March 21, 2016


Noninvasive ventilation (NIV) is considered the milestone treatment for immunocompromised patients suffering from acute respiratory failure (ARF)[1,2]. Indeed, though morbidity and mortality of immunocompromised patients admitted to ICU due to ARF remains quite remarkable, a significant improvement in survival has been reported over the last decade [3]. In order to compare the effect on mortality of NIV sessions vs. low flow oxygen (LFO) immediately after ICU admission in immunocompromised patients with hypoxemic non hypercapnic ARF, Lemiale and colleagues conducted a rigorous, pragmatic, multicentre randomised controlled trial, recently published in JAMA [4]. They showed no benefit from NIV on crude 28-day mortality, endotracheal intubation (ETI), as well as on oxygenation and respiratory rate, so the authors concluded that early NIV as compared to LFO does not affect survival in this category of patients.

In addition to the conclusions noted by the authors, there are some aspects of this study which warrant further discussion. In spite of a baseline PaO2/FiO2 ratio (P/F) comparable or even lower than those observed in other studies with analogue design [5] or involving similar population [1], patients in the this study surprisingly showed a lower respiratory rate (breaths per minute: 26 vs. 335 vs. 361). In addition, while in previous investigations baseline FiO2 during oxygen therapy was accurately measured to stratify patients [5] or computed according to the Venturi effect [1], in the present study, FiO2 was derived only from oxygen flow. Since hypoxemic patients with ARF show a high peak inspiratory flow, delivered FiO2 becomes significantly lower than the nominal one: such issue may have led to an overestimation of the severity of oxygenation impairment, as yet suggested by the lower degree of tachypnea. This aspect, along with loose inclusion criteria (are PaO2<60 mmHg in room air or respiratory rate>30 or dyspnea alone criteria for NIV requirement?) may have contributed to the enrollment of less severe patients with a low risk of ETI and death, so the study was underpowered, as recognised by the authors.

The application of NIV in intermittent sessions, along with the application of non-adequate peep in more severe and, thus, possible recruited patients, may have made patients prone to ventilator-induced lung injury (due to the phenomenon of recruitment-derecruitment) and may have contributed to underestimate NIV benefit. Also, no data are provided regarding patients’ comfort, patient-ventilator interaction and ventilator settings that were not thoroughly standardised during NIV session, so it is impossible to evaluate the effectiveness of such treatment.

Finally, the open-label, non standardised, non stratified use of nasal high flow oxygen (HFO) was more frequent in patients receiving LFO and may have seriously biased the results. Interestingly, HFO has been recently shown to affect ETI rate and survival in critically ill severely hypoxemic patients with ARF [5].  Surprisingly, the authors do not clarify whether ETI in the NIV group occurred during the NIV session, LFO or HFO.

In conclusion, the results of the present paper lack of the necessary generalisability and should be carefully construed. A trial of NIV to treat immunocompromised hypoxemic patients with ARF before endotracheal intubation can still be safely encouraged.

This article review was submitted by ESICM Journal Review Club member Domenico Luca Grieco.


1.        Reiffers J CJHGGDVFVRG-BGDM. Noninvasive ventilation in immunosuppressed patients with pulmonary infiltrates, fever, and acute respiratory failure. N. Engl. J. Med. 2001;344(7):481-7. doi:10.1056/NEJM200102153440703.

2.        Gristina GR, Antonelli M, Conti G, et al. Noninvasive versus invasive ventilation for acute respiratory failure in patients with hematologic malignancies: A 5-year multicenter observational survey*. Crit. Care Med. 2011;39(10):2232-2239. doi:10.1097/CCM.0b013e3182227a27.

3.        Azoulay E, Lemiale V, Mokart D, et al. Acute respiratory distress syndrome in patients with malignancies. Intensive Care Med. 2014;40(8):1106-1114. doi:10.1007/s00134-014-3354-0.

4.        Lemiale V, Mokart D, Resche-Rigon M, et al. Effect of Noninvasive Ventilation vs Oxygen Therapy on Mortality Among Immunocompromised Patients With Acute Respiratory Failure. Jama 2015:1. doi:10.1001/jama.2015.12402.

5.        Frat J-P, Thille AW, Mercat A, et al. High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. N. Engl. J. Med. 2015;372(23):2185-96. doi:10.1056/NEJMoa1503326.

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