Systematic review of randomized clinical trials on the use of hydroxyethyl starch for fluid management in sepsis

Abstract

Background: Patients with sepsis typically require large resuscitation volumes, but the optimal type of fluid remains unclear. The aim of this systematic review was to evaluate current evidence on the effectiveness and safety of hydroxyethyl starch for fluid management in sepsis.

Methods: Computer searches of MEDLINE, EMBASE and the Cochrane Library were performed using search terms that included hydroxyethyl starch; hetastarch; shock, septic; sepsis; randomized controlled trials; and random allocation. Additional methods were examination of reference lists and hand searching. Randomized clinical trials comparing hydroxyethyl starch with other fluids in patients with sepsis were selected. Data were extracted on numbers of patients randomized, specific indication, fluid regimen, follow-up, endpoints, hydroxyethyl starch volume infused and duration of administration, and major study findings.

Results: Twelve randomized trials involving a total of 1062 patients were included. Ten trials (83%) were acute studies with observation periods of 5 days or less, most frequently assessing cardiorespiratory and hemodynamic variables. Two trials were designed as outcome studies with follow-up for 34 and 90 days, respectively. Hydroxyethyl starch increased the incidence of acute renal failure compared both with gelatin (odds ratio, 2.57; 95% confidence interval, 1.13-5.83) and crystalloid (odds ratio, 1.81; 95% confidence interval, 1.22-2.71). In the largest and most recent trial a trend was observed toward increased overall mortality among hydroxyethyl starch recipients (odds ratio, 1.35; 95% confidence interval, 0.94-1.95), and mortality was higher (p < 0.001) in patients receiving > 22 mL.kg-1 hydroxyethyl starch per day than lower doses.

Conclusion: Hydroxyethyl starch increases the risk of acute renal failure among patients with sepsis and may also reduce the probability of survival. While the evidence reviewed cannot necessarily be applied to other clinical indications, hydroxyethyl starch should be avoided in sepsis.

Figure 1

Randomized trial selection process.

Figure 2

Incidence of acute renal failure, use of renal replacement therapy and mortality in patients receiving HES or crystalloid. Abbreviations: CI, 95% confidence interval; HES, hydroxyethyl starch. Based on the data of Brunkhorst et al. [27].