Prophylactic Intravenous Ketorolac for Prevention of Intraventricular Hemorrhage in Preterm Infants < 32 Weeks and < 1500 Grams: A Double-Blind, Randomized, Placebo-Controlled Trial

Kathlynne Anne Abat-Senen,1 Loudella Calotes-Castillo2 and Jacinto Blas V. Mantaring III1

1 Section of Newborn Medicine, Department of Pediatrics, College of Medicine and
Philippine General Hospital, University of the Philippines Manila
2 Section of Neurology, Department of Pediatrics, College of Medicine and
Philippine General Hospital, University of the Philippines Manila

 

Intraventricular hemorrhage (IVH) remains an important cause of morbidity and mortality in Very Low Birth Weight (VLBW) infants. Since 2004, Indomethacin, which is effective in preventing IVH, has been removed from the Philippine market. Ketorolac is a nonselective cyclooxygenase inhibitor which is structurally-related and of equal potency to Indomethacin.

Objective. This study aims to determine if prophylactic ketorolac compared to placebo will decrease IVH and its associated morbidities among preterm neonates.

Methods. We conducted a double-blind, randomized, placebo-controlled trial among neonates born in a tertiary government university hospital. Newborns with gestational age <32 weeks and birth weight <1500 g were eligible for inclusion. Participants were randomized to either ketorolac (0.5 mg/kg, at 6-12 hours) or placebo. Randomization concealment was maintained using sealed opaque envelopes. Cranial ultrasonography was performed on postnatal day 2 and 7, and at 36 to 40 weeks postconceptional age. IVH at postnatal day 7 was the outcome of interest. Adverse effects and complications were monitored and recorded.

Results. A total of 134 infants were included in the study. There was no difference in the proportion of infants who developed IVH between the ketorolac and placebo groups (46% vs 45%). The mean serum creatinine levels were significantly higher in the ketorolac group (1.15 + 0.69 vs. 0.79 + 0.38; p = 0.002). The rates of death, sepsis, necrotizing enterocolitis, bleeding, platelet counts of <50,000/mm3, mean urine output and the lengths of hospital stay were similar in the two groups.

Conclusion. Prophylactic intravenous ketorolac was ineffective in preventiving IVH among preterm infants. Ketorolac cannot be recommended for the prevention of IVH.

Key Words: intraventricular hemorrhage, ketorolac, preterm, infants