- Journal club critique
- Open Access
Epinephrine: Is it really the black sheep of vasoactive agents?
© BioMed Central Ltd 2010
- Published: 13 May 2010
Evidence-Based Medicine Journal Club
Edited by Eric B Milbrandt. University of Pittsburgh Department of Critical Care Medicine
Annane D, Vignon P, Renault A, Bollaert PE, Charpentier C, Martin C, Troche G, Ricard JD, Nitenberg G, Papazian L, Azoulay E, Bellissant E: Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: a randomised trial. Lancet 370:676-684 .
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.
To compare the efficacy and safety of norepinephrine plus dobutamine (whenever needed) with those of epinephrine alone in septic shock.
Prospective, multicenter, randomized, double-blind study.
19 participating intensive care units in France.
330 adult patients with septic shock. Inclusion criteria were the presence for less than 7 days of: evidence of infection; at least 2 of the 4 criteria of systemic inflammatory response syndrome (SIRS); and at least two signs of tissue hypoperfusion or organ dysfunction. Additionally, subjects had to have had to meet the three following criteria for less than 24 hours: systolic blood pressure less than 90 mm Hg or mean BP less than 70 mm Hg; administration of fluid bolus of at least 1000 mL or capillary wedge pressure between 12 and 18 mm Hg; and need for more than 15 μg per kg bodyweight per min of dopamine or any dose of epinephrine or norepinephrine. Specific exclusion criteria were established to ensure other causes of shock were excluded.
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. The secondary outcomes were survival distribution from randomization to day 90; mortality rates at day 7, 14, at discharge from intensive care and from hospital, and at day 90; systemic hemodynamics; arterial pH and lactate; SOFA score; time to hemodynamic success and time to vaspressor withdrawal. Analyses were by intention to treat.
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 hemodynamic 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 similar.
There is no evidence for a difference in efficacy and safety between epinephrine alone and norepinephrine plus dobutamine for the management of septic shock.
(ClinicalTrials.gov number, NCT00148278).
In conclusion, this study is unlikely to change current recommendations for use of vasoactive agents in septic shock. Although cardiovascular adverse effects were similar for epinephrine and norepinephrine with dobutamine, the study was not adequately powered to assess small differences in mortality. The non-significantly higher mortality for subjects receiving epinephrine highlights the need to conduct larger studies before considering epinephrine as a first line agent for management of septic shock.
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