Comparison of Ketorolac and Indomethacin for the Closure of Patent Ductus Arteriosus among Preterm Infants Born at the Philippine General Hospital: A Randomized Controlled Crossover Design

Abstract

Background. Indomethacin has been the gold standard for the closure of patent ductus arteriosus (PDA). Still, the availability of the intravenous (IV) form has been a big issue precluding its use in the Philippines. IV ketorolac is another non-steroidal anti-inflammatory drug (NSAID) that is cheaper and more available in our country and used for post-cardiac surgery pain management among neonates.

Objectives. To compare the efficacy of ketorolac versus indomethacin in the closure of patent ductus arteriosus among preterm infants.

Methods. We conducted a randomized controlled, double-blind, crossover design, non-inferiority trial on the use of iindomethacin versus ketorolac among preterm infants with PDA. We enrolled preterm infants at 5-12 days postnatal life, diagnosed with PDA by echocardiography at the Philippine General Hospital (PGH). We excluded infants with upper gastrointestinal bleeding, renal failure, birthweight < 500 grams, septic shock, and lethal anomalies. Patients were randomly allocated between two treatment groups (indomethacin versus ketorolac). The primary outcome measure was PDA closure measured after the treatment course. Adverse events like oliguria and bleeding were recorded.

Results. A total of 27 preterm infants were randomly assigned to the indomethacin (0.2 mg/kg/dose) and ketorolac (0.6 mg/kg/dose) group. Ketorolac has a 60% success rate for PDA closure (9/15) compared to indomethacin 41.67% (5/12) (p=0.154). No renal insufficiency and bleeding diathesis were noted. Five patients died in the study, four in the group initially allocated in ketorolac and one in indomethacin. Causes of death were late-onset sepsis, bronchopulmonary dysplasia, and congenital adrenal hyperplasia.

Conclusion. The success rate of PDA closure between IV ketorolac and IV indomethacin was not significantly different. There was neither oliguria nor bleeding observed in both groups.