title: 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.
abstract: 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.
authors: Critical Care Department, Hospital Universitario de Canarias, Ofra s/n, La Cuesta, 38320-La Laguna, España. jjjimenezrivera@gmail.com
authors: Juan J
authors: JJ
authors: Jiménez
authors: José L
authors: JL
authors: Iribarren
authors: Maitane
authors: M
authors: Brouard
authors: Domingo
authors: D
authors: Hernández
authors: Salomé
authors: S
authors: Palmero
authors: Alejandro
authors: A
authors: Jiménez
authors: Leonardo
authors: L
authors: Lorente
authors: Patricia
authors: P
authors: Machado
authors: Juan M
authors: JM
authors: Borreguero
authors: José M
authors: JM
authors: Raya
authors: Beatriz
authors: B
authors: Martín
authors: Rosalía
authors: R
authors: Pérez
authors: Rafael
authors: R
authors: Martínez
authors: María L
authors: ML
authors: Mora
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D000933:Antifibrinolytic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001831:Body Temperature; D002315:Cardiopulmonary Bypass; D003402:Creatine Kinase / Q000097:blood; D052279:Creatine Kinase, MB Form / Q000097:blood; D004311:Double-Blind Method; D017558:Elective Surgical Procedures; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects; D006801:Humans; D018836:Inflammation Mediators / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000097:blood; D019344:Lactic Acid / Q000097:blood; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D010919:Placebos; D018709:Statistics, Nonparametric; D014148:Tranexamic Acid / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000933:Antifibrinolytic Agents; D005338:Fibrin Fibrinogen Degradation Products; D018836:Inflammation Mediators; D015850:Interleukin-6; D010919:Placebos; C036309:fibrin fragment D; D019344:Lactic Acid; D014148:Tranexamic Acid; D003402:Creatine Kinase; D052279:Creatine Kinase, MB Form; D009638:Norepinephrine