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Breathlessness in advanced disease
PHYSICAL PROBLEMS
Breathlessness in advanced disease
Key points C
Breathlessness is common in chronic malignant and noncancer conditions
C
Therapy should initially be directed to reducing or eliminating the underlying cause
C
Non-drug approaches can be useful in the earlier stages of a progressive disease
C
Drugs for breathlessness and/or associated anxiety include opioids and benzodiazepines
C
Oxygen is a treatment for hypoxia not breathlessness and should be reserved for those who have significant desaturation
Sam Hjelmeland Ahmedzai
Abstract Breathlessness is the subjective experience of breathing discomfort, which arises as a distressing symptom in many diseases. It has several pathophysiological causes involving peripheral and central receptors and is modulated by cortical processing including emotions. Older people and patients with sarcopenia or cachexia are more susceptible to breathlessness on exertion. In the last hours of life, breathing can become laboured and noisy, owing to upper airway secretions. Most patients can be assessed by physical examination and simple investigations. Research has shown that careful use of opioids can reduce the sensation of breathlessness without compromising ventilatory control. Benzodiazepines can also help, probably by their anxiolytic and sedative actions. The combination of an opioid and a shortacting benzodiazepine can compromise respiratory function, but it is especially useful at the end of life as a combined subcutaneous or intravenous infusion. Oxygen is indicated if there is hypoxaemia, but increased airflow around the face (e.g. with a fan) can also help. Non-invasive ventilation can be necessary in severe cases, such as neuromuscular disease. Non-medical approaches, including pulmonary rehabilitation programmes, breathing training and relaxation, can also help.
increased effort of breathing (discomfort and tiredness) chest tightness (feeling of constriction). Patients whose episodes of shortness of breath have specific triggers try to avoid these. If the trigger is physical exertion, avoidance leads to inactivity, muscle deconditioning and a vicious cycle of increased dyspnoea and social isolation. Carers’ experience of looking after a patient with advanced disease and dyspnoea is also often negative, with high levels of anxiety and poor sleep that increase with the severity of the patient’s distress.
Keywords Breathlessness; dyspnoea; fan therapy; MRCP; opioids; oxygen; pulmonary rehabilitation
Epidemiology Breathlessness is common in many advanced illnesses, including chronic obstructive pulmonary disease (COPD), heart failure, neuromuscular diseases (e.g. motor neurone disease (MND)) and cancer.1 A British retrospective survey found that the terminal stage of COPD was associated with dyspnoea in 76% of patients, compared with 60% of a comparable lung cancer group. Cancers in which at least 50% of patients report breathlessness included lung, head and neck, genitourinary, breast and lymphoma. In many chronic conditions, dyspnoea becomes increasingly prevalent and refractory to treatment with disease progression. It is a poor prognostic factor in the palliative care setting.
Definition Breathlessness is defined as the subjective experience of breathing discomfort. It arises from physiological, psychological, social and environmental factors, and significantly affects daily activities. The term ‘dyspnoea’ is derived from the Greek for ‘bad breathing’ and in this article is used interchangeably with ‘breathlessness’.
Patient experience
Pathology and pathogenesis
Short-term breathlessness is an everyday experience, for example during voluntary hard exercise; however, when it is prolonged or occurs with little cause it can be frightening. In severe episodes, patients report fear and panic, feeling as if they are drowning or choking to death. Three elements contribute to the sensation of breathlessness: air hunger (an unpleasant sensation of the need to breathe, while being unable to increase ventilation)
The common pathophysiological changes that lead to breathlessness are described in Table 1. The main causes are: increased chemical or neurological drive to breathe (e.g. by stimulation of chemoreceptors) increased work of breathing (e.g. cardiac failure, pleural effusion, pulmonary fibrosis, ascites) decreased neuromuscular power (e.g. MND, sarcopenia, cachexia).
Sam Hjelmeland Ahmedzai BSc MB ChB FRCP is Emeritus Professor at the University of Sheffield, UK and NIHR Clinical Research Network National Specialty Lead for Supportive Care and Community-based Research. Competing interests: none declared.
Chemical and neurological drives The subjective sensation of breathlessness is thought to arise from a mismatch between incoming afferent impulses from sensory receptors and outgoing central motor signalling to the thoracic wall muscles and diaphragm.
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Please cite this article as: Ahmedzai SH, Breathlessness in advanced disease, Medicine, https://doi.org/10.1016/j.mpmed.2019.10.004
PHYSICAL PROBLEMS
The chemical drivers controlling normal respiration are the response to hypercapnia and hypoxia: hypercapnia exerts its effect via increased arterial partial pressure of carbon dioxide (PaCO2), detected primarily in the medullary chemoreceptors (and partly in the carotid bodies) hypoxia is detected in the carotid bodies.
and being socially disadvantaged are predictors of chronic breathlessness. Ageing is associated with anatomical and functional pulmonary and cardiac changes that predispose to dyspnoea. Obesity can contribute through mechanisms involving changes in lung volumes, oxygen cost of breathing and muscle deconditioning. Sarcopenia is the loss of skeletal muscle mass and is associated with normal ageing. Together with cachexia that arises from cancer, COPD or heart failure, this skeletal muscle wasting is a major contributor to breathlessness. A further mechanism implicated in heart failure is the interaction of skeletal muscle metaboreceptors and the control of cardiovascular loading through the autonomic system, described as the ‘metaboreflex’.
Central receptors: in healthy people, respiratory drive in response to hypercapnia is more sensitive than to hypoxia. However, hypercapnic drive can be blunted in patients with longstanding ventilatory failure, for example because of advanced COPD. Functional magnetic resonance imaging techniques have shed light on how the ventilatory drive is processed in conscious and subconscious parts of the brain. Air hunger is correlated with increased blood flow in the mesencephalic and hypothalamic areas, limbic and paralimbic areas (amygdala), motor areas and insula. Opioid receptors in some of these areas are probably involved in the sensation of dyspnoea, as well as in the regulation of normal breathing. There is evidence that endogenous opioids such as b-endorphin may be involved in the response to exercise in patients with COPD, as administration of naloxone causes an increase in exercise-related dyspnoea. Many opioid drugs initially cause a dose-related depression of ventilatory frequency and minute volume, which are not in themselves life-threatening. Thus, when opioids are carefully titrated against the level of dyspnoea, there is no significant ventilatory compromise even when the respiratory rate falls. The danger arises when opioids are given in excessive doses relative to the patient’s needs; there is then a risk that reduced ventilation, especially in the presence of a blunted hypercapnia ventilatory drive, will lead to acute hypercapnic respiratory failure.
Diagnosis Breathlessness is readily apparent when it is severe and the patient is panicking. However, it is important to distinguish
Causes of breathlessness in advanced disease System
Example of pathology
Example of disease
Pulmonary
Airflow obstruction COPD, asthma, cancer Reduced lung compliance Pulmonary fibrosis, emphysema, pulmonary consolidation Pleural effusion Cancer, heart failure Chest wall restriction Neuromuscular disease, mesothelioma Diaphragmatic restriction Ascites Ventilationeperfusion Pulmonary embolism mismatch Cachexia affecting the Cancer, COPD, heart respiratory musculature failure Cardiovascular Pump failure Acute or chronic heart failure Pericardial effusion Cancer Hypovolaemia Bleeding, too rapid drainage of ascites Systemic Anaemia Chronic disease, cancer Biological effects of Decrease in lung elasticity ageing Decrease in respiratory muscle strength Reduction in forced vital capacity and peak flow rate Increased air-trapping Deterioration in gas exchange Reduction in ventilatory response to hypoxia and hypercapnia Increased ventilatory response to exercise Effects of co-morbid disease (e.g. heart failure) Sarcopenia
Peripheral receptors: peripheral carotid body receptors respond primarily to decreased PaO2 but are also sensitive to decreased arterial pH, respiratory oscillations of PaCO2, increased blood temperature and chemical stimulants. Hypoxaemia results in the activation of peripheral chemoreceptors that send afferent impulses to the brainstem respiratory centres, leading to increased ventilatory motor drive. Other peripheral receptors that are important for the regulation of breathing and the pathogenesis of dyspnoea include the mechanical stretch receptors in the chest wall and diaphragm muscles, stretch receptors in the airways and J-receptors in the lung parenchyma. These send afferent signals to the brain about whether the respiratory pump and lungs are able to provide the necessary ventilation for the current level of activity. In COPD, there is hyperinflation and reduced compliance of the lungs, which contribute to the reduced exercise tolerance and dyspnoea on exertion. The J-receptors are stimulated by increased pulmonary pressure and fluid, for example in patients with pulmonary embolism or heart failure. Other factors: there is a clear relation between breathlessness and anxiety: for some patients, the sensory and affective dimensions, and triggers, of dyspnoea can as be important as the physical disease. Being older, female, living alone, being obese
Table 1
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PHYSICAL PROBLEMS
be treated with blood transfusion while taking care not to provoke heart failure, especially in older individuals with longstanding anaemia. It is also important to optimize the treatment of existing heart failure. Antibiotics help dyspnoea as well as cough in patients with respiratory infections, even in the advanced stages of disease. The patient’s fears should be addressed, with a clear explanation of both the causes of breathlessness and the treatment plan, taking into consideration for people who may be entering end-of-life care any advance care plan or declared preferences for acceptance or refusal of treatment. Figure 1 outlines how nonpharmacological methods, drug treatments and oxygen/airflow can be used as the disease progresses.
breathlessness from other types of abnormal breathing pattern, especially: tachypnoea associated with an increased metabolic rate as in fever, and air hunger associated with metabolic acidosis (e.g. diabetic ketosis) hyperventilation associated with panic disorders CheyneeStokes respiration (periods of increased and laboured breathing alternating with periods of hypopnoea or even apnoea). Severity of breathlessness can be rated using a recordable scale. Most patients with normal cognitive function can describe the symptom verbally (mild, moderate, severe) or numerically. Visual analogue scales (0e100 mm) are useful in research but not in clinical settings. Problems arise in rating the degree of breathlessness in people with cognitive impairment: the clinician should use observations of the patient’s activity, facial expressions and other behavioural changes. The patient’s regular carers can often give a proxy estimation of the distress. In making a differential diagnosis, consider particularly the relationship of dyspnoea to exercise and position (e.g. orthopnoea with heart failure), and the occurrence of paroxysmal dyspnoea with palpitations and fainting (e.g. with pulmonary embolism). However, physical examination and investigations are usually needed to make a definitive diagnosis. Important features to look for during the examination include pallor, central cyanosis, signs of heart failure, bronchospasm, pulmonary consolidation and pleural effusion. In dyspnoea arising for the first time, it is helpful to request investigations that will identify pathological (and treatable) causes. A list of useful tests, some of which can also be used for monitoring progress, is given in Table 2. A rapid bedside test, often helpful clinically in community, hospice or care home settings, is pulse oximetry. The doctor should be aware of when oximetry is less reliable, for example when the patient is in shock or has peripheral circulatory failure, when it may be appropriate to use a corroborative test of arterial blood gases. When a patient presents to the emergency department with acute severe breathlessness, there is seldom time to perform all these investigations before embarking on corrective or symptomatic (palliative) treatments. The minimum tests in this situation are: blood pressure pulse oximetry/arterial blood gases electrocardiogram chest X-ray. If pulmonary embolism is suspected, for example if there is recent painful leg swelling, urgent computed tomographic pulmonary angiography (CTePA) and peripheral blood flow (Doppler) tests are justified.
Urgent treatment In cancer patients, the development of pulmonary, pleural or pericardial disease causing acute dyspnoea can be a medical emergency, and palliative oncological measures should be instituted with minimal delay. Even in patients with a poor performance status, thoracocentesis, a single fraction of radiotherapy or the placement of an airway stent can provide rapid relief. Patients with cancer and upper airways obstruction arising from a central tracheobronchial mass or with lymphangitis carcinomatosa can be treated with high-dose corticosteroid (dexamethasone 8e16 mg/day (unlicensed use)) while awaiting an oncology opinion or a palliative procedure such as placement of an airway stent. The dosage of corticosteroid should be tapered after 5e7 days. Other causes of severe acute dyspnoea, including pulmonary embolism, pneumothorax, aspiration pneumonia and cardiac failure, should be treated accordingly, taking into consideration the patient’s performance status, disease trajectory and the burden and/or benefit of treatment options. Oxygen therapy Patients who have acute significant (<90%) oxygen desaturation at rest or on exertion should be offered oxygen, preferably via nasal cannulae unless higher flow rates (>6 litres/minute) are required. There is little evidence to support supplementary oxygen in patients with saturations >90% unless they are anaemic.2 Caution with oxygen is required in patients with COPD as they can be at risk of hypercapnic respiratory failure. Patients with chronic breathlessness may be discharged home with oxygen. However, unless the patient is hypoxaemic, the benefit of oxygen in improving feelings of breathlessness has not been clearly demonstrated: studies comparing cylinder air and oxygen have shown similar small effects, but with increased adverse effects with oxygen. In inpatient settings, with severe dyspnoea associated with cancer or COPD, a mixture of helium and oxygen (HelioxÒ) can give a quicker and greater relief of dyspnoea than oxygen alone, owing to the improved flow characteristics of helium gas. Part of the benefit of oxygen therapy derives from the increased airflow past the nose, mouth and anterior part of the face. Recent evidence has shown that passing cool air over these areas can reduce the sensation of breathlessness. Thus, providing the patient with a bedside or hand-held fan and if possible opening the windows to circulate the air can provide moderate additional benefit, at little cost.
Management Management should be directed towards relieving or eliminating the underlying cause of the breathlessness. Thus, acute bronchospasm from existing obstructive pulmonary disease (asthma, COPD) needs a bronchodilator (anticholinergic and/or b-adrenergic agent), initially by inhaler or nebulizer, and possibly with corticosteroid therapy. Anaemia causing breathlessness should
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PHYSICAL PROBLEMS
Useful investigations for the diagnosis and monitoring of breathlessness Imaging C Chest X-ray C CT scanning C Ultrasound scanning (for pleural or pericardial fluid) C CTePA (to diagnose pulmonary embolism) Blood tests C Haemoglobin C B-type natriuretic peptide (to exclude a cardiac element) Bedside tests C Pulse oximetry Functional C Pulmonary function tests (FEV1, FVC to diagnose fixed or reversible airflow obstruction; TLCO or KCO to identify gas exchange problem) C Flowevolume loop (to detect upper airways obstruction) C Exercise testing (6-minute walk, shuttle walking test) FVC, forced vital capacity; FEV1, forced expiratory volume in 1 second; KCO, carbon monoxide transfer coefficient; TLCO, single breath carbon monoxide transfer factor.
Table 2
Non-invasive ventilation (NIV) NIV is reserved for use in individuals with type 2 respiratory failure. This can be related to muscle weakness in neurological diseases such as MND or to increased airway resistance in COPD. In MND, the treatment has been shown to reduce hypercapnia and improve cognition. It can also improve breathlessness and relieve sleep disturbance. Signs and symptoms of respiratory muscle weakness can be insidious, but early identification and assessment are crucial as NIV improves both quality of life and survival. The use of NIV when patients with MND are approaching end of life has been ethically debated. However, carers have reported that the use of NIV helps the patient’s comfort and anxiety at the end of life.
Drug management It is essential first to treat reversible causes of dyspnoea such as airflow obstruction in COPD or heart failure, by optimizing conventional therapies for these conditions. For symptomatic treatment, the main drug classes are strong opioids and benzodiazepines. There is no convincing evidence that nebulized furosemide has a role in the management of dyspnoea in patients with advanced disease. Opioids: opioids are the mainstay of drug therapy for moderate to severe acute and chronic breathlessness. When dosing starts low and is titrated slowly upwards, there is good evidence for a reduction in breathlessness and distress with parenteral and oral
Flow chart of suggested management for patients with breathlessness in advanced disease • • • •
Hand-held fan Relaxation techniques Walking aids Pulmonary rehabilitation
Continue non-pharmacological interventions
Trial of prn opioids at low dose
• Regular opioid • Consider prn benzodiazepine
Non-pharmacological management as tolerated End-of-life care • Opioid + regular benzodiazepine • Continuous infusion + prn
Long-term oxygen therapy / non-invasive ventilation for appropriate patients Management of reversible causes of breathlessness in keeping with ACP Advancing disease ACP, advanced care plan; prn, as required. Figure 1
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PHYSICAL PROBLEMS
opioids, without impairing respiratory function, even in studies of patients with COPD. Morphine is the most commonly used opioid and is initially given in small doses (5 mg orally, 2.5 mg subcutaneously or intravenously) in ‘opioid-naive’ patients. This can be repeated 2 e4-hourly as necessary and titrated upwards on a daily basis as symptoms dictate, taking care not to provoke sedation or other adverse effects. For patients already taking strong opioids for pain, it is advisable to offer gradual stepwise increments of up to 25e50% of the current daily dose. Alternatively, for those taking ‘asrequired’ doses of opioids for breakthrough pain, a further increase of 25e50% of these doses can be given. For both opioidnaive and opioid-tolerant patients, regular long-term treatment is associated with the recognized adverse effect of constipation, so prophylactic laxatives should be considered. Sedation and somnolence are occasionally a problem as the dose of strong opioid is increased. Although opioid receptors are found in the airways, there is no evidence that intranasal or nebulized opioids are more effective for acute dyspnoeic episodes. The greatest barrier to using opioids for dyspnoea is the fear of provoking respiratory depression.3 It has been shown that lower doses of opioids, used judiciously by careful titration against symptom level as described above, can reduce the sensation of dyspnoea, presumably via the higher cortical receptors, without initiating hypercapnic ventilatory depression via the medulla oblongata. Even when used carefully, opioids reduce respiratory rate, although minute ventilation does not initially suffer. Thus, a reduced respiratory rate per se is not an indication of serious opioid toxicity in this situation. However, in patients with advanced COPD it is prudent to observe the patient carefully when initiating opioids or increasing the dose, and to be prepared to administer naloxone if significant respiratory depression occurs. Naloxone e the opioid receptor agonist naloxone is used to reverse opioid overdose. Doses of naloxone used in acute opioid overdose are often not appropriate for managing severe opioidinduced respiratory depression in patients being given palliative care. Life-threatening respiratory depression is indicated by: a low respiratory rate of <8 respirations/minute oxygen saturations <85% and cyanosis. In this situation in palliative care patients taking opioids, 400 micrograms of naloxone (one ampoule) should be diluted in to 10 ml with sodium chloride 0.9% injection in a 10-ml syringe, and then administered by slow intravenous injection, titrating the effect by monitoring the improvement in respiratory rate. Naloxone has a short duration of action so repeated doses or a naloxone infusion may be required. If opioid toxicity is less severe: omit the next regular dose of opioid and review the analgesia, being prepared to titrate downwards monitor the patient closely, maintaining hydration and oxygenation. Naloxone is not indicated for opioid-induced drowsiness and/ or delirium that is not life-threatening, and is not appropriate for patients on opioids who are dying within hours or days. It should be noted that buprenorphine, a complex opioid with actions on several opioid and non-opioid receptors, is inherently
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safer in this setting because it causes significantly less respiratory depression for the same degree of analgesia. Benzodiazepines: compared with opioids, there is little evidence that benzodiazepines modify the sensation of breathlessness, but they are useful when the dyspnoea is associated with anxiety or panic. Shorter acting benzodiazepines such as lorazepam are preferred as patients can be taught to take 0.5e1 mg sublingually at times of significant breathlessness. There is evidence that a combination of low-dose benzodiazepine and morphine best reduce dyspnoea with minimal adverse effects. For patients with severe episodes, subcutaneous midazolam is very helpful. Midazolam and opioids such as morphine or oxycodone can be administered in combination via a subcutaneous syringe driver in patients at the end of life.4 Diazepam is not commonly used in this situation because of its prolonged half-life. Non-drug approaches The initial focus of treatment for patients at earlier stages of disease who require ‘supportive’ rather than ‘end-of-life’ care should be non-pharmacological management. These treatments can be safer and more effective in managing symptoms of dyspnoea. Much of the research has been undertaken in individuals with advanced COPD. Hand-held fan: the use of a hand-held fan producing an increased airflow over areas innervated by the second and third branches of the trigeminal nerve has been shown to reduce feelings of breathlessness in patients with a variety of advanced disease including COPD, heart failure and lung cancer. Fan therapy is safe, provides patients with a sense of selfmanagement and can easily be used alongside pharmacological options. Exercise training: muscle weakness is commonly seen in patients with advanced disease. This can increase the work of mobilizing and thus leads to increased breathlessness. Deconditioning can also contribute to the metaboreflex described above. Improving muscle strength in patients with COPD has been shown to reduce the distress and anxiety associated with dyspnoea, as well as improve exercise tolerance. The aim is to encourage exercise training before significant deconditioning has occurred. However, once muscle dysfunction has occurred, there is increasing evidence that lower limb strength training and neuromuscular electrical stimulation can helpfully rebuild muscle strength. Walking aids should be considered when assessing patients with severe dyspnoea. A rollator walking aid can improve walking distance, particularly in individuals with a very short baseline walking distance, and is associated with an improvement in dyspnoea scores. Psychological interventions: the emotional distress associated with dyspnoea is well documented. Relaxation techniques such as meditation, yoga and cognitive behavioural therapy have shown variable benefit in improving shortness of breath. Supporting patients with education to understand the causes of breathlessness and discussions on symptom experience and self-
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PHYSICAL PROBLEMS
management techniques including muscle relaxation can reduce the severity of dyspnoea and improve functional ability.
KEY REFERENCES 1 Ahmadi Z. The burden of chronic breathlessness across the population. Curr Opin Support Palliat Care 2018; 12: 214e8. 2 Ekstrom M, Ahmadi Z, Bornefalk-Hermansson A, et al. Oxygen for breathlessness in patients with chronic obstructive pulmonary disease who do not qualify for home oxygen therapy. Cochrane Database Syst Rev 2016; 11: CD006429. 3 Verberkt CA, van den Beuken-van Everdingen MHJ, Schols JMGA, et al. Respiratory adverse effects of opioids for breathlessness: a systematic review and meta-analysis. Eur Respir J 2017; 50: 1701153. 4 Ruegger J, Hodgkinson S, Field-Smith A, Ahmedzai SH. Care of adults in the last days of life: summary of NICE guidance. BMJ 2015; 351: h6631. 5 Bausewein C, Schumacher P, Bolzani A. Integrated breathlessness services for people with chronic conditions. Curr Opin Support Palliat Care 2018; 12: 227e31.
Breathlessness programmes: pulmonary rehabilitation is widely used in the management of patients with COPD and has been shown to improve dyspnoea and fatigue. Patients often feel more in control of their dyspnoea, described as ‘breathlessness mastery’. Most previous randomized controlled trials were carried out in patients with moderate COPD. However, recent trials of breathlessness intervention services in more advanced COPD or in other diseases have also shown a benefit. These services combine palliative care assessment including pharmacological treatments if needed, occupational therapy and a physiotherapy review in the home with relaxation and pacing techniques.5 The studies showed increased ‘mastery of breathlessness’ and reduced healthcare costs compared with standard care. A
TEST YOURSELF To test your knowledge based on the article you have just read, please complete the questions below. The answers can be found at the end of the issue or online here. Investigation Haemoglobin 92 g/litre (130e180)
Question 1 A 72-year-old woman presented with a 3-day history of increasing breathlessness on minimal exertion. She had a 4-year history of severe chronic obstructive pulmonary disease and had recently been on holiday in South Africa, where she had run out of her inhalers and obtained a replacement at a pharmacy. Since returning home, she had taken some old prednisolone 5 mg tablets without improvement. She had a 55 packeyear smoking history. On clinical examination, she appeared agitated and distressed, and her face was puffy. She was pale but not cyanosed, with a heart rate of 115 beats/minute. There was prominent wheeze, especially on the right side of her chest. Oxygen saturations were 93% on air.
What is the most urgent next step in her management? A. Insert a new paracentesis drain into her abdomen B. Investigate for pleural effusions C. Start oxygen therapy D. Increase the morphine dose by 50% E. Transfuse two units of blood Question 3 A 52-year-old man presented with extreme breathlessness. He had been found to have advanced pancreatic cancer and a recent pulmonary thromboembolism. He also had severe abdominal and back pain. He was on full anticoagulation and oxycodone at a dose equivalent to 300 mg oral morphine subcutaneously via a syringe driver. On clinical examination, he appeared breathless and frightened. Oxygen saturations were 92%.on air. His family were concerned that he was dying, and in his advance care plan it had been noted that he wanted to die at home.
What is the most appropriate next step in her management? A. Increase the dose of prednisolone B. Give high-flow oxygen C. Request an opinion for non-invasive ventilation D. Order an urgent chest Xray or CT scan of the thorax E. Order a tropical medicine infection screen Question 2 A 67-year-old woman presented with abdominal discomfort and breathlessness. She had been found to have stage 4 ovarian cancer and recurrent ascites that had been drained 2 days previously. However, the breathlessness had persisted, especially on exertion. She had longstanding pelvic pain that was controlled with morphine 20 mg slow release 12-hourly. On clinical examination, there was residual shifting dullness and reduced breath sounds at both lung bases. Oxygen saturations were 88% on air.
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What is the next best step to enable his advance care plan? A. Increase the dose of oxycodone by 25% B. Start high-flow oxygen C. Convert the subcutaneous oxycodone syringe driver to the intravenous route D. Add dexamethasone 10 mg 12-hourly E. Give midazolam 5 mg subcutaneously immediately and add midazolam 10 mg to the syringe driver
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Please cite this article as: Ahmedzai SH, Breathlessness in advanced disease, Medicine, https://doi.org/10.1016/j.mpmed.2019.10.004
Breathlessness in advanced disease
Key points C
Breathlessness is common in chronic malignant and noncancer conditions
C
Therapy should initially be directed to reducing or eliminating the underlying cause
C
Non-drug approaches can be useful in the earlier stages of a progressive disease
C
Drugs for breathlessness and/or associated anxiety include opioids and benzodiazepines
C
Oxygen is a treatment for hypoxia not breathlessness and should be reserved for those who have significant desaturation
Sam Hjelmeland Ahmedzai
Abstract Breathlessness is the subjective experience of breathing discomfort, which arises as a distressing symptom in many diseases. It has several pathophysiological causes involving peripheral and central receptors and is modulated by cortical processing including emotions. Older people and patients with sarcopenia or cachexia are more susceptible to breathlessness on exertion. In the last hours of life, breathing can become laboured and noisy, owing to upper airway secretions. Most patients can be assessed by physical examination and simple investigations. Research has shown that careful use of opioids can reduce the sensation of breathlessness without compromising ventilatory control. Benzodiazepines can also help, probably by their anxiolytic and sedative actions. The combination of an opioid and a shortacting benzodiazepine can compromise respiratory function, but it is especially useful at the end of life as a combined subcutaneous or intravenous infusion. Oxygen is indicated if there is hypoxaemia, but increased airflow around the face (e.g. with a fan) can also help. Non-invasive ventilation can be necessary in severe cases, such as neuromuscular disease. Non-medical approaches, including pulmonary rehabilitation programmes, breathing training and relaxation, can also help.
increased effort of breathing (discomfort and tiredness) chest tightness (feeling of constriction). Patients whose episodes of shortness of breath have specific triggers try to avoid these. If the trigger is physical exertion, avoidance leads to inactivity, muscle deconditioning and a vicious cycle of increased dyspnoea and social isolation. Carers’ experience of looking after a patient with advanced disease and dyspnoea is also often negative, with high levels of anxiety and poor sleep that increase with the severity of the patient’s distress.
Keywords Breathlessness; dyspnoea; fan therapy; MRCP; opioids; oxygen; pulmonary rehabilitation
Epidemiology Breathlessness is common in many advanced illnesses, including chronic obstructive pulmonary disease (COPD), heart failure, neuromuscular diseases (e.g. motor neurone disease (MND)) and cancer.1 A British retrospective survey found that the terminal stage of COPD was associated with dyspnoea in 76% of patients, compared with 60% of a comparable lung cancer group. Cancers in which at least 50% of patients report breathlessness included lung, head and neck, genitourinary, breast and lymphoma. In many chronic conditions, dyspnoea becomes increasingly prevalent and refractory to treatment with disease progression. It is a poor prognostic factor in the palliative care setting.
Definition Breathlessness is defined as the subjective experience of breathing discomfort. It arises from physiological, psychological, social and environmental factors, and significantly affects daily activities. The term ‘dyspnoea’ is derived from the Greek for ‘bad breathing’ and in this article is used interchangeably with ‘breathlessness’.
Patient experience
Pathology and pathogenesis
Short-term breathlessness is an everyday experience, for example during voluntary hard exercise; however, when it is prolonged or occurs with little cause it can be frightening. In severe episodes, patients report fear and panic, feeling as if they are drowning or choking to death. Three elements contribute to the sensation of breathlessness: air hunger (an unpleasant sensation of the need to breathe, while being unable to increase ventilation)
The common pathophysiological changes that lead to breathlessness are described in Table 1. The main causes are: increased chemical or neurological drive to breathe (e.g. by stimulation of chemoreceptors) increased work of breathing (e.g. cardiac failure, pleural effusion, pulmonary fibrosis, ascites) decreased neuromuscular power (e.g. MND, sarcopenia, cachexia).
Sam Hjelmeland Ahmedzai BSc MB ChB FRCP is Emeritus Professor at the University of Sheffield, UK and NIHR Clinical Research Network National Specialty Lead for Supportive Care and Community-based Research. Competing interests: none declared.
Chemical and neurological drives The subjective sensation of breathlessness is thought to arise from a mismatch between incoming afferent impulses from sensory receptors and outgoing central motor signalling to the thoracic wall muscles and diaphragm.
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Please cite this article as: Ahmedzai SH, Breathlessness in advanced disease, Medicine, https://doi.org/10.1016/j.mpmed.2019.10.004
PHYSICAL PROBLEMS
The chemical drivers controlling normal respiration are the response to hypercapnia and hypoxia: hypercapnia exerts its effect via increased arterial partial pressure of carbon dioxide (PaCO2), detected primarily in the medullary chemoreceptors (and partly in the carotid bodies) hypoxia is detected in the carotid bodies.
and being socially disadvantaged are predictors of chronic breathlessness. Ageing is associated with anatomical and functional pulmonary and cardiac changes that predispose to dyspnoea. Obesity can contribute through mechanisms involving changes in lung volumes, oxygen cost of breathing and muscle deconditioning. Sarcopenia is the loss of skeletal muscle mass and is associated with normal ageing. Together with cachexia that arises from cancer, COPD or heart failure, this skeletal muscle wasting is a major contributor to breathlessness. A further mechanism implicated in heart failure is the interaction of skeletal muscle metaboreceptors and the control of cardiovascular loading through the autonomic system, described as the ‘metaboreflex’.
Central receptors: in healthy people, respiratory drive in response to hypercapnia is more sensitive than to hypoxia. However, hypercapnic drive can be blunted in patients with longstanding ventilatory failure, for example because of advanced COPD. Functional magnetic resonance imaging techniques have shed light on how the ventilatory drive is processed in conscious and subconscious parts of the brain. Air hunger is correlated with increased blood flow in the mesencephalic and hypothalamic areas, limbic and paralimbic areas (amygdala), motor areas and insula. Opioid receptors in some of these areas are probably involved in the sensation of dyspnoea, as well as in the regulation of normal breathing. There is evidence that endogenous opioids such as b-endorphin may be involved in the response to exercise in patients with COPD, as administration of naloxone causes an increase in exercise-related dyspnoea. Many opioid drugs initially cause a dose-related depression of ventilatory frequency and minute volume, which are not in themselves life-threatening. Thus, when opioids are carefully titrated against the level of dyspnoea, there is no significant ventilatory compromise even when the respiratory rate falls. The danger arises when opioids are given in excessive doses relative to the patient’s needs; there is then a risk that reduced ventilation, especially in the presence of a blunted hypercapnia ventilatory drive, will lead to acute hypercapnic respiratory failure.
Diagnosis Breathlessness is readily apparent when it is severe and the patient is panicking. However, it is important to distinguish
Causes of breathlessness in advanced disease System
Example of pathology
Example of disease
Pulmonary
Airflow obstruction COPD, asthma, cancer Reduced lung compliance Pulmonary fibrosis, emphysema, pulmonary consolidation Pleural effusion Cancer, heart failure Chest wall restriction Neuromuscular disease, mesothelioma Diaphragmatic restriction Ascites Ventilationeperfusion Pulmonary embolism mismatch Cachexia affecting the Cancer, COPD, heart respiratory musculature failure Cardiovascular Pump failure Acute or chronic heart failure Pericardial effusion Cancer Hypovolaemia Bleeding, too rapid drainage of ascites Systemic Anaemia Chronic disease, cancer Biological effects of Decrease in lung elasticity ageing Decrease in respiratory muscle strength Reduction in forced vital capacity and peak flow rate Increased air-trapping Deterioration in gas exchange Reduction in ventilatory response to hypoxia and hypercapnia Increased ventilatory response to exercise Effects of co-morbid disease (e.g. heart failure) Sarcopenia
Peripheral receptors: peripheral carotid body receptors respond primarily to decreased PaO2 but are also sensitive to decreased arterial pH, respiratory oscillations of PaCO2, increased blood temperature and chemical stimulants. Hypoxaemia results in the activation of peripheral chemoreceptors that send afferent impulses to the brainstem respiratory centres, leading to increased ventilatory motor drive. Other peripheral receptors that are important for the regulation of breathing and the pathogenesis of dyspnoea include the mechanical stretch receptors in the chest wall and diaphragm muscles, stretch receptors in the airways and J-receptors in the lung parenchyma. These send afferent signals to the brain about whether the respiratory pump and lungs are able to provide the necessary ventilation for the current level of activity. In COPD, there is hyperinflation and reduced compliance of the lungs, which contribute to the reduced exercise tolerance and dyspnoea on exertion. The J-receptors are stimulated by increased pulmonary pressure and fluid, for example in patients with pulmonary embolism or heart failure. Other factors: there is a clear relation between breathlessness and anxiety: for some patients, the sensory and affective dimensions, and triggers, of dyspnoea can as be important as the physical disease. Being older, female, living alone, being obese
Table 1
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PHYSICAL PROBLEMS
be treated with blood transfusion while taking care not to provoke heart failure, especially in older individuals with longstanding anaemia. It is also important to optimize the treatment of existing heart failure. Antibiotics help dyspnoea as well as cough in patients with respiratory infections, even in the advanced stages of disease. The patient’s fears should be addressed, with a clear explanation of both the causes of breathlessness and the treatment plan, taking into consideration for people who may be entering end-of-life care any advance care plan or declared preferences for acceptance or refusal of treatment. Figure 1 outlines how nonpharmacological methods, drug treatments and oxygen/airflow can be used as the disease progresses.
breathlessness from other types of abnormal breathing pattern, especially: tachypnoea associated with an increased metabolic rate as in fever, and air hunger associated with metabolic acidosis (e.g. diabetic ketosis) hyperventilation associated with panic disorders CheyneeStokes respiration (periods of increased and laboured breathing alternating with periods of hypopnoea or even apnoea). Severity of breathlessness can be rated using a recordable scale. Most patients with normal cognitive function can describe the symptom verbally (mild, moderate, severe) or numerically. Visual analogue scales (0e100 mm) are useful in research but not in clinical settings. Problems arise in rating the degree of breathlessness in people with cognitive impairment: the clinician should use observations of the patient’s activity, facial expressions and other behavioural changes. The patient’s regular carers can often give a proxy estimation of the distress. In making a differential diagnosis, consider particularly the relationship of dyspnoea to exercise and position (e.g. orthopnoea with heart failure), and the occurrence of paroxysmal dyspnoea with palpitations and fainting (e.g. with pulmonary embolism). However, physical examination and investigations are usually needed to make a definitive diagnosis. Important features to look for during the examination include pallor, central cyanosis, signs of heart failure, bronchospasm, pulmonary consolidation and pleural effusion. In dyspnoea arising for the first time, it is helpful to request investigations that will identify pathological (and treatable) causes. A list of useful tests, some of which can also be used for monitoring progress, is given in Table 2. A rapid bedside test, often helpful clinically in community, hospice or care home settings, is pulse oximetry. The doctor should be aware of when oximetry is less reliable, for example when the patient is in shock or has peripheral circulatory failure, when it may be appropriate to use a corroborative test of arterial blood gases. When a patient presents to the emergency department with acute severe breathlessness, there is seldom time to perform all these investigations before embarking on corrective or symptomatic (palliative) treatments. The minimum tests in this situation are: blood pressure pulse oximetry/arterial blood gases electrocardiogram chest X-ray. If pulmonary embolism is suspected, for example if there is recent painful leg swelling, urgent computed tomographic pulmonary angiography (CTePA) and peripheral blood flow (Doppler) tests are justified.
Urgent treatment In cancer patients, the development of pulmonary, pleural or pericardial disease causing acute dyspnoea can be a medical emergency, and palliative oncological measures should be instituted with minimal delay. Even in patients with a poor performance status, thoracocentesis, a single fraction of radiotherapy or the placement of an airway stent can provide rapid relief. Patients with cancer and upper airways obstruction arising from a central tracheobronchial mass or with lymphangitis carcinomatosa can be treated with high-dose corticosteroid (dexamethasone 8e16 mg/day (unlicensed use)) while awaiting an oncology opinion or a palliative procedure such as placement of an airway stent. The dosage of corticosteroid should be tapered after 5e7 days. Other causes of severe acute dyspnoea, including pulmonary embolism, pneumothorax, aspiration pneumonia and cardiac failure, should be treated accordingly, taking into consideration the patient’s performance status, disease trajectory and the burden and/or benefit of treatment options. Oxygen therapy Patients who have acute significant (<90%) oxygen desaturation at rest or on exertion should be offered oxygen, preferably via nasal cannulae unless higher flow rates (>6 litres/minute) are required. There is little evidence to support supplementary oxygen in patients with saturations >90% unless they are anaemic.2 Caution with oxygen is required in patients with COPD as they can be at risk of hypercapnic respiratory failure. Patients with chronic breathlessness may be discharged home with oxygen. However, unless the patient is hypoxaemic, the benefit of oxygen in improving feelings of breathlessness has not been clearly demonstrated: studies comparing cylinder air and oxygen have shown similar small effects, but with increased adverse effects with oxygen. In inpatient settings, with severe dyspnoea associated with cancer or COPD, a mixture of helium and oxygen (HelioxÒ) can give a quicker and greater relief of dyspnoea than oxygen alone, owing to the improved flow characteristics of helium gas. Part of the benefit of oxygen therapy derives from the increased airflow past the nose, mouth and anterior part of the face. Recent evidence has shown that passing cool air over these areas can reduce the sensation of breathlessness. Thus, providing the patient with a bedside or hand-held fan and if possible opening the windows to circulate the air can provide moderate additional benefit, at little cost.
Management Management should be directed towards relieving or eliminating the underlying cause of the breathlessness. Thus, acute bronchospasm from existing obstructive pulmonary disease (asthma, COPD) needs a bronchodilator (anticholinergic and/or b-adrenergic agent), initially by inhaler or nebulizer, and possibly with corticosteroid therapy. Anaemia causing breathlessness should
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Useful investigations for the diagnosis and monitoring of breathlessness Imaging C Chest X-ray C CT scanning C Ultrasound scanning (for pleural or pericardial fluid) C CTePA (to diagnose pulmonary embolism) Blood tests C Haemoglobin C B-type natriuretic peptide (to exclude a cardiac element) Bedside tests C Pulse oximetry Functional C Pulmonary function tests (FEV1, FVC to diagnose fixed or reversible airflow obstruction; TLCO or KCO to identify gas exchange problem) C Flowevolume loop (to detect upper airways obstruction) C Exercise testing (6-minute walk, shuttle walking test) FVC, forced vital capacity; FEV1, forced expiratory volume in 1 second; KCO, carbon monoxide transfer coefficient; TLCO, single breath carbon monoxide transfer factor.
Table 2
Non-invasive ventilation (NIV) NIV is reserved for use in individuals with type 2 respiratory failure. This can be related to muscle weakness in neurological diseases such as MND or to increased airway resistance in COPD. In MND, the treatment has been shown to reduce hypercapnia and improve cognition. It can also improve breathlessness and relieve sleep disturbance. Signs and symptoms of respiratory muscle weakness can be insidious, but early identification and assessment are crucial as NIV improves both quality of life and survival. The use of NIV when patients with MND are approaching end of life has been ethically debated. However, carers have reported that the use of NIV helps the patient’s comfort and anxiety at the end of life.
Drug management It is essential first to treat reversible causes of dyspnoea such as airflow obstruction in COPD or heart failure, by optimizing conventional therapies for these conditions. For symptomatic treatment, the main drug classes are strong opioids and benzodiazepines. There is no convincing evidence that nebulized furosemide has a role in the management of dyspnoea in patients with advanced disease. Opioids: opioids are the mainstay of drug therapy for moderate to severe acute and chronic breathlessness. When dosing starts low and is titrated slowly upwards, there is good evidence for a reduction in breathlessness and distress with parenteral and oral
Flow chart of suggested management for patients with breathlessness in advanced disease • • • •
Hand-held fan Relaxation techniques Walking aids Pulmonary rehabilitation
Continue non-pharmacological interventions
Trial of prn opioids at low dose
• Regular opioid • Consider prn benzodiazepine
Non-pharmacological management as tolerated End-of-life care • Opioid + regular benzodiazepine • Continuous infusion + prn
Long-term oxygen therapy / non-invasive ventilation for appropriate patients Management of reversible causes of breathlessness in keeping with ACP Advancing disease ACP, advanced care plan; prn, as required. Figure 1
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opioids, without impairing respiratory function, even in studies of patients with COPD. Morphine is the most commonly used opioid and is initially given in small doses (5 mg orally, 2.5 mg subcutaneously or intravenously) in ‘opioid-naive’ patients. This can be repeated 2 e4-hourly as necessary and titrated upwards on a daily basis as symptoms dictate, taking care not to provoke sedation or other adverse effects. For patients already taking strong opioids for pain, it is advisable to offer gradual stepwise increments of up to 25e50% of the current daily dose. Alternatively, for those taking ‘asrequired’ doses of opioids for breakthrough pain, a further increase of 25e50% of these doses can be given. For both opioidnaive and opioid-tolerant patients, regular long-term treatment is associated with the recognized adverse effect of constipation, so prophylactic laxatives should be considered. Sedation and somnolence are occasionally a problem as the dose of strong opioid is increased. Although opioid receptors are found in the airways, there is no evidence that intranasal or nebulized opioids are more effective for acute dyspnoeic episodes. The greatest barrier to using opioids for dyspnoea is the fear of provoking respiratory depression.3 It has been shown that lower doses of opioids, used judiciously by careful titration against symptom level as described above, can reduce the sensation of dyspnoea, presumably via the higher cortical receptors, without initiating hypercapnic ventilatory depression via the medulla oblongata. Even when used carefully, opioids reduce respiratory rate, although minute ventilation does not initially suffer. Thus, a reduced respiratory rate per se is not an indication of serious opioid toxicity in this situation. However, in patients with advanced COPD it is prudent to observe the patient carefully when initiating opioids or increasing the dose, and to be prepared to administer naloxone if significant respiratory depression occurs. Naloxone e the opioid receptor agonist naloxone is used to reverse opioid overdose. Doses of naloxone used in acute opioid overdose are often not appropriate for managing severe opioidinduced respiratory depression in patients being given palliative care. Life-threatening respiratory depression is indicated by: a low respiratory rate of <8 respirations/minute oxygen saturations <85% and cyanosis. In this situation in palliative care patients taking opioids, 400 micrograms of naloxone (one ampoule) should be diluted in to 10 ml with sodium chloride 0.9% injection in a 10-ml syringe, and then administered by slow intravenous injection, titrating the effect by monitoring the improvement in respiratory rate. Naloxone has a short duration of action so repeated doses or a naloxone infusion may be required. If opioid toxicity is less severe: omit the next regular dose of opioid and review the analgesia, being prepared to titrate downwards monitor the patient closely, maintaining hydration and oxygenation. Naloxone is not indicated for opioid-induced drowsiness and/ or delirium that is not life-threatening, and is not appropriate for patients on opioids who are dying within hours or days. It should be noted that buprenorphine, a complex opioid with actions on several opioid and non-opioid receptors, is inherently
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safer in this setting because it causes significantly less respiratory depression for the same degree of analgesia. Benzodiazepines: compared with opioids, there is little evidence that benzodiazepines modify the sensation of breathlessness, but they are useful when the dyspnoea is associated with anxiety or panic. Shorter acting benzodiazepines such as lorazepam are preferred as patients can be taught to take 0.5e1 mg sublingually at times of significant breathlessness. There is evidence that a combination of low-dose benzodiazepine and morphine best reduce dyspnoea with minimal adverse effects. For patients with severe episodes, subcutaneous midazolam is very helpful. Midazolam and opioids such as morphine or oxycodone can be administered in combination via a subcutaneous syringe driver in patients at the end of life.4 Diazepam is not commonly used in this situation because of its prolonged half-life. Non-drug approaches The initial focus of treatment for patients at earlier stages of disease who require ‘supportive’ rather than ‘end-of-life’ care should be non-pharmacological management. These treatments can be safer and more effective in managing symptoms of dyspnoea. Much of the research has been undertaken in individuals with advanced COPD. Hand-held fan: the use of a hand-held fan producing an increased airflow over areas innervated by the second and third branches of the trigeminal nerve has been shown to reduce feelings of breathlessness in patients with a variety of advanced disease including COPD, heart failure and lung cancer. Fan therapy is safe, provides patients with a sense of selfmanagement and can easily be used alongside pharmacological options. Exercise training: muscle weakness is commonly seen in patients with advanced disease. This can increase the work of mobilizing and thus leads to increased breathlessness. Deconditioning can also contribute to the metaboreflex described above. Improving muscle strength in patients with COPD has been shown to reduce the distress and anxiety associated with dyspnoea, as well as improve exercise tolerance. The aim is to encourage exercise training before significant deconditioning has occurred. However, once muscle dysfunction has occurred, there is increasing evidence that lower limb strength training and neuromuscular electrical stimulation can helpfully rebuild muscle strength. Walking aids should be considered when assessing patients with severe dyspnoea. A rollator walking aid can improve walking distance, particularly in individuals with a very short baseline walking distance, and is associated with an improvement in dyspnoea scores. Psychological interventions: the emotional distress associated with dyspnoea is well documented. Relaxation techniques such as meditation, yoga and cognitive behavioural therapy have shown variable benefit in improving shortness of breath. Supporting patients with education to understand the causes of breathlessness and discussions on symptom experience and self-
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PHYSICAL PROBLEMS
management techniques including muscle relaxation can reduce the severity of dyspnoea and improve functional ability.
KEY REFERENCES 1 Ahmadi Z. The burden of chronic breathlessness across the population. Curr Opin Support Palliat Care 2018; 12: 214e8. 2 Ekstrom M, Ahmadi Z, Bornefalk-Hermansson A, et al. Oxygen for breathlessness in patients with chronic obstructive pulmonary disease who do not qualify for home oxygen therapy. Cochrane Database Syst Rev 2016; 11: CD006429. 3 Verberkt CA, van den Beuken-van Everdingen MHJ, Schols JMGA, et al. Respiratory adverse effects of opioids for breathlessness: a systematic review and meta-analysis. Eur Respir J 2017; 50: 1701153. 4 Ruegger J, Hodgkinson S, Field-Smith A, Ahmedzai SH. Care of adults in the last days of life: summary of NICE guidance. BMJ 2015; 351: h6631. 5 Bausewein C, Schumacher P, Bolzani A. Integrated breathlessness services for people with chronic conditions. Curr Opin Support Palliat Care 2018; 12: 227e31.
Breathlessness programmes: pulmonary rehabilitation is widely used in the management of patients with COPD and has been shown to improve dyspnoea and fatigue. Patients often feel more in control of their dyspnoea, described as ‘breathlessness mastery’. Most previous randomized controlled trials were carried out in patients with moderate COPD. However, recent trials of breathlessness intervention services in more advanced COPD or in other diseases have also shown a benefit. These services combine palliative care assessment including pharmacological treatments if needed, occupational therapy and a physiotherapy review in the home with relaxation and pacing techniques.5 The studies showed increased ‘mastery of breathlessness’ and reduced healthcare costs compared with standard care. A
TEST YOURSELF To test your knowledge based on the article you have just read, please complete the questions below. The answers can be found at the end of the issue or online here. Investigation Haemoglobin 92 g/litre (130e180)
Question 1 A 72-year-old woman presented with a 3-day history of increasing breathlessness on minimal exertion. She had a 4-year history of severe chronic obstructive pulmonary disease and had recently been on holiday in South Africa, where she had run out of her inhalers and obtained a replacement at a pharmacy. Since returning home, she had taken some old prednisolone 5 mg tablets without improvement. She had a 55 packeyear smoking history. On clinical examination, she appeared agitated and distressed, and her face was puffy. She was pale but not cyanosed, with a heart rate of 115 beats/minute. There was prominent wheeze, especially on the right side of her chest. Oxygen saturations were 93% on air.
What is the most urgent next step in her management? A. Insert a new paracentesis drain into her abdomen B. Investigate for pleural effusions C. Start oxygen therapy D. Increase the morphine dose by 50% E. Transfuse two units of blood Question 3 A 52-year-old man presented with extreme breathlessness. He had been found to have advanced pancreatic cancer and a recent pulmonary thromboembolism. He also had severe abdominal and back pain. He was on full anticoagulation and oxycodone at a dose equivalent to 300 mg oral morphine subcutaneously via a syringe driver. On clinical examination, he appeared breathless and frightened. Oxygen saturations were 92%.on air. His family were concerned that he was dying, and in his advance care plan it had been noted that he wanted to die at home.
What is the most appropriate next step in her management? A. Increase the dose of prednisolone B. Give high-flow oxygen C. Request an opinion for non-invasive ventilation D. Order an urgent chest Xray or CT scan of the thorax E. Order a tropical medicine infection screen Question 2 A 67-year-old woman presented with abdominal discomfort and breathlessness. She had been found to have stage 4 ovarian cancer and recurrent ascites that had been drained 2 days previously. However, the breathlessness had persisted, especially on exertion. She had longstanding pelvic pain that was controlled with morphine 20 mg slow release 12-hourly. On clinical examination, there was residual shifting dullness and reduced breath sounds at both lung bases. Oxygen saturations were 88% on air.
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What is the next best step to enable his advance care plan? A. Increase the dose of oxycodone by 25% B. Start high-flow oxygen C. Convert the subcutaneous oxycodone syringe driver to the intravenous route D. Add dexamethasone 10 mg 12-hourly E. Give midazolam 5 mg subcutaneously immediately and add midazolam 10 mg to the syringe driver
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