NoPAC

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Reuben A, et al. "The Use of Tranexamic Acid to Reduce the Need for Nasal Packing in Epistaxis (NoPAC): Randomized Controlled Trial". Ann Emerg Med. 2021. 77:631-640.
PubMed

Clinical Question

In adult patients that present to ED with persistent epistaxis following 10 minutes of first-aid, dose does giving serial doses of 200mg tranexamic acid (up to 400mg total) topically for 10 minutes each after 10 minutes of topical vasoconstrictor, as compared to vasoconstrictor alone, decrease the need for anterior nasal packing

Bottom Line

Topical tranexamic acid, when given in a serial fashion after topical vasoconstriction did not improve outcomes as compared to placebo

Major Points

Atraumatic intractable epistaxis is a fairly common presenting complaint in Emerg. Tranexamic acid is comparatively inexpensive and has been used topically to control bleeding in a number of settings.[1] This trail gave each participant 10 minutes of topical vasoconstrictor (soaked in dental roll) and then removed and randomized to either placebo or 200mg of tranexamic acid soaked into dental roll and applied for 10 additional minutes (and a second dose was given for an additional 10 minutes of bleeding continued.) In this trial, conducted in 26 centres from across the UK between 2017 and 2019, randomized 252 to receive tranexamic acid and 242 for placebo. For their primary outcome, the authors found no difference between treatment and placebo (43.7% vs. 41.3% (OR 1.11, 95% CI 0.77 to 1.59)). They also found no statistical difference for length of stay, use of blood transfusions, or recurrent bleeding within 7 days requiring re-presentation to hospital.

There are several limitations with this trial. Unlike previous trails, this was a lower dose of tranexamic acid (200mg x2 as compared to 500mg) and it was given in a serial manner instead of concurrently. It could be argued that much of the drugs would be lost to the cotton and not make it to the patient so they higher dose would be inconsequential. This trail was potentially underpowered with a lower rate of patients requiring packing than expected in the placebo group. There is also a chance of selection bias as the main reason cited for non-enrollment was the lack of availability of a research nurse.

Guidelines

As of August 2022, no guidelines have been published that reflect the results of this trial.

Design

  • Multi-centre, double-blind, parallel-group, randomized, placebo-controlled trial
  • N=496
    • Tranexamic Acid (n=254)
    • Placebo (n=242)
  • Setting: 26 Type-1 ED from across the UK
  • Enrollment: 5 May 2017 to 31 March 2019
  • Follow-up: 7 days
  • Analysis: intention-to-treat
  • Primary Outcome: need for anterior nasal packing

Population

Inclusion Criteria

  • Adult (18 years and older)
  • Persistent epistaxis following basic first aid (squeezing the soft part of the nose, applying ice to the bridge of the nose, or both) for at least 10 minutes

Exclusion Criteria

  • hemodynamic instability
  • epistaxis from trauma
  • out-of-hospital packing
  • documented allergy to tranexamic acid
  • referred to ENT
  • known or suspected nasopharyngeal malignancy
  • previous inclusion in the study
  • pregnancy
  • hemophilia
  • inability or unwillingness to provide consent

Baseline Characteristics

Tranexamic Acid Group displayed

  • Demographics: Mean age 70.1 years, 49.6 female
  • Physiologic parameters: mean systolic blood pressure 150 mmHg, diastole blood pressure 86 mmHg, heart rate 83 beats per minute
  • Co-morbidities: 60% hypertension, 49% ischemic heart disease, 13% diabetes, 10% thromboembolic disease, 0.8% alcoholic liver disease, 2% any bleeding disorder
  • anticoagulant medications 61%

Interventions

  • all patients received 10 minutes of topical vasoconstrictor (clinician’s choice)
  • Intervention: Tranexamic acid 200mg (100 mg/mL) soaked into cotton dental roll, inserted into affected nostril and clipped in place for 10 minutes. If bleeding persisted then a second dose of 200mg was administered
  • Control: sterile water, soaked in dental roll and administered in same fashion as the intervention

Outcomes

Comparisons are Tranexamic Acid vs. Control.

Primary Outcomes

Anterior nasal packing
43.7% vs. 41.3% (OR 1.11, 95% CI 0.77 to 1.59)

Secondary Outcomes

Further ED treatment for epistaxis
61.8% vs. 60.7% (OR 1.05, 95% CI 0.73 to 1.52)
Requiring hospital admission for epistaxis treatment
43.3% vs. 45.5% (OR 0.92, 95% CI 0.64 to 1.32)
Length of hospital stay
2.2 days vs. 2.0 days (difference 0.2, 95% CI -0.19 to 3.1)
Requiring blood transfusion
2.8% vs. 2.5% (OR 1.11, 95% CI 0.37 to 3.37)
Recurrent epistaxis within 7 days, requiring re-presentation to hospital
19.4% vs. 16.1% (OR 1.26, 95% CI 0.79 to 2)

Subgroup Analysis

Patient receiving anticoagulants
61% vs. 68.5% (OR 1.29, 95% CI 0.59 to 2.81)

Adverse Events

Serious adverse events
4.3% vs. 2.1% (non-statistically significant)

Criticisms

  • no effort was made to distinguish between anterior and posterior bleeds
  • potentially under-powered, lower rate of packing in the placebo group than expected
  • selection bias may have occurred as the research nurse was not available at all times
  • dose of tranexamic acid was lower than previous trials
  • vasoconstrictor was given separately, previous trials gave concurrently
  • 25% of patients required silver nitrate cautery

Funding

  • National Institute for Health Research, Research for Patient Benefit program (project reference PB PG 0215-36142)

Further Reading