Anticonvulsant Overdose

KEY FEATURES

• Rapid intravenous injection of phenytoin can cause acute myocardial depression and cardiac arrest owing to the solvent propylene glycol (does not occur with fosphenytoin injection)

• Chronic phenytoin intoxication can occur following only slightly increased doses because of zero-order kinetics and a small toxic-therapeutic window

• Phenytoin intoxication can also occur following acute intentional or accidental overdose

CLINICAL FINDINGS

Symptoms and Signs

Phenytoin

• In overdose, often only mild symptoms even with high serum levels

• Most common manifestations

  • Ataxia

  • Nystagmus

  • Drowsiness

• Choreoathetoid movements have been described

Carbamazepine

• Most common manifestations

  • Drowsiness, stupor

  • Atrioventricular (AV) block, coma, and seizures (with high levels)

  • Dilated pupils

  • Tachycardia

Valproic Acid

• Most common manifestations

  • Encephalopathy

  • Elevated serum ammonia

  • Metabolic acidosis

  • Hypernatremia (from the sodium component of the salt)

  • Hypocalcemia

  • Mild liver aminotransferase elevations

  • Cerebral edema

• Hypoglycemia, as a result of hepatic metabolic dysfunction

• Coma with small pupils, can mimic opioid poisoning

Gabapentin, Levetiracetam, Lacosamide, Vigabatrin, and Zonisamide

• Generally cause somnolence, confusion, and dizziness

• One case report of hypotension and bradycardia after a large overdose of levetiracetam

Felbamate

• Can cause crystalluria and kidney dysfunction after overdose

• May cause idiosyncratic aplastic anemia with therapeutic use

Tiagabine, Lamotrigine, Topiramate

• Seizures after overdose

• Lamotrigine

  • Has sodium-channel blocking properties

  • May cause QRS prolongation and heart block

Differential Diagnosis

• Opioid intoxication

• Sedative-hypnotic overdose

DIAGNOSIS

• Phenytoin toxicity

  • Levels > 20 mg/L associated with ataxia, nystagmus, drowsiness; severe poisoning associated with concentrations > 35 mg/L

• Carbamazepine toxicity

  • May be seen with serum levels > 20 mg/L (85 mcmol/L), though severe poisoning is usually associated with concentrations > 30–40 mg/L (127–169 mcmol/L)

  • Because of erratic and slow absorption, intoxication may progress over several hours to a day

TREATMENT

• Emergency and supportive measures

  • For recent ingestions, give activated charcoal orally or by gastric tube

    • Repeated doses of activated charcoal, 20–30 g every 3–4 hours, are indicated for massive ingestions of valproic acid or carbamazepine

    • Sorbitol or other cathartics should not be used with each dose, or resulting large stool volumes may lead to dehydration or hypernatremia

  • For large ingestions of carbamazepine or valproic acid (especially of sustained-release formulations) consider whole bowel irrigation

• Specific treatment

  • There are no specific antidotes

  • Carnitine may be useful in patients with valproic acid–induced hyperammonemia

  • Carbapenem antibiotics can reduce serum valproic acid concentrations and have been used in some cases of acute toxicity

  • Consider hemodialysis for massive intoxication with valproic acid or carbamazepine

    • Carbamazepine levels > 60 mg/L (254 mcmol/L)

    • Valproic acid levels > 800 mg/L ...