Valproic acid toxicity: Difference between revisions
NadavNahumi (talk | contribs) |
ClaireLewis (talk | contribs) No edit summary |
||
| (2 intermediate revisions by one other user not shown) | |||
| Line 3: | Line 3: | ||
==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]] | ||
* | *[[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 | ||
| Line 33: | Line 34: | ||
*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 (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> | *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> | ||
Latest revision as of 21:20, 13 February 2021
Background
- Peak concentration occurs within 4hr (12-18hr for controlled release forms)
Clinical Features
- CNS depression
- Ataxia
- Hypotension
- Respiratory depression
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
- 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 (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
- ↑ 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.