect the severity of the septic process. According to some recent publications
CRRT might play a significant role in the elimination of pro-inflammatory
cytokines, in addition to clearing nitrogen products as well as other medium and
large sized molecules. The possible removal of proinflammatory mediators may
permit a blockade of systemic inflammation, a modulation of the altered immune
response in these patients, and it may lead to a partial or total restoration of the lost
homeostasis.[9–13] A statistically significant reduction in heart rate, increase in
systemic vascular resistance an systolic blood pressure were documented in the
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group of patients who underwent CRRT.[14–16] On the other side, according meta
analysis in published and unpublished trials in any language, CRRT in comparison
to IHD does not improve survival or renal recovery in unselected critically ill
patients with ARF.[17] On the other hand, continuous procedure of hemofiltration
has less effect on the stability of circulation. Comparison of value of intermittent
hemodialysis with continuous procedures of hemofiltration should therefore be
considered in the light of the mentioned fact. In our prospective randomized study
with 104 patients, we also did not observe any difference in 28 days survival, in total
survival, as well as in circulatory instability between two treatment modalities. Even
in subgroup of 80 patients with sepsis and septic shock there were no difference in
survival. Sepsis was the underlying disorder in 52 and septic shock in 28 patients out
For personal use only.

of 104 patients analyzed in this study. The statistical evaluation of the obtained data
revealed no significant difference in patient outcome between the two observed
methods of renal replacement therapy. This data is corroborated by the available
data in the literature. The number of hypotensive attacks defined by blood pressure
fall over 10 mmHg in our group of patients on continuous procedures was not
significantly smaller. However, there is a randomized prospective study, which
showed better survival with high volume hemofiltration 35 mL/kg/h compared to
low volume ultrafiltration in which 25 L of volume are replaced in 24 h.[18] We were
not able to validate this difference. When choosing the method of extracorporeal
circulation, despite the fact that prospective randomized studies did not prove better
survival using one of them, intensivists are advised to use the method with less side
effects, and of greater benefit in a given case. Our prospective randomized study did
not show a statistically significant difference between the two methods of renal
replacement therapy. Survival rates and the occurrence of hemodynamic instability
were not affected. We therefore believe that the management of the underlying
condition outweighs the choice of the procedure of renal replacement. Currently,
the use of these methods in the world varies. Almost all intensive care units in
England utilize continuous methods. In the USA intermittent procedures are used
more commonly than continuous ones, which is similar to the situation presently
found in Croatia. We believe that both methods are complementary; IHD for faster
elimination of electrolytes and waste products elimination, CRRT for regulation
of higher calories requirements and for hemodynamically unstable patients. The
expectation that one method is superior to the other in terms of better survival
have not been corroborated by the current data available in the literature. The
choice of the method should be individualized because both methods have
advantages and disadvantages. ARF, which is an integral part of MOF, is a problem
frequently encountered in critically ill patient treated in the ICU, but outcome of
 CRRT and IHD 861

these patients depends closely on the control of basic event. Evaluation of each of the
supportive procedures is therefore hindered by the fact that the underlying disease
has the crucial effect on survival and the type of supportive procedure less so. It is
our opinion that these patients will more likely be treated by continuous methods by
appropriately trained ICU personnel.

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