See Anticipatory prescribing

• All patients should have medication for symptom control available as required. Anticipatory medicines will need to be adapted to take renal function into account.
• Opioid analgesic (for pain relief or breathlessness):
  • Alfentanil is drug of choice when eGFR is 20ml/min or less although specialists may recommend earlier, especially where a rapid decline in renal function is anticipated
  • Oxycodone can be used in renal failure/renal disease at end of life, but there is greater potential for opioid toxicity than with alfentanil and so caution is advised when using Oxycodone and increased dosing intervals may be appropriate. Different care settings may impact on ease of availability of medicines
  • Oxycodone SC as required up to 2-hourly (1mg to 2mg if not on regular opioid). If 3 or more doses have been given within 6 hours with little or no benefit seek urgent advice or review. If more than 6 doses are required in 24 hours seek advice or review. If ‘as required’ doses are needed, consider using a syringe pump with, for example, oxycodone 5mg to 10mg over 24 hours and titrate according to response. Monitor for signs of opioid toxicity which are a greater risk, especially at higher opioid doses. Elderly patients and opioid naïve patients should be started on the lowest dose possible.
  • Please seek specialist advice if considering commencing alfentanil (e.g. eGFR very low 10ml/min); alfentanil SC as required hourly; (100micrograms, if not on a regular opioid). If 3 or more doses have been given within 4 hours with little or no benefit seek urgent advice or review. If more than 6 doses are required in 24 hours seek advice or review. The short duration of action may mean repeated dosing is necessary and there should be a low threshold for starting a syringe pump in these circumstances. Consider using a syringe pump with, for example, alfentanil 500micrograms over 24 hours (1mg of alfentanil≈30mg oral morphine) and titrate according to response.
• Anxiolytic sedative: midazolam SC 2mg as required hourly.
• Antisecretory medication: hyoscine butylbromide (Buscopan) SC 20mg as required up to hourly.
• Anti-emetic: QThaloperidol SC 500micrograms to 1mg, 8 hourly or levomepromazine SC 2.5mg to 5mg, 12 hourly.
• If using three or more doses in 24 hours consider starting a syringe pump which can be titrated according to response and use of breakthrough medication.

Diagnosis of the terminal phase can be difficult. Potentially reversible causes of deterioration include hypercalcaemia, infection, and opioid toxicity. Clinical signs include:

• bed-bound and drowsy or semi-comatose
• only able to take sips of fluid or having difficulty swallowing tablets
• poor tolerance of renal replacement therapy
• background of deterioration.

• Plan and document care of the patient including taking account of family considerations; an individualised care plan or checklist may be useful.
• Discuss prognosis (patient is dying), goals of care (maintaining comfort), and preferred place of death with patient and family, as appropriate.
• Clarify resuscitation status; check DNACPR form has been completed (refer to national policy and ReSPECT).
• Reassure the patient and family that full supportive care will continue.
• Stop unnecessary investigations and monitoring (blood pressure, pulse, temperature).
• Discontinue unnecessary medication not needed for symptom control, and review daily.
• Prescribe anticipatory medications for symptom control ('Just in case' container in community).
• Some patients may still benefit from oral diuretics, adjuvant analgesics and bicarbonate.
• If able to swallow, consider liquid formulations. Otherwise use the subcutaneous (SC) or rectal route.
• Offer oral fluids, maintaining any fluid restriction; review the patient’s requirement for clinically-assisted hydration in order to maintain comfort.
• Comfort nursing care (pressure relieving mattress, reposition for comfort only), eye care, mouth care (sips of fluid, oral gel), bladder and bowel care.

Pain

See Pain guidelines

• Paracetamol or an NSAID (NSAIDs are usually contraindicated in renal failure however benefits may outweigh risks in a dying patient) can help bone, joint, pressure sore, inflammatory pain.
• Morphine, diamorphine and oxycodone are renally excreted, as are their active metabolites and repeated doses can lead to significant toxicity.
• Alfentanil is the opioid of choice where eGFR is less than 20ml/min, although specialists may recommend earlier – less renal excretion of parent drug and the metabolites are not active – but may not be advised for breakthrough doses in the dying phase due to short duration of action.
• Oxycodone can be given if the patient is not opioid toxic, but patient must be reviewed to ensure toxicity is not developing. This may continue to be appropriate to manage symptoms. In circumstances where alfentanil may be considered (e.g. eGFR less than 20ml/min [or earlier under specialist advice] or for patients stopping dialysis) seek specialist advice. Oxycodone may be used whilst a supply of alfentanil is obtained. Use the lowest effective dose on an as required basis and monitor for toxicity.
• No regular opioid: oxycodone 1mg to 2mg SC as required 2 hourly or seek specialist advice if considering alfentanil SC 100micrograms as required up to hourly.
• Fentanyl patch: continue patch, seek specialist advice for correct SC opioid dose for breakthrough pain.
• If stable on current opioid and very close to end of life (24 to 48 hours) it may be appropriate to continue current opioid but monitor closely for signs of toxicity and have a low threshold for switching to alfentanil if concerns about toxicity (please seek specialist advice).
• If pain significant or difficult to control, seek specialist advice.

Myoclonus or muscle stiffness or spasm

• Midazolam SC infusion, 5mg to 10mg over 24 hours (could be titrated to 20mg if necessary).
• Clonazepam 500micrograms orally or SC at night may be useful. Refer to clonazepam information sheet.
• Consider opioid toxicity and rotation to alfentanil if not already implemented.

Anxiety and distress

• Midazolam SC 2mg as required hourly or 5mg to 10mg over 24 hours via syringe pump.
• Lorazepam sublingual 500micrograms 8 hourly as required.
• If agitation worsening despite midazolam, consider QThaloperidol 500micrograms to 1mg 8 hourly or QTlevomepromazine 10mg to 25mg SC 12 hourly, use lower dose if not used before or in frail elderly. 

Delirium

See Delirium

• Delirium is common and may worsen as uraemia increases – drug of choice is QThaloperidol 500micrograms to 2mg 8 hourly.
• Try to address psychological and family concerns causing patient anxiety.

Terminal agitation

• Seek specialist advice if delirium or agitation worsening.
• First step: Midazolam SC 10mg to 20mg over 24 hours in a syringe pump + midazolam SC 5mg hourly, as required.
• Second step: Titrate Midazolam with advice, starting at 10mg over 24 hours in a syringe pump. Doses can be gradually titrated up to 60mg over 24 hours under specialist advice.QTlevomepromazine may need to be used in addition to midazolam under specialist advice. Use lower doses if not used previously and in frail elderly, for example, 2.5mg to 5mg SC as required 2 hourly. Higher doses may be needed for persistent distress or delirium for example, 10mg to 25mg SC as required 2 hourly.
• May need to be given more frequently initially, for example, hourly to control symptoms.

Breathlessness

See breathlessness

• May be due to pulmonary oedema, acidosis, anxiety or lung disease.
• Follow guidelines above for anxiety and distress, use opioid as per pain guidelines above and consider syringe pump.

Thin, upper respiratory tract secretions

• Consider repositioning.
• Try to avoid suction in case this stimulates distress or more secretions.
• First line: hyoscine butylbromide SC 20mg, up to hourly as required (up to 120mg in 24hours).
• Second line: glycopyrronium bromide SC 100micrograms, 6 to 8 hourly as required.

Nausea and vomiting

See Nausea and vomiting (Also refer to Subcutaneous medication guideline)

• Nausea is common due to uraemia and comorbidity.
• If already controlled with an oral antiemetic, continue it as a subcutaneous infusion or use a long acting anti-emetic:
  • QThaloperidol SC 500micrograms to 1mg 8 hourly
  • levomepromazine SC 2.5mg to 5mg 12 hourly.

• Opioid analgesics should not be used to sedate dying patients.
• Avoid renally excreted opioids (codeine, dihydrocodeine, morphine, diamorphine, oxycodone).
• SC infusions provide maintenance treatment only; additional SC doses of medication will be needed if the patient’s symptoms are not controlled.
• Single SC doses of midazolam in renal patients can last 2 to 4 hours. Can also be useful as an anticonvulsant.
• A marked increase in pain in the dying patient is unusual; reassess and seek advice.

Bennett, M., Lucas, V., Brennan, M., Hughes, A., O'donnell, V. and Wee, B. 2002. Using anti-muscarinic drugs in the management of death rattle: Evidence-based guidelines for palliative care. Palliative Medicine, 16(5), pp. 369-374.

Brown, E., Chambers E.J. and Eggeling, C. 2007. End of Life Care in Nephrology: From Advanced Disease to Bereavement. Oxford: Oxford University Press.

Bunn R. and Ashley C. 2008. The renal drug handbook. 3rd ed. Oxford: Radcliffe Medical Press

Chambers E.J., Germain, M. and Brown, E., Eds., 2004. Supportive care for the renal patient Oxford: Oxford University Press.

Dean, M. 2004. Opioids in renal failure and dialysis patients. Journal of Pain and Symptom Management, 28(5), pp. 497-504.

Do Not Attempt Cardiopulmonary Resuscitation (DNACPR): Integrated Adult Policy: Decision Making and Communication.https://www.gov.scot/publications/attempt-cardiopulmonary-resuscitation-dnacpr-integrated-adult-policy-decision-making-communication/

Douglas, C., Murtagh, F. E. M., Chambers, E. J., Howse, M. and Ellershaw, J. 2009. Symptom management for the adult patient dying with advanced chronic kidney disease: a review of the literature and development of evidence-based guidelines by a United Kingdom Expert Consensus Group. Palliative Medicine, 23(2), pp. 103-110.

Kirvela, M., Ali-Melkkila, T., Kaila, T., Iisalo, E. and Lindgren, L. 1993. Pharmacokinetics of glycopyrronium in uraemic patients. British Journal of Anaesthesia, 71(3), pp. 437-9.