[The design of the VISEP trial. Critical appraisal].

The survey transcript of the VISEP interventional trial "Prospective randomized multicenter study on the influence of colloid vs crystalloid volume resuscitation and of intensive vs conventional insulin therapy on outcome in patients with severe sepsis and septic shock" [Clinical trials.gov. identifier: NCT00135473; study start April 2003] comprises, according to the data of the year 2003, methodological shortcomings which challenge a priori the study design and thus the resolution of the purpose of the study, i.e., "determination of the influence of the studied volume and insulin interventions on morbidity and mortality of patients with severe sepsis and septic shock". The most important points of criticism are: 1. A volume therapy with exclusively crystalloids or colloids with the chosen colloid hyperoncotic, hyperchloremic HES solution (10% hydroxyethyl starch: 10% Hemohes) or the crystalloid solution with high lactate content (Sterofundin) is neither acceptable nor practicable, even if only due to exceeding the maximum dosage as recommended by the manufacturer. 2. The fact known since the year 2001 that high molecular weight, poorly biodegradable HES preparations can present an independent risk-factor for acute kidney failure in patients with sepsis or septic shock was ignored: the exclusion criterion of a serum-creatinine value of >320 micromol/l (>3.6 mg/dl) was doubled in relation to the manufacturer's specification. 3. The hyperoncotic colloid solution used (10% Hemohes) may only be employed for a brief period: it is highly hyperchloremic and causes extravascular hypohydration with consecutive reduction of renal excretion, which together with HES is a fatal combination. 4. The crystalloid solution used, i.e., Sterofundin, which contains 45 mmol/l lactate, is contraindicated with septic shock as it increases the patient's O2 consumption, hinders lactate diagnostics as a hypoxia marker by simultaneous lactate infusion, and through increased gluconeogenesis leads to hyperglycemia, at least with diabetics. 5. It is doubtful whether an intensified insulin therapy (Actrapid) can be successful if insulin is administered simultaneously with iatrogenic hyperglycemia as a result of lactate influx. Due to these flaws in the design of the VISEP trial, the only consequence can be that the results of the survey are unusable, especially with regard to the point "HES and kidney function". Thus, any further advance presentations and interpretations should be shelved in expectation of the authors' publication of all the data, in order to begin further discussions including the flaws in study design listed here.

RCT Entities:   Population Interventions Outcomes