VACEP's EBM Series: Tranexamic Acid to Reduce Nasal Packing in Epistaxis?
VACEP Evidence-Based Medicine for General Emergency Physicians Series
Authors: Timothy Fortuna, DO (faculty, Carilion Clinic) and Justin Lackey (emergency medicine resident, Carilion Clinic)
Reviewers: Joshua Easter, MD, MSc & Justin Yaworksy, MD | University of Virginia School of Medicine| UVA Faculty
CASE
A 77-year old male presents to the emergency department with a chief complaint of nosebleed. He states that the bleeding began approximately four hours prior to arrival and that it has not improved. He denies recent history of trauma and states he has had two similar episodes previously which were resolved with pressure at home. He has a history of atrial fibrillation for which he takes rivaroxaban. Patient’s vital signs are heart rate 87, respiratory rate 18, blood pressure 142/91, and oxygen saturation 97% on room air. On exam the patient has blood dripping from the left nares. You instruct the patient to blow his nose and administer oxymetazolone followed by placement of a nose clip. The patient states that this seems similar to what he tried at home and asks what you plan to do if this treatment is ineffective.
Epistaxis is a common presenting complaint in the emergency department, occurring in 1 in 200 patients presenting to the ED (1). As many as 6% of patients who experience epistaxis will seek medical attention (2). The vast majority of cases are not life-threatening with only 0.2% of patients with nosebleeds requiring hospitalization (3).
However, epistaxis has been shown to have a significant impact on health-related quality of life in the few studies which have sought to measure the outcome (4,5).
The Academy of Otolaryngology-Head and Neck Surgery Clinical Practice Guidelines recommend the use of firm, sustained compression to the lower third of the nose for 5 minutes or longer. They also recommend topical vasoconstrictors, nasal cautery, and moisturizing or lubricating agents (6).
However, the evidence for topical vasoconstrictors is limited with a single RCT comprising 150 patients demonstrating modest efficacy (7).
Tranexamic acid (TXA) is a synthetic lysine amino acid derivative which is thought to prevent the process of fibrinolysis and decrease bleeding, and it may be helpful for epistaxis. It has been studied for a variety of indications with several large, notable RCTs recently investigating its use for postpartum hemorrhage, upper GI bleeding, and polytrauma with varying efficacy (8-10). Previous studies have evaluated TXA for epistaxis, but they were limited by their retrospective nature and small sample size.
Recently, The Use of Tranexamic Acid to Reduce the Need for Nasal Packing in Epistaxis (NoPAC): Randomized Controlled Trial (11) sought to determine if tranexamic acid delivered via soaked pledgets after administration of a topical vasoconstrictor and pressure prevented the need for anterior nasal packing in patients presenting to the emergency department with epistaxis. The study was a well-conducted multicenter, double-blinded, randomized controlled trial held at several EDs in the United Kingdom. The investigators enrolled 496 patients with atraumatic epistaxis which was not controlled by initial simple first aid measures, such as applying pressure to the soft part of the nose, applying ice packs to the nose, or both.
If bleeding persisted, topical vasoconstrictors and pressure were applied for 10 minutes via a cotton dental roll soaked with a vasoconstrictor held in place by plastic clamp.
Those participants with persistent bleeding were then randomized to either TXA delivered by placement of soaked cotton roll in the nares or placebo cotton roll soaked in sterile water. The primary outcome was the need for anterior nasal packing. There was no difference between the TXA group (44%) and the placebo group (41%) in regards to the need for subsequent nasal packing. Five secondary outcomes were evaluated, none of which demonstrated statistical significance. These secondary outcomes included hospital admission, need for blood transfusion, recurrent epistaxis and any thrombotic events requiring repeat visits within 1 week.
Overall, this is a well done study which enrolled more patients than any previous study. Clinicians, patients, and outcome assessors were all blinded to treatment intervention, follow-up was adequate and an intention to treat analysis was performed. It is worth noting, this was a convenience sample limited by the availability of research assistants and they did not reach their target enrollment.
About the EBM Review Series
This is a literature review series started by the University of Virginia’s Josh Easter, MD, MSc, a VACEP board member working to connect the academic community in Virginia. We invite each residency in Virginia (and D.C.) to create a faculty/resident team to submit and review articles. Email Executive Director Sarah Marshall to take the next step.
Goals
Provide a brief monthly synopsis of a high yield article germane to the practice of emergency medicine for distribution to all VACEP members
Provide an opportunity for a peer reviewed publication and invited presentation for faculty and trainees
Foster an academic community focused on evidenced based medicine for emergency medicine residency programs in the region
There are several key points to note when assessing the applicability of the results to the ED population.
The first is that nearly two thirds of patients in this study were on anticoagulants. The authors also did not describe the type of anticoagulation.
The second potential issue regards how epistaxis care is traditionally managed in the United Kingdom. The authors state that once an anterior nasal pack is inserted the average hospital admission is 3 days. In this study nearly half of patients were admitted for an average length of stay of over 2 days (11). This may be different from standard practice in the United States, and the prospect of a multi-day admission could conceivably make physicians more reluctant to place nasal packing.
Finally, 25% of patients in the study ultimately had their epistaxis managed with silver nitrate cautery. It has previously been postulated that the antifibrinolytic effects of TXA would predict greater efficacy in diffuse, slower bleeding rather than more brisk bleeding from a single vessel that is typically amenable to cautery. If this were proven true, it may suggest a more appropriate role for TXA in patients who were previously evaluated and treated for a culprit bleeding vessel.
Overall, this large randomized controlled trial presents the most compelling evidence regarding the use of TXA in epistaxis. It suggests that TXA is unlikely to provide additional benefit beyond compression and topical vasoconstrictors, albeit in a population with a high proportion of anticoagulant and antiplatelet use. While it certainly does not close the door on the utility of TXA as an initial strategy in lieu or in addition to topical vasoconstrictors or in particular sub-populations, TXA is unlikely to represent an ideal definitive therapy.
Conclusion
Your patient has ongoing bleeding after 10 minutes of nasal pressure. Rhinoscopy is performed and no culprit vessel amenable to cauterization is identified. Based on your review of this article and the lack of convincing evidence to use the expensive TXA, you place an anterior nasal (5,6) pack and refer the patient to otolaryngology for ambulatory follow-up.
Review: TXA is worth trying for epistaxis
By Joshua Easter, MD, MSc and Justin Yaworksy, MD | University of Virginia School of Medicine
With great interest we read the excellent review by Drs. Fortuna and Lackey of the recent NoPAC trial. We agree that this represents the largest and most robust study of TXA to date for epistaxis. However, as the authors note, there are several significant limitations to the conclusions that limit the applicability to our practice in the ED. These limitations include:
The study investigators elected to apply TXA only after administration of other topical vasoconstrictors. Prior studies of TXA have shown that it works better at stopping bleeding compared to other topical vasoconstrictors (Janapala, 2022).
The primary outcome measure in the study was the need for anterior nasal packing, and this is in contrast to prior studies of epistaxis that have focused on cessation of bleeding. While the outcome of need for packing/further intervention may seem clinically relevant, it must be interpreted in the context of the study. The NoPAC trial was conducted in the United Kingdom, where the authors acknowledge that anterior nasal packing often leads to hospital admission, which is not standard of care in the United States. This might bias the results, as physicians may have been reluctant to perform nasal packing in patients with ongoing bleeding, due to the resulting need for hospital admission. Despite failing to control bleeding with initial treatment in most patients, the investigators only packed 43% of patients, which seems low. This suggests the study interventions may have lessened bleeding to the point that packing was not necessary, which is clinically relevant.
Perhaps the most concerning limitation is that nearly two thirds of patients in the NoPAC trial were anticoagulated. The authors combined the data from these patients with patients that were not anticoagulated, and there were no distinctions made regarding the various anticoagulants (direct oral anticoagulants, vitamin K antagonists, antiplatelet agents, etc.). These cohorts are drastically different in terms of the etiology of their bleeding, which may have a profound impact on the results. TXA has shown varied efficacy for patients receiving anticoagulation (de Abreu, 2017; Pabinger, 2017; Ockerman, 2021). It would have been enlightening for the authors to compare the results and to differentiate between the different forms of anticoagulation.
As the reviewers nicely note, the current trial suggests that there is little benefit to TXA for epistaxis; however, other smaller trials have shown benefit. A recent meta analysis combining data from 8 smaller trials, including 1,299 patients, found TXA was associated with reduced bleeding compared to other topical vasoconstrictors (OR=7.8; 95% CI: 4.5-13) (Janapala, 2022). Other smaller unblinded studies showed topical TXA resulted in less rebleeding compared to nasal packing (OR=2.3; 95% CI: 1.7-3.1) (Zahed, 2013; Akkan, 2019).
Still others suggest it reduces the need for intervention, reduces time to ED discharge, and improves patient satisfaction with epistaxis compared to nasal packing (Zahed, 2018). Moreover, TXA is safe. Systemic absorption of topical TXA is minimal and unlikely to produce significant side effects. It is also inexpensive and relatively painless to administer.
Given the conflicting data on the potential benefits of TXA for epistaxis as well as the major limitations of the current NoPAC study, we will continue to trial administration of topical TXA initially for our patients with epistaxis, as it is safe, inexpensive, and may obviate the need for more costly and painful interventions, such as nasal packing.
REFERENCES
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9. HALT-IT Trial Collaborators. Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial. Lancet Lond Engl. 2020;395(10241):1927-1936. doi:10.1016/S0140-6736(20)30848-5
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