Post-anesthesia vomiting: impact of isoflurane and morphine on ferrets and musk shrews

Although partially controlled with antiemetic drugs, postoperative nausea and vomiting (PONV) continues to be a problem for many patients. Clinical research suggests that opioid analgesics and volatile anesthetics are the main triggers of PONV. The aim of this study was to develop an animal model for post-anesthesia vomiting for future studies to further determine mechanisms and preclinical drug efficacy. Ferrets (N=34) were initially used because they have served as a gold standard for emesis research. Ferrets were tested with several doses of morphine, inhaled isoflurane, and a positive control injection of cisplatin (a chemotherapy agent) to induce emesis. Musk shrews (a small animal model; N=36) were also tested for emesis with isoflurane exposure. A control injection of cisplatin produced emesis in ferrets (ip, 129.8±22.0 retches; 13.7±2.3 vomits; mean±SEM). Morphine also produced a dose-response on emesis in ferrets, with maximal responses at 0.9 mg/kg (sc, 29.6±12.6 retches; 1.8±0.9, vomits). Isoflurane exposure (2-4% for 10 min to 6h exposure) failed to induce vomiting, was not associated with an increased frequency in emesis when combined with a low dose of morphine (0.1 mg/kg, sc), and failed to produce consistent effects on food and water intake. In contrast to ferrets, musk shrews were very sensitive to isoflurane-induced emesis (0.5 to 3%, 10 min exposure; up to 11.8±2.4 emetic episodes). Overall, these results indicate that ferrets will not be useful for delineating mechanisms responsible for isoflurane-induced emesis; however, musk shrews may prove to be a model for vomiting after inhalation of volatile agents.