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.
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.
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=0.31; relative risk 0.86, 95% CI 0.65-1.14).
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=0.69), at hospital discharge
(84 [52%] vs 82 [49%], p=0.51), and by day 90 (84 [52%] vs 85 [50%], p=0.73), time
to haemodynamic success (log-rank p=0.67), time to vasopressor withdrawal (log-rank
p=0.09), and time course of SOFA score. Rates of serious adverse events were also
There is no evidence for a difference in efficacy and safety between epinephrine alone
and norepinephrine plus dobutamine for the management of septic shock.