Bleeding and risk of death with hydroxyethyl starch in severe sepsis: post hoc analyses of a randomized clinical trial

We aimed to characterize the degree and clinical importance of bleeding in patients treated with hydroxyethyl starch (HES). In post hoc analyses, we examined the associations between fluid assignment, hemostatic variables, bleeding events, transfusions, and death among 798 patients with severe sepsis randomized to fluid resuscitation with HES 130/0.42 versus Ringer's acetate. We used Cox regression analysis adjusted for fluid assignment and baseline characteristics. Overall, 93 (23 %) patients assigned to HES versus 60 (15 %) patients assigned to Ringer's acetate bled in the ICU (relative risk (RR) 1.55; 95 % CI 1.16-2.08; P = 0.003). Of these, 38 and 25 (RR 1.52; 95 % CI 0.94-2.48; P = 0.09), respectively, had severe bleeding (intracranial or concomitant transfusion with three units of red blood cells). Most patients bled in the first days after randomization when most trial fluid was given. The hazards ratios for occurrence of any bleeding and severe bleeding in patients treated with HES versus Ringer's acetate were 1.70 (95 % CI 1.23-2.36; P = 0.001) and 1.55 (95 % CI 0.93-2.56; P = 0.09), respectively. The adjusted hazard ratios for death among patients with any bleeding and severe bleeding compared to those without bleeding were 1.36 (95 % CI 1.04-1.79; P = 0.03) and 1.74 (95 % CI 1.20-2.53; P = 0.004), respectively. In post hoc analyses of patient with severe sepsis, treatment with HES increased the risk of bleeding which was associated with increased risk of death. HES-induced bleeding complications may negatively affect outcome in patients with severe sepsis.