Oxygen or air for palliation of breathlessness in advanced cancer

Breathlessness—difficult laboured or uncomfortable breathing, dyspnoea—is a complex experience of the body and the mind. It is the most common and distressing symptom of advanced lung cancer¹ and also frequently affects those whose cancer originates outside the thorax. Unlike cancer pain, breathlessness is difficult to treat successfully; a survey of patients treated by a community palliative care team demonstrated that its prevalence rose as death approached and that treatment was ineffective.² Although clinicians and patients alike tend to associate cancer with pain, breathlessness has a comparable incidence: in one recent study 85% patients with cancer experienced pain and 78% breathlessness in the last year of life.³

The neural pathways serving the sensation of breathlessness are poorly understood, but dyspnoea is not simply an abnormality of the heart and lungs; it is a multisystem disorder with many accompanying subtle neurohormonal abnormalities and alterations in skeletal and respiratory muscle structure and function. The higher centres responsible for thinking and feeling can strongly influence the severity of the symptom. The ‘nervous system is not hard-wired’:⁴ it is characterized by plasticity and, just as with pain, the experience of breathlessness is likely to be modified both by previous experience of the sensation and by pathways from different areas in the central nervous system. Patients with apparently similar disease can have breathlessness of widely different severity.

In this review we outline the causes of breathlessness in advanced cancer and the use of air and oxygen in management of the symptom.

AETIOLOGY AND ASSESSMENT OF BREATHLESSNESS IN ADVANCED CANCER

Breathlessness in advanced cancer is usually multifactorial but the different mechanisms may be divided into four main groups:

• An increase in the sense of respiratory drive or effort to overcome an imposed load (e.g. chronic obstructive pulmonary disease, COPD)

• An increase in the proportion of available respiratory muscle force required for breathing, observed in neuromuscular weakness in which respiratory motor output and the sense of effort increase (e.g. paraneoplastic syndromes)

• An increase in the patient's ventilatory requirements (e.g. anaemia, hypoxaemia⁵)

• The contribution of higher cortical experience to the sensation. Memory and previous experience as well as fear and anxiety will all modify the sensation of breathlessness.

The contributions of the higher centres can be modified to reduce breathlessness. People can learn relaxation and breathing techniques and consciously use them whenever they feel threatened by an episode of breathlessness. Anxiety is a potent trigger of dyspnoeic episodes in advanced cancer—a stigmatizing and still terrifying disease for many people.

The pathophysiology of dyspnoea in advanced cancer is manifold (Box 1). The mechanisms can be summarized as the direct effects of cancer in the thorax and respiratory tract, the systemic non-metastatic effects of the cancer, sequelae of cancer treatments and coexistent non-malignant disease. A patient with advanced malignancy will often have several of these, along with many psychological and social concerns triggering anxiety. The relative importance of each is not always clear in an individual, but the treatable cause must be identified.

Most studies of the causes of breathlessness are retrospective but from a prospective study of 100 ‘terminally ill’ patients Dudgeon and Lertzman⁶ concluded that severe respiratory muscle weakness contributed substantially to dyspnoea. Among the potentially treatable causes of breathlessness in this series were hypoxia (40%), anaemia (20%) and bronchospasm (52%). Patients had a ‘median of five different abnormalities that could have contributed to their shortness of breath.’ More work is needed to confirm these preliminary findings. As in all areas of medicine, accurate diagnosis of the causes of the symptom in the individual is the best guide to effective treatment. In someone who is at the very end of life and breathless at rest, advanced imaging techniques or even transfer to hospital for investigation may not be appropriate because the discomfort will outweigh possible benefits. The treatment can then be based only on history, examination and the choice of individual patients and their doctors.

Box 1 Causes of breathlessness in advanced cancer

Effect of cancer

Large/small airways obstruction with tumour

Lymphangitis carcinomatosa

Lung/segmental collapse

Pleural effusion

Pericardial/cardiac infiltration

Hepatomegaly

Infection

Rib/spinal metastasis

Systemic non-metastatic disease

Weakness/cachexia

Anaemia

Pain

Paraneoplastic syndromes

Pulmonary embolism

Secondary to treatment

Radiation pneumonitis/fibrosis

Chemotherapy fibrosis

Infection

Coexistent disease

COPD/asthma

Heart failure/dysrhythmia

Ischaemic heart disease

Motor neuron disease

The presence and severity of breathlessness can be assessed during history-taking or by more formal measurement such as visual analogue scales. It is important to distinguish breathlessness at rest from breathlessness during exercise. One method for doing this, validated in patients with advanced cancer is the shuttle-walking test.⁷ This is an externally paced exercise test during which the pace increases as the patient increases the distance walked. As it requires a 10 m clear corridor and a trained assessor, it is not a realistic option for every patient in most palliative care facilities. An additional benefit from an exercise test is greater confidence in the ability and capacity to walk, which increases motivation to take exercise. Families and healthcare professionals tend to encourage patients to rest, and their obvious alarm when the patient becomes breathless discourages further activity.⁷ The observation of a shuttle-walking test, performed by an experienced member of staff with the patient becoming comfortable again after exercise, can help relatives understand that breathlessness is not of itself harmful. The benefits of exercise are becoming clear from many areas of medicine, and the changes found in skeletal muscle of breathless patients resemble those in patients who are deconditioned. Appropriate exercise and activity should be encouraged, even in patients with advanced cancer.

PALLIATION OF BREATHLESSNESS

Palliative care focuses on maintaining and improving the quality of life for patients with advanced incurable disease (and their families). The four dimensions of palliative care, first discussed by Cicely Saunders in the 1960s, are physical, social, spiritual and psychological. All of these must be considered when one tries to improve the experience of people with breathlessness. Therefore, although in this article we concentrate on the use of oxygen, we must stress that it will only be part of excellent palliative care, never the complete answer. The patient, whole and entire, has relatives, friends, beliefs and previous experiences all of which must be integrated into the strategy. Oxygen treatment, in particular, requires the involvement of relatives or friends. As with all subjective symptoms the extent of the breathlessness should be established with the patient, and the aims of treatment should be discussed. In dying patients, pharmacological management with opioids and benzodiazepines should be the mainstay of care, although sometimes patients wish to keep using their oxygen as well.

THE USE OF OXYGEN AND AIR

Air

The simplest device we have for palliating breathlessness is the electric fan, and many patients will volunteer that they even gain relief from sitting in a draught or by an open window. Simple facial cooling in the area served by the 2nd and 3rd branches of the Vth cranial nerve can reduce the sensation of breathlessness.⁸ A fan has many advantages as a way of treating breathlessness: it can be portable or fixed, and the patient can use it whenever the need arises. This in turn will increase their sense of ‘mastery’ over the illness. In chronic disease, patients who have a sense of control have a lower incidence of depression and a greater ability to function. A fan is also a treatment which is simple, safe and cheap. The clinician recommending it needs to spend time describing and demonstrating its use, otherwise the usefulness of such an everyday object may be dismissed by the patient.

Oxygen

The following definitions are important when prescribing oxygen therapy.⁹ Short-burst oxygen therapy (intermittent oxygen therapy) is the intermittent use of oxygen for the relief of breathlessness, before exercise or for recovery after exercise. Ambulatory oxygen therapy is the provision of oxygen therapy during exercise and activities of daily living. Ambulatory oxygen equipment is any oxygen equipment that can be carried by a patient during the activities of daily living; usually it weighs less than 4.5 kg.

There is little published evidence on use of oxygen for breathlessness in advanced cancer; most work has been done in patients with COPD and did not use quality of life or the severity of breathlessness as endpoints. In addition, many patients with COPD have a different pattern of breathlessness. They tend to experience a slow descent into breathlessness, and are older by the time they have severe disease. Over the years they become familiar with doctors, nurses, hospitals and oxygen equipment. Patients with cancer may experience a rapid onset of breathlessness from previous good health, at a young age. Some have the double fear that death is imminent and that they will die gasping for breath. In a different category are the patients with lung cancer who have lived with COPD for many years. In every case knowledge of the previous experience of the patient and the history of the onset of breathlessness is crucial to management of the symptom.

The recommendations here are based on reports from the Royal College of Physicians (Domiciliary Oxygen Therapy Services⁹) and a working group of the scientific committee of the Association of Palliative Medicine (Booth S, Wade R, Johnson M, Kite S, Swanwick M, Anderson H, unpublished). Long-term oxygen therapy—i.e. the provision of oxygen at home, to be used long term for at least 15 hours a day—will not be considered here. It is not prescribed primarily to relieve symptoms but to reduce morbidity and mortality in patients with COPD and chronic hypoxaemia (defined as PaO₂ <7.3 Kpa, one-second forced expiratory volume <1.5 L, forced vital capacity <2 L and cor pulmonale with or without hypercapnia).

Breathlessness at rest

Patients with breathlessness at rest are very ill. In one study of 38 cancer patients who were breathless at rest¹⁰ rather than on minimal exertion, the median survival was only 19 days after entry into the trial. Several studies have indicated that oxygen supplementation gives relief in some patients whether or not they are hypoxic.^10,11,12,13 In these studies oxygen was used for only short periods (if specified, 15 minutes maximum). The mix of patients with and without hypoxaemia differed between the studies, and this may have affected the findings and the conclusions.

A point to note is that oxygen was not consistently beneficial, even in patients initially hypoxaemic on air or those who had previously reported benefit from oxygen. The use of air from a cylinder reduces breathlessness in some patients.

Some of the authors proposed that the reductions in breathlessness could be due to some other factor—the facial cooling produced by a stream of oxygen;¹⁰ or movement of the gases across nasal receptors.¹³ Relief of breathlessness was not necessarily related to the reversal of hypoxaemia.^10,11

The RCP report⁹ says that domiciliary oxygen therapy can be prescribed for palliation of dyspnoea in pulmonary malignancy and other terminal disease. It does not specify hypoxaemia, because not all breathless patients are hypoxaemic and not all hypoxaemic patients benefit from oxygen therapy. Evidence of hypoxaemia on pulse oximetry may strengthen the case for use of oxygen but is not sufficient by itself. Before oxygen is prescribed, simple but formal tests must show clear evidence of benefit, because the treatment is not without adverse effects. Testing may simply entail the use of a visual analogue scale before and after a test dose, or a more formal blinded ‘n of 1’ study.¹²

Breathlessness on exertion

The shuttle-walking test and other standardized assessment exercise tests are becoming routine in patients with COPD. The recommendation⁹ is that ambulatory oxygen therapy be prescribed if patients, breathing air, show ‘a fall in oxygen saturation of 4% or more below 90%, or [that] exercise endurance is increased by 10% measured by walking distance or breathlessness scores by breathing oxygen.’ In some patients there is no doubt that ambulatory oxygen therapy increases the capacity for exercise and it may also speed recovery from breathlessness after exercise.^9,14 Knower et al.¹⁵ have suggested that in certain patients—those with an oxygen saturation of 95% or less at rest—desaturation to below 90% is likely on walking and that such patients will benefit from oxygen therapy. The results need confirmation since they were derived from a retrospective study of case notes. A simple therapeutic trial of oxygen is at present the best predictor. Ambulatory oxygen therapy is indicated for patients who desaturate 4% or more below 90% on exercise when breathing air and/or if there is an improvement of 10% in walking distance or breathlessness scores when breathing oxygen: this can be diagnosed by formal exercise testing and oximetry. There is no medical reason why formal exercise testing should not be done in people with advanced cancer, though it seldom is. An alternative, since the focus of care is to improve and maintain quality of life at home, is to ask patients to keep a simple record of the frequency and severity of breathlessness at home over a period of time at first without and then with oxygen therapy.

Careful selection is necessary to identify those people who will benefit from oxygen therapy. Clearly a few get useful palliation from both short-burst and ambulatory oxygen while a larger number do not. Those who do benefit from oxygen should receive it; those who do not should not be burdened with its disadvantages. Individualized care is paramount.