Successful treatment by direct hemoperfusion of coma possibly resulting from mitochondrial dysfunction in acute valproate intoxication.
OBJECTIVE
We evaluated the efficacy of direct hemoperfusion (DHP) for treatment of acute valproate (VPA) intoxication and speculate on the biochemical perturbations that suggest a mechanism of coma induced by VPA overdose.


METHODS
The comatose patient was hospitalized approximately 6 h after ingesting 18 g VPA. DHP, with 200 g activated charcoal, was performed for 6 h. The plasma concentrations of VPA and Glasgow coma scale scores after admission were estimated. Before and after DHP, urine samples were tested in serial fashion for VPA metabolites, organic acids, and acyl carnitine esters of fatty acids.


RESULTS
Plasma VPA was efficiently adsorbed on activated charcoal. The patient's plasma concentration of VPA decreased from 471 microg/ml (2,830 microM) to 45 microg/ml (270 microM), at which point the patient became alert. The half-life (t1/2) of VPA was calculated as 4.4 h before DHP and as 1.8 h during DHP. Before DHP, lactate and VPA-glucuronide markedly increased in urine samples, but beta-keto-VPA, a major mitochondrial metabolite, was not detected. Urinary excretion of carnitine esters of medium chain (C8-C10) dicarboxylic acids was increased. After DHP, lactate and VPA-glucuronide decreased, but a significant amount of beta-keto-VPA was demonstrated. Carnitine esters of medium chain dicarboxylic acids were decreased.


CONCLUSIONS
DHP with activated charcoal was effective treatment for the patient with acute VPA intoxication and coma. The onset of coma may have been related to inhibition of beta-oxidation in the mitochondria, which was reversible by elimination of plasma VPA by DHP.
Matsumoto
J
J
Department of Internal Medicine, Saga Prefectural Hospital Koseikan, Saga City, Japan.
Ogawa
H
H
Maeyama
R
R
Okudaira
K
K
Shinka
T
T
Kuhara
T
T
Matsumoto
I
I
D000208:Acute Disease; D000328:Adult; D002331:Carnitine / Q000652:urine; D002606:Charcoal; D003128:Coma / Q000139:chemically induced* / Q000175:diagnosis / Q000628:therapy*; D062787:Drug Overdose / Q000097:blood / Q000628:therapy; D005260:Female; D015600:Glasgow Coma Scale; D006464:Hemoperfusion / Q000379:methods*; D006801:Humans; D007773:Lactates / Q000652:urine; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D014635:Valproic Acid / Q000097:blood / Q000506:poisoning*
D007773:Lactates; D002606:Charcoal; D014635:Valproic Acid; D002331:Carnitine