Effect of prophylactic indomethacin in extremely low birth weight infants

초극소 저출생체중아에서 예방적 indomethacin 투여효과

  • Lee, Bo Lyun (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Kim, Su Jin (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Koo, Soo Hyun (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Jeon, Ga Won (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Chang, Yun Sil (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Park, Won Soon (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine)
  • 이보련 (성균관대학교 의과대학 삼성서울병원 소아과) ;
  • 김수진 (성균관대학교 의과대학 삼성서울병원 소아과) ;
  • 구수현 (성균관대학교 의과대학 삼성서울병원 소아과) ;
  • 전가원 (성균관대학교 의과대학 삼성서울병원 소아과) ;
  • 장윤실 (성균관대학교 의과대학 삼성서울병원 소아과) ;
  • 박원순 (성균관대학교 의과대학 삼성서울병원 소아과)
  • Received : 2006.06.28
  • Accepted : 2006.08.10
  • Published : 2006.09.15

Abstract

Purpose : The purpose of this study was to investigate the effect of prophylactic indomethacin on reduction of patent ductus arteriosus(PDA) and intraventricular hemorrhage(IVH) in extremely low birth weight infants(ELBWI). Methods : Retrospective review of 84 ELBWI who were admitted to our neonatal intensive care unit from June 2004 to April 2006 was performed. Patients were divided into prophylactic group(n=28) and control group(n=56), where prophylactic indomethacin were given within 6 hours after birth. Clinical outcomes were compared between these groups. Results : There were no significant differences in gestational age, birth weight, incidence of hemodynamically significant PDA and severe IVH, and mortality between prophylactic group and control group. However, there were more frequent indications for therapeutic indomethacin, higher incidence of intestinal perforation, and longer time to achieve full enteral feeding in prophylactic group than control group. The incidence of other adverse events attributed to indomethacin prophylaxis did not differ between two groups. Conclusions : Prophylactic indomethacin may not prevent hemodynamically significant PDA and severe IVH in ELBWI. On the contrary, it may be associated with increased risk of adverse events. Further efforts should be investigated to decrease PDA and severe IVH in ELBWI.

목 적 : 신생아 중환자실에서 환자 치료의 질적, 양적 성장으로 인해 초극소 저출생체중아의 생존률은 많은 향상을 보였음에도 불구하고 동맥관개존증 및 뇌실내출혈과 연관된 이환율 및 사망률은 높은 실정이다. 이에 저자들은 초극소 저출생체중아에서 동맥관개존증과 뇌실내출혈을 예방하기 위한 시도된 약물 중 indomethacin의 예방적 투여에 대한 효과와 부작용을 분석하고자 하였다. 방 법 : 2004년 6월부터 2006년 4월까지 삼성서울병원 신생아 집중치료실에 입원한 재태연령 29주, 출생체중 1,000 g 미만의 초극소 저출생체중아 84명을 대상으로 후향적으로 의무기록을 조사하였다. Indomethacin을 생후 6시간 이내에 24시간 간격으로 0.1 mg/kg를 투여받은 예방군 28명과 대조군 56명으로 분류하여 두 군의 인구학적 및 주산기 인자, 동맥관개존증과 뇌실내출혈의 발생율 및 합병증과 사망률에 대해서 비교하였다. 결 과 : 인구학적 및 주산기 인자로서 재태연령과 출생체중은 각각 예방군에서 $25.1{\pm}1.3$주, $746{\pm}132g$이었으며 대조군에서는 $25.2{\pm}1.6$주, $738{\pm}142g$으로 두 군간에 차이가 없었다. 그 외에 성 비, 부당경량아, 쌍생아의 비율, 1분 및 5분 아프가 점수, 분만 방법, 임신성 고혈압, 임신성 당뇨, 산전 스테로이드 투여, 호흡곤란증후군의 유무, 융모양막염의 여부에서도 두 군간에 차이가 없었다. Indomethacin의 예방효과가 있을 것이라 기대했던 동맥관개존증과 3도 이상의 고도의 뇌실내출혈의 발생 비율에서는 두 군간에 의미 있는 차이는 없었다. 그러나 첫 번째 치료적 indomethacin이 투여된 빈도는 예방군에서 더 많았고 indomethacin 투여된 시간은 예방군에서 유의하게 늦었다. 사망률은 두 군 사이에 차이가 없었고 합병증과 관련된 인자로 폐출혈, 기흉, 기관지폐이형성증, 미숙아 망막증, 괴사성 장염의 발생에서는 유의한 차이는 없었다. 그러나 자발성 회장 천공의 발생은 대조군에서는 없었던 반면에 예방군에서는 10.7%로 나타났고, 괴사성 장염에서 천공된 경우를 합한 경우에도 예방군에서 의미있게 증가하였다. 또한 완전장관영양에 도달한 시기는 예방군에서 $31.5{\pm}17.1$일이었고, 대조군에서는 $22.1{\pm}7.6$일로 예방군에서 유의하게 늦었다. 태변이 배출되는 데까지 걸린 기간과, 위장관 출혈의 발생빈도, 신 기능의 손상 정도의 평가에서는 두 군간의 의미있는 차이는 없었다. 결 론 : 초극소 저출생체중아에서 출생 후 저용량 indomethacin을 예방적으로 사용하여 뇌실내출혈이나 동맥관개존증의 비율을 감소시키진 못하였고, 오히려 장관 천공의 비율을 증가시키고 장관영양의 진행이 늦어지는 부작용을 초래할 수 있다.

Keywords

Acknowledgement

Supported by : (재)인성의과학연구재단

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