Aspirin synergistically potentiates isoflurane minimum alveolar concentration reduction produced by morphine in the rat.
BACKGROUND
The combination of opioids and nonsteroidal antiinflammatory drugs is more analgesic than the summed effect of each drug administered separately. This synergism has been used to obtain analgesia in the postoperative period at doses at which side effects are minimal. The aim of this study is to evaluate the analgesic interaction between aspirin and morphine in the rat during isoflurane anesthesia. The reduction in minimum alveolar concentration of isoflurane (MAC(ISO)) was used as an objective measure of the analgesic potency of individual drugs and their use in combination.


METHODS
Thirty-seven male Wistar rats were anesthetized with isoflurane in oxygen, and the MAC(ISO) was determined before and after the intravenous administration of aspirin and morphine. Rats were administered morphine alone (1, 3, and 10 mg/kg) or morphine (1 and 3 mg/kg) and aspirin (30 mg/kg). The MAC(ISO) was determined from alveolar gas samples at the time of tail clamp. The duration of MAC(ISO) reduction was recorded.


RESULTS
Aspirin did not have an effect on MAC(ISO), (average, 1.35+/-0.1%), whereas the combination of morphine (1 and 3 mg/kg) and aspirin (30 mg/kg) produced a reduction in the dose of morphine needed to produce the same degree of MAC(ISO) reduction. Actual MAC(ISO+drug) data were as follows: 1 mg/kg morphine, 1.17+/-0.14%; 3 mg/kg morphine, 0.98+/-0.15%; 1 mg/kg morphine plus aspirin, 0.90+/-0.04%; 10 mg/kg morphine, 0.63+/-0.13%; and 3 mg/kg morphine plus aspirin, 0.64+/-0.06%.


CONCLUSIONS
The synergistic effects of aspirin and morphine allow a clinically significant reduction in the requirements of isoflurane and isoflurane plus morphine, and these drug combinations may decrease the side effects associated with the use of single higher, equianalgesic doses of these drugs.
Gomez de Segura
I A
IA
Department of Experimental Surgery, University Hospital La Paz, Madrid, Spain. iagsegur@ctv.es
Criado
A B
AB
Santos
M
M
Tendillo
F J
FJ
D000701:Analgesics, Opioid / Q000494:pharmacology* / Q000633:toxicity; D018685:Anesthetics, Inhalation / Q000493:pharmacokinetics* / Q000633:toxicity; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000633:toxicity; D001241:Aspirin / Q000494:pharmacology* / Q000633:toxicity; D004357:Drug Synergism; D004562:Electrocardiography; D006439:Hemodynamics / Q000187:drug effects; D007530:Isoflurane / Q000493:pharmacokinetics* / Q000633:toxicity; D008297:Male; D009020:Morphine / Q000494:pharmacology* / Q000633:toxicity; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015656:Respiratory Mechanics / Q000187:drug effects
D000701:Analgesics, Opioid; D018685:Anesthetics, Inhalation; D000894:Anti-Inflammatory Agents, Non-Steroidal; D009020:Morphine; D007530:Isoflurane; D001241:Aspirin