Combination Antiemetics for Postoperative Nausea


Am Fam Physician. 2004 Oct 1;70(7):1348-1351.

Clinical Question: What is the best approach for the prevention and treatment of post-operative nausea and vomiting?

Setting: Inpatient (any location)

Study Design: Randomized controlled trial (single-blinded)

Allocation to Groups: Concealed

Synopsis: This well-designed study examined the possible permutations of six approaches to reducing postoperative nausea and vomiting. The first three interventions involved the anesthesia itself: (1) propofol or a volatile anesthetic; (2) nitrogen or nitrous oxide; and (3) remifentanil or fentanyl. The three other interventions occurred postoperatively: (1) 4 mg of ondansetron or no ondansetron; (2) 4 mg of dexamethasone or no dexamethasone; and (3) 1.25 mg of droperidol or no droperidol. There were 64 different combinations of these six interventions.

Of the 5,199 patients who were randomized initially, outcome data were incomplete for 38 patients, and because some centers did not execute the protocol correctly, only 4,086 patients were assigned randomly to the full complement of 64 protocols. The remaining patients could be evaluated only for the following interventions: ondansetron, dexamethasone, droperidol, and propofol. All of the patients were adults undergoing general anesthesia expected to last at least one hour, and all were at higher-than-average risk for postoperative nausea and vomiting on the basis of a risk factor score that included previous experience following surgery, age, sex, smoking, and history of motion sickness. The average age of patients was not given, 81.5 percent were women, 81.2 percent were nonsmokers, and more than one half had a history of postoperative nausea and vomiting. Allocation was concealed, and although treating physicians and patients were not blinded, the outcome assessors were.

Overall, 34 percent of patients had postoperative nausea and vomiting. The two-way comparisons showed that all of the interventions but one (remifentanil instead of fentanyl) reduced the likelihood of postoperative nausea and vomiting, with absolute risk reductions of 4.3 percent for nitrogen instead of nitrous oxide, 7.3 percent for propofol instead of inhaled anesthetic, and approximately 10 percent for each of the three antiemetics. Unlike many situations in medicine, more interventions were definitely better. The likelihood of postoperative nausea and vomiting was 52 percent without antiemetics, 37 percent with one antiemetic, 28 percent with any combination of two antiemetics, and 22 percent when all three were given. Regarding anesthetic agents, the best results were in patients given propofol and nitrogen (29 percent experienced postoperative nausea and vomiting), and the worst results were among patients given a volatile anesthetic and nitrous oxide (41 percent experienced postoperative nausea and vomiting).

Bottom Line: This study provides guidance regarding the selection of anesthetic and antiemetic agents. Use of several antiemetics concurrently is more effective than use of an individual agent, although this is probably only cost-effective in patients at particularly high risk for postoperative nausea and vomiting. In patients at lower risk, dexamethasone in a dose of 4 mg is a good choice because of its low cost and safety. The use of remifentanil instead of fentanyl did not improve outcomes. (Level of Evidence: 1b)

Study Reference:

Apfel CC, et al., for the IMPACT Investigators. A factorial trial of six interventions for the prevention of postoperative nausea and vomiting. N Engl J Med. June 10, 2004;350:2441–51.

Used with permission from Eebell M. Combinations of antiemetics better for post-op nausea, vomiting. Accessed online July 27, 2004, at: http://www.InfoPOEMs.com.



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