The study by Rivers and colleagues targeted a MAP of 65 mmHg sellectchem in severe sepsis patients but the actual MAP levels were much higher [6]. Therefore, no clinical conclusions about the optimum MAP level can be drawn from this study either. Moreover, in clinical practice, individually different safety limits are often added to the prescribed targets thus resulting in relevantly higher MAP levels than originally prescribed [6-8]. Furthermore, despite the latest recommendations on MAP targets of at least 65 mmHg [2], even the most recent large clinical trials of septic shock have used higher targets and resulted in still substantially higher actual blood pressure levels during sustained administration of catecholamines [8,9].
As vasopressor and inotropic agents are, by definition, required to attain a certain MAP level in septic shock [10], the MAP goal targeted crucially determines the extent of vasopressor or inotropic support. Almost all recommendations of the Surviving Sepsis Campaign regarding the use of vasopressors and inotropes in septic shock are based on catecholamine agents [2]. Whereas it is unquestionable that catecholamines are highly effective drugs to counteract cardiovascular instability [11], they can be associated with disease-related events, particularly at higher dosages [12]. Numerous side effects of catecholamines have been reported for almost all organs and appear particularly devastating on the heart [12]. Hence, finding the lower safe MAP levels could help to reduce excess exposure to exogenous catecholamines and possibly improve outcome.
This post hoc analysis of a multicenter trial investigates the influences of MAP levels of 70 mmHg or higher and the vasopressor load on 28-day mortality and disease-related events in septic shock. Our hypothesis was that there would be no association between 28-day mortality and MAP levels of 70 mmHg or higher. Furthermore, we hypothesized that increasing vasopressor dosages may be associated with an increased risk of disease-related events and mortality in septic shock patients.Materials and methodsThe present study is a post hoc analysis of data of an international, multicenter, randomized, double-blind, placebo-controlled clinical trial that investigated the effects of the nitric oxide inhibitor 546C88 on mortality in 797 septic shock patients [13]. The dataset of the control group was provided to the authors by GlaxoSmithKline, UK, the owner of the complete original Anacetrapib database.The original trial was conducted from June 1997 to April 1998. The study protocol was approved by the local ethics committee or institutional review board of each participating center. Written informed consent was obtained from all study patients or their next of kin.