Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock:: a randomised trial

Background International guidelines for management of septic shock recommend that dopamine or norepinephrine are preferable to epinephrine. However, no large comparative trial has yet been done. We aimed to compare the efficacy and safety of norepinephrine plus dobutamine (whenever needed) with those of epinephrine alone in septic shock. Methods This prospective, multicentre, randomised, double-blind study was done in 330 patients with septic shock admitted to one of 19 participating intensive care units in France. Participants were assigned to receive epinephrine (n=161) or norepinephrine plus dobutamine (n=169), which were titrated to maintain mean blood pressure at 70 mm, Hg or more. The primary outcome was 28-day all-cause mortality. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00148278. Findings There were no patients lost to follow-up; one patient withdrew consent after 3 days. At day 28, there were 64 (40%) deaths in the epinephrine group and 58 (34%) deaths in the norepinephrine plus dobutamine group (p=0 center dot 31; relative risk 0 center dot 86, 95% Cl 0 center dot 65-1 center dot 14). There was no significant difference between the two groups in mortality rates at discharge from intensive care (75 [47%] deaths vs 75 [44%] deaths, p=0 center dot 69), at hospital discharge (84 [52%] vs 82 [49%], p= 0 center dot 51), and by day 90 (84 [52%] vs 85 [50%], p= 0 center dot 73), time to haemodynamic success (log-rank p= 0 center dot 67), time to vasopressor withdrawal (log-rank p= 0 center dot 09), and time course of SOFA score. Rates of serious adverse events were also similar. Interpretation There is no evidence for a difference in efficacy and safety between epinephrine alone and norepinephrine plus dobutamine for the management of septic shock.