This prospective observational study was performed in 17 ICUs in China from September 2017 to December 2019. We enrolled ARDS patients who used NIV as a first-line therapy. Exclusion criteria were as follows: previous use of NIV > 2 h before admission to participating centers, ventilation support from high-flow nasal cannula to NIV or from NIV to high-flow nasal cannula, NIV carried out within the 48 h after extubation, and transfer to another hospital during NIV. As we aimed to assess the impact of ARDS etiology on NIV failure, we also excluded patients with treatment limitation. The study protocol was approved by our ethics committee (No. 2016150). Informed consent was obtained from patients or their family members. ARDS was determined as follows: 1) the presence of acute hypoxemic respiratory failure with PaO2/FiO2 < 300 mmHg; 2) within 1 week of a clinical insult or the presence of new (within 7 days) or worsening respiratory symptoms; 3) bilateral opacities on computed tomography or chest X-ray not fully explained by effusions, lobar or lung collapse, or nodules; and 4) respiratory failure not fully explained by cardiac failure or fluid overload . The etiology of ARDS was recorded by the attending physician.
The initiation of NIV was based on a protocol we published previously: respiratory rate > 25 breaths/min, or clinical presentation of respiratory distress at rest (such as active contraction of the accessory inspiratory muscles or paradoxical abdominal motion), and PaO2 < 60 mmHg at room air or PaO2/FiO2 < 300 mmHg with supplemental oxygen . However, the use of NIV was at the attending physician’s discretion. A face mask was the first choice for patients with acute respiratory failure, and the size was selected based on the patient’s facial type. The straps of the mask were kept as tight as possible while remaining comfortable for the patient. The parameters of the ventilator were adjusted as follows. The initial positive end-expiratory pressure (PEEP) was 4 cm H2O and was increased gradually to avoid alveolar collapse. The initial inspiratory positive airway pressure (IPAP) was 8 cmH2O (above zero) and was increased gradually to reduce the work of breathing. Usually PEEP was maintained at 6–8 cmH2O and IPAP was maintained at 12–16 cmH2O. The fraction of inspiration oxygen (FiO2) was set to maintain SpO2 around 95%.
Liberation from NIV was considered if the respiratory failure was reversed. The reversal of respiratory failure was defined according to previously published criteria: PaO2/FiO2 > 300 mmHg, respiratory rate < 25 breaths/min, and no clinical symptoms indicating respiratory distress . However, if respiratory failure deteriorated progressively and required intubation, intubation for invasive mechanical ventilation was performed. Major criteria for intubation were loss of consciousness (such as a sudden change from being awake to being unconscious), respiratory or cardiac arrest, the development of conditions necessitating intubation to protect the airway (coma or seizure disorders) or to manage copious tracheal secretions, heart rate < 50 beats/min with loss of alertness, and hemodynamic instability without response to fluids and vasoactive agents. Minor criteria were respiratory rate > 35 breaths/min, failure to maintain PaO2/FiO2 above 150 mmHg, acidosis with pH < 7.35, inability to correct dyspnea, and lack of improvement in respiratory muscle fatigue. Intubation was recommended if the patient reached one major criterion or more than two minor criteria. NIV failure was defined as requiring intubation .
A predefined case report form was used to collect data during the study period. We recorded age, sex, underlying disease, presence of septic shock, organ dysfunction, and etiology of ARDS. Organ dysfunction was assessed with the sequential organ failure assessment (SOFA) score . Septic shock was diagnosed according to the Third International Consensus Definitions for Sepsis and Septic Shock . Data were collected when NIV was performed. ARDS resulting from pneumonia, pulmonary contusion or drowning was classified as ARDSp; that resulting from pancreatitis, intra-abdominal infection, urinary infection, soft tissue infection, non-pulmonary trauma, or other non-pulmonary disease was classified as ARDSexp [12, 13]. All patients were followed to discharge or 28 days.
We used SPSS (version 25.0) to analyze the data in this study. Missing data were present in 4.6% of cases and multiple imputations were performed. Continuous variables are reported as means and standard deviations or medians and interquartile ranges when appropriate. Normally distributed continuous variables were analyzed by unpaired Student’s t test, and non-normally distributed continuous variables were analyzed by Wilcoxon rank sum test. Proportions are reported as frequencies and percentages and compared with the chi-square test or Fisher’s exact test. Cox regression was used to identify independent risk factors associated with NIV failure or 28-day mortality. Differences in PaO2/FiO2 from initiation to 24 h of NIV between groups were analyzed by two-way repeated measures analysis of variance.
Propensity score matching was used to evaluate possible effects of treatment (ARDSp vs. ARDSexp) on NIV failure and 28-day mortality. We matched patients with similar propensity scores at a 1:1 ratio, using the nearest neighbor method, no replacement, and a caliper width of 0.05. The matched variables included age, sex, non-pulmonary SOFA score, presence of septic shock, underlying disease (chronic heart disease or chronic respiratory disease), severity of ARDS, vital signs collected before NIV (heart rate, respiratory rate, mean arterial blood pressure, pH, PaCO2, and PaO2/FiO2), tidal volume at 1–2 h of NIV, and PEEP at 1–2 h of NIV. We analyzed the cumulative 28-day probability of survival in the overall and propensity-matched cohorts by creating Kaplan-Meier curves, and the difference between the groups was analyzed by log-rank test. Sensitivity analysis in patients with different conditions was used to determine the effect of ARDS etiology on the failure of NIV and 28-day mortality. A p value less than 0.05 was considered statistically significant.