Safety and Effectiveness of two treatment regimes with tranexamic acid to minimize inflammatory response in elective cardiopulmonary bypass patients: a randomized double-blind, dose-dependent, phase IV clinical trial

Journal of Cardiothoracic Surgery

María L Mora³  Rafael Martínez¹  Rosalía Pérez³  Beatriz Martín⁵  José M Raya²  Juan M Borreguero⁵  Patricia Machado²  Leonardo Lorente³  Alejandro Jiménez⁴  Salomé Palmero³  Domingo Hernández⁶  Maitane Brouard³  José L Iribarren³  Juan J Jiménez³ 

[1] Cardiac Surgery Department. Hospital Universitario de Canarias. Ofra s/n, La Cuesta. 38320-La Laguna. Tenerife. España;Hematology Laboratory. Hospital Universitario de Canarias. Ofra s/n, La Cuesta. 38320-La Laguna. España;Critical Care Department. Hospital Universitario de Canarias. Ofra s/n, La Cuesta. 38320-La Laguna. España;Mixed Research Unit. Hospital Universitario de Canarias. Ofra s/n, La Cuesta. 38320-La Laguna. España;Biochemical laboratory. Hospital Universitario de Canarias. Ofra s/n, La Cuesta. 38320-La Laguna. España;Nephrology Department. Hospital Universitario Carlos Haya, 29010-Málaga. España

关键词: Bleeding;    Inflammatory response;    Tranexamic acid;    Fibrinolysis;    Cardiopulmonary bypass;    Cardiac surgery;   

Others  :  1153723
DOI  :  10.1186/1749-8090-6-138

 received in 2011-07-06, accepted in 2011-10-14,  发布年份 2011

【 摘 要 】

Background

In cardiopulmonary bypass (CPB) patients, fibrinolysis may enhance postoperative inflammatory response. We aimed to determine whether an additional postoperative dose of antifibrinolytic tranexamic acid (TA) reduced CPB-mediated inflammatory response (IR).

Methods

We performed a randomized, double-blind, dose-dependent, parallel-groups study of elective CPB patients receiving TA. Patients were randomly assigned to either the single-dose group (40 mg/Kg TA before CPB and placebo after CPB) or the double-dose group (40 mg/Kg TA before and after CPB).

Results

160 patients were included, 80 in each group. The incident rate of IR was significantly lower in the double-dose-group TA2 (7.5% vs. 18.8% in the single-dose group TA1; P = 0.030). After adjusting for hypertension, total protamine dose and temperature after CPB, TA2 showed a lower risk of IR compared with TA1 [OR: 0.29 (95% CI: 0.10-0.83), (P = 0.013)]. Relative risk for IR was 2.5 for TA1 (95% CI: 1.02 to 6.12). The double-dose group had significantly lower chest tube bleeding at 24 hours [671 (95% CI 549-793 vs. 826 (95% CI 704-949) mL; P = 0.01 corrected-P significant] and lower D-dimer levels at 24 hours [489 (95% CI 437-540) vs. 621(95% CI: 563-679) ng/mL; P = 0.01 corrected-P significant]. TA2 required lower levels of norepinephrine at 24 h [0.06 (95% CI: 0.03-0.09) vs. 0.20(95 CI: 0.05-0.35) after adjusting for dobutamine [F = 6.6; P = 0.014 corrected-P significant].

We found a significant direct relationship between IL-6 and temperature (rho = 0.26; P < 0.01), D-dimer (rho = 0.24; P < 0.01), norepinephrine (rho = 0.33; P < 0.01), troponin I (rho = 0.37; P < 0.01), Creatine-Kinase (rho = 0.37; P < 0.01), Creatine Kinase-MB (rho = 0.33; P < 0.01) and lactic acid (rho = 0.46; P < 0.01) at ICU arrival. Two patients (1.3%) had seizure, 3 patients (1.9%) had stroke, 14 (8.8%) had acute kidney failure, 7 (4.4%) needed dialysis, 3 (1.9%) suffered myocardial infarction and 9 (5.6%) patients died. We found no significant differences between groups regarding these events.

Conclusions

Prolonged inhibition of fibrinolysis, using an additional postoperative dose of tranexamic acid reduces inflammatory response and postoperative bleeding (but not transfusion requirements) in CPB patients. A question which remains unanswered is whether the dose used was ideal in terms of safety, but not in terms of effectiveness.

Current Controlled Trials number

ISRCTN: ISRCTN84413719

【 授权许可】

   
2011 Jiménez et al; licensee BioMed Central Ltd.

【 图 表 】

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