Participants
In total, 813 patients were admitted to the two ICUs during our enrollment period. After excluding patients who did not meet the enrollment criteria, a total of 407 patients were included in the survey (Fig 1).
Characteristics of the study population by different PaO2/FiO2 levels
The average age of the participants was 54.40 years (standard deviation, 16.08 years), and 237 participants (58.2%) were male. Of the 407 patients, 184 (45.2%) developed delirium in this study. The characteristics of the study population at different PaO2/FiO2 levels are listed in Table 1. There were no statistical differences in age, gender, heart disease, history of cerebral vascular accident (CVA), diabetes, smoking habits, drinking habits, blood pressure at admission, mechanical ventilation, PaCO2 at 24 h after admission, or sedation among the different PaO2/FiO2 groups. In contrast, SOFA scores, APACHE II scores, and mechanical ventilation durations were significantly higher in lower-PaO2/FiO2 groups than in the normal group. Patients with lower PaO2/FiO2 were more likely to have complications such as hypertension, chronic pulmonary dysfunction, and delirium compared with those in the normal group.
Table 1
Characteristics of the Study Population by Different PaO2/FiO2 Levels.
PaO2/FiO2 (mmHg)
|
Normal
(> 300)
|
Slightly low
(200–300)
|
Moderately low (100–200)
|
Severely low
(< 100)
|
P value
|
N
|
203
|
128
|
63
|
9
|
|
Age (years, mean ± SD)
|
52.4 ± 17.1
|
56.3 ± 15.1
|
57.2 ± 14.2
|
59.4 ± 12.0
|
0.054
|
SOFA score (median, Q1–Q3)
|
4.0 (2.0–7.5)
|
5.0 (2.0–10.0)
|
8.0 (4.0–12.0)
|
8.0 (6.0–19.0)
|
< 0.001
|
APACHE II score
|
10.2 ± 5.7
|
11.2 ± 5.4
|
13.4 ± 5.2
|
17.0 ± 7.2
|
< 0.001
|
Mechanical ventilation time (median, Q1–Q3)
|
7.0 (2.0–12.0)
|
8.0 (2.0–17.2)
|
12.0 (5.0–38.8)
|
58.5 (37.0–85.2)
|
< 0.001
|
PaCO2 (mean ± SD)
|
37.9 ± 7.1
|
38.8 ± 9.7
|
39.4 ± 7.7
|
42.0 ± 7.3
|
0.263
|
Gender (n, %)
|
|
|
|
|
0.403
|
Male
|
112 (55.2%)
|
73 (57.0%)
|
42 (66.7%)
|
6 (66.7%)
|
|
Female
|
91 (44.8%)
|
55 (43.0%)
|
21 (33.3%)
|
3 (33.3%)
|
|
Hypertension (n, %)
|
|
|
|
|
0.005
|
No
|
151 (74.4%)
|
86 (67.2%)
|
32 (50.8%)
|
5 (55.6%)
|
|
Yes
|
52 (25.6%)
|
42 (32.8%)
|
31 (49.2%)
|
4 (44.4%)
|
|
Heart disease (n, %)
|
|
|
|
|
0.488
|
No
|
157 (77.3%)
|
93 (72.7%)
|
43 (68.3%)
|
7 (77.8%)
|
|
Yes
|
46 (22.7%)
|
35 (27.3%)
|
20 (31.7%)
|
2 (22.2%)
|
|
History of CVA (n, %)
|
|
|
|
|
0.536
|
No
|
198 (97.5%)
|
122 (95.3%)
|
62 (98.4%)
|
9 (100.0%)
|
|
Yes
|
5 (2.5%)
|
6 (4.7%)
|
1 (1.6%)
|
0 (0.0%)
|
|
Diabetes (n, %)
|
|
|
|
|
0.374
|
No
|
186 (91.6%)
|
111 (86.7%)
|
59 (93.7%)
|
8 (88.9%)
|
|
Yes
|
17 (8.4%)
|
17 (13.3%)
|
4 (6.3%)
|
1 (11.1%)
|
|
Chronic pulmonary dysfunction (n, %)
|
|
|
|
|
0.038
|
No
|
194 (95.6%)
|
116 (90.6%)
|
55 (87.3%)
|
7 (77.8%)
|
|
Yes
|
9 (4.4%)
|
12 (9.4%)
|
8 (12.7%)
|
2 (22.2%)
|
|
Smoking habits (n, %)
|
|
|
|
|
0.468
|
No
|
149 (73.4%)
|
84 (65.6%)
|
46 (73.0%)
|
6 (66.7%)
|
|
Yes
|
54 (26.6%)
|
44 (34.4%)
|
17 (27.0%)
|
3 (33.3%)
|
|
Drinking habits (n, %)
|
|
|
|
|
0.483
|
No
|
179 (88.2%)
|
108 (84.4%)
|
58 (92.1%)
|
8 (88.9%)
|
|
Yes
|
24 (11.8%)
|
20 (15.6%)
|
5 (7.9%)
|
1 (11.1%)
|
|
Postoperative surgery
|
|
|
|
|
< 0.001
|
No
|
26 (12.8%)
|
36 (28.1%)
|
19 (30.2%)
|
6 (66.7%)
|
|
Yes
|
177 (87.2%)
|
92 (71.9%)
|
44 (69.8%)
|
3 (33.3%)
|
|
Blood pressure at admission
|
|
|
|
|
0.835
|
Normal
|
99 (48.8%)
|
63 (49.2%)
|
27 (42.9%)
|
3 (33.3%)
|
|
Low
|
68 (33.5%)
|
42 (32.8%)
|
21 (33.3%)
|
3 (33.3%)
|
|
High
|
36 (17.7%)
|
23 (18.0%)
|
15 (23.8%)
|
3 (33.3%)
|
|
Mechanical ventilation
|
|
|
|
|
0.217
|
No
|
37 (18.2%)
|
30 (23.4%)
|
8 (12.7%)
|
3 (33.3%)
|
|
Yes
|
166 (81.8%)
|
98 (76.6%)
|
55 (87.3%)
|
6 (66.7%)
|
|
Sedation (n, %)
|
|
|
|
|
0.250
|
No
|
57 (28.1%)
|
39 (30.5%)
|
12 (19.0%)
|
4 (44.4%)
|
|
Yes
|
146 (71.9%)
|
89 (69.5%)
|
51 (81.0%)
|
5 (55.6%)
|
|
Delirium (n, %)
|
|
|
|
|
0.001
|
No
|
121 (59.6%)
|
73 (57.0%)
|
24 (38.1%)
|
1 (11.1%)
|
|
Yes
|
82 (40.4%)
|
55 (43.0%)
|
39 (61.9%)
|
8 (88.9%)
|
|
Partial pressure of arterial oxygen (PaO2), the fraction of inspired oxygen (FiO2), Acute Physiology and Chronic Health Evaluation II score (APACHE II score), Sequential Organ Failure Assessment (SOFA score), arterial partial pressure of carbon dioxide (PaCO2), cerebral vascular accident (CVA). |
Risk factor for delirium evaluated by univariate analysis
The association for variables and delirium by univariate analysis are shown in Table 2. The results showed that age(OR = 1.05, 95% CI [1.0, 1.1], P < 0.001), SOFA score (OR = 1.1, 95% CI [1.1, 1.2], P < 0.001), APACHE II score (OR = 1.2, 95% CI [1.12, 1.2], P < 0.001), and mechanical ventilation time (OR = 1.2, 95% CI [1.0, 1.1], P < 0.001),were positively correlated with the development of delirium. Hypertension, heart disease, history of CVA, postoperative surgery, low blood pressure at admission, and sedation were also positively correlated with delirium. The value of PaO2/FiO2 was significantly associated with delirium, the OR was 1.0, 95%CI was 1.0 to 1.0, P = 0.005. However, gender, diabetes, chronic pulmonary dysfunction, smoking habits, drinking habits, mechanical ventilation, and PaCO2 were not associated with delirium.
Table 2
Association for Variables and Delirium Evaluated by Univariate Analysis.
|
Statistics
|
OR (95% CI), P value
|
Gender
|
|
|
Male
|
237 (58.2%)
|
1.0
|
Female
|
170 (41.8%)
|
1.32 (0.9, 2.0), 0.165
|
Age
|
54.4 ± 16.1
|
1.05 (1.0, 1.1), < 0.001
|
Hypertension
|
|
|
No
|
278 (68.3%)
|
1.0
|
Yes
|
129 (31.7%)
|
1.9 (1.2, 2.9), 0.004
|
Heart disease
|
|
|
No
|
304 (74.7%)
|
1.0
|
Yes
|
103 (25.3%)
|
1.6 (1.0, 2.5), 0.048
|
History of CVA
|
|
|
No
|
395 (97.1%)
|
1.0
|
Yes
|
12 (2.9%)
|
6.2 (1.3, 28.5), 0.020
|
Diabetes
|
|
|
No
|
368 (90.4%)
|
1.0
|
Yes
|
39 (9.6%)
|
1.6 (0.8,3.1), 0.171
|
Chronic pulmonary dysfunction
|
|
|
No
|
376 (92.4%)
|
1.0
|
Yes
|
31 (7.6%)
|
2.0 (0.9, 4.2), 0.079
|
Smoking habits
|
|
|
No
|
286 (70.3%)
|
1.0
|
Yes
|
121 (29.7%)
|
0.7 (0.5, 1.1), 0.152
|
Drinking habits
|
|
|
No
|
355 (87.2%)
|
1.0
|
Yes
|
52 (12.8%)
|
1.0 (0.6, 1.8), 0.974
|
Postoperative surgery
|
|
|
No
|
90 (22.1%)
|
1.0
|
Yes
|
317 (77.9%)
|
2.2 (1.4, 3.6), 0.001
|
SOFA score
|
6.1 ± 5.0
|
1.1 (1.1, 1.2), < 0.001
|
APACHE II score
|
11.2 ± 5.8
|
1.2 (1.12, 1.2), < 0.001
|
Blood pressure at admission
|
|
|
Normal
|
195 (47.9%)
|
1.0
|
Low
|
135 (33.2%)
|
1.7 (1.1, 2.6), 0.019
|
High
|
77 (18.9%)
|
1.6 (0.9, 2.7), 0.095
|
Mechanical ventilation
|
|
|
No
|
77 (18.9%)
|
1.0
|
Yes
|
330 (81.1%)
|
1.5 (0.9, 2.5), 0.107
|
Mechanical ventilation time
|
18.40 ± 36.05
|
1.0 (1.0, 1.1), < 0.001
|
Sedation
|
|
|
No
|
112 (27.5%)
|
1.0
|
Yes
|
295 (72.5%)
|
2.5 (1.6, 3.9), < 0.001
|
PaCO2
|
38.5 ± 8.1
|
1.0 (1.0, 1.1), 0.131
|
PaO2/FiO2
|
306.1 ± 121.4
|
1.0 (1.0, 1.0), 0.005
|
The relationship between PaO2/FiO2 and delirium
Multivariate regression analysis models were used to analyze the association between PaO2/FiO2 and delirium. The non-adjusted, minimally adjusted, and fully adjusted models are shown in Table 3. In the non-adjusted model, the PaO2/FiO2 showed a significant correlation with delirium (OR = 1.0, 95% CI [1.0, 1.0], P = 0.006). The effect size showed no obvious change (OR = 1.0, 95% CI [1.0, 1.0], P = 0.038) in the minimally adjusted model (i.e., we adjusted for age and sex). However, we did not detect a significant correlation in the fully adjusted model (OR = 1.0, 95%CI [1.0,1.0], P = 0.854), which we adjusted for the following covariates: gender, age, hypertension, heart disease, history of CVA, diabetes, smoking habits, drinking habits, chronic pulmonary dysfunction, infection, blood pressure at admission, postoperative surgery, mechanical ventilation, mechanical ventilation time, PaCO2, sedation, APACHE II score, and SOFA score.
Table 3
Relationship between PaO2/FiO2 and Delirium in Different Models.
Variable
|
Crude model, OR (95% CI), P value
|
Minimally adjusted model, OR (95% CI), P value
|
Fully adjusted mode, OR (95% CI), P value
|
PaO2/FiO2 group
|
1.0, (1.0, 1.0), 0.006
|
1.0, (1.0, 1.0), 0.038
|
1.0, (1.0, 1.0), 0.854
|
Normal
|
Ref
|
Ref
|
Ref
|
Mild lower
|
1.11, (0.7, 1.7), 0.643
|
0.93, (0.6, 1.5), 0.785
|
0.83, (0.5, 1.5), 0.486
|
Moderate lower
|
2.4, (1.34, 4.29), 0.003
|
2.31, (1.24, 4.33), 0.009
|
1.18, (0.57, 2.43), 0.658
|
Severe lower
|
11.8, (1.45, 96.18), 0.021
|
11.6, (1.34, 100.85), 0.026
|
6.0, (0.53, 67.91), 0.148
|
Crude model: We did not adjust other covariates. |
Minimally adjusted model: We adjusted for age and sex. |
Fully adjusted model: We adjusted for sex, age, hypertension, heart disease, history of CVA, diabetes, smoking habits, drinking habits, chronic pulmonary dysfunction, blood pressure at admission, postoperative surgery, mechanical ventilation, mechanical ventilation time, sedation, PaCO2, APACHE II score, and SOFA score (CI: confidence interval; Ref: reference). |
We explored the non-linear relationship between PaO2/FiO2 and the risk of delirium using a generalized additive model (Fig. 2). We found that the relationship between PaO2/FiO2 and the probability of delirium was non-linear after adjusting for the following: gender, age, hypertension, heart disease, history of CVA, diabetes, smoking habits, drinking habits, chronic pulmonary dysfunction, blood pressure at admission, postoperative surgery, mechanical ventilation, mechanical ventilation time, PaCO2, sedation, APACHE II score, and SOFA score. We used a two-piecewise linear regression model to calculate the threshold of 247 mmHg. On the left of the inflection point, we found a negative relationship between the PaO2/FiO2 and the probability of delirium, where the OR was 0.91 (95% CI [0.84, 0.98]; P = 0.019) per 10 mmHg change in PaO2/FiO2. In contrast, we observed a positive relationship between PaO2/FiO2 and the probability of delirium on the right side of the inflection point, where the OR was 1.03 (95% CI [1.00, 1.06]; P = 0.050 with the PaO2/FiO2 per 10 mmHg change; Table 4).
Table 4
Threshold Effect Analysis of the Relationship between PaO2/FiO2 and Delirium Using A Two-Piecewise Linear Regression Model.
Inflection point of PaO2/FiO2 (per 10 mmHg change)
|
OR
|
95% CI
|
P value
|
< 247
|
0.91
|
0.84–0.98
|
0.019
|
≥ 247
|
1.03
|
1.00–1.06
|
0.050
|