Valproic acid toxicity: Difference between revisions
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*Hypotension | *Hypotension | ||
*Respiratory depression | *Respiratory depression | ||
==Diagnosis== | ==Diagnosis== | ||
*Level | *Level | ||
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**Adverse effects increase w/ level >150 | **Adverse effects increase w/ level >150 | ||
*Chemistry | *Chemistry | ||
**Hypocalcemia, hypernatremia, hypophosphatemia, AG metabolic acidosis | **[[Hypocalcemia]], [[hypernatremia]], [[hypophosphatemia]], AG [[metabolic acidosis]] | ||
*LFT | *LFT | ||
**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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==Treatment== | ==Treatment== | ||
*GI detox | *GI detox | ||
**Activated charcoal PO x1 or multidose (for delayed-release preparations) | **[[Activated charcoal]] PO x1 or [[multidose activated charcoal]] (for delayed-release preparations) | ||
*levo-carnitine | *levo-carnitine | ||
**Increases valproate metabolism | **Increases valproate metabolism | ||
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***Lethargy, coma, VPA assoc hyperammonemic encephalopathy, hepatic dysfunction | ***Lethargy, coma, VPA assoc hyperammonemic encephalopathy, hepatic dysfunction | ||
**100mg/kg IV bolus, followed by 50mg/kg Q8h or alternatively 50mg/kg/day IV in 3 divided doses | **100mg/kg IV bolus, followed by 50mg/kg Q8h or alternatively 50mg/kg/day IV in 3 divided doses | ||
*Naloxone | *[[Naloxone]] | ||
**May be effective in reversing CNS depression | **May be effective in reversing CNS depression | ||
*Dialysis | *Dialysis | ||
Revision as of 03:24, 13 November 2014
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
- GI detox
- Activated charcoal PO x1 or multidose activated charcoal (for delayed-release preparations)
- levo-carnitine
- Increases valproate metabolism
- Recommended for pts with:
- Lethargy, coma, VPA assoc hyperammonemic encephalopathy, hepatic dysfunction
- 100mg/kg IV bolus, followed by 50mg/kg Q8h or alternatively 50mg/kg/day IV in 3 divided doses
- Naloxone
- May be effective in reversing CNS depression
- Dialysis
- Effective
Disposition
- Consider d/c for pt with declining levels and pt is asymptomatic
Source
- Tintinalli
- Academic Life in Emergency Medicine: Valproic Acid-Induced Hyperammonemic Encephalopathy (Logan, Jill)