Contrast-enhanced ultrasound-guided precision fibrinolysis for refractory loculated chylothorax after lung transplantation: a case report

Introduction

Lung transplantation remains the definitive therapeutic option for end-stage pulmonary diseases, including pulmonary lymphangioleiomyomatosis (PLAM) (1). However, pleural complications occur in up to 30% of recipients, significantly impacting morbidity and graft survival. Among these, chylothorax is notoriously difficult to manage, with an incidence of 2.6–9.5% after lung transplantation (2). While standard management involves conservative measures and chemical pleurodesis, these agents can occasionally trigger excessive fibrin deposition. This imbalance in pleural fibrin turnover, driven by the overexpression of plasminogen activator inhibitor-1 (PAI-1), leads to the formation of complex, multi-loculated effusions that render conventional catheters ineffective (3).

Intrapleural fibrinolytic therapy (IPFT) with agents such as urokinase or tissue plasminogen activator (tPA) is well-established for empyema and complicated parapneumonic effusions (4). However, its safety profile in the early post-lung transplant period remains under scrutiny. The primary concern is the risk of intrapleural hemorrhage and disruption of the bronchial anastomosis, particularly in patients on immunosuppression and prophylactic anticoagulation. Although Kao et al. (5) reported the general safety of IPFT in a retrospective cohort of 128 transplant recipients, their study relied on standard radiographic monitoring, which lacks the spatial resolution to guide treatment in complex, multi-loculated cases. Blind administration in such scenarios carries the risk of “overshooting”, which may damage the lymphatic vessels or injure the hyperemic allograft pleura.

Herein, we present the first case utilizing contrast-enhanced ultrasound (CEUS) to guide precision fibrinolysis in a lung transplant recipient. This visualized approach allowed for the targeted lysis of septations while sparing the surgical bed, successfully resolving a refractory loculated chylothorax that had complicated a failed pleurodesis. We present this case in accordance with the CARE reporting checklist (available at https://qims.amegroups.com/article/view/10.21037/qims-2026-1-0298/rc).

Case presentation

A 31-year-old female diagnosed with PLAM underwent bilateral lung transplantation at The First Affiliated Hospital of Guangzhou Medical University on April 25, 2021. The immediate postoperative course was uneventful. However, on June 3, 2021 (Day 39 post-transplant), she was readmitted with progressive dyspnea and chest tightness. Thoracentesis revealed a chylous effusion with triglycerides greater than 1.24 mmol/L, confirming post-transplant chylothorax. A chest tube was inserted, and chemical pleurodesis was attempted to seal the lymphatic leak. We also established a specific dietary protocol for the patient. Initially, we instructed the patient to adhere to a fat-restricted diet. Subsequently, based on the recommendations from the clinical nutrition team, we advised the patient to consume a low-fat complete nutritional formula at a target caloric intake of 500 kcal/day, administered in 150–200 mL doses, 2–3 times per day.

Unfortunately, the patient’s symptoms worsened despite initial management. A follow-up two-dimensional (2D) ultrasound on June 15 revealed that the pleurodesis had induced a “honeycomb-like” multi-loculated effusion in the right hemithorax (Figure 1). The fluid was encapsulated in multiple non-communicating septated pockets, making effective drainage through the indwelling catheter impossible. The clinical team faced a paradox: the extensive septations required fibrinolysis (urokinase) to drain, but systemic or excessive fibrinolysis could damage the fragile lymphatic vessels or cause alveolar hemorrhage in the transplant graft.

Figure 1 Pre-procedural ultrasound assessment. Two-dimensional ultrasound on June 15 showing a “honeycomb-like” multi-loculated effusion in the right hemithorax. Red arrow indicates a fibrinous septum.

To navigate the paradox of requiring fibrinolysis while avoiding graft injury, a multidisciplinary decision was made to perform CEUS-guided precision fibrinolysis. On June 16, a pre-procedural CEUS (SonoVue, Bracco, Italy) was performed via the indwelling catheter. Imaging confirmed multiple isolated septations with no flow communication between pockets, and crucially, distinguished avascular fibrin strands from vascularized pleural tissue (Figure 2A). Under real-time ultrasound guidance, a 22G fine needle was used to puncture the septations at multiple points, and a low dose of urokinase (15,000 U dissolved in 10 mL saline) was injected sequentially into the targeted locules. Within 30 minutes, a second CEUS assessment demonstrated the dissolution of fibrin septa and the restoration of communication between pockets (Figure 2B). The indwelling catheter was then opened. Unlike the typical milky chylous fluid observed initially, this drainage yielded 150 mL of bloody, dark-red chylous fluid, suggesting the presence of hemorrhagic chylous fluid or a loculated hematoma component.

Figure 2 CEUS-guided fibrinolysis. (A) Pre-injection CEUS showing multiple non-communicating septations within the effusion. White arrow indicates the avascular fibrin strands (non-enhancing). (B) 30 minutes after urokinase injection, CEUS demonstrates the dissolution of septations. Red arrow indicates the restoration of communication between locules. CEUS, contrast-enhanced ultrasound.

Twenty-four hours later (June 17), repeat CEUS showed a significant reduction in the effusion size with minor residual septations (Video 1). We repeated the same fibrinolytic approach using urokinase at a dosage of 10,000 U. The subsequent drainage yielded clear fluid, indicating resolution of the hemorrhagic component. At this point, the encapsulated pleural effusion had largely resolved, allowing us to proceed with a final intervention—chemical pleurodesis (type III iodophor and normal saline)—to address the lymphatic leak. The patient reported immediate symptom relief. Follow-up 2D ultrasound at Day 3 post-discharge showed a minimal fluid rim (<5 mm) (Figure 3A). At Day 9, chest X-ray confirmed full lung re-expansion. At 3 weeks, imaging confirmed pleural thickening with no residual effusion (Figure 3B and Video 2).

Figure 3 Follow-up assessment. (A) 2D ultrasound at Day 3 post-discharge. The arrow indicates the minimal residual fluid (<5 mm). (B) 2D ultrasound at 3 weeks. The arrow indicates the thickened pleural line (successful pleurodesis) with no residual effusion. 2D, two-dimensional.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for publication of this case report and accompanying images and videos. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

This case highlights a novel salvage strategy for a complex complication: post-transplant loculated chylothorax. Patients with PLAM are prone to lymphatic complications due to the proliferation of lymphangioleiomyomatosis (LAM) cells that obstruct lymphatics and predispose them to persistent chyle leakage (1,6). In this case, the initial pleurodesis was complicated by unexpected fibrin deposition, creating a closed-off, septated space that effectively trapped the lung graft.

The use of IPFT in lung transplantation is controversial. While the Second Multicenter Intrapleural Sepsis Trial (MIST2) established the efficacy of tPA/deoxyribonuclease (DNase) for empyema in the general population (4), lung transplant recipients represent a unique high-risk cohort. They often possess fragile bronchial anastomoses, altered pleural vascularity, and are exposed to systemic anticoagulation (5). Piccolo et al. reported a bleeding risk of approximately 4% with IPFT in general pleural infection, but this risk is theoretically elevated in the early post-transplant period due to graft hyperemia (7). Retrospective data from Kao et al. suggest that fibrinolysis can be performed safely in selected transplant patients (5), but these studies relied primarily on radiographic monitoring and did not address the spatial complexity of multi-loculated effusions. Blind administration in such scenarios poses a significant risk of treatment failure or recurrence.

The innovation of our approach lies in the integration of CEUS as a real-time decision-making tool. Unlike computed tomography (CT) or standard 2D ultrasound, CEUS provides functional imaging of microvascular perfusion by using strictly intravascular microbubbles (8). This capability offered three critical advantages in our case. First, CEUS clearly differentiated between fibrin strands (avascular, non-enhancing) and viable pleural tissue or lung graft (vascular, enhancing). This allowed us to target the injections precisely into the fibrin locules, avoiding accidental injury to the lung parenchyma or intercostal vessels (9). Second, it enabled real-time efficacy monitoring. We utilized CEUS to visually verify the “opening” of loculations in real-time, as the spread of microbubbles from the injection site into adjacent locules served as an immediate confirmative sign of septal lysis.

Third, and perhaps most importantly, CEUS visualization facilitated a “just enough” dosing strategy. Traditional IPFT regimens often employ high empiric doses, such as 100,000 U of urokinase or 10 mg of tPA daily (10-12). By visualizing the restoration of cavity communication within 30 minutes, we could terminate the fibrinolytic exposure early. Our total dose (25,000 U of urokinase) was significantly lower than standard regimens, minimizing the systemic fibrinolytic effect. This dose reduction is crucial for transplant recipients, as it balances the need for drainage against the catastrophic risk of anastomotic hemorrhage (5,13,14). Similar fibrinolytic and imaging-guided strategies have been described for complex pleural interventions (15-17), though typically outside the setting of post-transplant chylothorax.

Several limitations should be acknowledged. This report describes a single case and should be regarded as a proof-of-concept. The technique may not be applicable in patients with diffuse pleural hypervascularity, uncontrolled coagulopathy (14), or inaccessible septations. Further experience in larger cohorts is required to assess reproducibility and long-term outcomes. Our team has previously reported the efficacy of this CEUS-guided technique in general multiloculated effusions (18), and this case extends its application to the challenging post-transplant setting.

Conclusions

In summary, CEUS-guided precision fibrinolysis represents a visualization-driven approach that may reduce the risks inherent in blind IPFT. For carefully selected lung transplant recipients with refractory loculated chylothorax, this strategy may offer an effective salvage option.

Acknowledgments

We would like to thank Editage (www.editage.cn) for English language editing.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://qims.amegroups.com/article/view/10.21037/qims-2026-1-0298/rc

Funding: This study was supported by the National Key Research and Development Program of China (No. 2023YFC2411705).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-2026-1-0298/coif). All authors report that this study was supported by the National Key Research and Development Program of China (No. 2023YFC2411705). The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for publication of this case report and accompanying images and videos. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. McCarthy C, Gupta N, Johnson SR, Yu JJ, McCormack FX. Lymphangioleiomyomatosis: pathogenesis, clinical features, diagnosis, and management. Lancet Respir Med 2021;9:1313-27. [Crossref] [PubMed]
2. Herridge MS, de Hoyos AL, Chaparro C, Winton TL, Kesten S, Maurer JR. Pleural complications in lung transplant recipients. J Thorac Cardiovasc Surg 1995;110:22-6. [Crossref] [PubMed]
3. Komissarov AA, Rahman N, Lee YCG, Florova G, Shetty S, Idell R, Ikebe M, Das K, Tucker TA, Idell S. Fibrin turnover and pleural organization: bench to bedside. Am J Physiol Lung Cell Mol Physiol 2018;314:L757-68. [Crossref] [PubMed]
4. Rahman NM, Maskell NA, West A, Teoh R, Arnold A, Mackinlay C, et al. Intrapleural use of tissue plasminogen activator and DNase in pleural infection. N Engl J Med 2011;365:518-26. [Crossref] [PubMed]
5. Kao CC, Cuevas JF, Tuthill S, Parulekar AD. Pleural catheter placement and intrapleural fibrinolysis following lung transplantation. Clin Transplant 2019;33:e13592. [Crossref] [PubMed]
6. Khawar MU, Yazdani D, Zhu Z, Jandarov R, Dilling DF, Gupta N. Clinical outcomes and survival following lung transplantation in patients with lymphangioleiomyomatosis. J Heart Lung Transplant 2019;38:949-55. [Crossref] [PubMed]
7. Piccolo F, Pitman N, Bhatnagar R, Popowicz N, Smith NA, Brockway B, Nickels R, Burke AJ, Wong CA, McCartney R, Choo-Kang B, Blyth KG, Maskell NA, Lee YC. Intrapleural tissue plasminogen activator and deoxyribonuclease for pleural infection. An effective and safe alternative to surgery. Ann Am Thorac Soc 2014;11:1419-25. [Crossref] [PubMed]
8. Sidhu PS, Cantisani V, Dietrich CF, Gilja OH, Saftoiu A, Bartels E, et al. The EFSUMB Guidelines and Recommendations for the Clinical Practice of Contrast-Enhanced Ultrasound (CEUS) in Non-Hepatic Applications: Update 2017 (Long Version). Ultraschall Med 2018;39:e2-e44. [Crossref] [PubMed]
9. Corcoran JP, Tazi-Mezalek R, Maldonado F, Yarmus LB, Annema JT, Koegelenberg CFN, St Noble V, Rahman NM. State of the art thoracic ultrasound: intervention and therapeutics. Thorax 2017;72:840-9. [Crossref] [PubMed]
10. Bouros D, Schiza S, Tzanakis N, Chalkiadakis G, Drositis J, Siafakas N. Intrapleural urokinase versus normal saline in the treatment of complicated parapneumonic effusions and empyema. A randomized, double-blind study. Am J Respir Crit Care Med 1999;159:37-42. [Crossref] [PubMed]
11. Alemán C, Porcel JM, Alegre J, Ruiz E, Bielsa S, Andreu J, Deu M, Suñé P, Martínez-Sogués M, López I, Pallisa E, Schoenenberger JA, Bruno Montoro J, de Sevilla TF. Intrapleural Fibrinolysis with Urokinase Versus Alteplase in Complicated Parapneumonic Pleural Effusions and Empyemas: A Prospective Randomized Study. Lung 2015;193:993-1000. [Crossref] [PubMed]
12. Janda S, Swiston J. Intrapleural fibrinolytic therapy for treatment of adult parapneumonic effusions and empyemas: a systematic review and meta-analysis. Chest 2012;142:401-11. [Crossref] [PubMed]
13. Gilbert CR, Lee HJ, Skalski JH, Maldonado F, Wahidi M, Choi PJ, Bessich J, Sterman D, Argento AC, Shojaee S, Gorden JA, Wilshire CL, Feller-Kopman D, Amador RO, Nonyane BAS, Yarmus L. The Use of Indwelling Tunneled Pleural Catheters for Recurrent Pleural Effusions in Patients With Hematologic Malignancies: A Multicenter Study. Chest 2015;148:752-8. [Crossref] [PubMed]
14. Goralski JL, Bromberg PA, Haithcock B. Intrapleural hemorrhage after administration of tPA: a case report and review of the literature. Ther Adv Respir Dis 2009;3:295-300. [Crossref] [PubMed]
15. Altmann ES, Crossingham I, Wilson S, Davies HR. Intra-pleural fibrinolytic therapy versus placebo, or a different fibrinolytic agent, in the treatment of adult parapneumonic effusions and empyema. Cochrane Database Syst Rev 2019;2019:CD002312. [Crossref] [PubMed]
16. Light RW. Parapneumonic effusions and empyema. Proc Am Thorac Soc 2006;3:75-80. [Crossref] [PubMed]
17. Bi K, Wang B, Zhang Y, Shen MJ, Chen HW, Zhu HM, Tang CH, Wang Y. Contrast-Enhanced Ultrasound of the Pleural Cavity: A Method to Locate Pleural Catheters and Identify Fibrous Septa. Ultrasound Med Biol 2021;47:1261-8. [Crossref] [PubMed]
18. He L, Tang Q, Liao H, Zhou X, Li Y, Hu Y, Tang M, Zhang Y, Chen W, Wei D. Contrast-enhanced ultrasound guided urokinase injection for precise treatment of encapsulated pleural effusion. Chinese Journal of Medical Ultrasound (Electronic Edition) 2022;19:1250-5.