Background
Bleeding that occurs after noncardiac surgery has emerged as a significant contributor to postoperative morbidity and mortality. A study of over 40,000 patients undergoing noncardiac surgery found that major bleeding affected 15% of patients, and was independently associated with 30-day mortality [1]. These results are consistent with previously published studies that showed perioperative bleeding increased morbidity, mortality, and resource utilization [2-4]. This association of perioperative bleeding and major adverse events may be associated with a drop in perioperative hemoglobin, producing a decrease in arterial oxygen content. This pathology suggests that preventing perioperative blood loss may translate to fewer postoperative complications in noncardiac surgery. Tranexamic acid (TXA) is an antifibrinolytic approved for the prevention and treatment of bleeding in numerous clinical settings.
These include cardiac surgery with cardiopulmonary bypass, joint arthroplasty, acute trauma, and in obstetrics to prevent post-partum hemorrhage [5, 6, 7,8]. TXA acts as a synthetic lysine analog, inhibiting the conversion of plasminogen to plasmin by blocking the lysine-binding sites on the plasminogen molecule. This creating a reversable reduction in plasminogen-fibrin activity, decreasing fibrinolysis and clot degradation. TXA has shown blood loss prevention and blood transfusion avoidance in numerous noncardiac surgery populations, including joint arthroplasty [9], spine surgery [10], gynecological [11], and urological surgery [12]. While efficacy has clearly demonstrated in many noncardiac surgery populations, clinical trials of TXA in noncardiac surgery have been insufficiently powered to evaluate both efficacy and safety, limiting its use in a broader range of noncardiac surgery population.
POISE-3 Trial
The Perioperative Ischemic Evaluation-3 (POISE-3) study was a multicenter, international randomized controlled trial of TXA vs placebo in noncardiac surgery patient ages 45 and older. [13] Primary outcomes of the study included both efficacy and safety endpoints. These included;
• Efficacy: Composite 30-day incidence of; life-threatening bleeding, major bleeding, and bleeding into a critical organ (Assessed via superiority with 2-sided confidence interval of 95% (p< 0.05))
• Safety: Composite 30-day incidence of; myocardial injury after noncardiac surgery (MINS), nonhemorrhagic stroke, peripheral arterial thrombosis, and symptomatic proximal venous thromboembolism (Assessed via non-inferiority with 1-sided CI of 97.5%, (p<0.025)) Patients included were ≥45 years of age with, or at risk of, atherosclerotic disease, and undergoing major noncardiac surgery. Included comorbidities were a history of coronary artery disease, peripheral vascular disease, a history of stroke, a history of TIA, a history of diabetes, or a history of smoking within 2 years. Excluded populations were patients with; a hypersensitivity to TXA, CrCl <30mL/min or chronic dialysis, a history of seizures, recent (<3 months) stroke, MI, arterial or venous thrombosis, subarachnoid hemorrhage within 30 days, or a fibrinolytic condition following consumptive coagulopathy.
Dosing: 1000mg IV over 10 minutes, prior to incision and 1000mg IV over 10 minutes at wound closure
Administration of Tranexamic acid
Maximum infusion rate: 100mg/min
• For weight-based bolus doses that are not able to be rounded to 1000mg, consider using tranexamic acid vial (1000mg/10mL). Tranexamic acid may be administered undiluted by IV injection max rate 100mg/min
• For continuous infusion administration, use 1000mg/100mL stock bag
Hospital Committee Endorsements
• Pharmacy & Therapeutics Committee (September 2022)
• Perioperative P&T Subcommittee (August 2022)
• Antithrombosis Stewardship P&T Subcommittee (September 2022)
References
1. Vascular Events in Noncardiac Surgery Patients Cohort Evaluation (VISION) Study Investigators, Spence J, LeManach Y, Chan MTV, et al. Association between complications and death within 30 days after noncardiac surgery. CMAJ. 2019 Jul 29;191(30):E830-E837. doi: 10.1503/cmaj.190221.
2. Obi AT, Park YJ, Bove P, et al. The association of perioperative transfusion with 30-day morbidity and mortality in patients undergoing major vascular surgery. J Vasc Surg 2015; 61: 1000. 9.e1
3. Smilowitz NR, Oberweis BS, Nukala S, et al. Association between anemia, bleeding, and transfusion with long-term mortality following non-cardiac surgery. Am J Med 2015; 129: 315e23. e2
4. Wu WC, Smith TS, Henderson WG, et al. Operative blood loss, blood transfusion, and 30-day mortality in older patients after major noncardiac surgery. Ann Surg 2010; 252: 11e7
5. Fergusson DA, Hébert PC, Mazer CD, Fremes S, MacAdams C, Murkin JM, Teoh K, Duke PC, Arellano R, Blajchman MA, Bussières JS, Côté D, Karski J, Martineau R, Robblee JA, Rodger M, Wells G, Clinch J, Pretorius R; BART Investigators. A comparison of aprotinin and lysine analogues in high-risk cardiac surgery. N Engl J Med. 2008 May 29;358(22):2319-31
6. Fillingham YA, Ramkumar DB, Jevsevar DS, et al. Reg Anesth Pain Med 2019;44:7–11.
7. CRASH-2 trial collaborators Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomized placebo-controlled trial. , Lancet. 2010;376(9734): 23–32.
8. Shakur H, Roberts I, Fawole B, Chaudhri R, El-Sheikh M, Akintan A, et al. Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial. Lancet. 2017 May;389 (10084):2105–16.
9. Zhou XD, Tao LJ, Li J, Wu LD. Do we really need tranexamic acid in total hip arthroplasty? A meta-analysis of nineteen randomized controlled trials. Arch Orthop Trauma Surg 2013;133:1017–27.
10. Li ZJ, Fu X, Xing D, Zhang HF, Zang JC,Ma XL. Is tranexamic acid effective and safe in spinal surgery? A meta-analysis of randomized controlled trials. Eur Spine J and the European Section of the Cervical Spine Research Society 2013;22:1950–7.
11. Martin-Hirsch PP, Bryant A. Interventions for preventing blood loss during the treatment of cervical intraepithelial neoplasia. Cochrane Database Syst Rev 2013; 12:CD001421.
12. Zaid HB, Yang DY, Tollefson MK, Frank I, Winters JL, Thapa P, Parker WP, Thompson RH, Karnes RJ, Boorjian SA. Efficacy and Safety of Intraoperative Tranexamic Acid Infusion for Reducing Blood Transfusion During Open Radical Cystectomy. Urology. 2016 Jun;92:57-62
13. Devereaux PJ, Marcucci M, Painter TW. Tranexamic Acid in Patients Undergoing Noncardiac Surgery. N Engl J Med. 2022 May 26;386(21):1986-1997. doi: 10.1056/NEJMoa2201171. Epub 2022 Apr 2. PMID: 35363452.BJA 172-8
Published 10/8/22 Eric Johnson/A Bernard