Bupivacaine causes CNS toxicity at plasma levels greater than 4 mg/mL. Seizures can occur with lower plasma levels after accidental intravenous injection during obstetric epidural anesthesia.89 A more dangerous concern with bupivacaine toxicity is intractable ventricular fibrillation.


Cocaine produces electrical and clinical seizure activity in animals. Electrographic discharges arise in the amygdala. Protection against such cocaine-induced seizures is afforded by dibenamine, chlorpromazine, reserpine, pyridoxine, and hydroxylamine, but not with traditional anticonvulsants. Thus, cocaine may cause seizures by potentiating noradrenergic or dopaminergic activity in the amygdala.90

Seizures occurred in an 11-week-old infant who received intranasal installation of a 4% cocaine solution91 and in a child who received topical cocaine solution through a bronchoscope.92 Edematous and inflamed mucosa may absorb excessive amounts of anesthetic. In these settings, recommended ways of managing cocaine-induced seizures in children include:91

  • administering benzodiazepines or short-acting barbiturates
  • using local vasoconstrictors
  • rinsing the mucosal surface with water or normal saline to prevent further drug absorption


At low doses, procaine has anticonvulsant properties.93 Given at 18–29 mg/kg, it causes generalized tonic-clonic seizures.

In one study, thiopental pretreatment failed to prevent procaine-induced seizures, but it increased the dose of procaine necessary to produce seizures. Thiopental given during a procaine-induced seizure stopped the seizure.84

Para-aminobenzoic acid (PABA) is a procaine metabolite that can prevent seizures induced by local anesthetics.94 This metabolite might explain the low incidence of generalized convulsions reported during the continuous infusion of intravenous procaine.

Chloroprocaine, a halogenated derivative of procaine, shares the same pharmacologic properties as procaine.

Tetracaine hydrochloride, a derivative of PABA, is 10 times more active and potent than procaine after intravenous injection.

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
Wednesday, March 31, 2004