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

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Abstract

Purpose

We aimed to characterize the degree and clinical importance of bleeding in patients treated with hydroxyethyl starch (HES).

Methods

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.

Results

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.

Conclusions

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.

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Conflicts of interest

A.P. was the sponsor-investigator of the Scandinavian Starch for Severe Sepsis/Septic Shock (6S) trial and J.W. and N.H. were members of the steering committee. The 6S trial was funded by the Danish Research Council, the Rigshospitalet Research Council, and the Scandinavian Society of Anaesthesiology and Intensive Care Medicine (the ACTA Foundation). B Braun Medical delivered trial fluid to all sites free of charge. Neither the funders nor B Braun Medical had an influence on the protocol, trial conduct, data analyses, or reporting of the 6S trial. A.P. is head of research in his department, which receives research funds from Fresenius Kabi, Germany, Cosmed, Italy, and BioPorto Diagnostics, Denmark. B Braun Medical has covered his travel expenses for presenting 6S trial data at the German Anaesthetic Congress 2012. A.P. has received honoraria from Ferring Pharmaceuticals and LFB. P.W. declares that he has no conflict of interests.

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Authors and Affiliations

  1. Department of Intensive Care, Copenhagen University Hospital, Rigshospitalet, 2100, Copenhagen, Denmark

    Nicolai Haase & Anders Perner

  2. Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital, Rigshospitalet, 2100, Copenhagen, Denmark

    Jørn Wetterslev & Per Winkel

Authors
  1. Nicolai Haase
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  2. Jørn Wetterslev
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  3. Per Winkel
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  4. Anders Perner
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Corresponding author

Correspondence to Nicolai Haase.

Additional information

For the 6S Trial Group and the Scandinavian Critical Care Trials Group. 6S trial ClinicalTrials.gov number NCT00962156.

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Haase, N., Wetterslev, J., Winkel, P. et al. Bleeding and risk of death with hydroxyethyl starch in severe sepsis: post hoc analyses of a randomized clinical trial. Intensive Care Med 39, 2126–2134 (2013). https://doi.org/10.1007/s00134-013-3111-9

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