After trial inclusion, patients were randomized to a treatment group receiving 546C88 and a control group in which patients received placebo.Only data of patients allocated selleck chemical Ixazomib to the control group (n = 358) with a mean MAP of 70 mmHg or higher (MAP targeted by the hemodynamic study protocol) during the shock period (n = 290) were included in this post hoc analysis. Sixty-eight patients were excluded because their average MAP during the shock period was below the targeted level of 70 mmHg. Characteristics of these patients are shown in Table S1 and S2 of Additional data file 1.Clinical and hemodynamic managementThroughout the study, patients were resuscitated according to a strict hemodynamic protocol and local standards of care [13].

Briefly, the hemodynamic protocol included a MAP target of 70 mmHg or higher to be reached by infusion of vasopressors (norepinephrine, dopamine, epinephrine, phenylephrine). Fluid resuscitation was guided at the discretion of the attending physician and was required to attain a pulmonary capillary occlusion pressure of 8 to 18 mmHg if cardiac index was less than 5 L/min/m2. Inotropic therapy was instituted to maintain cardiac index of more than 3 L/min/m2 [13].Data for the post hoc analysisFor the present post hoc analysis the following data were retrieved from the original trial’s database: demographic data, chronic diseases, details on the infection leading to septic shock, need for surgery or mechanical ventilation, the Simplified Acute Physiology Score (SAPS) II [14] assessed during 24 hours after intensive care unit admission and study randomization, as well as 28-day mortality. MAP values (documented at eight-hourly intervals) were averaged during the shock period (definition see below) after randomization. Based on these average MAP values, study patients were grouped into quartiles. Furthermore, the type and duration of infusion, as well as the mean dosage of catecholamine drugs during Brefeldin_A the shock period were documented.