Matsumoto J, Ogawa H, Maeyama R, Okudaira K, Shinka T, Kuhara T, Matsumoto I
Department of Internal Medicine, Saga Prefectural Hospital Koseikan, Saga City, Japan.
Epilepsia. 1997 Aug;38(8):950-3. doi: 10.1111/j.1528-1157.1997.tb01263.x.
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.
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.
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.
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.
我们评估了直接血液灌流（DHP）治疗急性丙戊酸盐（VPA）中毒的疗效，并推测提示VPA过量所致昏迷机制的生化紊乱情况。
该昏迷患者在摄入18g VPA后约6小时入院。使用200g活性炭进行了6小时的DHP。测定了入院后VPA的血浆浓度和格拉斯哥昏迷量表评分。在DHP前后，对尿液样本进行连续检测，以分析VPA代谢产物、有机酸和脂肪酸的酰基肉碱酯。
血浆VPA被有效地吸附在活性炭上。患者的血浆VPA浓度从471μg/ml（2830μM）降至45μg/ml（270μM），此时患者变得清醒。DHP前VPA的半衰期（t1/2）计算为4.4小时，DHP期间为1.8小时。DHP前，尿液样本中的乳酸和VPA - 葡萄糖醛酸显著增加，但未检测到主要的线粒体代谢产物β - 酮基 - VPA。中链（C8 - C10）二羧酸的肉碱酯尿排泄增加。DHP后，乳酸和VPA - 葡萄糖醛酸减少，但检测到大量的β - 酮基 - VPA。中链二羧酸的肉碱酯减少。
活性炭DHP是治疗急性VPA中毒和昏迷患者的有效方法。昏迷的发生可能与线粒体β - 氧化的抑制有关，通过DHP清除血浆VPA可使其逆转。
