Among 758 patients screened, 565 patients were included in the study who received pharmacological VTE prophylaxis at ICU admission. Patient characteristics and demographic data are described in supplemental data (Additional file 1). The high dosing regimen of pharmacological VTE prophylaxis was given to 185 patients, whereas 380 patients received a standard dosing regimen. We matched 352 patients using propensity score matching (1:1) according to the baseline severity scores (i.e., APACHE II score, SOFA score), history of CKD, and AKI within 24 hours of ICU admission. We observed that all included patients received early pharmacological VTE prophylaxis within 24 hours of ICU admission with 96.4 % and 95.8% in standard and high dosing regimens, respectively.
Demographic and Clinical Characteristics
Most of the patients in both groups were men (72.3%), and the average age of the patients was 60.9 ± 14 years (Additional file 1). Severity scores (i.e., APACHE II and SOFA scores), procalcitonin levels, fibrinogen levels, serum creatinine, acute kidney injury within 24 hours of ICU admission were higher in patients who received standard dosing of pharmacological VTE prophylaxis (Additional file 1). The most common comorbidities in both arms were diabetes mellitus (60%), hypertension (55.9%), and dyslipidemia (22.8%). Moreover, chronic kidney disease and history of VTE were higher in standard dosing compared with high dosing of pharmacological VTE prophylaxis (Additional file 2). There were no significant differences in baseline and demographic characteristics after adjustment using propensity score matching for patients’ baseline severity scores and acute kidney injury within 24 hours of ICU admission.
Thrombosis/bleeding during ICU stay
During ICU stay, for patients who received high dosing pharmacological VTE prophylaxis, venous thromboembolism (OR (95%CI): 0.75 (0.16–3.38), p-value = 0.70) and any case of thrombosis (OR (95%CI): 1.22 (0.52–2.86), p-value = 0.64) were not significant compared with standard dosing (Table 1).
Table 1
Regression analysis for ICU complication (s) during ICU stay
Outcomes
|
VTE prophylaxis
|
P-value ^^
|
Odds Ratio (OR) (95%CI)
|
P-value $
|
High dose
|
Standard dose
|
Respiratory Failure Required MV, n/N (%) $*
|
23/66 (34.8)
|
26/73 (35.6)
|
0.92
|
0.98 (0.49, 1.96)
|
0.95
|
Any Thrombosis During ICU, n/N(%)
|
13/172 (7.5)
|
11/175 (6.2)
|
0.64
|
1.22 (0.52 ,2.86)
|
0.64
|
Venous Thromboembolism (VTE), n/N(%)
|
3/176 (1.7)
|
4/176 (2.27)
|
0.70
|
0.75 (0.16 ,3.38)
|
0.70
|
Major bleeding, n/N(%)
|
9/174 (5.2)
|
7/171 (4.09)
|
0.63
|
1.28 (0.46 ,3.53)
|
0.63
|
Minor bleeding, n/N(%)
|
13/173 (7.5)
|
4/171 (2.3)
|
0.03
|
3.39 (1.08 ,10.61)
|
0.04
|
Requiring RBCs transfusion during ICU stay, n/N(%)
|
23/165 (13.9)
|
29/173 (16.7)
|
0.47
|
0.80 (0.44 ,1.46)
|
0.46
|
ICU readmission within 3 months, n/N(%) ¥
|
10/103 (9.7)
|
13/112 (11.6)
|
0.65
|
0.81 (0.34 ,1.95)
|
0.63
|
- Denominator of the percentage is the total number of patients.
^^ Chi-square /**Fisher Exact test is used to calculate the P-value.
$ Propensity score after adjusting for patient’s APACHE II score, SOFA score, chronic kidney disease (CKD), and acute kidney injury (AKI) within 24 hours of ICU admission to calculate Odds ratio and p-value.
$* Denominator of the percentage is non-mechanically ventilated patients with 24 hours of ICU admission.
|
In patients who received high dosing pharmacological VTE prophylaxis, minor bleeding was higher by 3.5 folds compared with standard dosing of pharmacological VTE prophylaxis (OR (95%CI): 3.39 (1.08–10.61), p-value = 0.04). The proportion of minor bleeding was 2.3% in the standard dosing compared with 7.5% in patients who received high dosing pharmacological VTE prophylaxis. In term of major bleeding and requiring RBCs transfusion during ICU stay, there is no statistical differences between the two groups (OR (95%CI): 1.28 (0.46–3.53), p-value = 0.63) and (OR (95%CI): 0.80 (0.44–1.46), p-value = 0.46), respectively (Table 1).
Mortality and length of stay
As shown in Table 2, there was no difference in the 30-day ICU mortality nor in-hospital mortality between the two groups (OR (95%CI): 1.26 (0.77–2.05), p-value = 0.36 and OR (95%CI): 1.05 (0.66–1.68), p-value = 0.83 respectively). During ICU stay, the proportion of death was 27.8 % in the standard dosing compared with 31.1% in high dosing VTE pharmacological prophylaxis (Table 2).
Table 2
Regression analysis for the outcomes
Outcomes
|
VTE prophylaxis
|
|
Odds Ratio (95%CI)
|
P-value $
|
Standard dose
|
High dose
|
P-value
|
In-hospital mortality, n/N(%) ∆
|
62/169 (36.6)
|
63/167 (37.7)
|
0.84^^
|
1.05 (0.66 ,1.68)
|
0.83
|
30 day- ICU mortality, n/N(%) ∆
|
47/169 (27.8)
|
54/168 (31.1)
|
0.39^^
|
1.26 (0.77 ,2.05)
|
0.36
|
ICU readmission within 3 months, n/N(%) ¥
|
10/103 (9.7)
|
13/112 (11.6)
|
0.65
|
0.81 (0.338 ,1.946)
|
0.63
|
|
|
|
|
Beta- coefficient (95%CI)
|
P-value $*
|
MV duration, Median (IQR) &
|
6.0 (1.0,13.0)
|
3.0 (0.0,10.0)
|
0.29
|
-0.17 (-0.58, 0.24)
|
0.41
|
ICU Length of Stay Days, Median (IQR) &
|
9.0 (5.0,15.0)
|
8.0 (5.0,13.0)
|
0.39
|
-0.12 (-0.31, 0.07)
|
0.23
|
Hospital Length of Stay Days, Median (IQR) &
|
17.0 (11.0,24.0)
|
14.0 (10.0,24.0)
|
0.22
|
-0.11 (-0.27, 0.06)
|
0.20
|
∆ The Denominator is the total number of patients
&* Denominator is the number of patients who have respiratory failure requiring MV during ICU stay
& Denominator is the number of patients who survived.
* Unpaired t-test / ^ Wilcoxon rank-sum test is used to calculate the P-value.
^^ Chi-square test is used to calculate the P-value.
** Fisher Exact test is used to calculate the P-value.
$* Propensity score-adjusted negative binomial regression is used to calculate Beta- coefficient (estimate) and p-value.
$ Propensity score after adjusting for patient’s APACHE II score, SOFA score, chronic kidney disease (CKD), and acute kidney injury (AKI) within 24 hours of ICU admission to calculate Odds ratio and p-value.
¥ Denominator of the percentage is survival in 30-day ICU mortality.
|
Among survival, no differences were observed between the two dosing regimens in MV duration (Beta coefficient = -0.17; CI = -0.58,0.24; p = 0.41), ICU LOS (Beta coefficient = -0.12; CI = -0.31, 0.07; p = 0.23) and hospital LOS (Beta coefficient = -0.11; CI = -0.27, 0.06; p = 0.20) (Table 2).