Dyspnea in Palliative and End-of-Life Care

How to Cite This Chapter: Pereira J, Panju M, Srivaratharajah K, Merali Z, Krajnik M, Sobański P. Dyspnea in Palliative and End-of-Life Care. McMaster Textbook of Internal Medicine. Kraków: Medycyna Praktyczna. https://empendium.com/mcmtextbook/chapter/B31.II.22.19. Accessed July 06, 2022.
Last Updated: February 2, 2022
Last Reviewed: February 2, 2022
Chapter Information

Also see Dyspnea: General Considerations.

Palliative Care PrinciplesTop

The management of dyspnea resulting from serious illnesses, such as cancer and advanced heart, lung, and/or neurologic illnesses, requires application of the principles of a palliative care approach. This includes:

1) Initiating a palliative care approach early in the illness and not just in the terminal or end-of-life (EOL) phase.

 2) Optimizing management of the underlying disease.

 3) Initiating timely advanced care planning that recognizes the reality of the illness trajectory and identifies patients’ values and wishes for EOL care and quality-of-life priorities, regardless of prognosis (be it months, years, or just weeks or days).

 4) Periodic goals-of-care discussions at key illness transition points to ensure that the care plans align with the illness realities and trajectory and with EOL wishes and preferences.

 5) Identifying and managing other symptoms and psychological, spiritual, and/or religious needs that affect the person’s quality of life.

 6) Establishing a trusting therapeutic rapport with the patient.

7) Using interprofessional and multidisciplinary care that leverages the expertise of various professions and specialty areas.

 8) Ensuring inclusion throughout the illness journey of care providers, especially those needed at end of life, such as the patient’s primary care providers.

 9) Supporting family and loved ones.

10) Engaging in EOL care preparations when the patient enters the terminal or EOL phase. The latter includes timely discussions related to resuscitation status to avoid the burdens and futility of cardiopulmonary resuscitation when death is expected as well as inappropriate intensive care admissions for EOL care.

Symptomatic TreatmentTop

 Management usually requires a combination of nonpharmacologic and pharmacologic measures.

1. Nonpharmacologic treatment involves ≥1 of the following: Pulmonary rehabilitation in the earlier phases of the illness in the case of advanced lung diseases; providing an optimal environment (appropriate room ventilation and humidity), inducing air movement across the perioral area with a fan (to activate receptors that reduce the sensation of breathlessness), education (teaching how to breathe and expectorate effectively), appropriate body positioning (eg, a sitting position in pulmonary edema), relaxation techniques, and supportive counseling.

2. Pharmacotherapy in palliative care:

1) Oxygen therapy: Used to relieve dyspnea in patients with hypoxemia. In patients without hypoxemia, the beneficial effects of oxygen are similar to administering air.

Oxygen delivery methods and oxygen volumes in the EOL phase need to be adjusted not only to the oxygen needs of patients as measured by oxygen saturation levels or blood gas levels, but also by the patients’ own subjective sense of breathlessness. Some patients, for example, may experience reduction or alleviation of dyspnea even if oxygen saturation levels may be suboptimal, while others may find noninvasive methods such as continuous or bilevel positive airway pressure delivery methods (CPAP or BiPAP), or even rebreathing masks and air entrainment masks, intolerable.

To support care in the home when patients have high oxygen needs, strategies could include oxygen conserving devices (oxygen delivered from the tank only during inspiration) and even high-flow nasal cannula (HFNC).

2) Opioids: Oral or parenteral agents may be very useful in patients who continue to experience moderate to severe dyspnea despite optimization of the underlying disease and increasing oxygen needs. Principles of using opioids: Table 14.1-1. Opioids provide significant relief of dyspnea through a number of mechanisms, and there is a growing body of evidence that when used appropriately, they are very effective and safe. Their use does not need not be limited to the terminal phase of the illness only.

3) Bronchodilators: Inhaled beta-agonists or anticholinergic agents improve dyspnea in most patients with chronic obstructive pulmonary disease (COPD) or obstructive airway disease. Their role is limited in dyspnea related to other lung diseases, unless accompanied by airway constriction with wheezing.

4) Glucocorticoids: Useful as an adjunct in the management of dyspnea related to lymphangitis carcinomatosis, superior vena cava syndrome, bronchospasm (in asthma or COPD), and radiation-induced pneumonitis. They are generally used in the short term to help control a dyspnea crisis related to one of these illnesses. Tapering of the dose is required if the patient has taken it for >5 to 7 days. Dexamethasone at a starting dose of 4 mg or 8 mg a day is usually the preferred systemic opioid in the palliative care context.

5) Benzodiazepines: Benzodiazepines are only useful for the palliation of dyspnea if the dyspnea is induced or aggravated by panic attacks or if it causes significant, sustained anxiety. Otherwise, they do not have an inherent special dyspnea-reducing role. Benzodiazepines, specifically midazolam, can also be used to administer palliative sedation when the patient is terminal and the dyspnea is intractable and responding to all other modalities. Principles of using benzodiazepines: Table 14.1-2.

Note that dyspnea is a subjective symptom, best expressed and described by the patient. While most patients with advanced disease who have tachypnoea and/or are using accessory breathing muscles experience dyspnea, there are some who may have these signs but not be experiencing dyspnea. Others, including patients with advanced cancer with no lung involvement, may look comfortable yet be experiencing significant breathlessness. Therefore, in the context of palliation, clinicians should take into consideration the patient’s expression of dyspnea whenever possible.

Simple numerical rating scales (0 to 10) are very useful to screen for symptoms and to monitor responses to treatments in the palliative care setting. One of them is the Edmonton Symptom Assessment System (ESAS, revised version), which asks about 9 regularly experienced symptoms in patients with serious illnesses (including dyspnea).

At the very end of life, in the terminal phase, there is no need to automatically initiate opioid therapy or a midazolam infusion simply on the basis of the presence of tachypnea, reduced oxygen saturation levels, or both, unless a patient reports dyspnea or shows signs of potentially being dyspneic with labored breathing as a result of an acute complication such as pneumonia or pulmonary embolism.

Special ConsiderationsTop

Special Clinical Considerations in Palliative Care

 

1. Upper airway secretions in the terminal phase (the term “death rattle” has been used in the past but is generally now avoided). These result from accumulation of normal airway secretions, such as saliva, in the laryngopharynx when patients who are dying (in the final terminal stage of life) are no longer able to swallow.

In most cases, upper airway secretion accumulation is mild to moderate and usually managed simply with repositioning (turning to the side) and reassurances (explaining to family that they are not distressing to patients and will not result in suffocation). If this is severe and distressing to patients and family members, anticholinergic agents such as scopolamine or glycopyrrolate may be used as needed (scopolamine 0.4 mg every 4 hours as needed, subcutaneous or transdermal [1-mg patch applied every 72 hours for mild symptoms]; glycopyrrolate, usually subcutaneous, at a dose 0.2 or 0.4 mg every 4 hours as needed). Scopolamine is more sedating than glycopyrrolate.

Airway suctioning, especially deeper suctioning, is generally not beneficial and discouraged (an exception being superficial suctioning in the case of severe secretions related to terminal amyotrophic lateral sclerosis). Also see Last Days and Hours.

Upper airway secretions, a relatively common EOL phenomenon, should be differentiated from lower airway sounds caused by complications such as pulmonary edema or acute respiratory distress syndrome (which sometimes occurs spontaneously at the very end of life). These are managed differently (eg, using IV or subcutaneous furosemide).

2. Intractable dyspnea when death is imminent (last hours or days of life) causing severe distress and suffering. In a relatively small proportion of patients with advanced cancer or noncancerous diseases (~1% to 5%), dyspnea at the very end of life does not respond to the usual treatments described above and in the accompanying table including adequately titrated opioid doses, high-flow oxygen, and the addition of adjuvants such as methotrimeprazine (INN levomepromazine). If death is imminent (last hours or days), palliative sedation is indicated in these situations. Palliative sedation refers to the use of a strong sedative, usually in the form of a midazolam, by continuous subcutaneous or IV infusion. It is usually started with a bolus of midazolam (1 mg or 2.5 mg) subcutaneously or IV, followed by an infusion at a starting dose of midazolam 0.5 mg to 2 mg per hour (IV or subcutaneously). Doses can be titrated in increments of 0.5 mg per hour to 1 mg per hour every 30 minutes to 60 minutes until comfort is achieved. For many patients comfort is achieved with lower doses and without requiring deep sedation. For others, it is only possible with deeper sedation and sometimes higher doses. The goal is to achieve comfort at the lowest dose and lightest level of sedation possible. Evidence shows that, when used proportionally and appropriately, this is appropriate and does not invariably shorten life.

TablesTop

Table 14.1-1. Use of opioids for the management of dyspnea in palliative and end-of-life care

Clinical setting

Dosagea

General principles

Opioids are very useful in the context of moderate to severe dyspnea related to advanced disease that is not controlled despite optimizing treatments and oxygen. They are generally safe if started at appropriate doses and titrated appropriately. Their usefulness and safety have been demonstrated in studies for patients with dyspnea related to cancer or noncancerous diseases (such as advanced heart, lung, renal, and neurologic diseases).

Morphine is a good and useful agent to start with when a strong opioid is required. Claims that hydromorphone is more effective than morphine and has a better adverse effect profile are not supported by evidence. The pharmacokinetics and pharmacodynamics of these 2 are very similar; some of their metabolites are active (can cause opioid toxicity) and are renally eliminated (therefore they can accumulate with significant renal impairment).

The oral route is the preferred route in most cases as it is the most practical, especially for nonhospitalized patients. Parenteral routes (SC or IV) are reserved for patients who are not able to swallow or experiencing a dyspnea (or pain) crisis and need immediate onset of action.

Starting doses of opioids are smaller and the intervals between doses are longer when patients have advanced frailty or age, or heart, lung, renal, and/or neurologic diseases. Dose titrations are also more gradual (over many days rather than daily or every few days).

The more common adverse effects of a regular opioid regimen are constipation, nausea, and somnolence. Constipation does not resolve spontaneously, so a laxative (senna, lactulose, or polyethylene glycol) is required as long as the patient is on an opioid. Nausea, if present, usually resolves after a few days. Upon starting the opioid, an as-needed dose of metoclopramide or domperidone can be ordered (eg, 10 mg tid PO as needed). Somnolence also usually resolves after a few days. Encourage patients to rest and drink fluids. If constipation is very severe, reduction of the opioid dose may be needed.

Provide education on opioids to patients and families, including the adverse effects to expect. Advise them not to drive or operate any machinery while opioids are being started, increased, or titrated (this can be started once there are no adverse effects).

Titration of the dose is often required initially to identify the optimal dose for the patient. Initial titration can be done over several days or a few weeks, with the goal of achieving control of dyspnea (or pain) without intolerable adverse effects. Titration involves increasing the dose by ~25% to 50% (and sometimes even higher in the lower dose ranges). Titration is slower in patients who have frailty or advanced heart, lung, renal, and/or neurologic diseases.

Titration is very variable from patient to patient and depends on circumstances. Once the right dose is found for a patient, the opioid can be changed to a slow-release (controlled release) formulation, as this is more convenient for the patient (eg, no need to wake during the night to take a dose).

Dose increases over time are also sometimes required to maintain effect in the presence of progressing disease and development of tolerance to the opioid.

If parenteral opioids are required, the SC route is as effective as the IV route (and often more convenient). The SC route is about twice more equipotent than the oral route (divide the oral dose by 2 for the SC equivalent), and the IV route is ~2 to 3 times more equipotent than the oral route (divide the oral dose by 2 or 3) for the conversion.

Opioid neurotoxicity versus opioid overdose: Opioid neurotoxicity is an opioid adverse effect that has to be differentiated from an overdose (or narcotization). Their clinical presentations and management are different. Opioid neurotoxicity presents clinically with ≥1 of the following: myoclonus, cognitive impairment, hallucinations, agitation or motor retardation, somnolence, hyperalgesia or allodynia. The management is relatively straightforward and consists of switching to a different opioid (eg, morphine to hydromorphone, or vice versa, if dyspnea or pain are not well controlled and if the toxicity is moderate to severe) or reducing the opioid (if pain or dyspnea are well controlled and the toxicity is mild). An opioid overdose presents with the classical triad of respiratory depression, miosis, and reduced level of consciousness. If severe and life threatening, administer naloxone and withhold the opioid temporarily. Once resolved, restart the opioid to avoid withdrawal with an exacerbation of pain or dyspnea but at a lower dose than previously (~30% to 50% lower and then titrate to effect again). If mild, one may simply withhold the next opioid doses and restart at a lower dose (~20% to 30% lower).

Respiratory depression is exceptionally rare when these principles of opioid use are adhered to (namely, appropriate starting doses and appropriate titration).

Screen for opioid use disorder or risk of opioid diversion prior to initiating an opioid. The Opioid Risk Tool is a simple tool to help with screening. If positive or if there are concerns about possible opioid diversion, implement strategies to mitigate. These include a contract (in which the patient will have a single prescriber, will not misplace opioid prescriptions, will not deviate from prescribed doses), do not prescribe breakthrough as-needed dosing, dispense in small amounts, and order periodic urine testing for drugs.

Opioid-naive patients with none of the following:

– Advanced heart, lung, renal or neurological diseases

– Very advanced age

– Advanced frailty  

The selection of the opioid type and the starting dose is similar as in the management of cancer pain. Morphine remains a good starting opioid in these situations.

Morphine: Start with morphine immediate release formulation 5 mg PO every 4 hours plus a breakthrough dose of 2.5 mg or 5 mg PO every 2 hours as needed. In some cases this starting dose relieves dyspnea. If not, the dose is titrated daily or every 2-3 days (proportionately to the level of dyspnea and how the patient is tolerating the opioid and the dose increases). When dose titration is needed, dose increases of up to 50% are usually well tolerated, but slower or smaller dose titrations may be needed in more frail patients or if the patient is experiencing somnolence.

Once the optimal dose is achieved (usually after several days or a 1-2-week titration) when dyspnea or pain are well controlled and there are no significant adverse effects, the opioid can be switched to a long-acting formulation (slow-release formulation). The total daily dose of the slow-acting form should be equivalent or as close as possible to the daily opioid dose of the immediate-release formulation used.

Breakthrough doses are usually one-sixth to one-tenth of the regular total daily dose. Patients should be instructed to contact the prescribing clinician for reassessment and probable dose adjustment if >3 breakthrough doses have been used within 24 hours.

If the patient is truly allergic to morphine (which is rare), an alternative option could be hydromorphone or oxycodone. The principles of dosing are as described above. The starting dose of hydromorphone (immediate release) is 1 mg PO every 4 hours and breakthrough doses of 0.5 mg or 1 mg PO every 2 hours as needed.

Opioid-naive patients with ≥1 of the following conditions:

– Advanced heart, lung, renal, or neurologic diseases

– Very advanced age

– Advanced frailty 

Start the opioid at a much lower dose and titrate slower than where the patient has none of these underlying conditions.

Morphine: Start at 2.5 mg PO every 6 or 8 hours (or even 1 mg PO every 6 or 8 h).

Hydromorphone: Start at 0.2 mg PO (liquid form, if available, may be required to administer such low doses) or 0.5 mg PO every 6 or 8 hours.

Titrations occur slower than previously described when patients have these underlying conditions.

In the case of mild to moderate renal impairment, both morphine and hydromorphone may be used, but starting at much lower doses (eg, morphine 1 mg PO every 8 h or hydromorphone 0.2 mg of the liquid form PO every 8 h) and then gradually titrated. Monitor for opioid neurotoxicity. In the case of severe renal impairment, morphine and hydromorphone are not recommended, requiring the use of an alternative opioid such as fentanyl, buprenorphine, or methadone (as these do not have known neurotoxically active metabolites and are not dependent on renal elimination). Note that a small proportion of methadone itself is renally eliminated, so a small dose reduction in the setting of significant renal impairment is wise. Obtain assistance from a palliative care service when considering starting fentanyl infusion or methadone, as these are complex.

CNS, central nervous system; COPD, chronic obstructive pulmonary disease; IV, intravenous; PO, oral; SC, subcutaneous.

Table 14.1-2. Principles of using benzodiazepines in dyspnea accompanied by anxiety in patients receiving palliative care

Clinical setting

Dosagea

Dyspnea attacks causing anxiety or panic attacks causing dyspnea

Anxiolytic such as clonazepam 0.5 mg or 1 mg bid to tid PO, or lorazepam starting from 0.5 mg POb

a No strict dosage regimens exist. Dosage is determined on an individual basis. Consider dose reduction in elderly patients, patients with cachexia, frail patients, and in patients with severe pulmonary comorbidities (eg, COPD).

b In patients with coexistent COPD some authors recommend titration of the rescue dose starting from 0.25 mg.

COPD, chronic obstructive pulmonary disease; PO, oral.

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