J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website https://www.jocmr.org

Original Article

Volume 16, Number 1, January 2024, pages 15-23

Intubation Time, Lung Mechanics and Outcome in COVID-19 Patients Suffering Acute Respiratory Distress Syndrome: A Single-Center Study

Figure 1. Mortality differences in early vs. late intubation group of patients (a), differences in intubation timing (days) in survivors vs. non-survivors (b) and probability of survival between the two groups of patients (c).

Figure 2. Patients’ mortality and time to intubation (a) and Kaplan-Meier curve for survival in early, late, and very late intubated patients (b).

**Table 1.** Differences Between Early and Late Intubated Patients
	All patients	Early intubation (≤ 2 days from hospital admission)	Late intubation (> 2 days from hospital admission)	P value
^aStatistically significant differences between early and late intubated patients. SOFA: sequential organ failure assessment; BMI: body mass index; CPAP: continuous positive airway pressure; Ppl: plateau pressure; PEEP: positive end expiratory pressure; Compliance_stat,rs: respiratory system static compliance; WBCs: white blood cells; CRP: C-reactive protein; LDH: lactate dehydrogenase; IQR: interquartile range.
Patients’ characteristics
Number (%)	194	58 (29.9)	136 (70.1)
Age (years)	65 (57 - 72)	60 (52 - 69)	67 (60 - 73)	0.002^a
Gender male, n (%)	129 (66.5)	37 (63.8)	93 (68)	0.670
SOFA, median (IQR)	7 (7 - 9)	6 (5 - 8)	8 (6 - 9)	0.002^a
BMI, median (IQR)	28 (26 - 34)	30 (26 - 35)	28 (26 - 33)	0.554
PO₂/FiO₂ before intubation, median (IQR)	90 (78 - 110)	90 (77.7 - 115.7)	90 (78 - 110)	0.938
PO₂/FiO₂ after intubation, median (IQR)	120 (90 - 140)	120 (90 - 140)	110 (89 - 140)	0.295
CPAP use, n (%)	164 (84.5)	42 (72.4)	122 (89.7)	0.004^a
CPAP (days), median (IQR)	3 (1 - 6)	1 (0 - 2)	4.5 (3 - 6)	< 0.001^a
Mechanical ventilation mechanics, median (IQR)
Ppl (cm H₂O)	26 (24 - 28)	26 (24 - 28)	26 (24 - 28)	0.104
PEEP (cm H₂O)	12 (11 - 14)	12.5 (12 - 14)	12 (10 - 14)	0.016^a
Compliance_{stat, rs} (mL/cm H₂O), day 1	37.5 (32 - 45)	42 (35 - 49)	36 (30 - 44)	0.006^a
Compliance_{stat, rs} (mL/cm H₂O), day 6	35 (29 - 44)	40 (33 - 45)	33 (27 - 42)	< 0.001^a
Compliance_{stat, rs} (mL/cm H₂O), day 12	33 (26 - 41)	37.5 (32.7 - 44)	32 (25 - 41)	< 0.001^a
Driving pressure (cm H₂O)	14 (12 - 16)	13.5 (12 - 16)	14 (12 - 16)	0.081
Laboratory values, median (IQR)
WBCs (absolute number/mm³)	17,800 (14,000 - 21,832)	16,000 (12,945 - 18,567)	18,485 (14,892 - 22,975)	0.004^a
D-dimmer (µg/L)	2,569 (1,340 - 5,600)	2,554 (1,370 - 5,450)	2,650 (1,300 - 5,600)	0.747
CRP (mg/dL)	9 (6 - 15)	9 (5.2 - 13.2)	8.9 (5.9 - 16)	0.592
Ferritin (ng/mL)	1,790 (937 - 3,538)	1,466 (935 - 2,905)	1,900 (920 - 3,771)	0.276
LDH (U/L)	502 (320 - 789)	478 (320 - 683)	533 (320 - 858)	0.336
Comorbidities, n (%)
Hypertension	111 (57.2)	31 (53.4)	80 (58.8)	0.528
Heart failure	28 (14.4)	7 (12)	21 (15.4)	0.658
Coronary artery disease	34 (17.5)	7 (12)	27 (20)	0.221
Lung disease	16 (8.2)	3 (5.2)	13 (9.6)	0.401
Kidney injury	22 (11.3)	3 (5.2)	19 (14)	0.09
Diabetes	53 (27.3)	18 (31)	35 (25.7)	0.484
Cancer	10 (5.2)	3 (5.2)	7 (5.1)	1.00
Outcomes
Mortality n (%)	124 (64)	26 (44.8)	98 (72)	< 0.001^a
ICU LOS, median (IQR)	13 (8 - 25)	14.5 (8.7 - 27)	12 (8 - 24.7)	0.344
Mechanical ventilation days, median (IQR)	12 (6 - 23)	12 (6 - 24)	12 (6 - 22)	0.992

Table 1. Differences Between Early and Late Intubated Patients

All patients

Early intubation (≤ 2 days from hospital admission)

Late intubation (> 2 days from hospital admission)

P value

^aStatistically significant differences between early and late intubated patients. SOFA: sequential organ failure assessment; BMI: body mass index; CPAP: continuous positive airway pressure; Ppl: plateau pressure; PEEP: positive end expiratory pressure; Compliance_stat,rs: respiratory system static compliance; WBCs: white blood cells; CRP: C-reactive protein; LDH: lactate dehydrogenase; IQR: interquartile range.

Patients’ characteristics

Number (%)

194

58 (29.9)

136 (70.1)

Age (years)

65 (57 - 72)

60 (52 - 69)

67 (60 - 73)

0.002^a

Gender male, n (%)

129 (66.5)

37 (63.8)

93 (68)

0.670

SOFA, median (IQR)

7 (7 - 9)

6 (5 - 8)

8 (6 - 9)

0.002^a

BMI, median (IQR)

28 (26 - 34)

30 (26 - 35)

28 (26 - 33)

0.554

PO₂/FiO₂ before intubation, median (IQR)

90 (78 - 110)

90 (77.7 - 115.7)

90 (78 - 110)

0.938

PO₂/FiO₂ after intubation, median (IQR)

120 (90 - 140)

110 (89 - 140)

0.295

CPAP use, n (%)

164 (84.5)

42 (72.4)

122 (89.7)

0.004^a

CPAP (days), median (IQR)

3 (1 - 6)

1 (0 - 2)

4.5 (3 - 6)

< 0.001^a

Mechanical ventilation mechanics, median (IQR)

Ppl (cm H₂O)

26 (24 - 28)

0.104

PEEP (cm H₂O)

12 (11 - 14)

12.5 (12 - 14)

12 (10 - 14)

0.016^a

Compliance_{stat, rs} (mL/cm H₂O), day 1

37.5 (32 - 45)

42 (35 - 49)

36 (30 - 44)

0.006^a

Compliance_{stat, rs} (mL/cm H₂O), day 6

35 (29 - 44)

40 (33 - 45)

33 (27 - 42)

< 0.001^a

Compliance_{stat, rs} (mL/cm H₂O), day 12

33 (26 - 41)

37.5 (32.7 - 44)

32 (25 - 41)

< 0.001^a

Driving pressure (cm H₂O)

14 (12 - 16)

13.5 (12 - 16)

14 (12 - 16)

0.081

Laboratory values, median (IQR)

WBCs (absolute number/mm³)

17,800 (14,000 - 21,832)

16,000 (12,945 - 18,567)

18,485 (14,892 - 22,975)

0.004^a

D-dimmer (µg/L)

2,569 (1,340 - 5,600)

2,554 (1,370 - 5,450)

2,650 (1,300 - 5,600)

0.747

CRP (mg/dL)

9 (6 - 15)

9 (5.2 - 13.2)

8.9 (5.9 - 16)

0.592

Ferritin (ng/mL)

1,790 (937 - 3,538)

1,466 (935 - 2,905)

1,900 (920 - 3,771)

0.276

LDH (U/L)

502 (320 - 789)

478 (320 - 683)

533 (320 - 858)

0.336

Comorbidities, n (%)

Hypertension

111 (57.2)

31 (53.4)

80 (58.8)

0.528

Heart failure

28 (14.4)

7 (12)

21 (15.4)

0.658

Coronary artery disease

34 (17.5)

7 (12)

27 (20)

0.221

Lung disease

16 (8.2)

3 (5.2)

13 (9.6)

0.401

Kidney injury

22 (11.3)

3 (5.2)

19 (14)

0.09

Diabetes

53 (27.3)

18 (31)

35 (25.7)

0.484

Cancer

10 (5.2)

3 (5.2)

7 (5.1)

1.00

Outcomes

Mortality n (%)

124 (64)

26 (44.8)

98 (72)

< 0.001^a

ICU LOS, median (IQR)

13 (8 - 25)

14.5 (8.7 - 27)

12 (8 - 24.7)

0.344

Mechanical ventilation days, median (IQR)

12 (6 - 23)

12 (6 - 24)

12 (6 - 22)

0.992

**Table 2.** Predictors of Intensive Care Unit Mortality Based on Uni- and Multivariable Logistic Regression Model
Variable	Vital status	Univariate regression	Multivariable regression
^aFactors that were included in the multivariable regression. ^bFactor Independently associated with mortality in the multivariable regression. OR: odds ratio; CI: confidence interval; aOR: adjusted odds ratio; WBCs: white blood cells; CRP: C-reactive protein; IQR: interquartile range; SOFA: sequential organ failure assessment; BMI: body mass index; Ppl: plateau pressure; PEEP: positive end expiratory pressure; Compliance _{stat, rs}: respiratory system static compliance; LDH: lactate dehydrogenase.
Age, mean (SD)	69.5 (62 - 75)	57 (46 - 64)	1.12 (1.08 - 1.16)	< 0.001^a	1.15 (1.08 - 1.23)	< 0.001^b
Gender (male)	81 (65.3)	48 (68.6)	1.24 (0.66 - 2.33)	0.340
BMI	28 (26 - 33)	28 (26 - 35)	0.99 (0.96 - 1.02)	0.497
SOFA score, median (IQR)	8 (7 - 9)	6 (5.0 - 6.5)	2.28 (1.76 - 2.95)	< 0.001^a	1.81 (1.27 - 2.58)	< 0.001^b
Group (early intubation), n (%)	26 (21)	32 (45.7)	3.3 (3.00 - 3.30)	< 0.001^a
Time to intubation (days)	7 (4 - 10)	3 (2 - 7)	1.17 (1.08 - 1.26)	< 0.001^a	1.15 (1.05 - 1.27)	0.004^b
ICU LOS (days), median (IQR)	12 (6.25 - 21.75)	15 (10 - 17.7)	0.98 (0.97 - 1.00)	0.060
Mechanical ventilation days, median (IQR)	10.5 (6 - 20)	13 (7.75 - 25.25)	0.99 (0.98 - 1.01)	0.353
CPAP duration before intubation (days), median (IQR)	4 (2 - 6)	2 (1 - 4)	1.26 (1.12 - 1.42)	< 0.001^a
Comorbidities, n (%)
Hypertension	84 (67.7)	27 (38.6)	3.3 (1.80 - 6.10)	< 0.001^a
Heart failure	24 (19.4)	4 (5.7)	3.9 (1.31 - 11.90)	0.01^a
Coronary artery disease	31 (25)	3 (4.3)	7.4 (2.18 - 25.36)	< 0.001^a
Lung disease	13 (10.5)	3 (4.3)	2.6 (0.72 - 9.50)	0.17
Kidney injury	18 (14.5)	4 (5.7)	2.8 (0.91 - 8.64)	0.97
Diabetes	36 (29)	17 (24.3)	1.2 (0.65 - 2.49)	0.50
Cancer	9 (7.3)	1 (1.4)	5.4 (0.67 - 43.54)	0.10
Clinical laboratory data
PO₂/FiO₂ ratio before intubation, median (IQR)	86 (77 - 110)	100 (80 - 116)	0.98 (0.97 - 0.99)	0.022
PO₂/FiO₂ ratio after intubation, median (IQR)	95 (80 - 120)	130 (115 - 150)	0.98 (0.97 - 0.99)	< 0.001^a	0.96 (0.94 - 0.98)	0.001^b
Ppl (cm H₂O), median (IQR)	27 (25 - 28)	25 (23 - 27)	1.14 (1.04 - 1.25)	0.004^a
PEEP (cm H₂O), median (IQR)	12 (10 - 14)	12 (12 - 14)	0.94 (0.80 - 1.10)	0.487
Compliance_{stat, rs} (mL/cm H₂O), day 1, median (IQR)	34 (28 - 42)	44 (37 - 52)	0.92 (0.90 - 0.95)	< 0.001^a	1.12 (1.02 - 1.22)	0.012^b
Compliance_{stat, rs} (mL/cm H₂O), day 6, median (IQR)	31 (25 - 38)	42 (37 - 47)	0.89 (0.86 - 0.93)	< 0.001^a
Compliance_{stat, rs} (mL/cm H₂O), day 12, median (IQR)	28 (22 - 35)	42 (37 - 47)	0.85 (0.81 - 0.89)	< 0.001^a	1.14 (1.05 - 1.24)	< 0.001^b
Driving pressure (cm H₂O), median (IQR)	14 (12 - 17)	13 (12 - 15)	1.18 (1.06 - 1.33)	0.003^a
Lung CT severity, n (%)	38 (60.3)	11 (35.5)	2.7 (1.13 - 6.74)	0.03
WBCs (absolute number/mm³), median (IQR)	18,850 (15,687 - 23,367)	15,900 (12,255 - 18,135)	1.01 (1.00 - 1.02)	< 0.001^a	1.00 (1.00 - 1.00)	0.001^b
CRP (mg/dL), median (IQR)	9 (6 - 17)	8.36 (5 - 13)	1.03 (0.99 - 1.07)	0.066
Ferritin (ng/mL), median (IQR)	2,180 (1,107 - 3,700)	1,300 (828 - 2,674)	1.00 (1.00 - 1.00)	0.101
D-dimers (µg/L), median (IQR)	2,340 (1,330 - 5,720)	2,920 (1,375 - 5,407)	1.00 (1.00 - 1.00)	0.360
LDH (U/L), median (IQR)	533 (340 - 889)	465 (277 - 656)	1.00 (1.00 - 1.00)	0.43

Table 2. Predictors of Intensive Care Unit Mortality Based on Uni- and Multivariable Logistic Regression Model

Variable

Vital status

Univariate regression

Multivariable regression

Non-survivors

Survivors

OR (95% CI)

P value

aOR (95% CI)

P value

^aFactors that were included in the multivariable regression. ^bFactor Independently associated with mortality in the multivariable regression. OR: odds ratio; CI: confidence interval; aOR: adjusted odds ratio; WBCs: white blood cells; CRP: C-reactive protein; IQR: interquartile range; SOFA: sequential organ failure assessment; BMI: body mass index; Ppl: plateau pressure; PEEP: positive end expiratory pressure; Compliance _{stat, rs}: respiratory system static compliance; LDH: lactate dehydrogenase.

Age, mean (SD)

69.5 (62 - 75)

57 (46 - 64)

1.12 (1.08 - 1.16)

< 0.001^a

1.15 (1.08 - 1.23)

< 0.001^b

Gender (male)

81 (65.3)

48 (68.6)

1.24 (0.66 - 2.33)

0.340

BMI

28 (26 - 33)

28 (26 - 35)

0.99 (0.96 - 1.02)

0.497

SOFA score, median (IQR)

8 (7 - 9)

6 (5.0 - 6.5)

2.28 (1.76 - 2.95)

< 0.001^a

1.81 (1.27 - 2.58)

< 0.001^b

Group (early intubation), n (%)

26 (21)

32 (45.7)

3.3 (3.00 - 3.30)

< 0.001^a

Time to intubation (days)

7 (4 - 10)

3 (2 - 7)

1.17 (1.08 - 1.26)

< 0.001^a

1.15 (1.05 - 1.27)

0.004^b

ICU LOS (days), median (IQR)

12 (6.25 - 21.75)

15 (10 - 17.7)

0.98 (0.97 - 1.00)

0.060

Mechanical ventilation days, median (IQR)

10.5 (6 - 20)

13 (7.75 - 25.25)

0.99 (0.98 - 1.01)

0.353

CPAP duration before intubation (days), median (IQR)

4 (2 - 6)

2 (1 - 4)

1.26 (1.12 - 1.42)

< 0.001^a

Comorbidities, n (%)

Hypertension

84 (67.7)

27 (38.6)

3.3 (1.80 - 6.10)

< 0.001^a

Heart failure

24 (19.4)

4 (5.7)

3.9 (1.31 - 11.90)

0.01^a

Coronary artery disease

31 (25)

3 (4.3)

7.4 (2.18 - 25.36)

< 0.001^a

Lung disease

13 (10.5)

3 (4.3)

2.6 (0.72 - 9.50)

0.17

Kidney injury

18 (14.5)

4 (5.7)

2.8 (0.91 - 8.64)

0.97

Diabetes

36 (29)

17 (24.3)

1.2 (0.65 - 2.49)

0.50

Cancer

9 (7.3)

1 (1.4)

5.4 (0.67 - 43.54)

0.10

Clinical laboratory data

PO₂/FiO₂ ratio before intubation, median (IQR)

86 (77 - 110)

100 (80 - 116)

0.98 (0.97 - 0.99)

0.022

PO₂/FiO₂ ratio after intubation, median (IQR)

95 (80 - 120)

130 (115 - 150)

0.98 (0.97 - 0.99)

< 0.001^a

0.96 (0.94 - 0.98)

0.001^b

Ppl (cm H₂O), median (IQR)

27 (25 - 28)

25 (23 - 27)

1.14 (1.04 - 1.25)

0.004^a

PEEP (cm H₂O), median (IQR)

12 (10 - 14)

12 (12 - 14)

0.94 (0.80 - 1.10)

0.487

Compliance_{stat, rs} (mL/cm H₂O), day 1, median (IQR)

34 (28 - 42)

44 (37 - 52)

0.92 (0.90 - 0.95)

< 0.001^a

1.12 (1.02 - 1.22)

0.012^b

Compliance_{stat, rs} (mL/cm H₂O), day 6, median (IQR)

31 (25 - 38)

42 (37 - 47)

0.89 (0.86 - 0.93)

< 0.001^a

Compliance_{stat, rs} (mL/cm H₂O), day 12, median (IQR)

28 (22 - 35)

42 (37 - 47)

0.85 (0.81 - 0.89)

< 0.001^a

1.14 (1.05 - 1.24)

< 0.001^b

Driving pressure (cm H₂O), median (IQR)

14 (12 - 17)

13 (12 - 15)

1.18 (1.06 - 1.33)

0.003^a

Lung CT severity, n (%)

38 (60.3)

11 (35.5)

2.7 (1.13 - 6.74)

0.03

WBCs (absolute number/mm³), median (IQR)

18,850 (15,687 - 23,367)

15,900 (12,255 - 18,135)

1.01 (1.00 - 1.02)

< 0.001^a

1.00 (1.00 - 1.00)

0.001^b

CRP (mg/dL), median (IQR)

9 (6 - 17)

8.36 (5 - 13)

1.03 (0.99 - 1.07)

0.066

Ferritin (ng/mL), median (IQR)

2,180 (1,107 - 3,700)

1,300 (828 - 2,674)

1.00 (1.00 - 1.00)

0.101

D-dimers (µg/L), median (IQR)

2,340 (1,330 - 5,720)

2,920 (1,375 - 5,407)

1.00 (1.00 - 1.00)

0.360

LDH (U/L), median (IQR)

533 (340 - 889)

465 (277 - 656)

1.00 (1.00 - 1.00)

0.43