Two recent studies reporting adverse effects selleck chemical Axitinib of catecholamine vasopressors on organ function [23] and mortality [24] in septic shock support our results. Furthermore, the findings of the present analysis are in line with earlier data suggesting harmful effects of excess catecholamine exposition in general critically ill patient populations. For example, Boldt and colleagues showed that circulating plasma levels of catecholamines were higher in non-surviving when compared with surviving surgical intensive care unit patients [25]. A randomized trial that investigated the outcome effects of supranormal oxygen delivery in a diverse group of critically ill patients reported higher in-hospital mortality in patients receiving liberal catecholamine therapy than in control patients exposed to standard care [26].

Important limitations must be considered when interpreting the results of this study. First, and probably most importantly, mean values of punctually instead of continuously recorded MAPs were analysed. Thus, the true course of MAP may have been under- or over-estimated. Additionally, it is possible that some patients changed between MAP quartiles during the shock period but were eventually grouped into one quartile based on their average MAP. Second, as the original study was performed in the late 1990s the definition of some disease-related events does not correspond to current recommendations. This is particularly relevant for the definition of renal failure [27] and disseminated intravascular coagulation [28], which has recently been newly defined based on international consensus.

Furthermore, the occurrence of disease-related events was documented during the intensive care unit stay after study randomization. Although more than half of non-surviving study patients did not achieve shock resolution and developed disease-related events during the evaluated shock period, it is possible that some disease-related events occurred either after shock resolution or during a renewed shock episode during which MAP and the mean vasopressor load were not evaluated. When drawing clinical conclusions from our results caution is warranted because the MAP quartiles analysed were retrospectively defined and can not be considered as treatment goals. Finally, it must be considered that this post hoc analysis was performed in an uncontrolled patient cohort, and its results must not be considered to have the same validity as those of a randomized, controlled trial.

ConclusionsMAP GSK-3 levels of 70 mmHg or higher do not appear to be associated with improved survival in septic shock. However, augmenting vasopressor dosages to elevate MAP to more than 70 mmHg may increase mortality. Future trials are needed to identify the lowest acceptable MAP level to ensure tissue perfusion and avoid unnecessary high catecholamine infusions.