Comparison of ibuprofen and indomethacin therapy for patent ductus arteriosus in preterm infants.
BACKGROUND
Patent ductus arteriosus (PDA) is commonly found in very low-birthweight (VLBW) infants. The presence of respiratory distress syndrome (RDS) is also associated with increased frequency of significant PDA. Intravenous indomethacin has been used to treat and to prevent PDA in premature infants since 1976. However, concern remains regarding the safety of indomethacin, which affects renal, gastrointestinal and cerebral perfusion. Intravenous ibuprofen has recently been used to treat and to prevent PDA premature infants with PDA without reducing cerebral blood flow or affecting intestinal or renal hemodynamics. The aim of the present study is to compare intravenous ibuprofen and indomethacin with regard to efficacy and safety for the early treatment of PDA in preterm infants.


METHODS
A total of 63 preterm infants with RDS who had a birthweight of < or =1500 g and gestational age of < or =32 weeks, were enrolled in the present study. All patients were treated with nasal continuous positive airway pressure with additional oxygen supply in inspired air>30%, or with mechanical ventilation. The patients' serum platelet counts were>100,000/uL, and serum creatinine values were <1.5 mg/dL. There were no 3-4 grade intraventricular hemorrhages before randomization, and all patients were aged 2-7 days and had echo-cardio-graphic evidence of significant PDA. Patients were randomized into two groups: the first group of neonates (group A, n = 32) received intravenous ibuprofen lysine 10 mg/kg, followed by 5 mg/kg after 24 and 48 h; the second group (group B, n = 31) received intravenous indomethacin 0.2 mg/kg every 12 h for three doses.


RESULTS
Patent ductus arteriosus closed in 27 patients from the ibuprofen group (84.4%) and in 25 patients from the indomethacin group (80.6%). PDA reopened in three patients from the ibuprofen group (9.4%) and in three patients from the indomethacin group (9.7%). One patient in the ibuprofen group and two patients in the indomethacin group required ductal ligation. Serum creatinine and blood urea nitrogen (BUN) concentrations were lower in the ibuprofen group than in the indomethacin group. Urine output and creatinine clearance values were higher in the ibuprofen group than in the indomethacin group.


CONCLUSIONS
Ibuprofen therapy is as efficacious as indomethacin for the treatment of PDA in preterm infants. Infants treated with ibuprofen have higher creatinine clearance and urine output and lower serum creatinine and BUN values than infants treated with indomethacin.
Su
Pen-Hua
PH
Department of Pediatrics and Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan. ninaphsu@yahoo.com.cn
Chen
Jia-Yuh
JY
Su
Chi-Ming
CM
Huang
Tzu-Ching
TC
Lee
Hong-Shen
HS
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage*; D004374:Ductus Arteriosus, Patent / Q000150:complications / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage*; D007213:Indomethacin / Q000008:administration & dosage*; D007231:Infant, Newborn; D007235:Infant, Premature, Diseases / Q000188:drug therapy*; D007262:Infusions, Intravenous; D008297:Male; D012127:Respiratory Distress Syndrome, Newborn / Q000150:complications
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D007052:Ibuprofen; D007213:Indomethacin