Managing dyspnoea in cancer patients at end-of-life

Dyspnoea is a term used to define a subjective experience of difficult and uncomfortable breathing.¹ The American Thoracic Society defines breathlessness as: “...a subjective experience of breathing that consists of qualitatively distinct sensations that vary in intensity. The experience derives from multiple physiological, psychological, social and environmental factors, and may induce secondary physiological and behavioural responses”.² The terms dyspnoea and breathlessness may be used interchangeably. Dyspnoea is often described by patients as ‘frightening’, ‘painful’ or ‘hard work’.³

Dyspnoea is a prevalent symptom in many conditions such as advanced lung cancer, chronic obstructive pulmonary disease, end-stage heart failure and other advanced illnesses.⁴ It is one of the most common symptoms experienced by people approaching the end of life.⁵

Dyspnoea is not always related to the underlying disease severity. Measurements of lung function or oxygen saturation levels do not generally correlate with the sensation or with the severity of dyspnoea. Hypoxia per se does not mean dyspnoea. The level of patient activity, anxiety level and past experiences all impact on a patient’s perception of dyspnoea. 

Dyspnoea is often a source of considerable distress for patients, as well as for their families. The presence of dyspnoea in patients is interpreted as a poor prognostic sign. Regardless of the diagnosis, both the prevalence and severity of dyspnoea tend to increase over time, particularly in the last six months of life. 

Pathophysiology

The pathophysiology of dyspnoea is multifactorial and not completely understood. The respiratory centre in the medulla and pons of the brainstem co-ordinates the activity of the diaphragm, intercostal muscles and accessory muscles. Normal breathing is maintained by regular rhythmical activity in the respiratory centre. This is stimulated by mechanical receptors (stretch receptors) and by hypoxia and high CO2 levels (detected by chemoreceptors). Dyspnoea is usually due to the distortion and stimulation of the mechanical receptors.

Assessment of dyspnoea

A comprehensive patient assessment is required in order to establish which intervention is likely to be the most effective. The underlying pathology involved and the patient’s experience should be assessed and documented. 

The gold standard for assessment of dyspnoea is based  on patient self-report. No reliable objective measures of dyspnoea exist. Assessment of a patient’s respiratory rate, arterial blood gas analysis or oxygen saturation monitoring do not correlate with the subjectice experience of dyspnoea. A patient may be hypoxaemic but not dyspnoeic, or alternatively, a patient may be dyspnoeic but not hypoxaemic. 

Underlying pathology involved

The following may assist in determining the primary pathology involved:

• Past medical history, including co-morbidities 
• Recent history and symptoms, including medications trialled to date and response to same
• Physical examination
• Previous radiological investigations
• Targeted radiological and biochemical investigations as appropriate for the individual patient, eg.
  – Full blood count to identify anaemia
  – CXR to demonstrate infection or pleural effusion
  – CT Pulmonary Angiogram (CTPA) if pulmonary embolism is suspected.

Patient’s experience of dyspnoea

An essential prerequisite to managing dyspnoea involves understanding what the symptom means to the patient (See Table 1). 

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Causes of dyspnoea

Multiple potential causes of dyspnoea exist and more than one cause may be present in each individual patient. For patients with cancer, it is important not to assume that the primary cause of dyspnoea is the underlying cancer (See Table 2). 

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Principles of management 

The initial aims of dyspnoea management are to reduce the level of dyspnoea and, if appropriate, to treat any underlying condition(s) that may be aggravating the symptom. Dyspnoea is best managed by using a systematic evidence-based approach with multidisciplinary input. 

An individualised approach should be adopted, as treatment effectiveness varies between patients. A tailored management plan also helps to avoid unnecessary hospitalisations and futile treatment as the patient approaches the end of life. Interventions for dyspnoea are influenced by prognosis, the severity of the dyspnoea, the individual patient’s needs and the goals of care.⁷

General measures

Explanation to the patient and family of the management plan is a critical step in the management of dyspnoea. Providing reassurance, along with building confidence, is vital in reducing the distress caused by the symptom.

Treatment of reversible causes and disease-specific treatments

Any reversible cause of dyspnoea should be identified and managed appropriately. All interventions should be considered in terms of the potential benefit versus the potential burden of the intervention. In making this decision it is important to consider the patient’s current condition and performance status and stage of disease. The patient’s and family’s wishes should also be taken into consideration (See Table 2). 

Symptomatic management, including pharmacological and non-pharmacological measures

Once dyspnoea becomes refractory, the goal of treatment becomes symptomatic relief. At this point an approach focused on managing the symptom rather than addressing and trying to reverse specific causes is more appropriate. Symptomatic management of dyspnoea requires a pharmacological and non-pharmacological approach and should involve the multidisciplinary team.

Pharmacological treatment options

Opioids

Opioids are recommended as the first-line therapy for the symptomatic control of dyspnoea.⁸ The mechanism of action of opioids in the management of dyspnoea is not fully understood. It is possible that opioids alter the perception of dyspnoea in a manner analogous to their alteration of the perception of pain. Opioids, when prescribed using standard dosing guidelines, are safe and effective in controlling dyspnoea. There is an ongoing perception that the use of opioids in the management of dyspnoea can result in respiratory depression.⁹ Opioids can relieve dyspnoea by lowering the respiratory rate without causing hypoxia or hypercapnia and without causing clinically significant respiratory depression.^5,10 An initial low dose (ie. Oramorph 2.5mg) may be prescribed on an as-needed basis, and if frequent doses are needed, a consideration should be given to switching to a twice-daily sustained release preparation and the dose escalated if well tolerated. A continuous subcutaneous infusion (CSCI, or syringe driver) may be considered if the oral route is not suitable.

Benzodiazepines 

The presence of dyspnoea can lead to a fear of suffocation and panic with hyperventilation in patients, which in turn can exacerbate the underlying dyspnoea. Anxiolytics are frequently co-prescribed along with opioids for patients with dyspnoea to help control their anxiety.¹¹

The evidence base for the use of benzodiazepines is not strong, therefore, benzodiazepines should not be used alone for the management of dyspnoea. Lorazepam 0.5mg-1mg sublingually prn or alprazolam 0.125-0.25mg po prn are appropriate starting doses of benzodiazepines for dyspnoea-related anxiety.¹¹

Benzodiazepines may also be given via CSCI if required. Occasionally, in a terminal situation, dyspnoea can be difficult to relieve completely, despite maximal therapy. In such cases sedation may be warranted. This should always be discussed with the family and, if appropriate, with the patient.

Anticholinergics

In the last days of life, oropharyngeal secretions can accumulate and cause noisy, gurgling respirations. These secretions are perceived as distressing for the patient and can often be a source of considerable distress for the family. Typically non-pharmacological interventions, such as re-positioning and decreasing parenteral fluids, are recommended as first-line steps. Anticholinergic medications (ie. hyoscine butylbromide 20-40mg subcutaneously or glycopyrronium 200-400mcg subcutaneously) remain the most commonly used treatments.¹¹ A lack of robust evidence exists, however, supporting their use.¹² A 0.9% sodium chloride via nebuliser may also help reduce tenacious secretions.

Corticosteroids

A trial of dexamethasone should be considered for dyspnoea if there is evidence of lymphangitis carcinomatosis or if there is pressure from the primary tumour or metastatic lesions on lung structures. In these circumstances corticosteroids are thought to reduce peritumoural oedema. For dyspnoea due to superior vena cava obstruction (SVCO) or upper airways obstruction, intravenous dexamethasone is recommended prior to the definitive therapy. A benefit to corticosteroids should be seen in four to seven days. If no benefit is observed, stop.

Bronchodilators

Even in the absence of obvious wheeze, there may be an element of reversible bronchoconstriction and a trial of salbutamol 2.5-5mg via nebuliser or ipratropium 250-500mcg via nebuliser may be of benefit.

Supplemental oxygen therapy 

The use of supplemental oxygen for patients with dyspnoea should be considered on an individualised patient basis. For some patients the potential adverse-effects, such as restriction of mobility, drying effect on the upper airways and impact on self-image may not be acceptable. 

It is difficult to predict which patients will derive benefit from supplemental oxygen therapy based on their oxygen saturation. If hypoxaemia is the cause of a patient’s dyspnoea, the introduction of oxygen may be of benefit.^13,14 Hypoxia, however, is not an absolute indication for oxygen use. A therapeutic trial may be warranted, but continued use is only justified if there is an acknowledged symptomatic benefit.

Non-pharmacological treatment options

Non-pharmacological options compliment pharmacological approaches in managing dyspnoea and such options should always be explored. The effectiveness of each approach will depend on the individual patient. Evidence supports the use of physiotherapy in the management of dyspnoea.¹⁵ Electrical muscle stimulation has also shown to be effective. Cognitive behavioural therapy may help manage fears associated with dyspnoea and complementary therapies such as acupuncture may be of benefit.¹⁶

Other strategies that may help to improve patient comfort include the use of a fan or an open window to create a draft.^17,18 Positioning of the patient in the bed is also important in optimising patient comfort. Adopting an upright position uses gravity to assist lung expansion and reduces pressure from the abdomen on the diaphragm, or positioning a patient high on one side may help a patient with excessive oropharyngeal secretions. 

Conclusion

As a symptom, dyspnoea can cause significant distress among cancer patients, families and healthcare professionals. The management of dyspnoea can be complex, but through the implementation of a comprehensive patient assessment, discussions related to ongoing goals of care, and various pharmacological and non-pharmacological interventions as appropriate, much can be done to relieve the symptom and its associated distress and to improve the quality of life of the patient and their family.

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References

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