Department of Clinical Research, National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan.
Epilepsia. 2013 Jun;54(6):983-9. doi: 10.1111/epi.12125. Epub 2013 Feb 14.
To identify risk factors for hyperammonemia in pediatric patients with epilepsy.
A total of 2,944 pediatric patients (ages 0-15 years) were classified into the following three groups: a group without drug treatment (n = 445, group I), a group receiving antiepileptic drugs other than valproic acid (VPA) (n = 673, group II), and a VPA-treated group (n = 1,826, group III). Hyperammonemia was defined as a plasma ammonia level exceeding 100 μg/dl with reference to the standard range and previous reports.
The mean ammonia level of groups I, II, and III was 36.0, 56.0, and 86.8 μg/dl, respectively, and the incidence of hyperammonemia was 1.6%, 7.7%, and 31.7%, respectively. In each group, the mean ammonia level of patients aged 3 years or younger was significantly higher than that of patients aged 4-15 years. In group II, concomitant use of topiramate and zonisamide were risk factors for hyperammonemia (adjusted odds ratio [OR] 3.9, 95% confidence interval [CI] 1.7-9.2, and OR 3.5, 95% CI 1.9-6.5, respectively). In group III, the ammonia level increased in a VPA dose-dependent manner. At a VPA dose of 30 mg/kg, there was 4.3-fold increase in the incidence of hyperammonemia. The other significant risk factors identified were female gender (OR 1.3, 95% CI 1.0-1.6), symptomatic generalized epilepsy (OR 1.4, 95% CI 1.1-1.8), and the concomitant use of phenytoin (OR 4.7, 95% CI 3.3-6.9), phenobarbital (OR 2.2. 95% CI 1.6-3.2), acetazolamide (OR 6.6, 95% CI 2.5-17.2), topiramate, or zonisamide.
A young age and concomitant use of carbonic anhydrase inhibitors are associated with an increased risk of hyperammonemia regardless of whether the patient is taking VPA. In patients receiving VPA, concomitant use of phenytoin and/or phenobarbital enhances the risk of hyperammonemia. An increase in ammonia can be caused by multiple factors. Our results may help clinicians to avoid problems of hyperammonemia.
确定癫痫儿科患者高氨血症的危险因素。
将 2944 名儿科患者（0-15 岁）分为以下三组：无药物治疗组（n=445，I 组）、接受非丙戊酸抗癫痫药物治疗组（n=673，II 组）和丙戊酸治疗组（n=1826，III 组）。高氨血症定义为血浆氨水平超过 100μg/dl，参考标准范围和以往报告。
I、II 和 III 组的平均氨水平分别为 36.0、56.0 和 86.8μg/dl，高氨血症的发生率分别为 1.6%、7.7%和 31.7%。在每个组中，3 岁或以下患者的平均氨水平明显高于 4-15 岁患者。在 II 组中，托吡酯和左乙拉西坦的联合使用是高氨血症的危险因素（调整后的优势比[OR]分别为 3.9，95%置信区间[CI]为 1.7-9.2 和 3.5，95%CI 为 1.9-6.5）。在 III 组中，氨水平呈丙戊酸剂量依赖性增加。当丙戊酸剂量为 30mg/kg 时，高氨血症的发生率增加了 4.3 倍。确定的其他显著危险因素是女性（OR 1.3，95%CI 1.0-1.6）、症状性全面性癫痫（OR 1.4，95%CI 1.1-1.8）和苯妥英（OR 4.7，95%CI 3.3-6.9）、苯巴比妥（OR 2.2，95%CI 1.6-3.2）、乙酰唑胺（OR 6.6，95%CI 2.5-17.2）、托吡酯或左乙拉西坦的联合使用。
无论患者是否服用丙戊酸，年龄较小和同时使用碳酸酐酶抑制剂与高氨血症风险增加相关。在接受丙戊酸治疗的患者中，同时使用苯妥英和/或苯巴比妥会增加高氨血症的风险。氨的增加可能由多种因素引起。我们的结果可能有助于临床医生避免高氨血症的问题。
