Inhaled nitric oxide for prevention of bronchopulmonary dysplasia in premature babies (EUNO): a randomised controlled trial

Mercier, Jean-Christophe; Hummler, Helmut; Durrmeyer, Xavier; Sánchez‐Luna, Manuel; Carnielli, Virgilio P.; Field, David; Greenough, Anne; Overmeire, Bart Van; Jónsson, Baldvin; Hallman, Mikko; Baldassarre, James

doi:10.1016/s0140-6736(10)60664-2

Cited by 173 publications

(125 citation statements)

References 36 publications

Supporting

Mentioning

122

Contrasting

Unclassified

Order By: Relevance

“…11,28 Given increased iNO utilization in higher-acuity units, 24 it may be that iNO is directed at more critically ill neonates for which evidence of benefit and safety of use is most limited. 6- 16 The observation that neonatologists would increasingly prescribe iNO in a manner contrary to clinical evidence and expert opinion 22,23 is fascinating and provocative.…”

Section: Figurementioning

confidence: 99%

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

et al. 2015

View full text Add to dashboard Cite

BACKGROUND: Inhaled nitric oxide (iNO) therapy is an off-label medication in infants ,34 weeks' gestational age. In 2011, the National Institutes of Health released a statement discouraging routine iNO use in premature infants. The objective of this study was to describe utilization patterns of iNO in American NICUs in the years surrounding the release of the National Institutes of Health statement. We hypothesized that iNO prescription rates in premature infants have remained unchanged since 2011.

show abstract

Section: Figurementioning

confidence: 99%

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

et al. 2015

View full text Add to dashboard Cite

show abstract

“…[28][29][30] In an early study of iNO use in preterm infants, the incidence of BPD was reduced in treated infants who required ventilator support. 16 Of 3 subsequent large randomized trials designed to evaluate the effect of iNO therapy on survival without BPD, 20,24,25 2 found no significant benefit 20,25 (Table 1). A third trial, which featured late treatment (7-21 days of age), a longer duration of drug exposure (25 days), and a higher cumulative dose, demonstrated a modest but statistically significant beneficial effect (44% iNO vs 37% placebo; P = .042).…”

Section: Use Of Ino In Preterm Infants With Respiratory Failurementioning

confidence: 99%

Use of Inhaled Nitric Oxide in Preterm Infants

Kumar¹,

Papile²,

Polin³

et al. 2014

Pediatrics

116

View full text Add to dashboard Cite

Nitric oxide, an important signaling molecule with multiple regulatory effects throughout the body, is an important tool for the treatment of full-term and late-preterm infants with persistent pulmonary hypertension of the newborn and hypoxemic respiratory failure. Several randomized controlled trials have evaluated its role in the management of preterm infants ≤34 weeks' gestational age with varying results. The purpose of this clinical report is to summarize the existing evidence for the use of inhaled nitric oxide in preterm infants and provide guidance regarding its use in this population. Pediatrics 2014;133:164-170 INTRODUCTIONNitric oxide (NO) is an important signaling molecule with multiple regulatory effects throughout the body. In perinatal medicine, inhaled nitric oxide (iNO) was initially studied for its pulmonary vasodilating effects in infants with pulmonary hypertension and has since become an important tool for the treatment of full-term and late-preterm infants with persistent pulmonary hypertension of the newborn and hypoxemic respiratory failure. 1 Inhaled NO also has multiple and complex systemic and pulmonary effects. In animal models of neonatal chronic lung disease, iNO stimulates angiogenesis, augments alveolarization, improves surfactant function, and inhibits proliferation of smooth muscle cells and abnormal elastin deposition. [2][3][4][5][6] Although the evidence for similar benefits in preterm infants is lacking, the off-label use of iNO in this population has escalated. 7 A study published in 2010 reported a sixfold increase (from 0.3% to 1.8%) in the use of iNO among infants born at less than 34 weeks' gestation between 2000 and 2008. 7 The greatest increase occurred among infants who were born at 23 to 26 weeks' gestation (0.8% to 6.6%). The National Institutes of Health convened a consensus panel in October 2010 to evaluate the evidence for safety and efficacy of iNO therapy in preterm infants. After reviewing the published evidence, the panel concluded that the available evidence does not support the use of iNO in early routine, early rescue, or later rescue regimens in the care of infants born at less than 34 weeks' gestation and that hospitals, clinicians, and the pharmaceutical industry should avoid marketing iNO for this group of infants. 8 An individual-patient data meta-analysis of 14 randomized controlled trials reached similar conclusions. 9 The purpose of this clinical report is to summarize the Praveen Kumar MD, FAAP, and COMMITTEE ON FETUS AND NEWBORN KEY WORDS inhaled nitric oxide, preterm infants, hypoxic respiratory failure, bronchopulmonary dysplasia ABBREVIATIONS BPD-bronchopulmonary dysplasia iNO-inhaled nitric oxide NO-nitric oxide NOCLD-Nitric

show abstract

“…[19][20][21][22][23][24][25][26][27][28][29][30][31][32] The most recent Cochrane review, published in 2010, included the same studies. 33 These 14 studies differed not only in their design, intervention, and indications but also in the eligible patient populations.…”

mentioning

confidence: 99%

Inhaled Nitric Oxide in Preterm Infants: An Individual-Patient Data Meta-analysis of Randomized Trials

et al. 2011

Self Cite

View full text Add to dashboard Cite

BACKGROUND: Inhaled nitric oxide (iNO) is an effective therapy for pulmonary hypertension and hypoxic respiratory failure in term infants. Fourteen randomized controlled trials (n ϭ 3430 infants) have been conducted on preterm infants at risk for chronic lung disease (CLD). The study results seem contradictory. DESIGN/METHODS:Individual-patient data meta-analysis included randomized controlled trials of preterm infants (Ͻ37 weeks' gestation). Outcomes were adjusted for trial differences and correlation between siblings. RESULTS:Data from 3298 infants in 12 trials (96%) were analyzed. There was no statistically significant effect of iNO on death or CLD (59% vs 61%: relative risk [RR]: 0.96 [95% confidence interval (CI): 0.92-1.01]; P ϭ .11) or severe neurologic events on imaging (25% vs 23%: RR: 1.12 [95% CI: 0.98 -1.28]; P ϭ .09). There were no statistically significant differences in iNO effect according to any of the patient-level characteristics tested. In trials that used a starting iNO dose of Ͼ5 vs Յ5 ppm there was evidence of improved outcome (interaction P ϭ .02); however, these differences were not observed at other levels of exposure to iNO. This result was driven primarily by 1 trial, which also differed according to overall dose, duration, timing, and indication for treatment; a significant reduction in death or CLD (RR: 0.85 [95% CI: 0.74 -0.98]) was found.CONCLUSIONS: Routine use of iNO for treatment of respiratory failure in preterm infants cannot be recommended. The use of a higher starting dose might be associated with improved outcome, but because there were differences in the designs of these trials, it requires further examination.

show abstract

Inhaled nitric oxide for prevention of bronchopulmonary dysplasia in premature babies (EUNO): a randomised controlled trial

Cited by 173 publications

References 36 publications

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

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

Use of Inhaled Nitric Oxide in Preterm Infants

Inhaled Nitric Oxide in Preterm Infants: An Individual-Patient Data Meta-analysis of Randomized Trials

Contact Info

Product

Resources

About