Efficacy and safety of endotracheal instillation of iloprost for persistent pulmonary hypertension of the newborn

Abstract Objective: To determine the efficacy and safety of endotracheal instillation of iloprost as a rescue therapy for persistent pulmonary hypertension of the newborn. Methods: Neonates diagnosed with persistent pulmonary hypertension who were unresponsive to standard treatment protocol applied for persistent pulmonary hypertension in our unit, and who were being followed up with mechanical ventilation, were included in the study. Iloprost was instilled endotracheally as a rescue treatment. Systolic pulmonary artery pressure, oxygen saturation index, mean airway pressure, fraction of inspired oxygen, preductal and postductal venous oxygen saturation, heart rate, and blood pressure were recorded before and after 30 minutes of endotracheal iloprost instillation. Adverse events after endotracheal iloprost were recorded. Results: Twenty neonates were included. The median gestational age and birth weight were found to be 37 (30.5-38) weeks and 2975 (2125-3437.5) grams, respectively. When compared to the period before endotracheal iloprost instillation, systolic pulmonary artery pressure, oxygen saturation index, mean airway pressure, and fraction of inspired oxygen values significantly decreased (p < 0.001, p < 0.001, p = 0.021, p = 0.001, respectively), whereas preductal and postductal oxygen saturation values significantly increased 30 minutes after the endotracheal iloprost instillation (p = 0.002, p < 0.001, respectively). There were no significant differences in heart rate and blood pressure values before and after the iloprost administration. No adverse events were observed. Conclusion: Endotracheal instillation of iloprost was found to be an effective and safe therapy for persistent pulmonary hypertension unresponsive to conventional treatment.

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Nitric Oxide Story

Anesthesiology ◽

10.1097/aln.0000000000002579 ◽

2019 ◽

Vol 130 (3) ◽

pp. 435-440 ◽

Cited By ~ 1

Author(s):

Warren M. Zapol

Keyword(s):

Nitric Oxide ◽

Pulmonary Hypertension ◽

Oxygen Saturation ◽

Persistent Pulmonary Hypertension ◽

Pulmonary Vasculature ◽

Oxygen Tensions ◽

Low Levels ◽

Fraction Of Inspired Oxygen ◽

Inspired Oxygen ◽

Inhaled No

Abstract Inhaled Nitric Oxide in Persistent Pulmonary Hypertension of the Newborn. By Roberts JD, Polaner DM, Lang P, and Zapol WM. Lancet 1992; 130:435–40. Reprinted with permission. NO has vasodilatory effects on the pulmonary vasculature in adults and animals. We examined the effects on systemic oxygenation and blood pressure of inhaling up to 80 parts per million by volume of NO at fraction of inspired oxygen 0.9 for up to 30 min by six infants with persistent pulmonary hypertension of the newborn. In all infants, this treatment rapidly and significantly increased preductal oxygen saturation; in five infants, postductal oxygen saturation and oxygen tensions also increased. Inhalation of NO did not cause systemic hypotension or raise methemoglobin. These data suggest that low levels of inhaled NO have an important role in the reversal of hypoxemia due to persistent pulmonary hypertension of the newborn.

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Inhaled Epoprostenol for Pulmonary Hypertension Treatment in Neonates: A 12-Year Experience

American Journal of Perinatology ◽

10.1055/s-0038-1676483 ◽

2018 ◽

Vol 36 (11) ◽

pp. 1142-1149 ◽

Cited By ~ 2

Author(s):

Frédérique Berger-Caron ◽

Bruno Piedboeuf ◽

Geneviève Morissette ◽

David Simonyan ◽

Philippe Chétaille ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Side Effects ◽

Retrospective Cohort ◽

Rebound Effect ◽

Oxygenation Index ◽

Pediatric Intensive Care ◽

Primary Objective ◽

Hypertension Treatment ◽

Fraction Of Inspired Oxygen ◽

Inspired Oxygen

Background Persistent pulmonary hypertension of the newborn (PPHN) occurs in 10% of neonatal respiratory insufficiency. To selectively reduce pulmonary vascular resistance, several treatments have been tried. Inhaled epoprostenol (iPGI2) has been used for 12 years in our institution for the management of refractory PPHN despite the gaps in the literature to support this use. Objectives The primary objective was to evaluate the efficacy of iPGI2 for PPHN. The secondary objectives were to describe its use in neonates and assess side effects. Study Design This retrospective cohort study included infants < 28 days with PPHN treated with iPGI2 in the neonatal or pediatric intensive care units of our institution between 2004 and 2016. Results We reviewed 43 patient' care episodes (mean gestational age of 36 weeks). This was an extremely ill population with 54% mortality rate. Oxygenation index improved significantly after 12-hour treatment (p = 0.047), with a rebound effect when discontinuing nebulization. By the end of the therapy, the fraction of inspired oxygen had significantly dropped (p = 0.0018). Echocardiographic markers tended to normalize during treatment. No potential side effects were reported. Conclusion In these sick newborns, we observed an improvement in PPHN under iPGI2 without significant adverse effects. To our knowledge, this is the largest neonatal cohort reported to have received iPGI2 for PPHN.

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Correlation Between the Ratio of Oxygen Saturation to Fraction of Inspired Oxygen and the Ratio of Partial Pressure of Oxygen to Fraction of Inspired Oxygen in Detection and Risk Stratification of Pediatric Acute Respiratory Distress Syndrome

Cureus ◽

10.7759/cureus.18353 ◽

2021 ◽

Author(s):

Pooja D Lohano ◽

Sadam H Baloch ◽

Murtaza A Gowa ◽

Syed J Raza ◽

Lareb Soomro ◽

...

Keyword(s):

Acute Respiratory Distress Syndrome ◽

Risk Stratification ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Oxygen Saturation ◽

Partial Pressure ◽

Distress Syndrome ◽

Partial Pressure Of Oxygen ◽

Fraction Of Inspired Oxygen ◽

Inspired Oxygen

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Radiographic lung disease and response of persistent pulmonary hypertension to mean airway pressure and alkalosis

Pediatric Pulmonology ◽

10.1002/ppul.1950170407 ◽

1994 ◽

Vol 17 (4) ◽

pp. 239-245 ◽

Cited By ~ 1

Author(s):

Karl S. Deluga ◽

Alan E. Schlesinger

Keyword(s):

Pulmonary Hypertension ◽

Lung Disease ◽

Airway Pressure ◽

Persistent Pulmonary Hypertension ◽

Mean Airway Pressure

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Hypoxia inhibits adenylyl cyclase catalytic activity in a porcine model of persistent pulmonary hypertension of the newborn

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00130.2018 ◽

2018 ◽

Vol 315 (6) ◽

pp. L933-L944 ◽

Cited By ~ 1

Author(s):

A. S. Sikarwar ◽

M. Hinton ◽

K. T. Santhosh ◽

P. Dhanaraj ◽

M. Talabis ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Catalytic Activity ◽

Adenylyl Cyclase ◽

Specific Activity ◽

Pulmonary Arteries ◽

Persistent Pulmonary Hypertension ◽

Receptor Agonists ◽

Pulmonary Arterial ◽

Fraction Of Inspired Oxygen

Persistent pulmonary hypertension of the newborn (PPHN) features hypoxemia, pulmonary vasoconstriction, and impaired cardiac inotropy. We previously reported low basal and stimulated cAMP in hypoxic pulmonary artery smooth muscle cells (PASMCs). We now examine pulmonary arterial adenylyl cyclase (AC) activity and regulation in hypoxic PPHN. PPHN was induced in newborn swine by normobaric hypoxia (fraction of inspired oxygen 0.10) for 72 h and compared with age-matched normoxic controls. We studied relaxation of pulmonary arterial (PA) rings to AC activator forskolin and cGMP activator sodium nitroprusside (SNP) by isometric myography, ATP content, phosphodiesterase activity, AC content, isoform expression, and catalytic activity in presence or absence of Gαs-coupled receptor agonists, forskolin, or transnitrosylating agents in human and neonatal porcine PASMCs and HEK293T stably expressing AC isoform 6, after 72 h hypoxia (10% O2) or normoxia (21% O2). Relaxation to forskolin and SNP were equally impaired in PPHN PA. AC-specific activity decreased in hypoxia. PASMC from PPHN swine had reduced AC activity despite exposure to normoxia in culture; transient hypoxia in vitro further decreased AC activity. Prostacyclin receptor ligand affinity decreased, but its association with Gαs increased in hypoxia. Total AC content was unchanged by hypoxia, but AC6 increased in hypoxic cells and PPHN pulmonary arteries. Impairment of AC6 activity in hypoxia was associated with nitrosylation. PPHN PA relaxation is impaired because of loss of AC activity. Hypoxic AC is inhibited because of S-nitrosylation; inhibition persists after removal from hypoxia. Downregulation of AC-mediated relaxation in hypoxic PA has implications for utility of Gαs-coupled receptor agonists in PPHN treatment.

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