Valproic acid toxicity: Difference between revisions
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*[[Activated charcoal]] PO x1 or [[multidose activated charcoal]] (for delayed-release preparations) | *[[Activated charcoal]] PO x1 or [[multidose activated charcoal]] (for delayed-release preparations) | ||
===Levo-carnitine=== | ===[[Levo-carnitine]]=== | ||
*Increases valproate metabolism and recommended for patients with: | *Increases valproate metabolism and recommended for patients with: | ||
**Lethargy, coma, VPA associated hyperammonemic encephalopathy, hepatic dysfunction | **Lethargy, coma, VPA associated hyperammonemic encephalopathy, hepatic dysfunction | ||
**100mg/kg IV bolus, followed by 50mg/kg Q8h or alternatively 50mg/kg/day IV in 3 divided doses<ref>Ishikura H. et al. Valproic acid overdose and L-carnitine therapy. J Anal Toxicol. 1996 Jan-Feb. 20(1):55-8.</ref><ref>Russell S. Carnitine as an antidote for acute valproate toxicity in children. Curr Opin Pediatr. 2007 Apr. 19(2):206-10.</ref> | **100mg/kg IV bolus, followed by 50mg/kg Q8h or alternatively 50mg/kg/day IV in 3 divided doses<ref>Ishikura H. et al. Valproic acid overdose and L-carnitine therapy. J Anal Toxicol. 1996 Jan-Feb. 20(1):55-8.</ref><ref>Russell S. Carnitine as an antidote for acute valproate toxicity in children. Curr Opin Pediatr. 2007 Apr. 19(2):206-10.</ref> | ||
===[[Naloxone]]=== | ===[[Naloxone]]=== | ||
*May be effective in reversing CNS depression by unclear mechanism<ref>Roberge R. et al. Use of naloxone in valproic acid overdose: case report and review. J Emerg Med. 2002 Jan;22(1):67-70.</ref><ref>Thanacoody HK. Chronic valproic acid intoxication: reversal by naloxone. Emerg Med J. 2007 Sep. 24(9):677-8.</ref> | *May be effective in reversing CNS depression by unclear mechanism<ref>Roberge R. et al. Use of naloxone in valproic acid overdose: case report and review. J Emerg Med. 2002 Jan;22(1):67-70.</ref><ref>Thanacoody HK. Chronic valproic acid intoxication: reversal by naloxone. Emerg Med J. 2007 Sep. 24(9):677-8.</ref> | ||
Revision as of 17:03, 19 October 2016
Background
- Peak concentration occurs within 4hr (12-18hr for controlled release forms)
Clinical Features
- CNS depression
- Hypotension
- Respiratory depression
Evaluation
- Level
- Does not correlate well with toxicity
- Adverse effects increase with level >150
- Chemistry
- LFT
- Elevated transaminases
- Hyperammonemia
- Can be asymptomatic or cause Valproate associated Hepatic Encephalopathy (VPE)
- Secondary to L-Carnitine and Acetyl-CoA depletion which inhibits urea cycle
- Can be seen with therapeutic VPA levels and normal LFTs
- Level does not correlate with severity of VPE
Management
Activated charcoal
- Activated charcoal PO x1 or multidose activated charcoal (for delayed-release preparations)
Levo-carnitine
- Increases valproate metabolism and recommended for patients with:
Naloxone
Dialysis
- Effective but reserved for severe overdoses and refractory hemodynamic instability and metabolic acidosis that do not respond to fluid resuscitation[5]
Disposition
- Consider discharge for patient with declining levels and patient is asymptomatic
References
- ↑ Ishikura H. et al. Valproic acid overdose and L-carnitine therapy. J Anal Toxicol. 1996 Jan-Feb. 20(1):55-8.
- ↑ Russell S. Carnitine as an antidote for acute valproate toxicity in children. Curr Opin Pediatr. 2007 Apr. 19(2):206-10.
- ↑ Roberge R. et al. Use of naloxone in valproic acid overdose: case report and review. J Emerg Med. 2002 Jan;22(1):67-70.
- ↑ Thanacoody HK. Chronic valproic acid intoxication: reversal by naloxone. Emerg Med J. 2007 Sep. 24(9):677-8.
- ↑ Tank JE. et al. Simultaneous "in series" hemodialysis and hemoperfusion in the management of valproic acid overdose. Am J Kidney Dis. 1993 Aug. 22(2):341-4.