4. Comparison 1 (HFNC vs standard oxygen therapy): sensitivity analysis.
| Risk of selection: studies excluded from primary analysis owing to high or unclear risk of selection bias for random sequence generation or allocation concealment | ||
| Important outcomes | Excluded studies | Effect of sensitivity analysis |
| Failure of treatment | Frat 2015; Hu 2020; Lemiale 2015; Maggiore 2014; Song 2017; Yu 2017 | Effect estimate no longer indicated improvement with HFNC use (RR 0.85, 95% CI 0.62 to 1.17; 9 studies, 2457 participants; I2 = 55%) |
| In‐hospital mortality | Frat 2015; Hu 2020; Maggiore 2014; Yu 2017 | Interpretation of the effect estimate remained the same |
| Important adverse events: pneumonia | Frat 2015; Yu 2017 | Interpretation of the effect estimate remained the same |
| Important adverse events: nasal mucosa or skin trauma | ‐ | ‐ |
| Length of ICU stay | Brainard 2017; Frat 2015; Maggiore 2014; Yu 2017 | Interpretation of the effect estimate remained the same |
| PaO2/FiO2 up to 24 hours | Frat 2015; Maggiore 2014; Parke 2011 | Effect estimate indicated higher PaO2/FiO2 when standard oxygen therapy was used (MD 25.28 mmHg, 95% CI 7.23 to 43.32; 2 studies, 245 participants; I2 = 0%) |
| Comfort (short‐term) | Frat 2015; Maggiore 2014; Rittayamai 2014 | Interpretation of the effect estimate remained the same |
| Comfort (long‐term) | Maggiore 2014; | Interpretation of the effect estimate remained the same |
| High risks of other bias: studies excluded from primary analysis owing to high risks of other bias | ||
| Outcome | Excluded studies | Effect of sensitivity analysis |
| Failure of treatment |
Fernandez 2017; Hu 2020; Parke 2011; Parke 2013a; Zochios 2018 (selective reporting bias) Frat 2015 (selective reporting bias, and differences in treatment in the HFNC group) |
Interpretation of the effect estimate remained the same |
| In‐hospital mortality |
Fernandez 2017; Frat 2015; Hu 2020; Parke 2013a; Zochios 2018 (selective reporting bias) Frat 2015 (differences in treatment in the HFNC group) |
Interpretation of the effect estimate remained the same |
| Important adverse events: pneumonia | Frat 2015 (selective reporting bias, and differences in treatment in the HFNC group) | Interpretation of the effect estimate remained the same |
| Important adverse events: nasal mucosa or skin trauma | ‐ | ‐ |
| Length of ICU stay |
Brainard 2017 (attrition bias) Frat 2015 (selective reporting bias, and differences in treatment in the HFNC group) Parke 2013a (selective reporting bias) |
Interpretation of the effect estimate remained the same |
| PaO2/FiO2 up to 24 hours |
Frat 2015 (selective reporting bias, and differences in treatment in the HFNC group) Parke 2011 (selective reporting bias) |
Effect estimate indicated higher PaO2/FiO2 when standard oxygen therapy was used (MD 29.28 mmHg, 95% CI 13.86 to 44.70; 3 studies, 350 participants; I2 = 0%) |
| Comfort (short‐term) |
Frat 2015 (selective reporting bias, and differences in treatment in the HFNC group) Parke 2013a (selective reporting bias) |
Interpretation of the effect estimate remained the same |
| Comfort (long‐term) | Parke 2013a (selective reporting bias) | Effect estimate indicated improved comfort when HFNC was used (MD ‐2.10, 95% CI ‐3.16 to ‐1.04; 1 study, 105 participants) |
| Fixed effect versus random effects: we re‐analysed the data using a fixed‐effect model | ||
| Outcomes | Effect of sensitivity analysis | |
| Failure of treatment In‐hospital mortality Important adverse events: pneumonia Important adverse events: nasal mucosa or skin trauma Length of ICU stay PaO2/FiO2 up to 24 hours Comfort (short‐term) Comfort (long‐term) |
Interpretation of the effect estimate for all outcomes remained the same | |
| Funding: studies excluded from analysis in which funding was from commercial sources | ||
| Outcome | Excluded studies | Effect of sensitivity analysis |
| Failure of treatment | Azoulay 2018; Corley 2014; Frat 2015; Hernandez 2016b; Lemiale 2015; Maggiore 2014; Parke 2011; Parke 2013a; Zochios 2018 | Interpretation of the effect estimate remained the same |
| In‐hospital mortality | Azoulay 2018; Hernandez 2016b; Maggiore 2014; Parke 2013a; Zochios 2018 | Interpretation of the effect estimate remained the same |
| Important adverse events: pneumonia | Frat 2015; Hernandez 2016b | Interpretation of the effect estimate remained the same |
| Important adverse events: nasal mucosa or skin trauma | Hernandez 2016b | Interpretation of the effect estimate remained the same |
| Length of ICU stay | Corley 2014; Frat 2015; Maggiore 2014; Parke 2013a | Interpretation of the effect estimate remained the same |
| PaO2/FiO2 up to 24 hours | Corley 2014; Frat 2015; Maggiore 2014; Parke 2013a | Interpretation of the effect estimate remained the same (only one study remaining in analysis) |
| Comfort (short‐term) | Frat 2015; Maggiore 2014; Parke 2013a | Interpretation of the effect estimate remained the same (only one study remaining in analysis) |
| Comfort (long‐term) | Maggiore 2014; Parke 2013a | No studies remaining in analysis |
CI: confidence interval MD: mean difference RR: risk ratio PaO2/FiO2: partial pressure of arterial oxygen/fraction of inspired oxygen