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Palliative Care - Dyspnea - Fast Facts | NEJM Resident 360
Dyspnea is an uncomfortable sensation of breathlessness related to difficulty with air movement, increased breathing effort, general distress associated with respiration, or any combination of these. Dyspnea is a common symptom in patients with serious and life-limiting illness, including advanced cancer, heart failure, and chronic lung disease.
Nearly all patients nearing the end of life experience dyspnea, and its progression is often associated with a loss of independence as dyspnea becomes more prevalent during routine activities. Dyspnea progression can also complicate decision-making and advanced care planning, including decisions surrounding intubation, noninvasive ventilation, and ongoing care in hospital versus care at home. Patients receiving palliative care — even those without primary cardiopulmonary disease — frequently experience dyspnea that is refractory to treatment of the underlying disease process and requires symptom-focused care to relieve suffering and improve quality of life.
Pathophysiology and Etiology
Respiration is influenced by several physiologic parameters including gas exchange, acid–base status, and central nervous system regulation. However, the sensation of dyspnea and its severity often correlate poorly with objective measures of hypoxemia, hypercarbia, or tachypnea.
The etiology of dyspnea can be related to an underlying disease process, associated comorbidities, adverse effects from treatment, or a combination of these factors. Some common underlying disease states that contribute to dyspnea in patients receiving palliative care include:
Common Underlying Disease States That Contribute to Dyspnea
| Obstructive lung disease | Chronic obstructive pulmonary disease (COPD), bronchospasm, airway secretions, obstructive mass lesion |
| Restrictive lung disease | Fibrotic lung disease, chest-wall deformity, obesity, abdominal distention, pleural effusion |
| Ventilation–perfusion mismatch | Cardiogenic pulmonary edema, pneumonia, pulmonary embolism, pulmonary hypertension |
| Respiratory fatigue or weakness | Amyotrophic lateral sclerosis (ALS), cancer fatigue |
| Other | Anemia, acidosis, anxiety, cachexia |
Patients without an underlying respiratory, cardiac, or neuromuscular disease also frequently experience dyspnea, especially when nearing the end of life. Other systemic processes in advanced illness, including cachexia and asthenia, as well as comorbid anxiety and existential distress, may worsen breathlessness.
Assessment and Measurement
Dyspnea is a complex symptom that can comprise multiple domains, including physical, psychological, social, and spiritual suffering. Especially in patients with frequent breakthrough dyspnea or chronic dyspnea, caregiver stress can contribute to a patient’s suffering and vice versa.
The assessment of acute dyspnea may warrant laboratory and imaging tests to search for a reversible etiology. However, as noted above, lab and imaging findings often do not correlate well with dyspnea severity.
Several validated measurement tools include dyspnea as part of a comprehensive symptom burden assessment (e.g., the Edmonton Symptom Assessment Scale and Memorial Symptom Assessment Scale) or focus on dyspnea alone (see examples below). Using a numerical rating scale (0 to 10) for dyspnea severity is often the most practical for both initial assessment and for evaluating response to treatment.
Modified Borg Scale
(Source: Comparison of Modified Borg Scale and Visual Analog Scale Dyspnea Scores in Predicting Re-intervention After Drainage of Malignant Pleural Effusion. Support Care Cancer 2013.)
Visual Analog Scale
(Source: Comparison of Modified Borg Scale and Visual Analog Scale Dyspnea Scores in Predicting Re-intervention After Drainage of Malignant Pleural Effusion. Support Care Cancer 2013.)
Management
General principles of dyspnea treatment in palliative medicine include:
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Identify and treat underlying etiologies (e.g., diuresis for cardiogenic pulmonary edema, bronchodilators and glucocorticoids for chronic obstructive pulmonary disease [COPD] exacerbations).
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Continue disease-specific therapies unless contraindications arise or adverse effects from therapies become intolerable.
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When the underlying cause is not reversible or dyspnea becomes refractory to maximum medical therapy, the primary focus of treatment becomes symptom relief.
In addition to disease-specific therapies, several pharmacologic and nonpharmacologic treatments for refractory dyspnea are discussed below.
Pharmacologic Therapies
Opioids
Among pharmacologic treatments for refractory dyspnea, opioids are the most well studied and most widely used class of agents. The mechanism for opioid-mediated relief of dyspnea is not well understood; however, opioids may act at the medullary respiratory center to modify ventilator response to hypercarbia and hypoxia, as well as act at peripheral mu opioid receptors to induce pulmonary vasodilation.
Several systematic reviews and meta-analyses have demonstrated benefit in symptom relief for both oral and parenteral opioids. Morphine has been the most widely studied opioid agent, and small studies have shown hydromorphone to be effective as well. Hydromorphone has the added benefit of a better safety profile in patients with end-organ dysfunction, especially renal disease.
In the inpatient and hospice settings, treatment is often focused on acute or breakthrough dyspnea, which is most effectively managed by low-dose parenteral morphine or hydromorphone. Opioids have also been studied in the outpatient setting for management of chronic refractory dyspnea. Small studies suggest that once-daily long-acting morphine in COPD and as-needed short-acting morphine in heart failure improve dyspnea symptoms.
Opioid safety and adverse effects: Although the effective doses of opioids needed for relief of dyspnea are often much lower than doses needed for analgesia, patients taking opioids for dyspnea can experience the same adverse effects, including nausea, constipation, and pruritus (see the section on Pain Management in this rotation guide for more on opioid adverse effects). Although the primary safety concerns associated with opioids are sedation and respiratory depression, opioids can be used safely with close monitoring during initiation and active titration.
Anxiolytics
Benzodiazepines have also been used in the treatment of refractory dyspnea. A single small study that compared oral midazolam to oral morphine showed a benefit to treatment with midazolam in both baseline and breakthrough dyspnea, and another small study showed that midazolam combined with morphine was superior to morphine alone. The anxiolytic effects of benzodiazepines may be primarily responsible for symptom relief. However, evidence does not currently support routine use of benzodiazepines in refractory dyspnea, and concurrent use of benzodiazepines with opioids increases the risk of oversedation and respiratory depression.
Nebulized Furosemide
Weak evidence from small studies in COPD and cancer patients showed minimal benefit from using nebulized furosemide in the management of dyspnea. Furosemide delivered via the respiratory tract is thought to have effects on cough inhibition, prevention of bronchoconstriction, and neurosensory modulation on airway epithelium.
Oxygen
In patients with COPD and hypoxemia (partial pressure of oxygen [PaO2 <55 mm Hg]), supplemental oxygen therapy has a clear mortality benefit in addition to improving health-related quality of life. However, in other patient populations, the use of palliative oxygen therapy has not demonstrated a clear benefit. One study of nasal cannula delivery of room air versus oxygen in nonhypoxemic patients showed that both interventions improved dyspnea.
Nonpharmacologic Therapies
Rehabilitation and Aerobic Exercise
When able to participate, patients with advanced COPD and patients with cancer benefit from participation in pulmonary rehabilitation programs. Pulmonary rehab can take place in outpatient or inpatient settings and focuses on improving exercise capacity and reducing dyspnea severity.
Electric Fan
A small, randomized, controlled, crossover trial demonstrated that a small electric fan directed at a patient’s face was associated with statistically significant dyspnea relief.
Surgical Interventions
Dyspnea in patients with advanced cardiopulmonary disease or cancer may be amenable to procedural or surgical interventions in select cases.
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Symptomatic pleural effusions can be managed with indwelling pleural catheters or pleurodesis (mechanical or chemical) to prevent effusion recurrence.
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Patients with severe emphysema and large areas of anatomic dead space may be candidates for lung-volume–reduction surgery; however, this procedure carries significant morbidity.
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Large-airway obstruction from primary or metastatic lung cancer can be treated with endobronchial stenting.
Acupuncture
A small sham-controlled trial in COPD patients showed that acupuncture improved subjective dyspnea and performance scores on a 6-minute walk test when compared to placebo, but efficacy has not been replicated in other studies.