Inhaled nitric oxide in preterm infants: An individual-patient data meta-analysis of randomized trials

BACKGROUND: Inhaled nitric oxide (iNO) is an effective therapy for pulmonary hypertension and hypoxic respiratory failure in term infants. Fourteen randomized controlled trials (n = 3430 infants) have been conducted on preterm infants at risk for chronic lung disease (CLD). The study results seem co...

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Main Authors: Lisa M. Askie, Roberta A. Ballard, Gary R. Cutter, Carlo Dani, Diana Elbourne, David Field, Jean Michel Hascoet, Anna Maria Hibbs, John P. Kinsella, Jean Christophe Mercier, Wade Rich, Michael D. Schreiber, Pimol Wongsiridej, Nim V. Subhedar, Krisa P. Van Meurs, Merryn Voysey, Keith Barrington, Richard A. Ehrenkranz, Neil N. Finer
Other Authors: The University of Sydney
Format: Review
Published: 2018
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Online Access:https://repository.li.mahidol.ac.th/handle/123456789/12310
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spelling th-mahidol.123102018-05-03T15:25:38Z Inhaled nitric oxide in preterm infants: An individual-patient data meta-analysis of randomized trials Lisa M. Askie Roberta A. Ballard Gary R. Cutter Carlo Dani Diana Elbourne David Field Jean Michel Hascoet Anna Maria Hibbs John P. Kinsella Jean Christophe Mercier Wade Rich Michael D. Schreiber Pimol Wongsiridej Nim V. Subhedar Krisa P. Van Meurs Merryn Voysey Keith Barrington Richard A. Ehrenkranz Neil N. Finer The University of Sydney UCSF School of Medicine University of Alabama at Birmingham Azienda Ospedaliera Careggi London School of Hygiene &amp; Tropical Medicine University of Leicester Maternite Regionale de Nancy Rainbow Babies and Children's Hosp. University of Colorado School of Medicine Universite Paris 7- Denis Diderot University of California, San Diego University of Chicago Mahidol University Liverpool Women's Hospital Stanford University School of Medicine Centre Hospitalier de L'Universite de Montreal Yale University School of Medicine Medicine BACKGROUND: Inhaled nitric oxide (iNO) is an effective therapy for pulmonary hypertension and hypoxic respiratory failure in term infants. Fourteen randomized controlled trials (n = 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 ( < 37 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=.11) or severe neurologic events on imaging (25% vs 23%: RR: 1.12 [95% CI: 0.98-1.28]; P = .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 > 5 vs ≤5 ppm there was evidence of improved outcome (interaction P = .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. Copyright © 2011 by the American Academy of Pediatrics. 2018-05-03T08:25:38Z 2018-05-03T08:25:38Z 2011-10-01 Review Pediatrics. Vol.128, No.4 (2011), 729-739 10.1542/peds.2010-2725 10984275 00314005 2-s2.0-80053519757 https://repository.li.mahidol.ac.th/handle/123456789/12310 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=80053519757&origin=inward
institution Mahidol University
building Mahidol University Library
continent Asia
country Thailand
Thailand
content_provider Mahidol University Library
collection Mahidol University Institutional Repository
topic Medicine
spellingShingle Medicine
Lisa M. Askie
Roberta A. Ballard
Gary R. Cutter
Carlo Dani
Diana Elbourne
David Field
Jean Michel Hascoet
Anna Maria Hibbs
John P. Kinsella
Jean Christophe Mercier
Wade Rich
Michael D. Schreiber
Pimol Wongsiridej
Nim V. Subhedar
Krisa P. Van Meurs
Merryn Voysey
Keith Barrington
Richard A. Ehrenkranz
Neil N. Finer
Inhaled nitric oxide in preterm infants: An individual-patient data meta-analysis of randomized trials
description BACKGROUND: Inhaled nitric oxide (iNO) is an effective therapy for pulmonary hypertension and hypoxic respiratory failure in term infants. Fourteen randomized controlled trials (n = 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 ( < 37 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=.11) or severe neurologic events on imaging (25% vs 23%: RR: 1.12 [95% CI: 0.98-1.28]; P = .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 > 5 vs ≤5 ppm there was evidence of improved outcome (interaction P = .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. Copyright © 2011 by the American Academy of Pediatrics.
author2 The University of Sydney
author_facet The University of Sydney
Lisa M. Askie
Roberta A. Ballard
Gary R. Cutter
Carlo Dani
Diana Elbourne
David Field
Jean Michel Hascoet
Anna Maria Hibbs
John P. Kinsella
Jean Christophe Mercier
Wade Rich
Michael D. Schreiber
Pimol Wongsiridej
Nim V. Subhedar
Krisa P. Van Meurs
Merryn Voysey
Keith Barrington
Richard A. Ehrenkranz
Neil N. Finer
format Review
author Lisa M. Askie
Roberta A. Ballard
Gary R. Cutter
Carlo Dani
Diana Elbourne
David Field
Jean Michel Hascoet
Anna Maria Hibbs
John P. Kinsella
Jean Christophe Mercier
Wade Rich
Michael D. Schreiber
Pimol Wongsiridej
Nim V. Subhedar
Krisa P. Van Meurs
Merryn Voysey
Keith Barrington
Richard A. Ehrenkranz
Neil N. Finer
author_sort Lisa M. Askie
title Inhaled nitric oxide in preterm infants: An individual-patient data meta-analysis of randomized trials
title_short Inhaled nitric oxide in preterm infants: An individual-patient data meta-analysis of randomized trials
title_full Inhaled nitric oxide in preterm infants: An individual-patient data meta-analysis of randomized trials
title_fullStr Inhaled nitric oxide in preterm infants: An individual-patient data meta-analysis of randomized trials
title_full_unstemmed Inhaled nitric oxide in preterm infants: An individual-patient data meta-analysis of randomized trials
title_sort inhaled nitric oxide in preterm infants: an individual-patient data meta-analysis of randomized trials
publishDate 2018
url https://repository.li.mahidol.ac.th/handle/123456789/12310
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