Elsevier

The Lancet

Volume 357, Issue 9260, 24 March 2001, Pages 911-916
The Lancet

Articles
Effects of hydroxyethylstarch and gelatin on renal function in severe sepsis: a multicentre randomised study

https://doi.org/10.1016/S0140-6736(00)04211-2Get rights and content

Summary

Background

Hydroxyethylstarch used for volume restoration in brain-dead kidney donors has been associated with impaired kidney function in the transplant recipients. We undertook a multicentre randomised study to assess the frequency of acute renal failure (ARF) in patients with severe sepsis or septic shock treated with hydroxyethylstarch or gelatin.

Methods

Adults with severe sepsis or septic shock were enrolled prospectively in three intensive-care units in France. They were randomly assigned 6% hydroxyethylstarch (200 kDa, 0·60–0·66 substitution) or 3% fluid-modified gelatin. The primary endpoint was ARF (a two-fold increase in serum creatinine from baseline or need for renal replacement therapy). Analyses were by intention to treat.

Findings

129 patients were enrolled over 18 months. Severity of illness and serum creatinine (median 143 [IQR 88–203] vs 114 [91–175] μmol/L) were similar at baseline in the hydroxyethylstarch and gelatin groups. The frequencies of ARF (27/65 [42%] vs 15/64 [23%], p=0·028) and oliguria (35/62 [56%] vs 23/63 [37%], p=0·025) and the peak serum creatinine concentration (225 [130–339] vs 169 [106–273] mol/L, p=0·04) were significantly higher in the hydroxyethylstarch group than in the gelatin group. In a multivariate analysis, risk factors for acute renal failure included mechanical ventilation (odds ratio 4·02 [95% CI 1·37–11·8], p=0·013) and use of hydroxyethylstarch (2·57 [1·13–5·83], p=0·026).

Interpretation

The use of this preparation of hydroxyethylstarch as a plasma-volume expander is an independent risk factor for ARF in patients with severe sepsis or septic shock.

Introduction

Acute renal failure (ARF) is a common complication of severe sepsis and septic shock.1, 2, 3 Correction of volume depletion is crucial to the prevention of acute tubular necrosis, which is associated with mortality of about 75% in septic shock.4 The optimum fluid restoration regimen has not been defined, and clinical practice varies.5, 6 Hydroxyethylstarches are among the most widely used compounds because their volume-expanding effect is both large and long-lasting.5 However, the use of these substances in a selected population of brain-dead kidney donors was associated with immediate impairment of renal function in the transplant recipients.7 A combination of extreme renal ischaemia and osmotic-nephrosis-like lesions seemed a plausible explanation for this finding.8 However, the potential for hydroxyethylstarches to impair rena function remains controversial.9

Patients with severe sepsis or septic shock are at risk of ischaemic renal injury, and they require large amounts of plasma-volume expanders.1, 3 Prevention of renal dysfunction in patients with sepsis is crucial, because there is no curative treatment for acute tubular necrosis. To explore the possibility that the type of expander used may influence the renal outcome, we undertook a multicentre prospective randomised study in patients with severe sepsis or septic shock in intensive-care units. Our prospectively defined hypothesis was that the frequency of ARF would be lower when gelatin rather than hydroxyethylstarch was used as the plasma-volume expander. Our clinical objective was to assist in the choice of the optimum plasma-volume expander in patients at risk of renal impairment. No subgroup or covariate analyses were planned.

Section snippets

Patients

The study took place between April, 1998, and September, 1999, in the intensive-care units of three French hospitals, two medical units in university hospitals and one medical-surgical unit in a public community hospital. The institutional review board of these hospitals approved the study protocol. Before enrolment, informed consent was obtained from the patient, if possible, or from the patient's next of kin or legal representative.

Patients aged 18 years or older were eligible if they had

Results

Of 328 patients screened, 129 were eligible and consented to take part in the study (figure 1). The study groups were similar at admission to the intensive-care unit and at study inclusion (table 1). 26 patients in the hydroxyethylstarch group and 20 in the gelatin group were enrolled more than 24 h after admission to the intensive-care unit. The main sites of infection were the lungs (44% in the hydroxyethylstarch group, 52% in the gelatin group), the abdomen (9%, 5%), and the urinary tract

Discussion

None of the currently available plasma expanders offers a clear clinical advantage over the others. Whether crystalloids or colloids are preferable and whether one colloid is better than the others have been debated for three decades. No conclusive data on outcomes and adverse events are available to settle the issue.6, 9, 17, 18 Hydroxyethylstarch, a colloid plasma substitute, has been available for more than 20 years. It is a polymer of amylopectin substituted with hydroxyethyl groups to

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