University of Maryland Medical Center Postoperative Nausea and Vomiting Guidelines Rationale Postoperative nausea and vomiting (PONV

) are frequent complications of surgery and anesthesia. Currently the overall incidence of postoperative nausea and vomiting is estimated to be 25-30%.1-5 PONV can lead to delayed postanesthesia care unit recovery room discharge, prolonged hospitalization, decreased patient satisfaction and increased use of resources. However, given that only 25-30% of patients actually experiences PONV, routine prophylaxis for PONV is not indicated. The decision to use antiemetic prophylaxis should be based upon risk factors for nausea and vomiting and the potential for serious sequelae from vomiting. Methods A systematic search of a medical literature database (http://www.ncbi.nih.gov/ entrez/query.fcgi) revealed several studies on PONV and risk models. Risk models that were identified and evaluated include Apfel et al, Gan et al, and Sinclair et al.4,5,7 In addition, a comparative study of six models, including those previously identified was evaluated. Furthermore, a query to the United Health System Consortium listserv elicited several strategies for the control of postoperative nausea and vomiting. The University of Kentucky has also developed guidelines for the use of postoperative nausea and vomiting. However, these guidelines were created prior to the FDA black box warning for droperidol. Risk Factors for PONV The risk factors associated with postoperative nausea and vomiting can be classified as patient or operative.1,2,3 The risk of PONV is higher in adults than in children, in women than in men, in obese patients, in patients who have high preoperative anxiety, and in patients with a history of PONV or motion sickness. The type of operative procedure can increase the rate of postoperative nausea and vomiting, such as intra-abdominal, major gynecological, orthopedic, ear-nose-throat, laparoscopic surgery, adenotonsil-lectomy, and surgery for strasbismus. Intubation may also cause nausea and vomiting. Prevention/Treatment Three 5HT3 receptor antagonists have been studied for use in patients for prevention of postoperative nausea and vomiting. Placebo-controlled trials have demonstrated efficacy with ondansetron, dolasetron and granisetron. Ondansetron can be given as a 4 mg single IV dose at the induction of anesthesia. In two trials comparing ondansetron 4 mg IV the percentage of patients with no emetic episodes were 76% and 63%, respectively. Both studies showed greater response than in the placebo group. A pooled analysis of three trials determined that 12.5 mg of dolasetron given IV was effective in the prevention of postoperative nausea and vomiting. Dolasetron 12.5 mg, 25 mg, 50 mg, and 100 mg dolasetron doses were assessed for efficacy when given

near the end of anesthesia. Efficacy was measured as no emetic episodes and no rescue medications. Complete response rates were 55%, 55%, 57% and 58% for the 12.5 mg, 25 mg, 50 mg and 100 mg doses, respectively. All four doses were statistically greater than placebo; however, there was no statistical difference between the dolasetron doses. Thus, dolasetron 12.5 mg IV was the lowest maximally effective dose. Granisetron has also been studied for its role in the prevention of nausea and vomiting in postoperative patients. In one study 868 patients were assessed for emetic control. Of these patients, 63% had no episodes of vomiting within the first 24 hours. Each of these agents is effective in the prevention of nausea and vomiting. Patients who do fail prophylactic therapy do not appear to benefit from repeat doses of the same antiemetic. In a study by Kovac et al, patients were monitored for nausea before prophylactic ondansetron dosing, at 10, 20, 30, 60 and 120 minutes following randomized dosing, at PACU discharge, and 22 hours following PACU discharge. Complete response to repeat ondansetron doses (during the two-hour period following anesthesia) versus placebo was not significantly different.6 The authors also noticed that the patients who did not respond to the original ondansetron prophylactic dose appear less likely to respond to another dose in the same drug class. As the etiology of postoperative nausea and vomiting is multifactorial, a combination of drugs from different classes for the treatment may be necessary. For patients who received no prophylactic dose or failed to respond to prophylactic 5HT3 receptor antagonists, traditional antiemetics are appropriate treatment options. These antiemetics include metoclopramide 10 mg, prochlorperazine 2.5-10 mg, and promethazine 12.5 mg.2,3 Based on the literature the following key points can be made.

• Approximately 30% of surgery patients will experience nausea/vomiting • Patient risk factors can be used to determine patients at risk for PONV • Patients who do not respond to initial 5HT3 prophylaxis require treatment with a
different class of drug Guidelines for the use of antiemetics for postoperative nausea and vomiting based on these principles are shown below. Indications Patients who receive 5HT3 receptor antagonists for the prevention of postoperative nausea and vomiting (PONV) must meet the following criteria: 1. Prior history of postoperative nausea and vomiting or motion sickness. 2. Patient is undergoing a procedure associated with high rates of postoperative nausea and vomiting (laparotomy, ENT, or gynecologic). 3. Patient is receiving highly emetogenic medications.

Patients who fail prophylactic therapy with a 5HT3 receptor antagonist do not benefit from repeat doses an emetic of the same pharmacologic class and should receive traditional antiemetics such as promethazine, metoclopramide or prochlorperazine.
References: 1. Watcha M, White P. Postoperative Nausea and Vomiting: Its etiology, treatment and prevention. Anesthesiol 1992; 77: 162-84. 2. American Society of Health Systems Pharmacists. ASHP Therapeutic Guidelines on the Pharmacologic Management of Nausea and Vomiting in Adult and Pediatric Patients Receiving Chemotherapy or Radiation Therapy or Undergoing Surgery. Am J Health-Sys Pharm 1999; 56: 72964. 3. Kovac A. Prevention and Treatment of Postoperative Nausea and Vomiting. Drugs 2000; 59(2): 21343. 4. Gan T. Postoperative Nausea and Vomiting – Can It Be Eliminated? JAMA 2002; 287(10): 12331236. 5. Sinclair D, Chung F, Mezei G. Can Postoperative Nausea and Vomiting Be Predicted? Anesthesiol 1999; 91: 109-118. 6. Kovac A, O’Connor T, Pearman M, 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 Anesthesia 1999; 11: 453-459. 7. Apfel C, Laara E, Koivuranta M, et al. A Simplified Risk Score for Predicting Postoperative Nausea and Vomiting. Anesthesiol 1999; 91(3) 693-700. 8. Apfel C, Kranke P, Eberhart H, et al. Comparison of Predictive Models for Postoperative Nausea and Vomiting. Br J of Anesthes 2000; 88(2): 234-40. 9. Philip B, McLeskey C, Chelly J. Pooled Analysis of Three Large Clinical Trials to Determine the Optimal Dose of Dolasetron Mesylate Needed to Prevent Postoperative Nausea and Vomiting. J Clin Anesthesia 2000; 12: 1-8. 10. Kovac A, Scuderi P, Boerner T, et al. Treatment of Postoperative Nausea and Vomiting with Single Intravenous Doses of Dolasetron Mesylate: A Multicenter Trial. Anesth Analg 1997; 85: 546-52. 11. Diemunsch P, D’Hollander A, Paxton L, et al. Intravenous Dolasetron Mesilate in the Prevention of Postoperative Nausea and Vomiting in Females Undergoing Gynecological Surgery. J Clin Anesthesia 1997; 9: 365-73.

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