Late oral acetaminophen versus immediate surgical ligation in preterm infants with persistent large patent ductus arteriosus

J Thorac Cardiovasc Surg. 2018 Nov;156(5):1937-1944. doi: 10.1016/j.jtcvs.2018.05.098. Epub 2018 Jul 11.

Abstract

Objective: The study objective was to evaluate the association of oral acetaminophen therapy versus immediate surgical ligation with neonatal outcomes in infants with persistent patent ductus arteriosus.

Methods: We performed a retrospective cohort study of preterm infants born 28+6 weeks or less gestational age with persistent large patent ductus arteriosus being considered for surgical ligation after unsuccessful medical therapy. Infants in epoch 1 (July 2009 to June 2012) were immediately referred for ligation, and infants in epoch 2 (July 2012 to June 2015) were treated with oral acetaminophen and referred for ligation in the absence of improvement. The primary outcome was a composite of death or chronic lung disease.

Results: A total of 92 infants with median (interquartile range) gestational age 25.2 weeks (24.4-26.3) had persistent large patent ductus arteriosus (43 in epoch 1, 49 in epoch 2). Infants in epoch 2 had decreased surgical ligation (26 [53%] vs 31 [72%]; adjusted odds ratio [aOR], 0.32; 95% confidence interval [CI], 0.12-0.89) but increased chronic lung disease (36 [73%] vs 25 [58%]; aOR, 3.34; 95% CI, 1.05-10.58) and increased death/chronic lung disease of borderline significance (39 [80%] vs 29 [67%]; aOR, 3.09; 95% CI, 0.99-9.63). Infants in epoch 2 took longer to wean off of positive pressure ventilation (28.5 vs 24 days after enrollment; aOR, 0.52; 95% CI, 0.31-0.85).

Conclusions: Late oral acetaminophen therapy for infants with persistent patent ductus arteriosus is associated with reduced surgical ligation but increased chronic lung disease. In light of a lack of improvement in clinical outcomes, the individual contributory effects of acetaminophen, surgical ligation, and prolonged exposure to patent ductus arteriosus require further study to define the optimal approach.

Keywords: ELGAN; PDA; acetaminophen; bronchopulmonary dysplasia; mortality.

Publication types

  • Comparative Study

MeSH terms

  • Acetaminophen / administration & dosage*
  • Acetaminophen / adverse effects
  • Administration, Oral
  • Cardiac Surgical Procedures / adverse effects
  • Cardiac Surgical Procedures / methods*
  • Cardiac Surgical Procedures / mortality
  • Chronic Disease
  • Clinical Decision-Making
  • Drug Administration Schedule
  • Ductus Arteriosus, Patent / diagnostic imaging
  • Ductus Arteriosus, Patent / mortality
  • Ductus Arteriosus, Patent / therapy*
  • Female
  • Gestational Age
  • Humans
  • Infant, Newborn
  • Infant, Premature*
  • Ligation
  • Lung Diseases / etiology
  • Male
  • Retrospective Studies
  • Risk Factors
  • Time Factors
  • Time-to-Treatment*
  • Treatment Outcome

Substances

  • Acetaminophen