Inhaled nitric oxide for acute hypoxemic respiratory failure in children and adults

BACKGROUND: Acute hypoxemic respiratory failure affects all age groups and may result from a number of systemic diseases. It continues to be associated with high mortality and morbidity. Initial studies examining the effect of inhaled nitric oxide in respiratory failure demonstrated transient improvement in oxygenation but did not examine mortality or other significant morbidity outcomes. OBJECTIVES: To systematically examine randomized controlled trials addressing the effect of inhaled nitric oxide, compared with placebo inhaled gas, on mortality and morbidity in patients with acute hypoxemic respiratory failure. SEARCH STRATEGY: Randomized controlled trials were identified from electronic databases: The Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2, 2002;MEDLINE (January 1966-August 2002); EMBASE (1980-March 2001); CINAHL (1982-July 2002), 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and conference proceedings were hand searched and authors published in this field were contacted for knowledge of unpublished ongoing trials. SELECTION CRITERIA: Randomized controlled trials comparing inhaled nitric oxide with maximal conventional therapy and inhaled placebo, in either children or adults with acute hypoxemic respiratory failure. DATA COLLECTION AND ANALYSIS: Qualitative assessment of each trial was made and analyses performed according to statistical methods in Review Manager MetaView 4.1. A sub-group analysis was performed to assess the impact of inhaled nitric oxide at varied doses. MAIN RESULTS: Five randomized controlled trials were evaluated, assessing 535 patients with acute hypoxemic respiratory failure (Age range not provided). Lack of data prevented assessment of all outcomes. There was no significant difference of nitric oxide on mortality in trials without cross-over (RR 0.98, 95%CI 0.66,1.44). Published evidence from one study demonstrated nitric oxide to transiently improve oxygenation in the first 72 hours of treatment. Limited data demonstrated no significant difference in ventilator-free days between treatment and placebo groups, and no specific dose of nitric oxide 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 significant complications directly attributable to this treatment. REVIEWER'S CONCLUSIONS: Nitric oxide did not demonstrate any statistically significant effect on mortality and transiently improved oxygenation in patients with hypoxemic respiratory failure. Lack of data prevented assessment of other clinically relevant end points. If further trials comparing inhaled nitric oxide with an inhaled placebo are to proceed, they should be stratified for primary disease, assess the impact of other combined treatment modalities for respiratory failure, and must specifically evaluate clinically relevant outcomes, before any benefit of inhaled nitric oxide for respiratory failure can be excluded.