Acute normovolemic hemodilution in cardiac surgery: Rationale and design of a multicenter randomized trial.

BACKGROUND: Minimizing the use of blood component can reduce known and unknown blood transfusion risks, preserve blood bank resources, and decrease healthcare costs. Red Blood Cell (RBC) transfusion is common after cardiac surgery and associated with adverse perioperative outcomes, including mortality. Acute normovolemic hemodilution (ANH) may reduce bleeding and the need for blood product transfusion after cardiac surgery. However, its blood-saving effect and impact on major outcomes remain uncertain. METHODS: This is a single-blinded, multinational, pragmatic, randomized controlled trial with a 1:1 allocation ratio conducted in Tertiary and University hospitals. The study is designed to enroll patients scheduled for elective cardiac surgery with planned cardiopulmonary bypass (CPB). Patients are randomized to receive ANH before CPB or the best available treatment without ANH. We identified an ANH volume of at least 650 mL as the critical threshold for clinically relevant benefits. Larger ANH volumes, however, are allowed and tailored to the patient's characteristics and clinical conditions. RESULTS: The primary outcome is the percentage of patients receiving RBCs transfusion from randomization until hospital discharge, which we hypothesize will be reduced from 35% to 28% with ANH. Secondary outcomes are all-cause 30-day mortality, acute kidney injury, bleeding complications, and ischemic complications. CONCLUSION: The trial is designed to determine whether ANH can safely reduce RBC transfusion after elective cardiac surgery with CPB. STUDY REGISTRATION: This trial was registered on ClinicalTrials.gov in April 2019 with the trial identification number NCT03913481.

Esmolol in Cardiac Surgery: A Randomized Controlled Trial.

OBJECTIVE: To assess whether the administration of the ultra-short-acting ß-blocker esmolol in cardiac surgery could have a cardioprotective effect that translates into improved postoperative outcomes. DESIGN: Single-center, double-blinded, parallel-group randomized controlled trial. SETTING: A tertiary care referral center. PARTICIPANTS: Patients undergoing elective cardiac surgery with preoperative evidence of left ventricular end-diastolic diameter >60 mm and/or left ventricular ejection fraction <50%. INTERVENTIONS: Patients were assigned randomly to receive either esmolol (1 mg/kg as a bolus before aortic cross-clamping and 2 mg/kg mixed in the cardioplegia solution) or placebo in a 1:1 allocation ratio. MEASUREMENTS AND MAIN RESULTS: The primary composite endpoint of prolonged intensive care unit stay and/or in-hospital mortality occurred in 36/98 patients (36%) in the placebo group versus 27/102 patients (27%) in the esmolol group (p = 0.13). In the esmolol group, a reduction in the maximum inotropic score during the first 24 postoperative hours was observed (10 [interquartile range 5-15] v 7 [interquartile range 5-10.5]; p = 0.04), as well as a trend toward a reduction in postoperative low-cardiac-output syndrome (13/98 v 6/102; p = 0.08) and the rate of hospital admission at one year (26/95 v 16/96; p = 0.08). A trend toward an increase in the number of patients with ejection fraction ≥60% at hospital discharge also was observed (4/95 v 11/92; p = 0.06). CONCLUSIONS: In the present trial, esmolol as a cardioplegia adjuvant enhanced postoperative cardiac performance but did not reduce a composite endpoint of prolonged intensive care unit stay and/or mortality.

Anesthesiologic Management of Patients Undergoing Cardiac Transapical Procedures: Which Challenges in the Modern Era?

OBJECTIVE: Patients undergoing transapical cardiac procedure are a minority of cardiac surgery patients but represent a challenge for cardiac anesthesiologists because they generally are older and have more comorbidities than do open heart cardiac surgery patients. The aims of this study were to describe the anesthetic experience with transapical procedures in a single high-volume center and to analyze the most critical aspects for anesthetic management. DESIGN: Retrospective study. SETTING: IRCCS San Raffaele Scientific Institute, Milan, Italy. PARTICIPANTS: All patients undergoing a cardiac transapical procedure from January 2009 to April 2018 were included in this case series. INTERVENTIONS: Patients were managed by a multidisciplinary heart team. The perioperative anesthetic approach and hemodynamic management were consistent and performed by a group of trained cardiac anesthesiologists. MEASUREMENTS AND MAIN RESULTS: The study population comprised 143 patients: 81 (57%) underwent an aortic valve procedure, 60 (42%) a mitral valve intervention, 1 patient underwent a procedure involving both the aortic and mitral valves, and 1 patient underwent correction of a congenital heart defect. A major intraoperative complication occurred in 5 (3.5%) patients, the procedure was not technically feasible because of unsuitable anatomy in 3 patients, and conversion to open heart surgery was needed in 2 patients. All patients were admitted to the intensive care unit. Intensive care unit stay was 1 (1-3) days, and hospital stay was 6 (5-8) days. Hospital survival was 94%. CONCLUSIONS: Patients undergoing transapical cardiac procedures are a minority of cardiac surgery patients, but represent a high-risk population. A patient-tailored anesthetic approach, in the context of the therapeutic strategy shared by the heart team, is crucial to improve outcomes.

Esmolol before cardioplegia and as cardioplegia adjuvant reduces cardiac troponin release after cardiac surgery. A randomized trial.

BACKGROUND: Cardioplegic solutions are the standard in myocardial protection during cardiac surgery, since they interrupt the electro-mechanical activity of the heart and protect it from ischemia during aortic cross-clamping. Nevertheless, myocardial damage has a strong clinical impact. We tested the hypothesis that the short-acting beta-blocker esmolol, given immediately before cardiopulmonary bypass and as a cardioplegia additive, would provide an extra protection to myocardial tissue during cardiopulmonary bypass by virtually reducing myocardial activity and, therefore, oxygen consumption to zero. MATERIALS AND METHODS: This was a single-centre, double-blind, placebo-controlled, parallel-group phase IV trial. Adult patients undergoing elective valvular and non-valvular cardiac surgery with end diastolic diameter >60 mm and ejection fraction <50% were enrolled. Patients were randomly assigned to receive either esmolol, 1 mg/kg before aortic cross-clamping and 2 mg/kg with Custodiol® crystalloid cardioplegia or equivolume placebo. The primary end-point was peak postoperative troponin T concentration. Troponin was measured at Intensive Care Unit arrival and at 4, 24 and 48 hours. Secondary endpoints included ventricular fibrillation after cardioplegic arrest, need for inotropic support and intensive care unit and hospital stay. RESULTS: We found a reduction in peak postoperative troponin T, from 1195 ng/l (690-2730) in the placebo group to 640 ng/l (544-1174) in the esmolol group (p=0.029) with no differences in Intensive Care Unit stay [3 days (1-6) in the placebo group and 3 days (2-5) in the esmolol group] and hospital stay [7 days (6-10) in the placebo group and 7 days (6-12) in the esmolol group]. Troponin peak occurred at 24 hours for 12 patients (26%) and at 4 hours for the others (74%). There were no differences in other secondary end-points. CONCLUSIONS: Adding esmolol to the cardioplegia in high-risk patients undergoing elective cardiac surgery reduces peak postoperative troponin levels. Further investigation is necessary to assess esmolol effects on major clinical outcomes.

Routine Screening of Coronary Artery Disease With Computed Tomographic Coronary Angiography in Place of Invasive Coronary Angiography in Patients Undergoing Transcatheter Aortic Valve Replacement.

BACKGROUND: Coronary artery disease (CAD) screening is required before transcatheter aortic valve implantation (TAVR). Although invasive coronary angiography (CA) remains the gold standard for CAD assessment, computed tomographic CA (CTCA) could be a safe and effective noninvasive alternative for CAD screening in patients undergoing TAVR. METHODS AND RESULTS: From November 2007 to May 2013, all patients undergoing TAVR at our institution were included in the study cohort. CTCA was used as first-line imaging tool for CAD screening. Invasive CA was performed when any of the following were present: coronary anatomy at CTCA was not evaluable and presence of significant CAD at CTCA. The primary objective was to compare major adverse cardiovascular and cerebrovascular events at 30 days and 1 year between patients who performed CTCA as only screening test and those who performed CTCA and invasive CA. Of 491 patients treated with TAVR, 375 (76.3%) performed only CTCA, whereas 116 (21.7%) underwent also CA. No differences were present in crude major adverse cardiovascular and cerebrovascular event rates at 30 days and 1 year between the 2 groups. After multivariable adjustment, CTCA performed alone was not associated with higher risk of MACE at 1 year of follow-up (hazard ratio, 0.89; 95% confidence interval, 0.49-1.60; P=0.69). CONCLUSIONS: CTCA performed as a routine noninvasive imaging tool in patients undergoing TAVR seems safe and effective allowing, with a single test, acquisition of information on aortic annulus anatomy, peripheral access sites, and evaluation of coronary anatomy.

Do patients undergoing MitraClip implantation require routine ICU admission?

OBJECTIVES: Because of its reduced invasiveness, MitraClip (Abbott Vascular, Menlo Park, CA) therapy usually is reserved for patients with extreme left ventricular dysfunction or severe comorbidity contraindicating surgery. The appropriate post-procedural care in this high-risk population is yet to be defined. In this study, the postoperative course of such patients is reported, focusing on early complications and need for intensive care unit (ICU) management. DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis of patients with severe mitral regurgitation undergoing transcatheter mitral valve repair with the MitraClip system in the authors institution was performed. INTERVENTIONS: One hundred thirty patients underwent MitraClip implantation between 2008 and 2012. At the end of the procedure, all patients were admitted to the ICU. MEASUREMENTS AND MAIN RESULTS: Median ICU stay was 0.98 (0.82-1.87) days. Median mechanical ventilation time was 9.5 (6.8-14.1) hours. One hundred one patients (78%) required inotropic support and 13 patients (10%) suffered cardiogenic shock and required intra-aortic balloon pump support. No patient died during the procedure, but 3 patients died in the ICU. Three postoperative course profiles were identified: Fast-track, overnight stay, and critical illness. Twenty-four patients (18.5%) had an uneventful postoperative course, 89 patients (68.5%) suffered minor complications, and 17 patients (13.1%) required intensive care management and organ support. Preoperative serum creatinine (odds ratio [OR] 1.8; p = 0.014), cardiogenic shock (OR 34,8; p = 0.002), ventricular tachycardia (OR 2.8; p = 0.03), and intra procedural inotropes (OR 4; p = 0.001) were correlated with a complicated postoperative course. CONCLUSIONS: A large number of patients undergoing MitraClip could be managed with a fast-track ICU course; however, it still is difficult to predict the postoperative course based on preoperative characteristics.

Usefulness of baseline activated clotting time-guided heparin administration in reducing bleeding events during transfemoral transcatheter aortic valve implantation.

OBJECTIVES: This study sought to evaluate the impact of baseline activated clotting time (ACT)-guided heparin administration on major bleeding after transfemoral transcatheter aortic valve implantation (TAVI). BACKGROUND: Bleeding after TAVI is frequent and associated with unfavorable prognosis. Proper intraprocedural heparin dose administration may reduce the risk of potential overdosing in this frail study group. METHODS: Of the patients who underwent transfemoral TAVI in our center from November 1, 2007 to June 31, 2012, 362 were retrospectively analyzed. Because abnormally high baseline ACT values were noted, heparin was administered at the operator's discretion, according to baseline ACT (ACT-guided, n = 174) or patient's body weight (non-ACT-guided, n = 188). The primary study objective was 30-day major bleeding as defined by the Valve Academic Research Consortium criteria. Secondary objectives were any life-threatening, and minor bleeding, and other Valve Academic Research Consortium outcomes at 30 days. RESULTS: Bleeding occurred in 167 (46.1%) patients; of these, 76 (21.0%) had major bleeding. The ACT-guided group had a significantly lower occurrence of major (7.5% vs. 33.5%, p < 0.001), life-threatening (12.1% vs. 20.2%, p = 0.04), and any bleeding (25.9% vs. 64.9%, p < 0.001). Conversely, no differences were noted in the other study objectives. After adjustment for potential confounders, the protective odds ratio for ACT-guided therapy on major bleeding was 6.4 (95% confidence interval: 2.3 to 17.9; p < 0.001) at 30 days. CONCLUSIONS: In our experience, heparin administration according to baseline ACT was correlated with a significantly lower occurrence of major bleeding in transfemoral TAVI. This strategy might be a useful tool in reducing bleeding in this high-risk study group.

A comparison of the femoral and radial crossover techniques for vascular access management in transcatheter aortic valve implantation: the Milan experience.

OBJECTIVE: To compare radial and femoral crossover techniques (CT) for vascular access management in transcatheter aortic valve implantation (TAVI). BACKGROUND: Femoral crossover for controlled angiography and balloon inflation of the therapeutic access site to facilitate safe vascular closure is beneficial but technically challenging in patients with complex femoral anatomy. An alternative approach should be available. METHODS: Between June 2011 and March 2012, 41 transfemoral TAVI patients receiving the femoral CT were compared to 46 transfemoral TAVI patients receiving the radial CT. Outcomes were 30-day valve academic research consortium (VARC) endpoints. RESULTS: Patients undergoing the radial CT received higher median contrast volumes (150 interquartile range [IQR]: 105-180 vs. 111 IQR: 90-139 ml; P = 0.025) but procedural radiation dose and fluoroscopy times were comparable. Thirty day all cause and cardiovascular death were similar between radial and femoral CT groups (respectively 2.4% vs. 7.9%, P = 0.258 and 0% vs. 7.9%, P = 0.063). There were no differences in major vascular complications (4.3% vs. 7.3%, P = 0.553), life threatening or major bleeding events (respectively 9.1% vs. 19.5%, P = 0.168 and 13.6% vs. 22%, P = 0.315). CONCLUSION: In TAVI cases with unfavorable contralateral femoral anatomy, radial CT for vascular access management is a reasonable alternative to the femoral CT.

Impact of mean platelet volume on combined safety endpoint and vascular and bleeding complications following percutaneous transfemoral transcatheter aortic valve implantation.

BACKGROUND: Vascular and bleeding complications remain important complications in patients undergoing percutaneous transfemoral transcatheter aortic valve implantation (TF-TAVI). Platelets play an important role in bleeding events. Mean platelet volume (MPV) is an indicator of platelet activation. The objective of this study was to assess whether low MPV is an indicator of major vascular and bleeding complications following TF-TAVI. METHODS: A retrospective cohort study of 330 subjects undergoing TF-TAVI implantation was performed. The primary study endpoint was the occurrence of combined safety endpoint (CSEP); secondary endpoints included major vascular complications and life-threatening bleeding. Endpoints were defined according to Valve Academic Research Consortium 2. RESULTS: The CSEP at 30 days was reached in 30.9%; major vascular complications were observed in 14.9% while life-threatening bleeding occurred in 20.6%. Logistic Euroscore and MPV were independent predictors of CSEP. Predictors of vascular complications were female sex, previous myocardial infarction, red blood cell distribution width (RDW), and MPV while predictors of life-threatening bleeding were peripheral arterial disease, RDW, and MPV. CONCLUSION: A low baseline MPV was shown for the first time to be a significant predictor of CSEP, major vascular complications, and life-threatening bleeding following TF-TAVI.

Percutaneous valve replacement in a young adult for radiation-induced aortic stenosis.

A 46-year-old woman known with relapsing Hodgkin's lymphoma diagnosed at age 5, treated with repeated cycles of radiotherapy and chemotherapy, presented with severe symptomatic radiation-induced aortic stenosis. She also had other late sequelae of radiotherapy including thyroid cancer, mediastinal fribrosis and left pulmonary fibrosis with severe restrictive lung disease and a newly diagnosed renal carcinoma. Due to the prohibitively high surgical risk and need for urgent treatment, she underwent successful transcatheter aortic valve replacement with transfemoral implantation of a 23 mm Edwards SAPIEN-XT prosthesis, which was performed without valvuloplasty of the noncalcified fibrotic valve. The final result was excellent with reduction of the transaortic gradient and no residual aortic regurgitation.

Anaesthetic management of transcatheter aortic valve implantation.

Transcatheter aortic valve implantation (TAVI) is an emergent technique for high-risk patients with aortic stenosis. TAVI poses significant challenges about its management because of the procedure itself and the population who undergo the implantation. Two devices are currently available and marketed in Europe and several other technologies are being developed. The retrograde transfemoral approach is the most popular procedure; nevertheless, it may not be feasible in patients with significant aortic or ileo-femoral arterial disease. Alternatives include a transaxillary approach, transapical approach, open surgical access to the retroperitoneal iliac artery and the ascending aorta. A complementary approach using both devices and alternative routes tailored to the anatomy and the comorbidities of the single patient is a main component for the successful implementation of a TAVI program. Anaesthetic strategies vary in different centers. Local anaesthesia or general anaesthesia are both valid alternatives and can be applied according to the patient's characteristics and procedural instances. General anaesthesia offers many advantages, mainly regarding the possibility of an early diagnosis and treatment of possible complications through the use of transesophageal echocardiography. However, after the initial experiences, many groups began to employ, routinely, sedation plus local anaesthesia for TAVI, and their procedural and periprocedural success demonstrates that it is feasible. TAVI is burdened with potential important complications: vascular injuries, arrhythmias, renal impairment, neurological complications, cardiac tamponade, prosthesis malpositioning and embolization and left main coronary artery occlusion. The aim of this work is to review the anaesthetic management of TAVI based on the available literature.

The role of sex on VARC outcomes following transcatheter aortic valve implantation with both Edwards SAPIEN™ and Medtronic CoreValve ReValving System® devices: the Milan registry.

AIMS: To assess outcomes after transcatheter aortic valve implantation (TAVI) according to sex, with the two available valves and four recognised delivery approaches. METHODS AND RESULTS: VARC outcomes are reported according to sex for 305 high-risk patients consecutively treated in our centre, via available access routes utilising the Edwards SAPIEN™/SAPIEN™ XT or the Medtronic CoreValve ReValving System® devices. Three hundred and five patients underwent TAVI: 52.1% male and 47.9% female. Females had a smaller body surface area (1.84±0.16 m² vs. 1.70±0.16 m²; p<0.001) and aortic annulus (24.4±1.6 mm vs. 22.6±1.7 mm; p<0.001) with increased symptoms (NYHA Class III/IV 61.6% vs. 73.6%; p=0.026). Conversely, men had more comorbidities: diabetes mellitus (35.2% vs. 21.9%; p=0.010), chronic kidney disease (41.8% vs. 23.3%; p=0.001), chronic obstructive pulmonary disease (45.3% vs. 30.1%; p=0.006) and previous myocardial infarction (28.3% vs. 14.4%; p=0.003). Thirty-day mortality was 4.7% with no difference between groups. There was a trend for females to develop more major vascular complications (11.9% vs. 19.9%; p=0.058). Notably, females required more blood transfusion (38.4% vs. 50.0%; p=0.041). No differences were observed in device success (92.5%; p=0.667), combined safety endpoint (61.8%; p=0.211) or combined efficacy endpoint (72.0%; p=0.889). CONCLUSIONS: Female sex was a predictor of major vascular complications with females requiring more transfusion. No differences were noted amongst patients undergoing TAVI in composite safety and efficacy endpoints according to sex.

Anesthetic management of transcatheter aortic valve implantation with transaxillary approach.

OBJECTIVE: To describe the anesthetic management of transcatheter aortic valve implantation (TAVI) with the transaxillary approach. DESIGN: An observational cohort study. SETTING: Two university hospitals. PARTICIPANTS: Twenty-two patients with severe aortic stenosis (± regurgitation) at high risk for surgical valve replacement, with contraindications for transfemoral TAVI (81 ± 4.9 years; logistic EuroSCORE, 27% ± 16.9%). INTERVENTION: General anesthesia or local anesthesia plus sedation followed by postoperative care. MEASUREMENTS AND MAIN RESULTS: Local anesthesia plus sedation and general anesthesia were used in 14 and 8 patients, respectively. Two patients undergoing local anesthesia were monitored with transesophageal echocardiography and supported with noninvasive mask ventilation during the procedure. Main complications included hemodynamic instability requiring inotropes (2 patients), severe postimplant aortic regurgitation requiring immediate second valve-in-valve implantation (1 patient), valve embolization requiring open-valve surgery (1 patient), subclavian artery dissection compromising the flow to a mammary artery graft (1 patient), ascending aortic dissection (1 patient), stroke (2 patients), and atrioventricular block requiring pacemaker implantation (3 patients). Four patients experienced an increased (baseline value × 1.5) postoperative serum creatinine. Five patients required red blood cell tranfusions (2 units). Intensive care unit stay and hospital stay were 6 (4-23) hours and 8 (8-9) days, respectively. All patients were alive 30 days after the procedure. The 6-month mortality was 9%. CONCLUSIONS: Transaxillary TAVI is feasible in high-risk patients with aortic stenosis and peripheral vasculopathy. Nevertheless, severe procedural complications are possible, and anesthesiologists should be prepared to assist in the management of these conditions.

Reducing mortality in cardiac surgery with levosimendan: a meta-analysis of randomized controlled trials.

OBJECTIVES: The authors performed a meta-analysis to evaluate whether levosimendan is associated with improved survival in patients undergoing cardiac surgery. DESIGN: A meta-analysis. SETTING: Hospitals. PARTICIPANTS: A total of 440 patients from 10 randomized controlled studies were included in the analysis. INTERVENTIONS: None. MEASURMENTS AND MAIN RESULTS: Four investigators independently searched BioMedCentral and PubMed. Inclusion criteria were random allocation to treatment, comparison of levosimendan versus control, and cardiac surgery patients. Exclusion criteria were duplicate publications, nonhuman experimental studies, and no mortality data. The primary endpoint was postoperative mortality. Levosimendan was associated with a significant reduction in postoperative mortality (11/235 [4.7%] in the levosimendan group v 26/205 [12.7%] in the control arm, odds ratio = 0.35 [0.18-0.71], p for effect = 0.003, p for heterogeneity = 0.22, I(2) = 27.4% with 440 patients included), cardiac troponin release, and atrial fibrillation. No difference was found in terms of myocardial infarction, acute renal failure, time on mechanical ventilation, intensive care unit, and hospital stay. CONCLUSIONS: Levosimendan has cardioprotective effects that could result in a reduced postoperative mortality. A large randomized controlled study is warranted in this setting.

Human protein C zymogen concentrate in patients with severe sepsis and multiple organ failure after adult cardiac surgery.

PURPOSE: To describe outcome and changes in clotting and inflammatory parameters in an uncontrolled case series of consecutive patients with severe sepsis who received protein C concentrate soon after cardiac surgery. METHODS: From January 2007 to January 2008 nine consecutive adult patients with severe sepsis or septic shock and two or more organ failure after cardiac surgery received protein C concentrate, 50 IU/kg as a bolus followed by continuous infusion of 3 IU/kg per hour for 72 h. RESULTS: The increase in protein C levels was accompanied by an early drop in interleukins and near-normalization of prothrombin time, activated partial thromboplastin time, antithrombin and thrombin-antithrombin complex levels (p < or = 0.03). No patient experienced drug-related side effects. Thirty-day mortality was 11% (1 patient) compared to the expected mortality of 68%. CONCLUSIONS: In this pilot, uncontrolled study of nine patients with sepsis-induced double organ failure following cardiac surgery, treatment with protein C concentrate was associated with significant improvement in clinical, inflammatory and clotting parameters, no bleeding and low 30-day mortality.

Levosimendan reduces cardiac troponin release after cardiac surgery: a meta-analysis of randomized controlled studies.

OBJECTIVES: The authors performed a meta-analysis to investigate the effects of levosimendan in cardiac surgery. Inotropic drugs have never shown beneficial effects on outcome in randomized controlled studies, with the possible exception of levosimendan. DESIGN: A meta-analysis. SETTING: Hospitals. PARTICIPANTS: A total of 139 patients from 5 randomized controlled studies were included in the analysis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Four investigators independently searched BioMedCentral and PubMed. Inclusion criteria were random allocation to treatment, and comparison of levosimendan versus control performed on cardiac surgery patients. Exclusion criteria were duplicate publications, nonhuman experimental studies, and no outcome data. The endpoint was postoperative cardiac troponin release. Levosimendan was associated with a significant reduction in cardiac troponin peak release (weighted mean difference = 2.5 ng/dL [-3.86, -1.14], p = 0.0003) and in time to hospital discharge (weighted mean difference = -1.38 days [-2.78, 0.03], p = 0.05). No other relevant outcome (mortality, myocardial infarction, atrial fibrillation, time on mechanical ventilation, and intensive care unit stay) was improved in those patients receiving levosimendan. CONCLUSIONS: Levosimendan has cardioprotective effects, resulting in reduced postoperative cardiac troponin release.

Effects of tranexamic acid on postoperative bleeding and related hematochemical variables in coronary surgery: Comparison between on-pump and off-pump techniques.

OBJECTIVES: Bleeding and inflammation are major complications of extracorporeal circulation. Off-pump coronary artery bypass grafting may reduce the rate of complications, but it can only be applied in selected cases. Pilot studies have shown a potential benefit from the use of antifibrinolytic drugs, but efficacy in randomized double-blind studies evaluating off- and on-pump coronary artery bypass grafting has not been proved. METHODS: We enrolled 102 patients scheduled for on-pump (n = 51) or off-pump (n = 51) coronary artery bypass grafting. Patients were separately double-blind randomly assigned to treatment with tranexamic acid (1 g as 20-minute bolus before skin incision, followed by continuous infusion of 400 mg/h, with 500 mg added to priming in patients undergoing on-pump coronary artery bypass grafting) or placebo (saline solution of equivalent volume). Bleeding in the first 24 postoperative hours was the primary outcome. Requirement for allogeneic transfusions, thrombotic complications, outcomes, and monitoring of coagulation, fibrinolysis, and inflammation were also recorded. RESULTS: Tranexamic acid reduced total postoperative bleeding by 43% in patients undergoing on-pump coronary artery bypass grafting and by 27% in those undergoing off-pump coronary artery bypass grafting (P <.0001), with 80% reduction in bleeding exceeding 600 mL (P <.001), 58% reduction in the requirement for all allogeneic transfusions (P =.07), and no apparent effect on thrombotic complications or outcome. This was associated with a reduction in plasma D-dimer levels (P <.0001), to a greater degree in patients undergoing on-pump coronary artery bypass grafting (P <.0001), and interleukin 6 levels (P <.0001), to a greater degree in patients undergoing off-pump coronary artery bypass grafting (P <.001). CONCLUSIONS: By affecting fibrinolysis, tranexamic acid significantly reduces bleeding both in off- and on-pump coronary artery bypass grafting and may modulate inflammation in these surgical settings.