see also:
[goldfrank - valproate](x-devonthink-item://2F041FBD-FF1C-4E21-9CD5-5550C288F006?page=751&istart=6029&ilength=12&search=VALPROIC%20ACID)
> [!Key Points]
> - dose-dependent CNS depression **may be delayed up to 12 hours**
> - **risk dose:** 400-1000mg/kg+ . children > 200mg/kg. > 500mg/L in serum is bad
> - Antidote:: MDAC, haemodialysis
>
# Risk assessment
==dose-related risk==
|dose|effect|
|---|---|
|<200mg/kg|asymptomatic, mild drowsiness and ataxia|
|200-400mg/kg|variable CNS depression; airway control rarely needed|
|400-1000mg/kg|significant CNS depression likely, Coma requiring intubation may be delayed 12 hours after ingestion. as dose increase within this range, more severe multi-system tox is observed|
|>1000g/kg|potentially lethal with profound prolonged coma and multiple organ tox, cerebral oedema, hypotension, [[Lactic acidosis]], #hypoglycaemia , [[hypernatremia]], [[Hypocalcemia]], and bone marrow suppression|
| serum level | effect |
| :------------------------------------- | :------------------------------------------------- |
| <3,400 micromol/L (500mg/L) | not usually a/w multiple organ effects |
| >35000 micromol/L (>500 mg/L) | usually coma p+/- other organ effects |
| >7000 micromol/L (?1000mg/L) | frequently life-threatening multiple organ effects |
| >14,000 micro mol/L (>2000 mg/L) | death without urgent haemodialysis |
# Toxic Mechanism
- increases levels of **GABA** → CNS inhibition
- in large doses, interferes with mitochondrial metabolic pathways
## toxicokinetics
- well absorbed orally
- may be slow and erratic absorption in tox overdose; peak levels may be delayed 18 hours
- highly protein bound, small Vd
- hepatic metabolism to produce multiple active metabolites
# Clinical features
==dose dependent== CNS depression may be delayed 12 hours
- usually present asymptomatic
- progressive deterioration in consciousness
- in large ingestions, coma accompanied by
- ↑ AG metabolic acidosis
- #hypoglycaemia
- [[hypernatremia]]
- [[Hypocalcemia|hypocalcaemia]]
- ↑ ammonia
# Treatment
- decontamination activated charcoal in doses >400mg/kg
- in larger doses secure airway
- can give [[Decontamination#Multi dose activated charcoal]]
- [[haemodialysis]] removes valproic acid efficiently
- indicated if >1000 mg/kg with serum level >7000 micromol/L (1000mg/L)
- serum level > 10,400 mic mol/L (1500mg/L)
- [[Lactic acidosis]] or cardiovascular instability
# Disposition
- <200mg/kg observed in ward for 8 hours
- larger doses need close monitoring
# Related Questions
## activated charcoal
- [ ] 1Q: [Polypharmacy overdose](x-devonthink-item://5B3989BE-73BA-4EB6-8D42-758DAA229A56?page=20) -- [Answer](x-devonthink-item://F6B57015-DA53-404D-804A-55DCA60971A6?page=19)
- [ ] 2Q: [Overdose](x-devonthink-item://80040649-2DDB-4266-9A7C-4DE4E6DD4AE6?page=14) -- [Answer](x-devonthink-item://C96EDD2F-137A-43E5-80EE-5F42C5971D55?page=19)
- [ ] 3Q: [Paracetamol Overdose](x-devonthink-item://3D57C3FE-3B52-42E0-9FBD-E4034F60C5B7?page=6) -- [Answer](x-devonthink-item://75D8E35B-EE77-4D1B-A665-438451C976AE?page=22)
## charcoal
- [ ] 6Q: [Altered consciousness and altered ECG](x-devonthink-item://554C45F7-8661-4467-BD61-8A79B6ECABF4?page=5) -- [Answer](x-devonthink-item://554C45F7-8661-4467-BD61-8A79B6ECABF4?page=6)
## hypocalcaemia
- [ ] 11Q: [Abnormal VBG](x-devonthink-item://87BC05C2-0A6B-436D-B51A-75E14AA5EA7E?page=6) -- [Answer](x-devonthink-item://98D17FA0-225B-4E94-B21C-4E36D5C76A7C?page=58)