August 2025
| To obtain emergency consultation with a medical toxicologist, in the United States, call 1-800-222-1222 for the nearest regional poison center. Contact information for poison centers around the world is available at the WHO website and in the UpToDate topic on regional poison centers (society guideline links). |
| Clinical manifestations of poisoning |
| CNS depression, encephalopathy (therapeutic use or acute overdose) |
| Vital sign abnormalities (severe acute overdose): Hypotension; also, respiratory depression, tachycardia, hyperthermia |
| Elevated anion gap metabolic acidosis (severe acute overdose) |
| Hypernatremia, hypocalcemia (acute overdose) |
| Elevated liver biochemical tests (acute overdose or therapeutic use) |
| Hyperammonemia (acute overdose or therapeutic use) |
| Idiosyncratic hepatotoxicity (therapeutic use) |
| Laboratory evaluation |
| Measure valproic acid concentration every 2 to 4 hours until declining; check acid-base status, basic electrolytes, liver biochemical tests, ammonia concentration |
| Management |
| Provide supportive care. Patients with CNS or respiratory depression often require tracheal intubation and mechanical ventilation. |
| Gastrointestinal decontamination. |
| For acute overdose presenting within 1 hour, give a single dose of activated charcoal (1 g/kg; maximum dose 50 g). |
| For a patient with an elevated and rising VPA concentration, without evidence of CNS depression or airway compromise, a second dose of activated charcoal is a reasonable option to reduce ongoing absorption and block enterohepatic reabsorption. |
| Hypotension in acute overdose: Fluid resuscitation with IV boluses of isotonic crystalloid; vasopressors if necessary. |
Hemodialysis for any of the following:
|
| Carbapenem antibiotic (meropenem 1 g IV every 8 hours or ertapenem 1 g IV every 24 hours) for patients with severe poisoning to enhance elimination of VPA. |
| Carnitine for VPA toxicity associated with hyperammonemia, lethargy, coma, cerebral edema, severe hepatocellular injury, or serum VPA concentration >450 mcg/mL (>3120 micromol/L). |
| 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 8 hours. |
| Benzodiazepine for seizures (eg, lorazepam 2 mg IV; repeat after 5 to 10 minutes as needed for refractory seizures). |
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