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Short-term and long-term outcomes of preterm neonates with acute severe pulmonary hypertension following rescue treatment with inhaled nitric oxide
  1. Michelle Baczynski1,
  2. Shannon Ginty1,
  3. Dany E Weisz2,3,
  4. Patrick J McNamara3,4,5,
  5. Edmond Kelly3,6,
  6. Prakeshkumar Shah3,6,7,
  7. Amish Jain3,5,6,7
  1. 1Department of Respiratory Therapy, Mount Sinai Hospital, Toronto, Canada
  2. 2Department of Newborn and Developmental Paediatrics, Sunnybrook Health Science Center, Toronto, Canada
  3. 3Department of Paediatrics, University of Toronto, Toronto, Canada
  4. 4Division of Neonatology, Hospital for Sick Children, Toronto, Canada
  5. 5Physiology, University of Toronto, Toronto, Canada
  6. 6Department of Paediatrics, Mount Sinai Hospital, Toronto, Canada
  7. 7Lunnenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada
  1. Correspondence to Dr Amish Jain, Mount Sinai Hospital, 19-231 - 600 University Ave, Toronto, Ontario, M5G1X5, Canada; amishjain{at}


Objective To describe short-term and long-term outcomes of preterm neonates with severe acute pulmonary hypertension (aPHT) in relation to response to rescue inhaled nitric oxide (iNO) therapy.

Design Retrospective cohort studyover a 6 year period.

Setting Tertiary neonatal intensive care unit.

Patients 89 neonates <35 weeks gestational age (GA) who received rescue iNO for aPHT, including 62 treated at ≤3 days of age (early aPHT).

Interventions iNO ≥ 1 hour.

Main outcome measures Positive responders (reduction in fraction of inspired oxygen (FiO2) ≥0.20 within 1 hour of iNO) were compared with non-responders. Primary outcome was survival without moderate-to-severe disability at 18 months of age.

Results Mean (SD) GA and birth weight was 27.7 (3.0) weeks and 1077 (473) gm, respectively. Median (IQR) pre-iNO FiO2 was 1.0 (1.0, 1.0). Positive response rate to iNO was 46%. Responders showed improved survival without disability (51% vs 15%; p<0.01), lower mortality (34% vs 71%; p<0.01) and disability among survivors (17% vs 50%; p=0.06). Higher GA (adjusted OR: 1.44 (95% CI 1.10 to 1.89)), aPHT in context of preterm prolonged rupture of membranes (6.26 (95% CI 1.44 to 27.20)) and positive response to rescue iNO (5.81 (95% CI 1.29 to, 26.18)) were independently associated with the primary outcome. Compared with late cases (>3 days of age), early aPHT had a higher response rate to iNO (61% vs 11%; p<0.01) and lower mortality (43% vs 78%; p<0.01).

Conclusion A positive response to rescue iNO in preterm infants with aPHT is associated with survival benefit, which is not offset by long-term disability.

  • neurodevelopmental outcomes
  • hypoxic respiratory failure
  • sepsis
  • preterm prolonged rupture of membranes

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  • Contributors MB, SG, DEW, PJM, EK, PSS and AJ made substantial contribution to the study conception and design. MB, SG and AJ finalised data collection forms and DEW, PJM, EK, PSS provided critical input. MB and SG were responsible for data collection which were directly supervised by AJ. AJ performed the statistical analysis for the study with critical inputs from DEK and PSS. MB was responsible for producing the first draft of the manuscript which was directly supervised by AJ. SG, DEW, PJM, EK and PSS made significant contributions in data interpretation and revising the manuscript critically.

  • Competing interests None declared.

  • Ethics approval Mount Sinai Hospital Research Ethics Board.

  • Provenance and peer review Not commissioned; externally peer reviewed.