Palliative medicine

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chapter 39 Palliative medicine

INTRODUCTION AND OVERVIEW

In the mind of the general public, palliative care is commonly equated with terminal care, and many members of the medical community no doubt share this opinion. Traditionally, palliative care has predominantly provided service to cancer patients and their families. However, the role of palliative care is much richer and more varied than this. Palliative care principles can readily be applied to many incurable diseases as they become more severe, and can also be useful in the management of symptoms during the earlier stages of disease.

Palliative care, at its best, is provided by a team of individuals working towards common goals for a particular patient. The team may include doctors, nurses, allied healthcare staff, counsellors and family members. Symptom control, achievement of optimal quality of life and assistance with decision-making are all components of palliative care that can be provided by the general practitioner (GP). The critical role of the GP in the coordination of patient care is particularly pronounced for patients with advanced disease. Furthermore, a GP who has known a patient for much of their life is likely to have worthwhile insight into their values and wishes, and is well placed to assist them in negotiating difficult transitions.

GOALS OF CARE

It is often helpful to establish and focus upon the goals of care for a patient. These will be influenced by the nature and stage of the disease, the age of the patient, their general health and their life philosophy. As cancer progresses, the situation may become more complex and decisions may seem increasingly difficult. It is helpful at these times to return the focus to the goals of care and reflect on the outcome that we are trying to achieve. This will assist in more clearly identifying a pathway that is likely to accomplish these objectives. The GP should take an active role in reviewing the overall situation and incorporating a holistic understanding of their patient.

For example, a 55-year-old woman first confronted with a diagnosis of breast cancer is likely to elect to pursue chemotherapy if this is advised. She will consider the temporary side effects, reduction in quality of life and time taken to attend therapy to be worthwhile in view of the potential benefits. An 83-year-old woman with multiple other medical issues resulting in some frailty will often be more susceptible to adverse effects of routine chemotherapy for breast cancer. She may find the effort required to attend clinics, undergo invasive investigations or procedures and the time taken to recover from each cycle of chemotherapy to be an unacceptable trade-off for the potential benefits, which in all probability will be of a lesser magnitude.

Many important decisions may need to be made by a person confronted with a life-limiting illness. For an excellent and practical guideline on how to approach this, the reader is referred to Clayton & Hancock, ‘Clinical practice guidelines for communicating prognosis and end-of-life issues with adults in the advanced stages of a terminal illness, and their caregivers’, published as a supplement in the Medical Journal of Australia.¹

CARING FOR THE WHOLE PERSON

Nowhere is integrated and holistic care more important than when dealing with death and dying. Obviously the physical aspects of care need to be attended to, and dealing with various symptoms will be dealt with in detail in this chapter. Obvious also is the impact of emotional, social and spiritual/existential aspects involved in confronting end-of-life issues.

A deep-seated fear of dying, for example, or longstanding and unresolved guilt can have an enormous impact on how a patient deals with physical pain. It is not uncommon for deeper emotional and existential issues to influence and magnify such symptoms. If physical treatments only are administered (e.g. prescribing escalating doses of pain killers) but the underlying emotional and existential issues are not acknowledged or dealt with, then the problem of pain will likely be unsolvable, whereas if these deeper issues are dealt with well, the pain will often be far more manageable.

Most patients confronting life-threatening illnesses wish to speak to their medical team about spiritual and religious issues (see Ch 12, Spirituality). Whether the doctor provides such counselling or helps to link the patient with counsellors, pastoral care and allied healthcare professionals, one way or another this aspect of care needs to take place and not be ignored among the more obvious and apparently more pressing physical needs.

At all times one needs to also bear in mind that it is the whole family who will be experiencing the grief and anxiety associated with the illness—sometimes far more grief and anxiety that the patient, who may already have come to terms with their situation.

THE ROLE OF COMPLEMENTARY THERAPIES

The frequency of complementary therapy use by cancer patients may be as high as 83%² (see Ch 24, Cancer). This includes herbal medicines, music therapy and physical therapies such as acupuncture, among others. Patients use these therapies to improve symptoms, in the hope of curing cancer or increasing survival, and as a response to pressure from family or friends.³ It is certainly reasonable to encourage the use of those therapies that are proving helpful to the patient without causing undue hardship or interfering with conventional treatment. Some incur a considerable cost with little or no benefit, and occasionally there may be a risk of the therapy interfering with conventional medical care or causing harm to the patient. For example, many herbs can interact with drugs such as warfarin. The GP has an important role in discussing the use of such therapies with the patient.

PAIN

Pain is a complex experience involving specific neural pathways that convey nociceptive information to consciousness. Neuronal systems also exist that modify pain—for example, descending inhibitory pathways in the central nervous system. This chapter focuses mainly on cancer pain, but many of the principles can be applied to non-malignant pain in patients with advanced or near end-stage disease. Chronic pain, while sharing some features, requires important differences in approach and is not discussed here (see Ch 38, Pain management).

Pain is common is cancer and more so in advanced malignancy, with 70–90% of patients reporting pain.⁴ It is also common in the elderly (28–86% of nursing home residents⁵) and in those with other chronic disease (e.g. 40% of patients with Parkinson’s disease). As such, competent assessment and management of pain is a crucial skill for GPs.

The most effective approach to cancer pain requires consideration of the pathophysiology as well as the aetiology of the pain.

PATHOPHYSIOLOGY

Pathophysiology is important, as the different pain types respond differently to specific medications and thus can guide therapy.

• Somatic pain is caused by activation of peripheral nociceptors in response to inflammation or injury of surrounding tissues. Examples include bone metastases, arthritic pain and burn injury.

• Visceral pain occurs when nociceptors in thoracic or abdominal viscera are activated by infiltration, distension or compression of the organ. Liver metastases or bowel obstruction are examples.

• Neuropathic pain results from direct injury to the peripheral or central nervous system, such as peripheral neuropathy, spinal cord compression or cancer infiltration of a neural plexus.

It is common for cancer patients to have mixed somatic and neuropathic pain, for example when a rib metastasis causes bone pain and also has a neuropathic element by involving the intercostal nerve.

In addition, pain can also be classified on the basis of ‘timing’. Incident pain describes pain that occurs with movement; breakthrough pain refers to pain that ‘breaks through’ otherwise adequate levels of analgesia.

AETIOLOGY

In patients with cancer, pain may be:

• cancer-related—e.g. bone metastasis, infiltration of nerves or organs

• treatment-related—e.g. mucositis secondary to chemotherapy-induced neutropenia

• non-cancer-related—e.g. coexisting osteoarthritis.

HISTORY AND EXAMINATION

Careful history and examination can often assist in determining the likely pathophysiology and aetiology of a patient’s pain. The history will focus on the qualities, temporal features and other descriptive features of the pain. Details such as location, duration, onset, offset, relieving and exacerbating features should be elicited, along with a description of pain quality. It is clearly important to enquire about other symptoms such as nausea and vomiting, history of a recent fall, previous treatments and so on.

• Somatic pain descriptors include dull, constant, aching. Pain is usually well localised. This pain responds well to simple analgesics and to opioids.

• Visceral pain may have a gnawing, colicky or cramping character, feels deep and is less well localised. Be aware that visceral pain may be referred to other sites, e.g. shoulder tip pain from liver metastases, central abdominal pain from early appendicitis.

• Neuropathic pain may be described as burning, shooting or constricting, and often has a particularly unpleasant character. It can occur in paroxysms with or without a more constant component. Neuropathic pain may be felt in a dermatomal or peripheral nerve distribution. Features such as anaesthesia or allodynia strongly suggest an element of neuropathic pain.

The focus of the examination will be determined by the specifics of the pain and the patient’s previous history, but a general approach should include:

• overview of the patient—are they confused, markedly cachexic, dehydrated?

• a careful examination of the affected area, looking for tenderness, signs of deformity, infection, presence of a mass, loss of function and so on

• neurological examination to elicit any weakness or sensory abnormality, as it is possible that the patient will not have noticed these or recognised their importance.

INVESTIGATIONS

It is not possible to cover the scope of investigations that may be relevant. Some form of radiological imaging is generally useful to accurately determine the cause of the problem, but initiation of good analgesia should not be delayed while waiting for these results. In appropriate clinical circumstances, a variety of other investigations such as a full blood count, urine culture or calcium level will be indicated.

INTEGRATIVE MANAGEMENT

• Prevention—not realistic in the conventional sense, but severe, ongoing problems may potentially be minimised if pain is addressed promptly and effectively. For example, rapid initiation of therapy for shingles can reduce the incidence of postherpetic neuralgia.⁶

• Evaluation—in all cases, pain should be adequately evaluated. Some patients will choose not to pursue intervention but these are a minority, with relatively low levels of pain and greater general wellbeing.

• Self-help, lifestyle, home remedies—some strategies that patients are able to use in order to relieve pain include the use of heat or cold packs, resting the affected area (not always possible) and various relaxation strategies.

Non-pharmacological

• Transcutaneous electrical nerve stimulation (TENS) machines are useful for some patients, often as part of a comprehensive pain management strategy.

• Complementary therapies have a role in pain management, in providing analgesia and in raising the pain threshold.

• Acupuncture is increasingly being used in pain management, including by GPs. Limited evidence is available regarding its use in advanced cancer, although various reviews of the literature conclude that benefit is likely.^7,⁸

• Massage appears to be of some benefit in reducing pain and the anxiety associated with it. However, in some groups the benefit appears to be short-lived.⁹ A recent Cochrane review stated that overall there was insufficient evidence to draw firm conclusions about the benefit of massage.¹⁰ The addition of aromatherapy was not shown to provide any additional benefit.

• Music therapy is available through various avenues, including community palliative care services. It has been shown to reduce pain in cancer patients.^2,¹¹

• Other strategies employed by patients include hypnotherapy, meditation, relaxation and imagery. Trials are not consistent in demonstrating benefit.

Pharmacological

The choice of agent will depend on:

• pain severity

• likely aetiology of the pain

• presumed mechanism of pain (somatic, neuropathic etc)

• analgesics already tried

• patient preferences, fears and allergies.

Generally, analgesia for cancer pain should be given:

• around the clock rather than ‘as required’

• in adequate doses—using a combination of drugs may enable lower doses of each drug to be used, with fewer side effects.

Simple analgesics

• Paracetamol—the precise mechanism of action remains uncertain, although it may act on a cyclo-oxygenase enzyme (COX-3) only present in the brain. It can provide useful analgesia alone for mild pain or in combination with other agents for more severe pain. Newer preparations enable 8-hourly dosing to provide 24 hours of cover. Maximum doses should not be exceeded.

• NSAIDs—these have a particular role when the possibility of an inflammatory component to the pain exists, for example with bone metastases, cellulitis, thrombophlebitis. The side-effect profile should always be considered when using NSAIDs.

• Tramadol—this agent acts on multiple neurotransmitters, including weak affinity for the opioid receptor.

Opioids

Opioids are the mainstay of cancer pain management. They are particularly useful for somatic and visceral pain, as well as having an important role in neuropathic pain. The reader is referred to other textbooks for more in-depth advice on use of opioids in cancer pain. Some basic principles are listed here.

• In the elderly particularly, start low, go slow.

• Opioids should be used around the clock rather than ‘prn’. This has become much easier with the availability of slow-release preparations of morphine, oxycodone, fentanyl and so on.

• Injectable opioids have no advantage over oral where the patient is able to swallow and has a functioning gut.

• Provide ‘breakthrough’ medications to deal with exacerbations of pain. Ensure that these are rapid-acting rather than slow-acting. The breakthrough dose is approximately one-tenth of the total 24-hour baseline dose (see the example in Box 39.1; see Table 39.1 for conversions). The dose may need to be rounded to, for practical reasons.

• Calibrate the dose (see the example in Box 39.1).

• Avoid constipation. Most patients will experience constipation with opioids (although there is a lower frequency with fentanyl). Prescribe regular laxatives at the same time as the opioids are prescribed.

• Be mindful of other common side effects, such as nausea (∼30% initially) and drowsiness. Respiratory depression rarely, if ever, occurs without other signs of excessive dose, such as drowsiness.

• Patients must be warned that when opioids are commenced or increased, their ability to drive safely may be compromised. Once the dose is stable, patients can drive, provided they are not drowsy. They should be warned about additive effects of other sedative drugs, including alcohol, and advised not to drive if they use alcohol or other drugs.

BOX 39.1 Case study: opioid titration

Mr P is a 72-year-old man with pain due to metastatic colon cancer. In addition to simple analgesics he requires an opioid to adequately manage his pain. He is commenced on slow-release (SR) morphine 15 mg 12-hourly as baseline analgesia with immediate release (IR) morphine mixture 2.5–5 mg as needed for breakthrough pain (1/12 to 1/6 of 24-hour baseline dose). Aperients are prescribed prophylactically.

On review 3 days later he has consistently required 4–5 doses/24 hours of 2.5 mg morphine in order to control his pain, representing ~20 mg additional morphine. His baseline SR morphine is therefore increased to 25 mg 12-hourly with good effect. Thereafter he requires few additional doses.

TABLE 39.1 Opioid conversion to morphine equivalent

Adjuvant agents

Adjuvant agents are particularly useful in neuropathic pain. The traditional classes of drugs that have efficacy are the anticonvulsants (carbamazepine, sodium valproate, gabapentin etc) and tricyclic antidepressants. Corticosteroids have an important role in spinal cord compression, nerve root compression and so on. There are a number of other drugs that are used to manage neuropathic pain but consultation with a pain or palliative medicine specialist is advised. All these agents have side effects and the potential for drug interactions, and some require monitoring of levels or other blood parameters. Their use should be individualised.

• Radiotherapy, chemotherapy, surgery, antibiotics and so on may all have a role, depending on the cause of the pain. Many of these modalities will take some time to commence or for an effect to be seen, and so it is essential that analgesia is attended to simultaneously.

• Ongoing review is critical. Adequate control of pain requires ongoing efforts. Doses of drugs may need to be titrated to maximise effect and minimise side effects. Referral back to the treating specialist (medical oncologist, radiation oncologist or other) will be appropriate for many patients, but in the very late stages of disease, additional appointments, investigations and aggressive treatments may impose too great a burden on the patient. Advice from a palliative medicine physician or pain specialist may be appropriate.

PITFALLS

• Spinal cord compression—beware radicular pain, back pain or leg pain in a patient with known bone metastases! Approximately 90% of patients treated prior to developing weakness or paraplegia will retain independent mobility but this falls to 10% if they are unable to walk when treatment begins. Preserved continence is not reassuring.

• Continuing to escalate opioid dose without adequate response—this is a complex issue, but important concepts to consider are:

• Could the pain be neuropathic or visceral in origin and therefore poorly responsive to opioids?

• Are there psychosocial issues contributing to the distress, that could be dealt with?

• Could there be an element of opioid toxicity?

• Has there been diversion of the opioid?

Consultation with a palliative medicine specialist is strongly recommended. It is rare to achieve incremental analgesia with escalation of morphine above 1000 mg/24 h.

• Failure to prescribe aperients with opioids.

• Hypercalcaemia can present with pain as a symptom.

CONSTIPATION

Constipation may be defined in terms of frequency of defecation (< 3 times/week) or the passage of small, hard faeces with some difficulty. It is prevalent in chronic illness, particularly malignancy, affecting up to 63% of elderly inpatients. Many of the standard approaches to this common symptom are less helpful in the setting of advanced disease.

AETIOLOGY/PATHOLOGY

There are many factors that may contribute to the development of constipation in patients with cancer or other life-limiting disease. A common pathophysiological feature is slowed colonic transit time. Constipation may be a feature of the cancer itself, due to the general effects of advanced disease, a result of treatment or unrelated to the primary problem.

Cancer can cause constipation through intestinal obstruction, spinal cord or cauda equina compression and as a result of hypercalcaemia. Patients with advanced disease commonly have reduced food intake, particularly in relation to high-fibre foods, may be chronically dehydrated and suffer from generalised muscle weakness and tend to have reduced activity levels. These can all predispose to constipation.

Many medications cause constipation; most important in this context are the opioids, tricyclic antidepressants, other drugs with anticholinergic effects (e.g. hyoscine), iron supplements, certain chemotherapeutic agents (vinca alkaloids, thalidomide), diuretics, 5-HT₃ antagonists (ondansetron, tropisetron etc) and antacids. Comorbid conditions such as cerebrovascular disease may also contribute.

HISTORY AND EXAMINATION

History should include specific details of the symptoms, including:

• duration of symptoms—is this a long-term or recent complaint?

• onset—was it sudden (potentially implying bowel obstruction)?

• sensation of incomplete evacuation—suggests the presence of a rectal mass

• urge to defecate—absence may reflect damage to perineal nerves

• presence of blood.

Other important information includes:

• associated symptoms such as nausea, abdominal pain, bloating—specifically enquire about back pain, numbness and other symptoms that may suggest spinal cord/cauda equina compression

• medication list, including non-prescription items and complementary therapies—St John’s wort, goldenseal, echinacea and shark cartilage are among the herbal remedies that are reported to cause constipation in some patients

• assessment of diet, activity, mood and general wellbeing

• strategies already undertaken by the patient to relieve constipation.

Abdominal and anorectal examination can provide much information, completed by a general examination. Specific features to be alert for are:

• presence of palpable abdominal and pelvic masses, due to either organomegaly, metastatic deposits or faecal loading

• bowel sounds—‘tinkling’ or absent sounds suggest bowel obstruction

• loss of anal tone, decreased perianal sensation—consider urgent referral for evaluation of spinal cord compression

• faeces or other masses in the rectum, anal fissures—note whether faeces are hard or soft

• general features, dehydration, weakness.

INVESTIGATIONS

Routine investigations are not required. If clinical findings are suggestive of bowel obstruction, plain abdominal X-ray can help to confirm this. Occasionally it may be useful to demonstrate the extent of faecal loading. With a suggestive clinical situation, calcium levels should be checked and, potentially, thyroid function. Suspicion of spinal cord compression should prompt urgent referral and investigation as appropriate.

INTEGRATIVE MANAGEMENT

Preventative measures consist of optimal symptom control, physical activity within the patient’s limitations and maintaining adequate oral hydration. Patients with advanced disease are generally unable to consume sufficient fibre to reduce constipation, and use of fibre supplements without sufficient fluid intake can be counter-productive. Perhaps the most important preventative measure is to prescribe regular laxatives at the same time that an opioid is prescribed.

Not treating constipation is only a valid option in the very last days of life, as untreated constipation can cause severe discomfort and distress.

Many patients will be aware of particular foods or strategies that are of benefit. Some examples are licorice, beer or dried fruit. Natural therapies with demonstrated benefit include cascara, senna and pureed rhubarb.¹²

Pharmacological

Most patients, particularly those requiring opioid analgesia, will need laxatives to ease constipation. These should be taken regularly rather than ‘as needed’, with the dose titrated to maintain comfort. Laxatives can be classed as softening agents or peristaltic agents (Box 39.2), and the initial choice of drug can be guided by the predominant symptom—that is, hard faeces or faeces that are soft but difficult to pass. Bowel obstruction should be excluded prior to commencing laxatives, particularly the stimulants.

BOX 39.2 Laxatives

Softening agents

• sodium picosulfate

More recently available in Australia is methylnaltrexone bromide. This is a selective μ-opioid receptor antagonist, specifically targeted at the treatment of opioid-induced constipation. Because it has very limited capacity to cross the blood–brain barrier it is able to reverse the constipating effect of opioids in the bowel, without compromising analgesia. It is given as a subcutaneous injection and usually has a rapid onset of action, usually within 4 hours.¹³

Suppositories or enemas may be required, particularly when there is evidence of rectal loading or impaction, when oral therapy is not possible, or where a trial of oral laxatives has been unsuccessful. The mechanism of action is similar, with softening agents such as glycerine suppositories and stimulant agents such as bisacodyl Microlax™ (containing sodium citrate, sodium lauryl sulfoacetate and sorbitol) and sodium picosulfate.

Doses

Patients with advanced disease, particularly those requiring opioids for pain management, will require regular laxatives and commonly require higher than average doses. The aim of therapy is to ensure comfortable passage of faeces and relief of associated symptoms.

PITFALLS

• Faecal impaction with overflow presenting as diarrhoea.

• Failure to prescribe laxatives when opioids are commenced.

NAUSEA/VOMITING

Nausea is another symptom frequently encountered in general practice, occurring in a wide range of conditions including pregnancy (up to 80%) and myocardial infarction (50% experience nausea or vomiting). Between 40% and 70% of patients with advanced cancer are troubled by this symptom.

PATHOPHYSIOLOGY AND AETIOLOGY

Vomiting is controlled by the vomiting centre (VC), a number of adjacent, coordinated sites located in the lateral reticular formation of the medulla. The physiology of nausea is not as well understood but it may arise when stimuli excite the VC without sufficient amplification to trigger the vomiting cascade. A variety of neurotransmitters are involved at various sites, and knowledge of these can be exploited in order to target therapy (Table 39.2).

TABLE 39.2 Summary of nausea pathophysiology, aetiology and treatment

Inputs to the VC include the chemoreceptor trigger zone (CTZ), located in the floor of the fourth ventricle. An effective absence of the blood–brain barrier allows chemosensitive nerve cell endings direct contact with cerebrospinal fluid, which is in chemical equilibrium with blood. The relevant neurotransmitters are serotonin (5-HT₃) and dopamine (D₂). Vagal and sympathetic afferents are activated by gastric irritation, gastric distension, intestinal obstruction, constipation, liver disease and so on. Important neurotransmitters are 5-HT₄ and D₂. Vestibular nuclei activated by labyrinthitis, motion sickness and so on act via muscarinic (M) and histaminergic (H₁) neurotransmitters. Further input comes from the CNS (H₁) and is important in nausea induced by anxiety, fear, raised intracranial pressure, cerebral lesion, meningitis and the senses (taste, smell). Important neurotransmitters of the VC are H₁, M and 5-HT₃.

HISTORY

Obtain details from the patient when possible, in their own words. Consider frequency, volume and colour of vomitus. Does nausea precede vomiting? Have any triggers been identified? Enquire about the presence of other symptoms such as headache, dizziness, abdominal pain, constipation or features of anxiety. A complete list of medications, including non-prescribed and even illicit drugs, should be requested.

Various features can point to a possible cause:

• epigastric pain—gastritis

• small volume—squashed stomach

• very large volume—gastric stasis

• heartburn—reflux

• drowsy and confused—hypercalcaemia or raised ICP (e.g. due to cerebral metastases).

EXAMINATION

General examination needs to include vital signs, conscious state and an assessment of hydration. In the abdomen look for hepatomegaly, ascites, masses and a succussion splash. If the history raises the possibility of a CNS cause, a neurological examination is indicated.

INVESTIGATIONS

These should be tailored to the clinical situation but may reasonably include:

• electrolytes, including corrected or ionised calcium and estimation of renal function

• mid-stream urine examination (MSU).

The role of diagnostic imaging will depend not only on the particular symptoms but also on the overall condition of the patient and the goals of care. Transport to a radiology practice may not be in the best interests of patients who are particularly frail, who have very advanced disease or are confused, and where the clinical picture is unlikely to be clarified by available imaging. In other cases CT scanning of the brain or abdomen could be particularly helpful.

INTEGRATED MANAGEMENT

• Prevention of nausea and vomiting will be possible only in a limited number of circumstances, for example prior to emetogenic chemotherapy. Approximately one-third of patients who are prescribed morphine will experience nausea, often transiently, so routine prophylaxis is not generally recommended. It is reasonable to warn the patient that nausea can occur and even to provide a prescription for antiemetics, to be filled if required.

• Not actively treating nausea is seldom indicated, due to the unpleasant nature of the symptom.

• Self-help strategies can be of use. Some patients benefit from meditation, massage or other forms of relaxation therapy, particularly in the setting of chemotherapy. Home remedies include the use of ginger preparations, cinnamon tea and peppermint.¹²

• A Cochrane review of acupuncture for chemotherapy-induced nausea and vomiting showed benefit in reducing acute vomiting but not acute or delayed nausea.¹⁴ Acupuncture should be used in conjunction with antiemetics in this situation.

• Lifestyle measures include reducing activity after eating, reducing exposure to food smells, providing small portions of non-greasy food, and cold or warm rather than hot meals.

Pharmacological

Principles

1. Identify the likely cause of nausea and vomiting.

2. Identify the pathway and neurotransmitter involved.

3. Choose the most potent antagonist to the receptor identified. If several mechanisms are identified, choose the most potent for each one rather than one with several weak actions. It is also useful to identify previously helpful drugs.

4. Choose a route of administration that will ensure the drug reaches its site of action, e.g. 5-HT₃ antagonist wafers, rectal or IV administration.

5. Give antiemetics regularly and titrate the dose.

6. If symptoms persist, consider another cause.

Antiemetic drugs

• Dopamine antagonists—butyrophenones (haloperidol, droperidol), phenothiazines (prochlorperazine, chlorpromazine, levomepromazine (methotrimeprazine)). Starting dose of haloperidol may be as low as 0.25 mg b.i.d., titrate to 1.5–2.5 mg t.d.s.

• Prokinetics (metoclopramide and domperidone) act on D₂ and 5-HT₃ receptors.

• Antihistamines (cyclizine, promethazine)

• 5-HT₃ antagonists (ondansetron, tropisetron)

• Corticosteroids to reduce raised ICP.

Other management

Review other medications. If opioids are implicated, switching to another opioid can result in reduced nausea. Discussion with a palliative medicine specialist can be helpful in this situation and is recommended. Alternatives to selective serotonin reuptake inhibitors (SSRIs) may need to be considered. Digoxin doses often need to be reduced in frail patients.

Treat hypercalcaemia in appropriate circumstances. Once again, this may be unwarranted in very end-stage situations.

Treat underlying conditions such as infection or constipation. Referral back to treating specialists will be indicated for some patients, for example if raised ICP is suspected. Once again, the goals of care must be considered.

In refractory cases, such as persistent gastric outlet obstruction, it is sometimes necessary to resort to measures such as a nasogastric tube. Advice should be sought from a palliative medicine specialist.

PITFALLS

• Attempting to manage established vomiting with oral medications. A short course of parenteral therapy to gain control of vomiting is used, followed by oral antiemetics.

• Opioid-induced nausea responds well to D₂ antagonists. Another option is to change opioids, as patients vary in their susceptibility to nausea with different opioids.

• Drugs with prokinetic activity should be avoided when there is suspicion or evidence of bowel obstruction or gastric outlet obstruction.

ANOREXIA/CACHEXIA

Eating, food and meals are clearly much more than a means of sustenance. Joining family or friends at the table for dinner maintains social connections and has emotional benefits. There are also times when meals have particular cultural or religious significance. When a loved one is unable to enjoy specially prepared dishes, it can act as a harsh reminder of the toll taken by the disease. Some families will find this symptom intolerable and request that something be tried.

A cancer anorexia/cachexia syndrome has been described where:

• tissue wasting is out of proportion to anorexia

• fat loss is not preferential (as is the case with starvation) and

• supplemental feeding does not correct the weight loss.

Despite causing great distress to patients and their families, little is known about the pathophysiology of this condition.

Anorexia is common in advanced cancer, affecting up to 85% of patients. There are many contributing factors including (but not limited to) chronic nausea, constipation, dysphagia, infection, circulating cytokines, depression and altered taste. In cancer patients, the aetiology of anorexia is commonly multifactorial.

CLINICAL

A careful history and examination is required, aiming to detect the presence of treatable factors. Specific enquiry should be made about the presence of nausea, constipation, mouth pain, dysphagia and so on. Features indicative of depression or the presence of infection should also be sought (e.g. dysuria, productive cough, rigors) and a list of medications obtained.

Examination needs to be comprehensive. Note the presence and extent of wasting. Examine the mouth for evidence of mucositis or oral candidiasis, palpate for hepatomegaly or other abdominal masses that may be compressing the stomach. Consider any evidence of an infective process, such as fever, signs of pneumonia or cellulitis.

INVESTIGATIONS

There are few ‘routine’ investigations. The clinical findings will dictate the testing that should be done.

INTEGRATED MANAGEMENT

• Explanation to the patient and family is crucial. This may require a discussion of the possible causes contributing to the symptom in the individual patient, reassurance that the weight loss and reduced intake does not reflect poorly on the carer, and some practical advice. When a patient is in the last stages of their illness, further reassurance should be given that reduced appetite and intake is a normal part of the dying process and that it is rare for patients with advanced cancer to complain of being hungry. In the last stages, the most common symptom associated with inability to eat is a dry mouth. Patients and carers can be reassured that this can be readily managed with simple measures (mouth swabs, lip balm, small sips of water, grapeseed oil).

• Potentially reversible causes should be sought and treated (e.g. oral candidiasis, depression, constipation).

• Practical advice includes:

• providing small portions of food more frequently

• avoiding hot meals where the aromas can trigger nausea

• identifying foods that the patient can manage most easily; for example, many patients find softer food (custard, yoghurt) or soups easier to digest

• some patients find that a small amount of alcohol improves their appetite

• sometimes an appropriate exercise program is useful.

Pharmacological measures

Several appetite stimulants have been proposed but few have proven benefit in rigorous trials. The available options are often limited in their utility due to limited efficacy and the presence of side effects.

• Corticosteroids, e.g. dexamethasone 4–8 mg daily:

• May improve appetite, food intake, strength, performance status and wellbeing.

• Do not improve survival.

• There are many side effects (e.g. oral candidiasis, muscle weakness, fluid retention) and therefore if there is no benefit after 4–5 days, cease.

• Benefits seem to be transient—2–6 weeks in most studies.

• Progestational agents:

• Megestrol acetate is of benefit in patients with malignancy, although a Cochrane review in 2005 was unable to define the optimal dose.¹⁵ It has many potential side effects, including deep vein thrombosis and fluid retention, and can be expensive for patients.

• Cannabinoids:

• No benefit has been consistently demonstrated despite popular belief to the contrary. Side effects are troublesome, particularly in the elderly.

• Omega-3 fatty acids, especially eicosapentanoic acids:

• There are data to suggest that these agents are of benefit. Most studies have focused on pancreatic cancer. However, a recent Cochrane review concluded that the evidence was insufficient to support the use of eicosapentanoic acids to treat cachexia in advanced cancer patients.¹⁶

• They are thought to work by down-regulating pro-inflammatory cytokine and eicosanoid pathways.

• The main difficulty in practice is with the palatability of the products.

Supplemental Feeding

Many patients or families will wish to explore the possibility of supplemental feeding. The discussion needs to be handled sensitively but the salient points are as follows:

• Aggressive nutritional therapy does not significantly influence the outcome of patients with advanced cancer.

• No information is available to support or exclude improved quality of life with nutritional support in advanced cancer.

• It can make it more difficult for the patient to be cared for at home, particularly in the case of parenteral nutrition.

• There may be increased risk of infection or aspiration and, potentially, worsening of nausea.

Ongoing review

In the latter stages of disease, weighing the patient frequently is not recommended. Weight loss is often unavoidable, and repeated weighing merely reinforces the distress.

OTHER SYMPTOMS AND CARE IN THE LAST DAYS OF LIFE

Dyspnoea is a particularly difficult symptom to manage and often precipitates admission for inpatient care. A general approach would include assessment for readily reversible components (infection, new pleural effusion etc) and seeking advice from a palliative medicine specialist. Morphine and benzodiazepines are the mainstays of symptomatic management.

LAST DAYS OF LIFE

Many people express a wish to die at home, and support from a GP is a crucial part of assisting them to achieve this aim. Management in the terminal phase is dictated by attention to comfort and dignity, with the cessation of those treatments that no longer provide benefit or are no longer possible. Points to consider include the following:

• Cease unnecessary medications and interventions. Most drugs other than those directly providing symptom relief can be ceased—for example, antihypertensives, iron supplements, aspirin, antibiotics.

• Convert from oral to subcutaneous delivery where appropriate. The most common drugs required are opioid analgesics, benzodiazepines and antiemetics. Syringe drivers are a convenient method of providing continuous subcutaneous infusions, thereby obviating the need for regular injections in many situations. See Box 39.2 for a list of drugs that can be given subcutaneously.

• Provide a supply of medications that can be used if required, often by community nurses. Useful drugs include an injectable opioid, injectable antiemetic and a benzodiazepine, in either injectable or sublingual form (e.g. clonazepam drops).

• Accumulating oropharyngeal secretions occasionally cause noisy breathing or a ‘death rattle’. The most important aspects of management are explanation to the family that this is not a painful symptom for the patient and the use of judicious positioning to minimise the noise. If medication is required, glycopyrrolate is preferred over hyoscine or atropine as it does not cross the blood–brain barrier and therefore does not risk precipitating a delirium. None of these agents will significantly reduce respiratory secretions in a patient with respiratory sepsis.

• The use of an indwelling catheter may be appropriate for some patients who find that activity exacerbates pain or who develop urinary retention.

• Terminal restlessness or agitation represents an emergency situation due to the extremely distressing nature of this symptom for families. Reversible causes (e.g. urinary retention) should be excluded but otherwise pharmacological treatment is required. It may respond to relatively small doses of sedative but occasionally high doses are required, and resistant cases may require the use of agents such as levomepromazine (methotrimeprazine) or phenobarbitone. The aim is to control the distress without necessarily rendering the patient unconscious. Urgent consultation with a palliative care specialist is strongly urged.

• Mouthcare is an important aspect of terminal care. A dry mouth can be uncomfortable and distressing. This symptom can be readily managed with frequent sips of fluid or with drops of grapeseed oil applied as needed. This is cheaper and often more palatable than artificial saliva preparations.

• Supporting the family is a key aspect of care in the last days of life. They should be provided with explanations about common symptoms, what might be expected around the time of death and how to assist children at this time, as well as given opportunities to ask questions.

CareSearch, palliative care knowledge network—an online resource of palliative care information and evidence. http://www.caresearch.com.au.

Memorial Sloan Kettering Cancer Centre. http://www.mskcc.org.

Memorial Sloan Kettering Cancer Centre, Integrative Medicine Service. http://www.mskcc.org/mskcc/html/1979.cfm.

Palliative Care Australia—includes fact sheets, reports and a resource directory. http://www.pallcare.org.au.

Therapeutic Guidelines, Palliative Care—concise, practical information on all aspects of palliative care

Twycross R. Introducing palliative care, 2nd edn. Oxford: Radcliffe Medical Press, 1997. —a concise but comprehensive introduction to all aspects of palliative care, including communication, ethics, drug profiles and more

Woodruff R. Palliative medicine: evidence-based symptomatic and supportive care for patients with advanced cancer, 4th edn. Melbourne, Victoria: Oxford University Press, 2004. —written by an Australian oncologist/palliative care physician

1 Clayton JM, Hancock KM, Tattersall MHN, et al. Clinical practice guidelines for communicating prognosis and end-of-life issues with adults in the advanced stages of a terminal illness, and their caregivers. Med J Aust. 2007;186(12):S18.

2 Zappa SB, Cassileth BR. Complementary approaches to palliative oncological care. J Nurs Care Qual. 2003;18(1):22-26.

3 Oneschuk D, Hanson J, Bruera E. Complementary therapy use: a survey of community- and hospital-based patients with advanced cancer. Palliat Med. 2000;14(5):432-434.

4 Foley KM. Acute and chronic cancer pain syndromes. In: Doyle D, Hanks G, Cherny N, et al, editors. Oxford textbook of palliative medicine. 3rd edn. Oxford: Oxford University Press; 2004:298-316.

5 Pain in residential aged care facilities. Management strategies. Sydney: Australian Pain Society, 2005.

6 Bowsher D. The effects of pre-emptive treatment of postherpetic neuralgia with amitriptyline: a randomized, double-blind, placebo-controlled trial. J Pain Symptom Manage. 1997;13(6):327-331.

7 Bardia A, Barton DL, Prokop LJ, et al. Efficacy of complementary and alternative medicine therapies in relieving cancer pain: a systematic review. J Clin Oncol. 2006;24(34):5457-5464.

8 Deng G, Cassileth BR. Integrative oncology: complementary therapies for pain, anxiety, and mood disturbance. CA: Cancer J Clin. 2005;55:109-116.

9 Cassileth BR, Vickers AJ. Massage therapy for symptom control: outcome study at a major cancer center. J Pain Symptom Manage. 2004;28(3):244-249.

10 Fellowes D, Barnes K, Wilkinson S. Aromatherapy and massage for symptom relief in patients with cancer. Cochrane Database Syst Rev. 2004;3:CD002287.

11 Beck SL. The therapeutic use of music for cancer-related pain. Oncol Nurs Forum. 1991;18:1327-1337.

12 Cassileth BR. Complementary and alternative cancer medicine. J Clin Oncol. 1999;17(11 Suppl):44-52.

13 Portenoy RK, Thomas J, Moehl Boatwright ML, et al. Subcutaneous methylnaltrexone for the treatment of opioid-induced constipation in patients with advanced illness: a double-blind, randomized, parallel group, dose-ranging study. J Pain Symptom Manage. 2008;35(5):458-468.

14 Ezzo JM, Richardson MA, Vickers A, et al. Acupuncture-points stimulation for chemotherapy-induced nausea or vomiting. Cochrane Database Syst Rev. 2006;2:CD002285.

15 Berenstein EG, Ortiz Z. Megestrol acetate for the treatment of anorexia-cachexia syndrome. Cochrane Database Syst Rev. 2005;2:CD004310.

16 Dewey A, Baughan C, Dean T, et al. Eicosapentaenoic acid (EPA, an omega-3 fatty acid from fish oils) for the treatment of cancer cachexia. Cochrane Database Syst Rev. 2007;1:CD004597.

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