Tranexamic acid compared with high-dose aprotinin in primary elective heart operations: effects on perioperative bleeding and allogeneic transfusions.

OBJECTIVE: Since excessive fibrinolysis during cardiac surgery is frequently associated with abnormal perioperative bleeding, many authors have advocated prophylactic use of antifibrinolytic drugs to prevent hemorrhagic disorders. We compared the effects of tranexamic acid (a synthetic antifibrinolytic drug) with aprotinin (a natural derivative product with antifibrinolytic properties) on perioperative bleeding and the need for allogeneic transfusions. METHODS: In a single-center prospective randomized unblinded trial, 1040 consecutive patients undergoing primary, elective cardiac operations with cardiopulmonary bypass received either high-dose aprotinin or tranexamic acid. The aprotinin group (518 patients) received 280 mg in 20 minutes before the skin incision, 280 mg in the priming solution of the extracorporeal circuit, and a continuous infusion of 70 mg/h throughout the operation. The tranexamic acid group (522 patients) received 1 g in 20 minutes before the skin incision, 500 mg in the priming solution of the extracorporeal circuit, and a continuous infusion of 400 mg/h during the operation. Postoperative bleeding, perioperative transfusions, and hematologic variables were evaluated at fixed times. Postoperative thrombotic complications, intubation time, intensive care unit stay, and hospital stay were recorded. RESULTS: Postoperative bleeding was similar in the 2 groups: aprotinin 250 mL (150-400 mL) versus tranexamic acid 300 mL (200-450 mL) (median and 25th-75th quartiles), median difference of 50 mL (95% confidence intervals, 0-50 mL). The number of transfusions and the outcome did not differ. CONCLUSIONS: Tranexamic acid and aprotinin show similar clinical effects on bleeding and allogeneic transfusion in patients undergoing primary elective heart operations. Since tranexamic acid is about 100 times cheaper than aprotinin, its use is preferable in this type of patient.

Tranexamic acid in off-pump coronary surgery: a preliminary, randomized, double-blind, placebo-controlled study.

BACKGROUND: We evaluated the hemostatic effects of tranexamic acid, a synthetic antifibrinolytic drug, in patients undergoing beating-heart coronary surgery. METHODS: Forty consecutive patients were in a double-blind manner, prospectively randomized into two groups: 20 patients received tranexamic acid (bolus of 1 g before skin incision, followed by continuous infusion of 400 mg/hr during surgery), and 20 patients received saline. As primary outcomes, bleeding and allogeneic transfusions were considered. D-dimer and fibrinogen plasma levels were also evaluated to monitor the activation of fibrinolysis. Major postoperative thrombotic events, as a potential consequence of antifibrinolytic treatment, were recorded. RESULTS: The treatment group had significantly lower postoperative bleeding (median [25th to 75th percentiles]: 400 mL [337 to 490 mL] vs 650 ml [550 to 862 mL], p < 0.0001), lower need for allogeneic blood products (1,200 vs 5,300 mL, p < 0.001), and lower postoperative D-dimer plasma levels. No postoperative thrombotic complications were observed in either group. CONCLUSIONS: In this initial series of patients undergoing off-pump coronary surgery, tranexamic acid appears to be effective in reducing postoperative bleeding and the need for allogeneic blood products.

Hemostatic effects of aprotinin, tranexamic acid and epsilon-aminocaproic acid in primary cardiac surgery.

BACKGROUND: The effects of epsilon-aminocaproic acid (EACA) and tranexamic acid (TA) on bleeding and allogeneic transfusions, and the cost of pharmacological and transfusional treatment were compared to aprotinin (AP). METHODS: We randomized 210 patients subjected to elective cardiac surgery. Of these, 68 patients received EACA (a bolus of 5 g, an infusion of 2 g/h, and 2.5 g in the priming), 72 patients received TA (a bolus of 1 g, an infusion of 400 mg/h, and 500 mg in the priming), and 70 patients received AP (a bolus of 280 mg, an infusion of 70 mg/h, and 280 mg in the priming). Postoperative blood loss and homologous transfusions were collected and the cost of pharmacological treatment and homologous transfusions were calculated. RESULTS: Bleeding but not allogeneic transfusions was significantly higher in the EACA group (467+/-234 versus TA, 311+/-231 versus AP, 283+/-233; p < 0.001). Costs of pharmacological and transfusional treatment were significantly lower in the TA group ($58.10+/-$105.10) versus the EACA group ($100.70+/-$158.60) versus the AP group ($432.60+/-$118.70) (p < 0.0001). CONCLUSIONS: Compared to AP, TA has the same effects on bleeding and transfusions, but with a significant reduction of costs. Patients treated with EACA showed a significantly higher postoperative bleeding with an increased trend of transfusion requirement.

Heparin-coated circuits for high-risk patients: a multicenter, prospective, randomized trial.

BACKGROUND: Heparin-coated circuits (HCCs) in low-risk cardiac patients who have coronary revascularization have a limited impact on postoperative outcome. In this prospective, randomized investigation, we studied high-risk patients who had cardiac operations with or without HCCs. METHODS: A total of 886 patients who had cardiac operations with cardiopulmonary bypass and at least one patient-related or procedure-related risk factor were enrolled in a multicenter study. They were randomly allocated to have cardiopulmonary bypass with Duraflo II HCCs (HCC group, n = 442) or conventional circuits (control group, n = 444). Postoperative outcome was investigated with respect to the occurrence of organ dysfunction. RESULTS: HCCs are associated with a shorter intensive care unit and postoperative hospital stay and with a lower rate of patients having a severely impaired clinical outcome (stay in intensive care unit for more than 5 days or death) (relative risk 0.66, p = 0.045). Lung dysfunction rate was significantly lower for the patients in HCC group affected by chronic obstructive pulmonary disease or who had mitral procedure (relative risk, respectively, 0.31, p = 0.018 and 0.05, p = 0.02). Renal dysfunction rate was significantly (p = 0.05) lower for diabetics in the HCC group (relative risk 0.28). CONCLUSIONS: When HCCs were used postoperative times decreased and they had a protective effect on lung and kidney function in high-risk patients.

A simple way to treat chronic atrial fibrillation during mitral valve surgery: the epicardial radiofrequency approach.

OBJECTIVE: We describe an original radiofrequency ablation technique to treat chronic atrial fibrillation in patients undergoing mitral valve surgery. Most of the procedure is carried out epicardially, in order to avoid an undue increase of surgical time and trauma. METHODS: The ablations are performed using a temperature-controlled multipolar radiofrequency catheter. Two encircling lesions around the ostia of the right and of the left pulmonary veins are carried out epicardially, usually before cardiopulmonary bypass. Through a conventional left atriotomy the ablation procedure is completed with two endocardial lesions connecting the two encirclings between them and to the mitral valve annulus. After the mitral valve procedure is performed, the left appendage is sutured. RESULTS: From February 1998 to May 1999, 40 patients with chronic atrial fibrillation (43. 1+/-51.9 months) underwent combined radiofrequency ablation and mitral valve surgery. Mean left atrial diameter was 56.8+/-10.7 mm. Mean cardiopulmonary bypass and aortic cross-clamp time were, respectively, 119.1+/-26.3 and 76.7+/-21.0 min. Mean postoperative blood loss was 287.2+/-186.6 ml. No reexploration for bleeding occurred. One patient died of pneumonia 12 days after operation. No patient needed permanent pacemaker implantation. Mean postoperative hospital stay was 7.3+/-5.6 days. At follow-up (mean 11.6+/-4.7 months), 30/39 (76.9%) of the patients were in stable sinus rhythm. All patients in sinus rhythm 3 months after operation recovered both left and right atrial contractility at echocardiographic control (mean 7.3+/-3.4 months). The left atrial diameter decreased significantly in patients recovering sinus rhythm. CONCLUSIONS: Epicardial radiofrequency ablation is a safe means to achieve surgical ablation of atrial fibrillation with a high success rate. The simplicity of the technique and the low procedure-related risk should dictate combined treatment virtually in all patients with atrial fibrillation undergoing open heart operations.

Aortic valve repair for traumatic aortic insufficiency.

Prolapse of a commissural portion of the aortic valve due to partial intimal tear following a blunt chest trauma is a rare condition. Aortic valve repair is a technically demanding operation and the presence of aortic incompetence due to leaflet prolapse often leads to aortic valve replacement. We report the case of a patient with aortic insufficiency due to commissural disruption following a road traffic accident, and in whom aortic valve repair was performed.

[Epicardial ablation of atrial fibrillation during heart valve surgery]. / Ablazione epicardica della fibrillazione atriale durante chirurgia valvolare.

BACKGROUND: We report the results of an intraoperative ablation procedure for combined treatment of atrial fibrillation (AF) in patients affected by heart valve disease. METHODS: From February 1998 to June 2000, 80 patients scheduled for heart valve operations underwent combined surgical treatment of AF. Seventy-eight patients had mitral valve disease and 2 had aortic regurgitation; 74 patients were affected by chronic AF (mean 50 +/- 74 months, range 6-480 months) and 6 had paroxysmal AF. A left atrial set of radiofrequency ablations (mainly epicardial) was performed in all patients. RESULTS: Thirty-five patients underwent conservative mitral valve surgery, 43 had mitral valve replacement and 2 had aortic valve replacement. The combination of the ablation procedure did not lead to a substantial prolongation of cardiopulmonary and aortic cross clamp time and did not increase perioperative morbidity. No procedure-related complications were recorded. Operative mortality was favorably comparable with that of valvular surgery alone (2.5%). Mean hospital stay was 6.8 +/- 4.4 days. At follow-up (16.2 +/- 9.2 months, range 3-28 months), 61 patients (78.2%) were in stable sinus rhythm; all of them recovered left and right atrial contractility as assessed by Doppler echocardiography. CONCLUSIONS: The combined treatment of AF with a radiofrequency ablation surgical technique is effective in restoring stable sinus rhythm and atrial contractility. The procedure is low risk thereby allowing a prompt clinical recovery after operation. It should therefore be considered in all patients with AF undergoing open-heart surgery.

Off-pump coronary surgery in a patient with multiple sclerosis.

Surgery in patients with multiple sclerosis, the most common autoimmune demyelinating disorder of the central nervous system, represents a challenge for surgeons and anesthesiologists because of the reported risk of relapse of the neurologic symptoms in the perioperative period. In this report, we describe the management of a patient with relapsing-remitting multiple sclerosis and critical coronary artery disease, who underwent an uneventful off-pump coronary artery revascularization. The issues pertaining to the performance of coronary surgery revascularization on patients with multiple sclerosis are discussed.

Perioperative management of four anaemic female Jehovah's Witnesses undergoing urgent complex cardiac surgery.

Previous studies have demonstrated that preoperative haemoglobin concentration and female gender are related to an increased need for perioperative allogeneic transfusions in cardiac surgery. Hence, urgent cardiac surgery presents a dilemma for female patients who are Jehovah's Witnesses, because of their refusal of allogeneic transfusion. This report describes the management of four high-risk anaemic female patients undergoing urgent complex cardiac surgery. In these Jehovah's Witness patients, strict application of a comprehensive blood-sparing protocol permitted safe avoidance of allogeneic transfusions. The protocol involved intraoperative acute normovolaemic haemodilution, intraoperative administration of tranexamic acid, intra- and postoperative use of a cell-saver system, postoperative administration of erythropoietin, iron and folic acid, and a careful surgical technique to avoid perioperative bleeding.

Post-irradiation enzyme activities of the rat small intestine: effects on circadian fluctuations.

The effects of ionizing radiations on circadian fluctuations in the activities of small bowel mucosal enzymes were studied. The fluctuations in activities of brush-border enzymes disappeared after irradiation coincidentally with changes in their activity. This change was particularly pronounced with leucinaminopeptidase. At longer periods after irradiation (50 and 74 hours) when the whole epithelium showed morphological changes, the activity of brush-border enzymes was very low. The activity of lysosomal enzymes (which do not show circadian fluctuations) increased when the epithelium showed marked morphological modifications and the stroma contained numerous inflammatory cells.

Circadian activity of rat kidney enzymes.

Alkaline phosphatase, LAP, beta-glucuronidase and cathepsin D activities and protein content of the kidney homogenate did not show any circadian rhythm in animals sacrificed at different hours of the day. The fluctuations of maltase appear modest and not dependent on a ligh/dark cycle.

Effect of whole body irradiation on different tissues. Experiments with 14C leucine in the rat.

The uptake and elimination of 14C leucine were analysed in controls and in rats irradiated 2 h before injection with 8 Gy whole-body irradiation. Plasma, small intestine, kidney and skin were assayed after homogenization for TCA soluble activity curves. In highly differentiated tissues with poor proliferative activity and low protein turnover, the uptake and elimination of the tracer did not appear to be affected by irradiation. In the small intestine differences between control and irradiated animals seemed significant.

Activation of coagulation and fibrinolysis during coronary surgery: on-pump versus off-pump techniques.

BACKGROUND: The authors studied the changes in selected hemostatic variables in patients undergoing coronary surgery with on-pump coronary artery bypass grafting (CABG) or off-pump coronary artery bypass surgery (OPCAB) techniques. METHODS: Platelet counts and plasma concentrations of antithrombin, fibrinogen, D dimer, alpha(2) antiplasmin, and plasminogen were measured preoperatively, 5 min after administration of heparin, 10 min after arrival in the intensive care unit, and 24 h after surgery in patients scheduled to undergo OPCAB (n = 15) or CABG (n = 15). To correct for dilution, hemostatic variables and platelet counts were adjusted for the changes in immunoglobulin G plasma concentrations and hematocrit, respectively. RESULTS: Adjusting for dilution, antithrombin and fibrinogen concentrations decreased to a similar extent in patients undergoing OPCAB or CABG (pooled means and 95% confidence limits of the mean: 95.5% of baseline, 93-98%, P = 0.002, and 91.7% of baseline, 88-95%, P = 0.0001), respectively, whereas alpha(2)-antiplasmin concentrations were unchanged. Only CABG was associated with a reduction in platelet counts (76% of baseline, 66-85%, P = 0.0001), plasminogen concentrations (96% of baseline, 91-99%, P = 0.011), and increased D-dimer formation (476%, 309-741%, P = 0.004). Twenty-four hours after surgery, platelet counts were still lower in patients undergoing CABG (P = 0.049), but all the investigated variables adjusted for dilution were similar in the two groups. CONCLUSIONS: Coronary surgery causes a net consumption of antithrombin and fibrinogen. A transient decrease in platelet counts, with plasminogen activation and increased D-dimer formation, however, is only observed with CABG. Twenty-four hours after surgery, the hemostatic profiles of patients in both groups are similar.

[The effectiveness of enoximone in patients with serious left ventricular dysfunction submitted for aorto-coronary bypass]. / Efficacia dell'enoximone in pazienti con grave disfunzione ventricolare sinistra sottoposti a bypass aorto-coronarico.

BACKGROUND: The purpose of this study was to investigate whether the combined positive inotropic and vasodilating properties of enoximone have a short-term benefit when used in patients who underwent open heart surgery. METHODS: From 7/1994 to 1/1995 twenty-six patients with severe myocardial dysfunction (ejection fraction < 35%) were enrolled into a prospective trial before undergoing coronary artery bypass graft. They were randomly selected into two study groups: the first treated with enoximone (group E) and the other one with dopamine (group D). Anaesthesia was the same for both groups using high-dose fentanyl. Buckberg cardioplegia was used. All patients were followed by: conventional monitoring, Swan-Ganz catheter and transesophageal echocardiography. measurements (hemodynamic parameters, end-systolic and diastolic area and left ventricular wall motion) were recorded: after induction of anesthesia, after loading-dose and an intensive care unit. Enoximone- and dopamine infusions were started during weaning from cardiopulmonary bypass and tailored to hemodynamic parameters (cardiac index > 2.8 l/min, wedge pressure < 16 mmHg, mixed venous blood saturation > 65%). Major events were defined as: endotracheal intubation > 36 h, using intraortic balloon pump or centrifugal pump, intensive care timer > 48 h, in hospital cardiac death. Prices, were established by DRG-tables (diagnosis related groups). Statistical analysis were performed by X and "t" Student tests. RESULTS: Cardiac index increased more significantly in group E (CI 1.9-->3.9 vs 2.3-->3.3; p 0.05) thanks to a higher reduction of vascular systemic (SVRI 2889-->1447 vs 2536 -->1565; p 0.005) and pulmonary resistances (PVRI 271-->193 vs 288-->218; p 0.05). Fewer major cumulative events and intensive care costs were observed in group E rather than group D. CONCLUSIONS: Enoximone administer immediately after open heart surgery had more beneficial hemodynamic and clinical effects than dopamine in patients with severe left ventricular dysfunction.

Tranexamic acid administration after cardiac surgery: a prospective, randomized, double-blind, placebo-controlled study.

BACKGROUND: Many different doses and administration schemes have been proposed for the use of the antifibrinolytic drug tranexamic acid during cardiac surgery. This study evaluated the effects of the treatment using tranexamic acid during the intraoperative period only and compared the results with the effects of the treatment continued into the postoperative period. METHODS: Patients undergoing elective cardiac surgery with use of cardiopulmonary bypass (N = 510) were treated intraoperatively with tranexamic acid and then were randomized in a double-blind fashion to one of three postoperative treatment groups: group A: 169 patients, infusion of saline for 12 h; group B: 171 patients, infusion of tranexamic acid, 1 mg x kg(-1) x h(-1) for 12 h; group C: 170 patients, infusion of tranexamic acid, 2 mg x kg(-1) x h(-1) for 12 h. Bleeding was considered to be a primary outcome variable. Hematologic data, allogeneic transfusions, thrombotic complications, intubation time, and intensive care unit and hospital stay duration also were evaluated. RESULTS: No differences were found among groups regarding postoperative bleeding and outcomes; however, the group treated with 1 mg x kg(-1) x h(-1) tranexamic acid required more units of packed red blood cells because of a significantly lower basal value of hematocrit, as shown by multivariate analysis. CONCLUSIONS: Prolongation of treatment with tranexamic acid after cardiac surgery is not advantageous with respect to intraoperative administration alone in reducing bleeding and number of allogeneic transfusions. Although the prevalence of postoperative complications was similar among groups, there is an increased risk of procoagulant response because of antifibrinolytic treatment. Therefore, the use of tranexamic acid during the postoperative period should be limited to patients with excessive bleeding as a result of primary fibrinolysis.