Variability of thiopental clearance in routine critical care patients

Thiopental was administered to neurosurgical patients as a drug for cerebral protection for up to 9 days either by continuous infusion (seven subjects) or repeated intravenous bolus (nine subjects). The efficient levels of thiopental measured at steady state ranged between 5 and 63 mg.l-1. Steady-state clearance evidenced considerable interindividual variability. Overall mean plasma clearance was lower than 1 ml.min-1.kg-1 for one subjects, ranged between 1 and 2 ml.min-1.kg-1 for six subjects, between 2 and 3 ml.min-1.kg-1 for seven subjects and was up to 5 ml.min-1,kg-1 for one subject. Extreme values for apparent daily clearance were 0.268 ml.min-1.kg-1 and 5.40 ml.min-1.kg-1. Daily intersubject CV gradually increased from day to day, increasing from 37% on day 1 to 51% on day 7. During the treatment for seven subjects, variations were minimal and clearance was considered to be constant; the maximum variation of clearance expressed as a percentage of the initial value was lower than 21% over a period longer than 3 days. For the other subjects, clearance was not stable with time. A decrease in clearance was evidenced for four subjects over a period of 7 days and more; the maximum variation of clearance was greater than -35%. An increase in clearance was noted for three subjects after 2 days of treatment; the maximum variation of clearance was greater than +44%. Evaluation of clearance at steady state made it possible to analyse interindividual variability and its clinical implications.