R Perez

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

IntroductionExtracorporeal 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.MethodsA 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.ResultsIn 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.ConclusionThe use of TA attenuates the development of IR and VS after CPB.Trial registration numberISRCTN05718824.

Factors associated with excessive bleeding in cardiopulmonary bypass patients: a nested case-control study

IntroductionExcessive bleeding (EB) after cardiopulmonary bypass (CPB) may lead to increased mortality, morbidity, transfusion requirements and re-intervention. Less than 50% of patients undergoing re-intervention exhibit surgical sources of bleeding. We studied clinical and genetic factors associated with EB.MethodsWe performed a nested case-control study of 26 patients who did not receive antifibrinolytic prophylaxis. Variables were collected preoperatively, at intensive care unit (ICU) admission, at 4 and 24 hours post-CPB. EB was defined as 24-hour blood loss of >1 l post-CPB. Associations of EB with genetic, demographic, and clinical factors were analyzed, using SPSS-12.2 for statistical purposes.ResultsEB incidence was 50%, associated with body mass index (BMI)< 26.4 (25–28) Kg/m2, (P = 0.03), lower preoperative levels of plasminogen activator inhibitor-1 (PAI-1) (P = 0.01), lower body temperature during CPB (P = 0.037) and at ICU admission (P = 0.029), and internal mammary artery graft (P = 0.03) in bypass surgery. We found a significant association between EB and 5G homozygotes for PAI-1, after adjusting for BMI (F = 6.07; P = 0.02) and temperature during CPB (F = 8.84; P = 0.007). EB patients showed higher consumption of complement, coagulation, fibrinolysis and hemoderivatives, with significantly lower leptin levels at all postoperative time points (P = 0.01, P < 0.01 and P < 0.01).ConclusionExcessive postoperative bleeding in CPB patients was associated with demographics, particularly less pronounced BMI, and surgical factors together with serine protease activation.

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

BackgroundIn 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).MethodsWe 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).Results160 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.ConclusionsProlonged 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 numberISRCTN: ISRCTN84413719

Postoperative bleeding in cardiac surgery: the role of tranexamic acid in patients homozygous for the 5G polymorphism of the plasminogen activator inhibitor-1 gene.

Background:Plasminogen activator inhibitor 1 (PAI-1) attenuates the conversion of plasminogen to plasmin. Polymorphisms of the PAI-1 gene are associated with varying PAI-1 levels and risk of prothrombotic events in nonsurgical patients. The purpose of this study, a secondary analysis of a clinical trial, was to investigate whether PAI-1 genotype affects the efficacy of tranexamic acid (TA) in reducing postoperative chest tube blood loss of patients undergoing cardiopulmonary bypass. Methods:Fifty patients were classified according to PAI-1 genotype (4G/4G, 4G/5G, or 5G/5G). Twenty-four received 2 g TA before and after cardiopulmonary bypass, whereas 26 received placebo. The authors recorded data related to coagulation, fibrinolysis, and bleeding before surgery, at admission to the intensive care unit (0 h), and 4 and 24 h later. Results:In patients not receiving TA, those with the 5G/5G genotype had significantly higher chest tube blood loss and transfusion requirements compared with patients with the other genotypes at all time points. Patients with the 5G/5G genotype receiving TA showed significantly lower blood loss compared with the placebo group. There were no significant differences in blood loss or transfusion requirements between patients with the 4G/4G genotype when TA was used. Conclusions:Plasminogen activator inhibitor-1 5G/5G homozygotes who did not receive TA showed significantly greater postoperative bleeding than patients with other PAI-1 genotypes. 5G/5G homozygotes who received TA showed the greatest blood-sparing benefit.

A multifaceted educational intervention shortened time to antibiotic administration in children with severe sepsis and septic shock: ABISS Edusepsis pediatric study

Elisabeth Esteban, Sylvia Belda, Patricia García‐Soler, Antonio Rodríguez‐Núñez, Cristina Calvo, Javier Gil‐Anton, Amaya Bustinza, María‐Isabel Iglesias‐Bouzas, Montserrat Pujol‐Jove, Juan Carlos deCarlos, Juan‐Pablo García‐Iñiguez, Antonio Pérez‐Iranzo, Cinta Téllez, Irene Ortiz, Rosalía Pérez, Vanesa Bonil, Sonia Brió, Andrés Concha, José‐Domingo López, Vega Murga, Jose‐Carlos Flores, Alberto Trujillo, Aida Felipe, Clara Abadesso, María Pino, José León, María‐Carmen Martínez, Fernando Gómez, Rut Pérez‐Montejano, Rocío Tapia, Iolanda Jordan and Ricard Ferrer

Left Atrial Dysfunction and New-Onset Atrial Fibrillation After Cardiac Surgery

INTRODUCTION AND OBJECTIVES Postoperative atrial fibrillation is a common complication of carrying out cardiac surgery with extracorporeal circulation (ECC). The aim of this study was to determine whether preoperative left atrial contractile dysfunction, as assessed by tissue Doppler echocardiography, is associated with the development of postoperative new-onset atrial fibrillation (PAF). METHODS Transthoracic Doppler echocardiography was performed preoperatively in patients undergoing elective cardiac surgery. Left atrial contractile function was evaluated by tissue Doppler imaging (TDI) of the mitral annulus. RESULTS The study included 92 patients in sinus rhythm preoperatively who underwent elective cardiac surgery with ECC: 73 (79%) were male and 19 (21%) were female, and their mean age was 67 (10) years. Of these, 19 (20.6%) developed PAF 34 (12) h postoperatively. Bivariate analysis showed that PAF was associated with older age (71 [7] years vs 66 [10] years; P=.034), a large left atrial diameter (LAD), and a low peak atrial systolic mitral annular velocity (A velocity) and a high mitral E/A ratio on TDI. Logistic regression analysis showed that PAF was independently associated with a large LAD (odds ratio [OR] =2.23; 95% confidence interval [CI], 1.05-4.76; P=.033) and a low A velocity (OR=0.70; 95% CI, 0.55-0.99; P=.034). CONCLUSIONS Preoperative left atrial dysfunction, as assessed by TDI, was associated with an increased risk of PAF.