Based on the results of several small trials, the safety of colloid solutions containing high-molecular-weight hydroxyethyl starch (HES) has been questioned in patients with severe sepsis. In the July 12 issue of The New England Journal of Medicine, Perner and investigators from the 6S Trial Group and the Scandinavian Critical Care Trials Group reported the results from a multicenter, blinded, stratified, parallel-group randomized trial conducted in 26 Scandinavian intensive care units from 2009 to 2011. The effects of HES (130/0.42) were compared to those of Ringer’s acetate on the composite outcomes of death or end-stage renal failure in patients with severe sepsis.
Computerized allocation was used to blindly randomize 804 patients. Treatment assignments were concealed from investigators, clinicians and patients. Adults older than 18 and fulfilling criteria for severe sepsis were enrolled. The primary outcome was death or dependence on dialysis 90 days after randomization. The study was appropriately powered to detect an absolute difference in the primary outcome, with multivariate analyses used to adjust for differences in baseline variables.
The study followed 398 patients in the HES group and 400 in the Ringer’s group (N=798 total) for at least 90 days. Baseline characteristics were similar in the two groups, with each having an incidence of acute kidney injury over 35%. The median cumulative volume of fluid received was not statistically significantly different between the two groups. More patients in the HES group received blood products and required renal replacement therapy. The primary outcome of death was higher in the HES group (relative risk [RR], 1.17; 95% confidence interval [CI], 1.01 to 1.36; P=0.03); 53% of patients in the HES group died compared to 43% in the Ringer’s group. The authors hypothesized that one explanation for the findings may be that HES is deposited in tissues, and may act as a toxic foreign body.
This well-conducted study conformed to a modified intention-to-treat protocol. Although a high number of patients with acute kidney injury were included, this comorbidity was evenly balanced with the randomized design. Patients received strikingly similar amounts of fluids, though the trial did not employ advanced hemodynamic monitoring or protocols for titrating fluids.
HES was associated with an increase in absolute risk of death (number needed to harm=13). Based on the results of this trial and previous work in this area, the use of HES should be critically examined as an option for colloid resuscitation in patients with severe sepsis. Patients with severe sepsis who received HES were at increased risk of death at 90 days, more likely to receive renal-replacement therapy, and were alive for fewer days once discharged from the hospital.
Concise Critical Appraisal is a regular feature authored by SCCM member Samuel M. Galvagno Jr., DO, PhD. Each installment highlights journal articles most relevant to the critical care practitioner.