Sodium Valproate (VPA, valproic acid)
In large overdoses, VPA causes coma and multi-organ failure. Haemodialysis is indicated for life-threatening toxicity.
Toxicity / Risk Assessment
Management
Large overdoses may result in delayed onset of toxicity
Supportive care with airway protection as required
and may present asymptomatic. Peak serum
Decontamination:
concentration may be delayed up to 16 hours. Toxicity
Activated charcoal 50 g within 4 hours of >400 mg/kg ingestion, OR after intubation (NGT). Repeat dose
may last days post massive OD.
if rising VPA concentration and intubated
Predicted toxicity by ingested dose:
Consider Whole Bowel Irrigation if ingestion >1000 mg/kg, intubated and <4 hours (Discuss with
<200 mg/kg: mild sedation
Clinical Toxicologist)
200-400 mg/kg: deeper CNS depression
- Check VPA serum concentration 4-6 hourly until decreasing
400-1000 mg/kg: likely to require intubation
Extracorporeal elimination
>1000 mg/kg: multi-organ failure, coma, cerebral
Consider haemodialysis or high flux haemofiltration:
oedema and death
Clinical features:
- CNS: ↓conscious, ataxia, coma, seizures, cerebral
oedema
- If VPA concentration > 6000 umol/L (850 mg/L) OR
- in cases of cardiovascular instability /cerebral oedema / metabolic acidosis pH <7.1
Disposition
<200 mg/kg: observe for at least 6 hours + decreasing VPA concentrations + VPA <3500 umol/L (500 mg/L)
- GI: Nausea, vomiting, abdominal pain
>200 mg/kg: observe for at least 12 hours + decreasing VPA concentrations + VPA <3500 umol/L (500 mg/L)
- CVS: ↑HR, hypotension, ↑QT interval
Predicted toxic effects by VPA concentrations:
- Metabolic: ↑ Na⁺, ↑ lactate, ↑ ammonia, ↓ Ca²⁺,
<3500 umol/L (500 mg/L): unlikely multi-organ effects
↓ glucose, metabolic acidosis, respiratory depression
>3500 umol/L (500 mg/L): coma +/- other organ effects
- Haematology: Myelosuppression – ↓neutrophils and
>7000 umol/L (1000 mg/L): multi-organ toxicity expected
platelets
AUSTIN CLINICAL TOXICOLOGY SERVICE GUIDELINE
>14000 umol/L (2000 mg/L): likely death without urgent HD
POISONS INFORMATION CENTRE: 13 11 26