Lidocaine hydrochloride has proconvulsant and anticonvulsant effects, with CNS effects related to blood concentrations. Low doses (2–3 mg/kg) can terminate status epilepticus.

With increasing blood levels, CNS symptoms and signs of toxicity occur, from perioral numbness, lightheadedness, dizziness, tinnitus, and fine tremors to generalized seizures and coma. In animals, lidocaine produces epileptiform activity that is limited to the amygdala and hippocampus.86

Lidocaine doses that are commonly used for local anesthesia can cause CNS toxicity if they are inadvertently administered intravenously. For example, when administering epidural anesthesia, total doses of 5–8 mg/kg are commonly injected into the epidural space.84 Accidental intravascular injection of this dose can cause epileptic seizures.

In addition to direct intravascular injection and immediate toxicity, systemic lidocaine levels can rise to toxic levels by rapid systemic absorption from the area of injection. This can occur 10 to 20 minutes after injection. Anesthesiologists often add 5 mg/mL of epinephrine to the local anesthetic to decrease systemic absorption and peak serum lidocaine levels. When a regional anesthesia block is successful, early reinjection of local anesthesia can cause toxicity (including seizures), because peak absorption of the first injection occurs while additional medication is injected.

Efforts should be made to deliver minimum amounts of lidocaine to the lower respiratory tract in airway anesthesia (e.g., for bronchoscopy), because its pharmacokinetics at that site are similar to those with intravenous administration.87

High doses of lidocaine cause sedation. Increasing the arterial partial pressure of carbon dioxide (PaCO2) decreases the dose of lidocaine needed to produce a generalized electrical seizure.88 Higher PaCO2 levels increase cerebral blood flow, thus increasing the amount of anesthetic reaching the brain, and may directly excite the amygdala. In contrast to the usual pattern, in which hyperventilation activates seizure activity, hyperventilation may prevent seizures from occurring in patients with lidocaine overdose by decreasing cerebral blood flow.

Lidocaine is injected intravenously to provide local anesthesia (intravenous regional anesthesia or Bier blocks). In this technique, after an extremity is exsanguinated, and the blood supply is arrested by a tourniquet, lidocaine is injected into a vein to provide anesthesia. Doses of lidocaine up to 3 mg/kg of 0.5% solution without preservatives or epinephrine are used. Premature tourniquet release (less than 20 minutes) can result in high systemic lidocaine levels and possible seizure activity. Release after 20 minutes can also be associated with toxicity. Some physicians cycle the deflation of the tourniquet with an intermittent inflation-deflation-inflation cycle in an attempt to decrease rapid absorption of lidocaine from the extremity.

Seizures induced by lidocaine can be terminated with barbiturates.

Etidocaine hydrochloride, a long-acting derivative of lidocaine, as well as mepivacaine and prilocaine hydrochloride, share common pharmacologic properties with lidocaine hydrochloride.

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 (

Authored By: 
Orrin Devinsky MD
Souhel Najjar MD
Andrew D Rosenberg MD
Reviewed By: 
Steven C. Schachter MD
Wednesday, March 31, 2004