SEPSISPAM: effects of two levels of blood pressure on survival in patients with septic shock

Abstract

The treatment of hemodynamic failure in patients with septic shock is based on fluid resuscitation and vasoconstrictors like norepinephrine. Its objective is to achieve a sufficient mean arterial pressure (MAP) to maintain adequate tissue perfusion pressure and thus ensure tissue oxygenation. Current recommendations suggest maintaining MAP ≥ 65 mmHg, but as available data are sparse, the optimal MAP level to achieve is not defined in these recommendations, particularly in relation to patient characteristics (i.e. age, cardiovascular diseases). Only five prospective studies have compared the effect of increasing MAP using norepinephrine titration. The benefit of this strategy was not demonstrated, probably because these studies have included a small number of patients. However, in retrospective studies, mortality does not seem to be correlated with the level of MAP, except for the lowest values. Moreover, in large clinical trials assessing different vasopressor treatments, MAP levels of 75 to 90 mmHg are often achieved, without significant adverse effects. Finally, the effect of incremental infusion of norepinephrine has never been evaluated during the early phase of septic shock. Altogether, these data suggest that early administration of norepinephrine to achieve a MAP level between 80 and 85 mmHg may reduce mortality. This hypothesis has never been evaluated to date, and this is the objective of the SEPSIS-PAM multicenter and randomized French study. The primary endpoint will be the mortality rate at day 28. Two early resuscitation strategies based on two different MAP levels will be compared: a control group with a MAP level objective of 65 to 70 mmHg, in accordance with current recommendations, and an interventional group with a MAP target of 80 to 85 mmHg achieved with the optimization of vascular challenge and norepinephrine titration before the first six hours following the diagnosis of septic shock. This trial began in March 2010 in 29 French ICU centers and will include 800 patients.