Enflurane is the inhalation agent that anesthesiologists most often avoid when caring for patients with epilepsy, because it lowers seizure threshold. In children and adults with no history of epilepsy, enflurane can cause epileptiform activity with concomitant facial or appendicular myoclonus or generalized tonic-clonic movements.28–30 In epilepsy patients, the extent but not the frequency of spike activity on the electrocorticogram is increased.29 Epileptogenic foci may be activated during epilepsy surgery.23,31 As the depth of anesthesia is increased with enflurane, the EEG demonstrates high-voltage spikes and spike and slow-wave complexes, the spikes with burst suppression.

The mechanism of enflurane-induced hyperexcitability in humans is unclear. In animals, enflurane inhibits synapses and stimulates excitatory neuronal transmission in cortical and subcortical areas.27

Although low enflurane concentrations (1.0–1.5%) administered to a normocarbic patient (arterial partial pressure of carbon dioxide [PaCO2] equals 40 mm Hg) are not frequently associated with seizure activity,32 increasing enflurane concentrations (2–3%) or hyperventilating an anesthetized patient enhances seizure activity. Hyperventilation to a PaCO2 of 20 mm Hg from 40 mm Hg is associated with seizure activity at a 1% lower enflurane concentration. Because hyperventilation is frequently used by neuroanesthesiologists to decrease cerebral blood flow and intracranial pressure, enflurane is avoided when hyperventilation is indicated. An increase in PaCO2 from 40 mm Hg to 60 mm Hg increases the minimum enflurane concentration at which seizures occur by 1%.27

Generalized tonic-clonic and myoclonic seizures can occur within the immediate postoperative period and, potentially, for a few days after enflurane anesthesia. The role of other CNS-active drugs remains uncertain in these cases.33 The convulsant effects may result from enflurane's organic and inorganic nonvolatile fluorinated metabolites.34

Although anesthesiologists consider diazepam and thiopental to be anticonvulsants and use them extensively to treat seizure activity, there is some evidence that these drugs may potentiate enflurane-related epileptiform activity in humans.35 Nitrous oxide (N2O) does not alter epileptiform activity induced by enflurane.32

Adapted from: Najjar S, Devinsky O, Rosenberg AD, et al. Procedures in epilepsy patients. In: Ettinger AB and Devinsky O, eds. Managing epilepsy and co-existing disorders. Boston: Butterworth-Heinemann; 2002;499–513. With permission from Elsevier (www.elsevier.com).

Authored By: 
Orrin Devinsky MD
Souhel Najjar MD
Andrew D Rosenberg MD
Reviewed By: 
Steven C. Schachter MD
Thursday, April 1, 2004