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Abstract
Central venous catheters including totally implantable venous access devices (TIVADs) have revolutionised the management of pulmonary infections and exacerbations in patients with cystic fibrosis (CF). While being better tolerated by the patient, these have allowed aggressive intravenous antibiotic therapies during recurrent hospitalisations. Given improvement in procedural strategies and operator experience, many patients with CF undergo lung transplants in the course of their disease nowadays. TIVADs can be associated with thrombosis leading to superior vena cava (SVC) obstruction and SVC syndrome which can pose a challenge, especially during the transplant surgery. We describe a case of successful management of SVC syndrome in a patient with CF undergoing a lung transplant, highlighting the strategies used to minimise risks associated with such a procedure.
- Transplantation
- Cystic fibrosis
- Surgical diagnostic tests
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Background
Totally implantable venous access devices (TIVADs) provide long-term vascular access for patients with cystic fibrosis (CF). Despite being greatly beneficial and well-tolerated compared with frequent peripheral vascular access catheters, they do pose complications such as thrombosis of vessels due to the physical presence of a catheter in the vessel lumen on the background of thrombophilic disposition in patients with CF. Superior vena cava (SVC) syndrome is an uncommon complication of TIVADs that can lead to serious consequences.1 Despite the advent of highly effective pharmacotherapies to manage CF with reductions in the frequency of exacerbations and improved outcomes, lung transplant for patients with CF remains an important therapy option for patients with end-stage lung disease.2 Advanced CF-related lung disease is the third most common indication for lung transplant in adults.3 In patients requiring lung transplantation, the presence of SVC syndrome may complicate the surgical procedure. Certain prophylactic measures could be undertaken to smooth out the surgical process and allow the patient to receive effective lung transplantation in this scenario.
Case presentation
A male in his 20s with history of CF (F508/F508) status post-bilateral lung transplant in 2018, asthma, CF-related diabetes mellitus and pancreatic insufficiency with moderate protein-calorie malnutrition presented to the hospital with shortness of breath, increased oxygen requirements and right-sided chest pain. 8–12 months prior, he had developed progressively worsening stage III chronic allograft dysfunction (CLAD) with bronchiolitis obliterans syndrome which was managed on immunosuppressant regimen consisting of anti-thymocyte globin, prednisone, cyclosporine and extracorporeal photopheresis and had been listed for lung retransplant at our centre.
1 year prior during one of his hospitalisations, he was diagnosed with TIVAD-related SVC thrombosis, stenosis and obstruction with features of SVC syndrome from a chronic right-sided Port-a-Cath when he had presented with face and right arm swelling. He was started on therapeutic anticoagulation with low molecular weight heparin (LMWH) at 1 mg/kg two times per day, existing Port-a-Cath was removed and a new Port-a-Cath was placed via left IJV. The SVC stenosis was managed with balloon angioplasty and stenting at that time (figure 1a,b).
(a) Pre-angioplasty fluoroscopy showing occluded superior vena cava with no distal contrast flow (green arrow). (b) Post-angioplasty fluoroscopy showing a short wire mesh tube and stent in place with good distal contrast flow (red arrow).
On presentation this time, his vital signs were all normal except for mild tachypnea with respiratory rate of 24 breaths per minute and SpO2 of 99% on 8 L O2 via nasal cannula. Physical examination was remarkable for malnourished appearance with diffusely reduced bilateral breath sounds.
Investigations & diagnosis
A CT angiogram (figure 2) 1 year prior when he was diagnosed with SVC syndrome showed a filling defect indicative of thrombosis in the right internal jugular vein and SVC. A CT venogram (figure 3) performed later was significant for calcification and stenosis in SVC during that time.
CT of chest (coronal view) showing filling defect indicative of thrombosis in the right IJV and superior vena cava (red arrow).
CT venogram axial view showing filling defect in the superior vena cava (SVC) (green arrow) and coronal view showing stenosis of the SCV (yellow arrow).
An emergent CT scan of the chest during current presentation ruled out acute pulmonary embolism or any acute airway disease, and the Port-a-Cath was in a stable position. CT did show grossly unchanged occluded right SVC stent and sequela of bilateral lung transplant with worsening pleural thickening, right worse than left and bilateral scattered ground glass opacities of the lungs. Labs were significant for C-reactive protein (CRP) of 37.3 mg/L (normal<10), white cell count of 12.8 x109/L and troponin of 12 ng/mL (normal<19). Broad workup for infection including bronchoscopy/bronchoalveolar lavage was unremarkable. Hence, a diagnosis of acute on chronic respiratory failure secondary to progressive bronchiolitis obliterans syndrome was established.
Differential diagnosis
The differential diagnosis for respiratory failure in post-lung transplant setting included mainly typical or atypical pneumonia, allograft rejection, anastomotic airway complications, vascular anastomotic complications, pulmonary embolism, pleural complications and malignancy.
Treatment
The patient was maintained on supplemental oxygen and was started on morphine for chest pain and air hunger. Daily monitoring of CRPs showed progressive decline, and he was deemed unstable to be discharged without retransplantation.
A multi-disciplinary discussion including a pulmonologist, interventional cardiologist and transplant surgeon was held given concerns for lung transplantation with a history of SVC stenosis and stenting. Although there was no obvious facial or arm swelling to suggest dysfunction of the SVC stent, interventional cardiology suggested performing urgent fluoroscopy-guided SVC venogram in the cath lab to ensure no further balloon angioplasty or stenting was needed prior to transplant. SVC venogram revealed a patent SVC stent with an occluded IJV (figure 4), and it was deemed safe to proceed with lung transplant. On the availability of suitable donor lungs, the patient underwent a bilateral sequential lung transplant with extracorporeal circulatory support. The severity of the patient’s end-stage CLAD made it too difficult to maintain oxygenation without the assistance of extracorporeal membrane oxygenation intraoperatively.
Superior vena cava venogram showing stent patency with good contrast flow (blue arrow).
Outcome and follow-up
Postoperative course was complicated by shock and acute kidney injury requiring fluid resuscitation and brief vasopressor support. The patient was transferred to the intensive care unit, maintained on invasive ventilation and subsequently extubated to oxygen via nasal cannula on day 3. LMWH and aspirin were resumed post-transplant. Over the ensuing week, his oxygenation improved, and creatinine trended down to normal. The chest tubes were removed over time as output decreased. However, the patient developed persistent left-sided non-chylous pleural effusion which was managed with the placement of a Denver drain. Bronchoscopy showed evidence of acute rejection which was treated with three doses of intravenous 750 mg of methylprednisolone. He was started on belatacept infusions to reduce the risk of allograft rejection. Eventually, the left chest tube was also removed prior to discharge. Patient got left-sided PleurX catheter placement as an outpatient on 1-month follow-up for recurrent left-sided effusion which was eventually removed in the ensuing months given continual improvement in output. Anticoagulation was switched from LMWH to apixaban as outpatient. He has had recurrent hospitalisations since then over 3-year follow-up for various post-transplant complications mainly infections/pneumonia and graft dysfunction for which he got multiple courses of antibiotics, immunosuppression augmentation with higher dosing of steroids and two doses of basiliximab. He is currently maintained on antimicrobial and antifungal prophylaxis and immunosuppression regimen of tacrolimus, mycophenolate mofetil and prednisone and is doing reasonably well on 1–2 L of oxygen by nasal cannula at baseline. SVC stent remains patent. Patient’s course is complicated by chronic thrombus in the right atrium and elevated estimated right ventricular systolic pressure of 67 mm Hg by echocardiogram, and he is on chronic oral anticoagulation with apixaban, dose adjusted to 2.5 mg two times per day due to chronic antifungal prophylaxis with posaconazole.
Discussion
TIVADs have proven to be beneficial in maintaining long-term reliable vascular access in patients with CF in whom recurrent pulmonary exacerbations complicate the disease course warranting frequent hospitalisations and intravenous antibiotics.4 5 Generally well-tolerated, TIVADs are not completely risk-free and may be associated with mechanical, thrombotic and infectious complications.6–8 Thrombosis may be due to the mechanical stress on the vessel wall in the presence of the intravascular catheter over prolonged periods. In addition, several studies have shown CF to have a thrombophilic disposition due to a combination of factors including a chronic inflammatory state because of recurrent pulmonary exacerbations and CF-related liver disease.9–11 A study conducted to evaluate the increased thrombotic risk did not recommend thrombophilia workup before placement of TIVADs as no genetic deficiency could be found.10
Thrombosis associated with central venous catheters (CVCs) may have results ranging from subtle symptoms to severe including pulmonary embolism and strokes from paradoxical embolisation.12–14 The American College of Chest Physicians guidelines do not recommend prophylactic anticoagulation in adults with TIVADs/CVC to prevent catheter-associated thrombosis.15
SVC syndrome is the result of a partial or complete SVC obstruction with a range of symptoms from subtle to life-threatening emergencies depending on the speed of onset of obstruction and the resultant development of venous collaterals.16 Benign etiologies of SVC syndrome have become increasingly recognised.17 SVC stenosis associated with CVC endangers not only the much-needed vascular access in patients with CF but also may result in SVC syndrome of an alarming nature in cases of lung transplantation with additional venous catheters and physical traction on the SVC.
SVC syndrome is diagnosed with contrast studies including venography or enhanced CT scan. Ultrasound for checking patency may be limited due to decreased visibility but may show collaterals and flow reversal.18 Enhanced CT scan is the method of choice for defining underlying pathology while venography is best able to detect intraluminal obstructions like thrombus formation.19 20
Endovascular stenting is regarded as the cornerstone of management.17 21 In contrast to earlier studies that regarded the surgical approach as the preferred option for young patients with benign diseases given longer survival, balloon angioplasty with stent placement is easier and does not preclude the future performance of repeat endovascular procedures or surgical repair if the need arises. Anticoagulation after stenting is supported as the causative chronic indwelling devices remain in place and anticoagulation needs to be on an individual basis.20
The literature regarding management of SVC syndrome due to TIVADs-associated thrombosis particularly in patients with CF is lacking, and much of the knowledge we have is from isolated case reports/case series. Smith et al reported a series of five cases of SVC obstruction in patients with CF of which one was treated with thrombolysis with alteplase, anticoagulation and eventual TIVAD removal, two were treated with balloon angioplasty and TVAD removal, one with anticoagulation alone initially with subsequent TVAD removal and one with anticoagulation alone.22 Similarly, Peckham et al reported a case of SVC obstruction in a patient with CF with long-term indwelling catheter successfully treated with thrombolytic therapy with tissue plasminogen activator.23 Otani et al1 described strategies to minimise risks of intraoperative/perioperative acute life-threatening SVC obstruction in patients with CF after encountering an unexpected case during transplantation, and subsequent seven cases all got pretransplant endovascular stenting along with prophylactic anticoagulation prior to the lung transplant.
The situation gets complicated in a lung transplant recipient where an SVC stenosis could be presumed to be a relative contraindication to a bilateral lung transplant. Our patient was initially considered as a candidate for a single lung transplant given the history of SVC syndrome and stent placement. However, due to rapidly progressive bilateral end-stage lung disease, it was deemed necessary to do a bilateral lung transplant to remove both diseased lungs. With our approach of checking for stent patency before the procedure as Otani et al had suggested, the patient was able to undergo a smooth procedure and good recovery. Although a midline approach would theoretically help preserve venous collaterals as described by Otani et al,1 our patient had a difficult procedure due to adhesions because of a prior transplant and CF-related disease, and a clamshell thoraco-sternotomy was needed to be undertaken. Anticoagulation both pretransplant and post-transplant needs to be individualised with risk-benefit analysis as demonstrated in our patient.
Learning points
Superior vena cava (SVC) stenosis in a patient with end-stage lung disease can be managed successfully with endovascular stenting and is not a contraindication to subsequent lung transplantation.
An assessment of stent patency preprocedure and ensuring vascular access given thrombosed veins is necessary for successful administration of drugs, fluids and blood products perioperatively.
Societal recommendations and guidelines for the management of SVC stenosis in patients with CF with end-stage lung disease would be useful for guidance for successful lung transplantation for which we would need further large-scale studies or randomised controlled trials.
Ethics statements
Patient consent for publication
References
Footnotes
X @skeshavamurthy3
Contributors All authors contributed equally to the article, and MIA is the guarantor. The following authors were responsible for drafting of the text, sourcing and editing of clinical images, investigation results, drawing original diagrams and algorithms and critical revision for important intellectual content: BU, SK, JG and MIA. The following authors gave final approval of the manuscript: BU, SK, JG and MIA.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.