Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, USA.
Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, USA.
J Vet Pharmacol Ther. 2020 Nov;43(6):533-537. doi: 10.1111/jvp.12886. Epub 2020 Jun 17.
Different structurally related phenylpiperidine opioids exhibit different isoflurane-sparing effects in cats. Because minimum alveolar concentration (MAC) in cats is affected only by very high plasma concentrations of some phenylpiperidine opioids, we hypothesized these effects are caused by actions on nonopioid receptors. Using a prospective, randomized, crossover design, six cats were anesthetized with isoflurane, intubated, ventilated, and instrumented. Isoflurane MAC was measured in triplicate using a tail-clamp and bracketing technique. A computer-controlled intravenous infusion using prior pharmacokinetic models targeted plasma concentrations of 60 ng/ml fentanyl, 10 ng/ml sufentanil, or 500 ng/ml alfentanil, and isoflurane MAC was measured in duplicate. Next, naltrexone 0.6 mg/kg was administered to cats hourly during the opioid infusion, and isoflurane MAC was measured in duplicate. Blood was collected during MAC determinations to measure opioid concentrations. Responses were analyzed using repeated measures ANOVA with significance at p < .05. Alfentanil and sufentanil decreased isoflurane MAC by 16.4% and 6.4%, respectively, and these effects were completely reversed by naltrexone. Fentanyl had no significant effect on isoflurane MAC. Alfentanil and sufentanil modestly reduce isoflurane MAC via agonist effects on opioid receptors. However, these effects are too small to justify clinical use of phenylpiperidine opioids as single agents to reduce MAC in cats.
不同结构相关的苯哌啶类阿片类药物在猫体内表现出不同的异氟烷节省效应。由于猫的最低肺泡有效浓度(MAC)仅受某些苯哌啶类阿片类药物的极高血浆浓度影响,我们假设这些效应是由非阿片受体的作用引起的。使用前瞻性、随机、交叉设计,六只猫用异氟烷麻醉,插管、通气和仪器化。使用尾巴夹和括号技术三次重复测量异氟烷 MAC。使用先前的药代动力学模型,通过计算机控制的静脉输注将血浆浓度靶向 60ng/ml 芬太尼、10ng/ml 舒芬太尼或 500ng/ml 阿芬太尼,并且两次重复测量异氟烷 MAC。接下来,在阿片类药物输注期间每小时给猫注射纳曲酮 0.6mg/kg,并两次重复测量异氟烷 MAC。在 MAC 测定期间采集血液以测量阿片类药物浓度。使用重复测量方差分析分析反应,p<.05 时具有统计学意义。阿芬太尼和舒芬太尼分别使异氟烷 MAC 降低 16.4%和 6.4%,这些作用被纳曲酮完全逆转。芬太尼对异氟烷 MAC 无显著影响。阿芬太尼和舒芬太尼通过阿片受体的激动作用适度降低异氟烷 MAC。然而,这些作用太小,无法证明苯哌啶类阿片类药物作为单一药物在猫体内降低 MAC 的临床应用。