Effect of furosemide on ductal closure and renal function in indomethacin-treated preterm infants during the early neonatal period

Neonatology. 2010;98(2):191-9. doi: 10.1159/000289206. Epub 2010 Mar 16.


Background: Furosemide is known to increase renal prostaglandin synthesis. However, its influence on ductal closure and renal toxicities of indomethacin in preterm infants has not been conclusive, especially during the early neonatal period.

Objectives: To identify the effects of furosemide after indomethacin administration on the rate of patent ductus arteriosus (PDA) closure and renal function in preterm infants.

Methods: 68 infants (gestational age <34 weeks and birth weight <2,000 g) receiving indomethacin therapy (one course: 0.2-0.1-0.1 mg/kg q 12 h, mostly started <48 h after birth) were randomly assigned to the furosemide (n = 35) or control (n = 33) group. Each indomethacin dose was followed by furosemide (1.0 mg/kg) or placebo. The primary (PDA closure) and secondary (acute renal failure (ARF) and others) outcomes were assessed. Renal parameters before and 0-12 and 24-36 h after the first course of indomethacin were also investigated.

Results: In an intention-to-treat analysis, there were no differences in the PDA closure rate between the furosemide (29/34) and the control (27/29) group (p = 0.437). The incidence of ARF (serum creatinine >1.6 mg/dl) was greater in the furosemide group (20/34) than in the control group (3/29) (p < 0.001). Compared with the control group, serum creatinine and cystatin C levels and fractional excretion of sodium were significantly increased in the furosemide group for 24-36 h after indomethacin therapy (p < 0.01). There were no between-group differences in mortality and other neonatal morbidity rates.

Conclusions: Use of furosemide in combination with indomethacin increased the incidence of ARF but did not affect the PDA closure rate in preterm infants.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Acute Kidney Injury / chemically induced*
  • Acute Kidney Injury / physiopathology
  • Creatinine / blood
  • Cyclooxygenase Inhibitors / pharmacology*
  • Drug Interactions
  • Ductus Arteriosus, Patent / drug therapy*
  • Female
  • Furosemide / pharmacology*
  • Gestational Age
  • Glomerular Filtration Rate / drug effects
  • Humans
  • Indomethacin / pharmacology*
  • Infant, Newborn
  • Infant, Premature*
  • Intensive Care Units, Neonatal
  • Kidney / drug effects
  • Kidney / physiopathology
  • Male


  • Cyclooxygenase Inhibitors
  • Furosemide
  • Creatinine
  • Indomethacin