Inhaled nitric oxide for acute hypoxemic respiratory failure in children and adults.
OBJECTIVE
To determine the effect of iNO, compared with inhaled placebo, on outcome in AHRF in children and/or adults.


METHODS
Randomised controlled trials (RCT's) were identified from electronic databases; MEDLINE, EMBASE, the Cochrane Library, and CINAHL, as well as from bibliographies of retrieved articles. Relevant journals and conference proceedings were hand searched and authors published in this field were contacted for knowledge of unpublished ongoing trials.


METHODS
RCT's comparing iNO with maximal conventional therapy and inhaled placebo, for AHRF in either children or adults.


METHODS
Data were extracted and the analyses performed independently by two reviewers. All 5 authors were contacted for missing data. Qualitative assessment of each trial was made according to methodology described by Schulz (Schulz 1995), and analyses according to statistical methods in Review Manager MetaView 3.1. The fixed effect model was applied. Where possible, sub-group analyses were performed to assess the impact of iNO in varied doses.


RESULTS
Five RCT's were evaluated, assessing 535 patients with AHRF. Inhaled nitric oxide made no impact on mortality in trials without cross-over (RR 0.98, 95%CI 0.66, 1.44), or with cross-over of treatment failures to open-label iNO (RR 1.22, 95%CI 0.65, 2.29). Published evidence from one study demonstrated that iNO resulted in a transient improvement in oxygenation in the first 24 hours of treatment: the oxygenation index (OI) showed a mean difference of -3 [95% CI -5.354, -0.646], and PaO2/FiO2 ratio, a mean difference of 35 [95% CI 20.236, 49.764]. Limited data demonstrated no difference in ventilator-free days between treatment and placebo groups, and no specific dose of iNO was significantly advantageous over another. Other clinical indicators of effectiveness, such as duration of hospital and intensive care stay, were inconsistently reported. There were no complications reported to be directly attributable to this treatment.


CONCLUSIONS
From the data provided to date, iNO had no effect on mortality and only transiently improved oxygenation in AHRF in children and/or adults. There was a lack of data to assess other end points. The long term adverse effects of this drug are not known, as no long term follow-up of trial participants has been reported. If further trials comparing iNO with an inhaled placebo are to proceed, they should be stratified for primary disease and must specifically evaluate clinically relevant outcomes, before any benefit of iNO in AHRF can be excluded.
Sokol
J
J
Paediatric Intensive Care Unit, Great Ormond Street Hospital for Children, NHS Trust and the Institute of Child Health, Great Ormond Street, London, UK, WC1N 3JH. jenni.sokol@utoronto.ca
Jacobs
S E
SE
Bohn
D
D
D000208:Acute Disease; D000280:Administration, Inhalation; D000328:Adult; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D006801:Humans; D000860:Hypoxia / Q000150:complications*; D007223:Infant; D009569:Nitric Oxide / Q000008:administration & dosage*; D010101:Oxygen Consumption; D016032:Randomized Controlled Trials as Topic; D012128:Respiratory Distress Syndrome / Q000188:drug therapy; D012131:Respiratory Insufficiency / Q000188:drug therapy*
D001993:Bronchodilator Agents; D009569:Nitric Oxide