Comparison of High Flow Nasal Therapy with Non-Invasive Ventilation and Conventional Oxygen Therapy for Acute Hypercapnic Respiratory Failure: A Meta-Analysis of Randomized Controlled Trials

Figures & data

Figure 1 Flow chart of study selection and exclusion.

Abbreviations: RCTs, randomized controlled trials; n, number.

Table 1 The Characteristics of Included Studies

Study	Setting	Study Design	Patients	HFNC Group			Control Group			Outcomes
				Baseline Arterial pH and PaCO2 (mmHg), Mean ± SD	Baseline APACHE II, Mean ± SD	Intervention (Mean ± SD)	Baseline Arterial pH and PaCO2 (mmHg), Mean ± SD	Baseline APACHE II, Mean ± SD	Intervention
Cortegiani A, 2020	ED, ICU, or respiratory unit	Multi-center	AECOPD, N=79	pH, 7.30±0.03; PaCO2, 73.7±12.8	SAPS II (mean ± SD), 30±9	Flow rate, 50.0±11.1 L/min; FiO2, 0.36 ±0.10; Temperature, 37.0±2.2°C	pH, 7.29±0.03; PaCO2, 72.0±13.0	SAPS II (mean ± SD), 33±10	NIV: PSV mode, PS (cmH2O), 12.0±2.9; PEEP (cmH2O), 6.0±1.1; FiO2, 0.30 ±0.10	Intubation rate, mortality, treatment crossover rate, pH, PaCO2, PaO2/FiO2, RR, hospital stay, dyspnea score, discomfort score
Li C, 2019	ICU	Single-center	AECOPD, N=168	pH, 7.25±0.08; PaCO2, 72.1±16.3	NR	Flow rate, 30–35L/min; Temperature, 37.0°C	pH, 7.27±0.09; PaCO2, 72.9±16.4	NR	IPAP was set at 10 cmH2O and PEEP was set at 5 cm H2O at beginning and gradually increased after the patient adapted	pH, PaCO2, PaO2, hospital stay, adverse events
Wang J, 2019	RICU	Single-center	AECOPD, N=63	pH, 7.24±0.02; PaCO2, 66.8±3.9	19.0±2.6	NR	pH, 7.24±0.02; PaCO2, 68.3±3.1	19.8±2.3	NR	Intubation rate, mortality, ICU and hospital lengths, adverse events
Doshi PB, 2020	ED	Multi-center	Patients with AHRF, N=65	pH, 7.33±0.12; PaCO2, 56.0±17.7	31.0±4.4	Initial flow rate was 35 L/min, FiO2 was adjusted to maintain oxygen saturation above 88%	pH, 7.32±0.09; PaCO2, 64.6±31.8	29.0±5.9	NIV, initial settings: IPAP, 10–20 cmH2O; EPAP, 5–10 cmH2O; FiO2 was adjusted to maintain oxygen saturation above 88%	Intubation rate, treatment crossover rate, pH, PaO2, PaCO2, RR, HR, ICU and hospital stay, Modified Borg score
Papachatzakis Y, 2020	ED	Single-center	Patients with AHRF, N=40	pH, 7.40±0.10; PaCO2, 60.4±9.9	21.6±8.9	Initial flow rate was 35 L/min, titrating flow upward if tolerated to 45–50 L/min, in order to maintain SaO2 >90%	pH, 7.40±0.10; PaCO2, 56.8±9.7	19.3±6.1	NIV, S/T mode, expiratory and inspiratory pressures were gradually increased to the maximum tolerated to maintain SaO2 >90%	Mortality, pH, PaO2, PaCO2, RR, HR, hospital stay, comfort score, dyspnea score
Tan D, 2020	ICU	Multi-center	Post-extubation AECOPD, N=86	pH, 7.48±0.06; PaCO2, 50.5±7.2	14±5.7	Initial flow rate was 50 L/min, temperature was 37.0°C, FiO2, 0.32±0.074	pH, 7.45±0.06; PaCO2, 53.0±9.2	13±3.8	NIV, initial EPAP was set at 4 cmH2O, IPAP was set at 8 cmH2O and gradually increased to achieve a satisfactory tidal volume with acceptable tolerance, FiO2 (mean ± SD), 0.35±0.07	Intubation rate, mortality, treatment crossover rate, pH, PaO2, PaCO2, HR, RR, ICU and hospital lengths, adverse events, comfort score, dyspnea score
Jing G, 2019	RICU	Single-center	Post-extubation AECOPD, N=42	pH, 7.46±0.04; PaCO2, 53.2±6.7	11.8±3.1	Flow rate, 52.0±6.3L/min; FiO2, 0.40±0.10; temperature, 37.0°C	pH, 7.44±0.06; PaCO2, 53.7±8.6	10.4±2.5	NIV, IPAP (mean ± SD), 11.4±2.0 cmH2O; PEEP, 4.6±0.5 (cmH2O); FiO2 was adjusted to maintain SpO2 88–92%	Intubation rate, 28-day mortality, pH, PaCO2, PaO2/FiO2, RR, HR, comfort score, ICU stay, adverse events
Li X, 2020	Respiratory Unit	Multi-center	AECOPD with compensated AHRF, N=320	pH, 7.38±0.03; PaCO2, 54.9±7.1	15.8±6.5	Flow rate, 33.4 ± 5.6 L/min; FiO2, 0.28 ± 0.01; temperature, 33.8 ± 4.1°C	pH, 7.39±0.04; PaCO2, 54.2±6.0	14.7±6.0	COT, oxygen flow was set to achieve SpO2 at 90% to 93%	Intubation rate, mortality, treatment failure rate, pH, PaO2, PaCO2, RR, length of hospitalization, comfort score
Xia J, 2022	Respiratory Unit	Multi-center	AECOPD with mild hypercapnia, N=330	pH, 7.40±0.03; PaCO2, 50.4±6.6	10.0±4.4	Flow rate, 35.0±11.1 L/min; FiO2, 0.33±0 0.07; temperature, 34.0±2.2 °C	pH, 7.40±0.04; PaCO2, 51.7±7.7	10.0±4.8	COT, oxygen flow (mean ± SD), 2.0±0.7 L/min	Intubation rate, mortality, treatment failure rate, pH, PaCO2, PaO2, SpO2, RR, HR, hospital stay
Yu Z, 2019	RICU	Single-center	Post-extubation AECOPD, N=72	pH, 7.26±0.03; PaCO2, 73.5±6.9	28.6±2.8	Flow rate, 30–60L/min; FiO2, 0.30–0.80; temperature, 37.0°C	pH, 7.26±0.03; PaCO2, 73.5±6.2	28.5±3.4	NIV: S/T mode; IPAP (cmH2O), 10–14; PEEP (cmH2O), 4–6; FiO2, 0.30–0.80	Reintubation rate, 28-day mortality, pH, PaO2, PaCO2, PaO2/FiO2, RR, HR, ICU stay, adverse events

Figure 2 Results of risk assessment of bias using Cochrane risk of bias tool.

Figure 3 Forest plot comparing intubation rate between HFNC and control groups.

Abbreviations: HFNC, high flow nasal cannula; NIV, non-invasive ventilation; COT, conventional oxygen therapy; blue squares, the odds ratio value for an individual study result; black diamonds, the overall effect size for study results of the group; M–H, Mantel–Haenszel method; CI, confidence interval.

Figure 4 Forest plot comparing mortality between HFNC and control groups.

Abbreviations: HFNC, high flow nasal cannula; NIV, non-invasive ventilation; COT, conventional oxygen therapy; blue squares, the odds ratio value for an individual study result; black diamonds, the overall effect size for study results of the group; M–H, Mantel–Haenszel method; CI, confidence interval.

Figure 5 (a) Forest plot comparing treatment crossover rate between HFNC and NIV; (b) Forest plot comparing the need for NIV between HFNC and COT.

Abbreviations: HFNC, high flow nasal cannula; NIV, non-invasive ventilation; COT, conventional oxygen therapy; blue squares, the odds ratio value for an individual study result; black diamonds, the overall effect size for study results of the group; M–H, Mantel–Haenszel method; CI, confidence interval.

Figure 6 Forest plot comparing pH between HFNC and control groups.

Abbreviations: pH, potential of hydrogen; HFNC, high flow nasal cannula; NIV, non-invasive ventilation; COT, conventional oxygen therapy; green squares, the mean difference value for an individual study result; black diamonds, the overall effect size for study results of the group; IV, Inverse variance method; CI, confidence interval; SD, standard deviation.

Figure 7 Forest plot comparing PaCO₂ between HFNC and control groups.

Abbreviations: HFNC, high flow nasal cannula; NIV, non-invasive ventilation; COT, conventional oxygen therapy; PaCO₂, arterial partial pressure of carbon dioxide; green squares, the mean difference value for an individual study result; black diamonds, the overall effect size for study results of the group; IV, Inverse variance method; CI, confidence interval; SD, standard deviation.

Figure 8 Forest plot comparing oxygenation between HFNC and control groups.

Abbreviations: HFNC, high flow nasal cannula; NIV, non-invasive ventilation; COT, conventional oxygen therapy; PaO₂, partial arterial oxygen pressure; FiO₂, the fraction of inspired oxygen; green squares, the mean difference value for an individual study result; black diamonds, the overall effect size for study results of the group; IV, Inverse variance method; CI, confidence interval; SD, standard deviation.

Figure 9 Forest plot comparing RR between HFNC and control groups.

Abbreviations: HFNC, high flow nasal cannula; NIV, non-invasive ventilation; COT, conventional oxygen therapy; RR, respiratory rate; green squares, the mean difference value for an individual study result; black diamonds, the overall effect size for study results of the group; IV, Inverse variance method; CI, confidence interval; SD, standard deviation.

Figure 10 Forest plot comparing HR between HFNC and NIV.

Abbreviations: HFNC, high flow nasal cannula; NIV, non-invasive ventilation; HR, heart rate; green squares, the mean difference value for an individual study result; black diamonds, the overall effect size for study results of the group; IV, Inverse variance method; CI, confidence interval; SD, standard deviation.

Figure 11 (a) Forest plot comparing hospital stay between HFNC and NIV; (b) Forest plot comparing ICU stay between HFNC and NIV; (c) Forest plot comparing hospital stay between HFNC and COT.

Abbreviations: HFNC, high flow nasal cannula; NIV, non-invasive ventilation; COT, conventional oxygen therapy; ICU, intensive care unit; green squares, the mean difference value for an individual study result; black diamonds, the overall effect size for study results of the group; IV, Inverse variance method; CI, confidence interval; SD, standard deviation.

Figure 12 Forest plot comparing adverse events between HFNC and NIV.

Abbreviations: HFNC, high flow nasal cannula; NIV, non-invasive ventilation; blue squares, the odds ratio value for an individual study result; black diamonds, the overall effect size for study results of the group; M–H, Mantel–Haenszel method; CI, confidence interval.

Figure 13 (a) Forest plot comparing comfort score between HFNC and NIV; (b) Forest plot comparing dyspnea score between HFNC and NIV.

Abbreviations: HFNC, high flow nasal cannula; NIV, non-invasive ventilation; green squares, the mean difference value for an individual study result; black diamonds, the overall effect size for study results of the group; IV, Inverse variance method; CI, confidence interval; SD, standard deviation.

Figure 14 Forest plot and subgroup analyses comparing treatment crossover rate between pH<7.30 and pH>7.30.

Abbreviations: HFNC, high flow nasal cannula; NIV, non-invasive ventilation; pH, potential of hydrogen; blue squares, the odds ratio value for an individual study result; black diamonds, the overall effect size for study results of the group; M–H, Mantel–Haenszel method; CI, confidence interval.