%0 Journal Article
%T Translational research in sepsis - an ultimate challenge?
%A Tim G Kampmeier
%A Christian Ertmer
%A Sebastian Rehberg
%J Experimental & Translational Stroke Medicine
%D 2011
%I BioMed Central
%R 10.1186/2040-7378-3-14
%X In the era of evidence-based medicine, large, randomized, controlled, multicenter studies (together with meta-analyses) represent the "summit of evidence" [1]. In contrast to specialties like cardiology, the majority of randomized, controlled trials (RCT) in critical care medicine, however, have failed to demonstrate a survival benefit [2]; notably, despite encouraging results from experimental and phase-II clinical studies. The difficulty in translating our theoretical knowledge into successful multicenter RCTs and subsequent treatment recommendations may represent one reason, why the mortality of septic shock still averages between 40-60% [3], although the understanding of the underlying pathophysiology has considerably increased and international guidelines have widely been implemented.Just two examples for this dilemma: In 1995, Hebertson et al. described an attenuation of the decrease in left-ventricular contractility by tumor necrosis factor-alpha-(TNF¦Á) antibodies in endotoxemic pigs [4]. In the same year, Givner and colleagues reported a reduction in mortality of newborn rats with group B streptococcal disease due to the use of TNF¦Á-antibodies [5]. The subsequent pilot study on nine patients with septic shock revealed no side effects concerning the use of TNF¦Á-antibodies as an adjunct therapy regardless of the administered dose [6]. Only a few months later, the RCT with 141 patients receiving either placebo or TNF-receptor:Fc fusion protein in three different dosing regimens not only failed to show any survival benefit, but even suggested an increase in mortality associated with higher doses [7].The "VAsopressin and Septic Shock Trial" (VASST) represents another, more recent example. Whereas there was consistent and extensive evidence from numerous experimental [8,9] as well as small clinical trials [10-12] about the efficacy and benefit of a supplementary low-dose infusion of arginine vasopressin (AVP) on catecholamine requirements and several other outcome
%K randomized controlled trials
%K sepsis
%K septic shock
%K translational research
%U http://www.etsmjournal.com/content/3/1/14