Off-Label Use of Inhaled Nitric Oxide After Release of NIH Consensus Statement

Ellsworth, Marc A.; Harris, Malinda N.; Carey, William A.; Spitzer, Alan R.; Clark, Reese H.

doi:10.1542/peds.2014-3290

Cited by 68 publications

(60 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…There are no data to support routine or rescue use of inhaled nitric oxide (iNO) in preterm babies [172]. Despite this, iNO continues to be used in many units, particularly for ill babies with severe respiratory failure and poor oxygenation [173,174]. There is an argument for rationalizing the use of iNO for specific populations of preterm infants, for example those with premature rupture of membranes or documented pulmonary hypertension and conducting further clinical trials [175,176].…”

Section: Managing Blood Pressure and Perfusionmentioning

confidence: 99%

European Consensus Guidelines on the Management of Respiratory Distress Syndrome - 2016 Update

et al. 2016

View full text Add to dashboard Cite

Advances in the management of respiratory distress syndrome (RDS) ensure that clinicians must continue to revise current practice. We report the third update of the European Guidelines for the Management of RDS by a European panel of expert neonatologists including input from an expert perinatal obstetrician based on available literature up to the beginning of 2016. Optimizing the outcome for babies with RDS includes consideration of when to use antenatal steroids, and good obstetric practice includes methods of predicting the risk of preterm delivery and also consideration of whether transfer to a perinatal centre is necessary and safe. Methods for optimal delivery room management have become more evidence based, and protocols for lung protection, including initiation of continuous positive airway pressure and titration of oxygen, should be implemented from soon after birth. Surfactant replacement therapy is a crucial part of the management of RDS, and newer protocols for surfactant administration are aimed at avoiding exposure to mechanical ventilation, and there is more evidence of differences among various surfactants in clinical use. Newer methods of maintaining babies on non-invasive respiratory support have been developed and offer potential for greater comfort and less chronic lung disease. As technology for delivering mechanical ventilation improves, the risk of causing lung injury should decrease although minimizing the time spent on mechanical ventilation using caffeine and if necessary postnatal steroids are also important considerations. Protocols for optimizing the general care of infants with RDS are also essential with good temperature control, careful fluid and nutritional management, maintenance of perfusion and judicious use of antibiotics all being important determinants of best outcome.

show abstract

Section: Managing Blood Pressure and Perfusionmentioning

confidence: 99%

European Consensus Guidelines on the Management of Respiratory Distress Syndrome - 2016 Update

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Recent reports showed that the rate of iNO utilisation in the treatment of pre-term neonates continues to increase in the USA [17] with no established evidence of the beneficial effects of iNO on survival in babies without bronchopulmonary dysplasia [3, 4, 18]. In this context, understanding the side-effects of iNO, including the rebound pulmonary hypertension upon iNO withdrawal, could be useful.…”

Section: Discussionmentioning

confidence: 99%

Inhaled nitric oxide decreases pulmonary endothelial nitric oxide synthase expression and activity in normal newborn rat lungs

et al. 2016

View full text Add to dashboard Cite

Inhaled nitric oxide (iNO) is commonly used in the treatment of very ill pre-term newborns. Previous studies showed that exogenous NO could affect endothelial NO synthase (eNOS) activity and expression in vascular endothelial cell cultures or adult rat models, but this has never been fully described in newborn rat lungs. We therefore aimed to assess the effects of iNO on eNOS expression and activity in newborn rats.Rat pups, post-natal day (P) 0 to P7, and their dams were placed in a chamber containing NO at 5 ppm (iNO-5 ppm group) or 20 ppm (iNO-20 ppm group), or in room air (control group). Rat pups were sacrificed at P7 and P14 for evaluation of lung eNOS expression and activity.At P7, eNOS protein expression in total lung lysates, in bronchial and arterial sections, was significantly decreased in the iNO-20 ppm versus control group. At P14, eNOS expression was comparable among all three groups. The amounts of eNOS mRNA significantly differed at P7 between the iNO-20 ppm and control groups. NOS activity decreased in the iNO-20 ppm group at P7 and returned to normal levels at P14. There was an imbalance between superoxide dismutase and NOS activities in the iNO-20 ppm group at P7.Inhalation of NO at 20 ppm early after birth decreases eNOS gene transcription, protein expression and enzyme activity. This decrease might account for the rebound phenomenon observed in patients treated with iNO.

show abstract

“…An analysis of off-label use of iNO in premature infants 23–29 weeks gestation utilizing the Pediatrix Medical Group Clinical Data Warehouse for the period 2009–2013 showed a relative increase of 23%, from 5.03% to 6.19% (p=.003). 78 iNO utilization rates were inversely proportional to gestational age; iNO was used in 13.9% of infants at 23–24 weeks compared to 0.6% of infants born at 33 weeks. The reason for use was not collected.…”

Section: Use Of Ino In the Preterm Infantmentioning

confidence: 96%

“…Several authors have speculated that the increase in oxygen saturation following iNO exposure leads neonatologists to attribute their survival to this physiologic response. 66,78 Finer and Evans suggest that evidence-based guidelines for the use of iNO in preterm infants should be developed by units. 66 Guidelines should leave room for individual judgment; however, they should also recognize the accumulated data which has shown the highest risk and lowest efficacy in premature infants <1000 grams.…”

Section: Use Of Ino In the Preterm Infantmentioning

confidence: 99%

Inhaled nitric oxide therapy for pulmonary disorders of the term and preterm infant

Sokol

Konduri

Meurs

2016

Seminars in Perinatology

View full text Add to dashboard Cite

The 21st century began with the FDA approval of inhaled nitric oxide therapy for the treatment of neonatal hypoxic respiratory failure associated with pulmonary hypertension in recognition of the two randomized clinical trials demostrating a significant reduction in the need for extracorporeal support in the term and near-term infant. Inhaled nitric oxide is one of only a few therapeutic agents approved for use through clinical investigations primarily in the neonate. This article provides an overview of the pertinent biology and chemistry of nitric oxide, discusses potential toxicities, and reviews the results of pertinent clinical investigations and large randomized clinical trials including neurodevelopmental follow-up in term and preterm neonates. The clinical investigations conducted by the Eunice Kennedy Shriver NICHD Neonatal Research Network will be discussed and placed in context with other pertinent clinical investigations exploring the efficacy of inhaled nitric oxide therapy in neonatal hypoxic respiratory failure.

show abstract

Off-Label Use of Inhaled Nitric Oxide After Release of NIH Consensus Statement

Cited by 68 publications

References 35 publications

European Consensus Guidelines on the Management of Respiratory Distress Syndrome - 2016 Update

European Consensus Guidelines on the Management of Respiratory Distress Syndrome - 2016 Update

Inhaled nitric oxide decreases pulmonary endothelial nitric oxide synthase expression and activity in normal newborn rat lungs

Inhaled nitric oxide therapy for pulmonary disorders of the term and preterm infant

Contact Info

Product

Resources

About