M Brouard

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

Influence of tracheostomy on the incidence of central venous catheter-related bacteremia

Although there are many studies on catheter-related infection, there are scarce data about the influence of tracheostomy in the incidence of central venous catheter-related bacteremia (CRB). In this cohort study, we found a higher incidence of CRB in patients with tracheostomy than without (11.25 vs. 1.43 per 1,000 catheter-days; odds ratio [OR] = 7.99; 95% confidence interval [CI] = 4.38–infinite; P < 0.001). Besides, we found a higher incidence of CRB in patients with tracheostomy using the jugular access compared to subclavian access (21.64 vs. 5.11 per 1,000 catheter-days; OR = 4.23; 95% CI = 1.44–infinite; P = 0.0097).

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.

Relative adrenal insufficiency and hemodynamic status in cardiopulmonary bypass surgery patients. A prospective cohort study

BackgroundThe objectives of this study were to determine the risk factors for relative adrenal insufficiency in cardiopulmonary bypass patients and the impact on postoperative vasopressor requirements.MethodsProspective cohort study on cardiopulmonary bypass patients who received etomidate or not during anesthetic induction. Relative adrenal insufficiency was defined as a rise in serum cortisol ≤ 9 μg/dl after the administration of 250 μg of consyntropin. Plasma cortisol levels were measured preoperatively, immediately before, 30, 60, and 90 minutes after the administration of cosyntropin, and at 24 hours after surgery.Results120 elective cardiopulmonary bypass patients were included. Relative adrenal insufficiency (Δcortisol ≤9 μg/dl) incidence was 77.5%. 78 patients received etomidate and 69 (88%) of them developed relative adrenal insufficiency, (P < 0.001). Controlling for clinical characteristics with a propensity analysis, etomidate was the only independent risk factor associated with relative adrenal insufficiency (OR 6.55, CI 95%: 2.47-17.4; P < 0.001). Relative adrenal insufficiency patients showed more vasopressor requirements just after surgery (P = 0.04), and at 4 hours after surgery (P = 0.01). Pre and post-test plasma cortisol levels were inversely associated with maximum norepinephrine dose (ρ = -0.22, P = 0.02; ρ = -0.18, P = 0.05; ρ = -0.21, P = 0.02; and ρ = -0.22, P = 0.02, respectively).ConclusionsRelative adrenal insufficiency in elective cardiopulmonary bypass patients may induce postoperative vasopressor dependency. Use of etomidate in these patients is a modifiable risk factor for the development of relative adrenal insufficiency that should be avoided.

Lesser incidence of accidental catheter removal with femoral versus radial arterial access

BACKGROUND Arterial catheterization is a frequent procedure in Intensive Care Units (ICUs). Accidental catheter removal (ACR) can cause severe and potentially life-threatening complications such as severe bleeding and vascular damage. Few data are available on accidental arterial catheter removal, and no studies have been found comparing the incidence of ACR between different arterial catheter sites. OBJECTIVE To compare the incidence of ACR in femoral and radial arterial catheters. RESEARCH DESIGN Retrospective study. SETTING A polyvalent ICU. SUBJECTS All consecutive patients subjected to femoral or radial arterial catheterization. MEASURES The incidence of ACR per 100 catheter-days between groups was compared using Poisson regression. We considered ACR as the presence of unintended removal produced by the patient or healthcare personnel. RESULTS A total of 2419 radial and 1085 femoral arterial catheters were inserted and remained in situ during 14,742 and 6497 days, respectively. We detected 45 cases of ACR with the femoral access and 162 cases with the radial access. The ACR rate was lower with the femoral access (4.1% vs 6.7% in the case of the radial access; p=0.003). Poisson regression analysis confirmed a lower incidence of ACR with the femoral versus the radial access (0.69 vs 1.10 ACR events per 100 catheter-days; OR 0.6, p=0.006, CI95% 0.01-0.83). CONCLUSIONS The incidence of ACR was found to be lower with the femoral than with the radial arterial catheters. In order to improve patient safety, it could be interesting to exhaustively monitor the incidence of ACR and adopt preventive measures, since ACR can give rise to serious complications.Background Arterial catheterization is a frequent procedure in Intensive Care Units (ICUs). Accidental catheter removal (ACR) can cause severe and potentially life-threatening complications such as severe bleeding and vascular damage. Few data are available on accidental arterial catheter removal, and no studies have been found comparing the incidence of ACR between different arterial catheter sites.

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.

Aortic root full detachment from the aortic annulus. aortitis role in the formation of a pseudoaneurysm to 3 years of an aortic valve replacement.

Results Redo open-heart surgery was performed, using femoral cannulation, mild hypothermia at 28°C, and circulatory arrest during 4 minutes, just to open and inspect the aorta. A big cavity acting as the aortic root, with irregular contour was observed. The floor of the cavity was the aortic prosthesis, the roof the beginning of true aortic root including both coronary ostia and the walls were formed by the roof of the left atrium, the main pulmonary artery, superior vena cava, right pulmonary artery and the rests of fibrotic and adhered pericardium. Aortic prosthesis seemed normofunctional, but the walls of the ascending aorta and aortic root were inflamed. A Bentall-De bono technique was performed. An Enterococcus faecalis was identified in the aortic wall by polymerase chain reaction. He was given six weeks of antibiotic therapy.

Factors related to permanent disability employment on patients fewer than 62 years operated by open heart surgery.

Results A cohort of 204 patients was studied. Age 51 +/9 years; 156 (76,5%) were male; Logistic Euroscore (LE) of 5.1 +/8.4, LVEF 58 +/11. Surgery was 86 (42.2%) CABG, 79 (38.7%) valvular, 16 (7.8%) combined surgery and 23 (11.3%) others. 28 (13.7%) were self-employed. 15 of them already had a PI at the time of surgery. Patients with PI presented a LE of 6.7+/3.9 Vs. 11+/5 (p = 0.006); age 53+/-6 vs 48 +/-10 (p < 0.001), with no difference in LVEF. There were more PI among women (57%) than male 41% (p = 0.046). There was a higher percentage of valvular surgery in women. Higher number of CABG and valvular surgery was associated with PI (p = 0.015). Conclusions Permanent work cessation activity after open-heart surgery was statistically determined with an older age, comorbidity, female gender and type of intervention. Valve surgery, the number of valves operated or higher number of bypasses increase the probability of PI.