Perioperative clonidine administration does not reduce mortality or myocardial infraction, but does increase the risk of hypotension and non-fatal cardiac arrest.

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• P J Devereaux, Daniel I Sessler, Kate Leslie, Andrea Kurz, Marko Mrkobrada, Pablo Alonso-Coello, Juan Carlos Villar, Alben Sigamani, Bruce M Biccard, Christian S Meyhoff, Joel L Parlow, Gordon Guyatt, Andrea Robinson, Amit X Garg, Reitze N Rodseth, Fernando Botto, Giovanna Lurati Buse, Denis Xavier, Matthew T V Chan, Maria Tiboni, Deborah Cook, Priya A Kumar, Patrice Forget, German Malaga, Edith Fleischmann, Mohammed Amir, John Eikelboom, Richard Mizera, David Torres, C Y Wang, Tomas Vanhelder, Pilar Paniagua, Otavio Berwanger, Sadeesh Srinathan, Michelle Graham, Laura Pasin, Yannick Le Manach, Peggy Gao, Janice Pogue, Richard Whitlock, André Lamy, Clive Kearon, Clara Chow, Shirley Pettit, Susan Chrolavicius, Salim Yusuf, and POISE-2 Investigators.
• The authors' affiliations are listed in the Appendix.
• N. Engl. J. Med. 2014 Apr 17; 370 (16): 150415131504-13.

BackgroundMarked activation of the sympathetic nervous system occurs during and after noncardiac surgery. Low-dose clonidine, which blunts central sympathetic outflow, may prevent perioperative myocardial infarction and death without inducing hemodynamic instability.MethodsWe performed a blinded, randomized trial with a 2-by-2 factorial design to allow separate evaluation of low-dose clonidine versus placebo and low-dose aspirin versus placebo in patients with, or at risk for, atherosclerotic disease who were undergoing noncardiac surgery. A total of 10,010 patients at 135 centers in 23 countries were enrolled. For the comparison of clonidine with placebo, patients were randomly assigned to receive clonidine (0.2 mg per day) or placebo just before surgery, with the study drug continued until 72 hours after surgery. The primary outcome was a composite of death or nonfatal myocardial infarction at 30 days.ResultsClonidine, as compared with placebo, did not reduce the number of primary-outcome events (367 and 339, respectively; hazard ratio with clonidine, 1.08; 95% confidence interval [CI], 0.93 to 1.26; P=0.29). Myocardial infarction occurred in 329 patients (6.6%) assigned to clonidine and in 295 patients (5.9%) assigned to placebo (hazard ratio, 1.11; 95% CI, 0.95 to 1.30; P=0.18). Significantly more patients in the clonidine group than in the placebo group had clinically important hypotension (2385 patients [47.6%] vs. 1854 patients [37.1%]; hazard ratio 1.32; 95% CI, 1.24 to 1.40; P<0.001). Clonidine, as compared with placebo, was associated with an increased rate of nonfatal cardiac arrest (0.3% [16 patients] vs. 0.1% [5 patients]; hazard ratio, 3.20; 95% CI, 1.17 to 8.73; P=0.02).ConclusionsAdministration of low-dose clonidine in patients undergoing noncardiac surgery did not reduce the rate of the composite outcome of death or nonfatal myocardial infarction; it did, however, increase the risk of clinically important hypotension and nonfatal cardiac arrest. (Funded by the Canadian Institutes of Health Research and others; POISE-2 ClinicalTrials.gov number, NCT01082874.).

This article appears in the collection: Landmark articles in Anesthesia.

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