Noninvasive Ventilatory Support in Acute Respiratory Distress Syndrome

First author, year




Intubation rate

Risk factors for intubation

Wysocki, 1995


Monocenter RCT: NIV vs. O2

ARF not related to AECOPD

NIV: 62% vs. O2: 70%

Not reported

Antonelli, 1998


Monocenter RCT: NIV vs. IMV

ARDS (25%)

10/32 (31%)

Not reported

Confalonieri, 1999


Monocenter RCT: NIV vs. O2

Community acquired pneumonia and ARF

NIV: 21% vs. O2: 50%

Not reported

Delclaux, 2000


Multicenter RCT: CPAP vs. O2

ALI (1994 definition)

CPAP: 21 (34%) vs. 24 (39%)


Absence of cardiac disease

PaO2/FiO2 after 1h of NIV

Antonelli, 2001


Observational multicenter cohort study

ARDS (25%)

108/354 (30%)

Age > 40

SAPS II > 35


PaO2/FiO2 after 1h

Auriant, 2001


Monocenter, RCT: NIV vs. O2

ARF post lung surgery

NIV: 20% vs. O2: 50%

Not reported

Ferrer, 2003


Multicenter, RCT: NIV vs. O2

Severe acute hypoxemic respiratory failure, ARDS (14%)

NIV: 25% vs. O2: 52%


Rana, 2006


Observational prospective study, NIV first line

ALI, Berlin definition


Metabolic acidosis

Severe hypoxemia

Antonelli, 2007


Observational first-line NIV

ARDS (1994 definition)



Gender male


pH after 1 h>7.37

PaO2/FiO2 after 1 h>175

Agarwal, 2009

40 (21 ARDS/ALI)

Observational study with NIV in first line

ALI, Berlin definition

47%, 57% in ARDS/ALI and 37% in others

PaO2/FiO2 ratio

Zhan, 2012


Multicenter RCT: NIV vs. O2 (Venturi)

ALI, Berlin definition

NIV: 5% vs. O2: 21%

Not reported

Thille, 2013

113 (87 with ARDS)

Observational with NIV in first line

ALI, Berlin definition


Active cancer


Moderate/severe ARDS

Low Glasgow coma score

Kangelaris, 2015


Observational cohort study

ARDS (Berlin definition)

23% non-intubated

Not reported

Frat, 2015


Multicenter RCT: NIV vs. O2 vs. HFNC

ALI/ARDS (Berlin definition)

O2: 47% vs. HFNC: 38% vs. NIV: 50%

Not reported

ALI acute lung injury, ARDS acute respiratory distress syndrome, ARF acute respiratory failure, AECOPD acute exacerbation of chronic obstructive pulmonary disease, RCT randomized controlled trial, NIV noninvasive ventilation, CPAP continuous positive airway pressure, IMV invasive mechanical ventilation, HFNC high-flow oxygen through nasal cannula, SAPS II simplified acute physiology score

The role of NIV in the treatment of ALI was assessed in critically ill patients with bilateral infiltrates of different origin in a study from the Mayo Clinic [38]. In this observational cohort study, Rana et al. prospectively assessed the outcomes of 54 consecutive patients. They found that 70% of the patients failed NIV. It was of notice that in patients who failed NIV, the observed mortality was higher than APACHE-predicted mortality (68% vs. 39%, p < 0.01). Among 113 patients receiving NIV for acute hypoxemic respiratory failure (82 with acute ARDS and 31 without), Thille et al. reported intubation rates significantly different between ARDS and non-ARDS patients (61% vs. 35%, p = 0.015) and according to clinical severity of ARDS: 31% in mild, 62% in moderate, and 84% in severe ARDS ( p = 0.0016) [39].

More recently, Frat et al. randomized 310 patients presenting acute hypoxemic respiratory failure without hypercapnia to receive either high-flow oxygen therapy or standard oxygen therapy delivered through a face mask or NIV [36]. The intubation rate was similar between the three groups (38%, 47%, and 50%, respectively, for the high-flow oxygen group, the standard group, and the NIV group; p = 0.18). However, it is important to note that the hazard ratio for death at 90 days was 2.01 (95% confidence interval [CI], 1.01–3.99) with standard oxygen versus high-flow oxygen ( p = 0.046) and 2.50 (95% CI, 1.31–4.78) with NIV versus high-flow oxygen (p=0.006). Finally, another monocentric study reported intriguing results [40]. In this prospective study, investigators randomized 83 hypoxemic patients after 8 h of NIV to receive NIV provided with a helmet or NIV with a facial mask (as it was previously provided) [40]. The study was stopped earlier for safety since the preestablished criteria for stoppage were met. Hence, the main primary endpoint, the intubation rate, was 61.5% in the face mask group and 18.2% in the helmet group (absolute difference, −43.3%; 95% CI, −62.4% to −24.3%; p < .001). The helmet group had a higher PEEP (8 vs. 5 cmH2O), whereas the pressure support level was higher in the face mask group (11 vs. 8 cmH2O). With helmet, the assessment of tidal volume is not possible; however, the results could be explained by more protective ventilation provided by the helmet. Since it was a monocentric study, further studies are mandatory to confirm these challenging results.

15.3.6 When NIV Should Not Be Used in Acute Hypoxemic Respiratory Failure

Based on the high intubation rate reported above, it is important to know when NIV should not be applied in patients with acute hypoxemic respiratory failure. Most of the studies that reported the experience of using NIV in acute hypoxemic respiratory failure have proposed predictors of NIV failure. In 2001, Antonelli et al. investigated in a prospective multicenter cohort study factors involved in NIV failure [41]. In a heterogeneous population, the overall efficacy of NIV in avoiding intubation (70%) contrasted with the high rate of failure observed in 86 patients fulfilling the diagnosis of ARDS (51%). The intubation rate was similar among patients with ARDS of pulmonary versus extrapulmonary origin, but sepsis on admission was associated, among other variables, with NIV failure. In a large prospective observational study of NIV in 147 ARDS patients in experienced centers (NIV failure rate around 50%), a high Simplified Acute Physiology Score (SAPS) II and PaO2/FiO2 ≤ 175 mmHg 1 h after initiation of NIV were independently associated with NIV failure [42]. Rana et al. [38] found that NIV success was significantly correlated with low severity scores (Acute Physiology and Chronic Health Evaluation III or Sequential Organ Failure Assessment), with high PaO2/FiO2 (147 vs. 112), and with less pronounced acidosis than patients with NIV failure. Last, Thille et al. found that shock, active cancer, low level of consciousness, and mild/severe ARDS were independently associated with NIV failure [39].

15.3.7 Recommendations for clinical practice

The efficiency of NIV in patients with acute hypoxemic respiratory failure due to ALI, ARDS, or severe pulmonary infiltrates, and for whom endotracheal intubation is not mandatory, depends on the degree of hypoxia, the presence of comorbidities and complications, and the illness severity scores. It also probably depends on the respiratory drive of the patients. The high rate of NIV failure suggests a cautious approach with these patients, consisting of early NIV trial and no delay of needed intubation. Measurement of tidal volume under NIV may be important, and patients having tidal volume above 8 mL/kg of predicted body weight may be at higher risk of failure and of having an injurious breathing pattern. In those patients, lung-protective ventilation may be considered as a therapy. In addition, when using NIV in a patient with acute hypoxic respiratory failure, in an attempt to avoid intubation, one should always consider the risks of inappropriate intubation delay. Demoule et al. found that the effect of NIV differs between acute hypoxemic respiratory failure (including mainly in this definition, ALI and ARDS) and patients with cardiogenic pulmonary edema or acute exacerbation of COPD, because NIV failure was associated with higher mortality in patients with acute hypoxemic respiratory failure [32]. This finding should therefore raise a note of caution when applying NIV for this indication and make the clinician wonder whether a lung-protective ventilation is not more appropriate. Close monitoring is therefore crucial when using this technique as a first-line therapy in patients with ARDS. Delaying intubation may contribute to mortality [43]. NIV should not be considered primarily as an alternative to invasive ventilation.

15.4 Rationale, Benefits, and Risks of High-Flow Oxygenation Through Nasal Cannula in ARDS

The most conventional form of oxygen delivery relies on face masks, nasal cannula, or nasal prongs. However, some drawbacks limit their use in case of severe hypoxemia if oxygen flow higher than 15 L/min is needed and in case of high patients’ inspiratory flow that may induce a certain amount of oxygen dilution. An alternative to conventional oxygen therapy has received growing attention: heated, humidified high-flow nasal cannula oxygen (HFNC) is a technique that can deliver heated and humidified oxygen, with a controlled FiO2, at a maximum flow of 60 L/min of gas via nasal prongs or cannula. Many data with this technique have been published in the neonatal field where it is increasingly used [44]. Since a decade, the use of HFNC has been considered for patients with acute hypoxemic respiratory failure. The high flow rates used generate low levels of positive pressure in the upper airways [45, 46]. The high flow rates may also decrease physiological dead space by flushing the expired carbon dioxide from the upper airway [47, 48], a process that potentially explains the observed decrease in the respiratory rate and the work of breathing [49]. In patients with acute respiratory failure of various origins, HFNC has been shown to result in better comfort and oxygenation than standard oxygen therapy delivered through a face mask [5052]. HFNC has gained increasing clinical and scientific interest [36, 5053]. The larger study on the use of HFNC in patients with acute hypoxemic respiratory failure was conducted by Frat and coworkers in 2015 [36]. In this randomized controlled trial, investigators aimed at determining whether HFNC administered through a large-bore close-fitting nasal cannula or NIV could reduce the intubation rate and improve outcomes in acute hypoxemic patients compared with standard oxygen administration [36]. In this trial, patients had mild or moderate ARDS (PaO2/FiO2 ratio around 155 mmHg) mainly due to pneumonia. The primary outcome, the rate of endotracheal intubation, was lower among patients treated with high-flow oxygen than among those who received standard oxygen therapy or NIV, but the rates did not differ significantly (38% vs. 47% and 50%, respectively) (p = 0.18). However, in a post hoc adjusted analysis that included the 238 patients with severe initial hypoxemia (PaO2/FiO2 ≤200 mmHg), the intubation rate was significantly lower among patients who received high-flow oxygen than among patients in the other two groups ( p = 0.009). Furthermore, the hazard ratio for death at 90 days after randomization was 2.01 in the standard oxygen group versus the high-flow oxygen group ( p = 0.046) and 2.5 in the NIV group versus the high-flow oxygen group ( p = 0.006). One explanation proposed by the authors was that NIV and spontaneous breathing could have provided tidal volume greater than 9 mL/kg of predicted body weight. Hence, the degree of lung injury might have been increased in this group, contributing to a higher mortality than that observed in the high-flow oxygen group.

15.5 Noninvasive Ventilator Support in Immunocompromised Patients with ARDS

Acute respiratory failure remains the most common and severe life-threatening complication in immunocompromised patients [54, 55]. Many immunocompromised patients with acute respiratory failure require ventilatory support within a few hours after admission to the ICU. Avoiding invasive mechanical ventilation significantly decreases the risk of death. Thus, choosing the optimal device for delivering oxygen is of the utmost importance. In a large multicenter study of 1,004 patients with solid or hematologic malignancies and ARDS meeting the new operational Berlin definition, Azoulay et al. reported that NIV was used initially in one-third of the patients. They frequently failed, with the highest failure rates occurring in the most severe ARDS category [55]. Nevertheless, a favorable impact of NIV has been described in retrospective studies [5658] and in a few randomized controlled trials including a relatively small number of patients [25, 26, 59] (Table 15.2). Hence, the efficacy of NIV in this population appears to be promising. More recently, the use of HFNC has also been investigated in immunocompromised patients. Below, we will discuss the advantages and limits of using NIV and HFNC in immunocompromised patients.

Table 15.2
Studies exploring the effect of noninvasive ventilation on acute hypoxemic respiratory failure in immunocompromised patients

First author, year



Population description

Intubation rate

Risk factors for intubation

Hilbert, 2000


Monocenter RCT: NIV vs. O2

Immunocompromised patients with ARF

46% vs. 77% ( p = 0.03)

Not reported

Antonelli, 2000


Monocenter RCT: NIV vs. O2

Immunocompromised patients with ARF

20% vs. 70% ( p = 0.002)

Not reported

Adda, 2008


Retrospective cohort study, NIV in first line

Immunocompromised patients with ARF (32% ARDS)


Respiratory rate under NIV

Need for vasopressor

Need for RRT ARDS

Squadrone, 2010


Monocenter RCT, CPAP vs. O2

Hematologic malignancy

40% vs. 10% ( p< 0.001)

Not reported

Wermke, 2012


Monocenter RCT, NIV vs. 02

Allogenic hematopoietic stem cell transplant

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Aug 26, 2017 | Posted by in Uncategorized | Comments Off on Noninvasive Ventilatory Support in Acute Respiratory Distress Syndrome
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