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SURGERY

Meta-Analysis of the Safety of 5-HT₃ Antagonists with Dexamethasone or Droperidol for Prevention of PONV

Professor of Anesthesiology, College of Medicine, Mayo Clinic; Consultant, Mayo Clinic Hospital, Mayo Clinic Arizona, Scottsdale, AZ

Tong J Gan, MB FRCA

Professor and Vice Chairman, Department of Anesthesiology, Duke University Medical Center Durham, NC

Reprints: Dr. Leslie, Mayo Clinic Arizona, Scottsdale, AZ 85259-5404, fax 480/342-2319, leslie.john{at}mayo.edu

BACKGROUND: Antiemetic guidelines recommend a combination of serotonin (5-HT₃) with a second agent such as droperidol or dexamethasone. Physicians have been reluctant to employ these guidelines due to concerns over the black-box warning of droperidol and safety concerns with a steroid.

OBJECTIVE: To assess the safety profiles of 5-HT₃ receptor antagonist (5-HT₃RA) monotherapy and combination therapy with a steroid or droperidol for prophylaxis of postoperative nausea and vomiting (PONV).

METHODS: A MEDLINE search of English-language reports of randomized controlled trials (RCTs) was conducted (1966-September 2005) using the key terms 5-HT₃, granisetron, ondansetron, dolasetron, tropisetron, PONV, postoperative, vomiting, emesis, and nausea. RCTs with treatment arms comparing 5-HT₃RA monotherapy (granisetron, ondansetron, dolasetron, or tropisetron) with dexamethasone or droperidol or 5-HT₃RA combinations and providing incidence data on adverse events were identified and reviewed. Within-study odds ratios with 95% confidence intervals were calculated to determine the incidence rates of all adverse events in RCTs using 5-HT₃RA monotherapy and combination therapies. Overall effect sizes for frequently reported adverse events were estimated by pooling ORs using fixed- and random-effect models.

RESULTS: Pooled ORs (OR_pooled) for adverse events with 5-HT3RA/dexamethasone versus 5-HT₃RA for PONV prophylaxis were not significant for any reported adverse events or the overall incidence of adverse events; 5-HT₃RA/droperidol versus 5-HT₃RA was significant only for decreased headache incidence (fixed model: OR_pooled 0.35; 95% CI 0.18 to 0.69). The OR_pooled for 5-HT₃RA/dexamethasone versus dexamethasone was not significant for any reported adverse events except headaches (fixed model OR_pooled 1.75; 95% CI 1.01 to 3.03), none of which was serious. OR_pooled for 5-HT₃RA/droperidol versus droperidol was not significant for any reported adverse events. Avascular necrosis, occult infection, and delayed wound healing were not observed with either combination therapy. Cardiac abnormalities were observed with 5-HT₃RA/droperidol therapy.

CONCLUSIONS: This meta-analysis indicates that either therapy has a safety profile similar to that of dexamethasone, droperidol, or 5-HT₃RA.

Key Words: dexamethasone, dolasetron, droperidol, 5-HT₃, granisetron, ondansetron, PONV

Published Online, May 2, 2006. www.theannals.com, DOI 10.1345/aph.1G381

This article has been cited by other articles:

				A. S. Habib and T. J. Gan PRO: The Food and Drug Administration Black Box Warning on Droperidol Is Not Justified Anesth. Analg., May 1, 2008; 106(5): 1414 - 1417. [Full Text] [PDF]