Introduction
Materials and methods
Group assignment
Anesthetic, cardiopulmonary bypass, and intensive care management
Database management
Statistical methods
Results
Aprotinin | Tranexamic acid | ||||
---|---|---|---|---|---|
Mean | SD | Mean | SD |
P
| |
Age (years)
| |||||
All patients | 68 | 11 | 67 | 11 | 0.09 |
Open-heart procedures | 69 | 11 | 68 | 13 | 0.25 |
Height (cm)
| |||||
All patients | 171 | 9 | 172 | 9 | 0.88 |
Open-heart procedures | 171 | 9 | 170 | 11 | 0.71 |
Weight (kg)
| |||||
All patients | 80 | 15 | 80 | 16 | 0.74 |
Open-heart procedures | 77 | 17 | 77 | 15 | 0.94 |
Ejection fraction preop (%)
| |||||
All patients | 55 | 15 | 53 | 15 | 0.20 |
Open-heart procedures | 53 | 14 | 51 | 16 | 0.18 |
Creatinine preop (mg/dL)
| |||||
All patients | 1.18 | 0.76 | 1.24 | 0.87 | 0.28 |
Open-heart procedures |
1.14
| 0.46 |
1.31
| 1.03 |
0.04
|
Platelets preop (/nL)
| |||||
All patients | 235 | 88 | 239 | 80 | 0.51 |
Open-heart procedures | 241 | 86 | 241 | 88 | 0.97 |
WBC preop (/nL)
| |||||
All patients | 8.3 | 4.2 | 8.1 | 2.9 | 0.37 |
Open-heart procedures | 8.4 | 4.2 | 8.1 | 3.5 | 0.55 |
Hemoglobin preop (mg/dL)
| |||||
All patients |
13.6
| 1.8 |
13.1
| 2.0 |
< 0.01
|
Open-heart procedures |
13.2
| 1.9 |
12.5
| 1.8 |
< 0.01
|
Prothrombin time preop (%)
| |||||
All patients | 93 | 15 | 93 | 14 | 0.69 |
Open-heart procedures | 91 | 17 | 88 | 16 | 0.15 |
PTT preop (s)
| |||||
All patients | 41.1 | 23.7 | 42.3 | 24.0 | 0.49 |
Open-heart procedures | 40.6 | 22.2 | 41.3 | 17.8 | 0.76 |
AT III preop (%)
| |||||
All patients | 97 | 15 | 95 | 17 | 0.17 |
Open-heart procedures | 97 | 14 | 93 | 19 | 0.05 |
Aprotinin | Tranexamic acid | |||||
---|---|---|---|---|---|---|
CABG
|
n
| 349 | 231 | |||
% in group | 63.1% | 69.0% | ||||
Valve
|
n
| 106 | 48 | |||
% in group | 19.2% | 14.3% | ||||
Double valve
|
n
| 11 | 2 | |||
% in group | 2.0% | 0.6% | ||||
CABG plus valve
|
n
| 68 | 41 | |||
% in group | 12.3% | 12.2% | ||||
Other
|
n
| 19 | 13 | |||
% in group | 3.4% | 3.9% | ||||
Mean
|
SD
|
Mean
|
SD
|
P
| ||
Duration of surgery (min)
| ||||||
All patients | 206 | 60 | 211 | 71 | 0.28 | |
Open-heart procedures |
210
| 65 |
235
| 79 |
< 0.01
| |
CPB time (min)
| ||||||
All patients | 89 | 42 | 88 | 46 | 0.79 | |
Open-heart procedures | 104 | 47 | 114 | 53 | 0.07 | |
Cross-clamp time (min)
| ||||||
All patients | 59 | 34 | 57 | 36 | 0.37 | |
Open-heart procedures | 77 | 40 | 85 | 43 | 0.08 | |
Euroscore II
| ||||||
All patients | 6.3 | 3.9 | 5.8 | 3.7 | 0.08 | |
Open-heart procedures | 7.7 | 3.6 | 7.3 | 3.7 | 0.42 | |
ICU treatment (days)
| ||||||
All patients | 3.1 | 9.5 | 3.5 | 8.1 | 0.51 | |
Open-heart procedures | 4.3 | 13.8 | 5.7 | 11.8 | 0.38 | |
Hospital stay (days)
| ||||||
All patients | 17.0 | 17.1 | 18.9 | 18.6 | 0.11 | |
Open-heart procedures | 20.8 | 20.8 | 23.6 | 25.1 | 0.28 | |
Mechanical ventilation (h)
| ||||||
All patients | 25.6 | 128.0 | 45.4 | 187.3 | 0.06 | |
Open-heart procedures | 36.3 | 188.4 | 83.0 | 263.6 | 0.07 | |
APACHE II (admission ICU)
| ||||||
All patients | 19.4 | 6.8 | 19.3 | 7.0 | 0.89 | |
Open-heart procedures | 20.2 | 7.3 | 19.8 | 6.7 | 0.60 | |
SAPS II (admission ICU)
| ||||||
All patients |
34.3
| 12.4 |
36.4
| 12.5 |
0.02
| |
Open-heart procedures | 36.7 | 13.0 | 39.7 | 13.1 | 0.06 |
Aprotinin | Tranexamic acid | ||||
---|---|---|---|---|---|
Mean | SD | Mean | SD |
P
| |
Creatinine after surgery (mg/dL)
| |||||
All patients |
1.1
| 0.7 |
1.2
| 0.8 |
0.02
|
Open-heart procedures |
1.08
| 0.50 |
1.30
| 0.73 |
< 0.01
|
Creatinine POD 1 (mg/dL)
| |||||
All patients | 1.5 | 5.3 | 2.2 | 14.0 | 0.29 |
Open-heart procedures | 1.37 | 1.83 | 1.42 | 0.65 | 0.77 |
CK after surgery (U/mL)
| |||||
All patients | 521 | 635 | 474 | 782 | 0.33 |
Open-heart procedures | 521 | 605 | 589 | 1307 | 0.53 |
CK-MB after surgery (U/mL)
| |||||
All patients | 59 | 64 | 54 | 69 | 0.27 |
Open-heart procedures | 59 | 64 | 77 | 109 | 0.39 |
CK POD 1 (U/mL)
| |||||
All patients | 1013 | 1496 | 878 | 1131 | 0.16 |
Open-heart procedures | 1032 | 1462 | 914 | 1224 | 0.48 |
CK-MB POD 1 (U/mL)
| |||||
All patients | 55 | 69 | 52 | 80 | 0.51 |
Open-heart procedures | 59 | 64 | 67 | 103 | 0.42 |
WBC after surgery (/nL)
| |||||
All patients | 12.6 | 5.5 | 12.5 | 5.4 | 0.80 |
Open-heart procedures | 13.6 | 5.7 | 13.8 | 6.3 | 0.74 |
WBC POD 1 (/nL)
| |||||
All patients | 14.0 | 4.4 | 13.8 | 6.9 | 0.63 |
Open-heart procedures |
14.4
| 4.4 |
13.4
| 4.2 |
0.04
|
Hemoglobin after surgery (g/dL)
| |||||
All patients | 10.2 | 1.2 | 10.5 | 7.3 | 0.27 |
Open-heart procedures | 10.1 | 1.4 | 11.1 | 12.9 | 0.26 |
Hemoglobin POD 1 (g/dL)
| |||||
All patients | 10.4 | 1.2 | 10.3 | 3.8 | 0.77 |
Open-heart procedures | 10.3 | 1.1 | 10.7 | 6.6 | 0.44 |
Platelets after surgery (/nL)
| |||||
All patients | 144 | 50 | 153 | 56 | 0.01 |
Open-heart procedures | 143 | 55 | 149 | 62 | 0.35 |
Platelets POD 1 (/nL)
| |||||
All patients | 158 | 55 | 160 | 57 | 0.53 |
Open-heart procedures | 147 | 59 | 145 | 59 | 0.75 |
PT ratio after surgery (%)
| |||||
All patients |
65
| 10 |
64
| 10 |
0.03
|
Open-heart procedures |
64
| 11 |
61
| 10 |
< 0.01
|
PT ratio POD 1 (%)
| |||||
All patients |
75
| 12 |
74
| 11 |
0.04
|
Open-heart procedures | 73 | 13 | 71 | 13 | 0.12 |
aPTT after surgery (s)
| |||||
All patients |
51.0
| 16.7 |
41.0
| 14.5 |
< 0.01
|
Open-heart procedures |
53.6
| 19.0 |
43.4
| 21.0 |
< 0.01
|
aPTT POD 1 (s)
| |||||
All patients |
44.0
| 15.1 |
41.2
| 10.3 |
< 0.01
|
Open-heart procedures | 46.6 | 17.9 | 42.7 | 12.2 | 0.05 |
AT III after surgery (%)
| |||||
All patients | 67 | 12 | 68 | 13 | 0.37 |
Open-heart procedures | 69 | 12 | 69 | 15 | 0.67 |
AT III POD 1 (%)
| |||||
All patients | 76 | 14 | 74 | 14 | 0.31 |
Open-heart procedures | 78 | 13 | 75 | 15 | 0.34 |
Aprotinin | Tranexamic acid |
P
| |||
---|---|---|---|---|---|
Myocardial infarction (ICU) | All patients |
N
| 8 | 6 | 0.78 |
Open-heart procedures |
0
|
2
|
0.04
| ||
All patients | % in group | 1.4% | 1.8% | ||
Open-heart procedures |
0.0%
|
1.9%
| |||
Myocardial infarction (late) | All patients |
N
| 7 | 5 | 0.77 |
Open-heart procedures | 1 | 1 | 0.60 | ||
All patients | % in group | 1.3% | 1.5% | ||
Open-heart procedures | 0.5% | 1.0% | |||
Seizures (ICU) | All patients |
N
| 5 | 9 | 0.05 |
Open-heart procedures |
4
|
7
|
0.04
| ||
All patients | % in group | 0.9% | 2.7% | ||
Open-heart procedures |
1.9%
|
6.7%
| |||
Seizures (late) | All patients |
N
| 6 | 1 | 0.20 |
Open-heart procedures | 3 | 1 | 0.74 | ||
All patients | % in group | 1.1% | 0.3% | ||
Open-heart procedures | 1.4% | 1.0% | |||
Ischemic stroke (ICU) | All patients |
N
| 21 | 9 | 0.45 |
Open-heart procedures | 10 | 6 | 0.68 | ||
All patients | % in group | 3.8% | 2.7% | ||
Open-heart procedures | 4.7% | 5.7% | |||
Ischemic stroke (late) | All patients |
N
|
19
|
3
| 0.02 |
Open-heart procedures | 9 | 1 | 0.12 | ||
All patients | % in group |
3.4%
|
0.9%
| ||
Open-heart procedures | 4.2% | 1.0% | |||
Neurologic disability (ICU) | All patients |
N
| 21 | 11 | 0.85 |
Open-heart procedures | 12 | 9 | 0.34 | ||
All patients | % in group | 3.8% | 3.3% | ||
Open-heart procedures | 5.6% | 8.6% | |||
Neurologic disability (late) | All patients |
N
|
32
|
8
|
0.02
|
Open-heart procedures |
15
|
1
|
0.03
| ||
All patients | % in group |
5.8%
|
2.4%
| ||
Open-heart procedures |
7.0%
|
1.0%
| |||
Intracerebral hemorrhage (ICU) | All patients |
N
| 3 | 1 | 1.00 |
Open-heart procedures | 2 | 1 | 1.00 | ||
All patients | % in group | 0.5% | 0.3% | ||
Open-heart procedures | 0.9% | 1.0% | |||
Intracerebral hemorrhage (late) | All patients |
N
| 1 | 0 | 1.00 |
Open-heart procedures | 0 | 0 | n/a | ||
All patients | % in group | 0.2% | 0.0% | ||
Open-heart procedures | 0.0% | 0.0% | |||
Mortality (in-hospital) | All patients |
N
| 38 | 29 | 0.34 |
Open-heart procedures |
16
|
17
|
0.02
| ||
All patients | % in group | 6.9% | 8.7% | ||
Open-heart procedures |
7.5%
|
16.2%
|
Aprotinin | Tranexamic acid | |||||
---|---|---|---|---|---|---|
Mean | SD | Mean | SD |
P
| ||
Blood loss first 6 h (mL)
| ||||||
All patients |
230
| 338 |
366
| 492 |
< 0.01
| |
Open-heart procedures |
229
| 260 |
459
| 616 |
< 0.01
| |
Blood loss first 24 h (mL)
| ||||||
All patients |
437
| 669 |
613
| 705 |
< 0.01
| |
Open-heart procedures |
431
| 431 |
707
| 881 |
< 0.01
| |
Blood loss 48 h (mL)
| ||||||
All patients |
72
| 159 |
118
| 223 |
< 0.01
| |
Open-heart procedures |
77
| 177 |
137
| 284 |
0.02
| |
Packed red blood surgery (units)
| ||||||
All patients |
0.5
| 1.2 |
0.7
| 1.5 |
0.02
| |
Open-heart procedures | 0.6 | 1.2 | 0.8 | 1.4 | 0.19 | |
Packed red blood first 24 h (units)
| ||||||
All patients |
0.7
| 2.1 |
1.3
| 2.4 |
< 0.01
| |
Open-heart procedures |
0.8
| 1.8 |
1.9
| 2.9 |
< 0.01
| |
FFP surgery (units)
| ||||||
All patients |
0.3
| 1.1 |
0.4
| 1.4 |
0.09
| |
Open-heart procedures |
0.5
| 1.5 |
0.8
| 1.6 |
0.13
| |
FFP first 24 h (units)
| ||||||
All patients |
0.8
| 4.4 |
1.6
| 5.0 |
< 0.01
| |
Open-heart procedures |
1.0
| 3.2 |
2.8
| 7.3 |
< 0.01
| |
Platelet concentrates surgery (units)
| ||||||
All patients |
0.1
| 0.5 |
0.2
| 0.6 |
< 0.01
| |
Open-heart procedures |
0.1
| 0.5 |
0.3
| 0.7 |
< 0.01
| |
Platelet concentrates first 24 h (units)
| ||||||
All patients |
0.2
| 0.8 |
0.4
| 1.2 |
< 0.01
| |
Open-heart procedures |
0.2
| 0.9 |
0.6
| 1.7 |
< 0.01
| |
PPSB (IU)
| ||||||
All patients | 14.1 | 154.7 | 30.4 | 186.1 | 0.16 | |
Open-heart procedures | 19.5 | 168.0 | 57.1 | 269.9 | 0.13 | |
AT III (IU)
| ||||||
All patients | 23.5 | 200.5 | 41.8 | 275.8 | 0.26 | |
Open-heart procedures | 30.2 | 237.3 | 38.1 | 237.1 | 0.78 | |
F XIII (IU)
| ||||||
All patients | 9.0 | 130.0 | 14.2 | 161.8 | 0.60 | |
Open-heart procedures | 11.6 | 120.3 | 23.8 | 244.0 | 0.55 | |
aFVII (IU)
| ||||||
All patients | 3.1 | 46.8 | 5.0 | 39.1 | 0.52 | |
Open-heart procedures | 3.4 | 36.8 | 13.7 | 65.1 | 0.07 | |
Desmopressin (μg/kg)
| ||||||
All patients | 0.3 | 2.4 | 0.2 | 1.9 | 0.58 | |
Open-heart procedures | 0.5 | 3.2 | 0.4 | 2.5 | 0.71 | |
Rethoracotomy (bleeding)
| ||||||
All patients |
N
|
13
|
23
|
< 0.01
| ||
Open-heart procedures |
7
|
15
|
< 0.01
| |||
All patients | % in group |
2.4%
|
6.9%
| |||
Open-heart procedures |
3.3%
|
14.3%
|
Subgroup with open-heart procedures
B | SE | Sig. | Odds ratio (OR) | 95.0% CI for OR | |||
---|---|---|---|---|---|---|---|
Lower | Upper | ||||||
Step 1 | Age | -0.043 | 0.018 | 0.019 | 0.958 | 0.924 | 0.993 |
CPB time | 0.012 | 0.004 | 0.002 | 1.012 | 1.004 | 1.020 | |
EURO Score II | 0.278 | 0.063 | 0.000 | 1.321 | 1.168 | 1.493 | |
Creatinine preop | 0.146 | 0.207 | 0.481 | 1.157 | 0.772 | 1.734 | |
Hemoglobin preop | -0.148 | 0.125 | 0.238 | 0.863 | 0.675 | 1.103 | |
Antifibrinolytic | -0.788 | 0.437 | 0.071 | 0.455 | 0.193 | 1.070 | |
Constant | -0.940 | 1.959 | 0.631 | 0.391 | |||
Step 2 | Age | -0.041 | 0.018 | 0.023 | 0.959 | 0.926 | 0.994 |
CPB time | 0.012 | 0.004 | 0.001 | 1.012 | 1.005 | 1.020 | |
EURO Score II | 0.276 | 0.062 | 0.000 | 1.318 | 1.167 | 1.489 | |
Hemoglobin preop | -0.175 | 0.119 | 0.142 | 0.840 | 0.665 | 1.060 | |
Antifibrinolytic | -0.832 | 0.431 | 0.054 | 0.435 | 0.187 | 1.013 | |
Constant | -0.534 | 1.866 | 0.775 | 0.586 | |||
Step 3
|
Age
|
-0.044
|
0.018
|
0.014
|
0.957
|
0.923
|
0.991
|
CPB Time
|
0.011
|
0.004
|
0.003
|
1.011
|
1.004
|
1.019
| |
EURO Score II
|
0.300
|
0.060
|
0.000
|
1.350
|
1.200
|
1.518
| |
Antifibrinolytic
|
-0.947
|
0.424
|
0.025
|
0.388
|
0.169
|
0.890
| |
Constant
|
-2.554
|
1.302
|
0.050
|
0.078
|
Discussion
Conclusions
Key messages
-
The association between higher mortality and the minor efficiency of tranexamic acid questions the routine administration of high-dose tranexamic acid in cardiac surgery. In particular, our finding of the more than twofold increased mortality in patients undergoing open-heart procedures receiving tranexamic acid is worrying.
-
Aprotinin and tranexamic acid were associated with neurologic adverse reactions in this retrospective study.
-
The safety profile of antifibrinolytic treatment--aprotinin and tranexamic acid--warrants further evaluation to answer the question whether the benefit of this treatment outweighs its potential risks.