Ibuprofen for the treatment of patent ductus arteriosus in preterm or low birth weight infants

The standard dosing regimen in the following analyses for ibuprofen was 10 mg/kg followed by ibuprofen 5 mg/kg 24 and 48 hours later, and indomethacin 0.2 mg/kg at 12 hour intervals for three doses.

Systematic review of RCTs found intravenous ibuprofen (3 doses) reduced failure to close a PDA compared with placebo (RR; 0.62 (95% CI 0.44 to 0.86); RD; -0.18 (95% CI -0.30 to -0.06); NNTB 6 (95% CI 3 to 17); I2 = 65% for RR and I2 = 0% for RD; 2 studies, 206 infants; moderate-quality evidence) but was associated with increased oliguria (RR 39.0, 95% CI 2.40, 633.01) and increased creatinine (MD 29.17, 95% CI 12.60, 45.74 µmol/L). There was no difference in other morbidities including pulmonary hypertension, NEC and mortality.[6]

Twenty-four studies (1590 infants) compared ibuprofen (IV or oral) with indomethacin (IV or oral). No differences in failure rate for PDA closure was found (RR 1.07, 95% CI 0.92 to 1.24; RD 0.02, 95% CI -0.02 to 0.06; I2 = 0%; moderate-quality evidence). Ibuprofen reduced NEC (18 studies, 1292 infants; RR 0.68, 95% CI 0.49 to 0.94; NNTB 25, 95% CI 14 to 100), reduced oliguria (6 studies, 576 infants; RR 0.28, 95% CI 0.14 to 0.54; NNTB 11, 95% CI 7 to 20), was associated with low creatinine levels 72 hours after initiation of treatment (11 studies, 918 infants; MD -8.12 µmol/L, 95% CI -10.81 to -5.43) compared to indomethacin treated infants. [6]

Five studies compared treatment of PDA with paracetamol versus ibuprofen and enrolled 559 infants. There was no significant difference for failure of ductal closure after the first course of drug administration (RR 0.95, 95% CI 0.75 to 1.21; 5 trials, 559 infants). Ibuprofen was associated with a high rate of gastrointestinal bleeding (RR 0.28, 95% CI 0.12 to 0.69; NNTB 17 95% CI 11 to 50), higher creatinine and bilirubin levels, and lower platelet counts and daily urine output. There were no significant differences in the neurological outcomes at 18 to 24 months (n = 61). [7]