Why is phenytoin not the preferred initial treatment for seizures caused by local anesthesia toxicity?

Why Phenytoin is Not Given for Local Anesthetic Toxicity Seizures

Benzodiazepines, not phenytoin, are the recommended treatment for seizures caused by local anesthetic systemic toxicity (LAST), as explicitly stated in the 2023 American Heart Association guidelines. 1

Guideline-Based Recommendation

The 2023 AHA guidelines provide a Class 1 (strong) recommendation with Level C-LD evidence specifically stating: "We recommend the use of benzodiazepines to treat seizures associated with local anesthetic systemic toxicity." 1 Notably, phenytoin is completely absent from these recommendations for LAST management.

Mechanistic Reasons Why Phenytoin Fails in LAST

Different Seizure Mechanisms

• Local anesthetic-induced seizures result from disruption of the excitatory-inhibitory balance in otherwise normal neurons, not from abnormal electrical foci like idiopathic epilepsy 2
• Phenytoin works by blocking voltage-dependent sodium channels to inhibit propagation from active electrical foci—a mechanism useful for focal seizures but not for toxicological seizures 2
• Local anesthetics themselves already block sodium channels, making phenytoin's mechanism redundant and potentially counterproductive 2

Evidence of Harm

• Animal studies demonstrate that phenytoin markedly enhances local anesthetic-induced convulsions, shortening seizure latency and increasing mortality 3
• In rat models, phenytoin (5-20 mg/kg) potentiated both procaine- and lidocaine-induced convulsions, while benzodiazepines (diazepam, clonazepam) completely protected against seizures 3
• Phenytoin can paradoxically cause seizures at toxic levels (>38 mcg/mL), a phenomenon well-documented in clinical practice 4

Why Benzodiazepines Work

• Benzodiazepines enhance GABA-A receptor activity, increasing chloride channel opening duration and directly counteracting the excitatory imbalance caused by local anesthetics 2
• This mechanism directly addresses the pathophysiology of LAST-induced seizures 2
• Clinical evidence supports benzodiazepines as first-line therapy across all toxicological seizures 5, 2

Complete LAST Management Algorithm

Immediate Seizure Management

1. Administer benzodiazepines immediately (lorazepam 2-4 mg IV or diazepam 5-10 mg IV) 1, 5
2. Give 20% intravenous lipid emulsion (ILE) concurrently—this is a Class 1 recommendation for LAST 1
3. Maintain airway, prevent hypoxia and acidemia 1

If Seizures Persist

• Consider barbiturates (phenobarbital) as second-line, not phenytoin 2
• Barbiturates complement benzodiazepines at the GABA-A receptor by increasing chloride channel opening duration 2
• Animal studies show phenobarbital has greater effectiveness than phenytoin for toxicological seizures 2

Cardiovascular Support

• Sodium bicarbonate for wide-complex tachycardia (Class 2a recommendation) 1
• Atropine for bradycardia (Class 2a recommendation) 1
• VA-ECMO for refractory cardiogenic shock (Class 2a recommendation) 1

Critical Pitfalls to Avoid

• Never use phenytoin for LAST seizures—it may worsen outcomes based on animal data and lacks any supporting evidence in guidelines 3
• Do not delay lipid emulsion therapy—it should be given early alongside benzodiazepines, not as rescue therapy 1
• Avoid using phenytoin's mechanism of action as justification for its use in any toxicological seizure, as the pathophysiology differs fundamentally from epilepsy 2
• Remember that 77-89% of LAST patients develop CNS toxicity, but 32-55% develop life-threatening cardiovascular toxicity requiring aggressive management beyond seizure control 1

Comparison to Other Seizure Types

For context, phenytoin remains useful in non-toxicological status epilepticus as a second-line agent after benzodiazepines (44% efficacy as monotherapy, 56% when combined with diazepam) 1, 5, but this evidence does not translate to LAST because the underlying mechanisms are completely different 2.