Prescribing in palliative care

See also separate End of Life Care and Palliative Care articles.

What is palliative care?¹

Palliative care is defined as 'the active total care of patients whose disease is not responsive to curative treatment'. It has traditionally been associated with the care of cancer patients but is also increasingly applied to the care of others with end-stage conditions such as motor neurone disease or heart failure (see also separate Palliative Care of Heart Failure article).

Symptoms and problems are often predictable. Common symptoms like pain and dyspnoea can be anticipated. Planning to prevent them, or for when they occur, is more effective than waiting until they happen. Deprescribing is an effective way of preventing morbidity in this group. Getting to know a few medicines well for each symptom is important when providing palliative care for patients. Starting at low doses and increasing slowly is also important.²

Where symptom control proves difficult, access to specialist palliative care expertise and advice is usually available through day or inpatient hospice care, Macmillan teams and hospital-based palliative care teams.

General principles for prescribing in palliative care³

The use of non-drug treatment options for symptom management are an important part of palliative care and should always be considered. For example, pain or breathlessness can be managed by using positioning, relaxation, controlled breathing, and anxiety management techniques.

Medicines used in the palliative care setting are often unlicensed or used off-label.
Close collaboration between health professionals in different care settings is essential, especially for controlled drugs and special-order preparations, to ensure continuity of supply when transferring between care locations.

For parenteral drug administration, appropriate diluents and flushes may also need to be prescribed.

Particular care should be taken when prescribing for elderly or frail patients, and for patients who are malnourished, cachectic and/or oedematous, as for these patients, renal function tests may underestimate the actual degree of renal impairment.

The use of multiple medicines concurrently is common in palliative care, as patients may already be taking medicines for chronic conditions in addition to an increasing number of treatments for symptom management. Therefore stopping some medications should be considered where appropriate, with the safe withdrawal of medicines that are no longer appropriate, beneficial or wanted, to improve quality of life and reduce the burden of unnecessary treatments, particularly in the final months of life.

Medication reviews within all specialties should be undertaken regularly to meet the changing needs of the patient, and to reduce potential harm, such as stopping medicines that are not providing symptomatic benefit, are causing harm, or are deemed no longer necessary, and long-term prophylaxis medication such as statins and antihypertensives.

Parenteral administration

For patients who are unable to take or tolerate oral medicines, subcutaneous or intravenous administration should be considered, although the subcutaneous route is the preferred choice.

The use of continuous subcutaneous infusions (CSCIs) is common within palliative care in the UK, particularly for patients where swallowing medication has become increasingly difficult or impossible:

• CSCIs reduce the need for bolus injections, provide comfort from stable drug plasma concentrations, and allow control of multiple symptoms with a combination of drugs.

• CSCIs are usually administered via a portable continuous infusion device (such as a syringe driver or pump), thus supporting patient independence and mobility.

The use of intramuscular injections is not recommended.

Common problems³

Pain control

See separate Pain Control in Palliative Care article.

Nausea and vomiting⁴

See separate Nausea and Vomiting in Palliative Care article.

• Nausea and vomiting are common in patients with advanced cancer but have many different causes - choice of antiemetic should be based on the cause wherever possible.

• In end of life care, broad-spectrum antiemetics that can be delivered via a syringe driver are chosen, most usually phenothiazines - haloperidol (effective for vomiting caused by morphine, hypercalcaemia and uraemia) and levomepromazine (broad-spectrum but sedating).

• Where bowel obstruction is the cause of the vomiting, cyclizine, hyoscine butylbromide and octreotide are suitable choices.

Agitation

Non-pharmacological management of agitation should be considered, and any reversible causes treated:

• Pain/discomfort: treat any reversible causes - eg, catheterisation for urinary retention, bowel care for constipation, hyoscine to dry up excess secretions in the throat.

• Opiate toxicity - the dose of morphine may need to be reduced as the patient's renal function deteriorates.

• Biochemical abnormalities such as hypercalcaemia and uraemia may cause restlessness but, in the end of life phase, it is not usually appropriate to check for them. They may be associated with delirium.

• Psychological or spiritual distress.

A benzodiazepine should be considered for managing agitation where anxiety is prominent, or an antipsychotic (such as haloperidol) for managing agitation where delirium is prominent.

Specialist advice should be sought if the agitation or delirium diagnosis is uncertain, is not responding to treatment, or if treatment causes unwanted sedation.

Dyspnoea⁵

See also separate Dyspnoea in Palliative Care article.

• Usually multifactorial, as it is almost always associated with anxiety.

• General measures - reassurance and explanation, upright positioning, good ventilation (fan, open window), chest physiotherapy and relaxation exercises.

• Drug measures - nebulised saline, oral or SC morphine (start with oral morphine or equivalent), benzodiazepines (eg, diazepam), oxygen (variable effect).

Cough⁶

In people with cancer, the most common cause of acute cough is respiratory tract infection. Other possible non-malignant causes include post-nasal drip, asthma, chronic obstructive pulmonary disease, and gastro-oesophageal reflux disease.

The appropriateness of investigation and treatment should be considered against the prognosis, the likely benefit of treatment, and the person's wishes.

Managing symptomatic cough in palliative care can be done by a stepwise approach:

• Simple measures, such as humidified room air or simple linctus.

• A weak opioid cough suppressant, such as codeine linctus.

• A strong opioid cough suppressant, such as morphine.

• Measures to encourage expectoration in people with moist cough and an effective

• cough mechanism, such as nebulised saline solution or a mucolytic.

Excessive respiratory secretions

Fluid collection in the upper airway (most commonly from saliva) can cause a rattling noise.

If this causes distress in the patient’s last days of life, consider non-drug measures (such as positioning) or a trial of drug treatment (medicines may take up to 12 hours to become effective).

An antimuscarinic (such as hyoscine butylbromide or glycopyrronium bromide) given subcutaneously as soon as the rattle begins may be of benefit.

Anorexia

• Anorexia is common in patients with advanced disease. For patients with early satiety due to delayed gastric emptying, a trial of a prokinetic drug such as metoclopramide hydrochloride or domperidone (if benefits outweigh risks) can be considered.

• Dexamethasone, prednisolone, or a progestogen (such as megestrol acetate) may also be considered as treatment options to stimulate appetite, although there is no evidence that they improve muscle mass/strength, and corticosteroids themselves can cause myopathy.

• Thus, treatment should be closely monitored and stopped if no benefit is achieved after 1–2 weeks. If longer term treatment (beyond 2-3 weeks) is being contemplated, a progestogen may be more appropriate than a corticosteroid.

Bowel colic

• Bowel colic can occur with conditions such as bowel obstruction, or as a side-effect of some drugs. Bowel colic may be reduced by hyoscine butylbromide. If bowel colic is related to constipation, it is also important to ensure stool is adequately softened.

Constipation

• Constipation can cause psychological distress and agitation in patients, and is common with the use of opioid analgesics. All patients prescribed a strong opioid should be given a regular laxative.

• A stimulant laxative (such as bisacodyl or senna) is recommended, with the dose adjusted according to response. If there is a lack of response at the highest dose of a stimulant laxative and/or there has been no bowel movement within 3–4 days, an osmotic laxative (such as macrogol 3350 or lactulose) should be added to the regimen with further titration as needed.

• For patients with a history of colic with stimulant laxatives, initial treatment with an osmotic laxative is preferable.

• Docusate sodium may also be considered as an option in some patients who have failed to respond or have bowel colic.

• If oral laxatives are ineffective or unsuitable, suppositories of bisacodyl or glycerol, or a micro-enema of sodium citrate should be offered.

• If these options are also ineffective, an enema of sodium acid phosphate with sodium phosphate should be offered.

• The use of methylnaltrexone bromide is reserved for opioid-induced constipation when optimal use of other laxatives is ineffective.

Dry mouth⁷

• Certain drugs can cause dry mouth, including opioids, antimuscarinics, some antidepressants, and some antiemetics. If possible, alternative options should be considered.

• Dry mouth may be relieved by good mouth care, and measures such as sucking crushed ice and taking frequent sips of water. Chewing sugar-free gum acts as a saliva stimulant and is as effective as, and for some patients is preferred to, the use of artificial saliva.

• Artificial saliva may be considered for those who do not respond to non-drug measures; specialist options include systemic salivary stimulants.

• Dry mouth associated with candidiasis can be treated with oral preparations of miconazole or nystatin. Fluconazole is preferred for moderate-to-severe infections, or with concurrent odynophagia (suggesting oesophageal candidiasis), or if nystatin or miconazole are unsuitable or ineffective.

Dysphagia

• A corticosteroid such as dexamethasone may be used if there is an obstruction due to a tumour.

• Dysphagia caused by oesophagitis and oesophageal spasm may be treated with sublingual glyceryl trinitrate used before meals.

Anxiety

• There is comparable efficacy between drug treatment and cognitive behavioural therapy.

• For patients with a prognosis of days to weeks, a benzodiazepine (such as diazepam, lorazepam or midazolam) can be used.

• For patients with a prognosis of months, a selective serotonin reuptake inhibitor (SSRI) with or without a benzodiazepine initially, can be used.

Depression

• There is comparable efficacy between drug treatment and cognitive behavioural therapy, with treatment choice based on the severity of symptoms, their functional impact, and patient preference, with frequent patient reviews. When antidepressant treatment is considered, SSRIs are usually considered as first-line drug treatment for most patients, with citalopram or sertraline being the first-line drugs of choice, due to their lower risk in overdose and being better tolerated.

• Mirtazapine may be preferred for patients who also suffer from nausea, insomnia, or a reduced appetite.

• A serotonin-norepinephrine reuptake inhibitor (SNRI) (such as duloxetine) may be considered if depression and neuropathic pain co-exist.

Insomnia

• Contributing factors may include pain, certain drugs (such as corticosteroids or diuretics), or conditions such as delirium, depression, anxiety, or obstructive sleep apnoea.

• Initial treatment involves correction of any contributing factors (where possible) and non-drug measures (eg, sleep hygiene techniques) before drug treatments are considered.

• When drug treatment is required, consider the use of a drug to help the underlying cause, which may include the use of a benzodiazepine, Z-drug, melatonin, antidepressant, or antipsychotic.

Raised intracranial pressure

A corticosteroid (such as dexamethasone) can provide temporary symptomatic relief from pain due to raised intracranial pressure from cerebral oedema.

Seizures

• There are many potential causes of seizures in advanced disease (such as brain tumours or biochemical abnormalities) and specialist advice should be sought where the diagnosis of seizures, or choice or dose of antiepileptic drug is in doubt.

• Antiepileptic drugs should not be used prophylactically in the absence of a history of seizures.

• In palliative care, levetiracetam is generally preferred as a first-line option as the dose can be titrated rapidly and there are fewer drug interactions. In the last days of life, midazolam may be preferred due to benefit in concurrent symptoms and compatibility with other drugs in a CSCI.

Hiccups

In patients with hiccup due to gastric distension with or without gastro-oesophageal reflux, a prokinetic (such as metoclopramide), an antiflatulent (such as peppermint oil or simeticone), or a proton pump inhibitor (such as lansoprazole or omeprazole) can be given.

Capillary bleeding⁸

Capillary bleeding can be treated with oral tranexamic acid. Consider specialist referral to address the underlying cause and/or for advice if necessary.

Malignant skin ulcer⁹

The management of malignant skin ulceration includes:

• Wound cleansing and debridement: Gently irrigating the ulcer and surrounding skin using non-woven sterile swabs. Do not clean wounds by scrubbing, which causes pain and local tissue oedema. Irrigation is more protective of fragile tissue. Natural (autolytic) debridement may be promoted by the use of specialist dressings. Sharp debridement (using a sterile blade, scalpel, or scissors) is not recommended as it may cause bleeding in friable tissue. If sharp debridement is considered then consider referral for specialist surgical debridement to the local Tissue Viability Team. Mechanical debridement (removing necrotic tissue with gauze) is not recommended as it may indiscriminately remove granulation and epithelial tissue.

• Dressing choice and management: the choice of dressing will depend on the type, site, and size of the ulcer. Dressings should be changed as often as necessary to manage pain, infection, bleeding, exudate, and odour, but try to minimise changes where possible.

• Pain relief: prescribe analgesia if needed.¹⁰

• Infection: if infection is suspected, cleanse the surface, then take a swab. If considered necessary on clinical grounds, prescribe a suitable antibiotic (eg flucloxacillin) while awaiting swabs results.

• Bleeding: for mild bleeding, apply gentle pressure for 10–15 minutes with a moist, non-adherent dressing. Other options include gauze soaked in adrenaline 1:1000, sucralfate suspension or alginate dressings that also have haemostatic properties. Avoid causing unnecessary pain. For heavier bleeding, apply pressure and seek urgent advice from the person's oncologist or palliative care team. Admission may be appropriate depending on the stage of illness. Anti-fibrinolytic treatment (eg tranexamic acid) may be useful, but should only be prescribed on specialist advice.

• Odour: prescribe topical or oral metronidazole if the appropriate dressings do not control odour. Topical metronidazole (0.75%) is more effective if there is excess necrotic tissue present. Oral metronidazole may be better for deep tissue infections causing odour.

• Pruritus: if the ulceration is itchy, consider the use of a mild topical corticosteroid such as 1% hydrocortisone cream if the skin around the ulcer is red and scaly. Exclude other causes of irritation, such as a local infection or irritation from dressings or treatments applied to the area. Transcutaneous electrical nerve stimulation (TENS) may be considered in a specialist setting.

Pruritus

• Pruritus occurs commonly, and for some patients it can be very severe and distressing. Causes may include dry skin (very common in advanced cancer), other conditions such as renal or hepatic failure, or be drug-induced (eg, opioid-induced). Whenever possible, the treatment of pruritus should be cause-specific.

• Pruritus often responds to the application of an emollient.

• A topical antipruritic (such as levomenthol cream) can be used to relieve pruritus unresponsive to an emollient and/or cause-specific treatment. A trial of an antihistamine can also be considered.

• If pruritus persists, specialist options include SSRIs (cholestatic pruritus) and gabapentinoids (uraemic pruritus).

See separate Constipation in Adults, Dry Mouth (Xerostomia), Insomnia, Itching and Raised Intracranial Pressure articles.

Palliative care emergencies

Whilst anticipatory prescribing is vital, it is still appropriate that the doctor's bag should routinely contain injectable emergency medications to use in an unpredicted crisis.^{11 12}

Good emergency symptom control may avert an unnecessary hospitalisation. Emergencies can include:¹³

• Severe haemorrhage.

• Choking - see separate Choking and Foreign Body Airway Obstruction (FBAO) article.

• Acute tracheal compression.

• Grand mal convulsions.

• Psychiatric emergencies (eg, panic, acute severe agitation, agitated delirium).

• Severe acute pain (eg, biliary or ureteric colic, intrahepatic bleed, bladder spasm, acute vertebral collapse, pathological fracture of a long bone).

Disposal of medicines following death

See the separate Controlled Drugs article.