Ibuprofen Versus Indomethacin for Medical Closure of the Patent Arterial Duct: A Pooled Analysis by Route of Administration

Abstract

Introduction:Preterm infants are at increased risk of having a patent arterial duct (PAD). PADs may cause congestive heart failure, respiratory distress, necrotizing enterocolitis, and renal impairment. Consequently, in some infants, it becomes necessary to attempt closure of the PAD. Surgical closure can be difficult in small infants and is not without its risks; thus, medical closure offers advantages. Cyclooxygenase inhibitors have been used for medical closure of the PAD with both ibuprofen and indomethacin having been used clinically.Methods:We performed a systematic review of the literature to identify all studies comparing ibuprofen and indomethacin. Studies comparing ibuprofen and indomethacin for closure of the PAD in premature infants were included in the meta-analysis. A subanalysis was performed to compare the route of administration. Efficacy endpoints studied were PAD closure and surgical ligation while adverse effects studied were death in the first month of life, necrotizing enterocolitis, gastrointestinal bleeding, intestinal perforation, bronchopulmonary dysplasia in the first month of life, Grade 3 or 4 intraventricular hemorrhage, and change in the serum creatinine after treatment.Results:Ibuprofen and indomethacin were equally effective in closing the PAD in premature infants and demonstrated no difference in the incidence of adverse events. In respect to the route of administration, oral ibuprofen was as effective as intravenous indomethacin. When comparing both drugs via the intravenous route, the only difference noted between the ibuprofen and indomethacin was that ibuprofen was associated with a lesser increase in serum creatinine after treatment.Conclusion:Ibuprofen and indomethacin are equally effective in PAD closure without any difference in the incidence of adverse events. Importantly, oral ibuprofen was as effective as intravenous indomethacin.

Ibuprofen and indomethacin for the closure of the patent ductus arteriosus

“…Oliguria occurred in 5 (6.7%) infants treated with ibuprofen and in 14 (18.9%) infants treated with indomethacin (p = 0.03). 17 There were no significant differences with respect to other side effects and complications. Ibuprofen therapy on the third day of life is as efficacious as indomethacin for the treatment of patent ductus arteriosus in preterm infants with respiratory distress syndrome and is significantly less likely to induce oliguria.…”

“…12 The overall rate of ductal closure is similar in infants treated with intravenous indomethacin and oral ibuprofen. [17][18][19] Intravenous indomethacin is associated with higher side effects than oral ibuprofen. 18,19 Intravenous ibuprofen is associated with approximately 30% greater risk of chronic lung disease than intravenous indomethacin.…”

“…9 Oral ibuprofen appears to be as effective as intravenous ibuprofen and intravenous indomethacin for closing the patent ductus arteriosus. 17 The oral administration of ibuprofen is associated with a lesser increase in serum creatinine than the intravenous administration of indomethacin. 17 Indomethacin reduces the blood flow velocity in kidneys, intestine, and brain, ibuprofen has not this effect.…”

“…17 The oral administration of ibuprofen is associated with a lesser increase in serum creatinine than the intravenous administration of indomethacin. 17 Indomethacin reduces the blood flow velocity in kidneys, intestine, and brain, ibuprofen has not this effect. 1,14 In infants who received 2 or more courses, the decrease in urine output and the increase in serum creatinine concentration were not different between ibuprofen and indomethacin.…”

“…The discussion centers around the concepts of efficacy and cost. Loomba & Nijhawan 17 performed a systematic review of the literature comparing oral ibuprofen vs. intravenous indomethacin for closure of the patent ductus arteriosus in premature infants. Oral ibuprofen was as effective as intravenous indomethacin.…”