Abstract

We aimed to detail the effects of hydroxyethyl starch (HES) vs. Ringer's on kidney function including the interaction with mortality in post-hoc analyses as resuscitation with HES 130/0.42 increased mortality in the Scandinavian Starch for Severe Sepsis/Septic Shock (6S) trial. In all 798 randomised patients, we assessed the incidence and effect on mortality of acute kidney injury (AKI) in the HES vs. Ringer's acetate groups using the Kidney Disease: Improving Global Outcome criteria. We also assessed the intervention effect on time to and duration of renal replacement therapy (RRT). At baseline, the intervention groups were similar. The maximal AKI stage was higher in the HES vs. Ringer's group within the first 5 days after randomisation (P = 0.03), the average difference being 0.2 points (P < 0.01). An increase in AKI stage was associated with mortality (hazard ratio (HR) 1.35; 95% CI 1.22 to 1.49; P < 0.01). Significantly, more patients in the HES group received RRT within the first 5 days (P = 0.01), and the time to initiation of RRT was also shorter compared with the Ringer's group (HR 1.40; 95% CI 1.01-1.93; P = 0.04). The intervention effect of HES on mortality was reduced when adjusting for AKI stage as a time-dependent covariate (P = 0.15). In patients with severe sepsis, HES appeared to increase the rate of severe AKI and use of RRT within the first 5 days. The increased mortality observed with HES may have been partly mediated through acute kidney impairment.

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