Topical TXA in Atraumatic Anterior Epistaxis Yet Again

Background: The use of topical tranexamic acid (TXA) for anterior epistaxis has been studied in many trials with conflicting results. The largest and most methodologically rigorous study to date on the use of topical TXA in epistaxis has been the NoPAC trial (Link is HERE), published in 2021. In that trial there was no difference in the need for anterior nasal packing when comparing placebo to topical TXA. One of the interesting aspects of that trial was that it was not a study of all comers with anterior epistaxis.  Patients had local pressure applied followed by a topical vasoconstrictor (phenylephrine) prior to receiving TXA or placebo.  Only after failure of simple first aid (i.e. direct pressure) and application of a topical vasoconstrictor failed were patients enrolled into the study.

Paper: Hosseinialhashemi M et al. Intranasal Topical Application of Tranexamic Acid in Atraumatic Anterior Epistaxis: A Double-Blind Randomized Clinical Trial. Ann Emerg Med 2022. PMID: 35752521 [Access on Read by QxMD]

 Clinical Question: How effective is intranasal topical tranexamic acid at reducing need for anterior nasal packing in patients with atraumatic anterior epistaxis?

What They Did:

• Double-blind randomized clinical trial
• Single center ENT ED study in Iran
• Patients were randomized to:
  • Control Group: Cotton pledgets soaked in phenylephrine and lidocaine
  • Intervention Group: Cotton pledgets soaked in tranexamic acid with phenylephrine and lidocaine
  • Cotton pledgets inserted into the patients nostrils for 15min

Outcomes:

• Primary: Need for anterior nasal packing
• Secondary:
  • ED LOS >2hrs
  • Need for electrical cauterization
  • Rebleeding within 24hours and 1 to 7d 

Inclusion:

• Adult patients (Age ≥18 years)
• Active spontaneous atraumatic anterior epistaxis
• Failed squeezing of the soft area of the nose, applying an ice pack to the back of the neck, and continuous irrigation of mouth with cold water for at least 10 minutes

Exclusion:

• Unstable hemodynamic status
• Known allergy to TXA
• Lack of capacity or willingness to participate
• Known nasopharyngeal, nasal cavity, or paranasal malignancy
• Pregnancy
• Nasal packing prior to arrival
• Epistaxis caused by trauma (Excluding simple nose picking)*
• Any known bleeding disorders (including hemophilia)
• Recent use of anticoagulation drugs (Heparin, Warfarin, Rivaroxaban, Dabigatran, or enoxaparin
• Use of clopidogrel
• Prisoners
• Posterior nasal bleeding

*Traumatic epistaxis defined as hemorrhage derived from the nasopharynx, sinuses, nasal cavity, or nostrils caused by either internal or external injury to the nose, midfacial structures, or central skull base

Results:

• 240 patients (120 in each group) enrolled in the study
• Need for Nasal Packing (Primary Outcome)
  • Control: 64.2%
  • Intervention: 50%
  • OR 0.56; 95% CI 0.33 to 0.94
• ED LOS >2hrs:
  • Control: 20.8%
  • Intervention: 9.2%
  • OR 0.38; 95% CI 0.18 to 0.82
• Rebleeding at 24hrs:
  • Control: 30%
  • Intervention: 15%
  • OR 0.41; 95% CI 0.22 to 0.78
• No difference between groups for:
  • Need for electrical cauterization
  • Rate of rebleeding within 1 to 7d
• No minor or major side effects in either group 

Strengths:

• Physicians and patients were blinded to treatment
• All enrolled patients completed the study
• Baseline characteristics (Sex, age, BP, and aspirin consumption) were similar between groups
• Follow up was complete
• Randomization was appropriately performed

Limitations:

• Single center study at an ENT ED may not generalize to all facilities
• Convenience sample of patients between 8am and 8pm which creates a selection bias
• Nasal packing is a subjective decision and could bias the results
• No patients on anticoagulation, clopidogrel, and only 30% of the study population was on aspirin
• 1^st aid techniques (pressure, ice packs, etc) were not protocolized so patients may have been inconsistent between patients
• Traumatic epistaxis was excluded from this trial making it difficult to draw conclusions on this patient population
• Interventions prior to application of TXA/placebo don’t make a lot of sense (i.e. ice bag to neck, irrigation of mouth with cold water, and squeezing the soft part of the nose)
• Limited baseline characteristics makes it uncelar if the groups were well balanced at baseline

Discussion:

• In this trial intranasal topical application of TXA was beneficial when compared to standard care in terms of need for anterior nasal packing, rate of rebleeding within 24hours, and length of stay in the ED
• My biggest issue with the NoPAC trial was the initial management of patients. For me this is often TXA soaked pledget with pressure as my initial treatment. In the NoPAC trial patients got topical vasoconstrictors with pressure and only after they failed did they get randomized to TXA vs placebo.
• A systematic review of randomized controlled trials (Link is HERE) showed that TXA compared to other vasoconstrictors was 7.8x more likely to achieve bleeding control on first assessment and lowered the odds of recurrence of bleeding at days 1 and 3.

Author Conclusion: “Intranasal topical application of tranexamic acid is associated with a lower rate of need for anterior nasal packing and a shortened stay in the ED; it may be considered a part of the treatment for atraumatic anterior epistaxis.”

Clinical Take Home Point: Based on this trial and the systematic review published in 2021 (Link is HERE), the fact that topical TXA is low cost, simple to use, and has no untoward effects it seems the best 1^st line strategy in epistaxis is a TXA soaked pledget with direct pressure. It is unclear whether TXA has benefit in cases where compression with a topical vasoconstrictor fails.

References:

1. Hosseinialhashemi M et al. Intranasal Topical Application of Tranexamic Acid in Atraumatic Anterior Epistaxis: A Double-Blind Randomized Clinical Trial. Ann Emerg Med 2022. PMID: 35752521 [Access on Read by QxMD] 

For More Thoughts on This Topic Checkout:

• REBEL EM: Meta-Analysis on Topical TXA for Epistaxis
• REBEL EM: Topical TXA in Epistaxis
• REBEL Cast: Ep97 – The NoPAC Trial – TXA for Epistaxis?

Post Peer Reviewed By: Anand Swaminathan, MD (Twitter: @EMSwami)