Baseline characteristics of all cases in the recurrence group and Non-recurrence group
A total of 653 CSDH cases were enrolled in this study (Figure 1). This study group included 561 male cases (85.9%) and 92 female cases (14.1%). Patient’s age ranged from 21 to 100 years with a median of 72 years (interquartile range 64 to 80 years). (Table 1). 8 patients with hospitalized mortality were excluded and there was no mortality upon follow-up in this study.
Table 1
Clinical and Demographic Characteristics of Patients with CSDH.
Variables
|
All patients
(N=653)
|
Recurrence(n=96)
|
Non-Recurrence(n=557)
|
P-value
|
Postoperative BUN (mmol/L)
|
4.9 (4,6.4)
|
5.9 (4.4,6.9)
|
4.9 (3.9,6.3)
|
<0.001
|
Demographic parameters
|
|
|
|
|
Age (years)
|
72 (64,80)
|
75 (69,82)
|
71 (63,80)
|
0.012
|
Gender
|
|
|
|
0.263
|
Male, n (%)
|
561 (85.9%)
|
86 (89.6%)
|
475 (85.3%)
|
|
Female, n (%)
|
92 (14.1%)
|
10 (10.4%)
|
82 (14.7%)
|
|
Current drinking, n (%)
|
234 (35.8%)
|
34 (35.4%)
|
200 (35.9%)
|
0.926
|
Current smoking, n (%)
|
237 (36.3%)
|
33 (34.4%)
|
204 (36.6%)
|
0.672
|
Baseline SBP (mmHg)
|
138 (126,153)
|
135 (124,151)
|
140 (127,153)
|
0.122
|
Baseline DBP (mmHg)
|
79 (71,87)
|
77 (71,84)
|
79 (71,87)
|
0.091
|
Laboratory investigation
|
|
|
|
|
Blood glucose(mmol/L)
|
5.5 (4.7,6.6)
|
5.7 (5,6.7)
|
5.4 (4.7,6.6)
|
0.265
|
Cr (μmol/L)
|
67 (58,77)
|
68 (60,80)
|
66 (57,77)
|
0.097
|
Leukocyte (X10^9/L)
|
6.94 (5.81,8.43)
|
6.51 (5.52,7.55)
|
7.01 (5.85,8.62)
|
0.010
|
Neutrophil (X10^9/L)
|
4.62 (3.68,6.15)
|
4.30 (3.51,5.31)
|
4.70 (3.71,6.26)
|
0.012
|
Lymphocyte (X10^9/L)
|
1.46 (1.10,1.81)
|
1.46 (1.17,1.83)
|
1.47 (1.1,1.81)
|
0.650
|
Erythrocyte (X10^12/L)
|
4.23 ± 0.51
|
4.19 ± 0.52
|
4.24 ± 0.51
|
0.379
|
Hemoglobin (g/L)
|
132 (120,142)
|
132 (119,142)
|
132 (119,140)
|
0.442
|
Platelet (X10^9/L)
|
211 (172,249)
|
194 (164,239)
|
213 (175,251)
|
0.010
|
Prothrombin Time(s)
|
13.3 (12.8,13.9)
|
13.4 (12.8,14.0)
|
13.3 (12.8,13.9)
|
0.642
|
INR
|
1.02 (0.97,1.08)
|
1.02 (0.98,1.10)
|
1.02 (0.97,1.07)
|
0.719
|
Fibrinogen (g/L)
|
3.61 (3.09,4.28)
|
3.50 (2.89,4.15)
|
3.64 (3.15,4.30)
|
0.046
|
Comorbidities
|
|
|
|
|
Hypertension, n (%)
|
252 (38.6%)
|
40 (41.7%)
|
212 (38.1%)
|
0.503
|
Diabetes mellitus, n (%)
|
77 (11.8%)
|
11 (11.5%)
|
66 (11.8%)
|
0.913
|
Cardiovascular disease, n (%)
|
42 (6.4%)
|
6 (6.3%)
|
36 (6.5%)
|
0.937
|
Medication use
|
|
|
|
|
Atorvastatin therapy, n (%)
|
478 (73.2%)
|
74 (77.1%)
|
404 (72.5%)
|
0.352
|
PAMBA therapy, n (%)
|
189 (28.9%)
|
26 (27.1%)
|
163 (29.3%)
|
0.663
|
Hematoma location
|
|
|
|
0.957
|
Unilateral left, n (%)
|
288 (44.1%)
|
42 (43.8%)
|
246 (44.2%)
|
|
Unilateral right, n (%)
|
216 (33.1%)
|
31 (32.3%)
|
185 (33.2%)
|
|
Bilateral, n (%)
|
149 (22.8%)
|
23 (24.0%)
|
126 (22.6%)
|
|
Postoperative bleeding
|
136 (20.8%)
|
22 (22.9%)
|
114 (20.5%)
|
0.585
|
GOS at discharge
|
|
|
|
0.549
|
5, n (%)
|
593 (90.8%)
|
90 (93.8%)
|
503 (90.3%)
|
|
4, n (%)
|
48 (7.4%)
|
5 (5.2%)
|
43 (7.7%)
|
|
3, n (%)
|
12 (1.8%)
|
1 (1.0%)
|
11 (2.0%)
|
|
Preoperative investigation
|
N=632
|
n=95
|
n=537
|
|
BUN (mmol/L)
|
5.3 (4.4,6.5)
|
5.9 (4.8,6.9)
|
5.2 (4.3,6.4)
|
0.001
|
NOTE. SBP, systolic blood pressure; DBP, diastolic blood pressure; Cr, creatinine; INR, international normalized ratio; PAMBA, para-aminomethylbenzoic acid; BUN, blood urea nitrogen; GOS, Glasgow Outcome Scale.
The descriptive characteristics between groups with and without recurrence are shown in Table 1, including the demographics, laboratory, imaging, medication and comorbidity characteristics. In this study, 96 (14.7%) cases were diagnosed as CSDH recurrence, including 16 patients who needed a second operation. Compared with non-recurrence, the cases in the group of recurrence were older and have lower levels of serum leukocyte, neutrophil and platelet count. However, lower serum fibrinogen concentration was examined in recurrence cases (P<0.05). Moreover, there was a statistical difference between pre and post-operative groups on serum BUN concentration (P=0.001 and P<0.001, respectively). Table 2 revealed that the BUN level of the pre-operative group was significantly higher than the post-operative BUN level in the non-recurrence group (P<0.001) while it showed no obvious difference in the recurrence group.
Table 2
The comparison between pre- and post-operative BUN levels.
Variable
|
Preoperative BUN (mmol/L)
|
Postoperative BUN (mmol/L)
|
P-value
|
Total (n=632)
|
5.3 (4.4,6.5)
|
4.9 (4.0,6.4)
|
<0.001
|
Recurrence (n=95)
|
5.9 (4.8,6.9)
|
5.85 (4.4,6.9)
|
0.177
|
Non-Recurrence (n=537)
|
5.2 (44.3,6.4)
|
4.9 (3.9,6.25)
|
<0.001
|
BUN, blood urea nitrogen;
Baseline characteristics of all cases in BUN quartiles
For further exploration, the cases were divided into 4 groups based on quartiles of the postoperative BUN concentration. The cut-off points for this stratification of the BUN concentration into quartiles were: Q1 ≤ 4.0 mmol/L, 4.0 < Q2 ≤ 4.9 mmol/L, 4.9 < Q3 ≤ 6.4 mmol/L and Q4 > 6.4 mmol/L. Table 3 summarizes the characteristics of the CSDH cases by the quartiles of BUN. Cases with different postoperative BUN concentration appeared to be similar in most features except for age, Cr, erythrocyte and hemoglobin. These factors would be adjusted for multivariate-adjusted binary logistic regression for good measure. 22 (14%) of 157 patients in the highest quartile of BUN suffered moderate disability at discharge which was statistically higher than in other quartiles.
Table 3
Baseline Characteristics of Patients with Chronic Subdural Hematoma according to postoperative BUN quartile.
Variables
|
BUN quartiles
|
|
|
|
|
|
quartile 1 n=170(≤4.0)
|
quartile 2 n=162(>4.0,≤4.9)
|
quartile 3 n=164(>4.9,≤6.4)
|
quartile 4 n=157(>6.4)
|
P-value
|
BUN (mmol/L)
|
3.4 (3.0,3.7)
|
4.5 (4.3,4.8)
|
5.7 (5.3,6.0)
|
7.4 (6.9,8.3)
|
<0.001
|
Demographic parameters
|
|
|
|
|
|
Age (years)
|
68 (61,76)
|
72 (63,79)
|
73 (66,82)
|
76 (69,83)
|
<0.001
|
Gender, male, n (%)
|
140 (82.4%)
|
148 (91.4%)
|
141 (86.0%)
|
132 (84.1%)
|
0.103
|
Current drinking, n (%)
|
61 (35.9%)
|
62 (38.3%)
|
58 (35.4%)
|
53 (33.8%)
|
0.866
|
Current smoking, n (%)
|
68 (39.4%)
|
56 (34.6%)
|
63 (38.4%)
|
51 (32.5%)
|
0.526
|
Baseline SBP (mmHg)
|
138.4 ± 19.4
|
139.3 ± 19.7
|
141.0 ± 20.6
|
142.5 ± 21.0
|
0.274
|
Baseline DBP (mmHg)
|
79 (71,87)
|
79 (73,86)
|
77 (72,88)
|
78 (71,87)
|
0.984
|
Laboratory investigation
|
|
|
|
|
|
Blood glucose(mmol/L)
|
5.5 (4.8,6.5)
|
5.6 (4.7,6.6)
|
5.6 (4.7,6.8)
|
5.4 (4.5,6.7)
|
0.818
|
Cr (μmol/L)
|
60 (54,68)
|
66 (57,75)
|
69 (60,80)
|
74 (63,87)
|
<0.001
|
Leukocyte (X10^9/L)
|
7.00 (6.14,8.45)
|
6.97 (5.81,8.62)
|
6.98 (5.73,8.33)
|
6.77 (5.55,8.39)
|
0.677
|
Neutrophil (X10^9/L)
|
4.78 (3.84,6.31)
|
4.68 (3.76,6.30)
|
4.52 (3.59,5.92)
|
4.52 (3.60,5.95)
|
0.369
|
Lymphocyte (X10^9/L)
|
1.50 (1.10,1.80)
|
1.40 (1.10,1.71)
|
1.50 (1.11,1.87)
|
1.45 (1.10,1.81)
|
0.518
|
Erythrocyte (X10^12/L)
|
4.30 ± 0.51
|
4.27 ± 0.50
|
4.24 ± 0.52
|
4.12 ± 0.52
|
0.008
|
Hemoglobin (g/L)
|
133 (120,144)
|
133 (123,142)
|
132 (120,144)
|
130 (116,139)
|
0.047
|
Platelet (X10^9/L)
|
219 (174,259)
|
206 (175,250)
|
203 (175,243)
|
201 (162,249)
|
0.183
|
Prothrombin Time (s)
|
13.3 (12.7,13.8)
|
13.2 (12.9,13.9)
|
13.4 (12.9,13.9)
|
13.4 (12.9,14.1)
|
0.523
|
INR
|
1.02 (0.97,1.07)
|
1.02 (0.97,1.08)
|
1.03 (0.97,1.08)
|
1.03 (0.97,1.10)
|
0.484
|
Fibrinogen (g/L)
|
3.55 (3.11,4.38)
|
3.71 (3.10,4.35)
|
3.61 (2.97,4.18)
|
3.67 (3.12,4.26)
|
0.740
|
Comorbidities
|
|
|
|
|
|
Hypertension, n (%)
|
61 (35.9%)
|
61 (37.7%)
|
60 (36.6%)
|
70 (44.6%)
|
0.355
|
Diabetes mellitus, n (%)
|
18 (10.6%)
|
18 (11.1%)
|
17 (10.4%)
|
24 (15.3%)
|
0.480
|
Cardiovascular disease, n (%)
|
9 (5.3%)
|
10 (6.2%)
|
11 (6.7%)
|
12 (7.6%)
|
0.853
|
Medication use
|
|
|
|
|
|
Atorvastatin therapy, n (%)
|
124 (72.9%)
|
118 (72.8%)
|
114 (69.5%)
|
122 (77.7%)
|
0.427
|
PAMBA therapy, n (%)
|
40 (23.5%)
|
45 (27.8%)
|
53 (32.3%)
|
51 (32.5%)
|
0.222
|
Hematoma location
|
|
|
|
|
0.367
|
Unilateral left, n (%)
|
68 (40.0%)
|
82 (50.6%)
|
75 (45.7%)
|
63 (40.1%)
|
|
Unilateral right, n (%)
|
62 (36.5%)
|
48 (29.6%)
|
55 (33.5%)
|
51 (32.5%)
|
|
Bilateral, n (%)
|
40 (23.5%)
|
32 (19.8%)
|
34 (20.7%)
|
43 (27.4%)
|
|
GOS at discharge
|
|
|
|
|
0.042
|
5, n (%)
|
160 (94.1%)
|
149 (92.0%)
|
152 (92.7%)
|
132 (84.1%)
|
|
4, n (%)
|
8 (4.7%)
|
10 (6.2%)
|
8 (4.9%)
|
22 (14%)
|
|
3, n (%)
|
2 (1.2%)
|
3 (1.9%)
|
4 (2.4%)
|
3 (1.9%)
|
|
NOTE. SBP, systolic blood pressure; DBP, diastolic blood pressure; Cr, creatinine; INR, international normalized ratio; PAMBA, para-aminomethylbenzoic acid; BUN, blood urea nitrogen; GOS, Glasgow Outcome Scale.
Association between the BUN concentrations and recurrence
Significant differences were observed between the recurrence and non-recurrence groups in BUN concentration quartiles of cases (P= 0.003). The proportion of cases in the lowest quartile (≤4.0 mmol/L) was dramatically low in the recurrence group (P = 0.027), whilst the proportion of cases in the highest quartile (>6.4 mmol/L) was significantly high in the recurrence group (P= 0.012) (Table 4).
Table 4
BUN quartiles of patients.
Variable
|
Recurrence (n=96)
|
Non-Recurrence (n=557)
|
c²
|
P-value
|
BUN (mmol/L)
|
|
|
14.308
|
0.003
|
Quartile 1(≤4.0)
|
14 (14.6%)
|
156 (28.0%)
|
4.870
|
0.027
|
Quartile 2(>4.0,≤4.9)
|
22 (22.9%)
|
140 (25.1%)
|
0.132
|
0.717
|
Quartile 3(>4.9,≤6.4)
|
24 (25.0%)
|
140 (25.1%)
|
0.000
|
0.983
|
Quartile 4(>6.4)
|
36 (37.5%)
|
121 (21.7%)
|
6.283
|
0.012
|
BUN, blood urea nitrogen;
In Table 5, with all cases taken as a whole, the condition that CSDH recurrence was interpreted as a dependent variable and the lowest quartile was interpreted as the reference was used for postoperative BUN level in the binary logistic regression models. The highest quartile of BUN concentration (>6.4 mmol/L) was independently estimated as a risk factor of CSDH recurrence with an unadjusted OR of 3.315 (95%CI:1.711–6.423, P<0.001). After adjusting for the confounders including sex, age, current alcohol drinking, current smoking, comorbidities (hypertension, diabetes mellitus, coronary heart disease), medicine (Atorvastatin and PAMBA), and laboratory investigation (platelet, fibrinogen, leukocyte, erythrocyte, hemoglobin, Cr), the highest quartile of BUN remained significantly and independently associated with CSDH recurrence (model 1: OR=2.892, 95% CI:1.463–5.717, P=0.002; model 2: OR=2.939, 95% CI:1.480–5.836, P=0.002; model 3: OR=3.069, 95%CI:1.488–6.330, P=0.002). There was no multicollinearity between the independent variables in model 3. Furthermore, restricted cubic spline regressions were used to explore the linear relationship between BUN concentration and the risk of CSDH recurrence (Figure 3). Most importantly, it could be observed visually that the highest quartile had a significantly high OR value.
Table 5
Multivariate adjusted odds ratios for the association between BUN levels and Recurrence.
|
Quartile
|
ORa
|
95%CI
|
P-value
|
Unadjusted
|
Middle
|
1.751
|
0.863-3.554
|
0.121
|
|
Higher
|
1.910
|
0.951-3.837
|
0.069
|
|
Highest
|
3.315
|
1.711-6.423
|
<0.001
|
Model 1b
|
Middle
|
1.590
|
0.778-3.252
|
0.204
|
|
Higher
|
1.713
|
0.842-3.483
|
0.137
|
|
Highest
|
2.892
|
1.463-5.717
|
0.002
|
Model 2c
|
Middle
|
1.612
|
0.788-3.299
|
0.191
|
|
Higher
|
1.768
|
0.866-3.611
|
0.118
|
|
Highest
|
2.939
|
1.480-5.836
|
0.002
|
Model 3d
|
Middle
|
1.612
|
0.780-3.333
|
0.197
|
|
Higher
|
1.733
|
0.837-3.590
|
0.139
|
|
Highest
|
3.069
|
1.488-6.330
|
0.002
|
OR, odds radio; CI confidence level; Cr, creatinine; Recurrence of postoperative CSDH.
a Reference OR (1.000) is the lowest quartile of BUN for Recurrence of CSDH.
b Model 1: adjusted for age, sex, current smoking, current alcohol drinking.
c Modal 2: adjusted for covariates from Model 1 and further adjusted for medical history (coronary heart disease, diabetes mellitus, hypertension)and medicine(Atorvastatin and PAMBA)
d Modal 3: adjusted for covariates from Model 2 and further adjusted for Platelet, Fibrinogen, Leukocyte, Erythrocyte, Hemoglobin, Cr.