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Propofol Clearance and Volume of Distribution Are Increased in Patients With Major Burns

From the Department of Anesthesia, University of Iowa Hospitals and Clinics, Roy J. and Lucille A. Carver College of Medicine, Iowa City, Iowa (Dr Han); Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine and Tufts Medical Center, Boston, Massachusetts (Dr Greenblatt); and Department of Anesthesiology and Critical Care, Harvard Medical School, Massachusetts General Hospital and Shriners Hospital for Children, Boston, Massachusetts (Dr Martyn).

Propofol pharmacokinetics were examined in 17 adults with major burns during the hyperdynamic convalescent phase. Eighteen nonburned surgical patients served as controls. After a 2-mg/kg intravenous dose of propofol, blood samples were collected at multiple time points. Noncompartmental methods were used to calculate the pharmacokinetic parameters. The following indices were higher in burns than controls: propofol clearance (64 ± 17 vs 29 ± 4 mL/kg/min, P < .001) and volume of distribution (8 ± 3 vs 4 ± 1 L/kg, P < .001). The area under the curve was smaller in burns (556 ± 152 vs 1193 ± 183 µg/mL h, P < .001). The higher clearance of propofol in burned patients may imply that these patients require higher doses or infusion rates of propofol to attain a target plasma concentration or pharmacodynamic effect.

Key Words: Cardiac index • hepatic blood flow • hypnotics • pharmacokinetics

Address for reprints: Tae-Hyung Han, MD, PhD, Department of Anesthesia, 5937 JPP, University of Iowa Hospitals and Clinics, Carver College of Medicine, 200 Hawkins Drive, Iowa City, IA 52242; e-mail: anthony-han{at}uiowa.edu.

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