Author: Anila B. Elliott, MD - C.S. Mott Children’s Hospital, - University of Michigan
A 2-year-old male with a history of Trisomy 21 and large perimembranous ventricular septal defect (VSD), who underwent pulmonary artery (PA) banding as an infant, presents for PA band removal and VSD closure. After weaning from cardiopulmonary bypass, airway pressures increase, tidal volumes decrease, and the lungs appear hyperemic on visual inspection. Frank red blood is suctioned from the endotracheal tube. PEEP is increased, cold saline and epinephrine are given via endotracheally, residual heparin has been reversed with protamine, and blood products are being administered. Transesophageal echocardiography shows no residual VSD, normal biventricular function, and an estimated RV pressure one-third of systemic. Bleeding continues. Administration of which adjunctive hemostatic therapy is MOST APPROPRIATE as the next step in management?
EXPLANATION
Pulmonary hemorrhage is a potentially catastrophic clinical scenario requiring rapid and simultaneous airway, hemodynamic, and hemostatic management. The lungs receive blood supply from two circulations. The pulmonary circulation accounts for most of the pulmonary blood flow and supplies the alveolar capillary beds; it is typically a high-volume, low-pressure system. The bronchial circulation comes from the aorta and intercostal arteries and supplies the conducting airways. It accounts for only a small fraction of pulmonary blood supply, but since it is a high-pressure system, injury can lead to severe hemorrhage. 1,2
Children with congenital heart disease (CHD) may be at increased risk of pulmonary hemorrhage secondary to abnormal pulmonary vasculature, elevated pulmonary or left atrial pressures, systemic-to-pulmonary collateral vessels, endothelial damage during various procedures, and coagulopathy following cardiopulmonary bypass.1,2 Trisomy 21 has also been associated with pulmonary vascular disease and increased risk of pulmonary hemorrhage. 3,4 In this patient, potential contributors include coagulopathy, pulmonary vascular disease, mechanical injury, and abrupt changes in regional pulmonary pressure and flow following PA band removal. Along with hyperperfusion, elevated left atrial pressure, residual lesions, airway trauma, and focal surgical or collateral vessel bleeding should be assessed.1,2
Multiple treatment strategies have been described, but there is limited large-scale data in the pediatric patient population. In children with CHD following cardiopulmonary bypass, it is important to reverse residual heparin and administer blood products and/or factor concentrates to correct coagulopathy. PEEP may be increased to improve oxygenation and provide tamponade to bleeding vessels, while monitoring its impact on venous return and hemodynamics. 2,5 Neuromuscular blockade should be considered to suppress coughing and minimize disruption of clot formation. Other considerations include bronchoscopy to evaluate the source of bleeding and clear debris. If bleeding is found to be unilateral, consideration for one-lung ventilation to protect the unaffected lung and positioning the affected lung in the dependent position should be undertaken.2
Cold saline and dilute endotracheal epinephrine are often used for local vasoconstriction, although pediatric evidence and standardized dosing are limited. Small volumes of cold saline may be less effective, and endobronchial epinephrine has been associated with arrhythmias; some authors advise caution with its use in children with cyanotic CHD, particularly in the perioperative period. 2 If bleeding persists despite these initial measures, inhaled tranexamic acid is a reasonable adjunct (answer choice B). TXA inhibits plasminogen activation, preventing conversion of plasminogen to plasmin, preventing fibrin degradation and stabilizing the forming clot. Pediatric evidence remains limited, but observational studies and case series suggest that inhaled TXA may decrease airway bleeding with few reported adverse events. 2,5 Dosing and frequency vary as inhaled TXA remains off-label. In an observational study of critically ill children, with nearly half the cohort having underlying CHD, nebulized TXA (250-500mg per dose every 6-24 hours, most commonly 250mg every 8 hours) was associated with cessation of pulmonary hemorrhage within 48 hours in 18 out of 19 patients (95%), with no major adverse events. Notably, the only nonresponder was systemically heparinized on ECMO, underscoring the importance of heparin reversal.5
Repeating cold saline alone (choice A) is unlikely to be effective once initial vasoconstrictive measures have failed; in one adult trial, small aliquots of cold saline controlled severe endobronchial bleeding in only 3 of 20 episodes.2 Inhaled nitric oxide (choice C) may be appropriate for coexisting pulmonary hypertension or right ventricular dysfunction but is not a direct hemostatic treatment and may increase pulmonary blood flow thus worsening the hemorrhage; it also inhibits platelet aggregation. Additionally the echocardiographic findings in this patient do not suggest pulmonary hypertension or RV dysfunction. Surfactant (choice D) is not a hemostatic therapy. It has been used as rescue therapy for pulmonary hemorrhage in neonates, in whom blood inactivates endogenous surfactant, but a Cochrane review found no randomized trials to support its use, and it has no role in a 2-year-old with post-bypass hemorrhage. 6 Therefore, inhaled or endotracheal TXA is the most appropriate adjunct (answer choice B).
Summary of treatment strategies1,2,5
1. Reverse any residual heparin effect and correct coagulopathy
2. Increasing PEEP to improve oxygenation and tamponade airway
3. Consider neuromuscular blockade to suppress cough to prevent rupture of damaged capillaries
4. Perform bronchoscopy when feasible to clear obstructing clot and determine etiology or location of bleeding
5. Use cold saline and dilute endotracheal epinephrine for local vasoconstriction
6. Consider inhaled or endotracheal TXA – reported dosing 250-500mg per dose nebulized every 6-12 hours
7. For unilateral bleeding, position the affected lung down and consider one-lung ventilation to isolate the bleeding
8. Consider catheter-based, surgical or ECMO rescue support when bleeding or hypoxemia remains
REFERENCES
1. Baroutidou A, Arvanitaki A, Hatzidakis A, et al. Haemoptysis in Pulmonary Arterial Hypertension Associated with Congenital Heart Disease: Insights on Pathophysiology, Diagnosis and Management. J Clin Med. 2022;11(3):633. Published 2022 Jan 26. doi:10.3390/jcm11030633
2. Gipsman AI, Grant LMC, Piccione JC, et al. Management of severe acute pulmonary haemorrhage in children. Lancet Child Adolesc Health. 2025;9(5):349-360. doi:10.1016/S2352-4642(25)00060-4
3. Anton-Martin P, Young C, Sandhu H, Vellore S. Pediatric cardiac patients with pulmonary hemorrhage supported on ECMO: An ELSO registry study. J Extra Corpor Technol. 2025;57(1):2-8. doi:10.1051/ject/2024038
4. Bloom JL, Frank B, Weinman JP, et al. Diffuse alveolar hemorrhage in children with trisomy 21. Pediatr Rheumatol Online J. 2021;19(1):114. Published 2021 Jul 17. doi:10.1186/s12969-021-00592-4
5. 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. 2020;2(1):e0075. Published 2020 Jan 29. doi:10.1097/CCE.0000000000000075
6. Aziz A, Ohlsson A. Surfactant for pulmonary haemorrhage in neonates. Cochrane Database Syst Rev. 2020;2(2):CD005254. Published 2020 Feb 3. doi:10.1002/14651858.CD005254.pub4