Effect-site concentration of propofol target-controlled infusion at loss of consciousness in intractable epilepsy patients receiving long-term antiepileptic drug therapy

Abstract

BACKGROUND: Propofol dose requirement for loss of consciousness (LOC) in epilepsy patients would be probably affected by increasing factors [development of tolerance, up-regulated γ-aminobutyric acid (GABAA) receptors, or antiepileptic activity of propofol] and reducing factors [synergistic interaction between propofol and antiepileptic drugs (AEDs) or reduced neuronal mass in cortex] in complex and counteracting ways. Therefore, we determined the effect-site concentration (Ce) of propofol for LOC in intractable epilepsy patients receiving chronic AEDs in comparison with non-epilepsy patients.

METHODS: Nineteen epilepsy patients receiving long-term AEDs therapy and 20 non-epilepsy patients, with the age of 20 to 65 years, were enrolled. The epilepsy patients took their prescribed AEDs until the morning of the operation. Ce of propofol for LOC was determined with isotonic regression method with bootstrapping approach following Dixon's up-and-down allocation. The study was carried out before surgical stimulation.

RESULTS: Isotonic regression showed that estimated Ce50 and Ce95 of propofol for LOC were lower in epilepsy group [2.88 μg/mL (83% confidence interval, 2.82-3.13 μg/mL) and [3.43 μg/mL (95% confidence interval, 3.28-3.47 μg/mL)] than in non-epilepsy group [3.38 μg/mL (83% confidence interval, 3.17-3.63 μg/mL) and 3.92 μg/mL (95% confidence interval, 3.80-3.97 μg/mL)] with bootstrapping approach. Mean Ce50 of propofol of epilepsy group was also lower than that of non-epilepsy group without statistical significance (2.8240.19 μg/mL vs 3.16±0.38 μg/mL, P=0.056).

CONCLUSIONS: For anesthetic induction of epilepsy patients with propofol target-controlled infusion, Ce may need to be reduced by 10% to 15% compared with non-epilepsy patients.