By Richard Kallet, MS, RRT, FCCM

Director of Quality Assurance, Respiratory Care Services, San Francisco General Hospital

Mr. Kallet reports no financial relationships relevant to this field of study.

SYNOPSIS: Managing acute respiratory distress syndrome (ARDS) with non-invasive ventilation was associated with increased failure as the severity of ARDS increased.

SOURCE: Bellani G, Laffey JG, Pham T, et al. Non-invasive ventilation of patients with ARDS: Insights from the LUNG SAFE study. Am J Respir Crit Care Med 2016 Oct. 18 [Epub ahead of print].

This study was a subset analysis from a larger multinational observational study of adult patients presenting with acute hypoxemic respiratory failure. Those meeting the Berlin definition of acute respiratory distress syndrome (ARDS) within two days of acute hypoxemia onset and who received non-invasive ventilation (NIV) during the first two days of ARDS were studied. Patients who required invasive mechanical ventilation (MV) on ARDS day one were classified as invasive MV only. NIV failure was defined as those requiring invasive MV after day two of NIV for ARDS. Data were collected once daily during a reference period. Patients were followed until death or hospital discharge. Analysis was restricted to those without imposed care limitations prior to initiating NIV or invasive MV.

Only 18% of ARDS patients received NIV on day one, and 15.5% were managed with NIV on both ARDS days one and two. Of these, 28% were managed with continuous positive airway pressure only. Those initially managed with NIV were older and had a higher prevalence for comorbidities (e.g., chronic renal failure, congestive heart failure, chronic obstructive pulmonary disease) that coincided with delayed recognition of ARDS compared to those managed with invasive MV. Moreover, NIV was associated with lower positive end-expiratory pressure (PEEP), higher tidal volume (VT), and higher respiratory frequency.

NIV failure occurred in 37.5% of patients and was independently associated with increased non-pulmonary organ failure scores, lower arterial oxygen partial pressure to inspired oxygen fraction (PaO2/FiO2) and increased arterial carbon dioxide partial pressure (PaCO2). When compared to those successfully managed with NIV, those who failed NIV had a substantially higher mortality (10.6 vs. 42.7%, P < 0.001). Although there were no differences in either ICU or hospital mortality between those managed with NIV vs. invasive MV, Cox regression modeling adjusting for comorbidities demonstrated an independent association between NIV and ICU mortality. Moreover, matched comparisons between cohorts according to a PaO2/FiO2 cutoff < 150 mmHg found a significantly higher mortality in those receiving NIV vs. invasive MV (36.2% vs. 24.7%, P = 0.033).


In this study, NIV was attempted in < 20% of ARDS patients with an approximately 62% success rate, suggesting clinician bias favoring conservative application. Similar studies found lower NIV success rates (39%, 54%, 56%).1-3 NIV success also decreased with increasing ARDS severity from 78% to 58% to 53% (for mild, moderate, and severe forms, respectively). Similar studies also have reported that increasing ARDS severity corresponds with decreasing NIV success rates of 81%, 27%, 17% and 69%, 38%, 16% for mild, moderate, and severe forms, respectively.1-3

That those with moderately severe to severe ARDS (i.e., PaO2/FiO2 < 150 mmHg) failing NIV had a substantially higher mortality than those managed on invasive MV reinforces previous concerns about utilizing NIV for ARDS. The effectiveness of NIV in self-limiting, readily reversible forms of acute respiratory failure does not necessarily translate to ARDS, which can rapidly progress and require weeks of mechanical ventilation. In addition, the difficulty in applying higher levels of PEEP and precisely controlling VT in NIV likely increases the susceptibility to ventilator-induced lung injury. Moreover, the relatively prolonged course of ARDS raises other concerns with long-term use of NIV: severe skin ulceration (now publicly reportable), maintaining adequate nutritional intake, and increased aspiration risk associated with discoordinated swallowing during elastic loading of the respiratory muscles.4

In summary, previous recommendations regarding NIV in ARDS remain highly relevant; it should be restricted to milder manifestations and abandoned quickly in favor of invasive MV if it fails to stabilize gas exchange and reverse respiratory distress within a few hours.


  1. Thille AW, Contou D, Fragnoli C, et al. Non-invasive ventilation for acute hypoxemic respiratory failure: Intubation rate and risk factors. Crit Care 2013;17:R269.
  2. Antonelli M, Conti G, Esquinas A, et al. A multi-center survey on the use of in clinical practice of noninvasive ventilation as a first line intervention for acute respiratory distress syndrome. Crit Care Med 2007;35:18-25.
  3. Chawla R, Mansuriya J, Modi N, et al. Acute respiratory distress syndrome: Predictors of noninvasive ventilation failure and intensive care unit mortality in clinical practice. J Crit Care 2016;31:26-30.
  4. Nishino T. The swallowing reflex and its significance as an airway defensive reflex. Front Physiol 2013;3:489.