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
| Autor: | Beatriz Martín, José Luis Iribarren, JJ Jimenez, Patricia Machado, R Perez, M Brouard, Juan M Borreguero, Leonardo Lorente, José María Raya, Alejandro Jiménez, Domingo Hernández, Rafael Martínez, María L. Mora, S Palmero |
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| Přispěvatelé: | [Jimenez,JJ, Iribarren,JL, Brouard,M, Palmero,S, Lorente,L, Pérez,R, Mora,ML] Critical Care Department, Hospital Universitario de Canarias. [Hernández,D] Departamento de Nefrología, Hospital Universitario Carlos Haya, Málaga, España. [Jiménez,A] Mixed Research Unit, Hospital Universitario de Canarias. [Machado,P, Raya,JM] Hematology Laboratory, Hospital Universitario de Canarias. [Borreguero,JM, Martín,B] Biochemical laboratory. Hospital Universitario de Canarias. [Martínez,R] Cardiac Surgery Department. Hospital Universitario de Canarias. |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Male
Tranexamic acid medicine.medical_treatment Analytical Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures Operative::Extracorporeal Circulation::Cardiopulmonary Bypass [Medical Subject Headings] Phenomena and Processes::Circulatory and Respiratory Physiological Phenomena::Blood Physiological Phenomena::Blood Physiological Processes::Hemostasis::Blood Coagulation::Fibrinolysis [Medical Subject Headings] Body Temperature law.invention Placebos Norepinephrine Analytical Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures Operative::Surgical Procedures Elective [Medical Subject Headings] law Antifibrinolytic agent Creatine Kinase MB Form Creatine Kinase Cardiopulmonary bypass Fibrinolysis Health Care::Health Care Quality Access and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Epidemiologic Research Design::Double-Blind Method [Medical Subject Headings] General Medicine Middle Aged Cardiac surgery Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Hematologic Agents::Coagulants::Hemostatics::Antifibrinolytic Agents [Medical Subject Headings] Antifibrinolytic Agents Treatment Outcome Chemicals and Drugs::Organic Chemicals::Carboxylic Acids::Acids Carbocyclic::Cyclohexanecarboxylic Acids::Tranexamic Acid [Medical Subject Headings] Elective Surgical Procedures Anesthesia Female Inflammation Mediators Cardiology and Cardiovascular Medicine Research Article medicine.drug Pulmonary and Respiratory Medicine Antifibrinolytic medicine.drug_class lcsh:Surgery Placebo Lower risk Statistics Nonparametric Fibrin Fibrinogen Degradation Products lcsh:RD78.3-87.3 Double-Blind Method medicine Humans Lactic Acid Dialysis Aged Analytical Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Treatment Outcome [Medical Subject Headings] Analysis of Variance Interleukin-6 business.industry Bleeding Inflammatory response lcsh:RD1-811 Logistic Models lcsh:Anesthesiology Surgery business |
| Zdroj: | Journal of Cardiothoracic Surgery, Vol 6, Iss 1, p 138 (2011) Journal of Cardiothoracic Surgery |
| ISSN: | 1749-8090 8441-3719 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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