Tranexamic Acid Infusion in Low Dose Versus in High Dose for Reducing Blood Loss in Radical Cystectomy Operations

Overview

Bladder cancer is one of the most common cancers of the genitourinary tract in adults, and its incidence distinctly increases with age . In almost two-thirds of cases, the disease is superficial at presentation and involves the mucosal and sub mucosal layers or the lamina propria of the bladder, whereas ∼20% to 30% of patients have muscle-invasive tumors. Superficial bladder cancer is treated by transurethral endoscopic resection, which can be followed by endovesical therapy for patients at risk of disease recurrence and progression . In contrast, muscle-invasive bladder cancer is generally treated by radical cystectomy with pelvic lymph node dissection and then creation of urinary diversion to create an alternate route for urine passage, which demonstrates 10-year recurrence-free survival rates of 50% to 59% and overall survival rates of ∼45% . These major surgeries have a prolonged operative times and are associated with significant risk of complications including high risk of perioperative bleeding and subsequent need for blood transfusion with significant postoperative complications, which are reportedly in the range of 24% to 64% .

Among individual surgeons at institutions that perform many procedures, median intraoperative blood loss is between 600 and 1700 mL. The incidence of at least one intraoperative blood transfusion is 9 to 67%, and the postoperative transfusion risk is at least 15%. Among cystectomy patients who receive transfusion, a median of 2 units of blood cells are given. Therefore, it is very important to establish surgical and anesthetic protocols aimed at minimizing intraoperative blood loss and subsequent blood transfusion requirements in order to improve postoperative outcomes. Venous thromboembolism (VTE) in radical cystectomy can account for up to 22% of total deaths after surgery . In the bladder cancer literature, symptomatic thromboembolic events occur in up to 8.3% of patients , but subclinical deep vein thrombosis (DVT) rates can be as high as 24.4% when examining an ultrasonography (US)-screened population . In fact, undergoing a RC is a significant, independent risk factor on multivariable analysis for developing a deep venous thrombosis. Lysine analog drugs are synthetic derivatives of the amino acid lysine that reversibly block lysine-binding sites on plasminogen molecules. This action prevents the conversion of plasminogen to plasmin, the active enzyme that degrades fibrin clots. Therefore, lysine analogs decrease the breakdown of clots and are considered anti-fibrinolytics. There are two commonly studied lysine analogs, tranexamic acid and epsilon-aminocaproic acid. Both of these drugs have been shown to decrease blood loss and blood transfusion need during some surgeries without a significant increase in adverse events.