Evolution of thorax X-rays in ARDS patients with or without inhaled nitric oxide

Introduction

In a pilot randomized placebo-controlled clinical trial of acute respiratory distress syndrome (ARDS) patients treated with inhaled nitric oxide (inhNO), we have measured a chest X-ray score during 10 days post-randomization for control (15 patients receiving usual care) and experimental (15 patients with usual care plus inhNO) and compare its evolution in time and between groups with lung function and outcome.

Methods

This study was approved by the Human Research and Ethic Committee of Centre Hospitalier de I'Université de Montréal. All therapeutic interventions were standardized. Lung function was assessed by hypoxia score (HS = PaO₂/FiO₂), PEEP level, dead space ventilation, lung compliance, and venous admixture. The optimal dose of inhNO was determined daily between 0.5 and 40 parts-per-million. Nonresponders to inhNO were defined as patients presenting a 20% increase in HS after initial optimal dose of inhNO determination. Daily morning radiographs were obtained on portable chest X-ray equipment. After completing the study, 255 radiographs of the 30 ARDS patients were analyzed in blinded and serial fashion by three independent readers. Based on previous studies [1,2,3], radiographic criteria were selected in order to reflect the pattern of air-space consolidation (parenchymal opacification, atelectasia) associated with vascular pattern (indistinct vessels) and possible presence of interstitial pattern (septal lines, peribronchial cuffing, pleural effusion) particularly considering the evolution with time (until day 10 after randomization). The reliability of the technique was determined by looking at intra- (45 radiographs blindly evaluated twice) and inter-observer variabilities.

Results and discussion

ARDS resulted mainly from sepsis (25/30). Observed baseline characteristics were similar between groups. During the first day, HS increased greatly in patients treated with inhNO: +70.4 mmHg (+59%) vs. +14.2 mmHg (+9.3%) for control group (P = 0.02), venous admixture decreased from 25.7 to 15.2% in the inhNO group, and only from 19.4 to 14.9 % in the control group (P = 0.05). The status of the lung correlated well with the chest X-ray score. Intra- and inter-observer variability were reasonable. Five out of 15 patients were nonresponders. After the first day of therapy, no further beneficial effect of inhNO could be detected, whereas studied parameters were never affected by usual care in the control group. Forty percent of patients treated with inhNO were alive and weaned from mechanical ventilation 30 days after randomization compared to 33.3% in the control group (P = 0.83). The 30-day mortality rate was similar in the two groups: 60% in patients treated with inhNO vs 53.3% without inhNO (P = 0.71); most deaths (11/17) were due to multiple organ dysfunction syndrome (MODS). On the 5 direct lung injury-induced ARDS, only 1/3 died in the control, 0/2 in the inhNO group. The 30-day mortality rate of nonresponders, and responders to inhNO was 80%, and 50%, respectively. No correlation was found between the evolution of the chest X-ray score and the outcome, the ARDS origin or the treatment.