Tranexamic acid for orthognathic surgery: a narrative review

Introduction

Orthognathic surgery is a treatment for dentofacial misalignment by manipulation of the maxilla, the mandible or both, most commonly with Lefort I and bilateral sagittal split osteotomies. These surgeries can be associated with large amounts of blood loss, especially for Lefort I osteotomies. Piñeiro-Aguilar et al. in their systematic review found that the mean intraoperative bleeding volume for orthognathic surgery was 436 mL with the upper limit of about 1,500 mL of blood loss (1). Many of these surgeries are performed today in outpatient ambulatory surgical centers, where there are regulatory and practical limitations involving blood transfusion. Regardless of the setting, strategies to reduce the need for blood products are an important part of a surgical and anesthetic plan and reduce the incidence of transfusion with its associated potential for transfusion-related disease and complications (2,3). Tranexamic acid (TXA) has only two Food and Drug Administration (FDA)-approved indications. Orally, TXA is indicated for the treatment of cyclic heavy menstrual bleeding in females, and intravenously, TXA is indicated for short-term use in patients with hemophilia to prevent or reduce bleeding following tooth extractions (4). Despite these limited indications, there is wide acceptance of off label TXA use in many other surgical and trauma fields. Meticulous surgical hemostasis and deliberate hypotension are two techniques that are commonly used to reduce intraoperative blood loss in orthognathic surgery (1,5). Additionally, the administration of an antifibrinolytic, such as TXA, can be employed to further reduce blood loss (6,7), and may be particularly effective in the postoperative period, where there may still be hidden blood loss after the wound closure (8). TXA has been accepted and widely adopted as a blood reducing technique in orthognathic surgery. A recent survey showed that 25% of US Oral Maxillofacial training centers are utilizing TXA as a part of their hemostatic regimen (9). We present this article in accordance with the Narrative Review reporting checklist (available at https://joma.amegroups.com/article/view/10.21037/joma-24-1/rc).

Methods

A literature search using PubMed and Medline was done in August of 2023 using search terms of tranexamic acid, orthognathic surgery, orthognathic surgery complications and bloods loss during orthognathic surgery. Articles published prior to August 2023 and in English were included. Those deemed relevant were included (Table 1). The articles were then screened for their applicability to the topic of TXA use for orthognathic surgery. This literature was compared to the use of TXA in other non-oral surgery fields to evaluate the various dosing regimens and usage. Additional articles were identified during the writing of the manuscript that were added to the review to expand the clarity of the manuscript.

Pharmacology of TXA

TXA, a synthetic derivative of the amino acid lysine, functions as an antifibrinolytic agent by inhibiting the activation of plasminogen to plasmin. Plasmin is responsible for breaking down fibrin clots. TXA competitively inhibits the activation of plasminogen to plasmin, thus preventing the degradation of fibrin clots. By stabilizing the fibrin network, TXA enhances hemostasis and reduces bleeding. TXA is the preferred antifibrinolytic agent in orthognathic surgery because of its availability, and safety. TXA is 6–10 times more potent than the alternative lysine analogue ε-aminocaproic acid (10). The naturally occurring serine protease inhibitor aprotinin, which also exerts its antifibrinolytic effect by competitive antagonism of plasmin activation, is no longer available in the United States because of safety concerns (11).

TXA use in medicine

TXA has a long history of use for trauma patients, in cardiac and obstetric surgery and has demonstrated efficacy in decreasing bleeding and transfusion. The CRASH-2 trial demonstrated a significant reduction in mortality and risk of death due to bleeding in patients receiving TXA within 8 hours of traumatic injury (12). Additionally, the WOMAN trial demonstrated a significant reduction in death due to postpartum hemorrhage, though the authors did not find an overall reduction in death in the TXA versus placebo groups (13). Myles et al. showed a reduction in the total number of blood units transfused, and a reduction in major hemorrhages and cardiac tamponades needing reoperation in coronary artery bypass patients receiving TXA (14). Finally, in the POISE-3 trial, patients undergoing noncardiac surgery had significantly lower composite bleeding outcomes with TXA than placebo (15).

Advantages for orthognathic surgery

Intraoperative blood loss reduction is the best supported advantage of TXA administration during orthognathic surgery, though others have demonstrated, decreases in operative time, improved field visualization, and less decreases in postoperative hemoglobin with its use. Choi et al. found a 30% reduction in blood loss in patients receiving TXA for bimaxillary osteotomies (6), but the authors were unable to demonstrate a reduction in the rate of transfusion. Sharma found that patients receiving TXA along with dexmedetomidine anesthesia had a 35% reduction in blood loss and an improved surgical field visualization, demonstrating even with deliberately induced hypotensive anesthesia, TXA provided benefit in orthognathic surgery (16). Similarly, in their meta-analysis of TXA use with hypotensive technique, Olsen et al. found a reduction in intraoperative blood loss, as well as a 15-minute reduction in operative time with the use of TXA (17). In their meta-analysis of TXA in orthognathic surgery, Fu et al. found a significant reduction in intraoperative blood loss and reduced postoperative decreases in hemoglobin levels (18). Christabel et al. found that the quality of the surgical field as rated by the surgeon improved along with the reduction of intraoperative blood loss when TXA was administered along with a nitroglycerin hypotensive anesthesia (19).

Notably, TXA does not eliminate the need for transfusion in orthognathic surgery. Patients undergoing surgery who have bleeding disorders, vascular malformations, and fragile blood vessels should be evaluated preoperatively, have blood products available, and may still need a transfusion (20).

Other indications for TXAs use in dentistry

There are other applications and uses of TXA in dentistry. Besides orthognathic surgery, most procedures within dentistry and oral surgery have minimal to moderate blood loss. However, there are certain patients where even minimal bleeding could be problematic. Patients with bleeding disorders such Von Willebrand disease, Hemophilia, and factor V, VII, X and XIII deficiency may require TXA along with local control to prevent hospitalization and transfusion for procedures such as extractions, implant placement, or periodontal surgery. Likewise, patients on oral anticoagulant therapy such as warfarin or heparin undergoing even simple tooth extractions may bleed excessively from procedures that normally would cause minimal blood loss. Removing them from their anticoagulation may pose an increased risk. TXA along with other various local measures can aid in hemostasis (21). TXA can also be used as irrigation and a post operative mouth rinse for these patients and may allow patients to remain on their oral anticoagulation therapy during surgery, reducing the risk of a thrombotic event (22).

TXA regimens

The dosing range for administration of TXA for blood loss prevention ranges from 10 mg/kg up to 100 mg/kg of body weight. Doses of 50–100 mg/kg as used in cardiac surgery have been associated with an increased risk of seizure (14). In the CRASH-2 trial, TXA was administered as a 1 g loading dose over 10 minutes within 8 hours of injury and then infused 1 g over the next 8 hours (12). In the studies that used TXA for orthognathic surgery, doses of 10, 15 and 20 mg/kg have all been employed, with no difference in the anti-hemorrhagic effects, hospital stay, or complications between the various dosages. A dose of 10 mg/kg of TXA appears effective to reduce blood loss during orthognathic surgery (23,24). To date, there are no published guidelines for TXA dosing in orthognathic surgery.

Risks, complications, and precautions with TXA

There is a theoretical concern that the use of TXA in orthognathic surgery could lead to increased thrombotic events. In cardiac surgery there is some evidence that the use of TXA has led to an increased rate of strokes (25). The small increase in cardiovascular events in the POISE-3 trial did not meet the limits of noninferiority compared to placebo (15), and two large multicenter studies, CRASH-2 and WOMAN, did not show an increase in vascular occlusive events, or any adverse events with the use of TXA (12,13). As TXA does not promote clot formation, but rather stabilizes the existing clot and prevents its degradation, it seems unlikely to be a causative factor in new thrombotic events. Despite the lack of strong evidence supporting an increased risk of thrombosis with TXA administration, there are recommendations that caution should be taken in patients at higher risk of thrombosis including patients with a previous thrombotic event or hypercoagulation diseases (26,27).

TXA is excreted unchanged in the urine and its filtration is inversely proportional to plasma creatinine. Therefore, doses should be reduced in chronic kidney disease (27).

Higher doses of TXA doses are associated with increased rates of seizures (14), which are typically observed in the postoperative period (28). There is at least one case report of a healthy child having received a standard dose of 10 mg/kg over 10 minutes and developing tonic-clonic seizures postoperatively, which progressed to status epilepticus and death (29).

Rare side effects of TXA include visual and color disturbances. In the few reported cases there was resolution of these symptoms upon discontinuation of TXA. TXA was thus inferred to be causative (30).

Additionally, the package insert of TXA has warnings for anaphylaxis, dizziness and gastrointestinal distress (31).

Conclusions

TXA is an effective and safe antifibrinolytic agent that can be part of the orthognathic anesthesia plan to reduce blood loss, limit transfusions, and improve surgical field visualization. Further research is needed to elucidate optimal dosing strategies and long-term outcomes, ultimately contributing to enhanced patient care, and improved surgical outcomes in orthognathic surgery.

Acknowledgments

The Authors would like to thank Steven M. Frank, M.D., Professor, Department of Anesthesiology/Critical Care Medicine, Director, Johns Hopkins Health System Blood Management Program, Director, Center for Bloodless Medicine and Surgery, Johns Hopkins Medical Institutions for advice and editorial comments on the manuscript. This manuscript is based on the lecture given on the American Society of Dentist Anesthesiologists annual session on April 28, 2022.

Funding: None.

Footnote

Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://joma.amegroups.com/article/view/10.21037/joma-24-1/rc

Peer Review File: Available at https://joma.amegroups.com/article/view/10.21037/joma-24-1/prf

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://joma.amegroups.com/article/view/10.21037/joma-24-1/coif). L.N. serves as an unpaid editorial board member of Journal of Oral and Maxillofacial Anesthesia from July 2023 to June 2025. L.N. received payment for lectures from American Society of Dentist Anesthesiologist (ASDA). He is also on the 2-year term non-paid President of the American Society of Dentist Anesthesiologist (ASDA). The other author has no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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