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Open Access 12-03-2024 | Hypoxemia | RESEARCH

Occurrence of hyperoxia during iNO treatment for persistent pulmonary hypertension of the newborn: a cohort study

Authors: Justine de Jager, Fleur Brouwer, Jeroen Reijman, Roel L. F. van der Palen, Sylke J. Steggerda, Remco Visser, Arjan B. te Pas, Janneke Dekker

Published in: European Journal of Pediatrics | Issue 5/2024

Abstract

High concentrations of oxygen are often needed to optimize oxygenation in infants with persistent pulmonary hypertension (PPHN), but this can also increase the risk of hyperoxemia. We determined the occurrence of hyperoxemia in infants treated for PPHN. Medical records of infants ≥ 34 + 0 weeks gestational age (GA) who received inhaled nitric oxide (iNO) were retrospectively reviewed for oxygenation parameters during iNO therapy. Oxygen was manually titrated to target arterial oxygen tension (PaO₂) 10–13 kPa and peripheral oxygen saturation (SpO₂) 92–98%. The main study outcomes were the incidence and duration of hyperoxemia and hypoxemia and the fraction of inspired oxygen (FiO₂). A total of 181 infants were included. The median FiO₂ was 0.43 (IQR 0.34–0.56) and the maximum FiO₂ was 1.0 in 156/181 (86%) infants, resulting in at least one PaO₂ > 13 kPa in 149/181 (82%) infants, of which 46/149 (31%) infants had minimal one PaO₂ > 30 kPa. SpO₂ was > 98% in 179/181 (99%) infants for 17.7% (8.2–35.6%) of the iNO time. PaO₂ < 10 kPa occurred in 160/181 (88%) infants, of which 81/160 (51%) infants had minimal one PaO₂ < 6.7 kPa. SpO₂ was < 92% in 169/181 (93%) infants for 1.6% (0.5–4.3%) of the iNO time.

Conclusion: While treatment of PPHN is focused on preventing and reversing hypoxemia, hyperoxemia occurs inadvertently in most patients.

What is Known: • High concentrations of oxygen are often needed to prevent hypoxemia-induced deterioration of PPHN, but this can also increase the risk of hyperoxemia. • Infants with persistent pulmonary hypertension may be particularly vulnerable to the toxic effects of oxygen, and hyperoxemia could further induce pulmonary vasoconstriction, potentially worsening the condition.
What is New: • Hyperoxemia occurs in the majority of infants with PPHN during treatment with iNO. • Infants with PPHN spent a considerably longer period with saturations above the target range compared to saturations below the target range.

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Walsh-Sukys MC, Tyson JE, Wright LL et al (2000) Persistent pulmonary hypertension of the newborn in the era before nitric oxide: practice variation and outcomes. Pediatrics 105:14–20. https://doi.org/10.1542/PEDS.105.1.14CrossRefPubMed

Konduri GG, Vohr B, Robertson C et al (2007) Early inhaled nitric oxide therapy for term and near-term newborn infants with hypoxic respiratory failure: neurodevelopmental follow-up. J Pediatr 150:235–240. https://doi.org/10.1016/J.JPEDS.2006.11.065CrossRefPubMedPubMedCentral

Finer N (2000) Inhaled nitric oxide in term and near-term infants: neurodevelopmental follow-up of The Neonatal Inhaled Nitric Oxide Study Group (NINOS). J Pediatr 136:611–617. https://doi.org/10.1067/mpd.2000.104826CrossRef

Clark RH, Huckaby JL, Kueser TJ et al (2003) Low-dose nitric oxide therapy for persistent pulmonary hypertension: 1-year follow-up. J Perinatol 23:300–303. https://doi.org/10.1038/SJ.JP.7210908CrossRefPubMed

Lipkin PH, Davidson D, Spivak L et al (2002) Neurodevelopmental and medical outcomes of persistent pulmonary hypertension in term newborns treated with nitric oxide. J Pediatr 140:306–310. https://doi.org/10.1067/mpd.2002.122730CrossRefPubMed

Ball MK, Seabrook RB, Bonachea EM et al (2022) Evidence-based guidelines for acute stabilization and management of neonates with persistent pulmonary hypertension of the newborn. Am J Perinatol 40:1495–1508. https://doi.org/10.1055/A-1711-0778CrossRef

Bendapudi P, Rao GG, Greenough A (2015) Diagnosis and management of persistent pulmonary hypertension of the newborn. Paediatr Respir Rev 16:157–161. https://doi.org/10.1016/J.PRRV.2015.02.001CrossRefPubMed

Singh Y, Lakshminrusimha S (2021) Pathophysiology and management of persistent pulmonary hypertension of the newborn. Clin Perinatol 48:595–618. https://doi.org/10.1016/J.CLP.2021.05.009CrossRefPubMedPubMedCentral

Teitel DF, Iwamoto HS, Rudolph AM (1990) Changes in the pulmonary circulation during birth-related events. Pediatr Res 27:372–378. https://doi.org/10.1203/00006450-199004000-00010CrossRefPubMed

10.

Saugstad OD (2012) Hyperoxia in the term newborn: more evidence is still needed for optimal oxygen therapy. Acta Paediatr 101:34–38. https://doi.org/10.1111/J.1651-2227.2011.02546.XCrossRefPubMed

11.

Rawat M, Lakshminrusimha S, Vento M (2022) Pulmonary hypertension and oxidative stress: where is the link? Semin Fetal Neonatal Med 27:101347. https://doi.org/10.1016/J.SINY.2022.101347CrossRefPubMed

12.

Lakshminrusimha S, Swartz DD, Gugino SF et al (2009) Oxygen concentration and pulmonary hemodynamics in newborn lambs with pulmonary hypertension. Pediatr Res 66:539–544. https://doi.org/10.1203/PDR.0B013E3181BAB0C7CrossRefPubMedPubMedCentral

13.

Rudolph AM, Yuan S (1966) Response of the pulmonary vasculature to hypoxia and H+ ion concentration changes. J Clin Invest 45:399–411. https://doi.org/10.1172/JCI105355CrossRefPubMedPubMedCentral

14.

Lakshminrusimha S, Russell JA, Steinhorn RH et al (2007) Pulmonary hemodynamics in neonatal lambs resuscitated with 21%, 50%, and 100% oxygen. Pediatr Res 62:313–318. https://doi.org/10.1203/PDR.0B013E3180DB29FECrossRefPubMedPubMedCentral

15.

Lakshminrusimha S, Steinhorn RH, Wedgwood S et al (1985) (2011) Pulmonary hemodynamics and vascular reactivity in asphyxiated term lambs resuscitated with 21 and 100% oxygen. J Appl Physiol 111:1441–1447. https://doi.org/10.1152/JAPPLPHYSIOL.00711.2011CrossRef

16.

Fellman V, Raivio KO (1997) Reperfusion injury as the mechanism of brain damage after perinatal asphyxia. Pediatr Res 41:599–606. https://doi.org/10.1203/00006450-199705000-00001CrossRefPubMed

17.

Kilmartin KC, Al Balushi A, Altit G et al (2023) Impact of persistent pulmonary hypertension and oxygenation on brain injury in neonates with neonatal encephalopathy treated with therapeutic hypothermia. J Perinatol. https://doi.org/10.1038/s41372-023-01805-2CrossRefPubMed

18.

Klinger G, Beyene J, Shah P, Perlman M (2005) Do hyperoxaemia and hypocapnia add to the risk of brain injury after intrapartum asphyxia? Arch Dis Child Fetal Neonatal Ed 90:49–52. https://doi.org/10.1136/adc.2003.048785CrossRef

19.

Mitra S, Singh B, El-Naggar W, McMillan DD (2018) Automated versus manual control of inspired oxygen to target oxygen saturation in preterm infants: a systematic review and meta-analysis. J Perinatol 38:351–360. https://doi.org/10.1038/s41372-017-0037-zCrossRefPubMed

20.

Kelly R, Quine D, Stenson BJ (2023) Exploring the risk of hyperoxia in oxygen-dependent very low birthweight infants in the first week of life to plan future trials of oxygen targeting. Arch Dis Child Fetal Neonatal Ed 108:434–435. https://doi.org/10.1136/ARCHDISCHILD-2022-324717CrossRefPubMed

21.

Solberg MT, Bjørk IT, Hansen TWR (2013) Adherence to oxygenation and ventilation targets in mechanically ventilated premature and sick newborns: a retrospective study. BMC Pediatr 13:126. https://doi.org/10.1186/1471-2431-13-126CrossRefPubMedPubMedCentral

22.

Mandell E, Kinsella JP, Abman SH (2021) Persistent pulmonary hypertension of the newborn. Pediatr Pulmonol 56:661–669. https://doi.org/10.1002/ppul.25073CrossRefPubMed

23.

Alapati D, Jassar R, Shaffer TH (2017) Management of supplemental oxygen for infants with persistent pulmonary hypertension of newborn: a survey. Am J Perinatol 34:276–282. https://doi.org/10.1055/S-0036-1586754CrossRefPubMed

24.

Nakwan N, Chaiwiriyawong P (2016) An international survey on persistent pulmonary hypertension of the newborn: a need for an evidence-based management. J Neonatal Perinatal Med 9:243–250. https://doi.org/10.3233/NPM-16915133CrossRefPubMed

25.

Kaltsogianni O, Dassios T, Lee R et al (2023) Closed-loop automated oxygen control in ventilated infants born at or near term: a crossover trial. Acta Paediatr 112:246–251. https://doi.org/10.1111/APA.16598CrossRefPubMed

26.

Chan ED, Chan MM, Chan MM (2013) Pulse oximetry: understanding its basic principles facilitates appreciation of its limitations. Respir Med 107:789–799. https://doi.org/10.1016/J.RMED.2013.02.004CrossRefPubMed

27.

Chandrasekharan P, Rawat M, Lakshminrusimha S (2020) How do we monitor oxygenation during the management of PPHN? Alveolar, arterial, mixed venous oxygen tension or peripheral saturation? Children (Basel) 7:180. https://doi.org/10.3390/CHILDREN7100180CrossRefPubMed

28.

Quine D, Stenson BJ (2008) Does the monitoring method influence stability of oxygenation in preterm infants? A randomised crossover study of saturation versus transcutaneous monitoring. Arch Dis Child Fetal Neonatal Ed 93:347–350. https://doi.org/10.1136/ADC.2007.132282CrossRef

Title: Occurrence of hyperoxia during iNO treatment for persistent pulmonary hypertension of the newborn: a cohort study
Authors: Justine de Jager
Fleur Brouwer
Jeroen Reijman
Roel L. F. van der Palen
Sylke J. Steggerda
Remco Visser
Arjan B. te Pas
Janneke Dekker
Publication date: 12-03-2024
Publisher: Springer Berlin Heidelberg
Keywords: Hypoxemia
Pulmonary Hypertension
Pulmonary Hypertension
Pulmonary Hypertension
Pulmonary Hypertension
Published in: European Journal of Pediatrics / Issue 5/2024
Print ISSN: 0340-6199
Electronic ISSN: 1432-1076
DOI: https://doi.org/10.1007/s00431-024-05506-6

2024 ASCO Annual Meeting

Springer Medicine

Occurrence of hyperoxia during iNO treatment for persistent pulmonary hypertension of the newborn: a cohort study

Abstract

2024 ASCO Annual Meeting

Springer Medicine

Abstract

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