RESUMEN
OBJECTIVE: We conducted a multicenter, randomized, controlled trial to determine whether higher doses of indomethacin would improve the rate of patent ductus arteriosus (PDA) closure. STUDY DESIGN: Infants (<28 weeks gestation) who received a conventional, prophylactic 3-dose course of indomethacin were eligible if they had continued evidence of persistent ductus patency on an echocardiogram obtained before the third prophylactic indomethacin dose. Infants (n = 105) were randomized to receive an extended 3-day course of either low-dose (0.1 mg/kg/d) or higher-dose (0.2 or 0.5 mg/kg/d) indomethacin. An echocardiogram was obtained 24 hours after the last dose of study drug. RESULTS: Despite increasing serum indomethacin concentrations by 2.9-fold in the higher-dose group, we failed to detect a significant decrease in the rate of persistent PDA (low = 52%; higher = 45%, P = .50). The higher-dose group had a significantly higher occurrence of serum creatinine >2 mg/100 mL (low = 6%, higher = 19%, P < .05) and moderate/severe retinopathy of prematurity (ROP) (low = 15%, higher = 36%, P < .025). The incidence of moderate/severe ROP was directly related to the poststudy indomethacin concentrations (odds ratio = 1.75, confidence interval: 1.15-2.68, P < .01). CONCLUSION: Increasing indomethacin concentrations above the levels achieved with a conventional dosing regimen had little effect on the rate of PDA closure but was associated with higher rates of moderate/severe ROP and renal compromise.
Asunto(s)
Inhibidores de la Ciclooxigenasa/administración & dosificación , Conducto Arterioso Permeable/tratamiento farmacológico , Indometacina/administración & dosificación , Inhibidores de la Ciclooxigenasa/efectos adversos , Relación Dosis-Respuesta a Droga , Conducto Arterioso Permeable/diagnóstico , Ecocardiografía , Femenino , Humanos , Indometacina/efectos adversos , Recién Nacido , Recien Nacido Prematuro , Recién Nacido de muy Bajo Peso , Masculino , Insuficiencia Renal/etiología , Retinopatía de la Prematuridad/etiología , Resultado del TratamientoRESUMEN
OBJECTIVE: To test the hypothesis that patent ductus arteriosus that fail to close with prostaglandin inhibition may be regulated by mechanisms that act independently of prostaglandin production. STUDY DESIGN: We examined a cohort of 446 infants who were treated with indomethacin (within 15 hours of birth) to inhibit prostaglandin production. We used multiple logistic regression modeling to determine which perinatal/neonatal variables were most closely associated with the persistence of ductus patency in the presence of diminished prostaglandin production. RESULTS: We identified 4 variables (immature gestational age, lack of exposure to antenatal betamethasone, severity of respiratory distress, and Caucasian race) that were significantly and independently associated with the degree of ductus patency. CONCLUSION: Gestational age, antenatal glucocorticoid exposure, respiratory distress, and race are independent risk factors that appear to affect ductus closure even when indomethacin has been used to inhibit prostaglandin production. Future studies of these risk factors may identify new potential targets for patent ductus arteriosus treatment.