Pharmacokinetics of intravenous morphine in patients anesthetized with enflurane-nitrous oxide

Abstract

Morphine is used as an anesthetic supplement. Its disposition in surgical patients under enflurane-nitrous oxide anesthesia has not been determined. Available data on morphine concentrations in plasma after equivalent intravenous doses are conflicting, possibly as a result of varying degrees of specificity of the analytical methods for the unchanged, pharmacologically active form of the drug. This study determined the pharmacokinetics of morphine (0.05, 0.1, 0.14, or 0.2 mg/kg) injected intravenously in 10 surgical patients anesthetized with enflurane-N2O-O2. Arterial plasma was analyzed for unchanged morphine and conjugated morphine. Specificity of the analytical procedure for unchanged morphine was achieved by the combination of solvent extraction and radioimmunoassay techniques. Kinetic indices were derived by nonlinear least-squares analysis of log concentration (ng/ml) vs. time relationships. Morphine disposition was independent of dose in this fourfold range and was best described by a three-compartment model with a mean elimination half-time (t( 1/2 β)) of 104 ± 5 min. The apparent volumes of distribution (V(d)) and of the central compartment (V1) were 3.4 ± 0.2 and 0.13 ± 0.02 1/kg, respectively, while the clearance (Cl(β) was 23 ± 1 ml.min-1.kg-1. Extraction of morphine by the liver appeared to be complete. Conjugated morphine was eliminated from plasma with a t( 1/2 β) of 169 ± 15 min. The ultimate elimination of morphine from the body was dependent upon its reuptake from slowly perfused peripheral tissues, k10>k31(P<.001).