Dyspnea is a troubling symptom for many patients and those involved in their care. It is common in many advanced diseases and is frequently experienced at the end of life. The American Thoracic Society describes dyspnea as subjective breathing discomfort and sensations in varying intensities that a patient can distinctly qualify. Furthermore, dyspnea originates from multiple physiological, psychological, social, and environmental circumstances, causing secondary physiological and behavioral responses.
Dyspnea results from a complex interplay of multiple factors, and its treatment requires careful evaluation and an individualized approach to management. Generally speaking, the sensation of dyspnea arises from the awareness of a respiratory supply-and-demand mismatch. Such a mismatch can result from the perception of increased demand, decreased capacity, or a combination of both.
In advanced disease states, dyspnea is prevalent and often severe. It is most commonly experienced in advanced cancer, heart failure, and chronic lung disease. These 3 disease categories account for over 50% of deaths in the United States. In cancer patients, the prevalence of dyspnea is 50% to 70%, with a prevalence of up to 90% in patients experiencing lung cancer. In addition, 90% of patients with severe lung disease and 50% of patients with heart failure experience significant dyspnea. It is also a common symptom complex experienced by patients with the end-stage renal disease, dementia, advanced age, and HIV. Additionally, the experience of dyspnea is often frequent, severe and distressing.
Symptoms intensity and prevalence increases in the last six months of life. In fact, during the last 3 days of life, dyspnea is present at some point in 90% of patients.
Respiratory control in normal physiologic situations involves incoming messaging from various peripheral receptors: proprioceptors and mechanoreceptors in the musculature, joints of the chest wall; pulmonary stretch receptors; receptors in the airways; and trigeminal skin receptors. These signals combine with the signals from chemoreceptors in the aortic and carotid bodies and are then transmitted centrally to the pons and medulla via the vagus, glossopharyngeal, spinal, and phrenic nerves.
Voluntary input from the motor cortex via the limbic system contributes protective and emotional influences to motor control of breathing. Outgoing messaging travels back to the motor units via the vagus and other nerves and results in adjustments to the depth and rate of respiration.
Generally speaking, the sensation of dyspnea arises from the awareness of a respiratory supply-and-demand mismatch. Such a mismatch can result from the perception of increased demand, decreased capacity, or a combination of both.
There are 2 theories to explain how supply-and-demand imbalances generate the sensation of dyspnea. “Efferent-reafferent dissociation” occurs when the respiratory center sends a motor command in response to the peripheral messages received. In certain states, the respiratory muscles are unable to match the motor demands. As a result, additional feedback from the periphery communicates to the respiratory center this discrepancy between the output command that was sent and the subsequent inadequate response it generated. The severity of the experience of dyspnea is thought correlate to the degree of this discrepancy.
The second theory involves central corollary discharges. Copies of the descending motor commands sent from the central respiratory motor centers to the periphery are simultaneously sent to the sensory/perceptual areas of the brain. These corollary discharges, which serve to keep the sensory areas informed of the motor commands and impart a conscious awareness of respiratory effort, are thought to contribute to the sensation of dyspnea as well.
Inputs from the cortical and limbic system, much like other homeostatic stimuli like hunger, thirst, and pain, contribute to the subjective intensity and unpleasantness of the overall experience.
Receptors in lung parenchyma, when undergoing abnormal stimulation, produce sensations of chest tightness. This perception of chest tightness that occurs in bronchoconstriction is stimulated through pulmonary afferents rather than the increased work requirements.
A sense of air hunger from exercise, hypoxia, or hypercapnia can result from chemoreceptor signaling when mismatched with the motor drive. However, signaling of the pulmonary vagal stretch and chest wall receptors can inhibit (and therefore reduce) this sense of air hunger.
Specific pathologic and age-related changes contribute to pulmonary dysfunction and the experience of dyspnea. Respiratory muscles weaken, lung elasticity decreases, lung tissue shrinks, and the chest wall stiffens, all of which can result in impairment of efficient gas exchange.
Anxiety caused by the experience of dyspnea can lead to increased respiratory and heart rate, worsening dyspnea.
History and physical exam start with an exploration of the underlying illnesses. When exploring the symptom of dyspnea, relevant dimensions of the symptom include occurrence, distress, intensity, frequency, duration, whether it is constant or episodic, and its meaning.
The biopsychosocial model of “total dyspnea,” modeled after the concept of “total pain,” recognizes that many aspects of the patient’s situation affect the experience of their dyspnea. Physical aspects, psychological aspects such as anxiety, levels of coping, among others, spiritual aspects, for example, the degree of acceptance, meaning, suffering, and social aspects including relationships, family experience, financial situations all contribute to the experience.
Physical exam findings can vary based on the situation and underlying illness. Findings can correlate with the underlying illness, reveal new abnormalities responsible for acute or changing dyspnea, or may even be normal in patients that are nonetheless dyspneic.
A large part of the exam focuses on the respiratory system. While inspecting the patient, any abnormalities in respiratory rate should be noted. There may be visible indications of increased respiratory effort, such as retractions, accessory muscle use, or paradoxical abdominal breathing.
Auscultation can reveal a variety of findings. The presence of grunting, stridor, or voice changes should be noted. Lung fields should be auscultated, listening for prolonged expiratory phase, wheezing, rhonchi, or crackles. The overall degree of air excursion should be noted.
Physical exam findings outside the respiratory system will also contribute to identifying underlying causes of dyspnea. For example, the presence of peripheral edema, jugular venous pulse, heart rate and rhythm, the distance of heart sounds, tracheal positioning, hepatojugular reflux, abdominal distention, or pallor all contribute valuable information to the physical exam for dyspnea.
Furthermore, psychological, social, and spiritual factors can contribute to the overall burden of dyspnea and can be explored as indicated.
In the evaluation of dyspnea, a thorough history and physical exam are warranted with special attention to underlying and possibly reversible causes. Additional laboratory and radiologic evaluation can be useful in diagnosis and in guiding treatment. Pulse oximetry can provide information about oxygen saturation. Arterial blood gases can reveal the presence of acid-base disturbances, hypoxia, or abnormal partial pressures of carbon dioxide. Hemoglobin count can identify anemia. An abnormally high or low leukocyte count or an abnormal leukocyte differential may be suggestive of an infection.
Radiographic imaging, with such modalities as x-ray and computed tomography, can provide a great deal of information regarding the lung parenchyma, pleural space, pulmonary vasculature, and larger airway structures, as well as the bony elements of the thorax. Combined, the laboratory and radiographic information may help identify an underlying etiology of the dyspnea and as such can help guide disease-modifying and symptomatic treatment. However, as dyspnea is a subjective, multifactorial symptom, it may occur in the absence of any identifiable laboratory or radiographic abnormalities.
The management of dyspnea proceeds via one or more of several broad mechanisms. Decreasing respiratory impedance and reducing hypoxemia are treatments aimed at any underlying pulmonary pathophysiology. Other interventions can target reducing the respiratory drive and reducing the resistive load on the respiratory muscles. Altering the central perception of dyspnea at the level of the sensory cortex or brainstem can decrease the intensity and discomfort. Addressing any affective components of dyspnea, such as anxiety, is an important component of treatment.
There are pharmacologic and non-pharmacologic treatments. Pharmacologic interventions can be thought of as disease-modifying when they treat the underlying disease that triggered the dyspnea. A symptom-based approach aims to reduce awareness of the intensity and discomfort of dyspnea.
Diuretics treat fluid overload in congestive heart failure, renal failure, and hepatic failure.
Beta-adrenergic agonists and muscarinic antagonists can reduce symptoms in advanced stages of the chronic obstructive pulmonary disease.
Oxygen administration can improve dyspnea but only in patients with hypoxemia.
Opioids are considered a mainstay of treatment for dyspnea. The evidence is most robust regarding the use of immediate-release morphine. Opioids, via the mu opioid receptors, reduce the discomfort of air hunger but less the discomfort of the increased effort to breathe. It is theorized that morphine decreases spontaneous respiratory drive and the sensitivity of the central breathing center. Opioids may also affect cortical processing of dyspnea as they do in the setting of pain.
The use of benzodiazepines reduces the anxiety often associated with dyspnea, but not the sensation of dyspnea.
Nebulized furosemide has some evidence of efficacy in patients with chronic obstructive pulmonary disease (COPD). It is thought to activate pulmonary mechanoreceptors. In animal models, inhaled furosemide increases the activity of pulmonary vagal stretch receptors.
Nebulized lidocaine or morphine has no evidence of benefit.
Dexamethasone may be useful to improve dyspnea in lung cancer patients or those with COPD.
Mirtazapine has been shown to have some beneficial effect in patients with chronic dyspnea.
Non-invasive ventilation may provide symptomatic improvement in those with increased work of breathing but less helpful in situations of VQ mismatch or alveolar-arterial diffusion defects.
Cold air and the use of fans blowing air on the face can significantly improve dyspnea. Sensory afferents may mediate this effect in the second and third branch of the trigeminal nerve. Supplemental oxygen has only been shown to be useful in patients with hypoxia.
Pulmonary rehabilitation has proven beneficial, with exercise being the most beneficial component.
Cognitive behavioral therapy and anxiety-reduction techniques can address affective components.
Caregiver education with an emphasis on patient positioning, a personal crisis plan, and the use of pharmacologic and non-pharmacologic options may help reduce anxiety and provide an increased sense of control. Additionally, caregiver participation in dedicated support groups may help with coping.
Dyspnea results from an interplay of multiple factors in a variety of patients with advanced illness and at the end of life. It has a large impact on the quality of life of patients and caregivers. Assessment is typically focused on the underlying disease process, as well as the social, psychological, and spiritual factors that may be contributing. The use of non-pharmacologic treatments should be the first step in treating patients. Such interventions include positioning, pacing, and the use of cool air and fans. Oxygen is not more useful than air in patients with normal oxygen levels. Pharmacologic treatment includes optimization of treatment of the underlying disease and opioids for symptom-based treatment. Pharmacologic strategies predominate in care at the end of life, and dyspnea is a common reason for the use of palliative sedation at this stage.