Opioid Tolerance Blunts the Reduction in the Sevoflurane Minimum Alveolar Concentration Produced by Remifentanil in the Rat

Abstract

Background Acute opioid tolerance is a known entity leading to reduced analgesic efficacy of these drugs in the postoperative period. However, the development of acute opioid tolerance in the very short term, i.e., during the intraoperative period when opioids are being administered, has not been reported. Therefore, the aim of this study was to determine if acute opioid tolerance could develop and limit the opioid-induced reduction in the minimum alveolar concentration (MAC) for inhalant anesthetics. Methods Male Wistar rats were randomly allocated to receive two doses of remifentanil (120 and 240 microg . kg(-1) . h(-1)) under sevoflurane anesthesia, and the sevoflurane MAC was determined before and at two time intervals afterwards. In a second experiment, the low dose of remifentanil was increased once an acute opioid tolerance effect was observed. The sevoflurane MAC was determined from alveolar gas samples at the time of tail clamp. Results A remifentanil constant rate of infusion dose-dependently reduced the sevoflurane MAC from 2.4 to 1.8 +/- 0.2 vol% and from 2.3 +/- 0.3 vol% to 1.5 +/- 0.3 vol%, at the low and high doses, respectively. However, 90 min later, when the sevoflurane MAC was redetermined, the observed reduction was blunted to nearly 50% of the previous sevoflurane MAC values. When this acute opioid tolerance effect was observed with the low dose, the sevoflurane MAC reduction originally achieved could be reattained by doubling the dose; i.e., giving the high dose. Conclusions Remifentanil efficacy in reducing the sevoflurane MAC diminishes within a short term, suggesting that increased opioid doses may be required to maintain intraoperative analgesia during sevoflurane anesthesia.