Prescribing in Palliative Care

oPatientPlus articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use, so you may find the language more technical than the condition leaflets.

See also separate articles End of life care and Palliative care.

Palliative care, which is defined as 'the active total care of patients whose disease is not responsive to curative treatment', 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 article Palliative care of heart failure). Emphasis should be placed on improving quality of life for the patient and relieving troubling symptoms rather than prolonging life. Good palliative prescribing is important but drugs are rarely the total answer for the relief of pain and other symptoms. Always consider the psychological, social and spiritual needs of the person. The use of nondrug measures is as important as medication in relieving suffering.

Wherever end of life care is undertaken, good communication and close multidisciplinary teamwork are essential. In primary care, the Gold Standards Framework[1] aims to improve the quality of palliative care by focusing on the organisation of care of dying patients. Symptom control forms one of seven key tasks of the framework (the others being: communication, co-ordination, continuity, continued learning, carer support and care of the dying). Also important is the Liverpool Care Pathway for the Dying Patient which provides a template of best practice and is now the standard for record-keeping in end of life care. Although developed for inpatient use, it can be adapted for use in the community.[2] It encompasses a management checklist including discontinuation of inappropriate treatment, provision of anticipatory medication and review of common symptoms on a daily basis.

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.

Try to follow a systematic approach to symptom control in palliative care:[3]

  • Evaluation: always try to diagnose the cause of symptoms (not necessarily the disease process - consider treatment side-effects, general debility and concurrent disorders) as the treatment's efficacy will depend on the underlying mechanism. For example, vomiting can be due to hypercalcaemia or raised intracranial pressure and require different treatments.
  • Explanation: good explanation of the mechanism underlying the symptom, treatment options and involvement of family are all crucial.
  • Individualised treatment: the patient should determine treatment priorities. Set realistic goals of treatment together. Take precise drug histories - what is being taken currently, what has been tried before, problems with medication and concerns affecting concordance.
  • Supervision: regular monitoring of symptom control is important in order to ensure that the treatment goals are being achieved and to avoid unacceptable side-effects.

Other important palliative care prescribing issues:

  • Prophylactic prescribing - medication 'by the clock' for persistent symptoms.
  • Simple, acceptable treatment regimens:
    • Aim to use the minimum possible number of drugs.
    • Consider size, shape and taste of medication.
    • Try to avoid inconvenient doses or dose intervals.
    • Consider the risk of adverse effects and drug interactions.
  • Written advice - reinforce spoken instructions - a chart is usually helpful for the patient and family to work from, with timing, names of drugs and dose (as quantity of liquid, number of tablets, etc.) and purpose outlined.
  • Continuity of care - communication is essential between all prescribers (GP, out-of-hours service, palliative care specialists), nursing teams and pharmacists so all are aware of changes and so that the patient and family are not confused by any alterations to medication made. Availability of equipment and drugs needs to be assured, particularly out-of-hours,[4] and changes in prescriptions should be anticipated to avoid delays in obtaining vital medication.
  • Route of administration:
    • Oral administration can be limited by severe nausea or vomiting, dysphagia, bowel obstruction, weakness or coma and so is often not an option for palliative care.
    • Rectal, transdermal and parenteral routes offer different options. Analgesia is available in suppository form (morphine, oxycodone) and transdermal preparations (fentanyl, buprenorphine) can also be useful, particularly in ambulatory patients where the oral route is difficult, where intractable constipation or other problems tolerating morphine develop.
    • Oral or nasal transmucosal fentanyl may be useful for breakthrough pain, as it is swiftly absorbed, providing a more rapid onset of pain relief, compared with oral morphine.[5] However, there is no correlation between the dose of regularly administered strong opioid and prn ('as needed') requirements or fentanyl - these must be titrated.
  • Relative potencies - care must be taken when switching between different opioids and different routes of administration. Patients who have already received weak oral opioids (eg codeine, tramadol) should not be considered opioid-naive when converting to stronger opioids, so require an adjusted starting dose.
  • Unlicensed use of drugs - many palliative treatments involve the unlicensed use of drugs or by unlicensed routes.
  • Progressive disease - will alter how drugs are handled. In particular, worsening renal failure will lead to an accumulation of morphine-6-glucuronide (active metabolite of morphine). Signs of morphine toxicity may develop (increasing drowsiness, myoclonic jerks, delirium) and the morphine dose should be reduced down or the dose interval increased. Severe hepatic insufficiency will affect the metabolism of morphine and similarly may necessitate a dose reduction.[3]
  • Individual differences - some patients may require very high doses of morphine compared with others - this may reflect age (older patients tend to require less), use of adjuvant drugs and nondrug measures, pharmacokinetic differences (absorption, hepatic and renal function), pain tolerance threshold, previous use of strong opioids, duration of treatment and adequacy of management of other symptoms.[3]

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Diagnosis of dying[6]

One of the biggest barriers to good care of the dying is healthcare professionals' reluctance to diagnose dying. Recognising the key signs and symptoms is an important clinical skill. In cancer patients, usually death is preceded by a gradual deterioration in functional status:

  • The patient becomes bed bound.
  • The patient is semicomatose.
  • The patient is able to manage sips of fluid only.
  • The patient can no longer manage oral drugs.

The predictability of the dying phase is not as clear in some other chronic incurable diseases. Where a patient is recognised by his healthcare team to be in the dying phase (within days or hours of death), this can be communicated to the patient, if appropriate, and to the relatives. Appropriate care goals and prescribing can also be put into place to facilitate a 'good death'.

Prescribing when providing end of life care[2][7]

Always consult local guidelines and protocols where available. See the British National Formulary for further information regarding drug doses and equivalent doses when converting from one drug to another.[8]

  • Review current medication - stop all non-essentials. Also, stop any inappropriate monitoring (such as blood tests and vital signs).
  • Conversion to continuous subcutaneous infusion (CCSI) - see also separate article Syringe drivers. Essential drugs, eg opioids, anxiolytics, and antiemetics, should be converted to the SC route via a syringe driver in most instances. It is slightly more complicated where a patient has previously been using opioid transdermal patches (see below). The use of a 'just in case' box has been instituted in some areas, enabling these drugs to be prescribed in advance and stored at home until needed, once the dying trajectory has been recognised.
  • Use of SC diamorphine for pain control in dying patients:
    • If already on oral morphine, divide the daily dose of morphine by three to provide the total 24-hour CCSI of diamorphine. For example, morphine sulphate (MST) 30 mg bd PO is equivalent to diamorphine 20 mg SC over 24 hours.
    • If not already taking oral morphine, prescribe diamorphine 2.5-5 mg SC prn and, after 24 hours if three or more doses have been required, consider a continuous infusion via syringe driver.
    • For breakthrough pain, intermittent prn SC injections of 1/6 of total 24-hour infusion dose should be given and the diamorphine dose increased by 30-50% when the syringe is renewed.
  • Other drugs that can be used in syringe drivers[8]
  • Drug compatability - not all drugs can be mixed in a syringe driver. Those suitable to be mixed with diamorphine include:
    • Cyclizine - may precipitate at higher concentrations (>10 mg/mL), with increasing concentrations of diamorphine or where a solution is older than 24 hours.
    • Dexamethasone - care is needed with preparation to avoid precipitation
    • Haloperidol - precipitation beyond 24 hours is likely where haloperidol concentration is greater than 2 mg/mL
    • Hyoscine butylbromide.
    • Hyoscine hydrobromide.
    • Levomepromazine.
    • Metoclopramide - discard if it becomes discoloured.
    • Midazolam.
  • Patients using opioid transdermal patches - these can continue to be used into the last few days of life. However, titration is too slow to match any change in analgesic requirement at this time so, where there is increasing analgesic requirement, this should be given as diamorphine in addition to the patch.[9]
    • Where pain is well-controlled: continue the current patch regime, with diamorphine SC for breakthrough pain.
    • Where pain is not well-controlled:
      • Continue the current patch regime.
      • In addition, start diamorphine via a syringe driver with its dose based on the previous 24 hours' breakthrough requirements.
      • For the new breakthrough dose, calculate the patch dose (diamorphine equivalent) and pump diamorphine delivery/24 hours and divide by 6.
      • Further increments in pump diamorphine doses should also be calculated based upon the patch dose, as well as pump diamorphine and breakthrough doses over 24 hours.
  • As required medication should be prescribed and available, including:
    • Analgesics: eg diamorphine/morphine (as required dose will depend on regular dose).
    • Antiemetics: eg metoclopramide or levomepromazine.
    • Sedative: eg midazolam.
    • Antisecretory drug: eg hyoscine butylbromide.
    • Delirium: haloperidol.
  • Anticipatory prescribing should ensure that there is no delay in responding to a symptom if it occurs. All patients starting the Care Pathway for the last days of life at home should have diamorphine (or alternative), cyclizine, midazolam and hyoscine available in the home, with sufficient for use over a weekend (plus bank holidays). Do not omit water for injection.[10]
  • Patient comfort - consider, for example, the need for mouth care and urinary catheterisation or pads where the patient is incontinent.
  • Monitoring - regular checks should be made to ensure good symptom control is maintained and to assess response to any changes in medication. Also important is regular monitoring of syringe drivers to check for precipitation, discoloration and to ensure the driver is running at the correct rate. If there is evidence of an injection site reaction, if the infusion is running too slowly or if there is pain or obvious inflammation, the injection site should be changed.

Pain control

See separate article Pain control in palliative care.

Nausea and vomiting

See also separate article Nausea and vomiting in palliative care.

  • 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.

Restlessness

Consider:

  • Pain/discomfort - the patient may not be able to communicate the source. 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.

Management options:

  • Haloperidol - less sedating.
  • Midazolam - sedating.
  • Levomepromazine - highly sedating; use in place of haloperidol if the patient remains agitated despite haloperidol and midazolam.

Dyspnoea

See also separate article Dyspnoea in palliative care.

  • Usually multifactorial, as anxiety is almost always associated.
  • 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).

Excessive respiratory secretions ('death rattle')

  • This is particularly distressing for relatives.
  • If present, this may be reduced by use of hyoscine hydrobromide or glycopyrronium. Particular attention should be given to mouth care, as this will cause an extremely dry mouth.

Other common conditions[8]

  • Anorexia may be helped by prednisolone 15-30 mg daily or dexamethasone 2-4 mg daily.
  • Capillary bleeding can be treated with tranexamic acid, which is usually stopped one week after the bleeding has stopped or is continued at a reduced dose. The use of gauze soaked in tranexamic acid 100 mg/mL or adrenaline (epinephrine) solution 1 mg/mL (1 in 1,000) applied to the affected area is an alternative.

See separate articles Constipation in adults, Dry mouth (xerostomia), Hiccups, Insomnia, Itching (pruritus) and Raised intracranial pressure.

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:[3]

Palliative sedation and the doctrine of double effect[13]

Prescribing for patients at the end of life is often full of ethical anxiety for the prescriber, particularly in situations where a person at the end of life faces refractory symptoms. Palliative sedation is the poorly defined practice of continuous deep sedation used in patients at the end of life where normal medical treatment is failing to relieve severe symptoms of pain or agitation, and the ultimate option is to sedate beyond perception of these symptoms.

Doctors are duty-bound to relieve suffering but not to cause the patient's death. The use of medication to end someone's life constitutes euthanasia and is currently illegal in the UK. However, the doctrine of double effect is widely accepted and refers to the use of higher doses of opioids and sedatives to relieve end of life suffering without the intention of causing the patient's death, even though the risk of hastening death is foreseen. In reality, evidence suggests that palliative sedation in the last hours of life is not associated with shortened survival overall so that the doctrine of double effect need not routinely be invoked to excuse this aspect of end of life care.[14]

Disposal of medicines following death

See also separate article Controlled drugs.

The Misuse of Drugs Regulations 2001 has been amended and the Controlled Drugs (Supervision of Management and Use) Regulations 2006 came into effect on 1st January 2007.[15][16] Currently, all drugs once dispensed are the patient's property and pass to family on death. However, it is illegal to possess controlled drugs not prescribed for you. In the first instance, relatives should be encouraged to return unused medication to the community pharmacy after their family member's death. Where this is not possible, good practice is suggested as: destruction of unused controlled drugs by community nurses with another member of the team acting as witness or return of unused controlled drugs by involved healthcare professionals to the community pharmacy for destruction.[15]

Further reading & references

  1. Gold Standards Framework: Improving Community Care
  2. Liverpool Care Pathway for the Dying Patient (LCP), The Marie Curie Palliative Care Institute, Liverpool
  3. Symptom Management in advanced cancer by R. Twycross and A. Wilcock (3rd edition) 2001. Radcliffe Medical Press ISBN 1857755103
  4. Securing proper access to medicines in out-of-hours periods, Dept of Health, Dec 2004
  5. Palliativedrugs.com; online palliative care formulary
  6. Ellershaw J, Ward C; Care of the dying patient: the last hours or days of life. BMJ. 2003 Jan 4;326(7379):30-4.
  7. Supportive and palliative care; NICE (2004)
  8. British National Formulary; 63rd Edition (Mar 2012) British Medical Association and Royal Pharmaceutical Society of Great Britain, London
  9. Control of pain in adults with cancer; Scottish Intercollegiate Guidelines Network - SIGN (November 2008)
  10. Palliative Medicine Handbook Anticipatory prescribing in the community; Useful calculator for quantity of ampoules to prescribe
  11. Seidel R, Sanderson C, Mitchell G, et al; Until the chemist opens - palliation from the doctor's bag. Aust Fam Physician. 2006 Apr;35(4):225-31.
  12. Drugs for the doctor's bag: 1 - adults; Drug Ther Bull. 2005 Sep;43(9):65-8.
  13. Lo B, Rubenfeld G; Palliative sedation in dying patients: "we turn to it when everything else hasn't worked". JAMA. 2005 Oct 12;294(14):1810-6.
  14. Sykes N, Thorns A; Sedative use in the last week of life and the implications for end-of-life decision making. Arch Intern Med. 2003 Feb 10;163(3):341-4.
  15. Safer management of controlled drugs: early action, Dept of Health (February 2007)
  16. The Controlled Drugs (Supervision of Management and Use) Regulations 2006; legislation.gov.uk

Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. EMIS has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions.

Original Author:
Dr Chloe Borton
Current Version:
Peer Reviewer:
Dr John Cox
Last Checked:
19/07/2012
Document ID:
531 (v6)
© EMIS