📌 Key Points
- 🫁💨 Nebulized TXA stops bleeding faster! 72% of ED patients had cessation at 30 min vs 51% with IV TXA.
- 📉🏥 Fewer procedures needed: Neb TXA patients had lower rates of bronchial artery embolization (25% vs 47%).
- 🌬️💊 Easy to use: Neb TXA is cheap, non-invasive, doesn’t require an IV, and works fast.
- ⚠️📍 Study limits: Small sample size, single center in India, and most patients had TB—not broadly generalizable.
🛡️ Bottom line: Neb TXA is a promising early treatment for hemoptysis—safe, accessible, and effective.
📝 Introduction
Hemoptysis is a potentially life-threatening emergency that can lead to airway compromise and hemorrhagic shock. While definitive treatments like bronchoscopy, bronchial artery embolization (BAE), and surgery can be effective, they often require significant time and specialized resources—capabilities not universally available in all hospitals or emergency departments.
Tranexamic acid (TXA), an antifibrinolytic agent, has emerged as both an adjunctive and potentially definitive therapy in the acute management of hemoptysis. A 2020 systematic review by Tsai et al. analyzed 617 studies and found that TXA—whether administered intravenously or via inhalation—was associated with reduced bleeding volume, decreased need for invasive interventions, and shorter hospital stays.1
A small RCT by Wand et al. demonstrated that nebulized TXA significantly reduced expectorated blood volume compared to placebo by day two of admission.2 Inhaled medications are well-established in pulmonary medicine for delivering rapid, localized effects in conditions such as asthma, COPD, bronchiectasis, and even lung cancer.2 This targeted delivery to the lung parenchyma may offer advantages over systemic therapy in conditions like hemoptysis.
While there is growing evidence for the role of TXA in hemoptysis, no prior study has directly compared the efficacy of different routes of administration in this setting. The study reviewed here is the first randomized controlled trial to directly compare intravenous versus nebulized TXA in patients presenting to the emergency department with hemoptysis.
🧾 Paper
Gopinath B, Mishra PR, Aggarwal P, et al. Nebulized vs IV Tranexamic Acid for Hemoptysis: A Pilot Randomized Controlled Trial. Chest. 2023;163(5):1176-1184. PMID: 36410494
️ What They Did
📈 Results
- 110 total patients (55 in each arm)
- 70% men
- Median duration of hemoptysis was 3.5 days (IQR 2-5 days)
- Most common cause of hemoptysis was tuberculosis (76%)
- The median amount of hemoptysis in the 24 hours prior to presenting to the ED was about 100 mL (IQR, 50-150 mL)
- 3 patients in the nebulized arm and 4 patients in the IV arm were on anticoagulants
💥 Critical Results
Cessation of Hemoptysis at 30 Minutes (Primary Outcome):
- 72.7% (40/55) in the nebulized TXA group achieved cessation of bleeding (0 mL).
- 50.9% (28/55) in the IV TXA group achieved cessation of bleeding.
- Statistically significant: χ²(1, n=110) = 5.55, p = 0.0019
Median Hemoptysis Volume (mL) at Time Points:
- At 30 minutes:
- Nebulized TXA: 0 mL (IQR 0–5)
- IV TXA: 0 mL (IQR 0–20)
- p = 0.011
- At 6 hours:
- Nebulized TXA: 5 mL (IQR 0–15)
- IV TXA: 20 mL (IQR 0–60)
- p = 0.002
- At 12 hours:
- Nebulized TXA: 10 mL (IQR 0–20)
- IV TXA: 40 mL (IQR 0–100)
- p = 0.0008
- At 24 hours:
- Nebulized TXA: 10 mL (IQR 0–70)
- IV TXA: 80 mL (IQR 0–150)
- p = 0.005
Need for Bronchial Artery Embolization (BAE):
- 25.5% (13/51) in nebulized group underwent BAE
- 47.7% (21/44) in IV group underwent BAE
- p = 0.024
Discharged from ED:
- 67.9% (36/53) in nebulized group
- 39.0% (16/41) in IV group
- p = 0.005
💪 Strengths
- Clear Research Question: The study clearly defines a focused question: does nebulized TXA reduce hemoptysis compared to IV TXA in Emergency Department patients presenting with hemoptysis.
- Randomization: The randomization protocol used was robust.
- Explicity Eligiibility Criteria: The study provides clear inclusion and exclusion criteria, ensuring the study population was well-defined and appropriate for the research question.
- Intention-to-Treat Principle Maintained: All 110 randomized patients were retained in the analysis with no loss to follow-up or protocol deviations, preserving the benefits of randomization.
- Comparable Groups At Baseline: There were no significant differences in baseline characteristics between the two arms of the study, including age, gender, vital signs, use of anticoagulation prior to TXA administration, or ED diagnosis. This should have been helpful for controlling for confounding factors, likely increasing the validity of the study.
- Clinically Relevant Outcomes: The primary outcome (cessation of bleeding at 30 minutes) is patient-centered and clinically important. Secondary outcomes (hemoptysis volume, need for intervention, adverse effects) are also directly relevant to clinical practice.
- Standardized Intervention and Monitoring: Both groups received the same dose and frequency of TXA. Hemoptysis volume was assessed at predefined time points using calibrated measuring cups, increasing objectivity.
- Real-World Setting: Conducted in a high-volume academic ED, enhancing the external validity for similar emergency settings in low-resource or high-TB-burden countries.
- Transparency: The trial was registered prospectively, and ethics approval and informed consent were clearly documented.
⚠️ Limitations
- Limited External Validity:
- This study was a single-center study conducted in India, which limits external validity and relevance to the patient population of the high-resource countries.
- Approximately 76% of these patients had tuberculosis, which makes this study generalizable to other developing countries. However, the most common causes of nonmassive hemoptysis in developed countries include bronchial neoplasm, acute bronchitis, and bronchiectasis.3
- Lack of Blinding: Providers caring for the patients and administering the different forms of TXA were not blinded. This may have impacted their decision to admit the patient or proceed with a procedural intervention.
- Small sample size: With only 110 patients enrolled, the study may be underpowered to detect rare adverse events or differences in subgroups.
- Need for Clarification Regarding Quantifying and Qualifying Hemoptysis:
- They estimated that the median amount of hemoptysis prior to presentation to the Emergency Department was approximately 100mL, however they did not specify how they quantified this.
- The investigators also did not distinguish between blood-streaked mucous and frank hemoptysis which may affect the mL of blood reported. It is difficult to know how this may have affected the results. However, it would be physically challenging to separate sputum from blood.
- Missing Data:
- Data on bronchial artery embolization were missing for 15 patients: 11 in the IV arm and four in the nebulization arm.
- Data was missing because all the details had to be manually collected later from the patient’s hospital file, and a record of the patients’ files who are discharged from the ED is not always maintained.
- The hospital that conducted the study did not have an electronic medical record, making data collection more difficult.
- Limitations of Short-Term Follow-Up for Assessing Safety: The follow-up period for this study was only 72 hours, limiting the ability to capture potential side effects and more delayed hemoptysis recurrence.4
- No confidence intervals reported: The study did not provide confidence intervals for primary or secondary outcomes, limiting interpretation of the precision and clinical significance of the results.
🗣️ Discussion
Clinical Implications of Nebulized vs IV TA in ED Hemoptysis Management
The IV dose used in this study was 500mg IV TID. The dose of TXA commonly used by the IV route is 1g over 10 minutes, which allows the threshold of antifibrinolytic activity to be reached before the infusion is complete.5 Once administered, the concentration of TXA remains at or above goal for approximately 3 hours. Thus, after 3 hours, the antifibrinolytic activity decreases and seems to be completely gone by 7.9 hours, which is why the general dose is 1g TXA every 8 hours.5,6 While the dosing for inhaled TXA has varied in case reports, Wand et al1 also used 500 TID of inhaled TXA, and this seems to be standard dosing. While it is understandable for the authors to want to compare the same dosages for nebulized vs IV administration to eliminate dosing as a cofounder, future studies should compare the standard dosing of 1g IV TXA TID with the 500mg inhaled TXA. While data is lacking, one could conceive that the dose needed for optimal concentration in the lung may be lower than what is required for IV dosing due to direct delivery to the targeted region of bleeding. The lower dose and more targeted approach in nebulized TXA may also reduce the already minimal risks associated with IV use.
Limitations of Short-Term Follow-Up for Assessing Safety
TXA, particularly high-dose TXA, has been demonstrated to have some side effects such as nausea and diarrhea. The most feared side effect of TXA is thrombosis. However, in several studies where TXA is used for subarachnoid hemorrhage, orthopedic surgery, and cardiac surgery, there has been no demonstrated increased risk of DVT.7 In this study, there were minimal adverse events, as only two patients had asymptomatic and easily reversible bronchospasm using beta agonists. However, the study follow-up period was only 72 hours which may have limited their ability to detect side effects occurring at a later, post-treatment date. Similarly, Wand et al found no side effects throughout their follow up period. Overall, TXA seems to have an incredibly low risk profile.
Impact of Open-Label Design on Outcome Assessment
One of the limitations of this study is that the authors used an open-label design. Residents administering treatment were aware of the treatment arm for each patient, which may have introduced some bias. As they suggest in the article, future studies can eliminate this bias by using IV saline and nebulized saline arms to blind the treatment arms to the treating physicians.
📘 Author’s Conclusion
“Nebulized TXA may be more efficacious than IV TA in reducing the amount of hemoptysis and need for ED interventional procedures. Future larger studies are needed to further explore the potential of nebulized TA compared with IV TA in patients with mild hemoptysis.”
💬 Our Conclusion
This study demonstrates that nebulization of TXA appears to be more effective than intravenous TXA for treating hemoptysis. It is easy to administer, cost-effective, does not require an IV, and can rapidly be started in the pre-hospital setting. Thus, it seems like an excellent early option in the treatment algorithm to reduce bleeding. However, the study’s small sample size, open-label design, single-center setting at a tertiary hospital in India, and predominance of tuberculosis-related hemoptysis limit the generalizability of its findings to broader patient populations. More studies are needed for fu
🚨 Clinical Bottom Line
The best available evidence supports the use of nebulized TXA in hemoptysis. Literature regarding the use of TXA in other bleeding conditions demonstrates that it has a favorable safety profile and minimal side effects. Overall, it is safe, cheap, easy to use, and there are no good alternatives.
🔄 REBEL Recap
📚 References
- Tsai YS, Hsu LW, Wu MS, Chen KH, Kang YN.
Effects of Tranexamic Acid on Hemoptysis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Clin Drug Investig. 2020 Sep;40(9):789-797.
PMID: 32661913 - Wand O, Guber E, Guber A, Epstein Shochet G, Israeli-Shani L, Shitrit D.
Inhaled Tranexamic Acid for Hemoptysis Treatment: A Randomized Controlled Trial.
Chest. 2018 Dec;154(6):1379-1384.
PMID: 30321510 - Mondoni M, et al. Observational, multicentre study on the epidemiology of haemoptysis.
Eur Respir J. 2018 Jan 4;51(1):1701813.
PMID: 29301924 - Chang J, Ma KC.
Tranexamic Acid in the Treatment Paradigm for Hemoptysis.
Chest. 2023 May;163(5):1011-1012.
PMID: 37164570. - Grassin-Delyle S, et al.
Pharmacokinetics of tranexamic acid after intravenous, intramuscular, and oral routes: a prospective, randomised, crossover trial in healthy volunteers.
Br J Anaesth. 2022 Mar;128(3):465-472.
PMID: 34998508 - Dowd NP, Karski JM, Cheng DC, Carroll JA, Lin Y, James RL, Butterworth J.
Pharmacokinetics of tranexamic acid during cardiopulmonary bypass.
Anesthesiology. 2002 Aug;97(2):390-9.
PMID: 12151929 - Tengborn L, Blombäck M, Berntorp E.
Tranexamic acid–an old drug still going strong and making a revival.
Thromb Res. 2015 Feb;135(2):231-42.
PMID: 25559460
Post Peer Reviewed By: Anand Swaminathan, MD (Twitter/X: @EMSwami), and Marco Propersi, DO (X: @Marco_Propersi)
👤 Co Editor-In-Chief
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