The pharmacokinetics of morphine and lidocaine in critically ill patients

Objective: To evaluate the pharmacokinetic parameters of morphine and lidocaine after a single intravenous dose in critically ill patients. Design: Prospective, clinical study. Setting: General intensive care unit (ICU) in a university hospital. Patients: Patients admitted to the ICU with severe systemic inflammatory response syndrome of various etiologies. Interventions: A single intravenous dose of morphine (0.025 mg/kg) and lidocaine (1.5 mg/kg) were given separately 12-36 h after admission, and arterial blood samples for serum drug levels were taken. Measurments and results: Morphine pharmacokinetics were studied in 30 patients. The clearance (Cl) was found to be 5.7 ± 2.3 ml/kg per min, volume of distribution of the central compartment (Vc) 0.16 ± 0.12 l/kg and volume of distribution at steady state (Vss) 1.08 ± 0.69 l/kg. These values are lower then those described previously for healthy volunteers (33.5 ± 9 ml/kg per min, 1.01 ± 0.31 l/kg, and 5.16 ± 1.4 l/kg, respectively), and similar to those described in trauma and burned patients. Lidocaine pharmacokinetics were tested in 24 subjects. The Cl was 6.9 ± 3.8 ml/kg per min, Vc 0.25 ± 0.1 l/kg and Vss 0.78 ± 0.26 l/kg. These values are not different from parameters published previously for healthy volunteers (10 ml/kg per min, 0.53 l/min and 1.32 l/min, respectively). No correlation was found between clinical variables and pharmacokinetic parameters of both drugs (ANOVA). Conclusions: Both morphine and lidocaine have a reduced volume of distribution in critically ill patients. The normal lidocaine clearance indicates preserved hepatic blood flow and suggests that other mechanisms are involved in the reduced morphine clearance. These findings may have application for the treatment of ICU patients.