title: Extracorporeal management of valproic acid overdose: a large regional experience.
abstract: BACKGROUND
  Valproic acid intoxication is common in North America. Although extra-corporeal therapy has been proposed as beneficial in managing significant exposures, evidence to support its use is limited to isolated case reports. A systematic review has not been performed.
  
  
  METHODS
  All cases of valproic acid overdose in Ontario, Canada, reported to the Hospital for Sick Children Poison Information Centre (PIC) between January 1st and July 31st 2002 were reviewed. Patients with valproic acid levels > 100 microg/mL were divided into two groups: those treated with and without extra-corporeal therapy. All hospital-measured valproic acid levels and additional clinical information including elimination half-life and clearance were obtained for patients treated with extra-corporeal therapy.
  
  
  RESULTS
  There were 28,362 calls to the PIC, of which 139 related to valproic acid poisoning. Thirty-two patients had peak levels > 100 microg/mL. 26 patients were managed conservatively and 6 with extra-corporeal therapy. Survival was 100% in both groups. Patients who received extra-corporeal therapy had higher peak levels (p=0.005), were more frequently treated with charcoal (P=0.006), required intensive care admission (P=0.019), intubation (P<0.001), and vasopressors (P=0.004). Valproic acid elimination was enhanced about tenfold through extra-corporeal methods. Complications included tonic-clonic seizures in 1 patient who received hemodialysis, and thrombocytopenia in 1 patient who underwent hemoperfusion.
  
  
  CONCLUSIONS
  Hemodialysis and hemoperfusion are safe, effective adjuncts in the management of serious valproic acid intoxication and should be considered for patients with hemodynamic or neurological instability. Further study is needed to determine whether hemodialysis alone versus combined hemodialysis-hemoperfusion is more effective for this condition.
authors.affiliation: Division of Nephrology, Department of Medicine, University of Toronto, ON, Canada.
authors.forename: Sheldon M
authors.initials: SM
authors.lastname: Singh
authors.forename: Brendan B
authors.initials: BB
authors.lastname: McCormick
authors.forename: Stefan
authors.initials: S
authors.lastname: Mustata
authors.forename: Margaret
authors.initials: M
authors.lastname: Thompson
authors.forename: G V Ramesh
authors.initials: GV
authors.lastname: Prasad
mesh_terms: D000328:Adult; D062787:Drug Overdose / Q000628:therapy; D005112:Extracorporeal Circulation / Q000009:adverse effects; D005260:Female; D006207:Half-Life; D006464:Hemoperfusion / Q000009:adverse effects; D006801:Humans; D008297:Male; D006435:Renal Dialysis / Q000009:adverse effects; D014635:Valproic Acid / Q000493:pharmacokinetics / Q000506:poisoning*
chemical_list: D014635:Valproic Acid