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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 (t1/2 beta) of 104 +/- 5 min. The apparent volumes of distribution (Vd) and of the central compartment (V1) were 3.4 +/- 0.2 and 0.13 +/- 0.02 l/kg, respectively, while the clearance (ClB) was 23 +/- 1 ml x min-1 x kg-1. Extraction of morphine by the liver appeared to be complete. Conjugated morphine was eliminated from plasma with a t1/2 beta of 169 +/- 15 min. The ultimate elimination of morphine from the body was dependent upon its uptake from slowly perfused peripheral tissues, K10 greater than k31(P less than .001).
Insights
This study investigated morphine pharmacokinetics in surgical patients under enflurane-nitrous oxide anesthesia. Morphine elimination was dose-independent, characterized by a three-compartment model with a 104-minute half-life.
Area of Science:
- Pharmacology
- Anesthesiology
- Clinical Pharmacokinetics
Background:
- Morphine is a common anesthetic supplement.
- Pharmacokinetics of morphine under enflurane-nitrous oxide anesthesia are not well-defined.
- Conflicting data exists regarding plasma morphine concentrations due to analytical method variability.
Purpose of the Study:
- To determine the pharmacokinetics of morphine in surgical patients.
- To analyze morphine disposition during enflurane-nitrous oxide anesthesia.
- To specifically quantify unchanged, pharmacologically active morphine.
Main Methods:
- Intravenous administration of morphine (0.05–0.2 mg/kg) to 10 surgical patients.
- Anesthesia maintained with enflurane-N2O-O2.
- Analysis of arterial plasma for unchanged and conjugated morphine using solvent extraction and radioimmunoassay.
- Pharmacokinetic parameters derived via nonlinear least-squares analysis.
Main Results:
- Morphine disposition was dose-independent across the tested range.
- A three-compartment model best described morphine pharmacokinetics.
- Mean elimination half-time (t1/2 beta) was 104 ± 5 min.
- Apparent volume of distribution (Vd) was 3.4 ± 0.2 L/kg; central compartment volume (V1) was 0.13 ± 0.02 L/kg.
- Clearance (ClB) was 23 ± 1 mL/min/kg.
- Hepatic extraction of morphine appeared complete.
- Conjugated morphine had a t1/2 beta of 169 ± 15 min.
Conclusions:
- Morphine pharmacokinetics are characterized by a three-compartment model with a prolonged elimination half-life in this patient population.
- Hepatic extraction is complete, with elimination dependent on peripheral tissue uptake.
- The findings provide crucial data for optimizing morphine use in anesthesia.