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Considerations in the management of hypoxemic respiratory failure and persistent pulmonary hypertension in term and late preterm neonates

Journal of Perinatology volume 36, pages S12–S19 (2016)Cite this article

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Abstract

Recent advances in our understanding of neonatal pulmonary circulation and the underlying pathophysiology of hypoxemic respiratory failure (HRF)/persistent pulmonary hypertension of the newborn (PPHN) have resulted in more effective management strategies. Results from animal studies demonstrate that low alveolar oxygen tension (PAO2) causes hypoxic pulmonary vasoconstriction, whereas an increase in oxygen tension to normoxic levels (preductal arterial partial pressure of oxygen (PaO2) between 60 and 80 mm Hg and/or preductal peripheral capillary oxygen saturation between 90% and 97%) results in effective pulmonary vasodilation. Hyperoxia (preductal PaO2 >80 mm Hg) does not cause further pulmonary vasodilation, and oxygen toxicity may occur when high concentrations of inspired oxygen are used. It is therefore important to avoid both hypoxemia and hyperoxemia in the management of PPHN. In addition to oxygen supplementation, therapeutic strategies used to manage HRF/PPHN in term and late preterm neonates may include lung recruitment with optimal mean airway pressure and surfactant, inhaled and intravenous vasodilators and ‘inodilators’. Clinical evidence suggests that administration of surfactant or inhaled nitric oxide (iNO) therapy at a lower acuity of illness can decrease the risk of extracorporeal membrane oxygenation/death, progression of HRF and duration of hospital stay. Milrinone may be beneficial as an inodilator and may have specific benefits following prolonged exposure to iNO plus oxygen owing to inhibition of phosphodiesterase (PDE)-3A. Additionally, sildenafil, and, in selected cases, hydrocortisone may be appropriate options after hyperoxia and oxidative stress owing to their effects on PDE-5 activity and expression. Continued investigation into these and other interventions is needed to optimize treatment and improve outcomes.

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Acknowledgements

This work is based on discussions at a roundtable meeting supported by a grant from Mallinckrodt Pharmaceuticals, formerly Ikaria. Presentations and discussions were developed solely by the participants, without grantor input. The meeting chair (RHS) determined the agenda and attendees. SL, GGK and RHS developed the presentations and led the discussions upon which this article is based, provided critical review and revisions to the outline and manuscript drafts, provided final approval of the version to be published and are accountable for the integrity of the content and for addressing questions. We thank the contributions of the following individuals who participated in discussion that shaped the content of this article: Namasivayam Ambalavanan, MD, Judy L Aschner, MD, Jason Gien, MD, John Kinsella, MD and Ola Didrik Saugstad, MD, PhD, FRCPE. Writing and editorial assistance was provided by John Kross, and Sharon Suntag and Julie Gerke of Quintiles.

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Authors and Affiliations

  1. Department of Pediatrics, University of Buffalo, Buffalo, NY, USA

    S Lakshminrusimha

  2. Department of Pediatrics and Children’s Research Institute, Medical College of Wisconsin, Milwaukee, WI, USA

    G G Konduri

  3. Department of Pediatrics, Children’s National Medical Center, Washington, DC, USA

    R H Steinhorn

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  1. S Lakshminrusimha
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  2. G G Konduri
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  3. R H Steinhorn
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Corresponding author

Correspondence to S Lakshminrusimha.

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Competing interests

SL, GGK and RHS received honoraria for their participation in a roundtable meeting supported by a grant from Mallinckrodt Pharmaceuticals, formerly Ikaria. SL was a member of the speaker’s bureau for Ikaria from June 2010 to October 2014 and has received grant support from the American Academy of Pediatrics and Canadian Pediatric Society. GGK has received consulting fees from Boston Health Economics and Actelion Clinical Research and lecture fees from Quintiles. RHS has received research grant support from Pfizer. NIH Grants: 5R01HD072929-03 (to SL); 5R01HL057268-11 (to GGK); 5R01HL054705-13 (to RHS).

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Lakshminrusimha, S., Konduri, G. & Steinhorn, R. Considerations in the management of hypoxemic respiratory failure and persistent pulmonary hypertension in term and late preterm neonates. J Perinatol 36 (Suppl 2), S12–S19 (2016). https://doi.org/10.1038/jp.2016.44

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