title: [Thiopental kinetics in high-dose use].
abstract: The kinetics of thiopentone when administered in high doses were investigated in two patients with elevated intracranial pressure and three patients with focal cerebral ischemia. Initial saturation of the tissues is best achieved by a series of infusions with decreasing infusion rate. Administration of a bolus followed by maintenance doses proved unsuitable. The course of concentration under maintenance dosage was extremely variable, mainly due to interindividual and intraindividual variations in clearance. The apparent distribution volumes in these patients (1.38-3.10 l/kg, mean 2.43 l/kg) corresponded to the volumes determined after bolus administration. The total body clearance was low (45.8-103.4 ml/min, mean 72.3 ml/min) and was the reason for long elimination half-times (15.6-25.0 h, mean 23.2 h). Four patients biotransformed thiopentone regardless of the concentration. In one female patient the biotransforming enzyme systems may have been saturated. While conversion of thiopentone to pentobarbitone is generally only of secondary importance, an unusually high plasma pentobarbitone concentration was observed in one patient, reaching 50% of the concentration of the original substance. On the average, thiopentone was 75-80% proteinbound. The binding rate changed considerably with time. It could not be shown that this was influenced by albumin concentration between 25 and 50 g/l. The thiopentone concentration in the ventricular fluid corresponded approximately to that in the plasma fluid. Owing to the variability of the total body clearance and plasma protein binding, and the possibility of changes in tolerance, thiopentone administration must be controlled individually according to the EEG and intracranial pressure. Monitoring of the drug concentration in plasma is recommended.
mesh_terms: D000328:Adult; D001812:Blood-Brain Barrier; D001929:Brain Edema / Q000097:blood / Q000188:drug therapy*; D002545:Brain Ischemia / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007427:Intracranial Pressure / Q000187:drug effects*; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D010424:Pentobarbital / Q000097:blood; D011485:Protein Binding; D013874:Thiopental / Q000008:administration & dosage / Q000097:blood*
chemical_list: D010424:Pentobarbital; D013874:Thiopental
vernacular_title: Thiopentalkinetik bei hochdosierter Anwendung.