Association between inhaled nitric oxide treatment and long-term pulmonary function in survivors of acute respiratory distress syndrome

Introduction: Assessment of treatments for acute respiratory distress syndrome (ARDS) has focused on short-term outcomes (for example, mortality); little information exists regarding long-term effects of ARDS treatment. Survivors of ARDS episodes may have long-term obstructive/restrictive pulmonary abnormalities and pulmonary gas exchange impairment. A 2004 prospective randomized placebo-controlled trial assessed the efficacy and safety of inhaled nitric oxide (iNO) in patients with non-septic ARDS; the primary endpoint was days alive and off assisted breathing. This analysis examined potential effects of iNO or placebo on pulmonary function six months post-treatment in ARDS survivors from that original study. Methods: ARDS survivors (N = 92) from a large-scale randomized, placebo-controlled study evaluating mortality after either 5 ppm iNO or placebo for up to 28 days were assessed six months post-treatment. Pulmonary function testing across seven parameters was conducted. Results: At 6 months post-treatment, results indicated significantly better absolute values for iNO versus placebo for mean +/- SD total lung capacity (TLC, 5.54 +/- 1.42 vs. 4.81 +/- 1.00; P = 0.026). There were also significantly better values for mean +/- SD percent predicted values for a) forced expiratory volume in 1 second (FEV1, 80.23 +/- 21.21 vs. 69.51 +/- 28.97; P = 0.042), b) forced vital capacity (FVC, 83.78 +/- 19.37 vs. 69.84 +/- 27.40; P = 0.019), c) FEV1/FVC (96.14 +/- 13.79 vs. 87.92 +/- 19.77; P = 0.033), and d) TLC (93.33 +/- 18.21 vs. 76.10 +/- 21.84; P < 0.001). Nonsignificant differences were found in absolute FEV1, FEV1/FVC, FVC, forced expiratory flow from 25% to 75% of FVC, functional residual capacity, and CO diffusion. Conclusions: ARDS patients surviving after treatment with low-dose iNO had significantly better values for select pulmonary function tests at six months post-treatment than placebo-treated patients. Further trials are warranted to determine the effects of iNO on chronic lung function in ARDS survivors, a factor in long-term morbidity and quality of life in this population.