The pharmacokinetics of morphine and lidocaine in critically ill patients

Objective: To evaluate the pharmacokinetic parameters of morphine and lidoc aine 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 re sponse syndrome of various etiologies. Interventions: A single intravenous dose of morphine (0.025 mg/kg) and lido caine (1.5 mg/kg) were given separately 12-36 h after admission, and arteri al blood samples for serum drug levels were taken. Measurements and results: Morphine pharmacokinetics were studied in 30 pati ents. 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 volu me of distribution at steady state (Vss) 1.08 +/- 0.69 l/kg. These values a re 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), a nd similar to those described in trauma and burned patients. Lidocaine phar macokinetics were tested in 24 subjects. The Cl was 6.9 +/- 3.8 ml/kg per m in, Vc 0.25 +/- 0.1 l/kg and Vss 0.78 +/- 0.26 l/kg. These values are not d ifferent 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 f ound between clinical variables and pharmacokinetic parameters of both drug s (ANOVA). Conclusions: Both morphine and lidocaine have a reduced volume of distribut ion in critically ill patients. The normal lidocaine clearance indicates pr eserved hepatic blood now and suggests that other mechanisms are involved i n the reduced morphine clearance. These findings may have application for t he treatment of ICU patients.