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      Inhaled nitric oxide in preterm infants: An updated meta-analysis

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          Abstract

          Background:

          In the past several years, randomized controlled trials (RCTs) have indicated that inhaled nitric oxide (iNO) can potentially lower for both the incidence of bronchopulmonary dysplasia (BPD) and mortality in affected infants. Other research has, however, disagreed with these findings.

          Materials and Methods:

          We performed an updated meta analysis of all relevant RCTs to assess the benefits of iNO in preterm infants by searching PubMed, EMBASE, Cochrane databases, Wanfang, VIP, and CNKI databases for English and Chinese references.

          Results:

          Ultimately, 22 RCTs were incorporated. (1) Risk of BPD was significantly lower in preterm infants supplemented with iNO (relative risk [RR] = 0.88; P = 0.0007). There are no differences concerning pulmonary hemorrhage (PH) (RR = 0.94; P = 0.72). (2) Incidences of necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), and severe intracranial hemorrhage (ICH) were compared. No significant difference was discovered concerning these risks (RR = 1.21, P = 0.08; RR = 1.01, P = 0.89; and RR = 0.99, P = 0.86). (3) In addition, no significant differences were found between experimental and control groups with respect to morality. (RR = 1.00, P = 0.98).

          Conclusion:

          Our meta analysis has shown a beneficial effect in BPD and morality. In addition, our meta analysis suggests that iNO therapy does not increase the risk of common complications, such as NEC and ROP, and that it may also have no adverse effect on bleeding tendency diseases (severe ICH and PH).

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          Inhaled nitric oxide in full-term and nearly full-term infants with hypoxic respiratory failure.

          (1997)
          Neonates with pulmonary hypertension have been treated with inhaled nitric oxide because of studies suggesting that it is a selective pulmonary vasodilator. We conducted a randomized, multicenter, controlled trial to determine whether inhaled nitric oxide would reduce mortality or the initiation of extracorporeal membrane oxygenation in infants with hypoxic respiratory failure. Infants born after a gestation of > or =34 weeks who were 14 days old or less, had no structural heart disease, and required assisted ventilation and whose oxygenation index was 25 or higher on two measurements were eligible for the study. The infants were randomly assigned to receive nitric oxide at a concentration of 20 ppm or 100 percent oxygen (as a control). Infants whose partial pressure of arterial oxygen (PaO2) increased by 20 mm Hg or less after 30 minutes were studied for a response to 80-ppm nitric oxide or control gas. The 121 infants in the control group and the 114 in the nitric oxide group had similar base-line clinical characteristics. Sixty-four percent of the control group and 46 percent of the nitric oxide group died within 120 days or were treated with extracorporeal membrane oxygenation (P=0.006). Seventeen percent of the control group and 14 percent of the nitric oxide group died (P not significant), but significantly fewer in the nitric oxide group received extracorporeal membrane oxygenation (39 percent vs. 54 percent, P=0.014). The nitric oxide group had significantly greater improvement in PaO2 (increase, 58.2+/-85.2 mm Hg, vs. 9.7+/-51.7 mm Hg in the controls; P<0.001) and in the oxygenation index (a decrease of 14.1+/-21.1, vs. an increase of 0.8+/-21.1 in the controls; P<0.001). The study gas was not discontinued in any infant because of toxicity. Nitric oxide therapy reduced the use of extracorporeal membrane oxygenation, but had no apparent effect on mortality in critically ill infants with hypoxic respiratory failure.
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            Low-dose nitric oxide therapy for persistent pulmonary hypertension of the newborn. Clinical Inhaled Nitric Oxide Research Group.

            M Keszler, G Southgate, T Kueser … (2000)
            Inhaled nitric oxide improves gas exchange in neonates, but the efficacy of low-dose inhaled nitric oxide in reducing the need for extracorporeal membrane oxygenation has not been established. We conducted a clinical trial to determine whether low-dose inhaled nitric oxide would reduce the use of extracorporeal membrane oxygenation in neonates with pulmonary hypertension who were born after 34 weeks' gestation, were 4 days old or younger, required assisted ventilation, and had hypoxemic respiratory failure as defined by an oxygenation index of 25 or higher. The neonates who received nitric oxide were treated with 20 ppm for a maximum of 24 hours, followed by 5 ppm for no more than 96 hours. The primary end point of the study was the use of extracorporeal membrane oxygenation. Of 248 neonates enrolled, 126 were randomly assigned to the nitric oxide group and 122 to the control group. Extracorporeal membrane oxygenation was used in 78 neonates in the control group (64 percent) and in 48 neonates in the nitric oxide group (38 percent) (P=0.001). The 30-day mortality rate in the two groups was similar (8 percent in the control group and 7 percent in the nitric oxide group). Chronic lung disease developed less often in neonates treated with nitric oxide than in those in the control group (7 percent vs. 20 percent, P=0.02). The efficacy of nitric oxide was independent of the base-line oxygenation index and the primary pulmonary diagnosis. Inhaled nitric oxide reduces the extent to which extracorporeal membrane oxygenation is needed in neonates with hypoxemic respiratory failure and pulmonary hypertension.
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              Inhaled nitric oxide in preterm infants undergoing mechanical ventilation.

              Roberta Ballard, William E. Truog, Avital Cnaan … (2006)
              Bronchopulmonary dysplasia in premature infants is associated with prolonged hospitalization, as well as abnormal pulmonary and neurodevelopmental outcome. In animal models, inhaled nitric oxide improves both gas exchange and lung structural development, but the use of this therapy in infants at risk for bronchopulmonary dysplasia is controversial. We conducted a randomized, stratified, double-blind, placebo-controlled trial of inhaled nitric oxide at 21 centers involving infants with a birth weight of 1250 g or less who required ventilatory support between 7 and 21 days of age. Treated infants received decreasing concentrations of nitric oxide, beginning at 20 ppm, for a minimum of 24 days. The primary outcome was survival without bronchopulmonary dysplasia at 36 weeks of postmenstrual age. Among 294 infants receiving nitric oxide and 288 receiving placebo birth weight (766 g and 759 g, respectively), gestational age (26 weeks in both groups), and other characteristics were similar. The rate of survival without bronchopulmonary dysplasia at 36 weeks of postmenstrual age was 43.9 percent in the group receiving nitric oxide and 36.8 percent in the placebo group (P=0.042). The infants who received inhaled nitric oxide were discharged sooner (P=0.04) and received supplemental oxygen therapy for a shorter time (P=0.006). There were no short-term safety concerns. Inhaled nitric oxide therapy improves the pulmonary outcome for premature infants who are at risk for bronchopulmonary dysplasia when it is started between 7 and 21 days of age and has no apparent short-term adverse effects. (ClinicalTrials.gov number, NCT00000548 [ClinicalTrials.gov] .). Copyright 2006 Massachusetts Medical Society.
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Res Med Sci
                Journal ID (iso-abbrev): J Res Med Sci
                Journal ID (publisher-id): JRMS
                Title: Journal of Research in Medical Sciences : The Official Journal of Isfahan University of Medical Sciences
                Publisher: Medknow Publications & Media Pvt Ltd (India )
                ISSN (Print): 1735-1995
                ISSN (Electronic): 1735-7136
                Publication date Collection: 2016
                Publication date (Electronic): 14 June 2016
                Volume: 21
                Electronic Location Identifier: 41
                Affiliations
                [1]Department of Neonates, Nanjing Children's Hospital of Nanjing Medical University, Nanjing 210008, P. R. China
                [1 ]Department of Pediatrics, Jiangsu Provincial Hospital of Nanjing Medical University, Nanjing 210029, P. R. China
                Author notes
                Address for correspondence: Prof. XiaoYu Zhou, Department of Neonates, Nanjing Children's Hospital of Nanjing Medical University, 72 Guangzhou Road, Nanjing, Jiangsu 210008, P. R. China. E-mail: yy860507@ 123456126.com
                [*]

                Yun Feng and Yang Yang are contributes equally

                Article
                Publisher ID: JRMS-21-41
                DOI: 10.4103/1735-1995.183990
                PMC ID: 5122073
                PubMed ID: 27904587
                SO-VID: 757de080-d515-4f41-9bdc-b7ff2caab167
                Copyright © Copyright: © 2016 Journal of Research in Medical Sciences
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

                History
                Date received : 17 August 2015
                Date revision received : 24 February 2016
                Date accepted : 07 April 2016
                Categories
                Subject: Review Article

                ScienceOpen disciplines: Medicine
                Keywords: meta-analysis,nitric oxide,preterm
                Data availability:
                ScienceOpen disciplines: Medicine
                Keywords: meta-analysis, nitric oxide, preterm

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