Table 3.

Summary of findings table for review on HFNC for acute hypoxemic respiratory failure

Certainty assessment							№ of patients		Effect		Certainty	Importance
№ of studies	Study design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	HFNC	Usual care	Relative (95% CI)	Absolute (95% CI)
Mortality (follow-up: range 7 days to 90 days; assessed with longest available)
4a	Randomized trials	Not serious	Not serious	Not serious	Seriousb	None	187/722 (25.9%)	186/685 (27.2%)	RR, 0.94 (0.67 to 1.31)	16 fewer per 1,000 (from 90 fewer to 84 more)	⊕⊕⊕ MODERATE	CRITICAL
Invasive ventilation (follow-up range: 2 days to 28 days)
8c	Randomized trials	Seriousd	Not serious	Not serious	Seriouse	None	206/862 (23.9%)	236/825 (28.6%)	RR, 0.85 (0.74 to 0.99)	44 fewer per 1,000 (from 76 fewer to 3 fewer)	⊕⊕ LOW	CRITICAL
Escalation of therapy (follow-up: range 2 days to 28 days; assessed with any escalation to HFNC, NIV, or invasive ventilation)
8f	Randomized trials	Seriousd	Not serious	Not serious	Seriouse	None	219/871 (25.1%)	266/832 (32.0%)	RR, 0.71 (0.51 to 0.98)	93 fewer per 1,000 (from 157 fewer to 6 fewer)	⊕⊕ LOW	CRITICAL
ICU length of stay (assessed with days)
2g	Randomized trials	Not serious	Serioush	Not serious	Seriousi	None	494	482	–	MD, 1.38 days fewer (0.90 fewer to 3.66 more)	⊕⊕ LOW	CRITICAL
Hospital length of stay (assessed with days)
4j	Randomized trials	Not serious	Not serious	Not serious	Seriousi	None	636	611	–	MD, 0.67 days fewer (1.41 fewer to 0.08 more)	⊕⊕⊕ MODERATE	CRITICAL
Patient-reported dyspnea (assessed with variable score)
7k	Randomized trials	Seriousl	Not Seriousm	Not Serious	Seriouse	None	458	436	–	SMD, 1.17 SD lower (2.60 lower to 0.25 higher)	⊕⊕ LOW	CRITICAL
Patient-reported comfort (assessed with variable score)
7n	Randomized trials	Seriousl	Seriouso	Not serious	Seriousb	None	624	607	–	SMD, 0.12 SD lower (0.61 lower to 0.37 higher)	⊕ VERY LOW	CRITICAL

CI = confidence interval; ICU = intensive care unit; HFNC = high-flow nasal cannula; RR = risk ratio; MD = mean difference; SD = standard deviation; SMD = standardized mean difference

Explanations

^aAzoulay 201846, Frat 201548, Jones 201649, Makdee 201744

^bAlthough point estimate suggests no effect, confidence intervals do not exclude important benefit and important harm

^cAzoulay 201846, Bell 201547, Frat 201548, Geng 202041, Jones 201649, Lemiale 201545, Makdee 201744, Rittayamai 201551

^dNone of the included trials were at low risk of bias for blinding and decision to escalate therapy or intubate may be subjective

^eUpper end of 95% confidence interval does not exclude no effect

^fAzoulay 201846, Bell 201547, Frat 201548, Jones 201649, Lemiale 201545, Makdee 201744, Parke 201150, Rittayamai 201551

^gAzoulay 201846, Frat 201548

^hHigh I² and of two studies reporting this outcome, results are discrepant

ⁱLower end of the 95% confidence interval does not exclude benefit with HFNC

^jAzoulay 201846, Geng 202041, Jones 201649, Makdee 201744

^kAzoulay 201846, Lemiale 201545, Makdee 201744, Raeisi 201942, Rittayamai 201551, Ruangsomboom 201943, Schwabbauer 201452

^lSubjective outcome in unblinded trials. Also other risk of bias issues in the trials reporting this outcome

^mHigh I² however, studies showed benefit with HFNC so did not downgrade

ⁿAzoulay 201846, Bell 201547, Frat 201548, Lemiale 201545, Makdee 201744, Rittayamai 201551, Schwabbauer 201452

^oHigh I² with variable effect across included studies