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Influence of Inhaled Anesthetics on the Pharmacokinetics and Pharmacodynamics of Morphine

1993; Lippincott Williams & Wilkins; Volume: 77; Issue: 2 Linguagem: Inglês

10.1213/00000539-199377020-00023

1526-7598

EP Steffey, John H. Eisele, J. Desmond Baggot, M. J. Woliner, K. A. Jarvis, Ann R. Elliott,

Anesthesia and Pain Management

We determined the magnitude and duration of the effect of morphine (1.0 mg/kg intravenous bolus) on isoflurane and halothane minimum alveolar concentration (MAC) in six dogs anesthetized on two occasions in cross-over fashion. Plasma morphine concentrationtime profiles and changes in Paco2 were determined after morphine injection. After morphine injection, the end-tidal anesthetic dose was manipulated over the course of a 4-h observation period to account for the decline in plasma morphine concentration and to maintain an anesthetic level equivalent to 1.0 MAC isoflurane or halothane alone. Morphine decreased the MAC of halothane and isoflurane. The magnitude of MAC decrease was related to time after morphine injection and was similar for a given time with both halothane and isoflurane. For example, at 28.8 ± 3.6 ( ± SE) and 34.8 ± 6.3 min after morphine injection, the MAC for halothane and isoflurane were reduced by 35.7% ± 4.5% and 39.3% ± 3.4%, respectively. By 4 h after morphine injection, the MAC reduction for both anesthetics was less than 10% in most of the animals. Except for systemic clearance of morphine during halothane and isoflurane (40.1 ± 6.1 and 53.7 ± 5.6 mL·min−1·kg−1, respectively), there were no differences in disposition kinetics of free morphine associated with the two inhaled anesthetics. Morphine increased PaCO2 to a similar degree with both halothane (from 42.2 ± 2.1 mm Hg to 55.6 ± 2.3 mm Hg) and isoflurane (46.2 ± 2.4 mm Hg to 55.3 ± 2.1 mm Hg). Respiratory depression was abolished by noxious stimulation (tail clamp) and naloxone in all animals with both anesthesics. We conclude that: 1) intravenous morphine (1.0 mg/kg) reduces the halothane and isoflurane MAC to the same extent and that the magnitude of reduction is time-dependent; 2) during conditions of a similar constant level of anesthesia (inhaled anesthetic plus morphine) there is little or no difference in disposition kinetics of morphine; and 3) there is no anesthetic-related difference in the magnitude of morphine-induced respiratory depression during inhaled anesthesia, a depression that can be abolished by noxious stimulation and naloxone. (Anesth Analg 1993;77:346-51)