Intravenous epoprostenol improves oxygenation index in patients with persistent pulmonary hypertension of the newborn refractory to nitric oxide

Objective. To determine the clinical role of inhaled nitric oxide (iNO) in the treatment of persistent pulmonary hypertension of the newborn (PPHN). Study Design. Prospective open observational clinical study. Setting. A regional cardiac and pediatric intensive care unit. Methods. Twenty-five consecutive near-term neonates (>35 weeks gestation) with severe PPHN (oxygenation index [OI]> 25) were given a trial of iNO of 20 ppm for 20 minutes. Neonates who showed a greater than 20% improvement in Pao 2 as well as a decrease in the OI to below 40 were defined as responders and continued on this therapy. Results. Four patterns of response emerged to the iNO therapy: Pattern 1 neonates (n = 2) did not respond to the initial trial of iNO—one survived. Pattern 2 neonates (n = 9) responded to the initial trial of iNO, but failed to sustain this response over 36 hours, as defined by a rise in the OI to >40. Six survived, five with extracorporeal membrane oxygenation. Pattern 3 neonates (n = 11) responded to the initial trial of iNO, sustained this response, and were successfully weaned from iNO within 5 days—all survived to discharge. Pattern 4 neonates (n = 3) responded to the initial trial of iNO, but developed a sustained dependence on iNO for 3 to 6 weeks. All three died and lung histology revealed severe pulmonary hypoplasia and dysplasia. These neonates (pattern 4) not only required iNO for a longer period of time than did the sustained responders (pattern 3), but they required significantly higher doses of iNO during their first 5 days of iNO therapy. Conclusions. Early responses to iNO may not be sustained. Neonates with pulmonary hypoplasia and dysplasia may have a decreased sensitivity and differing time course of response to iNO when compared with patients who have PPHN in fully developed lungs.

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Nitric oxide in persistent pulmonary hypertension of the newborn

Jornal de Pediatria ◽

10.2223/jped.582 ◽

1996 ◽

Vol 72 (3) ◽

Author(s):

Humberto H. Fiori ◽

Renato M. Fiori

Keyword(s):

Nitric Oxide ◽

Pulmonary Hypertension ◽

Persistent Pulmonary Hypertension

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Inhaled Nitric Oxide at Birth Reduces Pulmonary Vascular Resistance and Improves Oxygenation in Preterm Lambs

Children ◽

10.3390/children8050378 ◽

2021 ◽

Vol 8 (5) ◽

pp. 378

Author(s):

Satyan Lakshminrusimha ◽

Sylvia F. Gugino ◽

Krishnamurthy Sekar ◽

Stephen Wedgwood ◽

Carmon Koenigsknecht ◽

...

Keyword(s):

Nitric Oxide ◽

Pulmonary Hypertension ◽

Pulmonary Vascular Resistance ◽

Preterm Infants ◽

Vascular Resistance ◽

Inhaled Nitric Oxide ◽

Persistent Pulmonary Hypertension ◽

Inhaled No ◽

Birth Preterm

Resuscitation with 21% O2 may not achieve target oxygenation in preterm infants and in neonates with persistent pulmonary hypertension of the newborn (PPHN). Inhaled nitric oxide (iNO) at birth can reduce pulmonary vascular resistance (PVR) and improve PaO2. We studied the effect of iNO on oxygenation and changes in PVR in preterm lambs with and without PPHN during resuscitation and stabilization at birth. Preterm lambs with and without PPHN (induced by antenatal ductal ligation) were delivered at 134 d gestation (term is 147–150 d). Lambs without PPHN were ventilated with 21% O2, titrated O2 to maintain target oxygenation or 21% O2 + iNO (20 ppm) at birth for 30 min. Preterm lambs with PPHN were ventilated with 50% O2, titrated O2 or 50% O2 + iNO. Resuscitation with 21% O2 in preterm lambs and 50%O2 in PPHN lambs did not achieve target oxygenation. Inhaled NO significantly decreased PVR in all lambs and increased PaO2 in preterm lambs ventilated with 21% O2 similar to that achieved by titrated O2 (41 ± 9% at 30 min). Inhaled NO increased PaO2 to 45 ± 13, 45 ± 20 and 76 ± 11 mmHg with 50% O2, titrated O2 up to 100% and 50% O2 + iNO, respectively, in PPHN lambs. We concluded that iNO at birth reduces PVR and FiO2 required to achieve target PaO2.

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Methemoglobin and the response to inhaled nitric oxide in persistent pulmonary hypertension of the newborn

Journal of Neonatal-Perinatal Medicine ◽

10.3233/npm-180082 ◽

2020 ◽

Vol 13 (2) ◽

pp. 175-182

Author(s):

R. Dadiz ◽

J. Nair ◽

C.T. D’Angio ◽

R.M. Ryan ◽

S. Lakshminrusimha

Keyword(s):

Nitric Oxide ◽

Pulmonary Hypertension ◽

Inhaled Nitric Oxide ◽

Persistent Pulmonary Hypertension

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Recombinant Human Superoxide Dismutase Enhances the Effect of Inhaled Nitric Oxide in Persistent Pulmonary Hypertension

American Journal of Respiratory and Critical Care Medicine ◽

10.1164/ajrccm.164.5.2010104 ◽

2001 ◽

Vol 164 (5) ◽

pp. 834-839 ◽

Cited By ~ 77

Author(s):

ROBIN H. STEINHORN ◽

GEORGE ALBERT ◽

DANIEL D. SWARTZ ◽

JAMES A. RUSSELL ◽

CAROLYN R. LEVINE ◽

...

Keyword(s):

Nitric Oxide ◽

Pulmonary Hypertension ◽

Superoxide Dismutase ◽

Inhaled Nitric Oxide ◽

Persistent Pulmonary Hypertension

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Efficacy of inhaled nitric oxide in neonates with hypoxic respiratory failure and pulmonary hypertension: the Japanese experience

Journal of Perinatal Medicine ◽

10.1515/jpm-2017-0040 ◽

2018 ◽

Vol 46 (6) ◽

pp. 657-663 ◽

Cited By ~ 6

Author(s):

Satoshi Suzuki ◽

Hajime Togari ◽

Jim L. Potenziano ◽

Michael D. Schreiber

Keyword(s):

Nitric Oxide ◽

Pulmonary Hypertension ◽

Respiratory Failure ◽

Negative Impact ◽

Survival Rates ◽

Oxygenation Index ◽

Inhaled Nitric Oxide ◽

Preterm Neonates ◽

Therapeutic Trial ◽

Hypoxic Respiratory Failure

AbstractObjective:To analyze data from a registry of Japanese neonates with hypoxic respiratory failure associated with pulmonary hypertension (PH) to compare the effectiveness of inhaled nitric oxide (iNO) in neonates born <34 weeks vs. ≥34 weeks gestational age (GA).Materials and methods:iNO was administered according to approved Japanese product labeling. Study data were collected before iNO administration and at predefined intervals until discontinuation.Results:A total of 1,114 neonates were included (n=431, <34 weeks GA; n=675, ≥34 weeks GA; n=8, missing age data). Mean decrease from baseline oxygenation index (OI) was similar in both age groups. OI reduction was more pronounced in the <34 weeks subgroups with baseline OI ≥25. Survival rates were similar in the <34 weeks GA and ≥34 weeks GA groups stratified by baseline OI (OI<15, 89% vs. 93%; 15≤OI<25, 85% vs. 91%; 25≤OI≤40, 73% vs. 79%; OI>40, 64% vs. 66%).Conclusion:iNO improved oxygenation in preterm neonates as effectively as in late preterm and term neonates, without negative impact on survival. If clinically significant PH is present, as measured by pulse oximetry or echocardiography, a therapeutic trial of iNO might be indicated for preterm neonates.

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The effect of inhaled nitric oxide therapy on thromboelastogram in newborns with persistent pulmonary hypertension

European Journal of Pediatrics ◽

10.1007/s00431-014-2325-3 ◽

2014 ◽

Vol 173 (10) ◽

pp. 1381-1385 ◽

Cited By ~ 8

Author(s):

Sema Tanriverdi ◽

Ozge Altun Koroglu ◽

Ozgun Uygur ◽

Can Balkan ◽

Mehmet Yalaz ◽

...

Keyword(s):

Nitric Oxide ◽

Pulmonary Hypertension ◽

Inhaled Nitric Oxide ◽

Persistent Pulmonary Hypertension ◽

Nitric Oxide Therapy

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Persistent Pulmonary Hypertension of the Newborn: Role of Nitric Oxide

Journal of Intensive Care Medicine ◽

10.1177/088506669501000602 ◽

1995 ◽

Vol 10 (6) ◽

pp. 270-282

Author(s):

Stella Kourembanas

Keyword(s):

Nitric Oxide ◽

Pulmonary Hypertension ◽

Structural Changes ◽

Critical Role ◽

Persistent Pulmonary Hypertension ◽

Cell Contractility ◽

Vasoactive Mediators ◽

Nitric Oxide Therapy

Persistent pulmonary hypertension of the newborn (PPHN) is a common cause of respiratory failure in the full-term neonate. Molecular and cellular studies in vascular biology have revealed that endothelial-derived mediators play a critical role in the pathogenesis and treatment of PPHN. Endothelial-derived vasoconstrictors, like endothelin, may increase smooth muscle cell contractility and growth, leading to the physiologic and structural changes observed in the pulmonary arterioles of infants with this disease. On the other hand, decreased production of the endothelial-derived relaxing factor, nitric oxide, may exacerbate pulmonary vasoreactivity and lead to more severe pulmonary hypertension. Exogenous (inhaled) nitric oxide therapy reduces pulmonary vascular resistance and improves oxygenation. The safety and efficacy of this therapy in reducing the need for extracorporeal membrane oxygenation and decreasing long-term morbidity is being tested in several trials nationally and abroad. Understanding the basic mechanisms that regulate the gene expression and production of these vasoactive mediators will lead to improved preventive and therapeutic strategies for PPHN.

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