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丙戊酸(Valproate)是治疗小儿癫痫常用药物之一。在使用中可发生两种类型的肝中毒。一种是与剂量有关的由于药物直接的损害,另一种是特发性原因不明的致死性损害。与剂量有关的肝中毒特点是在治疗的最初3个月期间,血清转氨酶(SGOT、SGPT)活性和血氨浓度短暂地升高,可占44%以上,常常没有症状,但亦可有恶心和萎靡,并不致死。另一类致死者与药物剂量无关而可能是由于特发性的反应,常是不可逆性损伤,肝功监测亦不易早期发现。至1982年为止。已知有62例因使用丙戊酸治疗而致肝中毒死亡。本文又报告2例因丙戊酸肝中毒死亡的小儿。其一在停药五天前血转氨酶活性正常,另1例停药前3周血转氨酶活性尚正常,在停药时仅有轻微肝中毒表现。病例例1,19个月,女孩,因癫痫持续状态于1982年住院。用苯巴比妥、苯妥英钠及安定均难以控制。出院时用卡巴咪嗪和丙戊酸联合疗法,两药的血浓度均在治疗范围。出院后每2周作SGOT检查,均正常。连用丙戊酸2个月,在一次正常SGOT之后1周,患儿呈萎靡,呕吐并再次住院。丙戊酸的血浓度达118μg/ml。停药3天后,血清浓度为6μg/ml。但大脑和肝功能进一步恶化。发生全身性水肿、黄疸、低血糖及反复性出血。为了清除有毒的代谢产物在第6天进行换血。第8天发生细菌性肺炎和败血症休克,第9天死亡。尸检时,光学显微镜显示明显的肝
Valproate is one of the commonly used drugs for treating epilepsy in children. There are two types of liver poisoning that can occur during use. One is dose-related due to direct damage to the drug and the other is lethal damage of unknown idiopathic causes. Dose-related hepatotoxicity is characterized by a transient increase in serum transaminase (SGOT, SGPT) activity and ammonia concentration, accounting for more than 44%, often without symptoms during the first 3 months of treatment, but may also have nausea and Sluggish, not lethal. Another type of lethal dose has nothing to do with the drug may be due to idiopathic reactions, often irreversible damage, liver function monitoring is not easy to find early. Until 1982. 62 are known to have died of liver toxicity due to valproic acid treatment. This article also reports 2 cases of children died of valproic acid liver poisoning. One of the five days before the withdrawal of serum aminotransferase activity was normal, the other 1 case 3 weeks before withdrawal of serum aminotransferase activity is still normal, only minor liver toxicity during withdrawal. Case 1, 19 months, girl, hospitalized in 1982 due to status epilepticus. With phenobarbital, phenytoin and diazepam are difficult to control. Discharged with carbamazepine and valproic acid combination therapy, the two drugs in the treatment of blood concentrations. SGOT examination every 2 weeks after discharge was normal. Even with valproic acid 2 months, 1 week after a normal SGOT, children were malaise, vomiting and hospitalized again. Valproic acid has a blood concentration of 118 μg / ml. Three days after discontinuation, the serum concentration was 6 μg / ml. But the brain and liver function worsened. Systemic edema, jaundice, hypoglycemia and recurrent bleeding. In order to remove toxic metabolites on the 6th day to exchange blood. Bacterial pneumonia and septic shock occurred on day 8 and died on day 9. At autopsy, light microscopy revealed a clear liver