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.
Russo
H
H
Pharmacie Saint-Eloi, Centre Hospitalier Universitaire, Montpellier, France.
Brés
J
J
Duboin
M P
MP
Roquefeuil
B
B
D000293:Adolescent; D000328:Adult; D003422:Critical Care; D004347:Drug Interactions; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D013874:Thiopental / Q000008:administration & dosage / Q000493:pharmacokinetics*
D006993:Hypnotics and Sedatives; D013874:Thiopental