Tranexamic acid attenuates inflammatory response in cardiopulmonary bypass surgery through blockade of fibrinolysis: a case control study followed by a randomized double-blind controlled trial.
BACKGROUND
Extracorporeal circulation induces hemostatic alterations that lead to inflammatory response (IR) and postoperative bleeding. Tranexamic acid (TA) reduces fibrinolysis and blood loss after cardiopulmonary bypass (CPB). However, its effects on IR and vasoplegic shock (VS) are not well known and elucidating these effects was the main objective of this study.


METHODS
A case control study was carried out to determine factors associated with IR after CPB. Patients undergoing elective CPB surgery were randomly assigned to receive 2 g of TA or placebo (0.9% saline) before and after intervention. We performed an intention-to-treat analysis, comparing the incidence of IR and VS. We also analyzed several biological parameters related to inflammation, coagulation, and fibrinolysis systems. We used SPSS version 12.2 for statistical purposes.


RESULTS
In the case control study, 165 patients were studied, 20.6% fulfilled IR criteria, and the use of TA proved to be an independent protective variable (odds ratio 0.38, 95% confidence interval 0.18 to 0.81; P < 0.01). The clinical trial was interrupted. Fifty patients were randomly assigned to receive TA (24) or placebo (26). Incidence of IR was 17% in the TA group versus 42% in the placebo group (P = 0.047). In the TA group, we observed a significant reduction in the incidence of VS (P = 0.003), the use of norepinephrine (P = 0.029), and time on mechanical ventilation (P = 0.018). These patients showed significantly lower D-dimer, plasminogen activator inhibitor 1, and creatine-kinase levels and a trend toward lower levels of soluble tumor necrosis factor receptor and interleukin-6 within the first 24 hours after CPB.


CONCLUSIONS
The use of TA attenuates the development of IR and VS after CPB.
Jimenez
Juan J
JJ
Intensive Care Department, Hospital Universitario de Canarias, Ofra s/n La Cuesta, La Laguna, 38320, Spain. jjjimenezrivera@gmail.com.
Iribarren
Jose L
JL
Lorente
Leonardo
L
Rodriguez
Jose M
JM
Hernandez
Domingo
D
Nassar
Ibrahim
I
Perez
Rosalia
R
Brouard
Maitane
M
Milena
Antonio
A
Martinez
Rafael
R
Mora
Maria L
ML
D000368:Aged; D000933:Antifibrinolytic Agents / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D016022:Case-Control Studies; D004311:Double-Blind Method; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000097:blood* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D019106:Postoperative Hemorrhage / Q000209:etiology / Q000473:pathology* / Q000517:prevention & control; D011446:Prospective Studies; D014148:Tranexamic Acid / Q000494:pharmacology / Q000627:therapeutic use*
D000933:Antifibrinolytic Agents; D018836:Inflammation Mediators; D014148:Tranexamic Acid