TXA for Everyone: Inhaled TXA for Hemoptysis

03 Dec
December 3, 2018

Background: Use of tranexamic acid (TXA), an antifibronlytic medication,  has certainly become popular for numerous indications (i.e. trauma, uterine bleeding, epistaxis).  Patients with hemoptysis, frequently come through EDs, and as an ED healthcare provider, I am unable to provide the definitive therapies of bronchial artery embolization and bronchoscopy for these patients at many of the institutions in which I work.  And, of course, it’s not like I can just put my finger on the bleeder. There is no real effective medical therapy for hemoptysis, other than antibiotics for infection.  I often find myself helpless with these patients as all I can do is transfer them to larger institutions where definitive therapies can be done.  Well hold on…It turns out inhaled TXA may be an option to reduce bleeding in patients with hemoptysis.  Thus far the evidence for this has  only been from small case series.  There have been no prospective studies evaluating nebulized TXAs effectiveness as an inhaled treatment for hemoptysis.  I have certainly used this treatment for post-tonsillectomy bleeding and have at times used it for hemoptysis, with great success, but it would be nice to see some evidence to support this practice.

What They Did:

  • Prospective, double-blind, placebo-controlled randomized controlled trial assessing the effectiveness of nebulized TXA (500mg/5mL TID) vs placebo (5mL of 0.9% normal saline) for treatment of non-massive hemoptysis

Outcomes:

  • Primary:
    • Rate of complete resolution of hemoptysis during first 5 days from admission
    • Difference in daily volume of expectorated blood
  • Secondary:
    • Rate of interventional bronchoscopy
    • Rate of angiographic embolization
    • Rate of surgery
    • Mean hospital LOS
  • Safety Outcome:
    • Rate of side effects
  • Follow Up Outcomes (30d and 1 year):
    • Mortality
    • Recurrence rate of hemoptysis 

Inclusion:

  • Adult patients (≥18 years of age) admitted with hemoptysis over previous 24 hours

Exclusion:

  • Massive hemoptysis (Expectorated blood >200mL/24hr)
  • Hemodynamic instability
  • Respiratory instability
  • Pregnancy
  • Renal failure (Cr Level > 3mg/dL or need for RRT)
  • Hepatic failure (Bilirubin >2mg/dL or AST > 3x upper limit of normal)
  • Coagulopathy (INR > 2)
  • Known hypersensitivity to TXA
  • Treatment with TXA prior to screening

Results:

  • 47 patients randomized
    • 25 patients received nebulized TXA
    • 22 patients received nebulized normal saline
    • 36% (9pts) and 41% (9pts) had lung malignancy in the TXA group and placebo group respectively
    • >50% of patients were treated with anticoagulants or antiplatelet medications as outpatients

 

  • Quantity of expectorated blood was significantly reduced by day 2 of admission (≈50cc/24hr vs 15cc/24hrs)
  • No side effects in either group including bronchospasm

Strengths:

  • 1st prospective RCT to assess the effectiveness of nebulized TXA in patients with hemoptysis
  • Both treatment and placebo were prepared in pharmacy and provided to pulmonary department in identical unmarked vials, to allow blinding of the treating team and patients
  • Patients collected expectorated blood in measuring cups daily during the trial to measure the amount of bleeding, instead of subjectively quantifying the amount of bleeding
  • Patients were balanced in baseline clinical characteristics and causes of hemoptysis

Limitations:

  • Hemodynamic and respiratory instability not clearly defined
  • Massive hemoptysis (>200cc/24 hr) patients were excluded
  • Small number of patients does not allow specific assessment of nebulized TXA in different subpopulations of hemoptysis (i.e. anticoagulant therapy)

Exact, time to resolution not given, so it is unclear if patients resolved early (i.e. minutes – hours) or late (i.e. hours to days), making it unclear if this would applicable in emergent situations

How do You Actually Make Nebulized TXA:

 

Discussion:

  • Study required 60 patients to have statistical significance and fell short of this with 47 patients randomized. This was due to an internal analysis showing perceived superiority of inhaled TXA to placebo after successful recruitment of 47 patients
  • The main advantage of inhaled TXA vs systemic TXA in hemoptysis, is a more rapid onset of action at the site of bleeding

Author Conclusion: “TA inhalations can be used safely and effectively to control bleeding in patients with nonmassive hemoptysis.”

Clinical Take Home Point: Although this was a small study, the advantages of inhaled TXA vs placebo in patients with non-massive hemoptysis (<200mL/24hrs) included faster resolution of hemoptysis, shorter hospital LOS, fewer invasive procedures, and although not statistically significant, a trend toward improved 30d mortality. Finally, it is important to state that it is unclear if this would be relevant in emergent situations as the results were resolution of symptoms in days, although resolution of symptoms in minutes to hours could be possible, it was not studied in this trial.

References:

  1. Wand O et al. Inhaled Tranexamic Acid for Hemoptysis Treatment: A Randomized Controlled Trial. CHEST 2018. PMID: 30321510

For More on This Topic Checkout:

Raniah Aljadeed at EMPharmD: A Breath of Fresh Air: Nebulized TXA for Hemoptysis

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

The following two tabs change content below.

Salim Rezaie

Emergency Physician at Greater San Antonio Emergency Physicians (GSEP)
Creator & Founder of R.E.B.E.L. EM
Tags: , ,
0 replies

Leave a Reply

Want to join the discussion?
Feel free to contribute!

Leave a Reply

Your email address will not be published. Required fields are marked *

Time limit is exhausted. Please reload CAPTCHA.