Furosemide in indomethacin-treated infants - systematic review and meta-analysis

This study was designed to assess: (1) whether furosemide modifies the inci dence of failure to close a symptomatic patent ductus arteriosus (PDA) in r esponse to indomethacin in premature infants, (2) whether furosemide decrea ses renal and hydromineral side effects of indomethacin, and (3) whether th e effects of furosemide on renal function depend on initial extracellular v olume [assessed by blood urea nitrogen (BUN)/creatinine ratio]. We did a sy stematic review and meta-analysis of all published controlled trials assess ing either ductal closure or renal function after randomized allocation to treatment with indomethacin and furosemide versus indomethacin alone. All o f the three studies meeting entry criteria were small and had methodologica l limitations. The number of patients was too small to rule out a 10% risk increase in failure of ductal closure. After the first dose of indomethacin , patients receiving furosemide had higher urine output, fractional excreti on of sodium, and osmolar clearance than controls. Among patients with init ial BUN/creatinine ratio <20, those on furosemide had a higher glomerular f iltration rate (GFR) than controls. Among patients with initial BUN/creatin ine of 20-30, those on furosemide had a lower GFR than controls. Thus, dehy dration appears to be a contraindication for furosemide administration in p remature infants treated with indomethacin for symptomatic PDA. The risk-be nefit ratio of administering furosemide in well-hydrated patients treated w ith indomethacin for symptomatic PDA could only be assessed by a large rand omized clinical trial.