Prediction of survival in infants with congenital diaphragmatic hernia and the response to inhaled nitric oxide

Fahad M S Arattu Thodika; Svilena Dimitrova; Mahesh Nanjundappa; Mark Davenport; Kypros Nicolaides; Theodore Dassios; Anne Greenough

doi:10.1007/s00431-022-04568-8

Prediction of survival in infants with congenital diaphragmatic hernia and the response to inhaled nitric oxide

Eur J Pediatr. 2022 Oct;181(10):3683-3689. doi: 10.1007/s00431-022-04568-8. Epub 2022 Jul 28.

Authors

Fahad M S Arattu Thodika¹, Svilena Dimitrova², Mahesh Nanjundappa², Mark Davenport³, Kypros Nicolaides⁴, Theodore Dassios^{1

2}, Anne Greenough^{5

6

7}

Affiliations

¹ Department of Women and Children's Health, School of Life Course Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK.
² Neonatal Intensive Care Centre, King's College Hospital NHS Foundation Trust, London, UK.
³ Department of Paediatric Surgery, King's College Hospital NHS Foundation Trust, London, UK.
⁴ Fetal Medicine Unit, King's College Hospital NHS Foundation Trust, London, UK.
⁵ Department of Women and Children's Health, School of Life Course Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK. anne.greenough@kcl.ac.uk.
⁶ Fetal Medicine Unit, King's College Hospital NHS Foundation Trust, London, UK. anne.greenough@kcl.ac.uk.
⁷ NIHR Biomedical Research Centre Based at Guy's and St Thomas NHS Foundation Trust and King's College London, London, UK. anne.greenough@kcl.ac.uk.

Abstract

The use of inhaled nitric oxide (iNO) in treating pulmonary hypertension in infants with congenital diaphragmatic hernia (CDH) is controversial. Our aims were to identify factors associated with survival in CDH infants and whether this was influenced by the response to iNO. Results of CDH infants treated in a tertiary surgical and medical perinatal centre in a ten year period (2011-2021) were reviewed. Factors affecting survival were determined. To assess the response to iNO, blood gases prior to and 30 to 60 min after initiation of iNO were analysed and PaO₂/FiO₂ ratios and oxygenation indices (OI) calculated. One hundred and five infants were admitted with CDH; 46 (43.8%) infants died. The CDH infants who died had a lower median observed to expected lung to head ratio (O/E LHR) (p < 0.001) and a higher median highest OI on day 1 (HOId1) (p < 0.001). HOId1 predicted survival after adjusting for gestational age, Apgar score at 5 min and O/E LHR (odds ratio 0.948 (95% confidence intervals 0.913-0.983)). Seventy-two infants (68.6%) received iNO; 28 survived to discharge. The median PaO₂ (46.7 versus 58.8 mmHg, p < 0.001) and the median PaO₂/FiO₂ ratio (49.4 versus 58.8, p = 0.003) improved post iNO initiation. The percentage change in the PaO₂/FiO₂ ratio post iNO initiation was higher in infants who survived (69.4%) compared to infants who died (10.2%), p = 0.018.

Conclusion: The highest OI on day 1 predicted survival. iNO improved oxygenation in certain CDH infants and a positive response was more likely in those who survived.

What is known: • The use of iNO is controversial in infants with CDH with respect to whether it improves survival.

What is new: • We have examined predictors of survival in CDH infants including the response to iNO and demonstrated that the highest oxygenation index on day 1 predicted survival (AUCROC =0.908). • Certain infants with CDH responded to iNO and those with a greater response were more likely to survive.

Keywords: Congenital diaphragmatic hernia; Inhaled nitric oxide; Oxygenation index; PaO2/FiO2 ratio.

MeSH terms

Administration, Inhalation
Gases / therapeutic use
Hernias, Diaphragmatic, Congenital*
Humans
Hypertension, Pulmonary* / drug therapy
Hypertension, Pulmonary* / etiology
Infant
Nitric Oxide / therapeutic use
Retrospective Studies

Substances

Gases
Nitric Oxide