title: Risk factors for hyperammonemia in pediatric patients with epilepsy.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Clinical Research, National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan. yamamoty@szec.hosp.go.jp
authors: Yoshiaki
authors: Y
authors: Yamamoto
authors: Yukitoshi
authors: Y
authors: Takahashi
authors: Katsumi
authors: K
authors: Imai
authors: Nobuyuki
authors: N
authors: Mishima
authors: Rei
authors: R
authors: Yazawa
authors: Kazuyuki
authors: K
authors: Inoue
authors: Kunihiko
authors: K
authors: Itoh
authors: Yoshiyuki
authors: Y
authors: Kagawa
authors: Yushi
authors: Y
authors: Inoue
mesh_terms: D000086:Acetazolamide / Q000009:adverse effects / Q000627:therapeutic use; D000293:Adolescent; D000367:Age Factors; D000927:Anticonvulsants / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D005632:Fructose / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D022124:Hyperammonemia / Q000139:chemically induced*; D007223:Infant; D007555:Isoxazoles / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D010634:Phenobarbital / Q000009:adverse effects / Q000627:therapeutic use; D010672:Phenytoin / Q000009:adverse effects / Q000627:therapeutic use; D012189:Retrospective Studies; D012307:Risk Factors; D012737:Sex Factors; D000077236:Topiramate; D014635:Valproic Acid / Q000009:adverse effects / Q000627:therapeutic use; D000078305:Zonisamide
chemical_list: D000927:Anticonvulsants; D007555:Isoxazoles; D000077236:Topiramate; D005632:Fructose; D000078305:Zonisamide; D014635:Valproic Acid; D010672:Phenytoin; D000086:Acetazolamide; D010634:Phenobarbital