TABLE 1

Network estimates evaluating the impact of the interventions on primary and secondary outcomes in the overall population

Comparison	MD or OR (95% CI)	p-value	I² (%)	τ²	K	GRADE^#	Classification of intervention^¶
Re-intubation			36	0.120
HFNO versus COT	0.60 (0.43–0.84)	0.003			11	Moderate^a	Large beneficial effect
NIV versus COT	0.61 (0.46–0.81)	<0.001			15	Moderate^a	Large beneficial effect
NIV versus HFNO	0.98 (0.69–1.40)	0.844			5	Moderate^b
VAP			0	0
HFNO versus COT	0.36 (0.18–0.71)	0.003			3	Moderate^a	Large beneficial effect
NIV versus COT	0.49 (0.34–0.73)	<0.001			7	Moderate^a	Large beneficial effect
NIV versus HFNO	0.74 (0.39–1.38)	0.855			1	Moderate^b
Discomfort			49	0.493
HFNO versus COT	2.60 (0.79–8.60)	0.117			7	Low^a,b	Large harmful effect
NIV versus COT	13.14 (5.94–29.04)	<0.001			1	Moderate^a	Large harmful effect
NIV versus HFNO	0.20 (0.06–0.62)	0.050			1	High
ICU mortality			6	0.017
HFNO versus COT	0.81 (0.44–1.48)	0.489			5	Low^a,b	Small beneficial effect
NIV versus COT	0.64 (0.39–1.05)	0.075			8	Moderate^a	Large beneficial effect
NIV versus HFNO	1.26 (0.63–2.52)	0.834			1	Low^a,b
Hospital mortality			6	0.017
HFNO versus COT	0.86 (0.62–1.18)	0.431			5	Moderate^a	Small beneficial effect
NIV versus COT	0.64 (0.47–0.87)	0.004			11	Moderate^a	Large beneficial effect
NIV versus HFNO	1.35 (0.97–1.86)	0.194			4	Moderate^b
ICU length of stay			87	1.048
HFNO versus COT	−0.12 (−0.85–0.61)	0.741			9	Very low^a,b,c,d	Trivial beneficial effect
NIV versus COT	−0.72 (−1.44–0.00)	0.049			14	Very low^a,c,d	Small beneficial effect
NIV versus HFNO	0.60 (−0.33–1.53)	0.320			4	Very low^b,c,d
Hospital length of stay			86	2.230
HFNO versus COT	−0.04 (−1.27–1.18)	0.264			8	Very low^a,b,c	Trivial beneficial effect
NIV versus COT	−2.38 (−3.69– −1.07)	<0.001			10	Low^a,c	Large beneficial effect
NIV versus HFNO	2.34 (0.80–3.88)	0.189			3	Very low^a,b,c
Time to re-intubation			89	87.485
HFNO versus COT	2.99 (−8.13–14.10)	0.564			3	Very low^a,b,c	Trivial harmful effect
NIV versus COT	9.17 (−1.06–19.40)	0.105			4	Very low^a,b,c	Small harmful effect
NIV versus HFNO	−6.18 (−18.86–6.5)	0.371			1	Very low^a,b,c

MD: mean difference; OR: odds ratio; τ² and I²: loop heterogeneity; K: number of studies providing direct evidence; GRADE: Grading of Recommendations Assessment, Development and Evaluations; HFNO: high-flow nasal oxygen; COT: conventional oxygen therapy; NIV: noninvasive ventilation; VAP: ventilator-associated pneumonia; ICU: intensive care unit. ^#: GRADE certainty of evidence: ^a: lowered one level for risk of bias; ^b: lowered one level for imprecision as confidence intervals do not allow excluding harm; ^c: lowered one level for inconsistency; ^d: lowered one level for incoherence. ^¶: for dichotomous outcome variables, large intervention effects were considered for OR >1.3 or <0.7, moderate intervention effects for 1.2<OR≤1.3 or 0.7≤OR<0.8, small intervention effects for 1.1<OR≤1.2 or 0.8≤OR<0.9 and trivial intervention effects for 1.0<OR≤1.1 or 0.9≤OR<1.0; for length of stay, large intervention effects were considered for MD>2, moderate intervention effects for 1<MD≤2, small intervention effects for 0.5<MD≤1 and trivial intervention effects for 0<MD≤0.5; for time to re-intubation, large intervention effects were considered for MD>24, moderate intervention effects for 12<MD≤24, small intervention effects for 6<MD≤12 and trivial intervention effects for 0<MD≤6. COT was considered as the reference intervention. Bold indicates p<0.05.