What is the relationship between lidocaine and seizures?

From the Guidelines

Lidocaine can cause seizures, particularly when plasma concentrations exceed 8-10 μg/mL, and its use should be carefully monitored, especially in patients with risk factors for toxicity, such as hepatic dysfunction or drug interactions that impair lidocaine metabolism 1.

Key Considerations

• The risk of lidocaine-induced seizures increases with rapid IV administration, excessive dosing (particularly above 4.5 mg/kg), and certain patient factors such as low body weight or high body mass index (BMI) 1.
• The mechanism behind lidocaine's dual effect involves its action on sodium channels - at therapeutic levels, it stabilizes neuronal membranes and reduces abnormal electrical activity, but at toxic levels, it can cause central nervous system excitation leading to seizures.
• If lidocaine-induced seizures occur, management includes immediate discontinuation of the drug, supportive care, and administration of benzodiazepines like diazepam or lorazepam 1.

Monitoring and Prevention

• Healthcare providers should monitor for early signs of toxicity such as perioral numbness, dizziness, or tinnitus, which may precede seizure activity.
• The use of lidocaine should be guided by the most recent and highest quality evidence, and its potential benefits and risks should be carefully weighed in each individual patient 1.

Clinical Context

• In the context of status epilepticus, lidocaine may be considered as a third or fourth-line agent at doses of 1-2 mg/kg IV bolus, followed by an infusion of 2-3 mg/kg/hr when standard anticonvulsants have failed 1.
• However, the primary treatment for seizures and status epilepticus remains benzodiazepines, and lidocaine should only be used in specific clinical contexts and with careful monitoring 1.

From the FDA Drug Label

Methemoglobin levels may continue to rise; therefore, immediate treatment is required to avert more serious central nervous system and cardiovascular adverse effects, including seizures, coma, arrhythmias, and death. Objective adverse manifestations become increasingly apparent with increasing venous plasma levels above 6. 0 mcg free base per mL. In the rhesus monkey arterial blood levels of 18–21 mcg/mL have been shown to be threshold for convulsive activity.

Lidocaine and Seizures: Lidocaine can cause seizures as a result of dose-related toxicity or methemoglobinemia.

• Key Factors:
  • Dose-related toxicity
  • Methemoglobinemia
  • High venous plasma levels (above 6.0 mcg free base per mL)
  • Arterial blood levels (18-21 mcg/mL) in rhesus monkeys
• Clinical Decision: Administer lidocaine with caution and monitor patients closely for signs of toxicity or methemoglobinemia to minimize the risk of seizures 2, 2.

From the Research

Lidocaine and Seizures

• Lidocaine has a concentration-dependent effect on seizures, with anticonvulsant properties at lower concentrations and pro-convulsant effects at higher concentrations 3.
• The use of lidocaine for status epilepticus in adults has been studied, with 70.7% of seizures responding to lidocaine, although the evidence is currently weak and further prospective studies are warranted 4.
• Lidocaine-induced seizures are potentiated by phenytoin and antagonized by various anticonvulsant agents, suggesting a complex mechanism of action 5.

Comparison with Other Anticonvulsants

• Intravenous lorazepam is better than intravenous diazepam or intravenous phenytoin alone for cessation of seizures, and carries a lower risk of continuation of status epilepticus requiring a different drug or general anaesthesia 6.
• Lidocaine's anticonvulsive action profile is similar to that of phenytoin, with both agents reducing sodium conductance of neuronal membranes, but lidocaine may also bind to the GABA recognition site and another site in the GABA-ionophore receptor complex 5.

Clinical Implications

• The use of lidocaine for status epilepticus is not widely established, and its effectiveness and safety compared to other anticonvulsants are uncertain 4, 6.
• Further research is needed to understand the mechanisms of action of lidocaine and other anticonvulsants, and to determine the best treatment options for status epilepticus 7, 6.