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

Abstract

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 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 6 h 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 produced 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.

Pharmacogenetics of Chemotherapy-Induced Nausea and Vomiting

“…The emetic behavior in these small animals is evoked by various emetic stimuli, such as motion, anesthetic or anti cancer agents [74][75][76]. Although much progress has been made in shrew research, genetic studies of these animals were difficult because a reference genome for the shrew has not yet been determined.…”

Role of the abdominal vagus and hindbrain in inhalational anesthesia-induced vomiting

“…0% isoflurane tests consisted of 100% O 2 . Gas was provided into a cylindrical induction chamber (10 × 8.5 cm, height and diameter of cylinder) and allowed to fill for 2 min prior to placing an animal inside (Horn et al, 2012). After 10 min of exposure in the induction chamber, shrews were transferred to the testing chamber (19 × 27 cm, width and length) for 30 min.…”

“…We used musk shrews ( Suncus murinus ) in these experiments because they have a vomiting reflex, which is lacking in mice and rats (Horn et al, 2013a); this species was also used in prior studies of inhalational anesthesia-induced emesis (Gardner and Perren 1998; Horn et al, 2012). Here we used isoflurane as the emetic stimulus because this agent produces emesis in musk shrews (Horn et al, 2012) and in humans, similar in intensity to other halogenated ethers (e.g., sevoflurane, Apfel et al, 2002). c-Fos protein, a measure of neuronal activation (Sharp et al, 1993), was used in the current project to assess activation of the hindbrain areas believed to play a role in producing emesis, including the NTS and AP (Miller and Leslie 1994a; Yamada et al, 2000).…”

The mouse and the rat in surgical research. The anesthetic approach

“…Several factors can predispose to aspiration of stomach contents including pregnancy, obesity, difficult airways management, full stomach and altered gastrointestinal mobility. In theory, increased fasting times could lead to decreased injury if aspiration occurs (Allman and Wilson, 2006); however, in rodents, this is generally deemed unnecessary because the emetic reflex is absent (Horn et al, 2012) and drinking water should be accessible until one hour prior to the induction of anesthesia (Luciano andReale, 1992, Toth andGardiner, 2000). Furthermore, in small animal practice nowadays there is a trend towards reducing the duration of preanesthetic fasting, because it does not guarantee an empty stomach and it lowers gastric content pH (Savvas et al, 2009).…”