Managing Respiratory Symptoms of Advanced Cancer

CLEVELAND—Common respiratory symptoms of advanced cancer include dyspnea, wheezing and broncho-spasm, cough, and pleural effusion. Shortness of breath is the symptom cancer patients fear most, with the exception of pain, Susan B. LeGrand, MD, said at a conference on Palliative Medicine held at the Cleveland Clinic Foundation.

Dyspnea a Subjective Symptom

Patients with dyspnea, defined as the “sensation of difficulty breathing, not necessarily related to exertion,” feel as if they are suffocating, said Dr. LeGrand, of the Cleveland Clinic’s Harry R. Horvitz Center for Palliative Medicine. Dyspnea is a very subjective symptom and one that is difficult to measure, since it doesn’t correspond with blood oxygen levels. In the literature, dyspnea is described as present in 24% to 79% of palliative care patients, she said.

Unfortunately, the pathophysiology of dyspnea is not well known. “Our understanding of dyspnea is about where we were 10 to 15 years ago with pain,” Dr. LeGrand said. It is possible that when respiratory muscles deteriorate, patients suffer from dyspnea, although no existing lab test can measure this kind of muscle deterioration, she said.

Dyspnea in palliative care patients can result from direct effects of the cancer or its treatment. Cancer patients may have preexisting asthma, chronic obstructive pulmonary disease, or congestive heart failure. For this reason, identifying the cause of dyspnea is difficult.

When trying to determine the cause of dyspnea, it can be helpful to think in terms of organ involvement. Consider which organ is affecting the symptom, Dr. LeGrand suggested. “Is it the lung? The heart?”

Pulmonary causes of dyspnea include asthma, chronic obstructive pulmonary disease, pleural disease, interstitial fibrosis, emboli, lymphangitic carcinomatosis, or tumor in the airway. Pulmonary infection is a major cause of dyspnea in patients with advanced cancer, Dr. LeGrand said.

In addition to congestive heart failure, cardiac causes of dyspnea include pericardial effusion and arrhythmia. “Although pericardial effusion is devastating,” she said, “it’s also easy to fix.” Textbooks don’t mention arrhythmia as a cause of dyspnea, but Dr. LeGrand sees it fairly often. Arrhythmia is also easy to address, she said.

There is a growing recognition that cachexia and weakness contribute to dyspnea. Ascites and hepatomegaly may prevent the diaphragm from moving correctly. Another cause of dyspnea to consider is anemia, although its contribution to dyspnea is hard to determine. Anxiety, too, may contribute, she said.

When evaluating the cause of dyspnea, taking a good history is very important, Dr. LeGrand said. Determine the time course of the symptom: Did it come on suddenly (embolism) or gradually (infection)? Is it worse in certain positions or with exercise? What treatment is the patient receiving for cancer?

A physical exam is necessary, she said. Tests, including a chest x-ray, hemoglobin testing, or digital oximetry, may be appropriate. Dr. LeGrand said she prefers digital oximetry to measuring blood gases because it is less painful to the patient and generally provides all the needed information.

Treating the Symptoms

Ideally, the physician should treat dyspnea by treating the underlying disease. However, with advanced cancer, or while waiting to treat the underlying disease, it is appropriate to begin treating the symptoms.

Systemic opioids remain the mainstay of symptom relief, she said. There is some clinical interest in nebulized narcotics; however, there are few controlled studies in the literature that demonstrate their superiority to systemic narcotics.

Supplemental oxygen is often used to treat dyspnea. Although some physicians believe it is overprescribed in the United States and that its benefit is primarily the result of placebo effect, Dr. LeGrand said that she was comfortable offering it to end-stage patients.

Methylxanthines can augment respiratory muscle function, particularly the diaphragm, but there are no studies in this population. Bronchodilators, often underutilized, are helpful, she said. Corticosteroids and anxiolytics also can play a role in symptomatic treatment.

Wheezing and Bronchospasm

Wheezing and bronchospasm are common causes of dyspnea and may be pulmonary or cardiac in origin. Wheezing is a frequent premorbid condition. It can be differentiated from stridor by its pitch and loudness.

The pulmonary function tests needed to diagnose the cause of wheezing are tiring, and Dr. LeGrand recommended avoiding such tests for weak patients. Instead, the physician can initiate a therapeutic trial of bronchodilators. Patients often benefit from bronchodilators thus obviating pulmonary function tests.

Cough Common in Lung Cancer

Coughing contributes to dyspnea, nausea and vomiting, and pain. A patient who coughs hard enough can break ribs. This symptom is present in 79% of patients who present with lung cancer.

Cough in palliative care patients can have many causes, Dr. LeGrand said. Gastroesophageal reflux is a common cause. Patients with cardiopulmonary disease will cough. Some medications, particularly angiotensin-converting enzyme (ACE) inhibitors given for congestive heart failure, can cause cough. A weak patient who is swallowing ineffectively may aspirate food and cough. Finally, a patient may have a cold or sinus infection that is responsible for the cough.

A cough should be addressed by treating the underlying disease, if possible. With palliative care patients, however, Dr. LeGrand said, it may only be possible to treat the symptom.

Opioids are effective cough sup-pressants, she said. No advantage has been shown for using one type of opioid over another, so there is no advantage for switching drugs. Dextromethorphan, present in many over-the-counter medications, may be useful.

There is some support in the literature for giving an elixir rather than a pill because it is more soothing. The literature also shows that the nonopioid benzo-natate (Tessalon Perles) is effective.

Although nebulized anesthetics have been shown to provide prolonged relief from an uncontrolled cough, Dr. LeGrand said she would like to see more controlled trials. One drawback to nebulized anesthetics is that the patient is required to fast after their use because the inhaled anesthetics eliminate the gag reflex and cause a local anesthesia of the buccal mucosa.

Pleural effusion should be suspected if the patient reports dyspnea that started with exertion and then was present even at rest. Dyspnea is often better when the patient sits up. Cough and chest pain may also be present. In 10% to 50% of patients, pleural effusion may signal the initial manifestation of tumor.

Pleural effusion can be diagnosed by chest x-ray and decubitus films. If the etiology is in question, a diagnostic tap is appropriate, but is not necessary if the patient is already known to have metastatic cancer. A detailed evaluation of fluid is not helpful in advanced cancer.

Treatment for pleural effusion “very much depends on where the patient is in his or her life,” Dr. LeGrand said. Tube thoracostomy with sclerosis is the predominant treatment and is successful in about 70% of patients. Pleurectomy is usually inappropriate for a patient with advanced cancer. With very short life expectancy, periodic thoracentesis might be appropriate. Treatment may also include thorascopic pleurodesis.