Valproic Acid Intoxication and Venovenous Hemofiltration
December 8, 2009, 11:24 pm
SEVERE VALPROIC ACID INTOXICATION: CASE STUDY ON THE UNBOUND FRACTION AND THE APPLICABILITY OF EXTRACORPOREAL ELIMINATION van den Broek MPH et al. European J Emerg Med 2009;:330-332.
This case report makes the point that although valproic acid (VPA) is largely bound to protein at therapeutic concentrations, in overdose the protein-binding sites become saturated and a greater percentage of the drug is unbound, making it susceptible to extracorporeal elimination, either hemodialysis or venovenous hemofiltration. Whether to initiate enhanced elimination is a clinical decision, based on the patient’s condition, the VPA level, and possibly the serum albumin and ammonia levels. A recent article we reviewed in TPR made a similar point. There has never been an adequate study comparing use of hemodialysis or hemofiltration versus supportive care alone in severe VPA intoxication — and there probably never will be.
precordialthump Says:
Hi Leon,
Nice to see a few papers highlighted on TPR about valproate OD and enhanced elimination.
I’m pretty comfortable with the absence of an RCT proving that hemofiltration/ hemodialysis improves outcomes in severe valproate toxicity – I will still use it! But how severe is severe enough?
I’d be interested in your personal rules of thumb. It seems a good idea to start hemodialysis before there is evidence of multi-organ toxicity.
In general, I’ve been taught these thresholds for starting hemodialysis:
1. ingestion of 1g/kg sodium valproate WITH a serum valproate level of >1000 mg/L
2. serum valproate level >1500mg/L at any time
3. evidence of severe toxicity – worsening lactic acidosis or hemodynamic instability.
But I’m sure there are lots of ways to skin this particular cat…
December 9th, 2009
Leon Says:
Hello precordialthump:
Although I’m generally reluctant in most poisonings solely on the basis of a number, I think that virtually all patients with valproate levels > 1000 mg/L would be clinically sick enough to justify starting extracorporeal removal. Certainly anyone who was getting worse or had increasing levels despite good supportive care would be candidate. Also anyone with significant impairment of hepatic function.
December 9th, 2009