Effects of Prophylactic Indomethacin on Vasopressor-Dependent Hypotension in Extremely Preterm Infants

• Published in: The Journal of pediatrics Vol. 182; pp. 21 - 27.e2
• Main Authors: Liebowitz, Melissa, MD, Koo, Jane, MD, Wickremasinghe, Andrea, MD, Allen, Isabel Elaine, PhD, Clyman, Ronald I., MD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2017
• Subjects: Cardiovascular Agents - therapeutic use; Cohort Studies; dopamine; Dopamine - therapeutic use; Ductus Arteriosus, Patent - complications; Ductus Arteriosus, Patent - drug therapy; Ductus Arteriosus, Patent - epidemiology; Echocardiography; Female; Humans; hypotension; Hypotension - drug therapy; Hypotension - epidemiology; Hypotension - etiology; Incidence; Indomethacin - therapeutic use; Infant, Extremely Premature; Infant, Newborn; Male; newborn; Pediatrics; premature birth; Retrospective Studies; hypotension; RCT; Patent ductus arteriosus; Respiratory severity score; Necrotizing enterocolitis; PINDO; newborn; PDA; NEC; Randomized controlled trial; BP; Fraction of inspired oxygen; premature birth; RSS; FiO 2; Blood pressure; dopamine; Prophylactic indomethacin; FiO2
• ISSN: 0022-3476; 1097-6833
• DOI: 10.1016/j.jpeds.2016.11.008

Objective To determine whether a moderate-to-large patent ductus arteriosus (PDA) is responsible for vasopressor-dependent hypotension, occurring at the end of the first postnatal week. Study design We performed a retrospective, double cohort controlled study of infants delivered at ≤27+6 weeks' gestation (n = 313). From January 2004 through April 2011, all infants were treated with prophylactic indomethacin ([PINDO] epoch). From May 2011 through December 2015, no infant was treated with indomethacin until at least 8 postnatal days (conservative epoch). Echocardiograms were performed on postnatal days 6 or 7. Hypotension was managed by a predefined protocol. The primary outcome was the incidence of dopamine-dependent hypotension, defined as having received at least 6 µg/kg/min dopamine for at least 24 hours during postnatal days 4-7. Results As expected, the incidence of moderate-to-large PDA at the end of the first week differed significantly between epochs (PINDO = 8%; conservative = 64%). In multivariate analyses, infants in the PINDO epoch had a significantly lower incidence of vasopressor-dependent hypotension (11%) than infants in the conservative epoch (21%; OR = 0.40, 95% CI 0.20-0.82). Infants in the PINDO epoch also required less mean airway pressure, had a lower respiratory severity score, and lower mode of ventilation score than infants in the conservative epoch during postnatal days 4-7. The effects of PINDO on both the incidence of vasopressor-dependent hypotension and the need for respiratory support were no longer significant when analyses were adjusted for “presence or absence of a moderate-to-large PDA.” Conclusion PINDO decreases vasopressor-dependent hypotension and the need for respiratory support at the end of the first postnatal week. These effects are mediated by closure of the PDA.