Inhaled nitric oxide does not reduce mortality in patients with acute respiratory distress syndrome regardless of severity: systematic review and meta-analysis.

Abstract

OBJECTIVE: Treatment with inhaled nitric oxide improves oxygenation but not

survival in mechanically ventilated patients with acute respiratory distress

syndrome, but the effect may depend on the severity of hypoxemia. Our objective

was to determine whether nitric oxide reduces hospital mortality in patients with

severe acute respiratory distress syndrome (PaO2/FIO2 </= 100 mm Hg) but not in

patients with mild-moderate acute respiratory distress syndrome (100 < PaO2/FIO2

</= 300 mm Hg) at the time of randomization. DATA SOURCES: Data were collected

from Medline, Embase, and Cochrane CENTRAL electronic databases (inception to May

2013); proceedings from five conferences (to May 2013); and trial registries

(http://www.clinicaltrials.gov and http://www.controlled-trials.com). No language

restrictions were applied. STUDY SELECTION: Two authors independently selected

parallel-group randomized controlled trials comparing nitric oxide with control

(placebo or no gas) in mechanically ventilated adults or postneonatal children

with acute respiratory distress syndrome. DATA EXTRACTION: Two authors

independently extracted data from included trials. Trial investigators provided

subgroup data. Meta-analyses used within-trial subgroups and random-effects

models. DATA SYNTHESIS: Nine trials (n = 1,142 patients) met inclusion criteria.

Overall methodological quality was good. Nitric oxide did not reduce mortality in

patients with severe acute respiratory distress syndrome (risk ratio, 1.01 [95%

CI, 0.78-1.32]; p = 0.93; n = 329, six trials) or mild-moderate acute respiratory

distress syndrome (risk ratio, 1.12 [95% CI, 0.89-1.42]; p = 0.33; n = 740, seven

trials). Risk ratios were similar between subgroups (interaction p = 0.53). There

was no between-trial heterogeneity in any analysis (I = 0%). Varying the

PaO2/FIO2 threshold between 70 and 200 mm Hg, in increments of 10 mm Hg, did not

identify any threshold at which the nitric oxide-treated patients had lower

mortality relative to controls. CONCLUSIONS: Nitric oxide does not reduce

mortality in adults or children with acute respiratory distress syndrome,

regardless of the degree of hypoxemia. Given the lack of related ongoing or

recently completed randomized trials, new data addressing the effectiveness of

nitric oxide in patients with acute respiratory distress syndrome and severe

hypoxemia will not be available for the foreseeable future.