High-Flow Nasal Cannula for Chronic Obstructive Pulmonary Disease with Acute Compensated Hypercapnic Respiratory Failure: A Randomized, Controlled Trial

Figures & data

Figure 1 Flow of patients with acute exacerbation of chronic obstructive pulmonary disease through the trial.

Abbreviations: AECOPD, acute exacerbation of chronic obstructive pulmonary disease; COT, conventional oxygen therapy; HFNC, high-flow nasal cannula; NIV, non-invasive ventilation; PaO₂, partial pressure of oxygen; PaCO₂, partial pressure of carbon dioxide.

Table 1 Characteristics of Patients at Randomization

Characteristic	HFNC Group (n=160)	COT Group (n=160)
Age (years)	68.4±7.7	68.3±6.9
Male no. (%)	101(63.1)	106(66.2)
Body mass index (kg/m^2)	23.1±4.5	22.7±3.9
COPD history(years)	16.8±13.4	14.6±12.1
Smoking history (years)	22.4±12.5	23.5±12.3
Current smokers no. (%)	102(63.8)	108(67.5)
CAT scores	20.3±5.5	21.5±5.5
APACHE II scores	15.8±6.5	14.7±6.0
Comorbidity, no. (%)
Hypertension	35(21.9)	37(23.1)
Diabetes mellitus	17(10.6)	20(12.8)
Coronary heart disease	20(12.5)	12(7.5)
Cerebrovascular Disease	9(5.6)	11(6.8)
Obsolete Pulmonary Tuberculosis	7(4.6)	6(3.7)
Baseline spirometry
Pre-bronchodilator FEV1 (L)	1.47±0.54	1.54±0.61
Post-bronchodilator FEV1 (L)	1.71±0.56	1.71±0.63
Post-bronchodilator FEV1, % predicted	61.2±18.1	59.9±18.2
Post-bronchodilator FEV1/FVC ratio, %	53.6±10.6	51.9±10.4
Vital signs
Body temperature (°C)	36.3±2.5	36.5±0.4
Heart rate (beats/min)	91.5±16.2	90.1±14.5
Mean arterial pressure (mmHg)	92.6±12.9	95.1±12.7
Respiratory rate (breaths/min)	21.0±1.7	21.1±1.9
Arterial blood gas (room air)
pH	7.38±0.03	7.39±0.04
PaO2 (mmHg)	54.7±5.2	54.9±4.9
PaCO2 (mmHg)	54.9±7.1	54.2±6.0
BE	6.6±3.6	6.2±4.1
HCO3^−	32.9±3.8	31.9±4.6
Laboratory parameters
White blood cell (×10^9/L)	7.7±4.6	8.2±4.1
Neutrophil (%)	66.8±19.3	67.0±18.0
Albumin (g/L)	36.9±5.0	37.2±4.7
Creatinine (umol/L)	66.8±43.1	68.3±27.1
NT-proBNP (pg/mL)	90.8±82.4	107.4±87.9

Notes: Data are presented as mean ± standard deviation or No. (%).

Abbreviations: APACHE, Acute Physiology and Chronic Health Evaluation; BE, base excess; COPD, chronic obstructive pulmonary disease; CAT score, COPD assessment test score; COT, conventional oxygen therapy; FEV1, forced expiratory volume in one second; FVC, forced vital capacity; FiO₂, fraction of inspired oxygen; HFNC, high-flow nasal cannula; NT-proBNP, N-terminal pro-brain natriuretic peptide; PaO₂, partial pressure of oxygen; PaCO₂, partial pressure of carbon dioxide.

Table 2 Primary Endpoint and Secondary Endpoints in the Two Groups

Outcome	All Patients (n=320)	HFNC Group (n=160)	COT Group (n=160)	P
Primary end point
Treatment failure, need of NIV, no. (%)	47(14.7)	16(10.0)	31(19.4)	0.026
Secondary end point
Patients received NIV, no. (%)	39(12.2)	13(8.1)	26(16.3)	0.039
CAT scores at discharge	15.2±7.8	12.0±7.6	17.0±7.3	0.002
Subjective discomfort score	3.3±1.6	2.3±1.1	3.9±1.6	<0.001
Hospital lengths of stay (days)	12.7±4.8	12.2±5.3	12.9±4.5	0.453
Readmission rate within 3 months, no. (%)	77 (24.1)	32 (20.0)	45 (28.1)	0.116
Reason for NIV
Respiratory acidosis	36(11.3)	12(7.5)	24(15.0)	0.050
Obvious dyspnea	11(3.4)	4(2.5)	7(4.4)	0.542

Notes: Data are presented as mean ± standard deviation or No. (%). Treatment failure was defined as worsening of the patients’ condition to the point that noninvasive or invasive mechanical ventilation was required.

Abbreviations: CAT score, COPD assessment test score; COT, conventional oxygen therapy; HFNC, high-flow nasal cannula oxygen therapy; NIV, noninvasive mechanical ventilation.

Figure 2 Kaplan–Meier estimates of the probability of treatment success at 28 d between the high-flow nasal cannula oxygen therapy (HFNC) group and the conventional oxygen therapy (COT) group. Significant differences were found for the cumulative probability of treatment success for the two groups (Log rank test: p = 0.019).

Table 3 Comparison of Physiological Parameters Between HFNC and COT Groups

Characteristic	Group	Baseline	24 h	48 h	72 h	120 h	Before Discharge	p^a
pH	HFNC	7.38±0.04	7.36±0.06	7.40±0.04	7.41±0.05	7.40±0.04	7.40±0.04	0.864
	COT	7.39±0.04	7.38±0.05	7.39±0.05	7.39±0.05	7.39±0.03	7.39±0.04	0.924
	p^c	0.376	0.730	0.182	0.049	0.017	0.530	0.888^b
PaO2 (mmHg)	HFNC	54.7±5.2	71.3±14.0	70.5±13.8	68.9±10.7	69.4±10.6	64.9±7.5	0.000
	COT	54.9±4.9	73.8±9.2	73.1±10.4	70.9±5.6	71.1±6.0	64.3±5.4	0.000
	p^c	0.680	0.119	0.143	0.151	0.237	0.578	0.219^b
PaCO2 (mmHg)	HFNC	54.9±7.1	54.1±9.8	52.8±7.9	53.3±8.3	52.1±10.2	51.4±7.2	0.001
	COT	54.2±6.0	56.9±10.1	54.1±8.6	54.1±8.7	54.4±10.2	49.1±9.7	0.034
	p^c	0.325	0.030	0.320	0.496	0.173	0.108	0.306^b
SaO2 (%)	HFNC	89.3±4.7	92.8±3.0	93.2±2.1	93.0±3.4	93.8±2.7	92.2±3.4	0.000
	COT	89.0±4.6	93.5±2.7	93.7±2.2	93.6±2.7	94.1±2.5	92.8±3.5	0.000
	p^c	0.649	0.079	0.111	0.185	0.395	0.227	0.325^b
Respiratory rate (bpm)	HFNC	21.0±1.7	21.5±2.0	21.4±2.4	22.4±5.7	21.4±2.5	21.5±2.7	0.066
	COT	21.1±1.9	23.1±7.6	22.4±5.7	21.8±2.2	21.8±2.3	21.4±1.9	0.024
	p^c	0.790	0.024	0.067	0.294	0.253	0.628	0.150^b

Notes: Results are mean ± SD. Total number of patients present in each group at each time point. p^a for overall comparisons of differences in each group over time. p^b for overall comparisons of differences between groups over time. p^c for comparisons of differences between groups at each time point.

Abbreviations: COT, conventional oxygen therapy; HFNC, high-flow nasal cannula oxygen therapy; PaO₂, partial pressure of oxygen; PaCO₂, partial pressure of carbon dioxide; SaO₂, arterial oxygen saturation.

Figure 3 Comparison of physiological parameters between the high-flow nasal cannula oxygen therapy (HFNC) group and the conventional oxygen therapy (COT) group. Shown are the time courses of partial pressure of arterial oxygen (PaO₂), partial pressure of arterial carbon dioxide (PaCO₂), arterial oxygen saturation (SaO₂), and respiratory rate. p^a represents the overall comparison of differences in each group over time, and p^b represents overall comparisons of differences between groups over time.

Table 4 Comparison of Physiological Parameters Between HFNC Success and Failure Groups

Characteristic	HFNC Group	Baseline	24 h	48 h	72 h	120 h	p^a
pH	Success	7.38±0.05	7.40±0.04	7.40±0.04	7.41±0.04	7.41±0.04	0.253
	Failure	7.40±0.04	7.38±0.04	7.39±0.02	7.38±0.06	7.37±0.07	0.197
	p^c	0.281	0.334	0.756	0.018	0.030	0.050^b
PaO2 (mmHg)	Success	54.8±4.8	72.1±8.7	70.6±14.0	71.3±15.5	71.2±16.4	0.000
	Failure	54.9±5.0	71.2±11.7	68.1±10.3	68.9±15.2	78.2±25.1	0.487
	p^c	0.518	0.786	0.649	0.629	0.384	0.878^b
PaCO2 (mmHg)	Success	54.6±6.9	52.4±8.0	51.5±5.6	52.2±7.2	50.9±8.9	0.000
	Failure	58.0±8.9	59.0±11.8	55.8±5.6	63.8±11.0	68.7±13.2	0.144
	p^c	0.086	0.006	0.012	0.006	0.000	0.000^b
SaO2 (%)	Success	89.1±4.7	93.3±2.7	93.3±2.2	93.1±3.3	93.7±2.6	0.000
	Failure	90.5±4.8	92.9±1.9	92.3±2.5	92.2±4.1	95.4±4.2	0.160
	p^c	0.295	0.592	0.237	0.460	0.179	0.628^b
Respiratory rate (bpm)	Success	20.1±1.5	21.3±2.3	22.4±5.9	21.8±2.8	21.4±2.4	0.013
	Failure	22.4±2.5	22.7±2.6	22.0±2.8	23.0±2.4	21.5±1.9	0.896
	p^c	0.032	0.059	0.829	0.205	0.936	0.784^b

Notes: Results are mean ± SD. Total number of patients present in each group at each time point. p^a for overall comparisons of differences in each group over time. p^b for overall comparisons of differences between groups over time. p^c for comparisons of differences between groups at each time point.

Abbreviations: HFNC, high-flow nasal cannula oxygen therapy; PaO₂, partial pressure of oxygen; PaCO₂, partial pressure of carbon dioxide; SaO₂, arterial oxygen saturation.

Table 5 Risk Factors Associated with HFNC Failure in Multivariate Analysis

Variable	Wald	Odds Ratios	95% Confidence Interval	P
Univariate logistic regression
Respiratory rate > 22 breaths per minute	8.807	1.562	1.163–2.097	0.003
PaCO2 (24 h) > 59 mmHg	6.775	1.079	1.019–1.143	0.009
PaCO2 (48 h) > 55 mmHg	5.794	1.139	1.024–1.267	0.016
Multivariate logistic regression
PaCO2 (24 h) > 59 mmHg	4.590	1.078	1.006–1.154	0.032

Abbreviations: HFNC, high-flow nasal cannula oxygen therapy; PaO₂, partial pressure of oxygen; PaCO₂, partial pressure of carbon dioxide.

Figure 4 Comparison of physiological parameters between high-flow nasal cannula oxygen therapy success and failure groups. Shown are the time courses of partial pressure of arterial oxygen (PaO₂), partial pressure of arterial carbon dioxide (PaCO₂), arterial oxygen saturation (SaO₂), and respiratory rate. p^a represents overall comparisons of differences in each group over time, and p^b represents overall comparisons of differences between groups over time.

Table 6 Side Effects of HFNC Treatment

Side Effects	Treatment Measures	HFNC Group (n=160)	HFNC Success Group (n=144, %)	HFNC Failure Group (n=16, %)	P
Condensate noise	Clear the water in the pipeline in time	43	38(26.4)	5(31.2)	0.767
Excessive or insufficient gas flow	Adjust appropriate flow according to patient comfort	38	32(22.2)	6(37.5)	0.214
Temperature too high	Adjust the appropriate temperature gear	23	20(13.9)	3(18.8)	0.705
Abnormal smell of nasal cannula	Communicate and explain with patients	4	3(2.1)	1(6.2)	0.347
Dizziness and vomiting	Refuse to continue application after 72 hours of treatment	1	1	0	–
Dryness of oropharynx	The humidification effect is not achieved, improved after reset	1	1	0	–

Abbreviation: HFNC, high-flow nasal cannula oxygen therapy.