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Morphine-isoflurane interaction in dogs, swine and rhesus monkeys
E P Steffey1, J D Baggot, J H Eisele
1Department of Surgery, School of Veterinary Medicine, University of California, Davis 95616.
Abstract:
In monkeys, dogs and swine (six each) we tested the reduction of the isoflurane MAC (minimal alveolar concentration) produced by 2 mg.kg-1 morphine intravenously (i.v.) and the concurrent effect on PCO2 with spontaneous ventilation. MAC fell to a minimum of 55% of control at 53 min in monkeys, 50% at 38 min in dogs and 13% at 33 min in swine. PaCO2 rose at constant MAC with morphine to 55-60 mmHg, but did not fall over the next several hours despite the decline of plasma morphine concentration, and the resulting needed rise in isoflurane concentration to keep the anaesthesia depth at 1 MAC. After isoflurane concentration had returned to pre-morphine control levels, naloxone immediately reduced PaCO2 to or below control level. Morphine pharmacokinetics in the three species studied conformed to a two-compartment model.
Insights
Morphine significantly reduces the minimum alveolar concentration (MAC) of isoflurane anesthesia in monkeys, dogs, and swine. It also causes a sustained increase in PaCO2, which is reversed by naloxone.
Area of Science:
- Veterinary Anesthesiology
- Pharmacology
Background:
- Isoflurane is a common inhalation anesthetic.
- Morphine is an opioid analgesic with known anesthetic-sparing effects.
- Understanding species-specific responses to anesthetic combinations is crucial for safe practice.
Purpose of the Study:
- To evaluate the anesthetic-sparing effect of morphine on isoflurane MAC in different species.
- To investigate the impact of morphine administration on PaCO2 during spontaneous ventilation.
- To assess the reversibility of morphine-induced respiratory effects with naloxone.
Main Methods:
- Three species (monkeys, dogs, swine) were administered intravenous morphine (2 mg/kg).
- The reduction in isoflurane MAC and changes in PaCO2 were monitored.
- Pharmacokinetic analysis and naloxone reversal were performed.
Main Results:
- Morphine reduced isoflurane MAC by a minimum of 55% in monkeys, 50% in dogs, and 13% in swine.
- PaCO2 increased to 55-60 mmHg with morphine and remained elevated despite falling plasma concentrations.
- Naloxone administration promptly reversed the elevated PaCO2.
Conclusions:
- Morphine exhibits significant anesthetic-sparing effects on isoflurane across species, with varying potency.
- Morphine causes a persistent hypercapnic effect independent of plasma concentration, suggesting central respiratory depression.
- Naloxone effectively antagonizes morphine-induced hypercapnia, highlighting opioid receptor involvement.