Prolonged thiopentone infusion for neurosurgical emergencies: Usefulness of therapeutic drug monitoring

Serial serum thiopentone concentrations were measured during and following completion of an intravenous infusion of thiopentone in 20 patients with ne urosurgical emergencies. The concentration data from a further 55 patients who had had some such measurements were reviewed retrospectively. The patie nts received an infusion for longer than 24 hours at a rate adjusted to mai ntain EEG burst suppression. The data were interpreted in terms of thiopent one pharmacokinetics and used to produce statistical models relating to cli nical outcomes. In these patients, the one-month mortality rate following c ommencement of thiopentone treatment was 20%; the mean durations of pupilla ry and motor unresponsiveness following cessation of an infusion were 22 an d 91 hours, respectively. Predictors of a prolonged duration of motor unres ponsiveness included a prolonged duration of pupillary unresponsiveness, a low thiopentone clearance and a high maximum serum concentration of thiopen tone. From pooled logistic regression, median effective serum thiopentone c oncentrations (EC50) were found to be 50 mg.l(-1) for recovery of pupillary responsiveness and 12 mg.l(-1) for the recovery of motor responsiveness. B ecause prolonged high-dose thiopentone leads to prolonged residual serum co ncentrations, it is difficult to distinguish the residual pharmacological e ffects of thiopentone from the clinical condition. This study suggests that , based on EC50 values for responses, monitoring of post-infusion serum thi opentone concentrations may help determine whether a patient's clinical sta te is due to residual thiopentone pharmacological effects.