Severity of acidosis affects long-term survival in COPD patients with hypoxemia after intensive care unit discharge

Figures & data

Figure 1 Flowchart of patient enrollment.

Abbreviations: ABG, arterial blood gas; ARF, acute respiratory failure; CBC, complete blood count; CRP, C-reactive protein; ICU, intensive care unit.

Table 1 Demographic characteristics and comorbidities of the study groups

Characteristics	Severe acidosis group (N=69)	Mild-to-moderate acidosis group (N=243)	p-value
Age, years, mean (±SD)	69±9	68±10	0.47
Gender, male, n (%)	50 (72.5)	192 (79)	0.25
BMI, kg/m^2, mean (±SD)	23±6	24±6	0.025
No smoke exposure, n (%)	10 (14.5)	36 (14.9)	0.55
Active cigarette smoker, n (%)	19 (27.5)	60 (24.8)
Ex-smoker, n (%)	40 (58)	146 (60)
Pack-years, mean (±SD)	51±32	50±33	0.73
Biomass exposure, n (%)	8 (11.9)	21 (8.9)	0.45
Long-term home device use before ICU
LTOT, n (%)	32 (47.8)	165 (68.5)	0.002
Long-term domiciliary ventilation, n (%)	17 (25.4)	97 (40.2)	0.56
Comorbid diseases
Diabetes mellitus, n (%)	17 (24.6)	47 (19.3)	0.33
Hypertension, n (%)	33 (47)	102 (41.9)	0.40
Congestive heart failure, n (%)	20 (28.9)	76 (31.2)	0.71
Ischemic heart disease, n (%)	18 (26)	39 (16)	0.057
Arrhythmia, n (%)	8 (11.6)	32 (13.2)	0.73
Chronic renal diseases, n (%)	4 (5.7)	3 (1.2)	0.024
Benign prostatic hyperplasia, n (%)	9 (13)	30 (12.3)	0.87
Chronic neurological disease, n (%)	9 (13.1)	22 (9.05)	0.32
Obstructive sleep apnea, n (%)	3 (4.3)	16 (6.5)	0.49
Depressive disorders, n (%)	7 (10.1)	28 (11.5)	0.74
Dementia, n (%)	6 (8.6)	14 (5.7)	0.33
Malignancy other than lungs, n (%)	1 (1.4)	6 (2.4)	0.61

Notes: Severe acidosis group: pH≤7.20; acidotic group: pH 7.21–7.34.

Abbreviations: BMI, body mass index; ICU, intensive care unit; LTOT, long-term oxygen therapy.

Table 2 ICU data of the study groups

	Severe acidosis group (N=69)	Mild-to-moderate acidosis group (N=243)	p-value
Reasons for ICU admission, n (%)
Pneumonia	27 (39.1)	84 (34.6)	0.72
Infection of LRT	28 (40.6)	115 (47.3)
Pulmonary embolism	0 (0)	1 (0.4)
Right heart failure	8 (11.6)	18 (7.4)
Other reasons	6 (8.7)	23 (9.5)
Laboratory values on the admission to the ICU
Leukocyte count, 10^9 L, median (IQR)	13.6 (10.5–17.8)	10.5 (8.2–14.6)	0.001
Hemoglobin, g/dL, median (IQR)	13 (11–14)	13 (11–14)	0.36
Hematocrit, % (±SD)	38±6	39±7	0.30
Platelet count, 10^9 L, median (IQR)	246 (198–325)	243 (179–306)	0.18
Blood urea nitrogen, mg/dL (±SD)	86±16	88±12	0.50
Serum creatinine, mg/dL, median (IQR)	0.91 (0.76–1.4)	0.81 (0.66–1.12)	0.007
CRP (mg/dL), median (IQR)	47 (13–124)	37 (13–96)	0.52
ABG values on the admission to the ICU
pH (±SD)	7.15±0.07	7.29±0.06	0.001
PaCO2, mmHg (±SD)	87±26	72±17	0.001
PaO2/FiO2, median (IQR)	169 (117–272)	175 (133–227)	0.67
HCO3, mmol (±SD)	29±8	33±8	0.001
BE, median (IQR)	2 (-4 to 5)	7 (3–12)	0.001
PaO2/FiO2 ratio<150, n (%)	29 (42)	87 (35)	0.001
Septic shock, n (%)	25 (36)	72 (29)	0.30
Two organ failures, n (%)	39 (56.5)	103 (42.4)	0.037
GCS (mean)	11.8±4.2	14.0±2.3	0.001
APACHE II score on admission, median (IQR)	25 (20–31)	19 (16–24)	0.001
APACHE II predicted mortality (±SD)	53.6±23.8	36.7±18.7	0.001
ICU mortality, N (%)	9 (13.0)	40 (16.5)	0.49
Length of ICU stay, days, median (IQR)	7 (5–10)	6 (4–9)	0.07

Notes: Severe acidosis group: pH≤7.20; acidotic group: pH 7.21–7.34.

Abbreviations: ABG, arterial blood gas; APACHE, acute physiology and chronic health evaluation; BE, base excess; CRP, C-reactive protein; FiO₂, fraction of inspired oxygen; GCS, Glasgow Coma Scale; ICU, intensive care unit; IQR, interquartile range; LRT, lower respiratory tract infection; PaCO₂, partial carbon dioxide pressure; PaO₂, partial arterial oxygen pressure.

Figure 2 The treatment of COPD patients with ARF in the ICU in the severe and mild-to-moderate acidosis groups.

Notes: (A) Patient group with severe acidosis admitted to the ICU due to ARF, who were followed up with oxygen and medical therapy. (B) Patient group with severe acidosis admitted to the ICU due to ARF, who were extubated during the follow-up with oxygen and medical therapy. (C) Patient group with severe acidosis admitted to the ICU due to ARF, who were applied NIMV. (D) Patient group with severe acidosis admitted to the ICU due to ARF, who were extubated because of NIMV failure. (E) Patient group with severe acidosis admitted to the ICU due to ARF, who were extubated at the time of ICU admission. (A′) Patient group with mild-to-moderate acidosis admitted to the ICU due to ARF, who were followed up with oxygen and medical therapy. (B′) Patient group with mild-to-moderate acidosis admitted to the ICU due to ARF, who were extubated during the follow-up with oxygen and medical therapy. (C′) Patient group with mild-to-moderate acidosis admitted to the ICU due to ARF, who were applied NIMV. (D′) Patient group with mild-to-moderate acidosis admitted to the ICU due to ARF, who were extubated because of NIMV failure. (E′) Patient group with mild-to-moderate acidosis admitted to the ICU due to ARF, who were extubated at the time of ICU admission. The significance of comparison of mortality was as follows: A–A′ p>0.053, B–B′ p<0.001, C–C′ p<0.001, D–D′ p<0.010, and E–E′ p<0.038.
Abbreviations: ARF, acute respiratory failure; ICU, intensive care unit; IMV, invasive mechanical ventilation; NIMV, noninvasive mechanical ventilation.

Table 3 Data of the study groups on the day of ICU discharge and follow-up period

	Severe acidosis group (N=61)	Mild-to-moderate acidosis group (N=201)	p-value
ABG values on the day of ICU discharge
pH (±SD)	7.41±0.04	7.40±0.04	0.10
PaCO2, mmHg (±SD)	50±10	59±34	0.001
PaO2/FiO2 (±SD)	288±95	272±111	0.27
HCO3, mmol (±SD)	33±9	34±5	0.49
History of long-term device use on the day of ICU admission
Domiciliary LTOT, n (%)	24 (39.3)	144 (72.4)	<0.001
Domiciliary NIMV, n (%)	15 (24.6)	90 (45.2)	0.005
Long-term device use when discharged from ICU
Domiciliary LTOT, n (%)	43 (70.5)	177 (88.1)	<0.001
Domiciliary NIMV, n (%)	33 (54.1)	154 (76.6)	<0.001
Mortality rates, n (%)
28th day	13.1 (8)	11.9 (24)	0.81
First year	27.9 (17)	38.8 (123)	0.12
Second year	54.1 (33)	52.2 (105)	0.80
Third year	62.3 (38)	63.7 (128)	0.84

Abbreviations: ABG, arterial blood gas; FiO₂, fraction of inspired oxygen; ICU, intensive care unit; LTOT, long-term oxygen therapy; NIMV, noninvasive mechanical ventilation; PaCO₂, partial carbon dioxide pressure; PaO₂, partial arterial oxygen pressure.

Figure 3 Survival functions of COPD with severe and mild-to-moderate acidosis.

Table 4 The comparison of survivors and non-survivors in COPD patients with ARF in the ICU

Variables	Survivor	Non-survivor	p-value
Number	262	69	–
Gender, male, n (%)	78 (204)	76 (38)	0.77
Age, years	68 (61–75)	77 (72–81)	<0.001
BMI≤20 kg/m^2, n (%)	62 (25)	14 (29)	0.54
LTOT use, n (%)	169 (65)	30 (60)	0.50
Domiciliary NIMV use, n (%)	106 (40)	11 (22)	<0.001
Smoking history
Current smoker	77 (30)	2 (4)	<0.001
Ex-smoker	145 (56)	41 (82)
Nonsmoker	39 (15)	7 (14)
pH≤7.20	61 (23)	8 (16)	0.26
Comorbid diseases, n (%)
Hypertension	110 (42)	24 (48)	0.44
Diabetes	56 (21)	8 (16)	0.39
Congestive heart failure	74 (28)	22 (44)	0.027
Chronic renal failure	5 (2)	2 (4)	0.36
Coronary heart diseases	47 (18)	9 (18)	0.99
Arrhythmia	31 (12)	9 (18)	0.23
ICU data
PaO2/FiO2<300	97 (38)	19 (38)	0.94
IMV, n (%)	102 (39)	45 (90)	<0.001
NIMV, n (%)	239 (91)	44 (88)	0.47
Septic shock, n (%)	78 (30)	45 (90)	<0.001
Two organ failures, n (%)	12 (5)	28 (56)	<0.001
Resistant pathogen, n (%)	26 (10)	22 (44)	<0.001
Use of two antibiotics, n (%)	127 (49)	38 (76)	<0.001
Use of three antibiotics, n (%)	12 (5)	17 (34)	<0.001
Antifungal use, n (%)	13 (5)	11 (22)	<0.001
Length of ICU stay, days	6 (4–8)	9 (5–15)	0.001

Abbreviations: ARF, acute respiratory failure; BMI, body mass index; ICU, intensive care unit; IMV, invasive mechanical ventilation; LTOT, long-term oxygen therapy; NIMV, noninvasive mechanical ventilation; PaO₂/FiO₂, partial arterial oxygen pressure to fractional inspired oxygen.

Table 5 ICU mortality risk factors for COPD with ARF

Variables	Odds ratio	CI		p-value
		Lower	Upper
Application of IMV in the ICU	0.03	5.42	36.75	<0.001
Age, for each year	1.17	1.10	1.25	<0.001
pH≤7.20	0.17	0.05	0.56	0.003
Presence of resistant pathogen	5.88	1.61	21.38	0.007
Presence of two organ failures	6.07	1.50	24.61	0.012
Chronic renal failure	22.58	1.99	256.84	0.012
Application of NIMV in the ICU	0.24	0.06	1.00	0.049
Coronary arterial diseases	0.45	0.13	1.51	0.20
BMI≤20 kg/m^2	0.56	0.19	1.65	0.29
PaO2/FiO2<300	1.95	0.52	7.31	0.33
ICU days, per each day	0.98	0.91	1.06	0.62
Presence of sepsis	1.60	0.11	22.37	0.73
Platelet counts<100,000 cell counts/L	0.72	0.10	5.10	0.74

Abbreviations: ARF, acute respiratory failure; BMI, body mass index; ICU, intensive care unit; IMV, invasive mechanical ventilation; NIMV, noninvasive mechanical ventilation; PaO₂/FiO₂, partial arterial oxygen pressure to fractional inspired oxygen.

Table 6 Cox regression analysis for short- and long-term mortality predictors in COPD patients after ICU discharge

	HR	95% CI		p-value
		Lower limit	Upper limit
28th day
Age, years	1.14	1.08	1.22	0.000
Intropic use in the ICU	3.31	1.28	8.60	0.014
PaO2/FiO2<300	2.32	1.01	5.34	0.047
pH≤7.20	0.31	0.10	1.04	0.058
First year
Age, years	1.07	1.04	1.10	<0.001
pH≤7.20	0.52	0.28	0.95	0.034
PaO2/FiO2<300	1.59	1.02	2.48	0.040
BMI≤20 kg/m^2	1.72	1.02	2.91	0.044
Second year
Age, years	1.06	1.03	1.08	<0.000
BMI≤20 kg/m^2	1.74	1.11	2.73	0.015
PaO2/FiO2<300	1.46	1.01	2.11	0.047
Third year
Age, years	1.06	1.03	1.08	<0.001
BMI≤20 kg/m^2	1.56	1.03	2.34	0.034
PaO2/FiO2<300	1.41	1.01	1.97	0.047

Notes: Cox regression model included the following: age, study group (pH<7.21, BMI<21 kg/m², PaO₂/FiO₂<300), male gender, comorbidities (diabetes mellitus, hypertension, chronic renal failure disease, coronary artery disease, congestive heart failure, days stay in the ICU, presence of septic shock, presence of resistant pathogen, use of domiciliary device [LTOT, NIMV]); only statistically significant (p<0.05) parameters are shown in the regression analysis.

Abbreviations: BMI, body mass index; HR, hazard ratio; ICU, intensive care unit; LTOT, long-term oxygen therapy; NIMV, noninvasive mechanical ventilation; PaO₂/FiO₂, partial arterial oxygen pressure to fractional inspired oxygen.

Figure 4 Survival functions of discharged COPD patients in long term follow-up according to severity of acidosis and LTOT use.

Notes: (A) Survival functions of COPD after discharge from hospital. (B) Survival functions of COPD patients with pH>7.20 group. (C) Survival functions of COPD patients in the pH<7.20 group.
Abbreviation: LTOT, long-term oxygen therapy.