Inhaled nitric oxide for acute respiratory distress syndrome (ARDS) and acute lung injury in children and adults

Background Acute hypoxaemic respiratory failure (AHRF), defined as acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), are critical conditions. AHRF results from a number of systemic conditions and is associated with high mortality and morbidity in all ages. Inhaled nitric oxide (INO) has been used to improve oxygenation but its role remains controversial. Objectives To systematically assess the benefits and harms of INO in critically ill patients with AHRF. Search strategy Randomized clinical trials (RCTs) were identified from electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 1); MEDLINE; EMBASE; Science Citation Index Expanded; International Web of Science; CINAHL; LILACS; and the Chinese Biomedical Literature Database (up to 31st January 2010). We contacted trial authors, authors of previous reviews, and manufacturers in the field. Selection criteria We included all RCTs, irrespective of blinding or language, that compared INO with no intervention or placebo in children or adults with AHRF. Data collection and analysis Two authors independently abstracted data and resolved any disagreements by discussion. We presented pooled estimates of the intervention effects on dichotomous outcomes as relative risks (RR) with 95% confidence intervals (CI). Our primary outcome measure was all cause mortality. We performed subgroup and sensitivity analyses to assess the effect of INO in adults and children and on various clinical and physiological outcomes. We assessed the risk of bias through assessment of trial methodological components and the risk of random error through trial sequential analysis. Main results We included 14 RCTs with a total of 1303 participants; 10 of these trials had a high risk of bias. INO showed no statistically significant effect on overallmortality (40.2% versus 38.6%) (RR 1.06, 95% CI 0.93 to 1.22; I-2 = 0) and in several subgroup and sensitivity analyses, indicating robust results. Limited data demonstrated a statistically insignificant effect of INO on duration of ventilation, ventilator-free days, and length of stay in the intensive care unit and hospital. We found a statistically significant but transient improvement in oxygenation in the first 24 hours, expressed as the ratio of partial pressure of oxygen to fraction of inspired oxygen and the oxygenation index (MD 15.91, 95% CI 8.25 to 23.56; I-2 = 25%). However, INO appears to increase the risk of renal impairment among adults (RR 1.59, 95% CI 1.17 to 2.16; I-2 = 0) but not the risk of bleeding or methaemoglobin or nitrogen dioxide formation. Authors' conclusions INO cannot be recommended for patients with AHRF. INO results in a transient improvement in oxygenation but does not reduce mortality and may be harmful.