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The age and dose-related hyponatremia during carbamazepine and oxcarbazepine therapy in epileptic children

소아 경련 환자에서 carbamazepine과 oxcarbazepine 치료 시 환자 연령과 약물 용량과 저나트륨혈증의 연관성에 대한 연구

  • Lee, Kyu Ha (Department of Pediatrics, College of Medicine, The Kyunghee University) ;
  • Song, Jun Hyuk (Department of Pediatrics, College of Medicine, The Kyunghee University) ;
  • Cha, Sung Ho (Department of Pediatrics, College of Medicine, The Kyunghee University) ;
  • Chung, Sa Jun (Department of Pediatrics, College of Medicine, The Kyunghee University)
  • 이규하 (경희대학교 의과대학 소아과학교실) ;
  • 송준혁 (경희대학교 의과대학 소아과학교실) ;
  • 차성호 (경희대학교 의과대학 소아과학교실) ;
  • 정사준 (경희대학교 의과대학 소아과학교실)
  • Received : 2007.10.20
  • Accepted : 2007.12.12
  • Published : 2008.04.15

Abstract

Purpose : To assess the prevalence of hyponatremia in epileptic children receiving carbamazepine or oxcarbazpine, we investigate serum sodium changes according to age, serum carbamazepine level, and daily oxcarbazepine dosage, and the prevalence of symptoms of hyponatremia. Methods : We reviewed the clinical data of the 197 children receiving carbamazepine and/or oxcarbazepine with or without antiepileptic therapy. And these were classified into the carbamazepine treated patients (group I), oxcarbazepine treated patients (group II), and carbamzepine or oxcarbazepine with other antiepileptics treated patients (group III). Potentially predictive values for development of hyponatremia were examined in each group: age, plasma level of carbamazepine and daily dosage of oxcarbazepine. We assessed the symptoms of hyponatremia. Results : The overall prevalence of hyponatremia was 20.8% (group I, II and III : 17.9%, 22.6%, and 21.8%, respectively), and the prevalence in groups II and III compared with controls (P<0.03) was significantly lower. The changes of serum sodium levels relation to age were not significantly different. The changes of serum sodium levels by increasing of serum levels of carbamazepine and dosage of oxcarbazepine were statistically significant (P<0.01). Among the 41 patients who had biochemical hyponatremia, the prevalence of hyponatremic symptoms was 17.1%. Conclusion : Hyponatremia may occur relatively more frequently with oxcarbazepine or combined other antiepileptics than carbamzepine therapy only. Age of children receiving carbamazepine or oxcarbazepine was no predictive value for occurrence of hyponatremia. The patients whose serum level were less than 125 mEq/L showed more severe clinical symptoms than any other study groups.

목 적 : Carbamazepine은 전신 긴장간대 발작과 부분발작에 효과적으로 사용되나 부작용으로 항이뇨 작용과 저 나트륨 혈증이 유발될 수 있다. 또한 oxcarbazepine도 carbamazepine의 케톤 유도체로서 저 나트륨 혈증을 유발 할 수 있다. 이에 저자들은 carbamazepine과 oxcarbazepine을 복용한 환자의 연령, 혈중 carbamazepine 농도, oxcarbazepine의 복용량과 저 나트륨 혈증과의 관계, 저 나트륨 혈증 증상의 유병률에 대한 연구를 시행하였다. 방 법 : 경희대학교 소아청소년과 외래에서 carbamazepine을 단독 투여한 환자와 oxcarbazepine 단독 투여한 환자와 carbamazepine 또는 oxcarbazepine과 다른 항경련제를 병용한 환자 197명을 대상으로 하였다. Carbamazepine을 단독 투여한 군( I군, 67명), oxcarbazepine 단독 투여한 군( II군, 75명), carbamazepine 또는 oxcarbazepine과 다른 항경련제를 병용 투여한 군( III군, 55명)으로 구분하여서 연령과 항경련제 투여 후의 혈중 나트륨 농도를 비교하고 I군에서는 carbamazepine의 혈중 농도와 혈중 나트륨 농도를, II군에서는 oxcarbazepine의 투여 용량과 혈중 나트륨 농도 변화를 비교하였다. 각 그룹의 저 나트륨 혈증의 의한 증상(두통, 구토, 피로감, 경련, 불안, 섬망, 정신 착란)을 기록하였다. 결 과 : 전체 조사 대상의 항경련제 투여 후 저 나트륨 혈증은 41명(20.8%)에서 발견되었고 각각 I군은 12명(17.9%), II군은 17명(22.6%), III군은 12명(21.8%)에서 저 나트륨 혈증이 나타났다. II군과 III군은 항경련제 투여 전과 비교 시 유의한 차이를 보였다(P<0.03). 혈중 나트륨 농도 변화와 환자의 연령 사이에는 통계학적으로 유의한 차이는 없었다. 혈중 carbamazepine 농도 증가와 혈중 나트륨 농도의 변화, oxcarbazepine의 하루 투여량 증가에 따른 혈중 나트륨 농도의 변화 사이에는 통계학적으로 유의한 차이를 보였다(P<0.01). 혈중 농도 135 mEq/L 미만의 저 나트륨 혈증을 보인 41명의 환자 중에서 저 나트륨 혈증 증상을 보인 환자는 7명(17.1%) 였고 혈중 나트륨 농도가 120 mEq/ L 이상 125 mEq/L 이하 인 환자는 5명으로 오심과 구토, 피로감, 두통을 호소하였다. 혈중 나트륨 농도가 120 mEq/L 미만의 2명의 환자들은 반복되는 경련, 의식 혼란, 불안감, 망상 증세를 보였다. 결 론 : Carbamazepine의 단독 투여 시 보다 oxcarbazepine이나 다른 항경련제와 병용 투여 시 저 나트륨 혈증의 발생율이 높았다. 연령과 carbamazepine과 oxcarbazepine 투여 후 혈중 나트륨 농도 사이에는 별 상관 관계가 없는 반면 carbamazepine의 혈중 농도 증가와 oxcarbazepine의 투여량 증가 시 혈중 나트륨 농도가 통계학적으로 의미있게 감소하였다. 혈중 나트륨 농도가 125 mEq/L 미만인 환자에서 심한 임상 증상을 보였다.

Keywords

References

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