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

Abstract

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.

Trial registration: A Double-blind, Randomized, Placebo-controlled, Dose-response Study of Inhaled Nitric Oxide in the Treatment of Acute Respiratory Distress Syndrome. NCT number: ISRCTN53268296.

Figure 1

Disposition of subjects. AOAB, alive and off assisted breathing by day 28; NO, nitric oxide; PFT, pulmonary function test.

Figure 2

Aggregate of individual subject data of daily change (mean ± SD) from baseline parameter for FiO₂ through day 28; FiO₂, fraction of inspired oxygen; NO, nitric oxide.

Figure 3

Aggregate of individual subject data of daily change (mean ± SD) from baseline parameter for PEEP through day 28. NO, nitric oxide; PEEP, positive-end expiratory pressure.

Figure 4

Aggregate of individual subject data of daily change (mean ± SD) from baseline parameter for P/F ratio through day 28. NO, nitric oxide; PF, PaO₂/FiO₂ ratio.

Figure 5

Mean percent predicted pulmonary function comparisons between placebo and inhaled nitric oxide. NO, nitric oxide.