Prescribing in Terminal 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 also applied to the care of others with end-stage terminal conditions such as motor neurone disease or heart failure. Approximately a quarter of all deaths are due to cancer, a quarter due to heart disease and a sixth due to respiratory disease.¹

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.

Two-thirds of deaths occur in hospital, a fifth at home and only 4% in hospice care.¹ Where ever terminal care is undertaken, good communication and close multi-disciplinary team work is essential. In primary care, the Gold Standards Framework² aims to improve the quality of palliative care by focussing 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 integrated care pathway of the dying patient which provides a template of best practice and is now the standard for record-keeping in terminal care. Although developed for in-patient use, it can be adapted for use in the community.³ It encompasses a management checklist including:

• Discontinuation of inappropriate treatment
• Provision of anticipatory medication
• Review of 12 common symptoms on a daily basis
• Identification of divergence from the pathway - this enables learning needs of individuals or organisations to be identified.
• Post death goals dealing with communication, support of the family and paperwork.

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 control⁴:

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.

Individualized 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.
In the community, there needs to be good liaison and sharing of information with out of hours services, pharmacists and district nursing teams to ensure continuity of care. Availability of equipment and drugs needs to be assured, particularly out-of-hours⁵ and changes in prescriptions should be anticipated to avoid delays in obtaining vital medication.

Other important palliative care prescribing issues:

• Prescribe prophylactically for persistent symptoms.
• Keep the treatment as simple as possible. Aim to use the minimum possible number of drugs.
• Consider the treatment goal for any new medication and how this will be monitored.
• Consider size, shape and taste of medication. Try to avoid inconvenient doses or dose intervals.
• Consider the risk of adverse effects and drug interactions.
• Reinforce with written advice. The drug regimen should be written out - 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.
• Ensure all those prescribing for a particular patient (GP, OOH, palliative care specialists) communicate changes and that the patient and family are not confused by any alterations to medication made.
• Consider the route of administration:
  • Oral administration can be limited by severe nausea or vomiting, dysphagia, bowel obstruction, weakness or coma so 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 of fentanyl can also be useful particularly in ambulatory patients where the oral route is difficult, where intractable constipation or other problems tolerating morphine develop.
  Be aware of relative potencies when switching between different opioids and different routes of administration.

Opioid potency ratios⁶

Note, if converting from weak oral opioids to strong ones, do not consider the patient to be opioid-naive. Codeine and dihydrocodeine are 1/10 morphine's potency and tramadol 1/5 morphine's potency. Adjust starting dose accordingly.

Diagnosis of dying¹

One of the biggest barriers to good care of the dying is health care 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 semi-comatose.
• 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^8,3

Always consult local guidelines and protocols where available:

• Assess current medication and stop all non-essentials.
• Essential drugs eg opioids, anxiolytics, antiemetics should be converted to the subcutaneous route and a syringe driver used for continuous infusion in most instances.

• Not all drugs are compatible to 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 solution is older than 24 hours.
  • Dexamethasone - care needed with preparation to avoid precipitation
  • Haloperidol - precipitation beyond 24 hours likely where haloperidol concentration is greater than 2 mg/ml
  • Hyoscine butylbromide
  • Hyoscine hydrobromide
  • Levomepromazine
  • Metoclopramide - discard if becomes discoloured
  • Midazolam
• PRN medication should be prescribed and available. Consider worsening pain, agitation, respiratory secretions, vomiting and dyspnoea.
• Anticipatory prescribing should ensure that there is no delay in responding to a symptom if it occurs.
• Inappropriate monitoring (such as bloodtests and vital signs) should be stopped.
• Consider need for mouth care and urinary catheterisation or pads where the patient is incontinent.
• 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

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 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 stabilization of fractures, use of paracetamol and NSAIDs, IV bisphosphonates, 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 (eg amitriptyline 10-75 mg nocte), anticonvulsants (eg valproate, gabapentin), Capsaicin cream, local blocks/epidurals, TENS, acupuncture.

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

• Requires an holistic approach.
• Consider: counselling or access to spiritual advisors, anti-depressants, anxiolytics, complementary therapies, PRN medication (giving the patient control).

Nausea and vomiting

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 (100-150 mg/24hours), hyoscine butylbromide (20-60 mg/24hours) and octreotide (300-600 micrograms/24hours) are suitable choices.

Terminal 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 terminal phase, it is not usually appropriate to check for them. They may be associated with delirium.
• Psychological or spiritual distress.

Management options:

• Haloperidol 1-3 mg tds po or 5-15 mg/24 hours subcut infusion - less sedating.
• Midazolam 20-100 mg/24 hours subcut infusion - sedating.
• Levomepromazine 12.5-200 mg/24 hours subcut infusion - highly sedating, use in place of haloperidol if patient remains agitated despite haloperidol and midazolam.

Dyspnoea

• Usually multifactorial as anxiety almost always associated.
• General measures - reassurance and explanation, upright positioning, good ventilation (fan, open window), chest physio and relaxation exercises.
• Drug measures - nebulised saline, oral or subcutaneous morphine (start with oral morphine 5 mg q4h or equivalent), benzodiazepines (eg diazepam 5-10 mg po daily), oxygen (variable effect).

Excessive respiratory secretions ('death rattle')

• Particularly distressing for relatives.
• If present, may be reduced by use of hyoscine hydrobromide (0.6-2.4 mg/24hour subcut infusion) or glycopyrronium (0.6-1.2 mg/24hour subcut infusion). Particular attention should be given to mouth care as this will cause an extremely dry mouth.

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.^10,11 Good emergency symptom control may evert an unnecessary hospitalisation. Terminal emergencies can include:⁴

• 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)

Palliative sedation and the doctrine of double effect¹²

Terminal prescribing is often full of ethical anxiety for the prescriber particularly in situations where a terminally ill person faces refractory symptoms. Doctors are duty-bound to relieve suffering but not to cause the patient's death. The use of medication to purposively 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 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.¹³

Disposal of medicines following death

Following the Shipman Inquiry,¹⁴ 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 the 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 CDs by Community Nurses with another member of the team acting as witness or return of unused CDs by involved healthcare professionals to the community pharmacy for destruction.¹⁵