Study characteristics

Methods

RCT, parallel‐group design. Multicentre study

Participants

Total number of randomized participants: 778

Setting: 32 ICUs; France

Inclusion criteria: ICU admission; ≥ 18 years of age; AHRF with PaO₂ < 60 mmHg or SpO₂ < 90% on room air, or tachypnoea > 30 breaths/min or laboured breathing or respiratory distress; need for oxygen flow of ≥ 6 L/min; known immunosuppression; written informed consent

Exclusion criteria: people with AIDS; imminent death; refusal to participate in study; anatomical factors precluding use of nasal cannula; hypercapnia indicting NIV; isolated cardiogenic pulmonary oedema indicating NIV; pregnancy or breastfeeding; absence of health insurance coverage; surgery within the last 6 days

Baseline characteristics:

Intervention group (HFNC):

• Age, median (IQR): 64 (55 to 70) years

• Gender, M/F: 270/118

• BMI, mean (SD): not reported

• SOFA, median (IQR) : 6 (4 to 8)

• SAPS II, median (IQR): 36 (28 to 46)

• PaCO₂, mean (SD): not reported

• PaO₂/FiO₂, median (IQR): 136 (96 to 187) mmHg

• Respiratory rate, median (IQR): 33 (28 to 39) breaths/min

Control group (standard oxygen therapy):

• Age, median (IQR): 63 (56 to 71) years

• Gender, M/F: 247/141

• BMI, mean (SD): not reported

• SOFA, median (IQR): 6 (4 to 8)

• SAPS II, median (IQR): 37 (28 to 48)

• PaCO₂, mean (SD): not reported

• PaO₂/FiO₂, median (IQR): 128 (92 to 164) mmHg

• Respiratory rate, median (IQR): 32 (27 to 38) breaths/min

Interventions

Intervention group:

• Randomized, n = 389; losses, n = 1 (withdrew consent), 13 did not receive intervention as randomized; analysed, n = 388

• Details: started within 15 minutes of randomization, and for whole duration of ICU stay. Flow initiated at 50 L/min and 100% FiO₂, then subsequent flow to achieve SpO₂ ≥ 95% up to ≥ 50 L/min within the first 3 days then up to 60 L/min as needed. If participants needed MV, HFNC was used during laryngoscopy and immediately after extubation. Standard oxygen therapy was only used if significant nasal discomfort or skin breakdown.

Control group (standard oxygen):

• Randomized, n = 389 ; losses, n = 1 (withdrew consent), 31 did not receive intervention as randomized, 30 received HFNC; analysed, n = 388

• Details: started within 15 minutes of randomization, and for whole duration of ICU stay. Oxygen given by any device or combination of devices (nasal prongs or mask with or without reservoir bag and with or without Venturi system). Flow to achieve target SpO₂ ≥ 95%. HFNC only given if participants had a do‐not‐intubate order or for whom standard oxygen had failed. NIV only used as long as hypercapnia or pulmonary oedema were present.

Outcomes

Mortality within 28 days; hospital and ICU mortality; number needing MV by day 28; respiratory rate (normal values, 12‐20), lowest PaO₂/FiO₂, patient comfort score (range 0 to 10 = severe discomfort to perfect comfort); dyspnoea score (range 0 to 10 = no dyspnoea to severe dyspnoea); ICU and hospital lengths of stay; incidence of ICU‐acquired infections

Notes

Funding/declarations of interest: funded by the French Ministry of Health. Supplies for high‐flow oxygen from Fisher & Paykel Healthcare Ltd. Funders had no role in the design and conduct of the study, nor in preparation of the manuscript etc.

Some authors received fees from one or more of: Gilead; Astellas; Baxter; Alexion; Ablynx; Merk Sharp and Dohme, Fisher & Paykel Healthcare, Xenios; Boehringer Ingelheim; Pfizer; Astute; Bristol‐Myers Squibb; Jazz Pharma; Sanofi‐Aventis; Resmed; Philips; Hamilton; Medtronic; French Ministry of Health. One author serves on a data and safety monitoring board for the French Ministry of Health.

Study dates: 19 May 2016 to 31 December 2017

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Use of an electronic system

Allocation concealment (selection bias)

Low risk

Quote: "Randomization was achieved using an electronic system incorporated in the electronic case report from to ensure allocation concealment".

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Blinding was not possible. Although we expected that this would not influence outcome data, we could not be certain of this.

Blinding of outcome assessors (objective outcomes)

Low risk

Quote: "No blinding of adjudication was performed for outcome assessments". The assessors were unblinded; we did not anticipate that this would influence the assessment of objective outcome measures.

Blinding of outcome assessors (subjective measures)

Low risk

Participants were the outcome assessors for comfort and dyspnoea on a standardized scale: we did not anticipate that this would influence the assessment of these outcome measures.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Loss of only two participants

Selective reporting (reporting bias)

Low risk

Study was prospectively registered with a clinical trials register (NCT02739451). Outcomes relevant to the review were reported as described in the clinical trials register.

Other bias

Low risk

We identified no other sources of bias.

Study characteristics

Methods

RCT, parallel‐group design. Single‐centre study

Participants

Total number of randomized participants: 51

Setting: ICU, USA

Inclusion criteria: ≥ 18 years of age; undergoing thoracic surgery with scheduled admission to the ICU postoperatively

Exclusion criteria: < 18 years of age; pregnant or breastfeeding; known diagnosis of obstructive sleep apnoea; current or pervious lung transplantation; previous pneumonectomy; home oxygen > 4 L/min; inability to adhere to assigned treatment for the intended duration

Baseline characteristics (for those who continued treatment):

Intervention group (HFNC):

• Age, mean (SD): 57 (± 14) years

• Gender, M/F: 8/10

• BMI, mean (SD): 26 (± 5) kg/m²

• ASA II/III/IV: 5/12/1

• SAPS II, mean (SD): 19 (± 7)

• PaCO₂, mean (SD): not reported

• PaO₂/FiO₂, mean (SD): not reported

Control group (standard oxygen):

• Age, mean (SD): 59 (± 16) years

• Gender, M/F: 14/12

• BMI, mean (SD): 25 (± 5) kg/m²

• ASA II/III/IV: 1/19/1

• SAPS II, mean (SD): 23 (± 7)

• PaCO₂, mean (SD): not reported

• PaO₂/FiO₂, mean (SD): not reported

Interventions

Intervention group (HFNC):

• Randomized, n = 25; losses, n = 7 (discontinued due to discomfort); analysed, n = 18 (we included 7 lost participants as outcome data for comfort)

• Details: HFNC using MaxVenturi, started after transfer to ICU, following surgery, set flow of 40 L/min, FiO₂ titrated by respiratory therapists to maintain SpO₂ ≥ 90%. Therapy continued for 48 hours or until transfer from the ICU to a ward

Control group (standard oxygen):

• Randomized, n = 26; losses, n = 0; analysed, n = 26

• Details: standard oxygen given via nasal cannula or face mask titrated by nurses as required to maintain SpO₂ ≥ 90%. Therapy continued for 48 hours or until transfer from the ICU to a ward

Outcomes

Composite of postoperative pulmonary outcomes (severe hypoxaemia, acute respiratory failure, escalation of therapy to non‐invasive ventilation, re‐intubation, occurrence of hospital‐acquired pneumonia); ICU and hospital lengths of stay; postoperative oxygenation

Note: study authors did not separately report data for the each event in the primary outcome.

Notes

Funding/declarations of interest: one study author was supported by the NIS/National Institute on Drug Abuse. Study authors declared no conflicts of interest.

Study dates: August 2013 to June 2015

Study characteristics

Methods

RCT, cross‐over study. Single‐centre study

Participants

Total number of participants: 10

Setting: medical‐surgical ICU; Montpelier, France

Inclusion criteria: ≥ 18 years old hospitalized in a medical‐surgical ICU, planned for tracheostomy tube removal which was placed in the ICU for weaning from mechanical ventilation

Exclusion criteria: pregnancy, adult under tutelage, contraindications for NIV

Baseline characteristics (all patients):

• Age: 54 to 66 years

• Respiratory rate, median (IQR): 18 (22 to 20) breaths/min

• PaCO₂: not reported

• PaO₂/FiO₂: not reported

Interventions

Flow rates of 15, 30, and 45 litres per minute were tested in a randomized order for each device.

• High‐flow face mask with a reservoir bag

• Optiflow high‐flow nasal cannulae

• Boussignac oxygen therapy system&

For each device and flow rate, participants were asked to have their mouth open and mouth closed in a randomized order. Each device was used for 5 minutes, with 15‐minute washout between treatments.

Outcomes

Tracheal pressure, FiO₂ delivered, respiratory discomfort, respiratory rate (at end of each treatment period), noise intensity

Notes

Funding sources/declarations of interest: Study authors disclosed funding of €3000 from Fisher & Paykel Healthcare Ltd, France, which was used to acquire technical equipment and clinical research insurance, and to present results at scientific meetings.

Study dates: not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Method of randomization not stated

Allocation concealment (selection bias)

Unclear risk

Method of allocation concealment not stated

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Blinding was not possible. Although we expected that this would not influence outcome data, we could not be certain of this.

Blinding of outcome assessors (objective outcomes)

Low risk

Investigators were outcome assessors for objective outcomes, but standardized tools were used for measurement, reducing risk of bias.

Blinding of outcome assessors (subjective measures)

Low risk

Participants were outcome assessors for respiratory and auditory discomfort on a standardized scale. We did not think this would influence the subjective outcome data.

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

One participant was excluded owing to major intolerance to the device but possibly should have been regarded as a treatment failure. In such a small study, this is likely to have had an effect.

Owing to inability of 4 participants in the Boussignac group to adhere to the protocol, it is likely that data were incomplete; however it was not mentioned how this was handled in the analysis.

Selective reporting (reporting bias)

Unclear risk

ISRCTN15995925. Retrospectively registered in August 2012. Not possible to establish any reporting bias through comparison with the trial register protocol

Other bias

Low risk

We identified no other risks of bias.

Study characteristics

Methods

RCT, parallel‐group design. Single‐centre study

Participants

Total number of randomized participants: 168

Setting: ICU; China

Inclusion criteria: acute exacerbations of COPD, admitted to the ICU with severe illness and needing ventilation therapy

Exclusion criteria: unstable haemodynamics; with pneumonia, acute heart failure, bronchiectasis, asthma, acute respiratory acidosis needing NIV, lung cancer and other complications

Baseline characteristics:

Intervention group (HFNC):

• Age, mean (SD): 66.91(± 7.38) years

• Gender, M/F: 48/36

• BMI, mean (SD): not reported

• APACHE II: not reported

• PaCO₂, mean (SD): not reported

• PaO₂/FiO₂, mean (SD): 72.91 (± 16.41) mmHg

Control group (NIPPV):

• Age, mean (SD): 67.88 (± 8.38) years

• Gender, M/F: 50/34

• BMI, mean (SD): not reported

• APACHE II: not reported

• PaCO₂, mean (SD): not reported

• PaO₂/FiO₂, mean (SD): 72.91 (± 16.41) mmHg

Interventions

Intervention group (HFNC):

• Randomized, n = 84; losses, n = 0; analysed, n = 84

• Details: HFNC with OH‐60C high‐flow noninvasive breathing apparatus (Micomme, Hunan, China). Temperature set at 37 ºC, flow rate of 30 to 35 L/min

Control group (NIPPV):

• Randomized, n = 84; losses, n = 0; analysed, n = 84

• Details: ventilated by mouth and nose using Hamilton G5 ventilator (Hamilton Medical, Switzerland), initial inspiratory positive airway pressure set at 10 cm H₂O and expiration pressure set at 5 cm H₂O. FiO₂ adjusted to ensure oxygen saturation

Outcomes

Blood gases (PaO₂; PaCO₂; pH; SpO₂) at 12 hours and 5 days after therapy; ventilation support time; length of hospital stay; complications; comfort; nursing satisfaction

Notes

Funding/declarations of interest: funding not reported. Study authors declared no competing interests.

Study dates: January 2015 to December 2017

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Described as randomized, but no additional details

Allocation concealment (selection bias)

Unclear risk

No details

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Blinding was not possible. Although we expected that this would not influence outcome data, we could not be certain of this.

Blinding of outcome assessors (objective outcomes)

Low risk

Blinding of outcome assessors was not described; we did not anticipate that this would influence the assessment of objective outcome measures.

Blinding of outcome assessors (subjective measures)

Low risk

Participants were outcome assessors for comfort using a standardized scale: we did not anticipate that this would influence the assessment of this outcome measure.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No apparent losses

Selective reporting (reporting bias)

Unclear risk

Study authors did not report prepublished protocol or clinical trials registration. it was not feasible to effectively assess risk of selective reporting bias without these documents.

Other bias

Low risk

We identified no other sources of bias.

Study characteristics

Methods

RCT, parallel‐group design. Single‐centre study

Participants

Total number of participants: 155

Setting: ICU; Brisbane, Australia

Inclusion criteria: ≥ 18 years, BMI ≥ 30 kg/m², scheduled to undergo cardiac surgery on cardiopulmonary bypass

Exclusion criteria: ventilation time > 36 hours, extubation onto NIPPV, requirement for tracheostomy, extubation as part of end‐of‐life treatment

Baseline characteristics:

Intervention group (HFNC):

• Age mean (SD): 63 (± 11.4) years

• Gender, M/F: 58/23

• BMI, mean (SD): 36 (± 5.2) kg/m²

• APACHE II, mean (SD): 15 (3.6)

• Respiratory rate: not reported

• PaCO₂: not reported

• PaO₂/FiO₂: not reported

Control group (standard oxygen therapy):

• Age mean (SD): 65 (± 11.1) years

• Gender, M/F: 56/18

• BMI, mean (SD): 35 (± 4.3) kg/m²

• APCAHE II, mean (SD): 15 (3.9)

• Respiratory rate: not reported

• PaCO₂: not reported

• PaO₂/FiO₂: not reported

Interventions

Interventions group (HFNC):

• Randomized, n = 81; losses, n = 0; analysed, n = 81

• Details: Optiflow; Fisher & Paykel Healthcare Ltd; humidified to 37°C, flow rate commenced at 35 L/min, then titrated to a maximum of 50 L/min; FiO₂ titrated to maintain SpO₂ ≥ 95% for 8 hours, with short breaks for nasal care or mobilisation

Control group (standard oxygen therapy):

• Randomized, n = 74; losses, n = 0; analysed, n = 74

• Details: Oxygen delivered at 2 to 4 L/min via nasal cannulae or 6 L/min via simple face mask titrated to maintain SpO₂ ≥ 95%

Both applied after extubation

Outcomes

Atelectasis on chest X‐ray, oxygenation (PaO₂/FiO₂), respiratory rate, subjective dyspnoea, failure of allocated treatment

Notes

Funding/declarations of interest: unrestricted grant from Fisher & Paykel Healthcare Ltd; two study authors received travel and accommodation support from Fisher & Paykel Healthcare Ltd; manufacturer had no part in study design, data collection, data analysis, or creation of the manuscript.

Study dates: February 2011 to March 2012

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computerised random numbers table in blocks of 8

Allocation concealment (selection bias)

Low risk

Use of numbered, opaque envelopes to maintain allocation concealment

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Blinding was not possible. Although we expected that this would not influence outcome data, we could not be certain of this.

Blinding of outcome assessors (objective outcomes)

Low risk

Primary outcome assessment (atelectasis) blinded, but other outcome assessment not blinded. We did not anticipate that this would influence the assessment of objective outcome measures.

Blinding of outcome assessors (subjective measures)

Low risk

Participants were outcome assessors for subjective dyspnoea: we did not expect that this would influence the assessment of this outcome measure.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No losses

Selective reporting (reporting bias)

Low risk

ACTRN12610000942055. Prospective trial registration. All outcomes reported as stated in trial registry

Other bias

Low risk

We identified no other risks of bias.

Study characteristics

Methods

RCT, parallel‐group design. Single‐centre study

Participants

Total number of participants: 30

Setting: medical ICU; Paris, France

Inclusion criteria: acute hypoxaemic respiratory failure requiring at least 4 L/min oxygen to maintain SpO₂ above 95%

Exclusion criteria: use of NIV or invasive mechanical ventilation; presence of delirium that impaired the ability of the participant to rate dryness; preference for 1 of the 2 oxygen delivery systems

Baseline characteristics:

Interventions group (HFNC):

• Age, median (IQR): 66 (45 to 77) years

• Gender, M/F: 7/11

• BMI, mean (SD): not reported

• SAPS II, median (IQR): 27 (22 to 43)

• PaCO₂: not reported

• PaO₂/FiO₂: not reported

Control group (standard oxygen therapy):

• Age, median (IQR): 51 (39 to 77) years

• Gender, M/F: 6/6

• BMI, mean (SD): not reported

• SAPS II, median (IQR): 24 (12 to 35)

• PaCO₂, mean (SD): not reported

• PaO₂/FiO₂, mean (SD): not reported

Interventions

Intervention group (HFNC):

• Randomized, n = 19; losses, n = 1 (worsened); analysed, n = 18

• Details: Optiflow; Fisher & Paykel Healthcare; humidified to 37°C, flow rate at 40 L/min

Control group (standard oxygen therapy):

• Randomized, n = 12; losses, n = 6 (4 worsened, 2 rapidly recovered); analysed, n = 12

• Use of a flow meter from wall oxygen without humidification

• Randomized to receive therapy during first 24 hours, then crossed over to alternative therapy for 4 hours to reduce dropouts

Outcomes

Nasal airway calibre was measured by acoustic rhinometry at baseline, after 4 and 24 hours, and 4 hours after cross‐over. Dryness of the nose, mouth, and throat was auto‐evaluated and was assessed blindly by an otorhinolaryngologist. After cross‐over, participants were asked which system they preferred.

Notes

Funding/declarations of interest: received a research grant from Fisher & Paykel Healthcare Ltd, but manufacturers had no part in the analysis of results or writing of the paper.

Study dates: December 2009 to December 2010

Note: we noted potentially clinically important differences in baseline characteristics. Specifically, participants in the intervention group were older and had higher rates of infectious pneumonia.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not stated in the paper

Allocation concealment (selection bias)

Unclear risk

Not stated in the paper

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Blinding was not possible. Although we expected that this would not influence outcome data, we could not be certain of this.

Blinding of outcome assessors (subjective measures)

Low risk

Participants were outcome assessors for dryness scores: we did not anticipate that this would influence the assessment of this outcome measure.

Incomplete outcome data (attrition bias)
All outcomes

High risk

Of 37 participants randomized, 7 were excluded from analysis, as they were unable to complete the study (5 owing to deterioration and 2 because of rapid improvement in respiratory status).

Selective reporting (reporting bias)

Unclear risk

Trial registration not reported in the paper. Unable to establish whether outcomes were reported according to prepublished protocol or trial registration documents

Other bias

Low risk

We identified no other sources of bias.

Study characteristics

Methods

RCT, parallel‐group design. Multicentre study

Participants

Total number of randomized participants: 155

Setting: 4 ICUs; Spain

Inclusion criteria: adults receiving MV for > 12 hours and ready for scheduled extubation after a SBT; at high risk for extubation failure

Exclusion criteria: tracheotomy; inability to follow commands; do‐not‐reintubate order; hypercapnia during SBT

Baseline characteristics:

Intervention group (HFNC):

• Age, mean (SD): 67.3 (± 12.1) years

• Gender, M/F: 46/32

• BMI, > 30 kg/m², n: 14

• APACHE II, mean (SD) : 21 (± 8.8)

• PaCO₂, mean (SD): not reported

• PaO₂/FiO₂, mean (SD): not reported

Control group (conventional oxygen therapy):

• Age, mean (SD): 69.7 (± 13.0) years

• Gender, M/F: 55/22

• BMI, > 30 kg/m², n: 18

• APACHE II, mean (SD): 21 (± 8.2)

• PaCO₂, mean (SD): not reported

• PaO₂/FiO₂, mean (SD): not reported

Interventions

Intervention group:

• Randomized, n = 78; losses, n = 0; analysed, n = 78

• Details: HFNC via Optiflow, flow initiated at 40 L/min, humidifier temperature at 37 ºC, but switched to noninvasive mode (34 ºC) if participant felt excessive warmth. Oxygen titrated to achieve SpO₂ at 92 to 95%. After 24 hours, received conventional therapy

Control group:

• Randomized, n = 77; losses, n = 0; analysed, n = 77

• Details: oxygen after extubation via nasal prongs or facemask, regulated by Venturi. Oxygen titrated to achieve SpO₂ at 92 to 95%. After 24 hours, continued to receive conventional therapy

Outcomes

Respiratory failure within 72 hours post‐extubation (NIV as rescue treatment was discouraged but given at discretion of attending team); reintubation; ICU and hospital lengths of stay; hospital mortality

Notes

Funding/declarations of interest: funding not reported. Two authors received conference fees or postdoctoral grant from Fisher & Paykel Healthcare Ltd.

Study dates: 2013 to 2014

Note: study terminated early owing to low recruitment

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: “Randomization was performed via a computerized random‐number table in blocks of four for each hospital”.

Allocation concealment (selection bias)

Low risk

Quote: "“allocation was concealed through numbered opaque envelopes”.

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Blinding was not possible. Although we expected that this would not influence outcome data, we could not be certain of this.

Blinding of outcome assessors (objective outcomes)

Low risk

Blinding of outcome assessors is not described; we did not anticipate that this would influence the assessment of objective outcome measures

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No apparent losses

Selective reporting (reporting bias)

High risk

Study was prospectively registered with a clinical trials register (NCT01820507). We noted that some outcomes were reported in the published report but not listed in the trials register documents (hospital and ICU lengths of stay); this could indicate risk of selective reporting bias for these outcomes.

Other bias

Low risk

We identified no other sources of bias.

Study characteristics

Methods

RCT, parallel‐group design. Multicentre study

Participants

Total number of participants: 313

Setting: 23 ICUs; France and Belgium

Inclusion criteria: consecutive patients, aged ≥ 18 years, respiratory rate > 25 breaths per minute, PaO₂/FiO₂ ≤ 300 mmHg while patient was breathing oxygen at flow rate ≥ 10 L/min for at least 15 minutes, PaCO₂ not higher than 45 mmHg, absence of clinical history of underlying chronic respiratory failure

Exclusion criteria: PaCO₂ > 45 mmHg, exacerbation of asthma or chronic respiratory failure, cardiogenic pulmonary oedema, severe neutropenia, haemodynamic instability, use of vasopressors, GCS ≤ 12, contraindications to NIV, urgent need for tracheal intubation, a do‐not‐resuscitate order, or decision to not participate

Baseline characteristics:

Intervention group (HFNC):

• Age mean (SD): 61 (± 16) years

• Gender, M/F: 75/31

• BMI, mean (SD): 25 (± 5)

• SAPS II:, mean (SD): 25 (± 9)

• PaCO₂ mean (SD): 36 (± 6) mmHg

• PaO₂/FiO₂ mean (SD): 157 (± 89) mmHg

• Respiratory rate mean (SD): 33 (± 6) breaths/min

Control group 1 (standard oxygen therapy):

• Age mean (SD): 59 (± 17) years

• Gender, M/F: 63\31

• BMI, mean (SD): 26 (± 5)

• SAPS II:, mean (SD): 24 (± 9)

• PaCO₂ mean (SD): 35 (± 5) mmHg

• PaO₂/FiO₂ mean (SD): 161 (± 73) mmHg

• Respiratory rate mean (SD): 32 (± 6) breaths/min

Control group 2 (non‐invasive ventilation):

• Age mean (SD): 61 (± 17) years

• Gender, M/F: 74/36

• BMI, mean (SD): 26 (± 6)

• SAPS II:, mean (SD): 27 (± 9)

• PaCO₂ mean (SD): 34 (± 6) mmHg

• PaO₂/FiO₂ mean (SD): 149 (± 72) mmHg

• Respiratory rate mean (SD): 33 (± 7) breaths/min

Interventions

Intervention group (HFNC):

• Randomized, n = 106; losses, n = 0; analysed, n = 106

• Details: Oxygen passed through heated humidifier, applied continuously through large‐bore nasal prongs; gas flow rate 50 L/min, FiO₂ 1.0 at initiation (Optiflow); adjusted to maintain SpO₂ ≥ 92 %; for at least 2 calendar days, then this could be stopped or participant switched to standard oxygen therapy

Control group (standard‐oxygen therapy):

• Randomized, n = 9; losses, n = 2 (withdrew consent); analysed, n = 94

• Details: Continuously through non‐rebreather face mask; flow rate ≥ 10 L/min; adjusted to maintain SpO₂ ≥ 92%; until participant recovered or was intubated

Control group (non‐invasive ventilation):

• Randomized, n = 111, losses, n = 1; analysed, n = 110

• Details: Through a face mask connected to an ICU ventilator with pressure support applied in NIV mode; adjusted to obtain expired tidal volume of 7 to 10 mL/kg of predicted body weight, with initial PEEP between 2 and 10 cm of water; adjusted to maintain SpO₂ ≥ 92%; minimum of 8 hours per day for at least 2 calendar days; applied during sessions of at least 1 hour, could be resumed if respiratory rate > 25 breaths per minute or SpO₂ less than 92%; between non‐invasive ventilation sessions, participants received high‐flow oxygen

Outcomes

Participants requiring endotracheal intubation within 28 days of randomization, mortality in ICU, mortality at 90 days, number of ventilator‐free days between day 1 and day 28, duration of ICU stay, complications during ICU stay, dyspnoea, comfort

Notes

Funding/declarations of interest: equipment provided by Fisher & Paykel Healthcare Ltd, but manufacturer had no involvement in the study.

Study dates: February 2011 to April 2013

Note: we noted an unequal number of participants in each group which we could not explain. An appropriate method of randomization was described, and baseline characteristics were largely comparable.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Use of centralized Web‐based management system, blocks of 6, stratified by centre and history or no history of cardiac insufficiency

Allocation concealment (selection bias)

Unclear risk

No details

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Blinding was not possible. Although we expected that this would not influence outcome data, we could not be certain of this.

Blinding of outcome assessors (objective outcomes)

Low risk

Blinding of outcome assessors was not described; we did not anticipate that this would influence the assessment of objective outcome measures.

Blinding of outcome assessors (subjective measures)

Low risk

Participants were outcome assessors for dyspnoea and comfort: we did not anticipate that this would influence the assessment of these outcome measures.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

3 losses (2 in standard oxygen group and 1 in NIV group) due to withdrawal of consent. Small number of losses unlikely to influence outcome data

Selective reporting (reporting bias)

High risk

NCT01320384. Study prospectively registered. We noted that most outcomes were reported in the published paper or its supplementary appendix. However, study authors described an outcome as the use of NIV as an escalation therapy in the HFNC or standard oxygen therapy groups, but did not report data for this outcome; we judged selective reporting bias to be high because this was a primary outcome in our first comparison group.

Other bias

High risk

Participants in NIV monitoring group were given HFNC between ventilation sessions.

Study characteristics

Methods

RCT, parallel‐group design. Multicentre study

Participants

Number of randomized participants: 228

Setting: 3 ICUs; France

Inclusion criteria: adults scheduled for planned or unplanned abdominal, or abdominal and thoracic surgery with anticipated duration of ≥ 2 hours, and moderate to high risk of postoperative pulmonary complications

Exclusion criteria: lack of informed consent; BMI > 35 kg/m²; life‐threatening condition requiring emergency surgery; obstructive sleep apnoea syndrome, pregnant

Baseline characteristics:

Intervention group (HFNC):

• Age, mean (SD): 62 (± 12) years

• Gender, M/F: 61/47

• BMI, mean (SD): 25 (± 4) kg/m²

• ASA I/II/ ≥ III, n: 20/72/7

• PaCO₂, mean (SD): not reported

• PaO₂/FiO₂, mean (SD): not reported

Control group (standard oxygen therapy):

• Age, mean (SD): 61 (± 13) years

• Gender, M/F: 64/48

• BMI, mean (SD): 25 (± 4) kg/m²

• ASA I/II/ ≥ III, n: 20/75/17

• PaCO₂, mean (SD): not reported

• PaO₂/FiO₂, mean (SD): not reported

Interventions

Intervention group (HFNC):

• Randomized, n = 108; losses, n = 0; analysed, n = 108

• Details: HFNC using Optiflow, was delivered continuously at a flow rate of 50 to 60 L/min, starting after tracheal extubation at the end of surgery until the morning of postoperative day 1. Titrated to maintain SpO₂ of ≥ 95%

Control group (standard oxygen therapy):

• Randomized, n = 112; losses, n = 0; analysed, n = 112

• Details: standard oxygen therapy, using nasal prongs or facemask, was delivered continuously, starting after tracheal extubation at the end of surgery until the morning of postoperative day 1. Titrated to maintain SpO₂ of ≥ 95%.

Note: study authors reported that 220 participants were randomized, and that 8 of these were excluded (3 because surgery was < 2 hours, and 5 because of other protocol violations), then a further 8 participants were recruited. Study authors did not report to which group the 8 lost participants belonged.

Outcomes

Hypoxaemia, postoperative pulmonary complications within 7 days after surgery, need for additional oxygen therapy at end of treatment; development of postoperative hypoxaemia, pneumonia, reintubation and/or use of curative NIV because of postoperative respiratory failure; postoperative gas exchange after discontinuation of allocated treatment; respiratory comfort (numerical rating scale from 0 to 10); duration of hospital and ICU stay, in‐hospital mortality

Notes

Funding/declarations of interest: funding for study was not reported. Some individual authors received consulting fees, lecture fees, nonfinancial support, travel expenses, or research grants from one or more of: Fresenius Kabi, General Electrics Healthcare, Drager, Fisher & Paykel Healthcare Ltd, Merck Sharp & Dohme, Baxter Gambro, Astellas, LFB Bio‐medicaments, and Pfizer. Study authors declared no competing interests.

Study dates: 6 November 2013 to 1 March 2015

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated randomization

Allocation concealment (selection bias)

Low risk

Allocation managed externally by a centralised telephone system

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Blinding was not possible. Although we expected that this would not influence outcome data, we could not be certain of this.

Blinding of outcome assessors (objective outcomes)

Low risk

Treatment allocation was concealed to outcome assessors.

Blinding of outcome assessors (subjective measures)

Low risk

Treatment allocation was concealed to outcome assessors. Participants were outcome assessors for respiratory comfort: we did not anticipate that this would influence the assessment of this outcome measure.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Only small number of losses (8 participants)

Selective reporting (reporting bias)

Low risk

Study was prospectively registered with a clinical trials register (NCT01887015). Outcomes were reported according to those described in clinical trials register.

Other bias

Low risk

We identified no other sources of bias.

Study characteristics

Methods

RCT, cross‐over design. Single‐centre study

Participants

Total number of randomized participants: 15

Setting: ICU; Italy

Inclusion criteria: adults with AHRF

Exclusion criteria: exacerbation of asthma or COPD; clinical evidence of cardiogenic pulmonary oedema; acute respiratory failure occurring within 1 week after surgery; haemodynamic instability and/or shock; metabolic acidosis; GCS < 13; facial anatomy contraindicating helmet or nasal cannula application

Baseline characteristics:

Overall:

• Age, mean (SD): 70 (64 to 77) years

• Gender, M/F: 9/6

• BMI, mean (SD): 168 (165 to 175)

• SAPS II, mean (SD): 28 (24 to 29)

• SOFA, median (IQR): 45 (36 to 69)

• PaCO₂, mean (SD): 32 (30 to 34) mmHg

• PaO₂/FiO₂, mean (SD): 133 (92 to 154) mmHg

Interventions

Cross‐over study, with each phase lasting 60 minutes

• HFNC: using AIRVO₂ device, Fisher & Paykel Healthcare, with a heated humidifier (MR860). Gas flow set at 50 L/min, and humidifier temperature at 37 ºC. FiO₂ titrated to obtain SpO₂ ≥ 92% and ≤ 98%

• Helmet NIV: through bi‐tube circuit with no humidification. Initial pressure support was 8 to 10 cm H₂O, adjusted for peak inspiratory flow of 100 to 150 L/min, up to a maximum of 20 cm H₂O; PEEP at 10 to 12 cm H₂O; flow trigger was 2 L/min and increased in presence of auto‐triggering. FiO₂ titrated to obtain SpO₂ ≥ 92% and ≤ 98%

Between interventions, there was a 15‐minute washout period with heated and humidified (MR860; Fisher & Paykel Healthcare) oxygen therapy at a flow rate of 50 L/min via a non‐rebreathing face mask (temperature of the humidification chamber set at 37° C, FiO₂ set to achieve a SpO₂ > 92% and < 98%)

Outcomes

PaO₂/FiO₂; PaCO₂; respiratory rate; inspiratory effort; work of breathing; comfort; dyspnoea; end‐inspiratory and end‐expiratory transpulmonary pressure

Note: we did not include outcome data in the review because the study authors did not report outcome data from the first study period.

Notes

Funding/declarations of interest: research grant from Società Italiana di Anestesia Analgesia Rianimazione e Terapia Intensiva; and Merck Sharp and Dohme

Study dates: May 2017 and December 2018

Study characteristics

Methods

RCT, parallel‐group design. Multicentre study

Participants

Total number of participants: 604

Setting: 3 ICUs (to include medical, trauma, and surgical patients); Spain

Inclusion criteria: adult participants receiving MV for > 12 hours who were ready for extubation, and were at high risk of extubation failure

Exclusion criteria (information taken from clinical trials register): < 18 years of age; tracheotomized patients; recent facial or cervical trauma/surgery; active gastrointestinal bleeding; lack of co‐operation; any failed spontaneous breathing trial because of hypercapnia development

Baseline characteristics:

Intervention group (HFNC):

• Age, mean (SD): 64.6 (± 15.4) years

• Gender, M/F: 186/104

• BMI > 25 kg/m², n: 74

• APACHE II, median (IQR): 16 (13.8 to 22)

• PaCO₂, mean (SD): 41 (± 2.2) mmHg

• PaO₂/FiO₂, mean (SD): 191 (± 34) mmHg

Control group (NIV):

• Age, mean (SD): 64.4 (± 15.8)

• Gender, M/F: 202/112

• BMI > 25 kg/m²: 74

• APACHE II, median (IQR): 16 (14 to 21)

• PaCO₂, mean (SD): 39 (± 3.2) mmHg

• PaO₂/FiO₂, mean (SD): 194 (± 37) mmHg

Interventions

Intervention group (HFNC):

• Randomized, n = 290; losses, n = 2 (discontinued study or loss to follow‐up); analysed, n = 288 (study authors also calculated ITT analysis)

• Details: Optiflow high‐flow oxygen immediately after extubation through specific nasal cannulae; flow initially set at 10 L/min and titrated upwards in 5 L/min steps. FiO₂ regularly adjusted to target SpO₂ > 92%. After 24 hours, high flow was stopped and, if necessary, participants received standard oxygen therapy.

Control group (NIV):

• Randomized, n = 314; losses, n = 2 (discontinued study or loss to follow‐up); analysed, n = 312 (study authors also calculated ITT analysis)

• Details: full face mask with BiPAP Vision immediately after extubation for 24 hours. Then NIV was withdrawn and oxygen was given via Venturi mask. PEEP and inspiratory pressure support adjusted to target respiratory rate of 25 breaths/min and adequate gas exchange. Sedatives to increase tolerance to NIV were not allowed.

Outcomes

Reintubation within 72 hours; post‐extubation respiratory failure; respiratory infection, sepsis, multiple organ failure, ICU and hospital length of stay, ICU and hospital mortality; adverse events; time to reintubation; duration of respiratory support; respiratory effects (PaO₂/FiO₂ and PaCO₂)

Note: we did not report data for physiological variables (PaO₂/FiO₂ and PaCO₂) because these were reported only for participants who were reintubated or had post‐extubation respiratory failure. We did not include data for duration of respiratory support because these data were reported only for the NIV group.

Notes

Funding sources/declarations of interest: study received no external funding. One author declared travel expenses from Fisher and Paykel Healthcare Ltd; no other disclosures reported

Study dates: September 2012 to October 2014

Note: Hernandez 2016a and Hernandez 2016b were registered as one study in the clinical trials register.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Use of random number generator

Allocation concealment (selection bias)

Low risk

Allocation concealed through use of telephone call centre that generated randomization

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Blinding was not possible. Although we expected that this would not influence outcome data, we could not be certain of this.

Blinding of outcome assessors (objective outcomes)

Low risk

Blinding of outcome assessors was not described; we did not anticipate that this would influence the assessment of objective outcome measures.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Only two participants in each group were lost to follow‐up.

Selective reporting (reporting bias)

Low risk

Study was prospectively registered with a clinical trials register (NCT01191489). Outcomes were reported as described in the prospective registration documents.

Other bias

Low risk

We identified no other sources of bias.

Study characteristics

Methods

RCT, parallel‐group design. Multicentre study

Participants

Total number of participants: 527
Setting: 7 ICUs (to include medical, trauma, and surgical patients); Spain

Inclusion criteria: adult participants receiving MV for > 12 hours who were ready for extubation, and were at low risk of extubation failure

Exclusion criteria (information taken from clinical trials register): < 18 years of age; tracheotomized patients; recent facial or cervical trauma/surgery; active gastrointestinal bleeding; lack of co‐operation; any failed spontaneous breathing trial because of hypercapnia development; accidentally extubated; self‐extubated; do‐not‐resuscitate orders.

Baseline characteristics:

Intervention group (HFNC):

• Age, mean (SD): 51 (± 13.1) years

• Gender, M/F: 164/100

• BMI > 25 kg/m², n = 21

• APACHE II, median (IQR): 14 (9 to 16)

• PaCO₂, mean (SD): 39 (± 2.4) mmHg

• PaO₂/FiO₂, mean (SD): 227 (± 25) mmHg

Control group (conventional oxygen therapy):

• Age, mean (SD): 51.8 (± 12.2)

• Gender, M/F: 153/110

• BMI > 25 kg/m²: n = 14

• APACHE II, median (IQR): 13 (9 to 17)

• PaCO₂, mean (SD): 38 (± 2.9) mmHg

• PaO₂/FiO₂, mean (SD): 237 (± 34) mmHg

Interventions

Intervention group (HFNC):

• Randomized, n = 264; losses, n = 0; analysed, n = 264

• Details: Optiflow high‐flow oxygen immediately after extubation through specific nasal cannulae; flow initially set at 10 L/min and titrated upwards in 5 L/min steps. FiO₂ regularly adjusted to target SpO₂ > 92%. After 24 hours, high flow was stopped, and if necessary, participants received standard oxygen therapy.

Control group (standard oxygen therapy):

• Randomized, n = 263; losses, n = 0; analysed, n = 263

• Details: conventional oxygen therapy applied continuously through nasal cannula or non‐rebreather facemask immediately after extubation for 24 hours. Oxygen flow adjusted to target SpO₂ > 92%.

Outcomes

Re‐intubation within 72 hours, post‐extubation respiratory failure, respiratory infection, sepsis and multi‐organ failure, ICU and hospital length of stay, ICU and hospital mortality, adverse events, time to reintubation, respiratory effects (PaO₂/FiO₂ and PaCO₂), adverse events (nasal mucosa or skin trauma)

Note: we did not report data for physiological variables (PaO₂/FiO₂ and PaCO₂) because these were reported only for participants who were reintubated or had post‐extubation respiratory failure.

Notes

Funding/declarations of interest: no external funding. Fisher and Paykel Healthcare Ltd supplied air‐oxygen blenders to 2 of the ICUs; Fisher and Paykel had no involvement in study design and conduct, or in preparation of final manuscript etc.

Study dates: September 2012 to October 2014

Note: Hernandez 2016a and Hernandez 2016b were registered as one study in the clinical trials register.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Use of random number generator

Allocation concealment (selection bias)

Low risk

Allocation concealed through use of telephone call centre that generated randomization

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Blinding was not possible. Although we expected that this would not influence outcome data, we could not be certain of this.

Blinding of outcome assessors (objective outcomes)

Low risk

Blinding of outcome assessors was not described; we did not anticipate that this would influence the assessment of objective outcome measures.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No losses

Selective reporting (reporting bias)

Low risk

Study prospectively registered with a clinical trials register (NCT01191489). Outcomes were reported as described in the prospective registration documents.

Other bias

Low risk

We identified no other sources of bias.

Study characteristics

Methods

RCT, parallel‐group design. Single‐centre study

Participants

Total number of randomized participants: 56

Setting: medical ICU; Taiwan

Inclusion criteria: adults admitted to the ICU with acute respiratory failure and mechanically ventilated for > 48 hours, successfully passed a SBT; meeting at least one risk factor for high‐risk extubation failure

Exclusion criteria: < 20 years of age; tracheostomy; pregnancy; facial trauma with intolerable post‐extubation facial mask or HFNC use; acute gastrointestinal bleeding; planning to use NIV after extubation

Baseline characteristics:

Intervention group (HFNC):

• Age, mean (SD): 72.9 (± 13.1) years

• Gender, M/F: 22/7

• BMI, > 30 kg/m², n: 3

• APACHE II, median IQR: 27 (23 to 29)

• PaCO₂, mean (SD): 42 (± 7.9) mmHg

• PaO₂/FiO₂, mean (SD): 320 (± 89.6) mmHg

Control group (conventional oxygen therapy):

• Age, mean (SD): 74.9 (± 11.4) years

• Gender, M/F: 17/10

• BMI, > 30 kg/m², n: 3

• APACHE II, median (IQR): 25 (22‐30)

• PaCO₂, mean (SD): 38 (± 7.4) mmHg

• PaO₂/FiO₂, mean (SD): 279 (± 90.6) mmHg

Interventions

Intervention group:

• Randomized, n = 29; losses, n = 0; analysed, n = 29

• Details: HFNC using Optiflow, immediately after extubation, humidified temperature initially set to 37 ºC, flow rate initially at 40 L/min with adjustments of 5 to 10 L/min (to maximum of 60 L/min). FiO₂ titrated to maintain SpO₂ > 92% (or 88‐95% for compensated hypercapnia). Applied for at least 72 hours, then maintained or given conventional therapy

Control group:

• Randomized, n = 27; losses, n = 0; analysed, n = 27

• Details: post‐extubation, conventional oxygen therapy delivered continuously through nasal prongs with flow rate 1 to 4 L/min, or via Venturi facemask with oxygen and flow titrated to deliver FiO₂ between 35% and 100% and to maintain SpO₂ > 92% (or 88 to 95% for compensated hypercapnia). Applied for at least 72 hours, then maintained if required

Outcomes

Respiratory failure within 72 hours (requiring rescue management with oxygen therapy, NIV, or reintubation); time to post‐extubation failure within 72 hours; multiple organ failure; ICU length of stay; 28‐day all‐cause mortality (in‐hospital); 48‐hour respiratory and haemodynamic variables (heart rate, MAP, PaO₂, PaCO₂); causes of respiratory failure (dyspnoea or hypoxia, respiratory acidosis, decreased levels of consciousness, stridor or upper airway problems)

Notes

Funding/declarations of interest: funding not reported. Study authors declared no competing interests.

Study dates: September 2014 to December 2016

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

1:1 block randomization used

Allocation concealment (selection bias)

Unclear risk

No details

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Blinding was not possible and we did not expect it to influence outcome data. However, the influence on RoB remains unclear.

Blinding of outcome assessors (objective outcomes)

Low risk

Blinding of outcome assessors. Although we expected that this would not influence outcome data, we could not be certain of this.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No participant losses

Selective reporting (reporting bias)

High risk

Study was prospectively registered with a clinical trials register (NCT 02290548). Whilst most review outcomes were reported according to these trial register documents, we noted that study authors did not report data for hospital length of stay and for pneumonia; this may indicate selective reporting bias for these outcomes.

Other bias

Low risk

We identified no other sources of bias.

Study characteristics

Methods

RCT, parallel‐group design. Single‐centre study

Participants

Total number of randomized participants: 42

Setting: ICU; China

Inclusion criteria: people with COPD who were intubated for exacerbation, with hypercapnia (PaCO₂ > 45 mmHg) at time of extubation, met the 'pulmonary infection control window' criteria

Exclusion criteria: tracheotomy; severe dysfunction of other organs; haemodynamic instability; facial injury, burns, or deformities; unco‐operative; copious secretions with weak cough ability; gastric over‐distention, vomiting; untreated pneumothorax; rhinitis, nasal congestion, deformities or blockage; refusal to participate in the study

Baseline characteristics:

Intervention group (HFNC):

• Age, mean (SD): 77.4 (± 6.8) years

• Gender, M/F: not reported

• BMI, mean (SD): not reported

• APACHE II, mean (SD): 11.8 (± 3.1)

• PaCO₂, mean (SD): 53.2 (± 6.7) mmHg

• PaO₂/FiO₂, mean (SD): 239.2 (± 80.8) mmHg

• Respiratory rate, mean (SD): 18.3 (3.5) breaths/min

Control group (NIV):

• Age, mean (SD): 73.9 (± 6.9) years

• Gender, M/F: not reported

• BMI, mean (SD): not reported

• APACHE II, mean (SD): 10.4 (± 2.5)

• PaCO₂, mean (SD): 53.7 (± 8.6) mmHg

• PaO₂/FiO₂, mean (SD): 250.8 (± 75.8) mmHg

• Respiratory rate, mean (SD): 19.2 (4.1) breaths/min

Interventions

Intervention group (HFNC):

• Randomized, n = 22; losses, n = 2 (1 did not receive intervention; 1 discontinued after 25 hours because of transfer to another hospital); analysed for failure requiring NIV or reintubation, mortality, comfort score, and ICU length of stay, n = 22 (use of ITT analysis); analysed for respiratory rate, PaCO₂, PaO₂/FiO₂, n = 20 (per protocol analysis)

• Details: HFNC using either Optiflow or AIRVO₂, nasal cannulae chosen according to participants' nostrils. Humidifier temperature set to 37 ºC, FiO₂ adjusted to maintain SpO₂ at 88 to 92%. In the 48 hours post‐extubation, HFNC was used at least 8 hours/day.

Control group (NIV):

• Randomized, n = 20; losses, n = 0; analysed, n = 20

• Details: NIV using VPAP III ST, ResMed USA, with standard oral‐nasal mask. Inspiratory positive airway pressure initiated at 10 to 12 cm H₂O, and expiratory positive airway pressure started at 4 to 5 cm H₂O. Oxygen adjusted to maintain SpO ₂ at 88 to 92%. In the 48 hours post‐extubation, NIV was used at least 8 hours/day.

Outcomes

Arterial blood gases (pH, PaCO₂, PaO₂/FiO₂); vital signs (heart rate, MAP, respiratory rate) at 3 hours, 24 hours, and 48 hours after extubation; duration of respiratory support; length of ICU stay; all‐cause mortality at 28 days; respiratory failure (needing either NIV or reintubation); comfort score (scale 0 to 10 = very comfortable to very uncomfortable); adverse events (aspiration, and facial breakdown); need for bronchoscopy

Notes

Funding/declarations of interest: funded by National Fund of China

Study dates: January 2017 to July 2018

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Use of a predetermined random number table

Allocation concealment (selection bias)

Low risk

Randomization sheet was kept by a secretary who was not otherwise involved in the study.

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Blinding was not possible. Although we expected that this would not influence outcome data, we could not be certain of this.

Blinding of outcome assessors (objective outcomes)

Low risk

Blinding of outcome assessors was not described; we did not anticipate that this would influence the assessment of objective outcome measures.

Blinding of outcome assessors (subjective measures)

Low risk

Participants were outcome assessors for comfort and used a standardized approach: we did not anticipate that this would influence the assessment of these outcomes.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Two losses in the intervention group. Study authors reported ITT analysis.

Selective reporting (reporting bias)

Unclear risk

Study was retrospectively registered with a clinical trials register (NCT03458364). It was not feasible to effectively assess risk of selective reporting bias with these documents.

Other bias

Low risk

We identified no other sources of bias.

Study characteristics

Methods

RCT, cross‐over design. Single‐centre study

Participants

Total number of randomized participants: 26

Setting: ICU; South Korea

Inclusion criteria: age > 20 years; subjective dyspnoea in room air; SpO₂ < 90% in room air; oxygen requirement for nasal cannula < 6 L/min

Exclusion criteria: unstable vital signs; severe hypoxia; unable to co‐operate; symptomatic Ischaemic heart disease; use of accessory muscle heart disease; use of accessory muscle under oxygen therapy using nasal cannula; impracticality of HFNC or NC application; facial deformity

Baseline characteristics (overall):

• Age, mean (SD): 67.9 (± 13.4) years

• Gender, M/F: 15/9

• BMI, mean (SD): 24.0 (± 2.9) kg/m²

• APACHE II: not reported

• PaCO₂, mean (SD): 38.2 (± 7.8) mmHg

• PaO₂/FiO₂, mean (SD): 332.9 (± 112.9) mmHg

Interventions

Cross‐over study design, participants received each of two therapies for 20 minutes each:

• HFNC: oxygen delivered using OmniOx System, initial gas flow rate at 35 L/min with FiO₂ at 35% mmHg, then adjusted at discretion of the physician. One participant only received 15 L/min.

• Oxygen via conventional nasal cannula: no additional details

Randomized, n = 26; losses, n = 2 (withdrew consent); analysed, n = 24

Outcomes

Flow rates; tidal volumes; comfort (10‐point scale)

Note: we did not report outcome data in the review because study authors did not include outcome data from the first period.

Notes

Funding/declarations of interest: Draeger provided EIT monitor. Study author declared no potential conflict of interest, and funder had no role in the design, collection, analysis or interpretation of the study.

Study dates: 1 October 2014 to 28 February 2015

Note: we did not conduct 'Risk of bias' assessments for this study because we did not report outcome data in the review.

Study characteristics

Methods

RCT, parallel‐group design, multicentre study

Participants

Total number of participants: 102

Setting: 4 ICUs; France

Inclusion criteria: consecutive immunocompromised patients admitted to ICU for acute respiratory failure, aged > 18 years

Exclusion criteria: hypercapnia (> 45 mmHg), mechanical ventilation before ICU admission, need for immediate NIV or invasive mechanical ventilation, and patient refusal to participate in study

Baseline characteristics:

Intervention group (HFNC):

• Age, median (IQR): 59.3 (43 to 70) years

• Gender, M/F: 38/14

• BMI mean (SD): not reported

• SAPS II, median (IQR): 42 (29.5 to 52)

• SOFA, median (IQR): 3.5 (2 to 6)

• PaCO₂: not reported

• PaO₂/FiO₂, median (IQR): 128 (48 to 178) mmHg

• Respiratory rate, median (IQR): 26 (21.7 to 31.2) breaths/min

Control group (standard oxygen therapy):

• Age, median (IQR): 64.5 (53.25 to 72) years

• Gender, M/F: 32/16

• BMI mean (SD): not reported

• SAPS II, median (IQR): 37.5 (31.5 to 46.5)

• SOFA, median (IQR): 3 (2 to 5)

• PaCO₂: not reported

• PaO₂/FiO₂ median (IQR): 100 (40 to 156) mmHg

• Respiratory rate median (IQR): 27 (22 to 32.2) breaths/min

Interventions

Intervention group:

• Randomized, n = 53; losses, n = 1 (1 withdrew consent); analysed, n = 52

• Details: HFNC; heated, humidified circuit, with initial flow of 40 to 50 L/min; FiO₂ 100%, which was then adjusted to maintain SpO₂ ≥ 95 %

Control group

• Randomized, n = 49; losses, n = 1 (1 withdrew consent); analysed, n = 48

• Details: Venturi mask; FiO₂ initially 60%, 15 L/min, then adjusted to maintain SpO₂ ≥ 95%

Participants were randomly allocated to oxygen therapy groups for a 2‐hour period.

Outcomes

Need for invasive mechanical ventilation or NIV during or at the end of the 2‐hour study period; VAS scores for comfort, thirst, and dyspnoea (all at 120 minutes); respiratory rate (at 120 minutes); heart rate

Notes

Funding/declarations of interest: Fisher & Paykel Healthcare Ltd provided oxygen delivery devices and funds for study insurance and presentation of results. The sponsors had no role in designing or conducting the study.

Study dates: November 2012 to April 2014

Note: we noted some differences in baseline characteristics but these were not clinically significant.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Participants described as randomly allocated, with stratification on study centre by permuted block method

Allocation concealment (selection bias)

Low risk

Use of opaque, sealed envelopes to ensure identity concealment

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinding was not possible. Although we expected that this would not influence outcome data, we could not be certain of this.

Blinding of outcome assessors (objective outcomes)

Low risk

Blinding of outcome assessors was not described; we did not anticipate that this would influence the assessment of objective outcome measures.

Blinding of outcome assessors (subjective measures)

Low risk

Standardized approach to measuring subjective outcomes of comfort, thirst and dyspnoea: we did not anticipate that this would influence the assessment of these outcomes.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Loss of two participants after randomization due to withdrawal of consent. Low number, unlikely to influence results

Selective reporting (reporting bias)

Unclear risk

NCT02424773. Retrospective registration in April 2015. Therefore, not feasible to judge if any reporting bias. All outcomes reported from methods section

Other bias

Low risk

We identified no other risks of bias.

Study characteristics

Methods

RCT, cross‐over design. Multicentre study

Participants

Total number of randomized participants: 32

Setting: 2 ICUs; Italy

Inclusion criteria: COPD, NIV > 24 hours; fully co‐operative; pH ≥ 7.35 during NIV; respiratory rate ≤ 30 breaths/min; improvement of condition (no dyspnoea, no agitation, no fever)

Exclusion criteria: diaphragm paralysis; clinical signs of distress or impending respiratory muscle failure; haemodynamic instability; life‐threatening cardiac arrhythmia; ECG signs of ischaemia; impaired renal function; inclusion in other studies; refusal to consent

Baseline characteristics (overall, for analysed participants only):

• Age, mean (SD): 72.5 (± 8.2) years

• Gender, M/F: 17/13

• BMI, mean (SD): not reported

• SAPS II, mean (SD) : 31.5 (± 6.2)

• PaCO₂, mean (SD): not reported

• PaO₂/FiO₂, mean (SD): not reported

Interventions

Cross‐over study design, with 30 minutes for each 5 intervention stages. Three intervention stages, which were all NIV, were not randomized. Two randomized interventions were given as interruptions to the NIV stages:

• HFNO delivered using Optiflow via nasal cannula connected to a heated humidifier (MR850)

• Standard oxygen treatment using Venturi mask

Randomized participants, n = 32; losses, n = 2 (insufficient ultrasound imaging quality); analysed, n = 30

Outcomes

Evaluation of right hemidiaphragm; respiratory rate; pH; PaO₂; PaCO₂; comfort (using 11‐point NRS)

Note: we did not include outcome data in the review because study authors did not report outcome data from the first period.

Notes

Funding/declarations of interest: some authors received fees or institutional funding from one or more of the following: Chiesi; AIM ITALY SRL; Fisher and Paykel Healthcare Ltd; Maquet Critical Care; Draeger; Intersurgical SpA; Orionpharma; Phils; Resmed; Merck Sharp and Dohme; Novartis

Study dates: December 2015 to March 2017

Note: we did not complete 'Risk of bias' assessments for this study because we did not report outcome data in the review.

Study characteristics

Methods

RCT, parallel‐group design. Multicentre study

Participants

Total number of participants: 105

Setting: 2 ICUs; Rome and Novara, Italy

Inclusion criteria: patients who were mechanically ventilated for longer than 24 hours, passed a spontaneous breathing trial, PaO₂/FiO₂ ratio < 300 at the end of the trial

Exclusion criteria: tracheostomy, age < 18 years, pregnancy, anticipated need for non‐invasive ventilation after extubation

Baseline characteristics:

Intervention group (HFNC):

• Age mean (SD): 65 (± 18) years

• Gender, M/F: 33/20

• BMI, mean (SD): not reported

• SAPS II, mean (SD): 43 (± 14)

• PaCO₂ mean (SD): 34.7 (± 7.6) mmHg

• PaO₂/FiO₂ mean (SD): 239.4 (± 42.4) mmHg

• Respiratory rate mean (SD): 23 (± 5) breaths/min

Control group (standard oxygen therapy):

• Age mean (SD): 64 (± 17) years

• Gender, M/F: 35/17

• BMI, mean (SD): not reported

• SAPS II, mean (SD): 44 (± 16)

• PaCO₂ mean (SD): 36 (± 7.1) mmHg

• PaO₂/FiO₂ mean (SD): 241.7 (± 51.1) mmHg

• Respiratory rate mean (SD): 23 (6) breaths/min

Interventions

Intervention group (HFNC):

• Randomized, n = 53; losses, n = 0; analysed, n = 53

• Details: flow = 50 L/min. Optiflow, Fisher & Paykel Healthcare, Auckland, New Zealand

Control group (Venturi mask):

• Randomized, n = 52; losses, n = 0; analysed, n = 52

• Details: Venturi mask to deliver predetermined FiO₂

Both used after extubation. FiO₂ was set to obtain SpO₂ 92% to 98% (88% to 95% in COPD). Applied for 48 hours or until ICU discharge

Outcomes

Arterial blood gas, SaO₂, FiO₂, PaO₂/FiO₂ ratio, respiratory rate, MAP, heart rate, and discomfort (recorded at 1, 3, 6, 12, 24, 36, and 48 hours), PaCO₂ at 3 hours. Adverse events (displacement of oxygenation device, oxygen desaturation post‐extubation requiring NIV or endotracheal intubation). ICU length of stay and mortality

Note: we did not include data for SaO₂ because these data were presented in figures which we could not clearly translate into numerical data.

Notes

Funding/declarations of interest: supported by an unrestricted research grant from Fisher & Paykel Healthcare Ltd and by an independent research grant

Study dates: November 2010 to April 2011

Note: there are 3 secondary references to this study (conference reports).

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

A unique random number sequence that was computer generated

Allocation concealment (selection bias)

Unclear risk

Participants were randomly assigned, using a block size of 30, to Optiflow or Venturi mask in a blinded fashion with opaque envelopes ‐ no specific mention as to whether the envelopes were consecutively numbered.

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Blinding was not possible. Although we expected that this would not influence outcome data, we could not be certain of this.

Blinding of outcome assessors (objective outcomes)

Low risk

Database monitored by independent third parties, analysis performed as agreed before commencement of the study. However, we assumed that outcome assessors were not blinded; we did not anticipate that this would influence the assessment of objective outcome measures.

Blinding of outcome assessors (subjective measures)

Low risk

Participants were the outcome assessors for discomfort using a standardized visual scale: we did not expect this to influence the outcome data.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No apparent losses

Selective reporting (reporting bias)

Low risk

NCT01575353. Retrospectively registered in December 2010 (but only shortly before start of recruitment). All outcomes reported as stated in protocol. Length of stay and mortality rates reported but not previously stated in protocol

Other bias

Unclear risk

Multiple interim analyses performed (3 abstracts presented from same study)

Study characteristics

Methods

RCT, cross‐over design. Single‐centre study

Participants

Total number of randomized participants: 17

Setting: ICU; Italy

Inclusion criteria: non‐intubated people with AHRF admitted to the ICU; new or worsening respiratory symptoms following a known clinical insult lasting < 1 week; PaO₂/FiO₂ ≤ 300 mmHg while receiving additional oxygen; evidence of pulmonary infiltrates

Exclusion criteria: < 18 years of age; presence of tracheostomy; pregnancy or breastfeeding; haemodynamic instability; evidence of pneumothorax; respiratory failure explained by cardiac failure or fluid overload; severe COPD; history of nasal trauma and/or deviated nasal septum; altered mental status; contraindications to EIT; impossibility to position the EIT belt or position the oesophageal pressure catheter

Baseline characteristics (overall):

• Age, mean (SD): 62 (± 10) years

• Gender, M/F: 8/9

• BMI, mean (SD): not reported

• SAPS II, mean (SD): 48 (± 13)

• SOFA score, mean (SD): 11 (± 3)

• PaCO₂, mean (SD): not reported

• PaO₂/FiO₂, mean (SD): 167 (± 46) mmHg

Interventions

Cross‐over study design, with each phase lasting 20 minutes. Washout period was not specified (but not relevant to this review as we were considering only data from the first study period).

• HFNC: gas flow at 30 L/min

• HFNC: gas flow at 45 L/min

• HFNC: gas flow at 60 L/min

• Standard non‐occlusive oxygen facemask: gas flow at 12 L/min

HFNC was delivered through specific nasal prongs to fit the size of the nostrils. FiO₂ to achieve target SpO₂ of 90 to 95%

Outcomes

Blood gas analysis (PaO₂; PaO₂/FiO₂; PaCO₂); respiratory rate; haemodynamics

Note: we did not report any outcome data from this study, because study authors did not report data from the first period.

Notes

Funding/declarations of interest: funding not reported. Study authors declared no competing interests.

Study dates: not reported

Study characteristics

Methods

RCT, cross‐over design. Single‐centre study

Participants

Total number of randomized participants: 15

Setting: general ICU; Italy

Inclusion criteria: people with new or acutely worsening respiratory symptoms following a known clinical insult lasting < 1 week; PaO₂/FiO₂ ≤ 300 mmHg while receiving additional oxygen by a standard face mask

Exclusion criteria: age < 18 years; intubation or tracheostomy; pregnancy or breastfeeding; haemodynamic instability; pneumothorax; acute cardiogenic pulmonary oedema; COPD; history of nasal trauma and/or deviated nasal septum; contraindication to EIT use (e.g. patient with implantable defibrillator); impossibility to position the EIT belt (e.g. wound dressings or chest drains); impossibility to position the oesophageal pressure catheter (e.g. oesophageal surgery)

Baseline characteristics (overall):

• Age, mean (SD): 60 (± 14) years

• Gender, M/F: 9/6

• BMI, mean (SD): not reported

• SAPS II, mean (SD): 38 (± 9)

• PaCO₂, mean (SD): not reported

• PaO₂/FiO₂, mean (SD): 130 (± 35) mmHg

Interventions

Cross‐over study with each study phase lasting for 20 minutes.

• HFNC: via AIRVO 2, gas flow at 40 L/min

• standard non‐occlusive oxygen facial mask, with gas flow set at 12 L/min

FiO₂ to achieve SpO₂ between 90% and 95%

Outcomes

Arterial blood gases; respiratory rate; haemodynamics; EIT parameters

Note: we did not include outcome data in the review because the study authors did not report outcome data from the first study period.

Notes

Funding/declarations of interest: institutional funding of the Department of Medicine, University of Milan‐Bicocca, Monza, Italy. Fisher and Paykel Healthcare, Auckland, New Zealand, provided the device and disposables to deliver high‐flow nasal cannula therapy free of charge but had no role in the conception, design and conduct of the study, data analysis, and writing of the manuscript. The authors reported no conflicts of interest.

Study dates: not specified

Study characteristics

Methods

RCT, parallel‐group design. Single‐centre study

Participants

Total number of randomized participants: 56

Setting: cardiothoracic and vascular ICU; Auckland, New Zealand

Inclusion criteria: patients in a cardiothoracic and vascular ICU with mild to moderate hypoxaemic respiratory failure defined by study authors as follows: receiving ≥ 4 L/min of oxygen via nasal cannula for longer than 4 hours and/or respiratory rate ≥ 25 breaths/min and/or increased work of breathing, evidenced by clinical signs such as dyspnoea, in‐drawing, accessory muscle use, and diaphoresis; or receiving ≥ 6 L/min of oxygen via face mask for longer than 2 hours, or respiratory rate ≥ 25 breaths/min, or both, or increased work of breathing, as evidenced by clinical signs such as dyspnoea, in‐drawing, accessory‐muscle use, and diaphoresis, or both

Exclusion criteria: patients requiring imminent mechanical ventilation and those under orders to not receive mechanical ventilation

Baseline characteristics:

Intervention group (HFNC):

• Age, mean (range): 64 (39 to 83) years

• Gender, M/F: 23/4

• BMI, mean (SD): not reported

• APACHE II, mean (range): 12 (5 to 25)

• PaCO₂, mean (SD): 43 (± 7) mmHg

• PaO₂/FiO₂: not reported

• Respiratory rate, mean (SD): 21 (± 7) breaths/min

Control group (standard oxygen therapy):

• Age, mean (range): 64 (26 to 85) years

• Gender, M/F: 21/8

• BMI, mean (SD): not reported

• APACHE II, mean (range): 12 ( 1 to 21)

• PaCO₂, mean (SD): 42 (± 7) mmHg

• PaO₂/FiO₂: not reported

• Respiratory rate, mean (SD): 18 (± 8) breaths/min

Interventions

Intervention group (HFNC):

• Randomized, n = 30; losses, n = 1 (refused consent); analysed, n = 29

• Details: HFNC; Optiflow, Fisher & Paykel Healthcare, with MR880 humidifier, RT241 heated delivery tube, and RT033 large/RT034 small, wide‐bore nasal cannula; therapy commenced at an initial flow of 35 L/min; flow and FiO₂ titrated to SpO₂ or SaO₂ of 95%. Duration of oxygen therapy not reported

Control group (standard oxygen therapy):

• Randomized, n = 30; losses, n = 3 (1 refused consent, 2 failed screening); analysed, n = 27

• Details: HFFM (standard face mask, MR850 humidifier, RT308 heated delivery tube and air entrainer, Fisher & Paykel Healthcare) with an aerosol mask (HudsonRCI, TFX Medical, High Wycombe, UK); flow rate ≤ 15 L/min; humidified oxygen delivered at 31° C and 32 mg H₂O/L; titrated to an SpO₂ or SaO₂ 95%. Duration of oxygen therapy not reported

Outcomes

Assessment score, arterial blood gas values, SpO₂, respiratory rate, and heart rate at baseline, 30 minutes, 1 hour, 2 hours, and 4 hours after randomization, then as per unit protocol. Continuous SpO₂ data and instances of desaturation (SpO₂ 93% for longer than 5 seconds) were collected. Episodes were discounted if the SpO₂ trace indicated signal interference or signal loss. Allocated therapy was considered successful if participants were maintained on or were weaned from their assigned oxygen therapy within 24 hours of enrolment. Failure of therapy was defined as worsening respiratory failure that required a change in the respiratory support device within 24 hours of study enrolment.

Notes

Funding/declarations of interest: Fisher & Paykel Healthcare Ltd consulted regarding study design and data analysis, and paid for statistical analysis.

Study dates: not reported

Note: some additional outcome data retrieved through email contact with study authors

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Random numbers table

Allocation concealment (selection bias)

Unclear risk

Opaque sealed envelopes but no mention of whether numbered or not

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Blinding was not possible. Although we expected that this would not influence outcome data, we could not be certain of this.

Blinding of outcome assessors (objective outcomes)

Low risk

Blinding of outcome assessors was not described; we did not anticipate that this would influence the assessment of objective outcome measures.

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Of 60 enrolled in the study, 4 participants (1 from the HFNC group, and 3 from the HFFM group) were excluded: 2 refused consent for all data collection and 2 failed the screening. Five of 27 participants in the high‐flow face mask group were switched to nasal high flow ‐ no mention of how these data were treated

Selective reporting (reporting bias)

High risk

ACTRN012606000139572. Prospective registration in April 2006. Published study reported additional outcomes (to include respiratory failure) that were not stated in trial registration records; this may indicate selective reporting bias for these outcomes.

Other bias

Low risk

We noted no other sources of bias.

Study characteristics

Methods

RCT, parallel‐group design. Single‐centre

Participants

Total number of randomized participants: 340

Setting: ICU; Auckland, New Zealand

Inclusion criteria: undergoing elective cardiac surgery utilizing cardiopulmonary bypass were eligible for inclusion in this study if ≥ 18 years of age and undergoing surgery involving full median sternotomy

Exclusion criteria: contraindication to HFNC, e.g. presence of a nasal septal defect, and previous recruitment

Baseline characteristics:

Intervention group (HFNC):

• Age, median (range): 65 (19 to 88) years

• Gender, M/F: 129/40

• BMI, mean (SD): 28.4 (± 5.3) kg/m²

• APACHE II, mean (SD): not reported

• PaCO₂: not reported

• PaO₂/FiO₂: not reported

• Respiratory rate, mean (SD): 16.6 (± 1.9) breaths/min

Control group (simple face mask):

• Age, median (range): 66 (21 to 87) years

• Gender, M/F: 129/42

• BMI, mean (SD): 29.2 (± 5.5) kg/m²

• APACHE II, mean (SD): not reported

• PaCO₂: not reported

• PaO₂/FiO₂: not reported

• Respiratory rate, mean (SD): 16.5 (± 1.7) breaths/min

Interventions

Intervention group:

• Randomized, n = 170; losses, n = 1 (consent withdrawn); analysed, n = 169

• Details: HFNC; Optiflow system; flow rate 45 L/min

Control group:

• Randomized, n = 171; losses, n = 0; analysed, n = 171

• Details: Simple face mask; oxygen at 2 to 4 L/min via simple face mask or nasal prongs; FiO₂ in both groups was titrated to maintain SpO₂ > 93%.

Oxygen therapy started after extubation.

Outcomes

Number of participants with SpO₂/FiO₂ ratio ≥ 445 on day 3 after cardiac surgery; atelectasis score of chest X‐rays; spirometry; re‐admission to ICU for respiratory causes; ICU and hospital length of stay; duration of respiratory support; mortality; incidence of respiratory complications on day 28; respiratory rate; oxygenation; use of adjunctive respiratory support therapies; escalation of respiratory support; adverse events; patient comfort

Notes

Funding/declarations of interest: Study authors declared that research was supported by an unrestricted grant from Fisher & Paykel Healthcare Ltd, but that the sponsors had no part in the study design and no access to trial data.

Study dates: not reported. Conducted over a 14‐month period

Note: some additional outcome data retrieved through email contact with study authors

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated random numbers in blocks of 12

Allocation concealment (selection bias)

Low risk

Sequentially numbered opaque envelopes prepared by non‐study staff

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Blinding was not possible. Although we expected that this would not influence outcome data, we could not be certain of this.

Blinding of outcome assessors (objective outcomes)

Low risk

Blinding of outcome assessors was not described; we did not anticipate that this would influence the assessment of objective outcome measures.

Blinding of outcome assessors (subjective measures)

Low risk

Participants were outcome assessors for comfort scores: we did not expect blinding to influence the assessment of these outcome data.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Attrition fully reported. Small number of losses

Selective reporting (reporting bias)

High risk

ACTRN12610000973011. Prospective registration in November 2010. Published study reported additional outcomes that were not stated in trial registration records (ICU and hospital length of stay, duration of respiratory support, oxygenation, escalation of respiratory support, adverse events); this may indicate selective reporting bias for these outcomes.

Other bias

Low risk

We identified no other sources of bias.

Study characteristics

Methods

RCT, cross‐over design. Single‐centre

Participants

Total number of randomized participants: 17

Setting: respiratory ICU; Bangkok, Thailand

Inclusion criteria: mechanically ventilated patients who were 18 years of age, successfully weaned by spontaneous breathing, trial with oxygen T‐piece or low level of pressure support for 120 minutes, and ready for endotracheal extubation

Exclusion criteria: haemodynamic instability or decreased level of consciousness; patients who lacked co‐operation, tracheotomized patients, and pregnant women

Baseline characteristics:

• Age, mean (SD): 66.8 (± 13.8) years

• Gender, M/F: 10/7

• BMI, mean (SD): not reported

• SAPS II, mean (SD): 30.9 (± 4.4)

• Respiratory rate, mean (SD): recorded before each cross‐over period: baseline 1: 20.3 (± 4.5); baseline 2: 21.7 (± 3.8) breaths/min

• PaCO₂: not reported

• PaO₂/FiO₂: not reported

Interventions

Intervention group (HFNC):

• Details: HFNC, Optiflow system, Fisher & Paykel Healthcare; initial inspiratory flow of 35 L/min, and FiO₂ adjusted to achieve SpO₂ ≥ 94% within the first 5 minutes and to maintain this setting for 30 minutes

Control group (standard oxygen therapy):

• Details: Non‐rebreather face mask, 6 to 10 L/min to achieve SpO₂ 94% for another 30 minutes

Outcomes

Dyspnoea, patient comfort, breathing frequency, heart rate blood pressure, SpO₂

Notes

Funding/declarations of interest: study authors did not report funding sources. They disclosed no conflicts of interest.

Study dates: August to December 2011

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Methods used to generate group allocation not stated

Allocation concealment (selection bias)

Unclear risk

Methods of allocation concealment not stated

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Blinding was not possible. Although we expected that this would not influence outcome data, we could not be certain of this.

Blinding of outcome assessors (objective outcomes)

Low risk

Unable to blind outcome assessors owing to nature of the intervention: we did not anticipate that this would influence the assessment of objective outcome measures.

Blinding of outcome assessors (subjective measures)

Low risk

Unable to blind outcome assessors owing to nature of the intervention. Participants were outcome assessors for comfort: We did not expect that this would influence the outcome data.

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

No statement of how many reported. No participant numbers in tables or graphs

Selective reporting (reporting bias)

Unclear risk

Trial registration not reported in paper. Unable to establish whether outcomes were reported according to pre‐published protocol or trial registration documents

SpO₂ and mean arterial pressure not reported for all time points set out in methods

Other bias

Low risk

We identified no other risks of bias.

Study characteristics

Methods

RCT, cross‐over design. Single‐centre study

Participants

Total number of randomized participants: 14

Setting: medical ICU; Germany

Inclusion criteria: patients with hypoxic respiratory failure (PaO₂ < 55 mmHg under room air)

Exclusion criteria: ventilatory failure, haemodynamic instability, cardiogenic pulmonary oedema, non‐invasive ventilation contraindications, inability to co‐operate

Baseline characteristics (recorded before each cross‐over period)

• Age, mean (SD): 55.9 (± 20.36) years

• Gender, M/F: not reported

• BMI, mean (SD): 26.71 (± 3.99) kg/m²

• SAPS II, mean (SD): 41.21 (± 11.78)

• PaCO₂, mean (SD): baseline 1: 36 (± 5); baseline 2: 38 (± 5); baseline 3: 37 (± 5)

• PaO₂/FiO₂: not reported

• Respiratory rate, mean (SD): baseline 1: 28 (± 9); baseline 2: 28 (± 9); baseline 3: 26 (± 7) (breaths/min)

Interventions

Participants were treated in randomized order for 30 minutes.

Intervention group (HFNC):

• Details: HFNC, Optiflow system, Fisher & Paykel Healthcare; oxygen flow 55 L/min; FiO₂ 0.6, using active respiratory gas humidifier

Control group one (standard oxygen therapy):

• Details: Venturi mask, Oxygen flow 15 L/min; FiO₂ 0.6

Control group two (NIV):

• Details: Non‐invasive ventilation, Intensive care ventilators in pressure support mode; PEEP set to 5 cm H₂O; pressure support above PEEP adjusted individually to achieve tidal volume of 6 to 8 mL/kg ideal body weight; FiO₂ 0.6

Each treatment phase was preceded by a 15‐minute baseline phase during which participants received oxygen via a standard nasal prong (oxygen flow 4 to 12 L/min, SaO₂ goal ≥ 88%).

Outcomes

PaO₂, respiratory rate, dyspnoea (Borg scale), discomfort (10‐point scale), PaCO₂, heart rate, blood pressure, SpO₂, global rating, patient preference

Note: we did not include outcome data in the review because the study authors did not report outcome data from the first study period.

Notes

Funding/declarations of interest: Fisher & Paykel Healthcare Ltd provided 2 Optiflow devices at no charge for the study. Investigators received no financial support and manufacturer had no part in study design, conduct, analysis, reporting, or publication.

Study dates: March 2009 to March 2011

Study characteristics

Methods

RCT, parallel‐group design. Single‐centre study

Participants

Total number of randomized participants: 70

Setting: ICU; Saudi Arabia

Inclusion criteria: adults with interstitial lung diseases and acute respiratory failure; with PaO₂/FiO₂ ≤ 300 mmHg despite oxygen supplementation at a flow rate ≥ 10 L/min for at least 15 minutes or manifestation of increased work of breathing

Exclusion criteria: < 18 years of age; pneumothorax, absolute indication for urgent intubation like coma; contraindication to NIV

Baseline characteristics:

Intervention group (HFNC):

• Age, mean (SD): 61.3 (± 13) years

• Gender, M/F: 11/23

• BMI, mean (SD): 22.9 (± 4.1) kg/m²

• APACHE II, mean (SD): 14.9 (± 4.12)

• PaCO₂, mean (SD): 38.8 (± 3.4) mmHg

• PaO₂/FiO₂, mean (SD): 178 (± 55) mmHg

Control group (NIV):

• Age, mean (SD): 60.95 (± 12) years

• Gender, M/F: 14/22

• BMI, mean (SD): 24.3 (± 3.7) kg/m²

• APACHE II, mean (SD): 15.2 (± 3.9)

• PaCO₂, mean (SD): 39.1 (± 2.6) mmHg

• PaO₂/FiO₂, mean (SD): 166 (± 42) mmHg

Interventions

Intervention group (HFNC):

• Randomized, n = 34; losses, n = 0; analysed, n = 34

• Details: oxygen delivered via Optiflow, using a large‐diameter nasal cannula. Therapy until the participant recovered or was intubated

Control group (NIV):

• Randomized, n = 36; losses, n = 0; analysed, n = 36

• Details: NIV using BiPAP Vision. Continuous positive airway pressure mode initiated for NIV, gradually incremented to 12 cm H₂O. Pressure support for respiratory acidosis of if respiratory rate > 30 breaths/min. FiO₂ adjusted at lowest level to maintain PaO₂ > 60 mmHg

Outcomes

Intubation within 28 days; ICU mortality; number of days without need for invasive MV within 28 days

Notes

Funding/declarations of interest: no funding. Study authors declared no conflicts of interest.

Study dates: January 2016 to May 2017

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Described as randomized, but no additional details

Allocation concealment (selection bias)

Unclear risk

No details

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Blinding was not possible. Although we expected that this would not influence outcome data, we could not be certain of this.

Blinding of outcome assessors (objective outcomes)

Low risk

Blinding of outcome assessors was not described; we did not anticipate that this would influence the assessment of objective outcome measures.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No losses

Selective reporting (reporting bias)

Unclear risk

Study authors did not report clinical trials registration or prepublished protocol. It was not feasible to effectively assess risk of selective reporting bias without these documents.

Other bias

Low risk

We identified no other sources of bias.

Study characteristics

Methods

RCT, parallel‐group design; single‐centre study

Participants

Total number of randomized participants: 60

Setting: ICU; China

Inclusion criteria: people with acute respiratory failure, mechanically ventilated in the ICU for at least 48 hours and were ready to be extubated after clinical weaning assessments

Exclusion criteria: poor co‐operation; tracheotomy; decreased level of consciousness; < 18 years of age; pregnant; did not sign consent form

Baseline characteristics:

Intervention group (HFNC):

• Age, mean (SD): 66 (± 14) years

• Gender, M/F: 16/14

• BMI, mean (SD): not reported

• APACHE II, mean (SD): 12.87 (± 3)

• PaCO₂, mean (SD): 41.5 (± 6.7) mmHg

• PaO₂/FiO₂, mean (SD): not reported

Control group (NIV):

• Age, mean (SD): 71 (± 13) years

• Gender, M/F: 18/12

• BMI, mean (SD): not reported

• APACHE II, mean (SD): 12.36 (± 3.29)

• PaCO₂, mean (SD): 42.3 (± 7.1) mmHg

• PaO₂/FiO₂, mean (SD): not reported

Interventions

Intervention group (HFNC):

• Randomized, n = 30; losses, n = 0; analysed, n = 30

• Details: HFNC via PT101AZ, initial flow rate at 60 L/min with downward adjustments in 5 to 10 L/min decrements; target SpO₂ of 94% to 98% (or 88% to 92% for hypercapnic respiratory failure); FiO₂ set at 40%

Control group:

• Randomized, n = 30; losses, n = 0; analysed, n = 30

• Details: oxygen via air entrainment mask, with flow rate at 10 L/min; target SpO₂ of 94% to 98% (or 88% to 92% for hypercapnic respiratory failure); FiO₂ set at 40%

Outcomes

Success of oxygen therapy; needing NIV, or MV, or replacement of oxygen device; respiratory variables (PaO₂; SpO₂; PaCO₂; respiratory rate): haemodynamic variables; discomfort (scale 0 to 10 = no discomfort to maximum discomfort)

Notes

Funding/declarations of interest: funded by grants from the National Natural Science Foundation of China, the Medical and Health Research Program of Zhejiang Province, and the Medical and Health Research Program of Zheijing Province

Study dates: January 2013 to December 2014

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated randomization

Allocation concealment (selection bias)

Unclear risk

No details

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Blinding was not possible. Although we expected that this would not influence outcome data, we could not be certain of this.

Blinding of outcome assessors (objective outcomes)

Low risk

Blinding of outcome assessors was not described; we did not anticipate that this would influence the assessment of objective outcome measures.

Blinding of outcome assessors (subjective measures)

Low risk

Participants were outcome assessors for discomfort using a standardized scale; we did not expect that this would influence the outcome data.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No apparent losses

Selective reporting (reporting bias)

Unclear risk

Study authors did not report clinical trials registration or prepublished protocol. It was not feasible to effectively assess risk of selective reporting bias without these documents.

Other bias

Low risk

We identified no other sources of bias.

Study characteristics

Methods

RCT, parallel‐group design, multicentre study

Participants

Total number of randomized participants: 830

Setting: 6 ICUs; France

Inclusion criteria: patients who had undergone cardiothoracic surgery and had failed a SBT, or had pre‐existing risk factors for post‐extubation acute respiratory failure, or had failed extubation

Exclusion criteria: obstructive sleep apnoea, tracheostomy, do‐not‐intubate status, delirium, nausea and vomiting, bradypnoea, impaired consciousness, haemodynamic instability

Baseline characteristics

Intervention group (HFNC):

• Age, mean (95% CI): 63.8 (62.5 to 65.2) years

• Gender M/F: 273/141

• BMI, mean (95% CI): 28.3 (27.8 to 28.8) kg/m²

• SAPS II, mean (95% CI): 29.0 (27.8 to 30.1)

• PaCO₂,mean (95% CI): 38.7 (38.1 to 39.4) mmHg

• PaO₂/FiO₂, mean (95% CI): 196 (187 to 204) mmHg

• Respiratory rate, mean (95% CI): 22.8 (22.1 to 23.5) breaths/min

Control group (BiPAP):

• Age, mean (95% CI): 63.9 (62.6 to 65.2) years

• Gender, M/F: 278/138

• BMI, mean (95% CI): 28.2 (27.6 to 28.7) kg/m²

• SAPS II, mean (95% CI): 28.8 (27.7 to 30.0)

• PaCO₂, mean (95% CI): 39.1 (38.4 to 39.8) mmHg

• PaO₂/FiO₂, mean (95% CI): 203 (195 to 212) mmHg

• Respiratory rate, mean (95% CI): 23.3 (22.6 to 24.0) breaths/min

Interventions

Intervention group (HFNC):

• Randomized, n = 414; losses, n = 0; analysed, n = 414

• Details: HFNC; Optiflow system at initial flow rate of 50 L/min. Delivered continuously

Control group (NIV: BiPAP):

• Randomized, n = 416; losses, n = 0; analysed, n = 416

• Details: BiPAP; pressure support started at 8 cm H₂O to achieve exhaled tidal volume of 8 mL/kg and respiratory rate < 25 breaths per minute, via full face mask and ventilator specifically designed for BiPAP or an ICU ventilator. BiPAP was delivered for 2 hours initially, then for approximately 1 hour every 4 hours, or more if needed.

Initial FiO₂ in both groups was 50%, adjusted to maintain SaO₂ at 92% to 98%

Outcomes

Treatment failure (defined as reintubation for MV, switch to other study treatment, or premature study treatment discontinuation), duration of respiratory support, respiratory variables, dyspnoea, comfort, skin breakdown, respiratory and extrapulmonary complications, number of bronchoscopies, mortality in ICU

Note:

• respiratory variables and respiratory rate reported at baseline, 1 hour, and 6 to 12 hours. For meta‐analysis in the review, data were taken at 6 to 12 hours.

• we did not include data for duration of respiratory support because of differences in method of use, with HFNC used continuously and BiPAP used for approximately one hour at four‐hourly windows.

Notes

Funding/declarations of interest: study authors did not report any funding sources. They disclosed no conflicts of interest.

Study dates: June 2011 to January 2014

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated random sequence in blocks of 2 or 4

Allocation concealment (selection bias)

Unclear risk

Use of opaque envelopes but no further details

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Blinding was not possible. Although we expected that this would not influence outcome data, we could not be certain of this.

Blinding of outcome assessors (objective outcomes)

Low risk

Blinding of outcome assessors was not described; we did not anticipate that this would influence the assessment of objective outcome measures.

Blinding of outcome assessors (subjective measures)

Low risk

Participants were outcome assessors for dyspnoea and comfort; we did not expect this to influence the outcome data. We did not know if outcome assessors for skin breakdown and other complications were blinded, however, complications were predefined to reduce bias.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No losses

Selective reporting (reporting bias)

Low risk

NCT01458444. Study registered retrospectively in October 2011 (although early in study period). All relevant outcomes were reported as stated in protocol.

Other bias

Low risk

No other sources of bias identified

Study characteristics

Methods

RCT, cross‐over design. Single‐centre study

Participants

Total number of randomized participants: 12

Setting: ICU; France

Inclusion criteria: people with AHRF

Exclusion criteria: people with tracheostomies; < 18 years of age; chronic retention of CO₂; respiratory acidosis; factors related to insertion of an oesophageal catheter; excessive amounts of respiratory secretions; SBP < 90 mmHg; ventricular arrhythmia; encephalopathy or coma; life‐threatening hypoxaemia; decision to limit life‐support treatments in the ICU

Baseline characteristics (overall):

• Age, median (IQR): 63 (59 to 73) years

• Gender, M/F: 10/2

• BMI, mean (SD): not reported

• SAPS II, median (IQR): 48 (35 to 56)

• PaCO₂: not reported

• PaO₂/FiO₂, median (IQR): 178 (157 to 199) mmHg

Interventions

Cross‐over study with each period lasting approximately 20 minutes. All participants were first given conventional oxygen therapy using a non‐rebreather face mask; participants were not randomized to this group.

Intervention group (HFNC):

• Randomized, n = 12; losses, n = 0; analysed, n = 12

• Details: HFNC via Optiflow, with largest cannula tolerated by the individual participants, gas flow set at 60 L/min, temperature set at 37 °C

Control group (NIV: BiPAP):

• Randomized, n = 12; losses, n = 0; analysed, n = 12

• Details: BiPAP fitted to a face mask. CPAP set at 5 cm H₂O

Outcomes

Oesophageal pressure; blood gas analysis and haemodynamic variables; comfort and dyspnoea

Note: we did not include outcome data in the review because the study authors did not report outcome data from the first study period.

Notes

Funding/declarations of interest: supported by a research grant from Fisher & Paykel Healthcare Ltd

Study dates: January 2011 to January 2012

Study characteristics

Methods

RCT, parallel‐group design. Single‐centre study

Participants

Total number of randomized participants: 98

Setting: ICU; France

Inclusion criteria: ≥ 18 years of age; admitted to the ICU after CABG presenting with severe hypoxaemia after extubation

Exclusion criteria: pregnancy; chronic respiratory failure; combined cardiac surgery; alteration of consciousness or requiring immediate intubation; surgical complications requiring re‐operation; haemodynamic instability or ventricular arrhythmia; adults subject to legal protection; already participating in an interventional study on oxygenation

Baseline characteristics:

Intervention group (HFNC):

• Age, mean (SD): 67.6 (± 9.4) years

• Gender, M/F: 36/7

• BMI, mean (SD): 28.7 (± 3.8) kg/m²

• SAPS II, mean (SD): 26.9 (± 9.4)

• PaCO₂, mean (SD): 39.8 (± 4.5) mmHg

• PaO₂/FiO₂, mean (SD): 131.5 (± 27.7) mmHg

Control group:

• Age, mean (SD): 65.8 (± 10.1) years

• Gender, M/F: 41/8

• BMI, mean (SD): 29.7 (4.5) kg/m²

• SAPS II, mean (SD): 26.4 (± 6.0)

• PaCO₂, mean (SD): 40.5 (± 3.8) mmHg

• PaO₂/FiO₂, mean (SD): 147.7 (± 30.7) mmHg

Interventions

Intervention group (HFNC):

• Randomized, n = 49; losses, n = 8 (2 withdrew consent; 6 not included in per protocol analysis: 1 without severe hypoxaemia, 4 received control group therapy, 1 intubation before day 1); analysed, n = 47 in ITT; 41 in per protocol

• Details: after extubation, HFNC via Optiflow, with gas flow rate of 45 L/min, FiO₂ of 100% and adjusted according to the SpO₂, and temperature of 37 ºC. Device was switched every 6 hours to a Venturi mask to avoid hyperoxia.

Control group:

• Randomized, n = 49; losses, n = 8 (6 withdrew consent; 2 not included in per protocol analysis: 1 without severe hypoxaemia; 1 received intervention group therapy); analysed, n = 43 in ITT, 41 in per protocol

• Details: non‐rebreather facemask (Hudson RCI) with humidified oxygen, gas flow rate of 15 L/min, with FiO₂ of 100% and adjusted according to the SpO₂. No CPAP valve on the face mask. Device was switched every 6 hours to a Venturi mask to avoid hyperoxia.

Outcomes

PaO₂/FiO₂ (1, 6, 24 and 48 hours); PACO₂, respiratory rate and heart rate at 48 hours; treatment failure defined as SpO₂ < 96% despite treatment or respiratory rate ≥ 25 breaths/min; need for NIV or reintubation for treatment failure; increased work of breathing, or hypercapnia; tolerance of the device (satisfaction; occurrence of nasal bleeding; mucus dryness during therapy); radiologic score on chest X‐ray; mortality; length of stay in the ICU

Note: data were available as ITT and per protocol. We used the ITT data because these data were clearly reported by study authors.

Notes

Funding/declarations of interest: source of funding (a grant for research and innovation missions) was not specified. However, funding was allocated to the university sponsor and Fischer & Paykel; Fischer & Paykel did not participate in study design, conduct, data management or interpretation of the results. Individual authors declared personal fees and funding from LFB, Fischer & Paykel, Baxter, MSD, and Pfizer for other work.

Study dates: June 2011 to April 2015

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated randomization

Allocation concealment (selection bias)

Low risk

Randomization controlled by an independent research unit, allocation provided via opaque envelopes

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Blinding was not possible. Although we expected that this would not influence outcome data, we could not be certain of this.

Blinding of outcome assessors (objective outcomes)

Low risk

Blinding of outcome assessors was not described; we did not anticipate that this would influence the assessment of objective outcome measures.

Blinding of outcome assessors (subjective measures)

Low risk

Study was described as open‐label, and we assumed that participants were aware of their group allocation. We did not think that lack of blinding would influence participants' assessment of subjective measures.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

We noted losses in each group, however, these were clearly reported and reasonably balanced and we did not expect the losses to cause risk of attrition bias.

Selective reporting (reporting bias)

Unclear risk

Registration with a clinical trials register, or a prepublished protocol was not reported. It was not feasible to effectively assess risk of selective reporting bias without these reports.

Other bias

Low risk

We identified no other sources of bias.

Study characteristics

Methods

RCT, parallel‐group design. Multicentre study

Participants

Total number of randomized participants: 110

Setting: ICUs in 3 hospitals; China

Inclusion criteria: undergoing planned thoracoscopic lobectomy because of lung tumour, and at intermediate or high risk for postoperative pulmonary complications

Exclusion criteria: immunocompromised; pregnant; converted to an open thoracotomy because of poor visualization or bleeding; < 18 or > 80 years of age; informed consent could not be obtained

Baseline characteristics:

Intervention group (HFNC):

• Age, mean (SD): 56.31 (± 7.03) years

• Gender, M/F: 30/26

• BMI, mean (SD): 26.32 (± 4.73) kg/m²

• APACHE II, mean (SD): 26.32 (± 4.73)

• PaCO₂, mean (SD): 41.73 (± 6.33) mmHg

• PaO₂/FiO₂, mean (SD): 350.35 (± 33.87) mmHg

• Respiratory rate, mean (SD): 18.43 (± 3.45) breaths/min

Control group (standard oxygen therapy):

• Age, mean (SD): 55.82 (± 7.92) years

• Gender, M/F: 28/26

• BMI, mean (SD): 25.19 (± 5.02) kg/m²

• APACHE II, mean (SD): 25.19 (± 5.02)

• PaCO₂, mean (SD): 43.52 (± 4.93) mmHg

• PaO₂/FiO₂, mean (SD): 340.98 (± 40.65) mmHg

• Respiratory rate, mean (SD): 17.98 (± 3.87) breaths/min

Interventions

Intervention group (HFNC):

• Randomized, n = 56; losses, n = 0; analysed, n = 56

• Details: after extubation, after tolerating SBT, HFNC delivered by Optiflow (using MR850 heated humidifier and RT202 breathing circuit) with flow rate of 35 to 60 L/min, FiO₂ titrated by treating clinician to maintain SpO ² ≥ 95%

Control group:

• Randomized, n = 54; losses, n = 0; analysed, n = 54

• Details: after extubation, after tolerating SBT, oxygen delivered via nasal prongs or facemask with oxygen flow titrated by treating clinician to maintain SpO₂ ≥ 95%

Outcomes

Incidence of hypoxaemia in first 72 hours after extubation; PaO₂; PaO₂/FiO₂, SpO₂/FiO₂, and PaCO₂; postoperative pulmonary complications (pneumonia and atelectasis); AHRF (for which participants were initially given NIV with BiPAP and, if required, were then reintubated); adverse effects (air leak, throat or nasal pain, abdominal distension); mortality; length of ICU and hospital stay; total hospitalization expenditure

Note: we did not include data for arterial gases in the review, because study authors presented these data in figures that we could not clearly interpret as numerical data.

Notes

Funding/declarations of interest: funding not reported. Study authors declared no competing interests.

Study dates: January 2015 to June 2016

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Randomization using STATA statistical package

Allocation concealment (selection bias)

Unclear risk

No details

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Blinding was not possible. Although we expected that this would not influence outcome data, we could not be certain of this.

Blinding of outcome assessors (objective outcomes)

Low risk

Blinding of outcome assessors was not described; we did not anticipate that this would influence the assessment of objective outcome measures.

Blinding of outcome assessors (subjective measures)

Low risk

Blinding of outcome assessors was not described; we did not anticipate that this would influence the assessment of subjective outcome measures.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No participant losses

Selective reporting (reporting bias)

Unclear risk

Study authors did not report clinical trials registration or a prepublished protocol. It was not feasible to effectively assess risk of selective reporting bias without these documents.

Other bias

Low risk

We identified no other sources of bias.

Study characteristics

Methods

RCT, parallel‐group design. Single‐centre study

Participants

Total number of randomized participants: 100

Setting: ICU; UK

Inclusion criteria: scheduled for CABG; > 18 years of age; ≥ 1 patient‐related risk factor for postoperative pulmonary complications; capable of performing 6MWT

Exclusion criteria: contraindications to HFNC; needing CPAP preoperatively; did not meet criteria for extubation by 10 a.m. the day after surgery

Baseline characteristics:

Intervention group (HFNC):

• Age, mean (SD): 67.3 (± 9.3 ) years

• Gender, M/F: 30/19

• BMI, mean (SD): 32 (± 5.5) kg/m²

• APACHE II: not reported

• PaCO₂, mean (SD): not reported

• PaO₂/FiO₂, mean (SD): not reported

Control group (NIV):

• Age, mean (SD): 69.1 (± 11.1) years

• Gender, M/F: 28/11

• BMI, mean (SD): 30.2 (± 6.6) kg/m²

• APACHE II: not reported

• PaCO₂, mean (SD): not reported

• PaO₂/FiO₂, mean (SD): not reported

Interventions

Intervention group:

• Randomized, n = 51; losses, n = 2 (delayed extubation); analysed, n = 49

• Details: post‐extubation in the ICU. FiO₂ titrated to SpO₂ ≥ 95% (or 93% for those at risk of hypercapnic respiratory failure). Standard starting flow rate was 30 L/min, adjusted up or down within a range of 20 to 50 L/min with aim of respiratory rate of < 16 breaths/min and patient comfort. HFNO for 24 hours or longer if deemed necessary

Control group:

• Randomized, n = 49; losses, n = 3 (2 delayed extubation; 1 withdrew consent; procedure cancelled); analysed, n = 45

• Details: standard oxygen therapy via nasal prongs or soft facemask. FiO₂ titrated to SpO₂ ≥ 95% (or 93% for those at risk of hypercapnic respiratory failure). Oxygen therapy for 24 hours or longer if deemed necessary

Outcomes

Hospital length of stay; ICU length of stay; ICU re‐admission rate; in‐hospital mortality; escalation of respiratory support (unplanned CPAP, NIV or MV); pulmonary function tests; 6MWT; postoperative quality of recovery

Notes

Funding/declarations of interest: funded by AAGBI. Fisher and Paykel Healthcare Ltd provided equipment and were not involved in data collection, analysis, and writing the manuscript. One author has received educational funding, honoraria or travel assistance from CSL Behring, Massimo, Pharmacosmos, Fisher and Paykel, Brightwake Ltd and Vifor Pharma. No other declarations or competing interests declared

Study dates: not specified

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated randomization

Allocation concealment (selection bias)

Low risk

Use of a centralised online system

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Blinding was not possible. Although we expected that this would not influence outcome data, we could not be certain of this.

Blinding of outcome assessors (objective outcomes)

Low risk

Blinding of outcome assessors was not described; we did not anticipate that this would influence the assessment of objective outcome measures.

Blinding of outcome assessors (subjective measures)

Low risk

Staff responsible for decisions regarding patient care were blinded to groups.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Few losses

Selective reporting (reporting bias)

High risk

Study was prospectively registered with a clinical trials register (NCT02496923). We noted that mortality was an additional outcome that was not listed in the clinical trials register. All other outcomes were reported as described in the register.

Other bias

Low risk

We identified no other sources of bias.