Duarte J, Macias S, Coria F, Fernandez E, Clavería L E
Department of Clinical Neurology, General Hospital of Segovia, Spain.
Ann Pharmacother. 1993 May;27(5):582-3. doi: 10.1177/106002809302700510.
To report a case of hyperammonemia without hepatic dysfunction as a possible cause of lethargy, stupor, and coma in a woman after valproic acid (VPA) administration, and discuss the possible different mechanisms of ammonia elevation and coma.
A woman diagnosed with complex partial seizures that secondarily generalize was treated with phenytoin (PHT) 250 mg/d for 18 years. Three months before admission, this dosage was increased to 300 mg/d and phenobarbital (PB) 100 mg/d was added because the seizures were incompletely controlled. The patient developed a progressive inability to walk. She was diagnosed as having PHT intoxication. VPA therapy was begun while PHT was being tapered and progressive impairment of consciousness occurred. This evolved into a coma without focal neurologic signs, and was accompanied by isolated hyperammonemia without hepatic failure.
Adverse effects attributable to VPA were reviewed in the literature. Occasionally, VPA may lead to severe secondary effects such as hepatic failure and coma. In these cases increased blood concentrations of transaminases, bilirubin, and ammonia have been found. Several reports have stressed the existence of hyperammonemic coma without biochemical evidence of hepatic failure, which is what occurred in our patient. This suggests that isolated hyperammonemia and hepatic failure after VPA treatment may have a different biochemical basis.
VPA-induced coma with hyperammonemia and without evidence of hepatic failure should be considered in patients being treated with PHT or PB when VPA is administered concomitantly. This case report shows the importance of clinical monitoring and immediate drug discontinuation when drowsiness, gastrointestinal symptoms, or lethargy occur.
报告一例在女性患者服用丙戊酸（VPA）后出现高氨血症且无肝功能障碍，这可能是导致其嗜睡、昏睡和昏迷的原因，并探讨氨升高和昏迷可能的不同机制。
一名被诊断为继发全身性发作的复杂部分性癫痫的女性，接受苯妥英钠（PHT）250mg/d治疗18年。入院前三个月，由于癫痫控制不完全，该剂量增加至300mg/d，并加用苯巴比妥（PB）100mg/d。患者逐渐出现行走困难，被诊断为PHT中毒。在逐渐减少PHT剂量的同时开始VPA治疗，随后出现意识进行性损害，进而发展为无局灶性神经体征的昏迷，并伴有孤立性高氨血症且无肝衰竭。
回顾了文献中归因于VPA的不良反应。偶尔，VPA可能导致严重的继发效应，如肝衰竭和昏迷。在这些病例中，已发现转氨酶、胆红素和氨的血浓度升高。几份报告强调了存在无肝衰竭生化证据的高氨血症昏迷，这正是我们患者所发生的情况。这表明VPA治疗后孤立性高氨血症和肝衰竭可能有不同的生化基础。
在同时使用VPA治疗接受PHT或PB治疗的患者时，应考虑VPA诱导的伴有高氨血症且无肝衰竭证据的昏迷。本病例报告显示了在出现嗜睡、胃肠道症状或嗜睡时进行临床监测和立即停药的重要性。
