Successful Treatment by Direct Hemoperfusion of Coma Possibly Resulting From Mitochondria1 Dysfunction in Acute Valproate Intoxication

Summary : Purpose: 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. Patient and Methods: The comatose patient was hospitalized ˜6 h afte...

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Published inEpilepsia (Copenhagen) Vol. 38; no. 8; pp. 950 - 953
Main Authors Matsumoto, Jyunji, Ogawa, Hisayuki, Maeyama, Ryutaro, Okudaira, Ken, Shinka, Toshihiro, Kuhara, Tomiko, Matsumoto, Isamu
Format Journal Article
LanguageEnglish
Published Oxford, UK Blackwell Publishing Ltd 01.08.1997
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Summary:Summary : Purpose: 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. Patient and Methods: The comatose patient was hospitalized ˜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 μml (2,830 μM) to 45 pg/ml (270 μM), 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 β‐keto‐VPA, a major mitochondria1 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 β‐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 β‐oxidation in the mitochondria, which was reversible by elimination of plasma VPA by DHP.
ISSN:0013-9580
1528-1167
DOI:10.1111/j.1528-1157.1997.tb01263.x