Inhaled Nitric Oxide for the Early Treatment of Persistent Pulmonary Hypertension of the Term Newborn: A Randomized, Double-Masked, Placebo-Controlled, Dose-Response, Multicenter Study

Davidson, Dennis; Barefield, Elaine S.; Kattwinkel, John; Dudell, Golde G.; Damask, Michael C.; Straube, Richard; Rhines, J; Chang, Cheng‐Tao

doi:10.1542/peds.101.3.325

Cited by 329 publications

(176 citation statements)

References 28 publications

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“…Methemoglobinemia was not evaluated as it is not generally a clinical problem with inhalation of 20 ppm NO or less. 5,7 The majority of the available literature on NO administration to neonates deal with mechanically ventilated infants, because NO has been used so far as a ''rescue'' therapy for infants not responding to conventional, and in some cases, high-frequency ventilation. Kakuya et al 17 reported on the use of inhaled NO via a nasopharyngeal tube in an infant with a severely hypoplastic lung and end-stage pulmonary hypertension, in whom clinical improvement was maintained for 7 days with 18 to 22 ppm NO inhalation.…”

Section: Discussionmentioning

confidence: 99%

Feasibility of Nitric Oxide Administration by Oxygen Hood in Neonatal Pulmonary Hypertension

et al. 2002

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Section: Discussionmentioning

confidence: 99%

Feasibility of Nitric Oxide Administration by Oxygen Hood in Neonatal Pulmonary Hypertension

et al. 2002

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“…In pivotal studies of late preterm and term neonates with hypoxic respiratory failure (HRF) and pulmonary hypertension (PH), iNO therapy has been shown to improve oxygenation and reduce the need for extracorporeal membrane oxygenation [3][4][5][6]. In the United States, iNO is indicated for the treatment of late preterm and term (>34 weeks' gestation) neonates with HRF associated with clinical or echocardiographic evidence of PH [7].…”

Section: Introductionmentioning

confidence: 99%

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

Suzuki

Togari

Potenziano

et al. 2018

Journal of Perinatal Medicine

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Objective: 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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“…64 Inhaled NO therapy has been reported to improve systemic oxygenation in infants with PPHN, and may reduce the need for more invasive treatments, including extracorporeal membrane oxygenation. [65][66][67] In vascular endothelial cells, eNOS is responsible for the production of the majority of NO mainly during conversion of L-arginine to L-citrulline. 68 There is more and more evidence that the levels of eNOS expression are conspicuously associated with PPHN.…”

Section: Pphn and Enosmentioning

confidence: 99%

Epigenetic regulation of pulmonary arterial hypertension

Cheng

2011

Hypertens Res

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Pulmonary arterial hypertension (PAH) is diagnosed as a sustained elevation of pulmonary arterial pressure to more than 25 mm Hg at rest or to more than 30 mm Hg with exercise. PAH is an intrinsic disease of the pulmonary vascular smooth muscle and endothelial cells in association with plexiform lesions, medial thickening, concentric laminar intimal fibrosis and thrombotic lesions. Pulmonary vascular remodeling is the characteristic pathological change of PAH. The pathogenesis of PAH has been studied at the level of smooth muscle and endothelial cells. Existing research does not adequately explain susceptibility to the disease, and recent evidence reveals that epigenetic alterations may be involved in PAH. Epigenetics refers to all heritable changes in phenotype or in gene expression states, including chromatin remodeling, DNA methylation, histone modification and RNA interference, which are not involved in the DNA sequence itself. This review will focus on recent advances in epigenetics related to PAH, including epigenetic changes of superoxide dismutase, endothelial nitric oxide synthase and the bone morphogenetic protein signaling pathway. This will provide new insight for improved treatment and prevention of PAH. Future work aimed at specific epigenetic treatments may prove to be an effective therapy for patients with PAH.

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Inhaled Nitric Oxide for the Early Treatment of Persistent Pulmonary Hypertension of the Term Newborn: A Randomized, Double-Masked, Placebo-Controlled, Dose-Response, Multicenter Study

Abstract: For term infants with PPHN, early I-NO as the sole adjunct to conventional management produced an acute and sustained improvement in oxygenation for 24 hours without short-term side effects (5 and 20 ppm doses), and the suggestion that ECMO use may be reduced.

Cited by 329 publications

References 28 publications

Feasibility of Nitric Oxide Administration by Oxygen Hood in Neonatal Pulmonary Hypertension

Feasibility of Nitric Oxide Administration by Oxygen Hood in Neonatal Pulmonary Hypertension

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

Epigenetic regulation of pulmonary arterial hypertension

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