Life-threatening PPHN refractory to nitric oxide: proposal for a rational therapeutic algorithm

Fortas, Feriel; Nardo, Matteo Di; Yousef, Nadya; Humbert, Marc; Luca, Danièle De

doi:10.1007/s00431-021-04138-4

Cited by 21 publications

(20 citation statements)

References 87 publications

(101 reference statements)

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“…Further studies are necessary to provide insight in the pathophysiological mechanisms in order to find an international accepted (consensus) definition. Also, further studies should focus on therapeutic options, especially for these vulnerable patients [ 26 , 27 ]. Recently, a proposal for a therapeutic algorithm for treating life-threatening PPHN has been published.…”

Section: Discussionmentioning

confidence: 99%

Neonatal pulmonary hypertension after severe early-onset fetal growth restriction: post hoc reflections on the Dutch STRIDER study

et al. 2022

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The aim was to reflect on the unexpected finding of persistent pulmonary hypertension of the neonate (PPHN) and pulmonary hypertension in infants born within the Dutch STRIDER trial, its definition and possible pathophysiological mechanisms. The trial randomly assigned pregnant women with severe early-onset fetal growth restriction to sildenafil 25 mg three times a day versus placebo. Sildenafil use did not reduce perinatal mortality and morbidity, but did result in a higher rate of neonatal pulmonary hypertension (PH). The current paper reflects on the used definition, prevalence, and possible pathophysiology of the data on pulmonary hypertension. Twenty infants were diagnosed with pulmonary hypertension (12% of 163 live born infants). Of these, 16 infants had PPHN shortly after birth, and four had pulmonary hypertension associated with sepsis or bronchopulmonary dysplasia. Four infants with PPHN in the early neonatal period subsequently developed pulmonary hypertension associated with bronchopulmonary dysplasia in later life. Infants with pulmonary hypertension were at lower gestational age at delivery, had a lower birth weight and a higher rate of neonatal co-morbidity. The infants in the sildenafil group showed a significant increase in pulmonary hypertension compared to the placebo group (relative risk 3.67; 95% confidence interval 1.28 to 10.51, P = 0.02).Conclusion: Pulmonary hypertension occurred more frequent among infants of mothers allocated to antenatal sildenafil compared with placebo. A possible pathophysiological mechanism could be a “rebound” vasoconstriction after cessation of sildenafil. Additional studies and data are necessary to understand the mechanism of action. What is Known:• In the Dutch STRIDER trial, persistent pulmonary hypertension in the neonate (PPHN) was more frequent among infants after antenatal sildenafil exposure versus placebo. What is New:• The current analysis focuses on the distinction between PPHN and pulmonary hypertension associated with sepsis or bronchopulmonary dysplasia and on timing of diagnosis and aims to identify the infants at risk for developing pulmonary hypertension.• The diagnosis pulmonary hypertension is complex, especially in infants born after severe early-onset fetal growth restriction. The research field could benefit from an unambiguous consensus definition and standardized screening in infants at risk is proposed.

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Section: Discussionmentioning

confidence: 99%

Neonatal pulmonary hypertension after severe early-onset fetal growth restriction: post hoc reflections on the Dutch STRIDER study

et al. 2022

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“…Fifth, the European iNO registry did not capture detailed data regarding the management of refractory pulmonary hypertension managements on these babies, which includes inhalational pulmonary vasodilators, etc. [ 20 ] (in our study, as mentioned in Table 3 , we have the data regarding % of the use of intravenous vasodilators and ECMO therapy in babies with refractory PH). In addition, vasoactive-inotropic score (VIS) is the validated score to measure the severity of illness and associated with outcome in critically ill babies.…”

Section: Discussionmentioning

confidence: 99%

Effects of inhaled nitric oxide (iNO) in pulmonary hypertension secondary to arteriovenous malformations: a retrospective cohort study from the European iNO registry

et al. 2022

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This study aims to assess the effects of inhaled nitric oxide (iNO) on oxygenation in the management of pulmonary hypertension (PH) secondary to arteriovenous malformations (AVMs) in neonates. This is a matched retrospective cohort study from January 1, 2013, to December 31, 2017. The European inhaled nitric oxide registry from 43 neonatal and pediatric ICUs in 13 countries across Europe was used to extract data. The target population was neonates treated with iNO for the management of PH. The cases (PH secondary to AVMs treated with iNO) were matched (1:4 ratio) to controls (PH without AVMs treated with iNO). The main outcome measure was the absolute change of oxygenation index (OI) from baseline to 60 min after starting iNO in cases and controls. The primary outcome of our study was that the mean absolute change in OI from baseline to after 60 min was higher among cases 10.7 (14), than in controls 6 (22.5), and was not statistically different between the groups. The secondary outcome variable — death before discharge — was found to be significantly higher in cases (55%) than in controls (8%). All the other variables for secondary outcome measures remained statistically insignificant. Conclusion: Infants with PH secondary to AVMs treated with iNO did not respond differently compared to those presented with PH without AVMs treated with iNO. Right ventricular dysfunction on echocardiography was higher in cases than controls (cases: 66.7% and controls: 28.6%) but was not statistically significant. What is Known:• Arterioenous malformation (AVM) is a well-known cause of persistent pulmonary hypertension in newborns. Inhaled nitric oxide (iNO) is most commonly used as first-line therapy for pulmonary hypertension in newborns.• Around 40–50% of vein of Galen malformations (VOGMs) are found to have congestive heart failure in the neonatal period. What is New:• Neonates may present with an isolated PH of the newborn as the main feature of the VOGMs. A large proportion of cases with AVMs have been associated with right ventricular cardiac dysfunction. • Results from one of the largest database registries in the world for iNO have been used to answer our research question.

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“…Moreover, higher doses do not provide any additional advantages. The absolute contra-indication of iNO is methemoglobinemia (36,37).…”

Section: Discussionmentioning

confidence: 99%

Controversies in neonatology: The efficacy of inhaled nitric oxide in preterm infants with persistent pulmonary hypertension

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Okan

Topçuoğlu

et al. 2022

Journal of Health Sciences and Medicine

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Life-threatening PPHN refractory to nitric oxide: proposal for a rational therapeutic algorithm

Cited by 21 publications

References 87 publications

Neonatal pulmonary hypertension after severe early-onset fetal growth restriction: post hoc reflections on the Dutch STRIDER study

Neonatal pulmonary hypertension after severe early-onset fetal growth restriction: post hoc reflections on the Dutch STRIDER study

Effects of inhaled nitric oxide (iNO) in pulmonary hypertension secondary to arteriovenous malformations: a retrospective cohort study from the European iNO registry

Controversies in neonatology: The efficacy of inhaled nitric oxide in preterm infants with persistent pulmonary hypertension

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