Version May 2024
| To obtain emergency consultation with a medical toxicologist, in the United States, call 1-800-222-1222 for the nearest regional poison control center. Contact information for poison control centers around the world is available at the WHO website and in the UpToDate topic on regional poison control centers (society guideline links). |
| Clinical presentation |
| CNS depression, encephalopathy (acute overdose or therapeutic use) |
| Vital sign abnormalities (severe acute overdose): Hypotension; also, respiratory depression, tachycardia, hyperthermia |
| Metabolic acidosis (severe acute overdose) |
| Electrolyte abnormalities (acute overdose) |
| Elevated transaminase levels (acute overdose or therapeutic use) |
| Hyperammonemia (acute overdose or therapeutic use) |
| Idiosyncratic hepatotoxicity (therapeutic use) |
| History |
| Ask about amount ingested (ingestion >200 mg/kg usually causes CNS depression) |
| Ask whether immediate or sustained release preparation was ingested |
| Ask about concurrent carnitine supplementation |
| Examination |
| Assess CNS depression |
| Look for stigmata of hepatotoxicity (eg, jaundice, hepatomegaly, right upper quadrant abdominal tenderness) |
| Laboratory |
| Measure valproic acid concentration every 2 to 4 hours until declining; check acid-base status, basic electrolytes, liver function tests, ammonia concentration |
| Treatment |
| Gastrointestinal decontamination |
| Give single dose of activated charcoal (1 g/kg; maximum dose 50 g) |
| Hypotension in acute overdose |
| Fluid resuscitation with IV boluses of isotonic crystalloid; vasopressors if necessary |
| Consider hemodialysis or hemoperfusion for refractory hypotension or other signs of severe toxicity; consult nephrology early |
| Carnitine for VPA toxicity associated with hyperammonemia, lethargy, coma, or hepatic dysfunction |
| Give carnitine, 100 mg/kg IV over 30 minutes (maximum dose 6 g), followed by 50 mg/kg IV (maximum dose 3 g) given every eight hours |
| CNS and respiratory depression in acute overdose |
| Supportive care: Patients with altered mental status often require tracheal intubation and mechanical ventilation |
| Naloxone (if no risk of acute opioid withdrawal) 0.04 mg IV initial dose, gradually escalate repeated doses every several minutes to 2 mg maximum dose per administration; discontinue if no response after total of 10 mg IV |
| Benzodiazepine for seizures (eg, lorazepam 2 mg IV; repeat after 5 to 10 minutes as needed for refractory seizures) |
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