Patient-centered outcomes and trials of hydroxyethyl starch

Meybohm and colleagues [1] propose that hydroxyethyl starch (HES) may be used safely in hypovolemicpatients by applying a clinical algorithm and by restricting the doseadministered.

The authors question the validity of the results of the two trials that constituteover 60% of current data [2, 3] and misleadingly state that in the Crystalloid vs. Hydroxyethyl StarchTrial (CHEST), HES administration did not increase the use of renal replacementtherapy by referring to the adjusted analyses that were published in the electronicsupplement [2]. The unadjusted analysis was pre-specified as the principal outcomemeasure and is the appropriate measure to influence clinical practice. The authorsalso ignore the consistent signal of harm associated with HES, specificallyincreased mortality and use of renal replacement therapy that is evident despitewide variations in aggregate doses of HES in the three major clinical trials: 70ml/kg in the Efficacy of Volume Substitution and Insulin Therapy in Severe Sepsistrial [4], 44 ml/kg in the Scandinavian Starch for Severe Sepsis/Septic Shock study [3], and 5 ml/kg in CHEST. Meybohm and colleagues make no comment thatadverse effects of HES represent an overall toxic effect caused by increased tissueaccumulation that is recognised as a dose-dependent, generic HES effect [5].

The ‘presumably correct indication’ and the algorithm they propose havenot been validated nor are they supported by any credible clinical evidence. Theirproposed algorithm and target population must be evaluated in rigorously conductedrandomized controlled trials before being considered for adoption into clinicalpractice. Given the consistent evidence that HES is nephrotoxic and may increasemortality [6], it is doubtful that institutional ethics committees would approve such atrial, or that informed patients would consent to participate.