Table 1:

Characteristics of randomized controlled trials included in the meta-analysis

Trial	Setting	No. of patients (% male)	Age, yr, mean	Disease severity scores, mean	Enrolment criteria	Oxygen therapy protocol, mean ± SD
Trial	Setting	No. of patients (% male)	Age, yr, mean	Disease severity scores, mean	Enrolment criteria	HFNC group	Control group
Frat et al., 2015 (19)	23 ICUs in France and Belgium	310 (68.4)	HFNC: 61 Conventional oxygen: 59 NIV: 61	SAPS II: HFNC: 25 Conventional oxygen: 24 NIV: 27	Pao₂:Fio₂ ratio ≤ 300 mm Hg; Paco₂ ≤ 45 mm Hg; respiratory rate ≥ 25 beats/min; no history of chronic respiratory failure	Gas flow rate: 48 ± 11 L/min Fio₂: 0.82 ± 0.21	Group 1: Non-rebreather mask Gas flow rate: 13 ± 5 L/min Fio₂: 0.82 ± 0.21
Frat et al., 2015 (19)	23 ICUs in France and Belgium	310 (68.4)	HFNC: 61 Conventional oxygen: 59 NIV: 61	SAPS II: HFNC: 25 Conventional oxygen: 24 NIV: 27		Gas flow rate: 48 ± 11 L/min Fio₂: 0.82 ± 0.21	Group 2: NIV PS: 8 ± 3 cm H₂O PEEP: 5 ± 1 cm H₂O Fio₂: 0.67 ± 0.24 Vt: 9.2 ± 3.0 mL/kg
Hernandez et al., 2016 (33)	7 ICUs in Spain	527 (62.0)	HFNC: 51 Conventional oxygen: 52	APACHE II: HFNC: 14 Conventional oxygen: 13	Pao₂:Fio₂ ratio > 150 mm Hg; Paco₂ ≤ 45 mm Hg; pH > 7.35	Gas flow rate: 30.9 ± 7.6 L/min Fio₂: 0.32 ± 0.08	Nasal cannula or non-rebreather mask Gas flow rate adjusted to maintain Spo₂ at ≥ 92 mm Hg Fio₂: 0.4 ± 0.09
Maggiore et al., 2014 (21)	2 ICUs in Italy	105 (64.8)	HFNC: 65 Conventional oxygen: 64	SAPS II: HFNC: 43 Conventional oxygen: 44	Pao₂:Fio₂ ratio ≤ 300 mm Hg; Paco₂ ≥ 45 mm Hg; respiratory rate ≥ 25 beats/min	Gas flow rate: 50 L/min Fio₂ adjusted to maintain Spo₂ at 92–98 mm Hg	Venturi mask Gas flow rate and Fio₂ adjusted to maintain Spo₂ at 92–98 mm Hg
Perbet et al., 2014 (34)^*	4 ICUs in France	80	NA	NA	NA	NA	Conventional oxygen therapy
Simon et al., 2014 (35)	1 ICU in Germany	40 (60.0)	HFNC: 64 NIV: 68	SAPS II: HFNC: 43 NIV: 46	Pao₂:Fio₂ ratio < 300 mm Hg	Gas flow rate: 50 L/min Fio₂ adjusted to maintain Sao₂ at > 90 mm Hg	NIV PEEP: 3–10 cm H₂O Inspiratory pressure: 15–20 cm H₂O
Stephan et al., 2015 (32)	6 ICUs in France	830 (66.4)	HFNC: 64 NIV: 64	SAPS II: HFNC: 29 NIV: 29	Pao₂:Fio₂ ratio ≤ 300 mm Hg; respiratory rate ≥ 25 beats/min	Gas flow rate: 50 L/min Fio₂ adjusted to maintain Spo₂ at 92–98 mm Hg	BiPAP PEEP: 4 cm H₂O PS: 8 cm H₂O (initial) Fio₂: 0.5 (initial)

Note: APACHE II = Acute Physiology and Chronic Health Evaluation II score (range 0 to 71 points, with higher scores indicating more severe disease), BiPAP = bilevel positive airway pressure, HFNC = high-flow nasal cannula oxygen therapy, ICU = intensive care unit, NA = not available, NIV = noninvasive ventilation, Paco₂ = partial pressure of arterial carbon dioxide, Pao₂:Fio₂ = ratio of partial pressure of arterial oxygen to fraction of inspired oxygen, PEEP = positive end-expiratory pressure, PS = pressure support, Sao₂ = arterial oxygen saturation, SAPS = Simplified Acute Physiology Score (range 0 to 163 points, with higher scores indicating more severe disease), SD = standard deviation, Spo₂ = peripheral capillary oxygen saturation, Vt = tidal volume.
↵* Conference abstract; details about the trial and some outcomes were not available after author contact.