Table 2 Characteristics of included studies

Cong et al. 

[28]

Parallel-group RCT

Mean age (SD), 67.52 (7.13)

Female sex, 41.2%

Mean APACHE II, NR

Mean pH on presentation, 7.26 (NR)

Mean PaCO₂ on presentation, 72.51 mmHg

ICU

Patients with a diagnosis of AECOPD, admitted to ICU, receiving ventilation therapy

None

N = 84

HFNC at 30–35L/min 37 °C

N = 84

NIV by facemask. Settings: IPAP 10 cm H₂O and EPAP 5 cm H₂O, titrated by patient symptoms and oxygenation

Arterial blood gases at 12 h and 5 days after treatment

Cortegiani et al. 

[18]

Multicenter parallel-group RCT

Mean age, 75.5 (NR)

Female sex, 19.5%

Mean SAPS II 31.2 (NR)

Mean pH on presentation, 7.30

Mean PaCO₂ on presentation, 72.9 mmHg (NR)

Emergency department, ICU, or respiratory unit

Adults > 18 years old with a diagnosis of AECOPD, pH 7.25–7.35 with PaCO₂ ≥ 55 mmHg

None

N = 40

HFNC initially set at 60L/min, 37 °C. Flows and temperature downregulated for tolerance

N = 39

NIV through full-face or oro-nasal mask

Settings: pressure support ventilation, EPAP 3–5 cm H₂O, titrated inspiratory pressure for tidal volume 6–8 mL/kg ideal body weight

Mean difference PaCO₂ at 2 h post randomization

Doshi et al. 

[30]

Parallel-group RCT, predefined subgroup analysis

Median age, 62 (NR)

Female sex, 52.3%

Mean APACHE II, 30 (NR)

Mean pH on presentation, 7.33 (NR)

Mean PaCO₂ on presentation, 60.3 mmHg (NR)

Emergency department

Adults > 18 presenting to the ED with acute respiratory failure, determined to need non-invasive positive pressure ventilation by physician assessment. Subgroup analysis of patients with a discharge diagnosis of AECOPD or acute hypercapnic respiratory failure. Impaired ventilation defined as elevated PaCO₂ and pH < 7.35

None

N = 34

HFNC at 35L/min, temperature 35–37 °C and FiO₂ 1.0. Adjustments made at discretion of treating physician

N = 31

NIV with an oronasal mask. Settings IPAP 10–20 cm H₂O and EPAP 5–10 cm H₂O with FiO₂ 1.0. Adjustments made at discretion of treating physician

Change in PaCO₂ and pH over time

Lee et al. 

[27]

Randomized controlled trial

Median age (IQR), 73 (66.5–79)

Female sex, 43%

Mean APACHE II, NR

Mean pH on presentation (SD), 7.32 (0.03)

Mean PaCO₂ on presentation (SD), 54.5 (9.6)

Inpatients, location not specified

Adult patients ≥ 45 years with smoking history ≥ 10 pack years hospitalized with severe AECOPD. Moderate hypercapnic respiratory failure defined as requiring NIV after oxygen therapy of FiO₂ > 50% for > 15 min and having a PaO₂/FiO₂ ratio of < 200 mmHg and PaCO₂ > 45 mmHg with pH 7.25–7.35 on room air

None

N = 44

HFNC initiated at 35L/min titrated as tolerated to 45-60L/min. FiO₂ initiated at > 50% and titrated for oxygen saturation of > 92%

N = 44

NIV delivered via nasal or full-face masks, based on patient comfort. Settings were in spontaneous/timed mode with initial IPAP at 10 cm H₂O and EPAP 5 cm H₂O, increased as tolerated over 1 h. Targeted tidal volumes of 7–10 mL/kg predicted body weight. FiO₂ adjusted for oxygen saturation of > 92%

Intubation rate due to continuous hypoxia and hypercapnia

Papachatzakis et al. 

[17]

Parallel-group RCT

Mean age (SD), 77.0 (11.0)

Female sex, 52.5%

Mean APACHE (SD), 20.5 (7.6)

Mean pH on presentation (SD), 7.4 (0.1)

Mean PaCO₂ on presentation, 61.2 mmHg (10.0)

Emergency department

Hypercapnic respiratory failure with PaCO₂ > 45 mmHg

pH < 7.20

N = 20

HFNC initiated at 35L/min and titrated up as tolerated to 45-50L/min for SaO₂ > 90% or per clinical order

N = 20

NIV, mask type not described. Settings: spontaneous/timed mode with pressures titrated by patient tolerance over 1 h for SaO₂ > 90% or per clinical order

Not specified. All outcomes: intubation and mortality rate, length of hospitalization, duration of therapy, differences between vital signs, arterial blood gases, and comfort

Rezaei et al. 

[29]

Randomized crossover trial

Mean age, 61.27 (NR)

Female sex, 20%

Mean APACHE II, NR

Mean pH on presentation, 7.32 (NR)

Mean PaCO₂ on presentation, 64.58 mmHg (NR)

Emergency department or ward

Patients between 18 and 65 years old with moderate to severe AECOPD and acute hypercapnic respiratory failure. Criteria for hypercapnia were pH between 7.25 and 7.35, PaCO₂ > 45 mmHg

None

N = 15

HFNC initiated at flows of 15-35L/min at 37 °C for 30 min followed by a 1 h washout and switch to the alternate intervention

Two patient groups in the study. The first started with HFNC and switched to NIV and the second started with NIV and switched to HFNC

N = 15

NIV delivered for 30 min followed by a 1 h washout and switch to the alternate intervention. Settings not described

Respiratory rate, heart rate, pH, dyspnea score, PaO₂ and PaCO₂

Sklar et al. 

[31]

Randomized crossover trial

Median age (IQR), 30 (23–34)

Female sex, 8%

Median APACHE II (IQR), 8 (7–9.5)

Mean pH on presentation, NR

Median transcutaneous CO₂ on presentation (IQR), 53 (42–60)

Inpatients, location not specified

Adult patients > 18 years old with cystic fibrosis and clinical indication for NIV at the time of admission based on: clinical respiratory distress (respiratory rate > 24/min or accessory muscle use, PaCO₂ > 45 mmHg from hospital admission, chronic nocturnal NIV now requiring daytime NIV, diurnal hypercapnia PaCO₂ > 45 mmHg or transcutaneous CO₂ > 40 mmHg in patients with serum bicarbonate ≥ 32 mmol/L

None

N = 15

30-min periods of time of HFNC at 55L/min if tolerated and FiO₂ adjusted for oxygen saturation > 92% and temperature at 37 °C or 34 °C as per patient preference

N = N/A (crossover)

30 min periods of time of NIV with facemask. Settings adjusted by respiratory therapy team; details not specified. FiO₂ adjusted for oxygen saturation of > 92%

Not specified

All outcomes: oxygen saturation, transcutaneous CO₂, respiratory rate, tidal volume, minute ventilation, diaphragm thickening fraction, dyspnea, comfort

Wang et al. 

[24]

Randomized controlled trial

Mean age, NR

Female sex, NR

Mean APACHE II, NR

Mean pH on presentation, NR

Mean PaCO₂ on presentation, NR

NR

Patients with AECOPD, criteria not specified

Not specified

HFNC, settings not specified

NIV, settings not specified

Intervention failure (switch to alternate intervention or endotracheal intubation), endotracheal intubation, complications, 28 day survival