Nebulisation of Tranexamic Acid (TXA)

http://emdaily.cooperhealth.org/content/advanced-practice-nebulized-txa-hemoptysis

Side Effects - One patient developed bronchospasm which was successfully treated with bronchodilators. No patients had systemic side effects or thromboembolic events.

How to Perform - 500mg of tranexamic acid IV formulation; placed in a traditional nebulizer; administered over 15 minutes. 

Hankerson et al. 2015

·         We chose to prepare a 10 mg/ml solution by diluting one gram of TXA intravenous formulation in 100 ml of 0.9% normal saline. The TXA solution was nebulized and delivered to the patient’s mouth and tracheostomy tube via facemask. The hemoptysis completely resolved over a period of 15 minutes with continuous nebulized TXA solution. We delivered the entire one gram of TXA via continuous nebulizer over the course of 30 to 45 minutes, even though the bleeding had resolved. 

·         One must also consider the possibility of bronchospasm when TXA is delivered via nebulizer, but thus far this has not been shown to occur.

·         In retrospect, if we used a more concentrated TXA solution similar to the 500 mg/5 ml preparation used by Solomonov et al., it would have likely been safe, and we may have reached hemostasis more quickly.

Solomonov et al. 2009

·         For unidentifiable bleeding episodes, we used inhaled tranexamic acid 500 mg/5 ml 3-4 times a day (Hexakapron, TEVA Group, Tel-Aviv, Israel), and for identifiable bleeding episodes we used boluses of tranexamic acid administered through the working channel of the flexible bronchoscope.

·         Each ampoule of 5 ml contained 500 mg of tranexamic acid dissolved in water for injection, sodium hydroxide and hydrochloric acid (for pH adjustment). A quantitative and qualitative (verbal) evaluation of the symptoms was made, such as general clinical  evaluation, chest X-ray, and blood tests.

·         The rationale for administrating inhaled TA to pulmonary bleeding was to enhance the activity of depleted anti-fibrinolytic factors in ongoing bleeding sites along the bronchial tree.

·         Based on this review, the treatment duration may vary from single dose to 3 months.

Bafaqih et al. 2015

Dosing	Children <25kg	250 mg/dose
	Children >25kg	500 mg/dose
Concentration	500 mg/5 mL
Frequency	3-4 times daily
Admini-stration	Jet nebulizer with a flow rate of 5 L of oxygen per minute
Remarks
	·      In case of response, n-TXA was continued for 2-3 doses after bleeding completely stopped. ·      If no or minimal response was seen after 3 to 4 doses of n-TXA (18 to 24 hours from the first dose of n-TXA) or if bleeding severity escalated as judged by the treating physician at any time before that, rFVIIa (Novoseven RT, 1mg lyophilized powder vials, Novo Nordisk, Denmark) nebulization was added every 4 hours until bleeding stopped. ·      Before each n-rFVIIa dose a judgment was made by the treating physician whether evidence of active DAH still existed or not. If not, n-rFVIIa was stopped and n-TXA continued for another 2-3 doses. ·      The maximum duration of therapy allowed was three days. If bleeding did not stop by three days of total therapy or if it reemerged after temporary cessation, nebulization therapy was not pursued further.

*TXA = Tranexamic Acid

*DHA = Diffuse alveolar hemorrhage

References:

1.    Hankerson et al. Nebulized Tranexamic Acid as a Noninvasive Therapy for Cancer-Related Hemoptysis. Journal of Palliative Medicine: Vol. 18, No. 12 (2015).

2.    Solomonov et al. Pulmonary hemorrhage: A novel mode of therapy. Respiratory Medicine (2009) 103, 1196-1200

3.    Bafaqih H, Chehab M, Almohaimeed S, Thabet F, Alhejaily A, AlShahrani M et al. Pilot trial of a novel two-step therapy protocol using nebulized tranexamic acid and recombinant factor VIIa in children with intractable diffuse alveolar hemorrhage. Ann Saudi Med 35(3): 231-239.

4.    http://emdaily.cooperhealth.org/content/advanced-practice-nebulized-txa-hemoptysis

[All references accessed on 17 Dec 2018]