Large Concentrations of Nitrous Oxide Decrease the Isoflurane Minimum Alveolar Concentration Sparing Effect of Morphine in the Rat

Many adjuvant drugs have demonstrated anesthetic-sparing properties when combined with volatile anesthetics. Nitrous oxide is combined with volatile anesthetics to reduce the concentrations of volatile anesthetics required to produce anesthesia. Analgesic doses of opioids clearly reduce the requirement for inhaled anesthetics in both human patients and experimental animals. We performed this study to determine whether the combination of nitrous oxide and morphine decreased isoflurane minimum alveolar anesthetic concentration (MAC) even further in the rat. Fifty-eight female rats were used. The rats were divided into 8 groups: isoflurane in 4 possible nitrous oxide concentrations (0%, 30%, 50%, or 70%) with saline or morphine (1 mg/kg). Then the MAC of isoflurane (MAC(ISO))was determined from alveolar gas samples at the time of tail clamp. The MAC of isoflurane was significantly different at each nitrous oxide concentration, and increasing nitrous oxide concentrations reduced anesthetic requirements for isoflurane. The administration of morphine reduced the MAC(ISO) when used with 0% or 30% nitrous oxide. This MAC(ISO) by morphine reduction was less with 50% nitrous oxide and nonexistent at 70% nitrous oxide. However, with morphine present the MAC(ISO) was independent of the nitrous oxide concentration in the 30%-70% range.