Table 1.
Certainty of Evidence for HFNO versus NIV
| Outcome: Population № of participants (studies) References | Relative effect or Standardized mean difference (95% CI) | Anticipated absolute event rates* | Absolute risk difference (95% CI) | Certainty | What happens | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| HFNO | NIV | ||||||||||||
|
Initial management of acute respiratory failure population trials | |||||||||||||
| Intubation: 420 (2 RCTs) (32,34) | RR 0.71 (0.53 to 0.95) | 23.0% | 32.4% | −9.4% (−15.2 to −1.6) | Low†‡ | HFNO may reduce intubations by a moderate amount | |||||||
| All-cause Mortality: 216 (1 RCT) (34) | RR 0.44 (0.24 to 0.79) | 12.4% | 28.2% | −15.8% (−21.4 to −5.9) | Low§ | HFNO may reduce all-cause mortality by a large amount | |||||||
| Hospital-acquired Pneumonia: 216 (1 RCT) (34) |
RR 0.46 (0.15 to 1.45) |
3.8% | 8.2% | −4.4% (−7.0 to 3.7) |
Low‖ | HFNO may reduce hospital-acquired pneumonia by a moderate amount. | |||||||
| ICU Admissions (yes/no): 204 (1 RCT) (32) |
RR 0.98 (0.73 to 1.32) |
46.1% | 47.0% | −0.9% (−12.2 to 15.0) |
Insufficient†‡¶ | It is uncertain if HFNO reduces ICU admissions. | |||||||
| Length of stay, ICU: 420 (2 RCTs) (32,34) |
Mean (days) 7.7 |
Mean (days) 8.3 |
MD −0.64 days (−1.67 to 0.39) |
Insufficient†‡¶ | It is uncertain if HFNO reduces ICU length of stay. | ||||||||
| Length of stay, hospital: 372 (2 RCTs) (29,32) |
Mean (days) 11.6 |
Mean (days) 11.1 |
MD 0.45 days (−0.69 to 1.59) |
Low†‡ | HFNO may make little or no difference in hospital length of stay. | ||||||||
| Patient comfort, including related to dryness, based on VAS or % improved: 644 (7 RCTs) (29,32,34,35,49,50,54) |
One trial (n=216) (34) reported HFNO improved comfort (SMD −0.51 [−0.78 to −0.24]) based on an unmarked 100 mm VAS and 1 (n=168) (29) reported higher percentage of patients feeling comfort with HFNO (88.2% vs. 67.9%; ARD 21.4% [9.4 to 33.4]). One trial (n=204) (32) reported little to no difference in patient comfort based on a 5-point VAS (medians 2 vs. 2 on scale, 5=most discomfort). Among 4 crossover trials (n=56), 3 reported little to no difference (35,50,54) and 1 reported improvement with HFNO in short-term patient comfort based on a 10-point numeric rating scale (49). | Low**†† | HFNO may improve patient comfort. | ||||||||||
| Dyspnea, based on VAS or Borg scale scores or % improved: 464 (7 RCTs) (32,34,35,48–50,54) |
One trial (n=177) (34) reported greater improvement in dyspnea short-term in patients allocated to HFNO compared with NIV (75.6% vs. 58.2%; ARD 17.3% [3.7 to 30.9]). One trial (n=180) (32) reported little to no difference in longer-term (SMD 0.21 [−0.12 to 0.54] dyspnea based on Borg. One trial (n=51) (48) reported little to no difference in short-term dyspnea based on 10-point VAS scale (mean change from baseline −0.1 vs. −0.9). Among 4 crossover trials (n=56), 2 reported little to no difference based on VAS, (50,54) 1 reported worsening based on VAS,(35) and 1 reported improvement in short-term dyspnea based on Borg with HFNO.(49) | Low**†† | HFNO may make little or no difference in dyspnea. | ||||||||||
| Skin breakdown (facial pressure sore or nasal ulceration): | Not reported | ||||||||||||
|
Post-extubation acute respiratory failure population trials | |||||||||||||
| Reintubation: 1476 (3 RCTs) (37,39,53) |
RR 1.13 (0.90 to 1.43) |
17.3% | 15.3% | 2.0% (−1.5 to 6.6) |
Low‖ | HFNO may increase reintubations by a small amount | |||||||
| All-cause Mortality: 1476 (3 RCTs) (37,39,53) |
RR 1.15 (0.88 to 1.51) |
12.9% | 11.2% | 1.7% (−1.3 to 5.7) |
Low‖ | HFNO may increase all-cause mortality by a small amount | |||||||
| Hospital-acquired Pneumonia: 1434 (2 RCTs) (37,53) |
RR 0.90 (0.70 to 1.16) |
13.2% | 14.7% | −1.5% (−4.4 to 2.3) |
Low‖ | HFNO may make little to no difference in hospital-acquired pneumonia | |||||||
| ICU Admissions (yes/no) |
Not applicable | ||||||||||||
| Length of stay, ICU: 1476 (3 RCTs) (37,39,53) |
Pooled mean differences from 2 trials (37,39) (n=646) found HFNO made little or no difference in ICU length of stay (mean days NA; MD −0.98 days [−1.99 to 0.03]. One trial (n=830) reported little to no difference in ICU length of stay (medians 6 vs. 6 days).(53) | Low‖ | HFNO may make little to no difference in ICU length of stay | ||||||||||
| Length of stay, hospital: 1434 (2 RCTs) (37,53) |
One trial (n=604) (37) reported a lower hospital length of stay with HFNO (medians 23 vs. 26 days; MD −3 days [−6.8 to −0.8]). One trial (n=830) (53) reported little to no difference in hospital length of stay (medians 13 vs. 14 days). | Insufficient‖** | It is uncertain if HFNO reduces hospital length of stay. | ||||||||||
| Patient comfort, based on % improved or VAS: 872 (2 RCTs) (39,53) |
One large trial (n=748) (53) reported little to no difference in the percentage of participants reporting good comfort (51.3% vs. 52.9%; ARD −1.6% [−8.7 to 5.6]). One small trial (n=42) (39) found HFNO may improve comfort (SMD −0.75 [−1.38 to −0.12]) based on VAS. | Low**†† | HFNO may make little or no difference in patient comfort. | ||||||||||
| Dyspnea, based on % improved: 752 (1 RCT) (53) |
RR 0.96 (0.86 to 1.08) |
58.0% | 60.4% | −2.4% (−8.5 to 4.8) |
Low‖ | HFNO may make little or no difference in dyspnea. | |||||||
| Skin breakdown (facial pressure sore or nasal ulceration): 1454 (3 RCTs) (37,39,53) |
Peto OR 0.15 (0.02 to 1.13) |
4.6% | 24.3% | −19.7% (−23.7 to 2.3) |
Low‡** | HFNO may reduce skin breakdowns by a large amount | |||||||
Abbreviations
ARD=absolute risk difference; CI=confidence interval; HFNO=high flow nasal oxygen; ICU=intensive care unit; MD=mean difference; NA=not available; NIV=noninvasive ventilation; OR=odds ratio; RCT=randomized controlled trial; RR=risk ratio; SMD=standardized mean difference; VAS=visual analog scale
GRADES of certainty of evidence
High certainty: We are very confident that the true effect lies close to that of the estimate of the effect Moderate
certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Insufficient certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
Thresholds for determining magnitude by outcome
Intubation: Little or no effect: <2%; Small effect: 2–3.9%; Moderate effect: 4–9.9%; Large effect ≥10%
All-cause mortality: Little or no effect: <1%; Small effect: 1–1.9%; Moderate effect: 2–4.9%; Large effect: ≥5%
Pneumonia: Little or no effect: <2%; Small effect: 2–3.9%; Moderate effect: 4–9.9%; Large effect: ≥10%
Length of Stay: Little or no effect: <1 day; Small effect: ≥1 day; Moderate effect: NA; Large effect: ≥3 day
Skin breakdown: Little or no effect: <2%; Small effect: 2–3.9%; Moderate effect: 4–9.9%; Large effect: ≥10%
Pooled event rates calculated with Freeman-Tukey double arcsine variance-stabilizing transformation can be found in Supplementary Table 11
Explanations
Downgraded for study limitations, particularly moderate attrition and/or unclear allocation concealment
Downgraded for imprecision (wide CIs)
Downgraded two levels based on results derived from one trial (n=216) and imprecision, difficult to determine if there is a definitive benefit based on only a single study.
Downgraded two levels for imprecision (very wide CIs) and/or difficult to interpret based on the variability in the reporting of the effects
Downgraded for indirectness, ICU stay possibly protocol driven
Downgraded due to inconsistency
Downgraded due to imprecision, difficult to interpret based on the variability in the reporting of the effects