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LETTER TO THE EDITOR

Clinical Experience with Small-Dose Granisetron and Dexamethasone for Prevention of Postoperative Nausea and Vomiting

Duke University Medical Center, Durham, NC, gan00001{at}mc.duke.edu, Roche Laboratories, Nutley, NJ, Brigham & Women’s Hospital, Boston, MA

In Response:

We appreciate Dr. Neustein’s letter (1) in response to our recent study comparing granisetron plus dexamethasone to ondansetron plus dexamethasone (2). The use of combination antiemetics to prevent postoperative nausea and vomiting (PONV) in high-risk patients is well established (3,4). A recent large, multicenter study found that combining various antiemetics, for example ondansetron, dexamethasone, and droperidol, with propofol as the maintenance anesthetic was an effective prophylactic strategy. Each antiemetic reduces the relative risk of PONV by 20% to 25%; the effect is additive when these antiemetics are used in combination (5).

When a patient does not respond to an adequate dose of a 5-HT₃ antagonist, evidence suggests that using an antiemetic from a different class is more appropriate than repeating the same dose (4). Kovac et al. (6), in a large multicenter study, found no advantage to administering ondansetron 4 mg again, after failure of an identical prophylactic dose. In turn, if a 5-HT₃ antagonist plus dexamethasone fails, then one should treat the patient with a drug from another class, for instance droperidol or promethazine (7).

In a pilot multicenter, randomized, placebo-controlled study, D’Angelo et al. (8) compared granisetron 0.1 mg, granisetron 0.2 mg, granisetron 0.3 mg, and placebo—each administered as a single IV injection approximately 15 min before the end of surgery. The investigators demonstrated that all three granisetron doses were more effective than a placebo in preventing PONV in the first 6 h after abdominal hysterectomy. However, this pilot study was not specifically designed to have adequate sample size to identify a dose-response relationship.

In summary, for patients at high-risk for PONV, one should combine antiemetics from different classes.

References

1. Neustein SM. Clinical experience with small-dose granisetron and dexamethasone for prevention of postoperative nausea and vomiting. Anesth Analg 2006;103:510–1.[Free Full Text]
2. Gan TJ, Coop A, Philip BK, Kytril Study Groups. A randomized double-blind study of granisetron plus dexamethasone versus ondansetron plus dexamethasone to prevent postoperative nausea and vomiting in patients undergoing abdominal hysterectomy. Anesth Analg 2005;101:1323–9.[Abstract/Free Full Text]
3. Gan TJ. Postoperative nausea and vomiting: can it be eliminated? JAMA 2002;287:1233–6.[Free Full Text]
4. Gan TJ, Meyer T, Apfel CC, et al. Consensus guidelines for managing postoperative nausea and vomiting. Anesth Analg 2003;97:62–71.[Abstract/Free Full Text]
5. Apfel CC, Korttila K, Abdalla M, et al. A factorial trial of six interventions for the prevention of postoperative nausea and vomiting. N Engl J Med 2004;350:2441–51.[Abstract/Free Full Text]
6. Kovac AL, O’Connor TA, Pearman MH, et al. Efficacy of repeat intravenous dosing of ondansetron in controlling postoperative nausea and vomiting: a randomized, double-blind, placebo-controlled multicenter trial. J Clin Anesth 1999;11:453–9.[Web of Science][Medline]
7. Kreisler NS, Spiekermann BF, Ascari CM, et al. Small-dose droperidol effectively reduces nausea in a general surgical adult patient population. Anesth Analg 2000;91:1256–61.[Abstract/Free Full Text]
8. D’Angelo R, Philip B, Gan TJ, et al. A randomized, double-blind, close-ranging, pilot study of intravenous granisetron in the prevention of postoperative nausea and vomiting in patients abdominal hysterectomy. Euro J Anaesthesiol 2005; 22:774–9.

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