Remifentanil and cyclooxygenase inhibitors interactions in the minimum alveolar concentration of sevoflurane in the rat.
BACKGROUND
Intraoperative opioids reduce anaesthetic requirements and thus limit the side-effects derived from high doses of the latter. Cyclooxygenase (COX) inhibitors can also be given but it remains unclear whether they further reduce the anaesthetic requirements. Our aim was to determine whether COX inhibitors potentiate the effect of remifentanil on the minimum alveolar concentration (MAC) of sevoflurane anaesthetized rats.


METHODS
Male Wistar rats received remifentanil under sevoflurane anaesthesia, and the MAC was determined before and at two time intervals after, separated by 1.5 h. Rats were randomly allocated to receive paracetamol, metamizole, ketoprofen, or parecoxib just before one of the two studied time intervals. The MAC was determined from alveolar gas samples at the time of tail clamp. Data were analysed with an analysis of variance for repeated measures.


RESULTS
Paracetamol potentiated the MAC reduction produced by remifentanil in rats (P=0.002), whereas metamizole, ketoprofen, and parecoxib failed to produce such an effect. Furthermore, paracetamol and remifentanil produced a maximum degree of MAC reduction [35 (10)%] even when a tolerance effect to remifentanil was observed in animals given remifentanil alone (P<0.001). A tolerance to remifentanil was not observed when metamizole, ketoprofen, or parecoxib was given once the opioid infusion has been started (P>0.05).


CONCLUSIONS
COX inhibitors differentially potentiate the analgesic effect produced by remifentanil on the sevoflurane MAC, and paracetamol was the most effective drug. However, since all COX inhibitors prevented a tolerance effect to opioids once it was established, intraoperative rather than preoperative administration of these drugs is suggested.
Benito
J
J
Department of Animal Medicine and Surgery, Veterinary Faculty, Universidad Complutense, Madrid, Spain.
Aguado
D
D
Abreu
M B
MB
García-Fernández
J
J
Gómez de Segura
I A
IA
D000082:Acetaminophen / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology*; D018685:Anesthetics, Inhalation / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004347:Drug Interactions; D004357:Drug Synergism; D004361:Drug Tolerance; D008297:Male; D008738:Methyl Ethers / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010880:Piperidines / Q000494:pharmacology*; D011650:Pulmonary Alveoli / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000077208:Remifentanil; D000077149:Sevoflurane
D000701:Analgesics, Opioid; D018685:Anesthetics, Inhalation; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D008738:Methyl Ethers; D010880:Piperidines; D000082:Acetaminophen; D000077149:Sevoflurane; D000077208:Remifentanil