TOEPASSING VAN THIOPENTAL BIJ VERHOOGDE INTRACRANIELE DRUK. KLINISCHE STUDIE EN VERGELIJKING VAN DIVERSE DOSEERSCHEMA'S MET COMPUTERSIMULATIE

Eight infusion regimens for thiopental in patients with increased intracranial pressure were evaluated by computer simulation. Seven thiopental infusion regimens were taken from the literature and one was developed using published pharmacokinetic parameters. The optimal regimen to rapidly achieve and maintain a predetermined thiopental serum concentration of 20-40 mg/l consisted of two loading doses followed by a maintenance infusion. Clinical evaluation of a dosing regimen comprising an induction dose of 10 mg/kg followed by a loading dose of 20 mg/kg over 30 min and a maintenance infusion of 1.5 mg · kg-1· h-1gave inadequate steady-state serum concentrations. The optimal maintenance dose was found to be 2.5 mg · kg-1· h-1or more. Within 6 h after initiation of the therapy according to this regimen, the optimal maintenance dose can be calculated by determination of the serum concentration of thiopental. The maintenance dose can be adjusted using linear kinetics.