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Assessment and management of dyspnea in palliative care

Assessment and management of dyspnea in palliative care
Author:
Deborah Dudgeon, MD, FRCPC
Section Editor:
Eduardo Bruera, MD
Deputy Editors:
Jane Givens, MD, MSCE
Helen Hollingsworth, MD
Literature review current through: Feb 2022. | This topic last updated: Oct 06, 2021.

INTRODUCTION — Dyspnea, or breathing discomfort, is a subjective experience described as air hunger, increased effort of breathing, chest tightness, rapid breathing, incomplete exhalation, or a feeling of suffocation. Dyspnea is a multidimensional symptom, consisting of affective as well as physical aspects derived from multiple physiological, psychological, and environmental factors [1]. Its presence and severity cannot be inferred from physical examination or laboratory investigations, as it can occur in the absence of physical signs (eg, rapid, deep, or labored breathing) or abnormal findings on investigations such as blood gases or chest radiographs.

This topic focuses on the assessment and care of patients with advanced terminal illness who develop dyspnea. An approach to the diagnosis of dyspnea in adults and the management of specific causes of dyspnea are addressed elsewhere:

(See "Approach to the patient with dyspnea".)

(See "Symptom-based management of amyotrophic lateral sclerosis", section on 'Respiratory function management'.)

(See "COPD exacerbations: Management".)

(See "Palliative care for adults with nonmalignant chronic lung disease".)

(See "Treatment of acute decompensated heart failure: General considerations".)

PREVALENCE — Dyspnea is common in patients with advanced life-threatening illness (table 1). It is one of the most common symptoms reported in patients with a terminal cancer in the last six months of life (figure 1). In a systematic review of the prevalence of 11 symptoms in patients with advanced illness from any of five diagnoses (cancer, AIDS, heart disease, chronic obstructive pulmonary disease [COPD], or renal disease), dyspnea was one of only three symptoms to be present in >50 percent of patients from all five groups [2]. Regardless of diagnosis, both the prevalence and severity of dyspnea tend to increase in the last months of life [3-5]. Idiopathic pulmonary fibrosis is similarly associated with progressive dyspnea [6].

PATHOPHYSIOLOGY — The neurophysiology of dyspnea is related to but distinct from the control of ventilation. (See "Physiology of dyspnea" and "Control of ventilation".)

EVALUATION

Symptom assessment — The goals of a formal assessment of dyspnea in palliative care are to understand the intensity, distress, and impact of dyspnea; to diagnose potentially reversible contributing factors; and to monitor the response to interventions [7]. The evaluation of dyspnea depends on its acuity; general approaches to acute and chronic dyspnea are provided separately. (See "Approach to the patient with dyspnea" and "Evaluation of the adult with dyspnea in the emergency department".)

Assessment of dyspnea involves taking a history of symptoms [7-11]. Patients use variety of terms to describe dyspnea. Certain descriptors tend to cluster with certain diagnoses (eg, “air hunger” and “feeling of suffocation” for heart failure versus “incomplete exhalation” and “chest tightness” for asthma [12]), suggesting that different disease processes, causing distinct pathophysiologic abnormalities, produce qualitatively distinguishable sensations [13,14].

The most commonly used tools for measuring the intensity of dyspnea in the clinical setting are numeric rating scales (0 to 10) and visual analogue scales (0 to 100 mm). Clinicians and family members should assess dyspnea by asking patients how short of breath they feel, rather than estimating their degree of dyspnea from the perceived degree of respiratory effort (eg, tachypnea, accessory muscle use) [15].

Patients with dyspnea inevitably reduce their activity level to accommodate dyspnea, so questions about limitations in performing specific activities can be used to assess the impact of dyspnea.

Screening for dyspnea with a validated symptom assessment tool, such as the Memorial symptom assessment scale, short form (MSAS-SF (figure 2)), or the revised Edmonton Symptom Assessment scale (rESAS (table 2)) [16], is a first step in recognizing the presence of dyspnea but not its specific characteristics.

Distress caused by dyspnea has functional and psychological aspects. Acute episodes of breathlessness are usually accompanied by feelings of anxiety, fear, and possibly panic [17,18]. Patients may express fear of dying during an acute episode or when waking in the middle of the night with intense air hunger [19,20]. (See "Approach to the patient with dyspnea", section on 'Evaluation of acute dyspnea'.) Scales are available that permit an assessment of the amount of distress caused by dyspnea [21-23].

Dyspnea is a major detriment to quality of life [24-27]. It has been identified as the most important variable influencing the will to live among terminally ill cancer patients [28] and the second most common reason to initiate palliative sedation [29,30]. Dyspneic patients frequently report social isolation as a consequence of reduced activity levels [31-33].

Assess for psychological factors — A person’s perception of the intensity of dyspnea can be affected by psychological factors such as anxiety and depression [34-39]. Depression scores alone [34] and in combination [39] with anxiety scores are significantly correlated with the intensity of dyspnea.

Anxiety is common in advanced illness and is discussed elsewhere. (See "Psychosocial issues in advanced illness", section on 'Anxiety' and "Management of psychiatric disorders in patients with cancer", section on 'Anxiety' and "Generalized anxiety disorder in adults: Epidemiology, pathogenesis, clinical manifestations, course, assessment, and diagnosis" and "Panic disorder in adults: Epidemiology, clinical manifestations, and diagnosis".)

The treatment of anxiety and depression are discussed elsewhere. (See "Unipolar major depression in adults: Choosing initial treatment" and "Generalized anxiety disorder in adults: Management".)

Testing to determine underlying cause — Laboratory testing and imaging studies (pulse oximetry, arterial blood gases, chest radiographs, pulmonary function tests, etc) are not helpful in detecting the presence or severity of dyspnea. As examples, normal oxygen saturation does not exclude dyspnea, and some patients with advanced lung disease are not troubled by dyspnea. However, such testing may help identify the underlying cause of dyspnea, if it is appropriate for the patient’s goals of care [7,11]. Several causes of dyspnea in palliative care patients are presented in the table (table 3) and are discussed in detail elsewhere. (See "Approach to the patient with dyspnea", section on 'Initial testing in chronic dyspnea'.)

MANAGEMENT — The ultimate goal in treating any symptom is to reduce the distress it causes. Among patients receiving palliative care for advanced terminal illness, the causes of dyspnea are often untreatable. However, if a specific treatable cause of dyspnea is found (eg, bronchospasm, pulmonary emboli, upper airway obstruction, pleural effusion), specific treatment of that process may be appropriate depending on the invasiveness of the therapy and the patient’s values and preferences. Management of these specific underlying causes of dyspnea is discussed briefly in this topic review (see 'Treatment of underlying disease' below) and is covered in detail in individual topic reviews. This section will focus on treatments that are aimed directly at the symptom of breathlessness [40,41].

General measures for all patients — A multidisciplinary approach to dyspnea that addresses various pathophysiological factors from symptom production to perception and interpretation of the symptom is outlined in the table (table 4). Nurses (education), physiotherapists (exercise therapy), respiratory therapists, occupational therapists (ergonomics and accommodation strategies), dieticians (to optimize nutrition), and psychologist/chaplains (to address symptom meaning) all have important roles to play [42,43]. Some of these interventions may be more suited to patients with chronic dyspnea.

General supportive measures used to alleviate the sensation of breathlessness in all patients include the following:

Relaxation techniques and psychosocial support [44].

Modification in activity level and the use of bathroom aids and wheelchairs to increase the autonomy of patients and their families.

Use of a fan with cool air blowing on the face [45-47].

Limited evidence suggests that chest wall and intrapulmonary percussive vibration and mechanical insufflation-exsufflation devices can be helpful for selected patients who have difficulty mobilizing secretions [48].

Treatment of underlying disease — Goal-directed therapies may be available for specific underlying causes of dyspnea [7].

COPD – Many patients with terminal cancer and dyspnea have a history of smoking or chronic obstructive pulmonary disease (COPD). Assessment and management of potentially reversible airway obstruction is appropriate in all dyspneic cancer patients. Bronchodilator therapy may be useful. In addition, pulmonary rehabilitation, which includes exercise training, psychosocial support, nutrition therapy, and self-management strategies, can improve exercise tolerance and psychological parameters among patients with COPD. However, pulmonary rehabilitation may not be appropriate for patients with a short estimated life expectancy. (See "Stable COPD: Overview of management" and "Pulmonary rehabilitation".)

Central airway obstruction – For patients with dyspnea due to central airway obstruction from a tumor, glucocorticoids may shrink the tumor and improve airflow [49]. Debulking of the tumor with endobronchial techniques, such as endoscopic laser, electrocautery, argon plasma coagulation, and cryotherapy, followed by placement of an airway stent may provide palliation [50,51]. However, such interventions may not be in line with the goals of care. The role of endoscopic laser, electrocautery, and stent placement in managing central airway obstruction is discussed separately. (See "Clinical presentation, diagnostic evaluation, and management of central airway obstruction in adults".)

Heart failure – Diuresis may be beneficial to reduce lung congestion in dyspneic patients with end-stage heart failure. (See "Palliative care for patients with advanced heart failure: Decision support and management of symptoms", section on 'Dyspnea'.)

Lymphangitic carcinomatosis – Symptomatic treatment of lymphangitic carcinomatosis may include diuresis (to avoid volume overload) and glucocorticoids, based on anecdotal reports [52-54].

Pleural effusions – Malignant pleural effusions can be an important cause of dyspnea. In addition to treatment of the underlying malignancy, treatment options include therapeutic thoracentesis, placement of an indwelling pleural catheter, pleurodesis, and (rarely) pleuroperitoneal shunt. These options are discussed separately. (See "Management of malignant pleural effusions".)

Other – Glucocorticoids may help to treat several underlying causes of dyspnea, including COPD exacerbations, tumor-related superior vena cava (SVC) syndrome in patients with glucocorticoid-responsive malignancies (eg, lymphoma, thymoma), radiation pneumonitis, and chemotherapy-induced pneumonitis [52,53]. (See "Malignancy-related superior vena cava syndrome", section on 'Glucocorticoids' and "Radiation-induced lung injury", section on 'Glucocorticoids' and "Pulmonary toxicity associated with systemic antineoplastic therapy: Clinical presentation, diagnosis, and treatment", section on 'Glucocorticoids'.)

Chronic dyspnea — After disease-modifying therapies have been utilized, further treatments for chronic dyspnea are aimed at symptom relief.

Oxygen

Hypoxemic patients — Supplemental oxygen is a standard therapy for symptomatic (and potentially therapeutic) management of patients who are hypoxemic on room air (pulse oxygen saturation ≤88 percent) [7,55,56]. We suggest a therapeutic trial of oxygen supplementation for relief of dyspnea in hypoxemic patients despite limited evidence supporting its use. Our approach is consistent with evidence-based guidelines from the American Society of Clinical Oncology (ASCO) and the American College of Physicians (ACP), which recommend oxygen for short-term relief of hypoxemia in adults with dyspnea and serious illness at the end of life [7,55]. (See 'Recommendations of expert groups' below.)

Studies of supplemental oxygen for relief of dyspnea have shown mixed results in hypoxemic and non-hypoxemic patients with cancer and severe lung disease [57-65]. Two systematic reviews of controlled trials of oxygen therapy for dyspnea have concluded that there was no consistent benefit for oxygen over air inhalation for dyspnea due to end-stage cancer or cardiac failure [66,67]. However, findings may have failed to show benefit due to the combination of hypoxemic and non-hypoxemic patients.

High-flow nasal cannula oxygen may provide short-term symptomatic relief but is generally not available outside the hospital setting [7,68,69]. The flow rate usually starts at 45 to 50 L/min and can be adjusted within a range of 20 to 60 L/min, decreasing the flow for comfort or increasing the flow if needed for better oxygenation [7]. (See "Heated and humidified high-flow nasal oxygen in adults: Practical considerations and potential applications".)

Although there is a likely a placebo effect of oxygen and the medical symbolism inherent in its administration, there may be other reasons for this perceived benefit (table 5). Several studies support the hypothesis that stimulation of the trigeminal nerve (V2 branch) has a central inhibitory effect on dyspnea [63,70]. Thus, part of the effect of oxygen may be attributed to sensory stimulation and, as noted above, might be duplicated by the application of cool moving air to the face. (See 'General measures for all patients' above.)

Non-hypoxemic patients — In patients who are not hypoxemic, supplemental oxygen has not been shown to improve dyspnea when compared with room air [71,72].

Opioids — For patients with advanced illness who have distressing dyspnea despite general measures noted above (table 4) (see 'General measures for all patients' above), we recommend use of systemic opioids. Guidelines for management of dyspnea from several expert groups, including the American Society of Clinical Oncology, American College of Chest Physicians (ACCP), ACP, American Thoracic Society (ATS), Canadian Thoracic Society, National Comprehensive Cancer Network (NCCN), and Cancer Care Ontario, all advise the use of systemic opioids for relief of dyspnea in patients with advanced terminal disease with appropriate caution regarding the risk of respiratory depression [7,55,56,73-77]. (See 'Recommendations of expert groups' below and 'Society guideline links' below.)

Morphine is the most widely studied drug, although codeine [78], dihydrocodeine [79-82], hydromorphone [83,84], and diamorphine [85] have also been effective. The benefit of transmucosal or subcutaneous fentanyl is less clear; the available data are conflicting [86-90].

We use morphine (or equivalent doses of an alternative opioid) as described in the Cancer Care Ontario’s symptom management guide to dyspnea in patients with cancer. Suggested doses are given below.

Opioid-naïve patients

For patients with moderate dyspnea (eg, on walking a short distance), we use oral morphine 5 mg every four hours regularly, with 2.5 mg every two hours as needed. Patients who cannot take an oral medication may be treated with morphine 3 mg subcutaneously every four hours regularly, with 1.5 mg every hour as needed. Once the effective regular dose is determined, an oral, sustained-release formulation can be substituted for the patient’s convenience.

For patients with severe dyspnea (eg, at rest or with minimal exertion), we use morphine as a subcutaneous or intravenous (IV) bolus of 2.5 mg.

-If dyspnea is not controlled, the intravenous doses can be repeated every 15 to 30 minutes if needed and well tolerated. Subcutaneous doses can be repeated every 30 to 60 minutes if needed and well tolerated.

-If two doses are well tolerated but fail to reduce dyspnea adequately, we generally double the dose.

After initial treatment with bolus administration, continue with regular dosing guided by the bolus doses used.

Patients with dyspnea despite already taking opioids

Adjusting daily dose – For patients with moderate or severe dyspnea, we increase the regular dose by approximately 25 percent, guided by the total dose (including breakthrough doses) used in the previous 24 hours.

Breakthrough dosing – For patients on oral opioids, we provide a breakthrough oral dose of 10 percent of the total 24-hour regular dose at two-hour intervals as needed.

For patients on oral opioids who need a subcutaneous or IV bolus to control a severe dyspneic episode, the dose would be 5 percent of the daily oral dose at approximately one-hour intervals.

For patients already taking a parenteral opioid, we provide a subcutaneous or IV bolus of approximately 10 percent of the daily dose of the patient’s current opioid for breakthrough dyspnea.

Monitoring and adverse effects – The patient’s respiratory rate should be monitored during treatment. The time to peak effect is approximately 10 to 15 minutes with intravenous treatment and greater than 30 minutes with subcutaneous treatment.

Although respiratory depression may occur with use of opioids [91], evidence of significant depression is limited [92,93], and no studies have found excess mortality associated with the use of opioids for dyspnea [94,95]. However, caution is warranted in patients with sleep apnea, those with concomitant use of benzodiazepines, and those with a history of carbon dioxide retention. In all cases, doses should be titrated slowly and monitored for effectiveness and adverse effects.

Nausea, constipation, and drowsiness are common adverse effects which may limit tolerability [96]. Careful monitoring and individual dose titration are vital. Steps to mitigate adverse effects are described separately. (See "Prevention and management of side effects in patients receiving opioids for chronic pain".)

Efficacy – Data from several but not all studies, trials, and meta-analyses demonstrate the benefits of systemically administered opioids in treating breathlessness; most of these trials enrolled patients with nonmalignant disease [97-107].

The Morphine for the Treatment of Dyspnea in Patients with COPD (MORDYC) trial randomized 124 patients with moderate to very severe chronic breathlessness (modified Medical Research Council [mMRC] grades 2 to 4) who had completed a pulmonary rehabilitation program to either sustained-release morphine 10 mg twice daily (dose could be increased to three times daily after one or two weeks) or placebo [106]. After four weeks, the COPD Assessment Test (CAT) score, a measure of disease specific health status (higher scores indicate worse status), was 2.18 points lower in the morphine group, exceeding the minimum clinically important difference of 2 points. Participants with more severe dyspnea (mMRC grades 3 and 4) derived the greatest benefit. Hypercapnia was not a problem.

In a randomized crossover trial of 38 patients with chronic breathlessness mostly due to COPD, 20 mg of sustained-release morphine reduced breathlessness and improved sleep when compared with placebo, although it also increased constipation [98].

In another phase II dose increment study in 85 patients, approximately one-half with COPD, escalating doses of sustained-release morphine were administered, starting with 10 mg daily and increasing by 10 mg a day to a maximum of 30 mg daily [108]. For 70 percent of patients, the beneficial dose of sustained-release morphine was 10 mg daily, and the benefit at any dose was sustained for three months in 53 percent.

Management of anxiety — Anxiety can contribute to dyspnea, and treatment of anxiety can help to relieve it. For patients with dyspnea accompanied by anxiety, we use benzodiazepines as adjunctive therapy. There is no role for benzodiazepines as a routine management strategy for dyspnea in the absence of anxiety [99,109]. The management of anxiety in patients with cancer is discussed separately. (See "Management of psychiatric disorders in patients with cancer", section on 'Anxiety'.)

A systematic review found insufficient evidence for or against a benefit to benzodiazepines as monotherapy for relief of dyspnea, based on trials that compared benzodiazepines with placebo or morphine [109]. In support of a role for benzodiazepines, a small trial randomly assigned 63 patients with advanced cancer and severe dyspnea (mean score >8.5 on a scale from 1 to 10) to oral morphine (starting dose 3 mg) or oral midazolam (starting dose 2 mg) [110]. Doses were rapidly increased to an effective dose using a fast titration schedule over two hours, and patients were then followed daily for five days. Midazolam was superior to morphine in controlling both baseline and breakthrough dyspnea. The most common adverse event, which was not significantly more prevalent in either group, was mild somnolence that did not interfere with function.

Small trials and clinical experience support the addition of benzodiazepines to opioids, although confirmatory research is needed [111,112]. The available evidence suggests that benzodiazepines can be added to opiates without risk of respiratory depression [112].

Acupuncture — Acupuncture may be a reasonable option for patients who are interested in trying this modality for amelioration of dyspnea. Acupuncture has been examined as a potential therapy to reduce dyspnea in patients with COPD and cancer and has yielded mixed, but mostly positive results in trials [113-116]. Further studies are needed before acupuncture can be recommended as a routine intervention for dyspnea control in terminally ill patients. (See "Acupuncture".)

Chronic hypercapnia — Patients with hypercapnia due to inadequate ventilation may benefit from noninvasive ventilation (NIV). It may be used to manage an episode of acute, reversible respiratory failure in a patient who has an advanced serious and/or life-threatening illness and wishes to avoid invasive mechanical ventilation [117]. Clinical benefit has been most strongly demonstrated in acute respiratory acidosis in exacerbations of COPD, in hypoxemia from cardiogenic pulmonary edema, in hypoxemic respiratory failure in the immunocompromised host, and in patients with advanced neuromuscular disorders such as amyotrophic lateral sclerosis (ALS). (See "Continuous noninvasive ventilatory support for patients with respiratory muscle dysfunction" and 'Limited role for noninvasive ventilation' below and "Nocturnal ventilatory support in COPD" and "Noninvasive ventilation in adults with acute respiratory failure: Practical aspects of initiation".)

Dyspnea crisis — A "dyspnea crisis" is defined as a "sustained and severe resting breathing discomfort that occurs in patients with advanced, often life-limiting illness and overwhelms the patient and caregivers’ ability to achieve symptom relief" [118]. These episodes can occur in patients with advanced cancer as well as nonmalignant diseases such as COPD and heart failure [119]. Management involves anticipation of events and implementation of an action plan that often includes medications and oxygen. Further details are provided elsewhere. (See "Palliative care for adults with nonmalignant chronic lung disease", section on 'Anticipating and managing "dyspnea crisis"'.)

Pre-terminal dyspnea

General approach — Opioids are commonly used for dyspnea in the last days of life. The use of a short-acting oral/sublingual opioids is preferred. Information on managing dyspnea in pre-terminal patients is provided separately. (See "Palliative care: The last hours and days of life" and "Palliative care: The last hours and days of life", section on 'Pain'.)

Palliative sedation — Among patients at the end of life, dyspnea sometimes causes severe distress that cannot be relieved with standard measures. In such cases, the use of palliative sedation proportionate to relief of distress, including doses titrated to achieve unconsciousness if necessary, is an accepted strategy. Palliative sedation refers to use of medications, such as opioids and benzodiazepines (table 6), to reduce a patient’s awareness of refractory symptoms by decreasing their level of consciousness. Refractory symptoms are those that have been assessed and treated by an expert interdisciplinary team and have not responded to conventional symptom management. This subject is discussed in detail elsewhere. (See "Palliative sedation".)

Limited role for noninvasive ventilation — NIV refers to positive pressure ventilation that is delivered through a noninvasive interface (nasal mask, facemask, or nasal plugs), rather than an invasive interface (endotracheal tube, tracheostomy). The use of NIV in the palliative setting remains a controversial area of clinical practice [120,121]. Nevertheless, 2017 guidelines from the European Respiratory Society (ERS) and the American Thoracic Society (ATS) support offering NIV to dyspneic patients for palliation in the setting of terminal cancer or other terminal conditions [122].

NIV may be considered as a palliative measure in dying patients who have severe dyspnea and have decided to forego life-prolonging therapies and focus only on comfort measures [122-124]. In this setting, NIV can be used with the intent of reducing the work of breathing, easing dyspnea, and helping to maintain wakefulness by reducing the amount of opioids needed to maintain comfort. NIV can also be used to prolong life to meet a patient’s short-term goals (eg, allowing time for the family to visit) while providing for a comfortable death [125]. If a trial of NIV is being considered, it is essential to clearly establish in advance the goals of the intervention, a timeframe for reevaluation, and markers of success or lack thereof. Patients and families should understand that the dying process may be prolonged by the use of NIV [120].

There is much variability in practice and attitudes regarding the use of NIV at the end of life [126]. Limited data are available about the use of NIV to alleviate dyspnea in this setting, its tolerability, and whether or not it is opioid-sparing [68,127-130].

NIV can be delivered using a standard ventilator or a portable ventilator. NIV is somewhat noisy and can be uncomfortable and frightening. Patient tolerance of the face mask is crucial to the success of NIV. Decreased mental status may be considered a contraindication to NIV because of the risk of aspiration. The cost and experience needed to implement NIV generally limit its initiation to the hospital setting, with some exceptions. While NIV can be used at home or at a hospice facility, it requires adequate nursing, respiratory therapy, and clinician support [120]. (See "Noninvasive ventilation in adults with acute respiratory failure: Practical aspects of initiation".)

Treatments with uncertain benefit

Cannabis – Limited data are available regarding the use of cannabis for palliative treatment of dyspnea. In a trial of 16 adults with advanced COPD, 35 mg of inhaled vaporized cannabis had no positive or negative effect on airway function, exertional breathlessness, or exercise endurance compared with placebo [131].

Nebulized opioids – The data are insufficient to justify use of any opioid by the inhaled route, although nebulized opioids have limited systemic absorption and may have fewer adverse effects than systemic administration.

Opioid receptors are found centrally (in respiratory control centers in the medulla oblongata) and peripherally (in airways and lung parenchyma [132]). Most hypotheses of opioid action for dyspnea (table 7) focus on central pathways. Nebulized opioids may act peripherally. However, trials have consistently demonstrated a lack of effect of nebulized morphine for dyspnea compared with placebo [94,101,133].

The only publication directly comparing nebulized versus systemic morphine for the treatment of dyspnea was too small to draw meaningful conclusions [134]. A study of hydromorphone (nebulized or systemic) versus placebo, adequately powered to detect a “medium-large” effect, found no difference between the three groups in dyspnea score 10 minutes post-treatment [135]. Nebulized fentanyl, which is lipophilic and thus more readily absorbed than morphine or hydromorphone, was superior to placebo for relief in dyspnea in patients with COPD in one small randomized trial [136].

Helium/oxygen – The lower density of helium/oxygen combinations (relative to nitrogen/oxygen) promotes laminar flow and enables greater alveolar ventilation at a given inspiratory pressure, thus diminishing the work of breathing. Helium/oxygen (HEO2, heliox) is therefore a potentially attractive alternative for patients with dyspnea from partial airway obstruction, impaired ability to generate inspiratory pressure, or both. (See "Physiology and clinical use of heliox".)

Studies in non-hypoxemic, exercising patients with either lung cancer [137] or COPD [138-140] have found that heliox is superior to room air for exercise tolerance and dyspnea. Due to the cost, uneven availability, and lack of experience with this therapy, the appropriate place for heliox therapy in the symptomatic management of dyspnea remains unclear.

Promethazine – While small studies suggest a potential role for promethazine in the treatment of dyspnea and exercise tolerance (off-label), a class effect of phenothiazines for dyspnea has not been established [78,141,142].

RECOMMENDATIONS OF EXPERT GROUPS — Guidelines for the treatment of dyspnea in patients with advanced life threatening disease are available from the American Thoracic Society (ATS) (table 8) [73,74], American College of Chest Physicians (ACCP) [56], American College of Physicians (ACP) [55], Canadian Thoracic Society [75], National Comprehensive Cancer Network (NCCN), Cancer Care Ontario [76], and the American Society of Clinical Oncology (ASCO) [7]. All recommend the use of systemic opioids for pharmacologic management of severe dyspnea.

Guidelines from the ACCP, ACP, NCCN, and ASCO recommend the use of supplemental oxygen for patients who are hypoxemic at rest or during minimal activity [55,56]. Guidelines from the NCCN also support the use of temporary ventilatory support by noninvasive ventilation (NIV) if clinically indicated for a severe reversible condition, while the joint European Respiratory Society (ERS)/ATS guidelines suggest that NIV may be an appropriate component of palliative care for relief of dyspnea and, sometimes, for short-term prolongation of life [73,122].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Dyspnea" and "Society guideline links: Palliative care" and "Society guideline links: Palliative care for advanced lung disease".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)

Basics topic (see "Patient education: Medical care during advanced illness (The Basics)" and "Patient education: Advance directives (The Basics)")

SUMMARY AND RECOMMENDATIONS

Dyspnea is a subjective experience of breathing discomfort or breathlessness that often affects patients with advanced life-threatening illness of all types. (See 'Prevalence' above.)

The goals of a formal assessment of dyspnea in palliative care are to understand the intensity, distress, and functional impact of dyspnea; to diagnose potentially reversible contributing factors; and to monitor the response to interventions. (See 'Symptom assessment' above.)

Interventions that may be of benefit to all patients include relaxation techniques and psychosocial support, modification of activity levels, and use of a fan to blow cool air on the face. General steps to ameliorate the experience of dyspnea are listed in the table (table 4). (See 'General measures for all patients' above.)

For patients who are hypoxemic at rest or with minimal exertion (pulse oxygen saturation ≤88 percent), a therapeutic trial of supplemental oxygen is reasonable. Oxygen has not been shown to relieve dyspnea in non-hypoxemic hypoxemic patients. (See 'Hypoxemic patients' above and 'Non-hypoxemic patients' above.)

For patients receiving palliative care who have distressing dyspnea despite general measures noted above, we recommend systemic opioids (Grade 1B). Studies have not documented excess mortality associated with the use of opioids for dyspnea. However, careful monitoring and individual dose titration are vital to avoid respiratory depression and other side effects. (See 'Opioids' above.)

For patients with dyspnea accompanied by anxiety, we suggest the use of benzodiazepines as adjunctive therapy (Grade 2C). Benzodiazepines are not part of routine management of dyspnea. (See 'Management of anxiety' above.)

Bronchodilators, glucocorticoids, and diuretics may provide relief of dyspnea in certain clinical settings depending on the underlying condition. (See 'Treatment of underlying disease' above.)

The use of noninvasive ventilation (NIV) in dyspneic patients at the end of life remains controversial because it generally requires initiation in hospital and may be life-prolonging without necessarily improving quality of life. NIV may be a reasonable choice for patients who otherwise require sedating doses of opioids to control dyspnea but wish to be as awake as possible and for dying patients who wish to forestall death briefly for a specific goal. Before such treatment is initiated, the goals, timeframe for re-evaluation, criteria for continuation, and plan for eventual withdrawal of NIV should be discussed. (See 'Limited role for noninvasive ventilation' above.)

For patients at the end of life with severe dyspnea that cannot be relieved with standard measures, the use of palliative sedation proportionate to relief of distress, including doses titrated to achieve unconsciousness if necessary, is an accepted strategy. The indications for palliative sedation and its implementation are discussed separately. (See 'Palliative sedation' above and "Overview of managing common non-pain symptoms in palliative care", section on 'Palliative sedation'.)

ACKNOWLEDGMENT — The editorial staff at UpToDate acknowledge Joshua Shadd, MD, CCFP, now deceased, who contributed to an earlier version of this topic review.

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Topic 14238 Version 69.0

References

1 : Dyspnea. Mechanisms, assessment, and management: a consensus statement. American Thoracic Society.

2 : A comparison of symptom prevalence in far advanced cancer, AIDS, heart disease, chronic obstructive pulmonary disease and renal disease.

3 : Do the trajectories of dyspnea differ in prevalence and intensity by diagnosis at the end of life? A consecutive cohort study.

4 : Trajectory of performance status and symptom scores for patients with cancer during the last six months of life.

5 : Trajectory of Dyspnea and Respiratory Distress among Patients in the Last Month of Life.

6 : Chronic breathlessness in patients with idiopathic pulmonary fibrosis: a major challenge for caregivers.

7 : Management of Dyspnea in Advanced Cancer: ASCO Guideline.

8 : Measurement of breathlessness in advanced disease: a systematic review.

9 : A review of quality of care evaluation for the palliation of dyspnea.

10 : Measurement of dyspnoea in the clinical rather than the research setting.

11 : Management of Refractory Breathlessness: a Review for General Internists.

12 : Distinguishable types of dyspnea in patients with shortness of breath.

13 : Distinguishable types of dyspnea in patients with shortness of breath.

14 : Episodes of breathlessness: types and patterns - a qualitative study exploring experiences of patients with advanced diseases.

15 : How well do patients and providers agree on the severity of dyspnea?

16 : A multicenter study comparing two numerical versions of the Edmonton Symptom Assessment System in palliative care patients.

17 : The experience of breathlessness in lung cancer.

18 : Dyspnea and panic among patients with newly diagnosed non-small cell lung cancer.

19 : Death stories: acute exacerbations of chronic obstructive pulmonary disease.

20 : Requests for euthanasia: origin of suffering in ALS, heart failure, and cancer patients.

21 : The Memorial Symptom Assessment Scale: an instrument for the evaluation of symptom prevalence, characteristics and distress.

22 : Psychometric testing of a respiratory distress observation scale.

23 : Assessment of the psychometric properties of an English version of the cancer dyspnea scale in people with advanced lung cancer.

24 : Palliative care in chronic obstructive airways disease: a needs assessment.

25 : The experience of dyspnea in late-stage cancer. Patients' and nurses' perspectives.

26 : Experiences of breathlessness: a systematic review of the qualitative literature.

27 : Comparison of respiratory health-related quality of life in patients with intractable breathlessness due to advanced cancer or advanced COPD.

28 : Will to live in the terminally ill.

29 : A multicentre international study of sedation for uncontrolled symptoms in terminally ill patients.

30 : Palliative sedation in patients with advanced cancer followed at home: a systematic review.

31 : Lung cancer and dyspnea: the patient's perception.

32 : The patient's burden: physical and psychological effects of acute exacerbations of chronic bronchitis.

33 : Chronic obstructive pulmonary disease: a phenomenological study of patients' experiences.

34 : Characteristics and correlates of dyspnea in patients with advanced cancer.

35 : Characteristics and correlates of dyspnea in patients with advanced cancer.

36 : Dyspnea in the advanced cancer patient.

37 : Physiological changes and clinical correlations of dyspnea in cancer outpatients.

38 : The frequency and correlates of dyspnea in patients with advanced cancer.

39 : Factors correlated with dyspnea in advanced lung cancer patients: organic causes and what else?

40 : The management of chronic breathlessness in patients with advanced and terminal illness.

41 : Palliative care and management of troublesome symptoms for people with chronic obstructive pulmonary disease.

42 : Palliative care and management of troublesome symptoms for people with chronic obstructive pulmonary disease.

43 : Non-pharmacological interventions for breathlessness management in patients with lung cancer: a systematic review.

44 : Multicentre randomised controlled trial of nursing intervention for breathlessness in patients with lung cancer.

45 : Effectiveness of a hand-held fan for breathlessness: a randomised phase II trial.

46 : Does the use of a handheld fan improve chronic dyspnea? A randomized, controlled, crossover trial.

47 : The Effect of Using an Electric Fan on Dyspnea in Chinese Patients With Terminal Cancer.

48 : Non-pharmacological interventions for breathlessness in advanced stages of malignant and non-malignant diseases.

49 : High-dose corticosteroids for the management of dyspnea in patients with tumor obstruction of the upper airway.

50 : Bronchoscopic intervention obviates the need for continued mechanical ventilation in patients with airway obstruction and respiratory failure from inoperable non-small-cell lung cancer.

51 : Ethical issues in laryngology: tracheal stenting as palliative care.

52 : Squamous cell carcinoma of the cervix presenting as lymphangitic carcinomatosis: a case report and review of the literature.

53 : Dyspnea in palliative care: expanding the role of corticosteroids.

54 : Pulmonary lymphangitis carcinomatosis: systematic review and meta-analysis of case reports, 1970-2018.

55 : Evidence-based interventions to improve the palliative care of pain, dyspnea, and depression at the end of life: a clinical practice guideline from the American College of Physicians.

56 : American College of Chest Physicians consensus statement on the management of dyspnea in patients with advanced lung or heart disease.

57 : Does oxygen help dyspnea in patients with cancer?

58 : A randomized, double-blind, crossover trial of the effect of oxygen on dyspnea in patients with advanced cancer.

59 : Effects of oxygen on dyspnoea in hypoxaemic terminal-cancer patients.

60 : Symptomatic benefit of supplemental oxygen in hypoxemic patients with terminal cancer: the use of the N of 1 randomized controlled trial.

61 : Symptomatic benefit of supplemental oxygen in hypoxemic patients with chronic lung disease.

62 : Acute effects of hyperoxia on dyspnea in hypoxemia patients with chronic airway obstruction at rest.

63 : The effect of nasal flow on breathlessness in patients with chronic obstructive pulmonary disease.

64 : Does palliative home oxygen improve dyspnoea? A consecutive cohort study.

65 : Oxygen is nonbeneficial for most patients who are near death.

66 : Evidence for improving palliative care at the end of life: a systematic review.

67 : Oxygen therapy for dyspnoea in adults.

68 : High-flow oxygen and bilevel positive airway pressure for persistent dyspnea in patients with advanced cancer: a phase II randomized trial.

69 : Use of Nasal High Flow in Stable COPD: Rationale and Physiology.

70 : Cold facial stimulation reduces breathlessness induced in normal subjects.

71 : Effect of palliative oxygen versus room air in relief of breathlessness in patients with refractory dyspnoea: a double-blind, randomised controlled trial.

72 : Update on the role of palliative oxygen.

73 : An official American Thoracic Society clinical policy statement: palliative care for patients with respiratory diseases and critical illnesses.

74 : An official American Thoracic Society statement: update on the mechanisms, assessment, and management of dyspnea.

75 : Managing dyspnea in patients with advanced chronic obstructive pulmonary disease: a Canadian Thoracic Society clinical practice guideline.

76 : Managing dyspnea in patients with advanced chronic obstructive pulmonary disease: a Canadian Thoracic Society clinical practice guideline.

77 : Managing dyspnea in patients with advanced chronic obstructive pulmonary disease: a Canadian Thoracic Society clinical practice guideline.

78 : Effects of chronic administration of codeine and promethazine on breathlessness and exercise tolerance in patients with chronic airflow obstruction.

79 : Dihydrocodeine for breathlessness in "pink puffers".

80 : Effects of dihydrocodeine on chemosensitivity and exercise tolerance in patients with chronic heart failure.

81 : Breathlessness, alcohol, and opiates.

82 : Effects of dihydrocodeine, alcohol, and caffeine on breathlessness and exercise tolerance in patients with chronic obstructive lung disease and normal blood gases.

83 : Early and Integrated Palliative Care to Achieve a Home Death in Idiopathic Pulmonary Fibrosis.

84 : Buccal Hydromorphone Syrup for Managing Dyspnea in Idiopathic Pulmonary Fibrosis.

85 : Oral diamorphine: lack of effect on dyspnoea and exercise tolerance in the "pink puffer" syndrome.

86 : Oral transmucosal fentanyl citrate for dyspnea in terminally ill patients: an observational case series.

87 : Effects of prophylactic subcutaneous fentanyl on exercise-induced breakthrough dyspnea in cancer patients: a preliminary double-blind, randomized, controlled trial.

88 : A randomized crossover clinical trial to evaluate the efficacy of oral transmucosal fentanyl citrate in the treatment of dyspnea on exertion in patients with advanced cancer.

89 : Intravenous Fentanyl for Dyspnea at the End of Life: Lessons for Future Research in Dyspnea.

90 : Fentanyl treatment for end-of-life dyspnoea relief in advanced cancer patients.

91 : Incident opioid drug use and adverse respiratory outcomes among older adults with COPD.

92 : Effect of hydromorphone on ventilation in palliative care patients with dyspnea.

93 : Opioids prescription for symptoms relief and the impact on respiratory function: updated evidence.

94 : The etiology and management of intractable breathlessness in patients with advanced cancer: a systematic review of pharmacological therapy.

95 : Pathophysiologies of dyspnea explained: why might opioids relieve dyspnea and not hasten death?

96 : Blinded Patient Preference for Morphine Compared to Placebo in the Setting of Chronic Refractory Breathlessness--An Exploratory Study.

97 : Interventions for alleviating cancer-related dyspnea: a systematic review.

98 : Randomised, double blind, placebo controlled crossover trial of sustained release morphine for the management of refractory dyspnoea.

99 : The management of dyspnea in cancer patients: a systematic review.

100 : Patient-Controlled Therapy of Breathlessness in Palliative Care: A New Therapeutic Concept for Opioid Administration?

101 : Opioids for the palliation of refractory breathlessness in adults with advanced disease and terminal illness.

102 : One evidence base; three stories: do opioids relieve chronic breathlessness?

103 : Effects of Oral Morphine on Dyspnea in Patients with Cancer: Response Rate, Predictive Factors, and Clinically Meaningful Change (CJLSG1101).

104 : Regular, sustained-release morphine for chronic breathlessness: a multicentre, double-blind, randomised, placebo-controlled trial.

105 : Controlled-Release Oxycodone vs. Placebo in the Treatment of Chronic Breathlessness-A Multisite Randomized Placebo Controlled Trial.

106 : Effect of Sustained-Release Morphine for Refractory Breathlessness in Chronic Obstructive Pulmonary Disease on Health Status: A Randomized Clinical Trial.

107 : Opioids for breathlessness: a narrative review.

108 : Once-daily opioids for chronic dyspnea: a dose increment and pharmacovigilance study.

109 : Benzodiazepines for the relief of breathlessness in advanced malignant and non-malignant diseases in adults.

110 : Morphine versus midazolam as upfront therapy to control dyspnea perception in cancer patients while its underlying cause is sought or treated.

111 : Midazolam as adjunct therapy to morphine in the alleviation of severe dyspnea perception in patients with advanced cancer.

112 : Dyspnoea associated with anxiety--symptomatic therapy with opioids in combination with lorazepam and its effect on ventilation in palliative care patients.

113 : Can a standardized acupuncture technique palliate disabling breathlessness: a single-blind, placebo-controlled crossover study.

114 : A randomized, placebo-controlled trial of acupuncture in patients with chronic obstructive pulmonary disease (COPD): the COPD-acupuncture trial (CAT).

115 : A randomised study comparing the effectiveness of acupuncture or morphine versus the combination for the relief of dyspnoea in patients with advanced non-small cell lung cancer and mesothelioma.

116 : Acupuncture for Breathlessness in Advanced Diseases: A Systematic Review and Meta-analysis.

117 : Noninvasive mechanical ventilation in patients having declined tracheal intubation.

118 : An official American Thoracic Society workshop report: assessment and palliative management of dyspnea crisis.

119 : Characterizing episodic breathlessness in patients with advanced disease.

120 : Practical aspects of using noninvasive positive pressure ventilation at the end of life #231.

121 : Palliative use of noninvasive ventilation: navigating murky waters.

122 : Official ERS/ATS clinical practice guidelines: noninvasive ventilation for acute respiratory failure.

123 : Using noninvasive ventilation at the end of life #230.

124 : Noninvasive ventilation as a palliative measure.

125 : Palliative ventilatory support: use of noninvasive positive pressure ventilation in terminal respiratory insufficiency.

126 : Noninvasive ventilation for acute respiratory failure near the end of life.

127 : Noninvasive ventilation for patients near the end of life: what do we know and what do we need to know?

128 : Palliative use of non-invasive ventilation in end-of-life patients with solid tumours: a randomised feasibility trial.

129 : Outcomes of patients with do-not-intubate orders treated with noninvasive ventilation.

130 : Noninvasive positive pressure ventilation reverses acute respiratory failure in select "do-not-intubate" patients.

131 : Effect of Vaporized Cannabis on Exertional Breathlessness and Exercise Endurance in Advanced Chronic Obstructive Pulmonary Disease. A Randomized Controlled Trial.

132 : Lung opioid receptors: pharmacology and possible target for nebulized morphine in dyspnea.

133 : The role of nebulised drugs in palliating respiratory symptoms from mlaignant disease

134 : Nebulized versus subcutaneous morphine for patients with cancer dyspnea: a preliminary study.

135 : Relief of incident dyspnea in palliative cancer patients: a pilot, randomized, controlled trial comparing nebulized hydromorphone, systemic hydromorphone, and nebulized saline.

136 : Inhaled fentanyl citrate improves exercise endurance during high-intensity constant work rate cycle exercise in chronic obstructive pulmonary disease.

137 : A double-blind, randomised, controlled Phase II trial of Heliox28 gas mixture in lung cancer patients with dyspnoea on exertion.

138 : The effect of helium and oxygen on exercise performance in chronic obstructive pulmonary disease: a randomized crossover trial.

139 : Heliox improves oxygen delivery and utilization during dynamic exercise in patients with chronic obstructive pulmonary disease.

140 : Expiratory flow-limitation and heliox breathing in resting and exercising COPD patients.

141 : Drug treatment of breathlessness: contrasting effects of diazepam and promethazine in pink puffers.

142 : Effect of 30 mg of morphine alone or with promethazine or prochlorperazine on the exercise capacity of patients with COPD.