[Comparison of the efficacy of ibuprofen and indomethacin in the treatment of patent ductus arteriosus in prematurely born infants].
OBJECTIVE
To assess the efficacy and safety of early treatment with ibuprofen (IBU) and indomethacin (INDO) of patent ductus arteriosus in preterm infants. Prospective study with blind trial.


METHODS
We studied 35 preterm infants (19 treated with INDO, 16 IBU) (gestation age <33 and birth weight < 1500 g), who had an echocardiographicaly confirmed patent ductus arteriosus (PDA). The infants were randomly assigned in two groups to receive INDO (0.2-0.2-0.2 mg/kg) or IBU (10-5-5 mg/kg) in first 72 hours of life (average 2 days of life). The rate of ductal closure, the need for surgical ligation, side effects, complications, and the infants clinical course were recorded.


RESULTS
The rate of ductal closure was similar in two groups (15/19, 80% INDO; 11/16, 69% IBU). 27 infants (15 INDO, 12 IBU) were treated per protocol (3 doses). For remaining 8 infants we stopped treatment due to side effects. In the IBU group the main reason to stop treatment was pulmonary hemorrhage (3/16, 19%) and pulmonary hypertension (1/16, 6%), but in the INDO group it was increased serum creatinine and urea nitrogen concentrations (3/19, 16%) and intraventricular hemorrhage (IVH IV) grade (1/19 5%). In IBU group vs. INDO, urine output decreased (p=0.02), but never before below the level of oliguria (defined as urine output below 1 ml/kg/h). Risk of necrotizing enterocolitis (NEC) grade II was similar in two groups, but only patients treated with INDO showed intestinal perforations (p=ns). They received also postnatal hydrocortisone and we showed near significant tendency (p=0.06) for intestinal perforation in patients treated with INDO and hydrocortisone. There were no significant differences with respect to IVH or PVL between the groups.


CONCLUSIONS
The efficacy of ibuprofen and indomethacin in PDA treatment is similar. Treatment of ibuprofen and indomethacin may cause transient renal dysfunction: diminished urine output and increase of serum creatinine and urea nitrogen concentrations. Indomethacin, especially with concomitant treatment with hydrocortisone, may increase the risk of intestinal perforation.
Klinika Neonatologii i Intensywnej Terapii Noworodka, Instytut Matki i Dziecka, ul. Kasprzaka 17a, 01-211 Warszawa, Poland.
Ewa
E
Adamska
Ewa
E
Helwich
Magdalena
M
Rutkowska
Ewa
E
Zacharska
Aldona
A
Piotrowska
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D003401:Creatine / Q000652:urine; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage*; D004311:Double-Blind Method; D004374:Ductus Arteriosus, Patent / Q000188:drug therapy*; D004452:Echocardiography; D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage*; D007213:Indomethacin / Q000008:administration & dosage*; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000188:drug therapy*; D008297:Male; D016896:Treatment Outcome; D014554:Urination / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D003401:Creatine; D007052:Ibuprofen; D007213:Indomethacin