Use of a high mean arterial pressure during initial resuscitation in patients with septic shock did not improve mortality at 28 or 90 days in the multicenter, open-label SEPSISPAM trial.
The Surviving Sepsis Campaign guidelines recommend targeting a mean arterial pressure (MAP) of at least 65 mm Hg, but suggest a higher target may be better for patients with atherosclerosis or previous hypertension. Retrospective data also suggest a MAP of more than 75 mm Hg may be needed to maintain kidney function during early sepsis.
For the current trial, investigators at 29 centers in France evenly randomized 776 patients to vasopressor treatment adjusted to maintain a MAP of 80-85 mm Hg (high-target group) or 65-70 mm Hg (low-target group).
The study’s primary endpoint of all-cause mortality at 28 days was 36.5% in the high-target group and 34% in the low-target group (nonsignificant hazard ratio in the high-target group, 1.07), according to data presented at the International Symposium on Intensive Care and Emergency Medicine and simultaneously published online (N. Engl. J. Med. 2014 March 18 [doi:10.1056/NEJMoa1312173]).
In addition, there were no significant differences between the high- and low-target groups in the secondary outcomes of 90-day mortality (43.7% vs. 42.3%; HR, 1.04), need for mechanical ventilation, ICU length of stay, or Sequential Organ Failure Assessment score at day 7.
Atrial fibrillation, however, was significantly more common in the high-target group than in the low-target group, at 6.7%, compared with 2.8%. This could be related to the high-target group receiving significantly higher doses of vasopressor catecholamines over a significantly longer time period, although other confounding factors cannot be ruled out, lead author Dr. Pierre Asfar of University Hospital of Angers (France), reported on behalf of SEPSISPAM investigators.
Among patients with chronic arterial hypertension, who comprised more than 40% of the study population, use of the high MAP target significantly reduced both the incidence of doubling of plasma creatinine (39% vs. 52%) and the rate of renal-replacement therapy (31.7% vs. 42.2%).
The authors noted that, although investigators were asked to treat patients to a MAP of 65-70 mm Hg in the low-target group, the observed pressures were for the most part between 70 and 75 mm Hg. The high-target group was likewise off goal, at a mean of 70 mm Hg. They also acknowledged that the lower-than-expected death rate, albeit in line with more recent trials, led to an underpowered study.
The French Ministry of Health funded the trial. Dr. Asfar reported lecture fees from LFB Biomedicaments.
Dr. Steven Q. Simpson, FCCP, comments: Since organ dysfunction in severe sepsis and septic shock is believed to be caused by inadequate perfusion, it was tempting to hypothesize that a higher MAP target could result in reduced organ dysfunction and improved survival. Unfortunately, we still are not certain that the negative result of this trial is the final word, because the average achieved MAP in both patient groups was so similar. Nevertheless, there remains, for now, no compelling reason to shoot for a higher MAP than 65 mm Hg in clinical practice.