Local Tranexamic Acid Reduces Surgical Blood Loss

Reference: Dong Y, Liang J, Tong B, Shen J, Zhao H, Li Q. Combined topical and IV administration of tranexamic acid further reduces postoperative blood loss in adolescent idiopathic scoliosis patients undergoing spinal fusion surgery: a randomized controlled trial. BMC Musculoskelet Disord. 2021;22(1):663. doi:10.1186/s12891-021-04562-5

Rationale: Used to treat patients with scoliosis, spinal fusion surgery often causes substantial blood loss, thereby requiring allogenic blood transfusions. Systemic TXA effectively reduced blood loss during orthopedic surgery, though small fractions of the systemic dose were delivered to the surgical site.

Objective: This study explored the effects of combined systemic and local delivery of TXA on blood loss in those with adolescent idiopathic scoliosis undergoing spinal fusion surgery.

Methods: With appropriate institutional review and patient consent, researchers at the Peking Union Medical College Hospital, Beijing, China, conducted a prospective RCT assigning patients with adolescent idiopathic scoliosis undergoing spinal fusion surgery to receive either combined topical and IV TXA (topical plus IV: n = 43) or IV TXA alone (IV: n = 42). Both groups received an initial IV dose of 1 g of TXA followed by a maintenance dose of 10 mg/kg per hour until surgical closure. The topical plus IV patients received an additional retrograde injection of 2 g TXA injected locally into a wound drain, clamped for 2 hours after surgery, whereas the IV group received an equivalent volume of saline through a similar wound drain similarly clamped. Blood loss volume was the primary outcome, measured as the sum of intraoperative (suction contents plus content of surgical sponges) and postoperative measured drainage. The secondary outcome was the number of transfusions required. Related blood parameters supported the results. A power analysis, assuming that a 20% difference in blood loss was clinically significant, indicated that at least 39 evaluable patients were needed for the study. Forty patients in each group were included in the study. Results were statistically significant if the alpha error level was less than or equal to 0.05

Results: The 2 groups were comparable at baseline and did not differ in the number of transfusions required during or after surgery or complications. Postoperative drainage, the primary outcome, was less for the topical plus IV group on each successive postoperative day (P <.05) and in total (P <.01). The topical plus IV group also experienced earlier drain removal (P <.01) and shorter hospital stay (P =.038). The limitations of the study included that the study did not measure plasma TXA or hematocrit levels or screen for deep vein thrombosis.

Authors’ Conclusions: Locally injected TXA added to IV systemic TXA reduced wound drainage and shortened hospital stays of adolescent patients undergoing surgery for idiopathic scoliosis.

Reference: Costain D, Elder G, Fraser B, Slagel B, Kelly A, Cheong Y, Fera L. Topical tranexamic acid in hip fractures: a randomized, placebo-controlled double-blinded study. Can J Surg. 2021;64(4):E449–E456. doi:10.1503/cjs.014220

Rationale: Intravenous TXA reduces blood loss in hip fracture surgery, though some studies have reported its use to be associated with increased mortality and morbidity.¹ Topical TXA, with lower systemic levels, may be a safer alternative to IV TXA during hip fracture surgery.

Objective: This study explored the safety and efficacy of using topical TXA in reducing blood loss associated with hip fracture surgery as compared with saline control treatment.

Methods: Consecutive consenting adult patients admitted to the Sault Area Hospital, Sault Ste. Marie, Ontario, for hip fracture surgery from November 2017 through February 2019 were invited to participate in a prospective, double-blind RCT previously reviewed by the hospital’s research ethics board. Patients were excluded if they were allergic to TXA, younger than 18 years, had documented acute renal or cardiac failure, history of deep vein thrombosis within 3 months of study entry, or if they declined allogenic blood product transfusions. Patients were also excluded if they were pregnant, lactating, or taking hormone replacement therapy or had fibrinolytic disorder(s), coagulopathy, or had psychiatric disorders that may have prevented consistent study participation. Treatments were 3 g TXA in 50 mL of saline (n = 31) applied for 3 minutes directly to the surgical wound for open surgery or by fluoroscopic-guided injection for percutaneous surgery. The control treatment was similarly applied with 50 mL of saline (n = 34). The primary outcomes were hemoglobin level on days 1, 2, and 3 after surgery and units of packed red blood cells (pRBC) received. The triggers for receiving 1 unit of pRBC were defined before the RCT as 1 unit given to patients with a hemoglobin level less than 70 g/L or less than 80 g/L with standardized symptoms of hypoperfusion. Power calculations determined that 26 patients per group would be needed to detect a 20% reduction in blood loss as statistically significant, and 33 patients would be required in each group to detect a 10% change in cardiac complications—the main safety outcome. Intent-to-treat repeated-measures multivariate analysis of variance was conducted to analyze the primary outcomes with an alpha error set at 0.05 and 1-beta error set at 0.80. An added post hoc sensitivity analysis on the primary outcome was performed to test effects of estimated glomerular filtration rate and smoking, because there were more patients who smoked and had a high estimated glomerular filtration rate in the TXA group. The secondary outcomes were analyzed using the Fisher exact test.

Results: Controlling for baseline hemoglobin, the TXA group had higher hemoglobin levels than saline-treated control patients on day 1 (P <.005), day 2 (P =.02), and day 3 (P =.06). The intent-to-treat analysis showed that the TXA-treated patients received a total of 2 units of pRBCs compared with 8 units for control patients (P =0.024), but the number of patients receiving transfusions (2 for the TXA group are 5 for saline control) was not significantly different (P =.43). Incidence of all safety parameters (venous thromboembolisms, perioperative acute cardiac syndromes, cerebrovascular accidents, surgical site infections, and all-cause 90-day mortality) were comparable for the 2 groups.

Authors’ Conclusions: A 3-minute application of topical TXA reduced perioperative blood loss without increasing complications in patients undergoing surgery for hip fracture.

The two RCTs reviewed here^8,9 add compelling evidence supporting the safety and efficacy of using topical TXA to reduce perioperative blood loss in surgical procedures where blood loss and transfusions are recognized risks. When searching the PubMed reference database compiled by the National Library of Medicine to write this Evidence Corner, there was a return of 84 RCTs using topical TXA on a variety of surgical procedures; most studies were published in the past 10 years. The concept of placing TXA where it is needed, rather than distributing it systemically where it may harm patients, is being adopted by surgeons around the world.

Costain et al⁹ noted that using topical TXA can result in substantial cost savings to health care systems at US costs of $1800 to $2600 per unit of blood. Additional cost savings may occur due to shortened hospital stays experienced by patients who do not receive allogeneic blood.¹ The research reported by Dong et al⁸ suggests that adding local TXA to a low dose of systemic TXA can also shorten hospital stays. There remains much to learn about TXA, including its optimal dosage and effects on surgical patient outcomes, but evidence seems to suggest that local TXA use improves outcomes for patients at risk of high blood loss.

Laura Bolton, PhD
Mentor, Thomas Edison State University

Adjunct Associate Professor

Department of Surgery
Rutgers Robert Wood Johnson Medical School
New Brunswick, NJ