Outline the diagnostic features, complications and treatment of patients with an overdose of sodium valproate (valproic acid).
Sodium valproate is becoming more widely used (seizures, bipolar disorders, migraine), and is often prescribed as a slow release preparation. Overdose results in a progressive onset of lethargy and CNS depression, with many potential associated features (including hypotension, hypothermia, vomiting, diarrhoea, agitation and tremors). Complications include cerebral oedema (with prolonged coma), encephalopathy (elevated ammonia), hepatotoxicity (rarely fulminant), and electrolyte disorders (with hypernatraemia, hypocalcaemia, increased osmolality and elevated anion gap metabolic acidosis). Treatment is generally supportive but gastrointestinal decontamination is essential (including multiple dose activated charcoal &/or whole bowel irrigation if sustained release preparations, and increasing valproic acid levels). Carnitine supplementation may attenuate hepatotoxicity and hyper-ammonaemia.
This is hard, because there are no characteristic clinical features in this overdose. There is non-specific lethargy which progresses to drowsiness and coma. Then, the LFTs come back deranged, and when you do the ammonium level it is through then roof, which makes you think.
Complications of valproate overdose
One report linked below is an account of a truly massive (25g) valproate overdose, which did not require anything but supportive management, and which was not accompanied by any sort of massive organ system failure.
Isbister, Geoffrey K., et al. "Valproate overdose: a comparative cohort study of self poisonings." British Journal of clinical pharmacology 55.4 (2003): 398-404.
Lakhani, Mayur, and M. E. McMurdo. "Survival after severe self poisoning with sodium valproate." Postgraduate medical journal 62.727 (1986): 409-410.
Löscher, Wolfgang. "The discovery of valproate." Valproate. Birkhäuser Basel, 1999. 1-3.
Licari, Elisa, et al. "Life-threatening sodium valproate overdose: A comparison of two approaches to treatment*." Critical care medicine 37.12 (2009): 3161-3164.
Lheureux, Philippe ER, et al. "Science review: Carnitine in the treatment of valproic acid-induced toxicity–what is the evidence?." Critical Care 9.5 (2005): 431.