Inhaled TXA in pulmonary (and post-tonsillectomy) hemorrhage

Myron Yaster MD, Justin L. Lockman MD, MSEd, and Anna Clebone MD

Good morning!  Expressing gratitude especially when we write it down can positively impact our mood and make us more optimistic.  This is an example of what Rebecca Margolis wrote: 

"I am grateful for the true community of pediatric anesthesiologists I have come to know and develop relationships with because of SPA & WELI. Many of these relationships transcend anesthesia and will be friends for life. I am also extremely grateful for my colleagues @ CHLA who despite the insanity of healthcare continue to RUN to stat calls and help during difficult cases--anesthesia is way more fun as a team sport."

Please take just a moment and write what you are grateful for this holiday season and send it to myasterster@gmail.com so we can have a robust December 24th PAAD!  We are grateful for all of you and the opportunity to work with you on the SPA Well-being committee. Happy holidays, Norah and Rebecca

Every once in a while, I discover an article and have a “wow/ah-ha” moment.  In today and tomorrow’s PAADs you, like I, may experience just such a moment. 

We’ve all experienced a terrifying moment during a bronchoscopy or in the cath lab when a patient develops hemoptysis or very bloody broncho-alveolar secretions/lavage with copious blood pouring out of the endotracheal tube.  Alternatively, when a patient presents with hemoptysis or a bleeding tonsil for emergency treatment, everyone, (the patient, the family and the medical staff) has that panicked look about them.  What if some of these cases could be treated, “off label,” medically with inhaled tranexamic acid (TXA)? In today and tomorrow’s PAAD, we’ll review 2 studies that show that medical and non-operative treatment of these events with inhaled TXA is safe, effective, and inexpensive. WOW!

Before reading our reviews, I’ve got to give a shout out to Dr. Anna Clebone who forwarded these articles to me.  Anna is a vice-chair of SPA’s quality and safety committee and is a leader on the checklist and the Pedicrisis v 2 app sub-committees.  She and Dr, Justin Lockman, the PAAD’s ICU editor, found these articles in our preparation for updates to the checklist and app in which the committee is considering adding TXA to the massive hemorrhage event checklist.  Because I want to give justice to this review, I’m going to split the PAAD into 2 parts. The first will discuss the use of inhaled TXA in pulmonary hemorrhage and the second will be devoted to its use in post-tonsillectomy hemorrhage.  Myron Yaster MD

PS: If in your readings you find an article that you believe is “PAAD worthy” please send me an email with the link and our team will review it.  MY

Original article

Erika R O'Neil, Lindsay R Schmees, Karla Resendiz, Henri Justino, Marc M Anders. Inhaled Tranexamic Acid As a Novel Treatment for Pulmonary Hemorrhage in Critically Ill Pediatric Patients: An Observational Study Crit Care Explor. 2020 Jan 29;2(1):e0075. doi: 10.1097/CCE.0000000000000075. eCollection 2020 Jan.  PMID: 32166295

Pulmonary hemorrhage may present as simple hemoptysis; alternatively it is sometimes severe, life-threatening, and terrifying to the patient, the family, and to the medical team.  Primary etiologies include cystic fibrosis, bronchiectasis, infection, vascular disorders, parenchymal lung disease, congenital heart disease, particularly pulmonary artery hypertension, arterial-venous malformations, ECMO, cancer, and post-surgical complications.1  Additionally, pulmonary hemorrhage can be the result of complications during bronchoscopy with or without biopsy, and during cardiac catheterization, particularly in children with congenital heart disease or with left-heart failure/high end-diastolic pressures. Initial treatment generally includes positive end-expiratory pressure via an endotracheal tube, with consideration for bronchoscopy, catheterization, and more invasive surgical interventions.  One of the hardest things to do in this situation is to realize that disconnection of the circuit to suction the tracheal tube often worsens the problem by dissipating the needed PEEP.  Unless there is actually a blood clot in the tube, we generally leave the circuit connected and turn up the PEEP to 10-12 cm H2O or higher.  Also an older therapy that we (MY and JLL) have also used very successfully and for which we admittedly cannot find a reference is instillation of dilute (1/4 strength or 1/8 strength) sodium bicarbonate through the endotracheal tube as a vasoconstrictor.

As we’ve discussed in several recent PAADs, tranexamic acid (TXA), a lysine analog that blocks the conversion of plasminogen to plasmin, inhibits binding of plasmin to fibrin which stabilizes the fibrin matrix and thereby reduces bleeding.  Several adult studies and case reports in the past few years have demonstrated rapid cessation of hemoptysis after a single dose of TXA via the inhaled route (inhaled TXA) with no reported major adverse events.2, 3  In a retrospective case series, O’Neil et al. found that inhaled or endotracheal TXA effectively and safely treated pulmonary hemorrhage in 18 of 19 patients after only a single dose.  The only failure was in a child on systemic anticoagulation with unfractionated heparin while on ECMO. No patient in this case series experienced major adverse events from the use of inhaled TXA.

OK, how did they administer the TXA? In the authors’ own words: “TXA was administered via inhalation or direct endotracheal instillation, 250–500 mg/dose, using the 100 mg/mL solution designed for IV/IM administration. In intubated and mechanically ventilated patients, TXA was nebulized using Aerogen Solo nebulizer (Aerogen, Galway, Ireland) for 15–20 minutes. [Note that this is the same nebulizer that some of you likely have in your ICUs for administration of albuterol to intubated patients.] One patient received inhaled TXA via the Aerogen Solo nebulizer in-line with noninvasive mechanical ventilation for 15–20 minutes. One patient received endotracheally instilled TXA during a bronchoscopy. Endotracheal suctioning was performed immediately prior to administration of TXA in order to remove secretions that could limit the distribution of TXA throughout the lungs, instilled TXA was administered as three equal aliquots directly into the endotracheal tube, followed by 3–5 positive pressure breaths during manual bagging, and suctioning was avoided for at least 15 minutes after the TXA was administered. After identification of pulmonary hemorrhage, inhaled TXA was initiated at 250–500 mg every 6–24 hours. The modal frequency was every 8 hours. Subsequent administrations were not timed with episodes of bleeding in most cases. Dosing frequency was subsequently decreased based on patients’ responses.”1

The authors rightly conclude that prospective studies should be performed to determine optimal dosing and delivery strategies for pediatric patients, to evaluate mortality benefit and side effects, and to define any etiology-based differential effects.1  All we can say is WOW!  If any of you are or have used inhaled TXA for pulmonary hemorrhage, please share your experience with us and I (MY) will post in a reader’s response.  If not, the next time you have such a patient, consider giving it a try.  Just remember that (like most medications we use) it’s not labeled/approved for use in this way.

References

1.           O'Neil ER, Schmees LR, Resendiz K, Justino H, Anders MM. Inhaled Tranexamic Acid As a Novel Treatment for Pulmonary Hemorrhage in Critically Ill Pediatric Patients: An Observational Study. Crit Care Explor. Jan 2020;2(1):e0075. doi:10.1097/cce.0000000000000075

2.           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. Dec 2018;154(6):1379-1384. doi:10.1016/j.chest.2018.09.026

3.           Dunn AS. Inhaled tranexamic acid improved recovery from hemoptysis compared with placebo. Annals of internal medicine. Apr 16 2019;170(8):Jc45. doi:10.7326/acpj201904160-045