Valproic acid toxicity: Difference between revisions
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**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> | |||
===Dialysis=== | ===Dialysis=== | ||
*Effective but reserved for severe overdoses and refractory hemodynamic instability and metabolic acidosis that do not respond to fluid resuscitation<ref>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. </ref> | *Effective but reserved for severe overdoses and refractory hemodynamic instability and metabolic acidosis that do not respond to fluid resuscitation<ref>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. </ref> | ||
Revision as of 23:50, 10 February 2016
Background
- Peak concentration occurs within 4hr (12-18hr for controlled release forms)
Clinical Features
- CNS depression
- Hypotension
- Respiratory depression
Diagnosis
- Level
- Does not correlate well w/ toxicity
- Adverse effects increase w/ 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
Treatment
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 d/c for pt with declining levels and pt is asymptomatic
Source
- ↑ 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.