Table 2.
Certainty of Evidence for HFNO versus COT
| 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 | COT | ||||||||||||
|
Initial management of acute respiratory failure population trials | |||||||||||||
| Intubation: 1694 (8 RCTs) (27,28,34,40,41,43,46,52) |
Peto OR 0.98 (0.34 to 2.82) |
26.1% | 26.5% | −0.4% (−15.6 to 23.9) |
Low†‡ | HFNO may make little or no difference in intubation | |||||||
| All-cause Mortality: 1407 (4 RCTs) (27,34,40,43) |
RR 0.97 (0.82 to 1.14) |
26.3% | 27.2% | −0.8% (−4.9 to 3.8) |
Low†‡ | HFNO may make little or no difference in all-cause mortality | |||||||
| Hospital-acquired Pneumonia: 200 (1 RCT) (34) |
RR 0.44 (0.14 to 1.43) |
3.8% | 8.5% | −4.7% (−7.3 to 3.7) |
Low§ | HFNO may result in a reduction in hospital-acquired pneumonia by a moderate amount | |||||||
| ICU Admissions (yes/no): 403 (2 RCTs) (28,40) |
RR 1.11 (0.58 to 2.12) |
8.8% | 7.9% | 0.9% (−3.3 to 8.8) |
Insufficient†‡‖ |
It is uncertain if HFNO reduces ICU admissions. | |||||||
| Length of stay, ICU: 1036 (3 RCTs) (27,34,44) |
Two trials (n=976) (27,34) found little or no difference in ICU length of stay (mean days NA; MD 0.41 days [−1.08 to 1.90]). One trial (n=60) reported little to no difference in ICU length (P=.20, no data reported).(44) | Insufficient†‡‖ | It is uncertain if HFNO reduces ICU length of stay | ||||||||||
| Length of stay, hospital: 1267 (4 RCTs) (27,40,43,44) |
Four trials reported little to no difference in hospital length of stay based on medians (medians ranged from 1 to 24 vs. 1 to 27 days) (27,40,43) and/or p-values.(44) | Low§ | HFNO may make little or no difference in hospital length of stay | ||||||||||
| Patient comfort, including comfort related to dryness, based on VAS or % improved: 1611 (12 RCTs total, some trials reported ≥1 measure of comfort) (27,28,31,34,40,41,43,45,46,49,52,54) |
Pooled results from 4 trials (n=415) (34,43,46,52) found HFNO improved comfort (SMD −0.61 [−0.81 to −0.41]) based on VAS. Results pertaining to patient comfort based on median or unclear (27) scale scores varied: 1 trial (n=100) (28) reported higher comfort based on a 5 point Likert scale (4 vs. 3 on a 5-point scale, 5=most comfort, P=.04) while 2 trials (n=876) (27,41) reported little to no difference in patient comfort on a 10-point scale (7.9 vs. 6.8, 10=perfect) (27) and medians 3 vs. 3 on a 10-point scale (10=worst).(41) One trial (n=158) (40) reported a lower percentage of participants with discomfort related to dryness (29.8% vs. 45.3%; ARD −15.5% [−30.8 to −0.2]). Four small crossover studies (n=62) (31,45,49,54) reported little to no difference in short-term patient comfort. | Low¶ ** | HFNO may improve patient comfort. | ||||||||||
| Dyspnea, based on VAS and Borg scale scores or % improved: 1799 (13 RCTs) (27,28,31,34,40,41,43,45–47,49,52,54) |
Pooled results from 4 trials (n=258) (43,46,47,52) found HFNO improved dyspnea (SMD −0.56 [−1.35 to 0.24]) based on VAS and Borg scales. Two trials (n=876) (27,41) reported little to no difference in short-term dyspnea based on median scale scores (medians 2.3 to 3 vs. 2.6 to 3 on a 10-point scale, 10=most severe). Three trials (n=417) (28,34,40) reported a greater percentage of participants with improvement in dyspnea or improved breathing (78.0% vs. 55.8%; ARD 22.2% [13.3 to 31.1]). Four small crossover studies (n=62) (31,45,49,54) reported little to no difference in short-term dyspnea. | Low¶ ** | HFNO may improve dyspnea. | ||||||||||
| Skin breakdown (facial pressure sore or nasal ulceration): 431 (2 RCTs) (40,43) |
Both trials reported no incidences of skin breakdown were observed with HFNO. For COT, one trial reported no incidences (40) and the other trial did not report this outcome.(43) | Insufficient†† | It is uncertain if HFNO reduces skin breakdown. | ||||||||||
|
Post-extubation acute respiratory failure population trials | |||||||||||||
| Reintubation: 1065 (7 RCTs) (30,38,42,51,55,56,58) |
Peto OR 0.60 (0.23 to 1.61) |
6.5% | 10.4% | −3.9% (−7.8 to 5.3) |
Low§ | HFNO may reduce reintubations by a small amount | |||||||
| All-cause Mortality: 782 (4 RCTs) (38,42,55,56) |
RR 1.01 (0.60 to 1.72) |
6.3% | 6.2% | 0.1% (−2.5 to 4.5) |
Low§ | HFNO may make little or no difference in all-cause mortality | |||||||
| Hospital-acquired Pneumonia: 527 (1 RCT) (38) |
RR 0.50 (0.13 to 1.97) |
1.1% | 2.3% | −1.1% (−2.0 to 2.2) |
Low§ | HFNO may make little or no difference in hospital-acquired pneumonia | |||||||
| ICU Admissions (yes/no) |
Not applicable | ||||||||||||
| Length of stay, ICU: 1006 (6 RCTs) (30,38,42,55,56,58) | Pooled results from 5 trials (n=479) (30,42,55,56,58) found HFNO makes little or no difference in ICU length of stay (approximately 6 days in each group; MD 0.19 days [−0.19 to 0.57]. One trial not pooled (n=527) (38) reported little to no difference in ICU length of stay (medians 6 vs. 6 days). | Moderate‡ | HFNO probably makes little or no difference in ICU length of stay | ||||||||||
| Length of stay, hospital: 587 (2 RCTs) (38,56) |
Study 1
Median 11 (IQR 6 to 15) Study 2 Mean 37.7 |
Study 1 Median 12 (IQR 6 to 16) Study 2 Mean 25.7 |
Study 1 (38) MD 4 days (−28 to 32) Study 2 (56) MD 12 days (0.15 to 23.85) |
Insufficient†† | It is uncertain if HFNO improves hospital length of stay. | ||||||||
| Patient comfort, including comfort related to dryness and interface, based on VAS or % improved: 324 (4 RCTs total, some trials reported ≥1 measure of comfort) (42,51,55,58) | One trial (n=105) (42) found HFNO improved comfort (SMD −0.70 [−1.10 to −0.31]) based on a 10 point VAS where lower is better. One trial (n=60) (51) reported higher comfort or less dryness with HFNO based on median scale scores. One trial (n=90) (55) reported a lower percentage of participants with discomfort related to dryness with HFNO (38.3% vs. 69.8%; ARD −31.5% [−51.0 to −11.9]). Two trials (n=165) (42,52) reported lower discomfort related to interface with HFNO versus COT (Trial 1 SMD −0.89 [−1.29 to −0.49]) (42) and Trial 2 medians 3 vs. 7 on a 10-point scale, 10=maximal discomfort, P<.001).(51) One trial (n=69) (58) reported little to no difference in any measure of discomfort on a 10-point scale (nasal, oral, or pharynx) based on medians. | Low§ | HFNO may improve patient comfort. | ||||||||||
| Dyspnea, based Borg scale score: 155 (1 RCT) (30) |
One trial reported little to no difference in short-term dyspnea (medians 1 vs. 0 on a 10-point scale, 10=maximal dyspnea). | Insufficient†† | It is uncertain if HFNO improves dyspnea. | ||||||||||
| Skin breakdown (facial pressure sore or nasal ulceration): 527 (1 RCT) (38) |
One trial reported no incidences of skin breakdown were observed with HFNO but this outcome was not reported for the COT arm. | Insufficient†† | It is uncertain if HFNO reduces skin breakdown. | ||||||||||
Abbreviations
ARD=absolute risk difference; CI=confidence interval; COT=conventional oxygen therapy; HFNO=high flow nasal oxygen; ICU=intensive care unit; IQR=interquartile range; MD=mean difference; NA=not available; 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 imprecision (wide CIs)
Downgraded for study limitations
Downgraded two levels for large imprecision (very wide CIs) and/or sparse data 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 effect
Downgraded to insufficient based on the enormity of the imprecision or difficult to interpret based on the variability in the reporting of the effects