Cardiopulmonary Syndromes (PDQ®)–Health Professional Version

Introduction

Dyspnea is defined as an uncomfortable awareness of breathing. It is a subjective experience involving many factors that modulate the quality and intensity of its perception. Patients with comparable degrees of functional lung impairment and disease burden may describe varying intensities of dyspnea. Patients use a host of different words and phrases to describe the sensation of breathlessness. Terms such as tightness and suffocating are sometimes used.[1]

Reports on the frequency of dyspnea also vary, depending on the setting and the extent of disease.[2] In one study, 49% of a general cancer population reported breathlessness, and 20% rated their breathlessness as moderate to severe.[3] Patients with advanced cancer experience this symptom more frequently and more intensely than do patients with limited disease. One study found that 75 of 135 patients with advanced cancer reporting to an outpatient palliative care clinic were experiencing moderate-to-severe dyspnea.[4] Breathlessness was a complaint at presentation in 60% of 289 patients with lung cancer.[5] Results of a large study showed that 70% of patients suffered from dyspnea in the last 6 weeks of life.[6] About one-third of patients who could report the intensity of their dyspnea rated it as moderate to severe. Another study revealed that one-half of patients with advanced cancer scored their dyspnea as moderate to severe.[7]

Pathophysiology and Etiology

The pathophysiological mechanisms of breathlessness are numerous and complex.[8] Peripheral and central mechanisms as well as mechanical and chemical pathways are involved with a variety of sensory afferent sources.[9-11]

The qualities of dyspnea can be appreciated as work/effort, tightness, and air hunger. The experience of excess work and effort is caused by sensory-perceptual mechanisms similar to those involved in muscles exercising. Tightness is caused by stimulation of airway receptors with bronchoconstriction. The intensity of air hunger and unsatisfied inspiration is caused by the following:[12]

The direct causes of dyspnea in patients with advanced cancer are numerous; categorizing them can assist in the etiologic work-up. One approach is to divide direct causes into the following four groups:

One study found that in patients experiencing dyspnea from advanced cancer, a median of five different abnormalities could have contributed to their shortness of breath.[7] Spirometry was abnormal in 93% of 100 patients examined, with 5% having obstructive patterns, 41% restrictive patterns, and 47% mixed patterns; 49% of patients had lung cancer, 91% had abnormal chest radiographs, and 65% had parenchymal or pleural involvement. These results indicate that a subset of patients will experience shortness of breath without any apparent lung involvement. The potentially correctable causes of dyspnea included:

No significant association between the type of respiratory impairment and the degree of dyspnea was found. Most of these patients were current or former smokers. Most patients also had a significant lowering of their maximum inspiratory pressures, suggesting severe respiratory muscle dysfunction.[7] This finding was duplicated in another study.[4] Of patients admitted to hospice care, 34% had histories of cardiac disease, and 24% had histories of respiratory disease.[6] Only 39% of terminally ill patients who reported dyspnea had lung or pleural involvement. The etiology of dyspnea could not be clearly identified in approximately one-quarter of patients. Another study found that 49% of lung cancer patients presented with airflow obstruction.[7,15]

Respiratory muscle dysfunction is an underrecognized factor contributing to dyspnea. Causes of respiratory muscle dysfunction include:[16]

Poor oxygenation, muscle fatigue, abnormal cortisol and catecholamine levels, and circulating cytokines are also implicated.[16]

Although it is commonly believed that anxiety is associated with breathlessness, researchers found that anxiety and shortness of breath do not invariably go together.[7] One study demonstrated that the involvement of the lungs by cancer, anxiety, and poor maximal inspiratory pressures were correlates of the intensity of dyspnea in patients with advanced cancer.[4]

Assessment

The multidimensional nature of dyspnea must be noted in the complicated assessment of this symptom. Patient-reported outcome is the gold standard for assessment of dyspnea. There is no consensus on what constitutes the best instrument for assessing dyspnea, but following are some of the tools used:

These tools are limited, however, because they are unidimensional and do not account for the relative contribution of different factors to a patient’s perception of breathlessness. Assessment should include the impact of dyspnea on the patient’s functional status and appreciation of the dynamic component of dyspnea—namely, exertional dyspnea.

Objective signs such as tachypnea or the use of accessory breathing muscles frequently do not match a patient’s perception of dyspnea and the degree of functional impairment it causes. Numerous factors, including psychosocial issues, may affect a patient’s experience of dyspnea. Pulmonary function tests, with few exceptions, play a limited role in the assessment of this syndrome. Lack of a clear understanding of the pathophysiological mechanisms underlying dyspnea hampers the clinician’s overall ability to effectively manage it.[8,17]

A comprehensive history and examination are essential to an accurate assessment of dyspnea.[8,17] The temporal onset, qualities of the symptom, associated symptoms, precipitating and relieving events or activities, and responses to medications should be reviewed. Sudden onset may herald a pulmonary embolism or infection, whereas gradual onset may suggest the development of a pleural effusion. A history of obstructive airways or cardiac disease can shed some light on possible underlying causes. Investigations such as measuring oxygen saturation can be useful in determining whether a patient is hypoxic. In the setting of advanced, incurable cancer, arterial blood gasses play a limited role.

Although one-third of patients in the study looking at checkpoint inhibitor immunotherapy–related pneumonitis were asymptomatic, the most common presenting symptoms were the following:[13]

Melanoma and non-small cell lung cancer were the most common cancers treated in this study. Interestingly, the duration of treatment before the onset of pneumonitis was quite variable, with a median time to onset of 2.8 months (range, 9 days–19 months). In addition, pneumonitis seemed to occur earlier in patients who received combination therapy than in those who received monotherapy (median, 2.7 months vs. 4.6 months).[13]

Diagnostic tests that may help to determine the etiology of dyspnea include the following:[7]

Maximal inspiratory pressure (MIP) measurements may be helpful, particularly if no apparent cause can be found. MIP is a reliable functional test of the strength of the diaphragm and other respiratory muscles. Functional assessments such as the 6-minute walk test and exercise ergometry may also provide valuable information about the severity and impact of dyspnea.[21,22]

Management of Dyspnea

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Significance

Malignant pleural effusions are a common complication of malignancy, and malignancy is a common cause of pleural effusions in general. Malignancy accounts for roughly 40% of symptomatic pleural effusions, with congestive heart failure and infection being the other leading causes.[1] The cancers that account for approximately 75% of all malignancy-associated effusions are the following:

Significant use of health care resources is attributable to malignant effusions, with approximately 100,000 cases per year being diagnosed in the United States and 43 cases being detected per 100,000 hospital admissions.[2]

Pathogenesis

The normal pleural fluid space is occupied with approximately 10 cc of fluid with 2 g/dL protein. A pleural effusion is an accumulation of an abnormal amount of fluid between the visceral and parietal pleura of the chest. Normally, pleural fluid is absorbed by pulmonary venous capillaries (80%–90%), with some of it also absorbed by pleural lymphatics. Malignant effusions are usually exudative rather than transudative. Exudative effusions exhibit any one of the following characteristics:[3]

These exudative malignant effusions are generally caused by:

Paramalignant effusions may result from chemotherapy, radiation therapy, atelectasis, or lymph node involvement.

Assessment

Common symptoms associated with malignant pleural effusions include:

About 20% of patients may experience weight loss and malaise. A chest x-ray is most commonly used for radiographic assessment. About 175 cc of pleural fluid will cause a blunted costophrenic angle discernible on chest radiography. A chest computerized tomography scan is more sensitive than a simple chest x-ray and is often used for assessment of loculated effusions because, in some instances, up to 500 cc of loculated fluid can be obscured behind the dome of the diaphragm.[1]

Not all pleural effusions detected in cancer patients will turn out to be malignant effusions. Cancer patients are prone to developing conditions such as:[1]

Each of these conditions may cause a symptomatic effusion for which the clinical management would substantially differ from the management of a malignant effusion. For this reason, cytologic assessment is important. Pleural fluid cytology requires a minimum sample of 250 cc. The morphology of cells obtained from the pleural space can be difficult to assess because of mesothelial and macrophage abnormalities. The diagnostic sensitivity of pleural fluid cytology is approximately 65%, with a specificity of 97%.[1]

Management of Malignant Pleural Effusions

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Incidence and Prevalence

Malignant pericardial effusion occurs in up to 21% of autopsy cases in patients with common malignancies.[4,7] Of patients with lung cancer, 33% have pericardial metastases at autopsy, and one-third of cases of pericardial metastases are caused by lung cancer. Breast cancer causes 25% of pericardial effusions, and about 25% of patients with breast cancer have pericardial effusion. Hematological malignancies (leukemia, Hodgkin disease, non-Hodgkin lymphoma) cause 15% of cases of malignant pericardial effusions.[11]

A retrospective review of 23,592 effusions over a 24-year period revealed 65 malignant effusions (17%) out of 375 pericardial effusions. Lung cancer was the most common cancer found among the malignant pericardial effusions in males, and breast cancer was the most common in females. In 43% of cases, pericardial effusion was the first detected sign of cancer. Of patients diagnosed with malignant pericardial effusions, 86% died within 1 year of diagnosis, with nearly one-third dying within the first month.[8]

In a study of 31 patients with both cancer and pericardial effusions, malignant pericardial effusion accounted for 58% of the effusions, 32% were caused by benign idiopathic pericarditis, and radiation pericarditis caused 10% of cases.[11,12]

Pathophysiology

Malignant involvement of the pericardium is the most common reason for development of pericardial effusions, which result from blockage of venous and lymphatic circulation of pericardial fluid. Such blockage may be caused by primary malignancy of the pericardium, as with pericardial mesothelioma, or by tumors arising in the myocardium, including angiosarcoma, rhabdomyosarcoma, and malignant fibrous histiocytosis. Malignancies can also involve the pericardium through direct extension from carcinomas of the lung or esophagus, thymoma, or lymphoma.[9] Lymphatic or hematogenous metastasis to the pericardium occurs most commonly with the following cancers:

Primary tumors of the pleura or pericardium have been termed primary intrathoracic malignant effusions.[13]

Nonmalignant causes of pericardial effusion include:[14-16]

AIDS may also cause pericardial effusion with pericarditis.[17] Radiation therapy or chemotherapy drugs can cause pericarditis without metastatic involvement of the pericardium. Radiation pericarditis is usually associated with radiation doses to the cardiac window exceeding 30 Gy [10] and occurs most frequently in patients who have received mediastinal radiation for Hodgkin disease or breast cancer.[10] Doxorubicin and cyclophosphamide have been associated with the development of acute pericarditis with effusions.[11,12] Other drugs that may cause acute pericarditis include procainamide, hydralazine, isoniazid, methysergide, phenytoin, and anticoagulants.

Pericardial tamponade results from progressive fluid accumulation in the pericardial sac, causing the following:[15]

Hemodynamic compromise occurs when the normal amount of pericardial fluid (approximately 15–50 cc) increases to 200 cc to 1,800 cc.[15,18] When fluid accumulates rapidly, as little as 250 cc of fluid can result in tamponade.[11,19]

Dyspnea occurs in 93% of patients with pericardial effusions.[6] The following are common symptoms:

Other symptoms of pericardial effusion include:

Signs of effusion include the following:

Pericardial friction rubs and fever are more commonly associated with nonmalignant causes of pericardial effusions than with malignant etiologies.[9]

Signs of pericardial tamponade include:

However, some patients may develop tamponade without this clinical pattern.[4]

Diagnosis

A chest x-ray may show widening of the cardiac silhouette [7] if the amount of pericardial fluid collection exceeds 250 cc;[20] however, a chest x-ray cannot determine the degree of cardiac dysfunction or tamponade. Loculated pericardial effusions may not be apparent on standard posterior/anterior or lateral chest radiographic views.[15]

Transthoracic echocardiography using apical, subxiphoid, and parasternal views can evaluate the presence, quantity, and quality of suspected pericardial effusions as well as associated pericardial masses and inflammation. Moderate effusions on echocardiography show an echo-free space of 10 mm to 20 mm during diastole in M-mode or 2-dimensional echocardiography, whereas severe effusions have an echo-free space exceeding 20 mm.[21,22] Echocardiography can also determine right and left ventricular function and the possibility of right ventricular or atrial diastolic collapse.[7] Left ventricular collapse caused by large pleural effusion without clinically significant pericardial effusions has been reported;[4,16,23,24] however, transesophageal echocardiography may be useful for loculated effusions resulting from adhesions adjacent to the atria, where the thinness of the atrial wall may not be well visualized on transthoracic echocardiography.[4,16]

Echocardiography in pericardial effusion with tamponade shows right atrial or right ventricular compression, or left atrial compression, decreased left ventricular dimension, and absence of collapse of the inferior vena cava on deep inspiration.[6,25] Echocardiography findings predictive of pericardial tamponade have been reported.[26] Right atrial collapse has a sensitivity of 55% to 60% and a specificity of 50% to 68%. Right ventricular diastolic collapse has a lower sensitivity of 38% to 48% but a higher specificity ranging from 84% to 100%. Because neither finding provides 100% sensitivity and specificity, patients who are clinically symptomatic should have a diagnostic pericardiocentesis, even in the absence of definitive findings on echocardiography.[4,27] One study found right atrial collapse present in only 42% of patients and right ventricular collapse in 62%.[27] Nonetheless, 80% of patients with malignant pericardial effusions had symptomatic relief following pericardiocentesis.

The most definitive test for the diagnosis of cardiac tamponade is equalization of diastolic pressures between all cardiac chambers on right-heart cardiac catheterization.[7] This invasive technique, however, is not necessary to diagnose tamponade.

Electrocardiograms in patients with pericardial effusions typically show diminished QRS amplitude in all leads. A classic but uncommonly seen finding in large effusions with pericardial tamponade is variation in the amplitude of the P wave and QRS complex in successive beats on EKG, referred to as electrical alternans. This finding results from movement of the heart within the pericardial sac.[6] Electrocardiography is not sufficiently sensitive to diagnose pericardial effusions.

Pericardial fluid cytology has an accuracy of 80% to 90% in diagnosing malignant pericardial effusion.[6,28] Lymphomas and mesothelioma have higher false-negative detection rates on cytology evaluation.[6,29] Pericardial fluid cytology has a specificity of up to 100%, but sensitivity ranges from 57% to 100% [10][Level of evidence: II] in patients with a known cancer diagnosis and pericardial fluid. Because nonmalignant causes of pericardial effusion can occur in 42% to 62% of patients with cancer and pericardial fluid, a negative cytology examination of pericardial fluid does not help distinguish malignant from nonmalignant causes. The use of more than one cytological preparation (such as concentrating the sample via cytospin, using special markers, or analyzing DNA content) increases the yield over a single preparation; however, multiple samples using the same technique did not significantly increase the diagnostic yield in a retrospective study of 215 patients.[30] In a survey of 80 samples, measurement of DNA index via flow cytometry of pericardial fluid has a sensitivity of 94.8% and a specificity of 100%, compared with routine cytology with a sensitivity of 98.5% and a specificity of 92.3%.[31][Level of evidence: II]

Pericardial biopsy may increase the sensitivity of diagnosing pericardial effusions of malignant origin. However, because pericardial effusions usually occur in advanced disease and portend a shorter survival than do other sites of metastatic involvement, the relief of symptoms rather than diagnosis should be the overriding factor in determining the extent of the evaluation and the course of treatment. Two studies failed to show a difference in survival in cancer patients with pericardial effusion dependent on the results of fluid cytology.[10,32]

In a study of patients with stage I esophageal cancer who underwent radiation and chemotherapy, risk factors for developing pericardial effusion included advanced age, higher pericardial volume 30 (≥41.6 percentage of cardiac volume receiving more than 30 Gy), high body mass index, and diabetes mellitus.[33]

Treatment

No large controlled, randomized, prospective clinical trials demonstrate the optimal management of malignant pericardial effusions or tamponade. Treatment should therefore be individualized to maximize symptom relief with minimal impact on quality of life. Treatment options include the following:[34][Level of evidence: III]

Considerations in the choice of therapeutic option should include:[34][Level of evidence: III]

Large, symptomatic, malignant pericardial effusions are managed by draining the fluid, unless the goals of therapy dictate a less invasive, conservative approach with concomitant shorter survival that should be balanced against quality-of-life concerns. If treatment is indicated for management of tamponade, percutaneous subxiphoid pericardiocentesis is the treatment of choice in the acute setting. Echocardiography is recommended for catheter guidance.[6,35] Catheter drainage is recommended for large effusions to prevent rapid reaccumulation of fluid and subsequent tamponade and for the anticipated survival of the patient.

Recurrent pericardial effusion occurs in 21% [36] to 50% [34,35] of patients following pericardiocentesis. Limited case series suggest rates of pericardial fluid reaccumulation at 30 days ranging from 5% to 33% after pericardial drainage followed by intrapericardial treatment with sclerosing agents or phosphorus-colloid versus more than 50% of those treated with pericardial drainage alone.[34,35]

Prolonged catheter drainage can be effective in preventing fluid reaccumulation; however, the mechanism is unclear. One series had a reported recurrence in 30% of patients at a median time of 39 days. In another series, the reported recurrence rate of the pericardial effusion was 13% by 1 year of follow-up.[37,38]

The prolonged catheter drainage could be left in for several days.[38,39] The catheter should be left in situ until the drainage is minimal (<25–50 mL in a 24-hour period) to none. It is noted that in one series of 171 patients with malignant pericardial effusion who received echocardiography-guided pericardiocentesis followed by extended catheter drainage, the average time to very little catheter output (<50 mL in 24 hours) was about 3 days.[39] Other treatment options to prevent reaccumulation include intrapericardial sclerosis to obliterate the space within the pericardial sac, or pericardiotomy to increase the quantity of fluid drained from the pericardium.

The most effective sclerosing agent for malignant pericardial effusions had been tetracycline, with success rates of up to 80%;[6] however, this agent is no longer available as an intravenous drug in the United States. Alternative sclerosants that have been used include the following:

Most cases may require three or more treatments to achieve adequate sclerosis.[6] Significant pain is reported by 16% of patients undergoing pericardial sclerosis.[6] Consideration must be given to the side effects of various sclerosing agents (e.g., chest pain and arrhythmias). Of patients undergoing pericardial sclerotherapy, 70% to 80% have no fluid reaccumulation within 30 days of the procedure.[35]

A retrospective comparison of pericardiocentesis with sclerotherapy to open surgical drainage among 60 patients showed similar rates for treatment complications, incidence of recurrent effusion, and survival following treatment in both treatment groups.[44] A retrospective review of 59 patients also found similar success rates, whether patients were managed with surgical subxiphoid pericardial window or by pericardiocentesis with or without sclerosis.[34] Patients who underwent pericardiocentesis followed by pericardial window had the longest survival, with a median of 6 months; however, selection bias toward patients with better performance status undergoing more aggressive surgical techniques may contribute to the reported survival advantage. The surgical procedure group had significantly higher average costs of $4,830 compared with $1,625 for patients managed with pericardiocentesis.[34]

Other studies have reported mortality, recurrence, and survival rates for sclerosis that are similar to or slightly lower than those for subxiphoid window or video-assisted thoracoscopy.[44,45];[46][Level of evidence: II][34][Level of evidence: III] Pericardiocentesis with or without sclerotherapy should be considered instead of more invasive procedures in patients with advanced disease or poor functional status.[47]

Transcutaneous balloon pericardiostomy is another technique that is less invasive than open surgical approaches, which include subxiphoid pericardial windows, thoracotomy with pericardiopleural window formation,[48] and thoracotomy with pericardectomy.

Video pericardioscopy has a diagnostic sensitivity of 97% for detecting malignant effusions.[49] Pericardioscopy also is useful for drainage of loculated effusions.[50][Level of evidence: II] Video-assisted thoracoscopy is preferable to more invasive surgical management and should be considered for patients requiring repeated pericardiocentesis for control of symptomatic effusions.[47]

Current Clinical Trials

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Overview

Superior vena cava syndrome (SVCS) is an array of symptoms caused by the impairment of blood flow through the superior vena cava (SVC) to the right atrium. Symptoms that prompt suspicion of this syndrome include the following:[1]

In rare instances, patients may complain of hoarseness, chest pain, dysphagia, and hemoptysis.

Physical signs that may be noted on presentation are the following:

Rarely, cyanosis, Horner syndrome, and a paralyzed vocal cord may also be present.[1]

SVCS is usually a sign of locally advanced bronchogenic carcinoma. Survival depends on the status of the patient’s disease. When small cell bronchogenic carcinoma is treated with chemotherapy, the median survival times with or without SVCS are almost identical (42 weeks or 40 weeks, respectively). The 24-month survival rate is 9% in patients without SVCS and 3% in those with the syndrome. When the malignancy is treated with radiation therapy, 46% of patients who have non-small cell lung cancer experience relief of symptoms compared with 62% of patients who have small cell bronchogenic carcinoma. The 2-year survival rate of 5% is almost the same for both groups.[2]

Most non-Hodgkin lymphoma patients with SVCS respond to appropriate chemotherapy or to combined modality regimens.

Etiology and Physiology

Since SVCS was first described by William Hunter in 1757, the spectrum of underlying conditions associated with it has shifted from tuberculosis and syphilitic aneurysms of the ascending aorta to malignant disorders. Almost 95% of SVCS cases described in published modern series result from cancer; the most common cause is small cell bronchogenic carcinoma, followed by squamous cell carcinoma of the lung, adenocarcinoma of the lung, non-Hodgkin lymphoma, and large cell carcinoma of the lung.[3] A nonmalignant cause of SVCS in cancer patients is thrombosis that is associated with intracaval catheters or pacemaker wires.[4] A rare cause of SVCS is fibrosing mediastinitis, either idiopathic or associated with histoplasmosis.[5] Additional rare causes of SVCS include metastatic germ cell neoplasms, metastatic breast cancer, colon cancer, Kaposi sarcoma, esophageal carcinoma, fibrous mesothelioma, Behçet syndrome, thymoma, substernal thyroid goiter, Hodgkin lymphoma, and sarcoidosis.[6]

Knowledge of the anatomy of the SVC and its relationship to the surrounding lymph nodes is essential to understanding the development of the syndrome. The SVC is formed by the junction of the left and right brachiocephalic veins in the mid third of the mediastinum. The SVC extends caudally for 6 to 8 cm, coursing anterior to the right mainstem bronchus and terminating in the superior right atrium, and extends anteriorly to the right mainstem bronchus. The SVC is joined posteriorly by the azygos vein as it loops over the right mainstem bronchus and lies posterior to and to the right of the ascending aorta. The mediastinal parietal pleura is lateral to the SVC, creating a confined space, and the SVC is adjacent to the right paratracheal, azygous, right hilar, and subcarinal lymph node groups. The vessel itself is thin-walled, and the blood flowing therein is under low pressure. Thus, when the nodes or ascending aorta enlarge, the SVC is compressed, blood flow slows, and complete occlusion may occur.

The severity of the syndrome depends on the rapidity of onset of the obstruction and its location. The more rapid the onset, the more severe the symptoms because the collateral veins do not have time to distend to accommodate an increased blood flow.[7]

One study suggested that the general recruitment of venous collaterals over time may lead to remission of the syndrome, although the SVC remains obstructed.[8]

Assessment and Diagnosis

Once SVCS is recognized, prompt clinical attention is important. For the following reasons, a diagnosis should be established before therapy is initiated:[3]

In the absence of tracheal obstruction, SVCS is unlikely to be a life-threatening oncologic emergency, and treatment prior to definitive diagnosis is not justified.

The initial evaluation of the patient should include a chest x-ray to look for mediastinal masses and associated findings, such as pleural effusion, lobar collapse, or cardiomegaly. Computed tomography (CT) scanning of the thorax yields the most useful diagnostic information and can define the anatomy of the involved mediastinal nodes. Venous patency and the presence of thrombi are assessed by using contrast and rapid scanning techniques.[9] Depending on local expertise, contrast or nuclear venography, magnetic resonance imaging, and ultrasound may be valuable in assessing the site and nature of the obstruction.

If bronchogenic carcinoma is suspected, a sputum specimen should be obtained. If the sputum specimen is negative, a biopsy specimen should be taken from the most accessible site that is clinically involved with disease. The biopsy approach depends on the working diagnosis, the location of the tumor, the physiologic status of the patient, and the expertise available at the facility. It may include:[10]

The biopsy findings will help the clinician plan appropriate treatment.

Treatment Options

The treatment of SVCS depends on the following:

Radiation therapy or chemotherapy should be withheld until the etiology of the obstruction is clear. The treatments discussed here focus on SVC obstruction caused by a malignant tumor. Because the treatment of malignant obstruction may depend on tumor histology, a histologic diagnosis—if not made earlier—should be made before treatment is initiated. Unless there is airway obstruction or cerebral edema, there appears to be no detriment in outcome when treatment is delayed for the assessment.[1,11-15] The following treatment approaches can be used for SVCS.

Psychosocial Considerations

Patients and family members are often frightened and anxious because of the symptoms produced by SVCS, particularly swelling, dysphagia, coughing, and hoarseness. Information about the cause of the symptoms and about short-term measures for palliation is needed by patients and family members, especially during the diagnostic period. When aggressive treatment is declined because of the terminal nature of the underlying disease, symptom management approaches may need to be taught to patients and family members.

Because most adult patients who develop SVCS have lung cancer, the treatment and psychologic support approaches that are developed for SVCS should take into account the patient’s prognosis and psychologic condition, goals of care, and other symptoms caused by the malignancy.[25]

Pediatric Considerations

As described in other sections of this summary, SVCS refers to the symptoms associated with the compression or obstruction of the SVC; the compression of the trachea is termed superior mediastinal syndrome (SMS). Because SMS and the resulting respiratory compromise frequently occur in children with SVCS, the two syndromes have become almost synonymous in pediatric practice.[26,27] In adults, the trachea and the right mainstem bronchus are relatively rigid structures compared with the vena cava, but in children these structures are more susceptible to compression. In addition, the relatively smaller intraluminal diameters of a child’s trachea and bronchus can tolerate little edema before respiratory symptoms occur. Because of this accompanying respiratory component, SVCS in children differs from the adult syndrome and constitutes a serious medical emergency.

The most common symptoms of SVCS in children are similar to those in adults and include:[26]

Symptoms that are less common but more serious are the following:

SVCS is rare in children and appears at presentation in 12% of pediatric patients with malignant mediastinal tumors.[28,29] The etiology, diagnosis, and treatment of SVCS in children differs from that in adults. Whereas the most frequent cause of SVCS in adults is bronchogenic carcinoma,[3] in children the most frequent malignant cause of the syndrome is non-Hodgkin lymphoma. As in adults, a frequent nonmalignant cause is thrombosis from catheterization for venous access.[26]

A physical examination, chest radiograph, and the medical history of the patient are usually sufficient to establish a diagnosis of SVCS. If lymphoma or other malignant disease is suspected, it is desirable to obtain a tissue sample for diagnosis. However, the procedure to obtain the specimen may involve significant risk and may not be clinically feasible. Children with SVCS have a poor tolerance for the necessary general anesthesia because the accompanying cardiovascular and pulmonary changes aggravate the SVCS, often making intubation impossible. Also, extubation may be difficult or impossible, thus requiring prolonged airway provision (intubation). A CT scan of the chest to determine tracheal size, upright and supine echocardiography, and a flow volume loop may help evaluate anesthetic risk. Because anesthesia use is a serious risk, the diagnosis should be made with the least invasive means possible.[30] Published reports suggest a stepwise approach to diagnosis.[26]

When a malignant mass is the cause of the SVCS, the situation may be a medical emergency with no opportunity to establish a tissue diagnosis. In these cases, the most appropriate course may be to initiate empiric therapy prior to biopsy. The traditional empiric therapy is irradiation, with the daily dose governed by the presumed radiosensitivity of the tumor. After irradiation, respiratory deterioration from the apparent tracheal swelling may occur because of the inability of narrow lumens in children to accommodate edema and because of the greater degree of edema at onset, which is the result of the rapid speed at which tumors grow in children. In these situations, a course of prednisone at 10 mg/m2 of body surface area 4 times per day may be necessary.[26]

In addition to radiation, empiric therapy of SVCS has included chemotherapeutic agents incorporating steroids, cyclophosphamide, or both in combination with an anthracycline and vincristine.[26] If the tumor fails to respond, it may be a benign lesion.

If surgery becomes necessary, it should be performed with the patient in the semi-Fowler’s position, allowing the surgeon the ability to rapidly change the patient's position to lateral or prone. Cardiopulmonary bypass facilities and a rigid bronchoscope should be available in a standby capacity.[30]

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the pathophysiology and treatment of cardiopulmonary syndromes, including dyspnea, malignant pleural effusion, malignant pericardial effusion, and superior vena cava syndrome. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.

Reviewers and Updates

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Board members review recently published articles each month to determine whether an article should:

Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.

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Levels of Evidence

Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Supportive and Palliative Care Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

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The preferred citation for this PDQ summary is:

PDQ® Supportive and Palliative Care Editorial Board. PDQ Cardiopulmonary Syndromes. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/about-cancer/treatment/side-effects/cardiopulmonary-hp-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389275]

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