Morphine-isoflurane interaction in dogs, swine and rhesus monkeys.

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.