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 neurosurgical emergencies. The concentration data from a further 55 patients who had had some such measurements were reviewed retrospectively. The patients received an infusion for longer than 24 hours at a rate adjusted to maintain EEG burst suppression. The data were interpreted in terms of thiopentone pharmacokinetics and used to produce statistical models relating to clinical outcomes. In these patients, the one-month mortality rate following commencement of thiopentone treatment was 20%; the mean durations of pupillary and motor unresponsiveness following cessation of an infusion were 22 and 91 hours, respectively. Predictors of a prolonged duration of motor unresponsiveness included a prolonged duration of pupillary unresponsiveness, a low thiopentone clearance and a high maximum serum concentration of thiopentone. From pooled logistic regression, median effective serum thiopentone concentrations (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. Because prolonged high-dose thiopentone leads to prolonged residual serum concentrations, it is difficult to distinguish the residual pharmacological effects of thiopentone from the clinical condition. This study suggests that, based on EC₅₀ values for responses, monitoring of post-infusion serum thiopentone concentrations may help determine whether a patient's clinical state is due to residual thiopentone pharmacological effects.