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


OBJECTIVE
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.
Division of Neonatology, Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Songpa-gu, Seoul, South Korea. mdleebs@amc.seoul.kr
Byong Sop
BS
Lee
Shin Yun
SY
Byun
Mi Lim
ML
Chung
Ji Young
JY
Chang
Hee Young
HY
Kim
Ellen Ai-Rhan
EA
Kim
Ki-Soo
KS
Kim
Soo-Young
SY
Pi
D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000503:physiopathology; D003404:Creatinine / Q000097:blood; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004347:Drug Interactions; D004374:Ductus Arteriosus, Patent / Q000188:drug therapy*; D005260:Female; D005665:Furosemide / Q000494:pharmacology*; D005865:Gestational Age; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D007231:Infant, Newborn; D007234:Infant, Premature; D007363:Intensive Care Units, Neonatal; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D008297:Male
D016861:Cyclooxygenase Inhibitors; D005665:Furosemide; D003404:Creatinine; D007213:Indomethacin