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Risk factors for hyperammonemia in pediatric patients with epilepsy
Author(s) -
Yamamoto Yoshiaki,
Takahashi Yukitoshi,
Imai Katsumi,
Mishima Nobuyuki,
Yazawa Rei,
Inoue Kazuyuki,
Itoh Kunihiko,
Kagawa Yoshiyuki,
Inoue Yushi
Publication year - 2013
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.12125
Subject(s) - hyperammonemia , epilepsy , odds ratio , medicine , valproic acid , concomitant , anticonvulsant , confidence interval , incidence (geometry) , phenytoin , zonisamide , gastroenterology , risk factor , topiramate , pediatrics , psychiatry , physics , optics
Summary Purpose To identify risk factors for hyperammonemia in pediatric patients with epilepsy. Methods 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. Key Findings 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. Significance 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.