Diferencia entre revisiones de «Valproic acid toxicity»

(Text replacement - "assoc " to "associated ")
(Fix drug name: use canonical Levocarnitine instead of redirect Levo-carnitine)
 
(No se muestran 6 ediciones intermedias de 4 usuarios)
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==Clinical Features==
==Clinical Features==
*CNS depression
*[[AMS|CNS depression]]
*Hypotension
*[[Ataxia]]
*[[Hypotension]]
*Respiratory depression
*Respiratory depression


==Evaluation==
==Evaluation==
*Level
*Level
**Does not correlate well with toxicity
**Does not correlate well with toxicity (can be therapeutic with toxicity)
**Adverse effects increase with level >150
**Adverse effects increase with level >150
*Chemistry
*Chemistry
**[[Hypocalcemia]], [[hypernatremia]], [[hypophosphatemia]], AG [[metabolic acidosis]]
**[[Hypocalcemia]], [[hypernatremia]], [[hypophosphatemia]], AG [[metabolic acidosis]]
*LFT
*[[LFTs]]
**Elevated transaminases  
**Elevated transaminases  
*Hyperammonemia
*[[Hyperammonemia]]
**Can be asymptomatic or cause Valproate associated Hepatic Encephalopathy (VPE)
**Can be asymptomatic or cause Valproate associated [[Hepatic Encephalopathy]] (VPE)
**Secondary to L-Carnitine and Acetyl-CoA depletion which inhibits urea cycle  
**Secondary to L-Carnitine and Acetyl-CoA depletion which inhibits urea cycle  
**Can be seen with therapeutic VPA levels and normal LFTs
**Can be seen with therapeutic VPA levels and normal LFTs
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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>


===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 (VPA level >500 mcg/mL) 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>


==Disposition==
==Disposition==
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<references/>
<references/>


[[Category:Toxicology]]
[[Category:Toxicology]
==Medication Dosing==
*{{MedicationDose|drug=Levocarnitine|dose=100 mg/kg IV bolus, then 50 mg/kg q8hr|route=IV|context=Antidote (enhances VPA metabolism)|indication=Valproic acid toxicity|population=Adult|notes=For lethargy, coma, hyperammonemia, hepatic dysfunction}}
*{{MedicationDose|drug=Naloxone|dose=0.4-2 mg, may repeat|route=IV|context=Reversal of CNS depression|indication=Valproic acid toxicity|population=Adult|notes=May reverse CNS depression by unclear mechanism}}
 
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Revisión actual - 17:44 20 mar 2026

Background

  • Peak concentration occurs within 4hr (12-18hr for controlled release forms)

Clinical Features

Evaluation

  • Level
    • Does not correlate well with toxicity (can be therapeutic with toxicity)
    • Adverse effects increase with level >150
  • Chemistry
  • LFTs
    • 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

Levo-carnitine

  • Increases valproate metabolism and recommended for patients with:
    • 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[1][2]

Naloxone

  • May be effective in reversing CNS depression by unclear mechanism[3][4]

Dialysis

  • Effective but reserved for severe overdoses (VPA level >500 mcg/mL) 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

  1. ↑ Ishikura H. et al. Valproic acid overdose and L-carnitine therapy. J Anal Toxicol. 1996 Jan-Feb. 20(1):55-8.
  2. ↑ Russell S. Carnitine as an antidote for acute valproate toxicity in children. Curr Opin Pediatr. 2007 Apr. 19(2):206-10.
  3. ↑ Roberge R. et al. Use of naloxone in valproic acid overdose: case report and review. J Emerg Med. 2002 Jan;22(1):67-70.
  4. ↑ Thanacoody HK. Chronic valproic acid intoxication: reversal by naloxone. Emerg Med J. 2007 Sep. 24(9):677-8.
  5. ↑ 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.

[[Category:Toxicology]

Medication Dosing

  • Levocarnitine 100 mg/kg IV bolus, then 50 mg/kg q8hr IV — For lethargy, coma, hyperammonemia, hepatic dysfunction
  • Naloxone 0.4-2 mg, may repeat IV — May reverse CNS depression by unclear mechanism

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