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Early use of combined exogenous surfactant and inhaled nitric oxide reduces treatment failure in persistent pulmonary hypertension of the newborn: a randomized controlled trial

A Correction to this article was published on 07 September 2020

This article has been updated



To evaluate whether combined surfactant with inhaled nitric oxide (iNO) use will prevent newborns with hypoxemic respiratory failure (HRF) from developing an Oxygenation Index (OI) > 40.


100 term newborns with acute HRF (OI ≥ 20) were randomized to: Surfactant+iNO: received iNO plus up to two doses of surfactant or iNO-Controls: received iNO+placebo. Main outcome was the development of severe HRF (OI > 40) despite iNO use.


Baseline mean ± SD OI was 37.4 ± 14 for the Surfactant+iNO group and 38.2 ± 16 for the controls. Infants receiving surfactant+iNO improved their oxygenation faster, resulting in lower OI at 24 h: 12.9 ± 9 vs 18.7 ± 11 of controls, p < 0.05; and a lower proportion developing OI > 40: 24%(12/50) vs 50%(25/50) of controls, p < 0.02. Fewer infants receiving surfactant+iNO presented the combined outcome of death or ECMO: 16%(8/50) compared to 36%(18/50) of controls, p < 0.05.


Early use of combined surfactant+iNO improves oxygenation preventing the progression to severe HRF. This may reduce mortality and ECMO need.

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Fig. 1: Consort diagram of eligible study infants.
Fig. 2: Change in Oxygenation Index.

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We are grateful to Angélica Domínguez for their statistical assistance and for the valuable help of the group of research collaborators of the five centers listed in Appendix 1.


Funded by the Chilean Fund for Health Research (FONIS): Project: SA07I20035.

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Correspondence to Alvaro González.

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Appendix 1: Collaborators

Appendix 1: Collaborators

The following members from the centers are non-author contributors to this study. They contributed with data collection and provided clinical care for study patients:

Hospital Clínico Universidad Católica de Chile, Santiago: Katherine Flores, Rodrigo Lagos, Claudia Miralles, María Eugenia Pérez, Solange Rojas, Angélica Vives.

Hospital Guillermo Grant, Concepción: Lilian Cifuentes, Andrea Saldías, Claudia Aburto.

Hospital Dr. Luis Tisné, Santiago: María Lidia Poblete, Paula Vasquez.

Hospital San José, Santiago: Ana María Pacheco, Paula Ponce.

Hospital Dr. Sótero del Rio, Santiago: Mónica Ahumada, Patricia Mena, Claudia Toro.

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González, A., Bancalari, A., Osorio, W. et al. Early use of combined exogenous surfactant and inhaled nitric oxide reduces treatment failure in persistent pulmonary hypertension of the newborn: a randomized controlled trial. J Perinatol 41, 32–38 (2021).

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