Fatigue and Dyspnea

Dyspnea

Dyspnea has been defined as an uncomfortable awareness of breathing. It is a subjective sensation and does not necessarily correlate with clinical findings in a given patient. It occurs in up to 75% of patients with advanced cancer, and good symptom control is less frequently achieved, even by experienced palliative care teams, than with other symptoms of terminal cancer, such as pain or nausea.The frequency of breathlessness increases rapidly with disease progression in advanced cancer patients.

Mechanisms

The pathophysiology of dyspnea is complex and has not been completely elucidated. The respiratory center in the medulla controls breathing, but dyspnea is the result of cortical stimulation. Abnormalities of blood gases detected by both lung and central chemoreceptors and stimulation of lung and respiratory muscle mechanoreceptors stimulate the respiratory center. Mechanoreceptors respond to stretch and irritants and also have a demonstrated effect on the brain cortex, causing dyspnea. In addition, it is possible that both the chemoreceptors and the medullary respiratory center stimulate the cerebral cortex, directly contributing to the sensation of dyspnea. Figure 3 summarizes the mechanisms of dyspnea.

Clinical Features

FIGURE 3Mechanisms of dyspnea. PCO₂ = partial pressure of carbon dioxide.

In patients with advanced cancer, there are many causes of dyspnea, such as pulmonary embolism, lung metastasis, pleural effusion, congestive heart failure, anemia, psychological distress, pneumonia, muscle weakness, and preexisting pulmonary disease.

Direct tumor effects

Dyspnea may be the result of direct primary or metastatic tumor effects such as airway obstruction, atelectasis, parenchymal lung involvement, phrenic nerve palsy, carcinomatous lymphangitis, or superior vena caval obstruction.

Indirect tumor effects

Indirect cancer effects include pneumonia, anemia, pleural effusion, and pulmonary embolism. Cardiac complications of cancer, such as congestive heart failure, pericarditis, or pericardial effusion, may contribute to the problem. Intra-abdominal disorders, such as gross ascites or hepatomegaly, may cause elevation of the diaphragm and may interfere with respiratory function. Generalized muscle weakness due to cachexia or fatigue may exacerbate breathlessness. Preexisting lung diseases, including asthma or chronic obstructive pulmonary disease (COPD), may contribute to the problem.

Treatment side effects

Contributing treatment side effects include pneumonitis or fibrosis following chemotherapy or radiotherapy.

Psychological conditions

Anxiety, depression, or somatization will alter a patient's perception of dyspnea. Anxiety has been found to be an independent correlate of the intensity of dyspnea in cancer patients with moderate to severe dyspnea. Any of these factors may occur in isolation or in combination, and care is needed during assessment, as there are often many contributors in an individual patient.

Assessment

TABLE 2Management of specific causes of dyspnea in cancer patients

Dyspnea is a subjective sensation, and researchers have found much variability in the expression of dyspnea in individuals with similar levels of functional abnormalities. In addition, patients' perception of dyspnea can be influenced by their beliefs and intrapsychic and cultural factors. The presence or absence of physical signs such as tachypnea, wheezing, or use of accessory muscles is not a reliable indicator of the degree of distress felt by patients. The intensity of dyspnea can be easily assessed using verbal, numeric, or visual analog scales similar to those used in pain or nausea. A descriptive study by Henoch et al examined dyspnea in correlation with other symptoms, as well as personal and health factors in 105 patients with advanced lung cancer. More than 50% of patients had perceived dyspnea. The intensity of dyspnea and the occurrence of activity-related dyspnea correlated with the presence of anxiety, depression, fatigue, and cough. A lower coping capacity was associated with a greater likelihood of dyspnea.

Recently, maximal inspiratory pressure has been found to be an independent correlate of the intensity of dyspnea. Physical examination, chest x-ray, and pulse oximetry should be performed. Other investigations, such as complete blood count, echocardiography, or pulmonary function tests, may be indicated.

Management

Specific causes

Underlying specific causes will require treatment as indicated in Table 2.

Symptomatic management

The three modalities of symptomatic treatment in cancer-related dyspnea are oxygen therapy, drug therapy, and counseling.

In patients with advanced malignant and nonmalignant disease, Bausewein et al found breathing training, walking aids, neuroelectrical muscle stimulation, and chest wall vibration to be effective in relieving dyspnea.

Oxygen therapy. In hypoxemic cancer patients with dyspnea, oxygen has been shown to provide significant symptomatic relief. Oxygen (O₂) can be administered by nasal cannula at 2–6 L/min or by mask and titrated to maintain an O₂ saturation at > 90%. Care must be taken in patients with COPD. Oxygen is not useful in patients with dyspnea and an O₂ saturation > 90%.

Drug therapy. There is substantial evidence that systemic opioids have a beneficial effect on cancer-related dyspnea. This is possible without inducing respiratory depression. The optimal type, dose, and mode of administration have not been determined. If the patient is already on opioids, the breakthrough dose can be used to manage dyspnea as well as pain. If not, morphine(Drug information on morphine) can be started at 5–10 mg PO (or 2.5–5 mg SC) q4h with additional prn doses of 2.5–5 mg PO (or 2.5 mg SC) every hour for breakthrough dyspnea. Nebulized opiates are not recommended, as there is insufficient evidence to support their use.

Benzodiazepines have not been found to be effective in the general management of dyspnea, but they may be useful for treatment of episodes associated with anxiety attacks. Regular use of benzodiazepines should be avoided where possible to limit side effects, such as confusion or falls.

Conditions that cause dyspnea in cancer patients and that respond to corticosteroid medication include superior vena caval obstruction, carcinomatous lymphangitis, and COPD. However, corticosteroids may adversely affect muscle function, and the diaphragm may be more susceptible than other muscles. This may be of importance because of the frequency of muscle weakness and fatigue in patients with advanced cancer.

In a recent Cochrane review, Simon et al found no evidence of beneficial effect from benzodiazepines given to treat dyspnea in patients with advanced cancer and COPD.

Counseling. Dyspnea is a variable symptom and is exacerbated by physical activities. Patients and families should be educated so they can identify factors likely to worsen dyspnea. Devices such as bathroom aids and wheelchairs can help reduce physical activity, and the addition of portable oxygen can enable the patient to remain active and autonomous. For symptomatic relief, medication such as opioids can be administered 30–45 minutes prior to dyspnea-causing maneuvers. The family should be educated that dyspnea is subjective and that tachypnea and use of accessory muscles do not necessarily indicate that the patient is suffering. The aim of treatment is to relieve the patient's subjective dyspnea, not to abate physical signs of respiratory distress.