Thiopental Disposition in Lean and Obese Patients Undergoing Surgery

Abstract

The effect of obesity on the disposition kinetics of thiopental was studied in 7 morbidly obese (age 25-46 yr) and 8 age-matched lean patients (age 25-43 yr), undergoing primarily abdominal surgery. Based upon total (bound + free) thiopental concentrations, the average volumes of distribution in the terminal disposition phase and at steady-state (V.beta. and V35) were significantly larger in the obese (7.94 .+-. 4.55 and 4.72 .+-. 2.73 l/kg, respectively) than in the age-matched lean patients (1.95 .+-. 0.63 and 1.40 .+-. 0.46 l/kg, respectively). Clearance of total thiopental, normalized for total body weight, was not significantly different between the obese (0.18 .+-. 0.08 l/h per kg) and lean patients (0.21 .+-. 0.06 l/h per kg). Total body clearance not normalized for total body weight was significantly larger in the obese (24.98 .+-. 14.87 l/h) than in the lean patients (11.86 .+-. 3.66 l/h). The elimination half-life of thiopental was significantly longer in the obese (27.85 h) than in the lean patients (6.33 h), and this difference was primarily a function of the larger apparent volume of distribution for thiopental. The unbound fraction of thiopental in serum (17.8-27.6%) was not correlated with the degree of obesity. The most appropriate means of comparing intrinsic metabolizing capacity (normalized vs. non-normalized for weight) between lean and obese subjects remains unresolved.