High-flow nasal oxygen alone or alternating with non-invasive ventilation in critically ill immunocompromised patients with acute respiratory failure: a randomised controlled trial.

BACKGROUND

Although non-invasive ventilation (NIV) is recommended for immunocompromised patients with acute respiratory failure in the intensive care unit (ICU), it might have deleterious effects in the most severe patients. High-flow nasal oxygen (HFNO) alone might be an alternative method to reduce mortality. We aimed to determine whether HFNO alone could reduce the rate of mortality at day 28 compared with HFNO alternated with NIV.

METHODS

FLORALI-IM is a multicentre, open-label, randomised clinical trial conducted in 29 ICUs (28 in France and one in Italy). Adult immunocompromised patients with acute respiratory failure, defined as respiratory rate of 25 breaths per min or more and a partial pressure of arterial oxygen to inspired fraction of oxygen ratio of 300 mm Hg or lower, were randomly assigned (1:1) to HFNO alone (HFNO alone group) or NIV alternating with HFNO (NIV group). Key exclusion criteria were severe hypercapnia above 50 mm Hg, patients who could strongly benefit from NIV (ie, those with underlying chronic lung disease, with cardiogenic pulmonary oedema, or who were postoperative), severe shock, impaired consciousness defined as Glasgow coma score ≤12, urgent need for intubation, do not intubate order, and contraindication to NIV. Patients were assigned using computer-generated permuted blocks and were stratified according to centre and to the type of immunosuppression using a centralised web-based management system. In the HFNO alone group, patients were continuously treated by HFNO with a gas flow rate of 60 L/min or the highest tolerated. In the NIV group, patients were treated with NIV with a first session of at least 4 h, and then by sessions for a minimal duration of 12 h a day, with a dedicated ventilator, targeting a tidal volume below 8 mL/kg of predicted bodyweight, and with a positive end-expiratory level of at least 8 cm H

FINDINGS

Between Jan 21, 2017 to March 4, 2019, of 497 eligible patients, 300 were randomly assigned but one patient withdrew consent, leaving 299 patients included in the intention-to-treat analysis (154 assigned to the HFNO alone group and 145 assigned to NIV group). Mortality rate at day 28 was 36% (95% CI 29·2 to 44·2; 56 of 154 patients) in the HFNO alone group and 35% (27·9 to 43·2; 51 of 145 patients) in the NIV group (absolute difference 1·2% [95% CI -9·6 to 11·9]; p=0·83). None of the other prespecified secondary outcomes were different between groups except for greater decreased discomfort after initiation of HFNO than with NIV (-4 mm on visual analogic scale [IQR -18 to 4] vs 0 mm [-16 to 17]; p=0·040).

INTERPRETATION

In critically ill immunocompromised patients with acute respiratory failure, the mortality rate did not differ between HFNO alone and NIV alternating with HFNO. However, study power was limited, so results should be interpreted with caution.

FUNDING

French Ministry of Health.

Informations de copyright

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Déclaration de conflit d'intérêts

Declaration of interests RC reports grants from French Ministry of Health, grants from Le nouveau souffle, and grants from AADAIRC (Association Prestataire de Santé à Domicile) during the conduct of the study; grants from European Respiratory Society, non-financial support from Fisher & Paykel Healthcare, and non-financial support from Merck Sharp & Dohme outside of the submitted work. J-PF reports grants and non-financial support from Fisher & Paykel Healthcare during the conduct of the study; grants, personal fees, and non-financial support from Aerogen Ltd outside of the submitted work. SE reports grants and non-financial support from Fisher & Paykel Healthcare during the conduct of the study; grants, personal fees, and non-financial support from Aerogen Ltd outside of the submitted work. FP reports grants from ALEXION and personal fees from GILEAD outside of the submitted work. NT reports personal fees from Pfizer outside of the submitted work. CGi reports travel expense coverage to attend scientific meetings, personal fees, and logistic support from Fisher & Paykel, Resmed, and Lowenstein Medical. SJ reports personal fees for lectures from Hamilton Medical and Nihon Kohden. SN reports personal fees from Pfizer, Gilead, MSD, BioMérieux, Fischer & Paykel, and Bio Rad outside of the submitted work. GC reports personal fees from GSK outside of the submitted work. GG reports grants and personal fees from Fisher & Paykel outside of the submitted work. AWT reports travel expense coverage to attend scientific meetings and payment for lectures from Fisher & Paykel, Covidien, Maquet-Getinge, General Electric Healthcare. MD, GP, CGa, DC, AG, JB, CV, JD, GL, AH, J-PQ, JD, DBe, EV, DT, DBo, MA, CGu, TL, AK, and SR report no competing interests.