Inhaled nitric oxide in premature neonates with severe hypoxaemic respiratory failure: a randomised controlled trial

Kinsella, John P.; Walsh, William F.; Bose, Carl; Gerstmann, Dale R.; Labella, JJ; Sardesai, Smeeta; Walsh-Sukys, Michele C.; McCaffrey, Martin J.; Cornfield, David N.; Bhutani, Vinod K.; Cutter, Gary; Baier, Monika; Abman, Steven H.

doi:10.1016/s0140-6736(99)03558-8

Cited by 250 publications

(167 citation statements)

References 26 publications

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“…This finding was also consistent with findings from a larger Japanese observational study conducted by Kusuda and colleagues [26], which showed that in the 2145 very low birthweight infants studied (mean [SD] birthweight, 1024 [302] g; mean [SD] GA, 28.9 [3.4] weeks), the observed incidence of grade 3 or 4 intraventricular hemorrhage was 7%. In prospective, controlled studies of iNO conducted in premature neonatal populations with respiratory failure in the United States, the overall safety profile observed (including reported incidences of intraventricular hemorrhage) has been similar in the iNO treatment arms compared with patient groups who received placebo or no iNO [27][28][29][30][31][32].…”

Section: Discussionmentioning

confidence: 93%

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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Section: Discussionmentioning

confidence: 93%

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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“…Pilot studies reported short-term improvement in oxygenation with iNO, but no significant benefit was observed in mortality or other morbidities. [10][11][12][13][14][15] Subsequently, several randomized clinical trials were undertaken. [16][17][18][19][20][21][22][23] Table 1 outlines the study population, entry criteria, and dose and duration of iNO treatment and summarizes the outcomes for all published randomized controlled trials.…”

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

122

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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

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“…(http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id ¼ 11080) In a meta-analysis of clinical studies involving term and late preterm neonates, Finer and Barrington 1 concluded that 'based on the evidence presently available, including the neurodevelopmental and general medical outcome information, near-term and term infants with hypoxic respiratory failure unresponsive to other therapy, excluding infants with diaphragmatic hernia, should have a trial of inhaled nitric oxide.' 1 The use of iNO in more premature (<34 weeks) infants has generally focused on two high-risk groups; those with severe acute respiratory distress 2,3 and those at high risk of developing bronchopulmonary dysplasia (BPD). [4][5][6] In a recent meta-analysis of the published clinical studies involving preterm infants, Barrington and Finer 7 concluded that 'y iNO should not be routinely used for preterm infants as a rescue therapy in cases of hypoxic respiratory failure.…”

Section: Introductionmentioning

confidence: 99%

The changing pattern of inhaled nitric oxide use in the neonatal intensive care unit

et al. 2010

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Objective: The purpose of this study was to evaluate the demographic characteristics and outcomes of neonates who were admitted to a neonatal intensive care unit and treated with inhaled nitric oxide (iNO) during the years 2000-08. The goal of studying this group of neonates was to evaluate how iNO use has evolved in infants and to estimate the frequency of off-label use of this drug in this population.Study Design: Retrospective review of the Pediatrix Clinical Data Warehouse de-identified data set. Pediatrix Medical Group provides intensive care services in 244 hospitals in 32 states and Puerto Rico. Nine (3.7%) centers provide extracorporeal membrane oxygenation.Result: There were 494 255 neonates in the data set; 4316 (0.9%) were treated with iNO. The use of iNO increased from 154 of 32 967 patients in 2000 to 921 of 75 911 patients in 2008; a 2.6-fold increase (0.47 to 1.23%). There were 155 872 infants <34 weeks estimated gestational age discharged between 1 January 2000 and 31 December 2008; 1656 (1.1%) were treated with iNO. Since approval in 2000, the reported use of iNO in neonates <34 weeks increased from 0.3 to 1.8% in 2008; a sixfold increase in the reported use of iNO. The biggest increase occurred in infants between 23 and 26 weeks' gestational age (0.8 to 6.6%). In contrast, the increase in iNO use among neonates born X34 weeks has only increased from 0.5 to 1%. Conclusion:The use of iNO has increased and the greatest increase has been the off-label use among preterm neonates. Journal of Perinatology (2010) In a meta-analysis of clinical studies involving term and late preterm neonates, Finer and Barrington 1 concluded that 'based on the evidence presently available, including the neurodevelopmental and general medical outcome information, near-term and term infants with hypoxic respiratory failure unresponsive to other therapy, excluding infants with diaphragmatic hernia, should have a trial of inhaled nitric oxide.' 1 The use of iNO in more premature (<34 weeks) infants has generally focused on two high-risk groups; those with severe acute respiratory distress 2,3 and those at high risk of developing bronchopulmonary dysplasia (BPD). [4][5][6] In a recent meta-analysis of the published clinical studies involving preterm infants, Barrington and Finer 7 concluded that 'y iNO should not be routinely used for preterm infants as a rescue therapy in cases of hypoxic respiratory failure. In contrast, the early routine use of iNO in ventilated preterm infants who are not severely ill, but nevertheless are at risk for serious brain injury or bronchopulmonary dysplasia, holds promise.' 7 The purpose of our study was to determine whether changes in practice are consistent with the suggestions of these two meta-analyses; more specifically, our goal was to evaluate how the off-label use of iNO has changed since its approval in late 1999.

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Inhaled nitric oxide in premature neonates with severe hypoxaemic respiratory failure: a randomised controlled trial

Cited by 250 publications

References 26 publications

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

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

Use of Inhaled Nitric Oxide in Preterm Infants

The changing pattern of inhaled nitric oxide use in the neonatal intensive care unit

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