See also separate articles Terminal Care and Palliative Care.

Terminal care refers to the care of the dying patient in the last hours or days of life. It fits into the broader camp of palliative care which is defined as 'the active total care of patients whose disease is not responsive to curative treatment'. Traditionally this has been associated with the care of cancer patients but, increasingly, is also applied to the care of others with end-stage terminal conditions such as motor neurone disease or 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 psychological, social and spiritual in addition to physical dimensions to care of the dying - the use of nondrug measures is as important as medication in relieving suffering.

Wherever terminal care is undertaken, good communication and close multidisciplinary teamwork is essential. In primary care, the Gold Standards Framework¹ aims to improve the quality of palliative care by focusing on the organisation of care of dying patients. Symptom control forms one of 7 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 terminal 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.

General principles

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 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 dosage is optimum and to avoid unacceptable side-effects. Are goals for treatment being met?

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 so is frequently not possible to the end of life.
  • 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 (e.g. 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

Opioid potency ratios

See also separate article Pain Control in Terminal Care.
Conversion tables are available online⁶ or in the BNF.⁷

Transdermal opioids^3,7

Prescribers of transdermal patches must be familiar with their correct use, as inappropriate use has caused fatalities.⁸ Fatal respiratory depression is a risk, particularly in patients not previously exposed to strong opioids, and manufacturers of fentanyl advise use only in opioid-tolerant patients.

Fentanyl

• Converting from oral morphine to transdermal fentanyl - approximate equivalents of 24-hour oral morphine intake to fentanyl patches:
  • Morphine salt 45 mg daily ≡ fentanyl '12' patch
  • Morphine salt 90 mg daily ≡ fentanyl '25' patch
  • Morphine salt 180 mg daily ≡ fentanyl '50' patch
  • Morphine salt 270 mg daily ≡ fentanyl '75' patch
  • Morphine salt 360 mg daily ≡ fentanyl '100' patch
• Patches are worn for 72 hours. Apply to dry, non-irritated, non-irradiated, non-hairy skin on the torso or upper arm. Steady-state plasma concentrations of fentanyl are achieved after 36-48 hours and minimal effective plasma concentration from 3-23 hours. Phase out previous analgesic therapy gradually from the time of the first patch application. Give morphine (either oral solution or standard formulation tablets) for breakthrough pain.
• If effective analgesia lasts less than 3 days, increase the patch strength rather than frequency of change of patch. Dose adjustment should not occur more rapidly than 72-hour intervals in steps of 12-25 micrograms/hour. Replacement patches should be sited on a different area to the previous patch. Where more than one patch is used (for doses greater than 100 micrograms/hour), these should be applied in synchronicity.
• Some patients experience withdrawal symptoms such as diarrhoea, colic, nausea, sweating and restlessness, when converting from oral morphine to transdermal fentanyl despite satisfactory analgesia. Such symptoms are easily treatable by using rescue doses of morphine until they resolve after a few days.
• Rate of delivery may be increased by high fever and exposure of patches to external heat sources such as heat pads or electric blankets.
• Fentanyl is less constipating than morphine so laxative dose can usually be reduced on conversion.
• Patches should not be cut as reservoir-based patches may rapidly leak and potentially cause an overdose.⁸
• Prescriptions should specify strength of a fentanyl patch in terms of release rate (it is acceptable to write 'fentanyl 25 patches' to specify a release rate of 25 micrograms/hour) and the interval between new patches.
• After removing a patch, elimination plasma half-life is almost 24 hours and patients who have had severe side-effects should continue to be monitored for up to 24 hours after patch removal.

Buprenorphine

Buprenorphine has both opioid agonist and antagonist properties; patches are available as 4- (Transtec®) and 7-day (BuTrans®) patches. Seek specialist palliative care advice if converting from oral morphine to transdermal buprenorphine. Time to reach steady-state plasma concentration is slower compared with fentanyl, and there is a half-life of approximately 30 hours, so that elimination may also take some time after patches are stopped. Its role in the palliative care formulary remains to be clarified but expert consensus supports its efficacy as well as good safety and tolerability profile.⁹

Care of patients in the dying phase

Diagnosis of dying¹⁰

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 for the dying^2,11

Always consult local guidelines and protocols where available:

• Review current medication - stop all nonessentials. Also, stop any inappropriate monitoring (such as bloodtests and vital signs).
• Conversion to continuous subcutaneous (SC) infusion (CSCI) - see also separate article Syringe Drivers. Essential drugs, e.g. 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.

• 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.¹²
  • 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.
• Prn medication should be prescribed and available, including:
  • Analgesics: e.g. diamorphine/morphine SC q1h (prn dose will depend on regular dose)
  • Antiemetics: e.g. metoclopramide 10-20 mg SC q1h or levomepromazine 6-25 mg SC q1h
  • Sedative: e.g. midazolam 2.5-10 mg SC q1h
  • Antisecretory drug: e.g. hyoscine butylbromide SC 20 mg q1h
  • Delirium: haloperidol 2.5-5 mg SC q1h
• 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.¹³
• 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.

Common problems

Pain control

Poor tolerance of standard analgesics (opioids)

Strategies for improving tolerance:
• Start with a low initial dose of opioids and titrate slowly upwards as needed. Avoid inducing tolerance unnecessarily.
• Use short-acting preparations until established.
• Sedation often improves after 48 hours. Warn patients that initial sedation is to be expected but usually settles.
• Pain may appear to be morphine-resistant if underdosing (too small doses, too infrequently or taken prn) or if alimentary absorption is poor.
• Consider alternative opioids (tramadol, fentanyl, hydromorphone, oxycodone, methadone) if problems persist - often worth discussing with the palliative care team first.
• Consider other causes.

Bone pain

• Suggested by pain on movement, which can often be difficult to control with opioids.
• Management options include radiotherapy, surgical stabilisation of fractures, use of paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs), IV bisphosphonates, and epidurals.

Neuropathic pain

• Sometimes suggested by specific features (burning, shooting quality, distribution and nerve vulnerability to pathological process) but often by poor response to opioids.
• Management usually involves prescribing a secondary analgesic - tricyclic antidepressants (e.g. amitriptyline 10-75 mg nocte), anticonvulsants (e.g. valproate, gabapentin), capsaicin cream, local blocks/epidurals, TENS machine, and acupuncture.

'Total pain' - physical expression of psychological/spiritual/social distress

• This requires an holistic approach.
• Consider: counselling or access to spiritual advisors, antidepressants, anxiolytics, complementary therapies, prn medication (giving the patient control).

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 terminal 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.

Terminal restlessness

Consider:

• Pain/discomfort - the patient may not be able to communicate the source. Treat any reversible causes, e.g. 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 terminal 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 5 mg q4h or equivalent), benzodiazepines (e.g. diazepam 5-10 mg PO daily), 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.

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.^14,15 Good emergency symptom control may avert an unnecessary hospitalisation. Terminal emergencies can include:³

• Severe haemorrhage.
• Choking.
• Acute tracheal compression.
• Grand mal convulsions.
• Psychiatric emergencies (e.g. panic, acute severe agitation, agitated terminal delirium).
• Severe acute pain (e.g. biliary or ureteric colic, intrahepatic bleed, bladder spasm, acute vertebral collapse, pathological fracture of a long bone).

Ethical and legal aspects to terminal prescribing

Palliative sedation and the doctrine of double effect¹⁶

Terminal prescribing is often full of ethical anxiety for the prescriber, particularly in situations where a terminally ill person faces refractory symptoms. Palliative sedation is the poorly defined practice of continuous deep sedation used in patients with terminal illness 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 purposively 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 terminal 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 terminal care.¹⁷

Disposal of medicines following death

See also separate article Controlled Drugs.

Following the Shipman Inquiry,¹⁸ the Government amended its legislation tackling the management of controlled drugs in the UK. 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.^19,20

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.¹⁹

Document references

1. Gold Standards Framework for England; A programme for community palliative care; A standard of excellence for carers
2. Liverpool Care Pathway of a Dying Patient (community)
3. Symptom Management in advanced cancer by R. Twycross and A. Wilcock (3rd edition) 2001. Radcliffe Medical Press ISBN 1857755103
4. Dept of Health; Securing proper access to medicines in out-of-hours periods, Dec 2004
5. Palliative care formulary
6. Opioid Potency Ratios; Palliative Medicine Handbook (online)
7. British National Formulary; 59th Edition (March 2010) British Medical Association and Royal Pharmaceutical Society of Great Britain, London (link to current BNF)
8. MHRA Drug Safety Update, Vol 2, issue 2, Sept 2008
9. Pergolizzi JV, Mercadante S, Echaburu AV, et al; The role of transdermal buprenorphine in the treatment of cancer pain: an expert panel consensus. Curr Med Res Opin. 2009 May 11. [abstract]
10. Ellershaw J, Ward C; Care of the dying patient: the last hours or days of life. BMJ. 2003 Jan 4;326(7379):30-4.
11. Supportive and palliative care, NICE (2004)
12. Control of pain in adults with cancer, SIGN (November 2008)
13. Palliative Medicine Handbook Anticipatory prescribing in the community; Useful calculator for quantity of ampoules to prescribe
14. 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. [abstract]
15. No authors listed; Drugs for the doctor's bag: 1--adults. Drug Ther Bull. 2005 Sep;43(9):65-8. [abstract]
16. 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. [abstract]
17. 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. [abstract]
18. Shipman Inquiry - 4th Report, recommendations; Shipman Inquiry - 4th Report
19. Dept of Health; Safer management of controlled drugs: early action (February 2007)
20. The Controlled Drugs (Supervision of Management and Use) Regulations 2006 (UK Government Website)

Internet and further reading

• Palliative care - dyspnoea, Clinical Knowledge Summaries (2007)
• Palliative care - nausea and vomiting, Clinical Knowledge Summaries (2007)
• Palliative care - oral problems, Clinical Knowledge Summaries (2007)
• Palliative care - pain; Palliative cancer care - pain, Clinical Knowledge Summaries (March 2009)
• Palliative cancer care - secretions, Clinical Knowledge Summaries (2007)
• National Council for Palliative Care

Acknowledgements