Hospital Medicine

Superior vena cava syndrome

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Superior Vena Cava Syndrome

I. What every physician needs to know.

Superior vena cava syndrome (SVCS) is defined by the obstruction of blood flow through the superior vena cava (SVC) as a result of intraluminal thrombus, invasion and/or external compression. Pathologic processes that can cause SVCS involve the lung, regional lymph nodes and other mediastinal structures, as well as the intravascular bed. This leads to thrombosis due to inflammatory processes (neoplastic, infectious) or foreign bodies (mainly central venous catheters, pacemaker leads).

As a consequence, the venous pressure in the upper body is increased and venous collaterals form, establishing alternate routes for the return of venous blood to the right atrium. This is the mechanism that explains most of the symptoms and clinical examination findings.

II. Diagnostic Confirmation: Are you sure your patient has superior vena cava syndrome?

The diagnosis requires confirmation with imaging, but the clinical suspicion is raised by signs and symptoms of central vein obstruction (dyspnea, facial edema, head fullness, arm swelling, neck venous distention, cyanosis, plethora). Symptoms are more severe if the SVC obstruction is distal to the azygos vein and are usually exacerbated by bending forward or lying down. Acute versus chronic onset (depending on etiology) will influence the magnitude of the clinical manifestations.

A. History Part I: Pattern Recognition:

Symptoms/findings that should raise suspicion for SVCS (exacerbated by bending forward or lying down) are described below. These symptoms can get better over time after several weeks of progression due to development of collaterals.

Signs suggesting cerebral edema

  • headache

  • dizziness, stupor, syncope

  • visual disturbances

Increased venous pressure

  • facial, upper extremity, neck swelling and/or cyanosis

  • dilated anterior chest or collateral veins

  • epistaxis, hemoptysis

Respiratory symptoms

  • dyspnea

  • stridor

  • hoarseness

Signs suggesting severe or life-threatening disease that require immediate treatment

  • syncope after bending or, even worse, without precipitating factors

  • hypotension/hemodynamic compromise

  • confusion, obtundation

  • significant laryngeal edema (stridor)

Once diagnosis is suspected, active surveillance for these clinical signs is crucial.

B. History Part 2: Prevalence:

SVCS is primarily a complication of malignancy, with non malignant conditions on the rise given increased use of intravascular devices.

Malignancy

(60-85% of cases, sometimes the presenting symptom of an undiagnosed malignancy)

  1. Non small cell lung cancer (NSCLC) - up to 50% of all cases of malignant SVCS

  2. Small cell lung cancer (SCLC) - up to 25% of all cases of malignant SVCS

  3. Non-Hodgkin lymphoma (NHL) - around 10% of all cases of malignant SVCS

  4. Other malignancies - thymoma, primary mediastinal germ cell neoplasms, mesotheliomas, solid tumors with mediastinal lymph node metastases (for example breast)

Nonmalignant

(15-40%)

  1. Intravascular devices (central venous catheters, pacemaker leads) - frequently, but not always, there is an associated procoagulant condition

  2. Fibrosing mediastinitis and infections (histoplasma - the most common, tuberculosis (TB), actinomycosis, aspergillosis, blastomycosis, filariasis, nocardia, syphilis)

  3. Postradiation to thorax

  4. Other rare causes - goiter, sarcoidosis, Behcet's disease

C. History Part 3: Competing diagnoses that can mimic superior vena cava syndrome.

Given the pathophysiology and clinical signs described above, venous stasis is bilateral and can rarely be confounded with upper extremity deep venous thrombosis.

D. Physical Examination Findings.

  • Edema and possibly cyanosis of face, neck and arms

  • Dilated neck veins and increased number of collateral veins covering the anterior chest wall

  • In severe cases, proptosis, obtundation, laryngeal edema, and stridor

  • Tongue swelling

  • All the above are exacerbated by bending forward or lying down and improved with upright position

  • Clinical signs of the inciting condition can be identified

E. What diagnostic tests should be performed?

A high clinical index of suspicion (based on the above mentioned symptoms and clinical signs) is necessary to make the diagnosis. Once diagnosis is suspected, a contrast enhanced chest computed tomography (CT) should be used to confirm the diagnosis.

Additional tests are usually needed to establish the etiology.

1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Laboratory tests are mostly used for etiologic diagnosis and for evaluation of comorbidities, rather than for the diagnosis of SVCS. Work-up for hypercoagulable state is rarely needed because usually the precipitating conditions are clearly identified (malignancy, catheters etc). Most of the time, the results of these tests do not influence the management of SVCS.

2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Tests that help making the diagnosis of SVCS

  1. Contrast enhanced CT chest can define the level and extent of venous blockage (symptoms are milder if obstruction is above the junction of the azygos vein), identify collaterals and often helps with etiologic diagnosis. Focal hepatic contrast enhancement can be seen in patients with SVCS and it can mimic metastatic liver disease.

  2. Venography is the gold standard and can be slightly superior to CT to define the level and extent of obstruction but it does not provide any etiologic information. Therefore it is rarely used with the exception of patients that are undergoing stent placement or other endovascular procedures.

  3. Magnetic resonance venography (MRV) does not add much to CT and is reserved mainly for patients with contrast dye allergy or other contraindications to iodine contrast dye.

Tests targeting the etiology of SVCS

  1. Contrast enhanced CT chest (see above)

  2. Chest X-ray is abnormal in most patients with SVCS, is usually done before the CT but does not have added value. Most common findings are mediastinal widening and pleural effusions.

  3. Histologic diagnosis is crucial for patients without a known malignancy but with imaging suggesting it. Ideally appropriate samples should be obtained before radiation therapy.

    • Sputum cytology

    • Pleural fluid cytology

    • Lymph node or mass biopsy (obtained by surgical excision of a peripheral node or by invasive procedures like bronchoscopy, mediastinoscopy, CT guided biopsies, video assisted thoracoscopy, thoracotomy)

    • Bone marrow biopsy can help with diagnosis and staging of NHL, SCLC

  4. Disease specific tests may be needed to make the diagnosis (for example, work-up for infectious diseases mentioned above) or if it will influence management (for example, staging work-up for a malignancy that would shed some light on prognosis and help with further management).

III. Default Management.

Once SVCS is diagnosed, the severity of the symptoms will dictate the management. Ideally, an etiologic diagnosis should be established (including tissue diagnosis for malignancy) before treatment is instituted.

Most of the time SVCS has a relatively chronic onset (most patients had an average of 45 days of symptoms before presentation) and the benefit of urgent treatment is outweighed by the importance of accurate etiologic diagnosis. Therefore for all stable patients the focus will be on etiologic diagnosis prior to treatment. If the patient is known to have a malignancy that likely explains the SVCS, treatment can be immediately initiated.

The patient, with proven intravascular thrombosis (and no malignancy suspected) that is secondary to intravascular devices can be treated immediately after diagnosis, as appropriate, with thrombolysis, possibly device removal and/or stent placement.

The only truly emergent situation in adults is the patient presenting with stridor or other signs of severe airway compromise or the patient with cerebral edema or hemodynamic compromise. These patients require immediate treatment as discussed below.

A. Immediate management.

Unstable patients with signs of airway compromise or cerebral edema

  1. Stabilize patient as appropriate (including emergent airway management if needed with intubation, tracheostomy)

  2. Endovascular stenting, possibly preceded by catheter directed intravascular thrombolysis. Offers the advantage not only of of rapid and sustained symptom palliation, but also does not interfere with additional testing that might be indicated (radiation therapy is associated with a significant reduction in rates of tissue diagnosis and in 60% of SVCS caused by malignancy, no tissue diagnosis was made before SVCS was diagnosed). Transfer to a larger medical center with more expertise might be necessary if procedure is not available at local institution.

  3. Radiation therapy used to be the main intervention in emergent situations, but now stenting is preferred, if available, unless a malignancy was previously diagnosed and there is no need for tissue diagnosis. Symptomatic improvement is much slower than with stenting (improvement seen after 72 hours with complete resolution at 2-4 weeks).

  4. Adjuvant therapies. Glucocorticoids can be effective for steroid responsive malignancies like lymphomas and thymomas. The only clear indication for steroids is in patients that receive radiation therapy on an emergency basis (short course to minimize risk of airway obstruction). Steroids have not been studied for other malignancies. Diuretics are used without clear evidence of benefit.

Stable patients with SVCS

The first step is to establish etiologic diagnosis. Endovascular stents and thrombolytic therapy have a role irrespective of etiology, other therapies are etiology specific. Management will be discussed based on etiology, except for the endovascular procedures.

1. Endovascular procedures

  • Endovascular procedures are an acceptable option irrespective of the etiology.

  • Stenting is the most effective for rapid symptom palliation.

  • Angioplasty has no durable effect, is used in selected situations for predilatation before stenting but should not be the only endovascular procedure performed for a patient.

  • Catheter directed thrombolysis and/or mechanical thrombectomy can be used prior to stent placement. Its use is dictated by venogram findings and operator experience.

  • Surgical bypass is effective but rarely used because of the success of endovascular stenting (lately used mostly for patients with histoplasmosis)

2. Small-cell lung cancer, non-hodgkin's lymphoma, germ cell tumors

  • A new diagnosis of SVCS is not influencing the prognosis of the underlying malignancy for these categories of malignancy.

  • Chemotherapy is the first line of treatment. Symptomatic improvement occurs within one to two weeks.

  • Radiation therapy alone is not indicated (unless the patient cannot tolerate chemotherapy), but it is used as an adjuvant.

  • As mentioned, stenting has a role for SVCS treatment in these patients.

3. Non-Small Cell Lung Cancer

  • SVCS is a strong predictor of poor prognosis, survival being limited to a median of 5 months in several case series.

  • Radiation therapy is considered the mainstay of treatment for SVCS symptoms because of the slow response to chemotherapy. Symptom improvement is generally noted in 48-72 hours. Relief of symptoms is obtained in up to four weeks (usually 2 weeks) and approximately 20% of patients do not obtain relief.

  • As mentioned, stenting has a role for SVCS treatment in these patients. If a stent was placed, chemotherapy only is an acceptable option.

4. Intravascular thrombosis due to intravascular device

Removal of device is recommended if possible, but not always needed. If the catheter/device is crucial for the treatment of another disease (for example malignancy, hemodialysis) the benefits of maintaining the line might outweigh the risks. Current recommendations include anticoagulation while the catheter remains in place and 3 months after the catheter is removed.

  • Anticoagulation regimens are similar with ones used in deep vein thrombosis of lower extremities/pulmonary embolism.

  • Concomitant malignancy should be treated as discussed in other sections.

  • Stenting with or without thrombolytics, followed by anticoagulation play an important role but evidently require catheter removal.

5. Other non malignant conditions that can cause superior vena cava syndrome

  • Treatment is condition specific (see other chapters for more details).

6. Anticoagulation

  • Anticoagulation plays an important role in catheter related SVC thrombosis. Its role is less clear in malignancy related SVCS.

  • Should not be used as the only therapeutic intervention for patients with malignancy.

  • Should be considered especially after stent placement, but duration, drug choice, and dosing are controversial and not evidence based, except when the etiology is an intravascular device.

  • Full anticoagulation after thrombolysis and stent placement recommended by most experts, at least for one month and up to nine months as long as there are no contraindications.

  • Low dose warfarin 1 milligram (mg) daily with goal international normalized ratio (INR) less than 1.6 is considered reasonable by some experts but evidence is lacking and we recommend against its routine use.

  • Dual antiplatelet therapy (clopidogrel plus aspirin) for 3 months post stent placement is another alternative for patients that cannot be anticoagulated but evidence backing this approach is weak. Therefore we recommend against its routine use.

B. Physical Examination Tips to Guide Management.

If SVCS is suspected or diagnosed, identifying patients that are unstable or have signs of airway compromise and cerebral edema is a priority. Please see discussion in pattern recognition and treatment section.

C. Laboratory Tests to Monitor Response To, and Adjustments in, Management.

Response to treatment is monitored primarily clinically. Some of the treatment measure require monitoring as follows:

1. Anticoagulation monitoring (see other chapters for more details)

  • PTT (partial thromboplastin time) if continuous infusion of heparin is used

  • In select cases monitoring of anti factor Xa activity if low molecular weight heparins are used

  • INR monitoring

  • Complete blood count (CBC) monitoring while on anticoagulation

2. Monitor for side effects of radiation therapy and chemotherapy as appropriate (see other chapters for more details)

D. Long-term management.

The management of the underlying condition should be implemented as soon as possible.

E. Common Pitfalls and Side-Effects of Management

Common pitfalls

  1. Delayed recognition of need for urgent treatment that results in delayed referral for stenting and potentially poor outcomes.

  2. Initiation of radiation therapy before histologic diagnosis completed.

Side effects of management

1. Complication of stent placement reported in 3-7% of patients:

  • Early complications: infection, pulmonary embolus, stent migration, hematoma at bleeding site, and very rare but severe, perforation or rupture of the SVC

  • Late complication: bleeding from anticoagulation, stent failure with reocclusion

2. Complications of radiation therapy and chemotherapy

3. Complications of anticoagulation

IV. Management with Co-Morbidities

N/A

A. Renal Insufficiency.

Anticoagulant selection should take in consideration the patient's renal function.

V. Transitions of Care

A. Sign-out considerations While Hospitalized.

Most of the patients remain stable after diagnosis and treatment initiation, but monitoring for clinical deterioration (see above for signs of life-threatening disease) is important. Evaluation at bedside looking for hemodynamic instability, signs of airway compromise or cerebral edema is important.

B. Anticipated Length of Stay.

  • For life-threatening cases that require emergent treatment, estimated length of stay is 4-7 days in order to closely monitor response to initial treatment.

  • For patients with a clear etiologic diagnosis (for example known with malignancy) the duration of hospitalization is estimated at 2-4 days, longer if etiology specific treatment requires inpatient stay and this is usually institution dependent (for example initiation of chemotherapy in the hospital).

  • Work-up for etiology and subsequently initiation of treatment can prolong hospitalization. Same applies if complications related to treatment or work-up develop.

C. When is the Patient Ready for Discharge.

Patients should be hemodynamically stable and free of signs of airway compromise or cerebral edema at discharge.

For patients that were stable at presentation, plans for discharge can start as soon as a diagnostic and treatment plan was decided. Ideally, improvement of SVCS symptoms and signs should be noted before discharge, but there is no need to wait for resolution. In these "chronic" cases no news is good news and if the patients remain stable and treatment is initiated, they can be discharged.

D. Arranging for Clinic Follow-up

1. Interventional radiology and/or vascular medicine/surgery if endovascular procedures were performed

2. Radiation therapy if radiation was initiated or is indicated

3. Oncology if a malignancy is the cause, especially if chemotherapy was initiated or is indicated

4. Anticoagulation clinic

1. When should clinic follow up be arranged and with whom.

1. Interventional radiology and/or vascular medicine/surgery if endovascular procedures were performed in 1-2 weeks after the procedure.

2. Radiation therapy if radiation was initiated or is indicated. Depending on treatment regimen, usually in the first 3 days after discharge.

3. Oncology if a malignancy is the cause, especially if chemotherapy was initiated or is indicated. Depending on treatment regimen, usually in the first week after discharge.

4. Anticoagulation clinic: If warfarin was initiated, INR should be followed within 3-5 days after discharge. In rare cases (see chapter on anticoagulation for more details) low molecular weight heparins might need monitoring (see above).

2. What tests should be conducted prior to discharge to enable best clinic first visit.

  • Anticoagulation monitoring

  • Disease specific monitoring (depends on etiology, see appropriate chapters for more details)

3. What tests should be ordered as an outpatient prior to, or on the day of, the clinic visit.

1. A contrast enhanced CT chest might be needed to evaluate degree of SVC obstruction and/or response to treatment (especially if radiation or chemotherapy only was used). Timing depends on etiology of SVCS.

2. Anticoagulation monitoring

3. Disease specific monitoring (depends on etiology, see appropriate chapters for more details)

E. Placement Considerations.

No specific placement considerations directly related to a new diagnosis of SVCS.

F. Prognosis and Patient Counseling.

  • SVCS is frequently caused by malignancy (especially if no intravascular devices are present) and every effort to diagnose the underlying etiology should be made if patient so desires.

  • Deferring treatment until a full diagnostic work-up is completed does not impact outcomes for stable patients.

  • For patients with SCLC, NHL and germ cell tumors, a new diagnosis of SVCS does not imply a worse prognosis than same stage patients without SVCS, as long as the syndrome is recognized and treated. Prognosis and survival are dependent on the primary malignancy and its response to treatment.

  • For patients with NSCLC, SVCS is a poor prognostic sign, with a median survival reported at 5 months in one patient series.

  • For non malignant conditions disease specific prognostic factors should be considered (see other chapters for more details)

VI. Patient Safety and Quality Measures

N/A

B. Appropriate Prophylaxis and Other Measures to Prevent Readmission.

  • Patients should be counseled regarding signs of SVCS that require immediate evaluation:

  • episodes of loss of consciousness that suggest syncope (after bending, or even worse, without precipitating factors)

  • confusion, obtundation

  • difficulty breathing, stridor

What's the evidence?

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