Abstract and Introduction
Background: Although high-bleed surgery routinely utilizes the antifibrinolytic drug tranexamic acid, most plastic surgical procedures are conducted in soft tissue with low-volume bleeding. Unease regarding possible systemic adverse effects prevents widespread systemic use, but local use of tranexamic acid is gaining popularity among plastic surgeons. Randomized controlled trials on topical use of tranexamic acid are mainly from high-bleed surgeries, and few studies address the effect in soft tissue. This article reviews the scientific evidence regarding local use of tranexamic acid in soft-tissue surgery, discusses pharmacological effects and possible adverse reactions, and presents recommendations for use in plastic surgery.
Methods: A systematic search of databases for studies on local use of tranexamic acid in soft-tissue surgery was performed. Randomized controlled trials were included for a systematic review on effect; a narrative review regarding other clinically relevant aspects is based on extensive literature searches combined with the authors' own research.
Results: Fourteen randomized controlled trials, including 1923 patients, were included in the systematic review on local use of tranexamic acid in soft-tissue surgery.
Conclusions: Local use of tranexamic acid may reduce blood loss comparably to intravenous prophylactic use with negligible risk of systemic adverse effects, but high-quality randomized controlled trials are few. Prolonged exposure to high local concentrations is discouraged, and direct contact with the central nervous system may cause seizures. No single superior means of administration or dosage is supported in the literature, and lowest effective dose is unknown. There may not be one single ideal dosing regimen, but rather many possibilities adaptable for different surgical situations.
Although most plastic surgical procedures are not associated with major blood loss, bleeding causes swelling, bruising and pain, need for drains and bandage changes, and reoperations, and may increase the risk of infection and wound ruptures. Keeping surgical bleeding to a minimum is, thus, beneficial for both patient and provider. Fear of bleeding may also prevent plastic surgeons from using adequate thromboprophylactic measures as addressed by the American Society of Plastic Surgeons Venous Thromboembolism Prevention Task Force.
In surgery, a balance between coagulation and fibrinolysis is needed to prevent bleeding yet maintain circulation. If fibrinolysis exceeds coagulation, bleeding may occur despite adequately performed hemostasis. While meticulous surgical technique, use of cautery, and local infiltration of wound edges with adrenaline can largely control bleeding in soft-tissue surgery, bony tissue cannot be infiltrated or manipulated to the same extent. Measures such as hypotensive anesthesia and pharmacological aids are, therefore, used to control bleeding in bony tissue.
Antifibrinolytic drugs have been the only available pharmacological means of a general reduction of bleeding with an acceptable safety profile in patients without coagulation deficiencies. Tranexamic acid is a synthetic low-cost antifibrinolytic drug manufactured and approved for intravenous and oral use, and systemic prophylactic use reduces both bleeding volume and transfusion needs by 30 to 40 percent.[3,4] Although large studies have found little evidence of a prothrombotic effect from tranexamic acid,[5–8] contradictory studies do exist.[9–11] Moreover, a dose-dependent increase in seizures has been documented from intravenous use of tranexamic acid in cardiac surgery. Fear of possible adverse effects has, therefore, limited routine systemic use to surgery with expected high-volume bleeding and frequent need of blood transfusions; this includes mostly surgery affecting skeletal structures, such as joint arthroplasties, craniomaxillofacial surgery, and cardiac surgery, with its associated thoracotomy, use of cardiopulmonary bypass, and high-dose anticoagulation. Use in burns[13,14] is not established, probably because of uncertainties regarding adverse effects of tranexamic acid during ongoing hyperfibrinolysis.
An alternative to systemic use of tranexamic acid is local administration, which may provide sufficient drug concentrations at the wound surface with negligible risk of systemic adverse effects. Three meta-analyses on the use of topical tranexamic acid in surgery[16–18] all demonstrate a significant reduction of blood loss and transfusion needs without any increase in adverse events. However, in the two first meta-analyses by Ker et al. in 2013 and Montroy et al. in 2018, only two of 29 and three of 66 studies, respectively, addressed surgery conducted in soft tissues. In the latest meta-analysis, by Teoh et al. in 2020, seven of 71 studies addressed soft-tissue surgery.
The term "plastic surgery" encompasses exceedingly diverse procedures. Both systemic and topical use of tranexamic acid have already been explored in plastic surgical fields that involve skeletal structures such as rhinoplasty, craniomaxillofacial, and orthognathic surgery.[19–22] Yet, the larger bulk of plastic surgery takes place in soft tissue, and the effect of tranexamic acid according to type of tissue may be as clinically relevant as the effect in specific procedures.
Local use of tranexamic acid has been adopted by influential plastic surgeons and is receiving increasing attention.[23–27] Four published reviews on the use of tranexamic acid in plastic surgery since 2016[19,21,26,28] have, however, only identified a total of three randomized controlled trials on topical use, with two in orthognathic surgery[29,30] and only one in soft tissue (i.e., reduction mammaplasty).
The aim of this article is to provide insight on the pharmacological effects and adverse effects of tranexamic acid, review the current scientific evidence regarding local use in soft-tissue surgery, and present recommendations for use of tranexamic acid in plastic surgery.
Plast Reconstr Surg. 2022;149(3):774-787. © 2022 Lippincott Williams & Wilkins