JOURNAL ARTICLE
RANDOMIZED CONTROLLED TRIAL

A comparison of epinephrine and norepinephrine in critically ill patients

John A Myburgh, Alisa Higgins, Alina Jovanovska, Jeffrey Lipman, Naresh Ramakrishnan, John Santamaria
Intensive Care Medicine 2008, 34 (12): 2226-34
18654759

OBJECTIVE: To determine whether there was a difference between epinephrine and norepinephrine in achieving a mean arterial pressure (MAP) goal in intensive care (ICU) patients.

DESIGN: Prospective, double-blind, randomised-controlled trial.

SETTING: Four Australian university-affiliated multidisciplinary ICUs.

PATIENTS AND PARTICIPANTS: Patients who required vasopressors for any cause at randomisation. Patients with septic shock and acute circulatory failure were analysed separately.

INTERVENTIONS: Blinded infusions of epinephrine or norepinephrine to achieve a MAP >or=70 mmHg for the duration of ICU admission.

MEASUREMENTS: Primary outcome was achievement of MAP goal >24 h without vasopressors. Secondary outcomes were 28 and 90-day mortality. Two hundred and eighty patients were randomised to receive either epinephrine or norepinephrine. Median time to achieve the MAP goal was 35.1 h (interquartile range (IQR) 13.8-70.4 h) with epinephrine compared to 40.0 h (IQR 14.5-120 h) with norepinephrine (relative risk (RR) 0.88; 95% confidence interval (CI) 0.69-1.12; P = 0.26). There was no difference in the time to achieve MAP goals in the subgroups of patients with severe sepsis (n = 158; RR 0.81; 95% CI 0.59-1.12; P = 0.18) or those with acute circulatory failure (n = 192; RR 0.89; 95% CI 0.62-1.27; P = 0.49) between epinephrine and norepinephrine. Epinephrine was associated with the development of significant but transient metabolic effects that prompted the withdrawal of 18/139 (12.9%) patients from the study by attending clinicians. There was no difference in 28 and 90-day mortality.

CONCLUSIONS: Despite the development of potential drug-related effects with epinephrine, there was no difference in the achievement of a MAP goal between epinephrine and norepinephrine in a heterogenous population of ICU patients.

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