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Morphine sulfate accumulates in renal failure with eGFR <45mL/min/1.73m2 and so the choice of opioid should be changed to one with less renal excretion. In those with eGFR 10-30mL/min/1.73m2, the most common choice is oxycodone. With eGFR <10mL/min/1.73m2, the most common choice is alfentanil.
 

 This would be the correct dosing of alfentanil, although paracetamol is not available as a subcutaneous injection and so must be given orally or IV
33252
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10mg alfentanil/24hrs and 4g/24hrs paracetamol subcutaneously via a syringe driver with 7.5-12.5mg subcutaneous oxycodone as required 4-hourly for breakthrough pain
QuestionChoice
This patient is on 90mg twice daily of morphine sulfate modified release and has used 4 doses of 30mg morphine immediate release, equating to a total of 300mg oral morphine sulfate in24hrs.
 

 Morphine sulfate accumulates in renal failure with eGFR <45mL/min/1.73m2 and so the choice of opioid should be changed to one with less renal excretion.
 

 In patient such as this one, with eGFR 10-30mL/min/1.73m2, the most common choice is oxycodone.
 

 To convert between opioids, always convert to the 24hr dose of oral morphine from the current opioid regime and then convert to the new drug of choice.
 

 If you are unsure, always look up conversions online or in your local trust guidance. The following table shows dose equivalents of 10mg oral morphine
 

| Analgesic/Route | Dose | Conversion Factor |
| -------------- | ------- | ----------------- |
| Codeine/tramadol/dihydrocodeine oral | 100mg  | x10  |
| Diamorphine IM/IV/Subcut  | 3mg  | ÷3.3 |
| Morphine IM/IV/Subcut | 5mg  | ÷2 |
| Oxycodone oral\*  | 6.6mg\*  | ÷1.5\* |
| Oxycodone Subcut\*  | 5mg\* | ÷2\* |
| Alfentanil Subcut | 0.3mg  | ÷30  |
 

 \*NB - oral oxycodone potency is between 1.3-2x that of oral morphine. Different trusts will adopt different guidance on which you should use. If in doubt, always opt for the lower dose and titrate up.
 

 This patient is on 300mg/24hrs oral morphine equating to 150mg subcutaneous oxycodone/24hrs. Breakthrough analgesia dose is calculated 1/10th-1/6th the 24hr dose. This equates to 15mg-25mg subcutaneous oxycodone as required.
 

 Paracetamol is not available as a subcutaneous injection and so must be given orally or IV. Often when patients approach the end of their life intravenous medications are stopped or converted to other routes to avoid repetitive cannulations
33248
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150mg oxycodone/24hrs subcutaneously via a syringe driver with 15-25mg subcutaneous oxycodone as required 4-hourly for breakthrough pain
QuestionChoice
Morphine sulfate accumulates (increased side effects and risk of overdose due to accumulation of active/toxic metabolites) in renal failure with eGFR <45mL/min/1.73m2 and so the choice of opioid should be changed to one with less renal excretion. In those with eGFR 10-30mL/min/1.73m2, the most common choice is oxycodone. Also note the 24hr dose of oral morphine sulfate is 300mg in this scenario. Always make sure to calculate total 24hr doses in twice daily dosed long-acting opioids
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210mg morphine sulfate/24hrs subcutaneously via a syringe driver with 20-35mg subcutaneous morphine sulfate as required 4-hourly for breakthrough pain
QuestionChoice
 This patient is on 300mg/24hrs oral morphine equating to 150mg subcutaneous oxycodone/24hrs. Subcutaneous oxycodone is twice as potent as as oral morphine
33249
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75mg oxycodone/24hrs subcutaneously via a syringe driver with 7.5-15mg subcutaneous oxycodone as required, 4-hourly for breakthrough pain
QuestionChoice
This patient is on 300mg/24hrs oral morphine equating to 150mg subcutaneous oxycodone/24hrs, therefore this answer is incorrect.
33251
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35mg oxycodone/24hrs and 4g/24hrs paracetamol subcutaneously via a syringe driver with 4-6mg subcutaneous oxycodone as required 4-hourly for breakthrough pain
QuestionComment
This question was too long to read
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Axillary Lymph Node
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Would the alfentil option not be possible?
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Benign Monoclonal
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# Summary

Medications in end-of-life care focus on alleviating distressing symptoms in patients nearing death. A holistic approach is vital, considering physical, emotional, and social aspects of symptoms, often involving a multidisciplinary team. For pain management, the WHO pain ladder guides pharmacological strategies, with morphine as the primary strong opioid. Specific treatments for other symptoms depend on the underlying cause and it is important to consider reversible causes and non-pharmacological measures.



# Definition

Medications used in end of life care aim to relieve distressing symptoms which may appear in the last days, weeks, or months of life. They are commonly prescribed as 'anticipatory' or 'just in case' medications for a patient known to be nearing the end of life.


They can be administered:


- Orally - if the patient is safely able to swallow
- Subcutaneously - via single dose or continuous syringe pump
- Transdermally - especially for stable symptoms and if available
- Intramuscularly - less common
- Intravenously - less common, but may be helpful if a patient already has access

## A note on holistic care

In palliative care, and in medicine, it is important to consider all symptoms in context. There are many different aspects to symptoms. These include the physical cause, the patient's beliefs about their illness and symptoms, social contributors and impacts, their emotional and behavioural responses. Holistic assessment and management are crucial, which is why the multidisciplinary team is so important. 

For example, a patient may have been prescribed very effective analgesia but is unable to administer medicines themselves. They may also have a very strong emotional response to pain or believe that they deserve their symptoms. They may benefit from a package of care or financial support for terminal illness which a social worker could help with, or an occupational therapist to help with activities of daily living. Counselling may give the patient a space to explore their feelings around their symptoms and their illness, while spiritual support could alleviate some existential distress. These additional interventions work alongside pharmacological therapy to optimise a person's quality of life through their illness.

This chapter focuses on medications for symptoms towards the end of life, but it is crucial to remember that each patient has a different combination of needs which requires an individual assessment and management plan, often with input from a range of health and social care professionals.

# Pain


Initial pharmacological management of pain should follow the WHO pain ladder. Once patients have reached the top of this ladder (requiring regular strong opioids), careful optimisation is necessary to ensure the right level of pain relief while minimising side effects.

- Morphine is the first-line strong opioid analgesic. This can be given as a modified release or immediate release form. 
- Generally, patients would have a regular 'background' dose based on their 24-hour requirements, plus a PRN dose available for **breakthrough pain.** PRN doses are usually 1/6-1/10 of the 24 hour dose. Analgesia requirements should be reviewed regularly, for example every 24 hours.
- Alternatives to morphine may be necessary for patients with poor renal function. These include oxycodone, alfentanyl or buprenorphine.
- When prescribing opioid analgesia consider co-prescribing a regular laxative and an as-required anti-emetic. Monitor for signs of opioid toxicity (respiratory depression, sedation, myoclonus) and switch to alternatives or dose reduce as necessary.

When switching analgesia, it is helpful to convert the dose first to oral morphine before converting to the desired medication. Please note that different routes also have different equivalent doses, so it is always safest to check guidelines.


The following table shows dose equivalents of 10mg oral morphine


| Analgesic/Route | Dose | Conversion Factor |
| ----------------------------- | ------- | ----------------- |
| Codeine/tramadol/dihydrocodeine oral | 100mg | x10 |
| Diamorphine IM/IV/Subcut | 3mg | x3.3 |
| Morphine IM/IV/Subcut | 5mg | x2 |
| Oxycodone oral\* | 5mg\* | x2\* |
| Oxycodone Subcut\* | 2.5mg\* | x4\* |
| Alfentanil Subcut | 0.3mg | x30 |


*NB - oral oxycodone potency is between 1.3-2x that of oral morphine. Different trusts will adopt different guidance on which you should use. If in doubt, always opt for the lower dose and titrate up.


# Breathlessness

Consider non-pharmacological measures for breathlessness first. For example, sitting the patient up, opening a window or setting up a fan can all help.

Pharmacological management may involve low-dose opioids, benzodiazepines or therapeutic oxygen, and should be tailored to the patient.


# Nausea and vomiting

It is important to consider the likely cause of nausea and vomiting, as medications target different parts of the vomiting pathway. Perform a full assessment to determine the likely cause of the nausea and vomiting. Consider parenteral routes of administration - patients may have severe gastrointestinal disturbance or at least may not be able to keep down oral antiemetics long enough to be effective.

The following table shows the primary site of activity and side effects of commonly used antiemetics:

| Antiemetic | Receptor activity | Side effects & cautions | Useful for |
|---|---|---|---|
| Metoclopramide | Dopamine antagonist | Extrapyramidal symptoms, drowsiness, restlessness, diarrhoea. Do not give with antimuscarinics or in mechanical bowel obstruction | Gastric stasis, functional bowel obstruction |
| Cyclizine | Histamine, acetylcholine antagonist | Drowsiness, antimuscarinic | Raised intracranial pressure, vestibular dysfunction |
| Hyoscine | Acetylcholine antagonist | Antimuscarinic | Motion sickness |
| Haloperidol | Dopamine antagonist | Less common in palliative care doses | Chemical |
| Levomepromazine | Dopamine, histamine, acetylcholine, 5HT2 antagonist | Sedation, postural hypotension, antimuscarinic |Broad range |
| Ondansetron | 5HT3 antagonist | Constipation, arrhythmias, movement disorder | Cytotoxic-related |

- For chemically-mediated symptoms (for example medications, metabolic derangemenet), aim to treat the underlying cause. Antiemetics that may be helpful include haloperidol, metoclopramide or levomepromazine.
- For nausea and vomiting due to raised intracranial pressure, cyclizine is usually used first-line. Dexamethasone or radiotherapy may be helpful to reduce the pressure-associated symptoms.
- For patients with vestibular disturbance (for example symptoms associated with movement), cyclizine usually used first-line. Alternatives include hyoscine hydrobromide.
- For patients with bowel obstruction, seek specialist advice. If due to peristaltic failure, review medications and consider starting metoclopramide (providing there is no colic). Likewise for gastric stasis, consider metoclopramide. For patients with mechanical obstruction and/or colic, do not give metoclopramide. Exclude constipation, give cyclizine for nausea and treat colic with hyoscine butylbromide.
- If nausea and vomiting is due to compression from an abdominal or pelvic tumour, cyclizine should be used first-line.
- For anxiety-related nausea and vomiting, begin with non-pharmacological measures for anxiety, such as CBT. A benzodiazepine or levomepromazine would be first-line pharmacological options.

# Agitation

As with other symptoms, aim to manage reversible causes of agitation and possible delirium first. Consider non-pharmacological measures such as environmental modification. For patients in their last days of life, haloperidol or low-dose midazolam may be prescribed. Often, this is done as part of anticipatory prescribing.


# Respiratory tract secretions

Respiratory tract secretions often occur in the last days of life as a person becomes less able to clear their airways. They are rarely a cause of distress to the patient, but may be upsetting for family members or those close to the patient. An antimuscarinic such as hyoscine butylbromide or glycopyrronium bromide may be prescribed for noisy respiratory secretions.


# NICE guidelines


[NICE Guidance: Care of dying adults in the last days of life](https://www.nice.org.uk/guidance/ng31)

[NICE CKS: Palliative care - general issues](https://cks.nice.org.uk/topics/palliative-care-general-issues/)

[NICE CKS: Palliative care - dyspnoea](https://cks.nice.org.uk/topics/palliative-care-dyspnoea/)

[NICE CKS: Palliative care - nausea and vomiting](https://cks.nice.org.uk/topics/)

[NICE CKS: Palliative care - secretions](https://cks.nice.org.uk/topics/)

[NICE CKS: Palliative cancer care - pain](https://cks.nice.org.uk/topics/)

# References

[Pallcare.info](https://www.pallcare.info/book.php)

[BNF: Ondansetron](https://bnf.nice.org.uk/drugs/ondansetron/#drug-action)

[BNF: Nausea and labyrinth disorders](https://bnf.nice.org.uk/treatment-summaries/nausea-and-labyrinth-disorders/)

[BNF: Prescribing in palliative care](https://bnf.nice.org.uk/medicines-guidance/prescribing-in-palliative-care/)
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75mg oxycodone/24hrs subcutaneously via a syringe driver with 7.5-12.5mg subcutaneous oxycodone as required 4-hourly for breakthrough pain
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In patients with renal impairment (eGFR <45 mL/min/1.73 m²), morphine sulfate should be converted to oxycodone using a rough equivalence of 1 mg morphine to 0.6 mg oxycodone, with dose reductions of 25-50% considered to prevent accumulation and side effects.
A 72-year-old man with metastatic colorectal cancer and chronic kidney disease is admitted with sepsis. After three days of treatment, he deteriorates. Following discussions, the decision is made to discontinue antibiotics and fluids, focusing on end-of-life care.

His current analgesia is paracetamol 1g QDS, morphine sulfate modified release (long-acting) 90mg BD, and morphine sulfate immediate release oral liquid (short acting) 30mg PRN, 4-hourly. He has used 4 doses of the PRN oral morphine in 24hrs.


His eGFR is 22 mL/min/1.73m². The patient asks if his oral medications can be reduced or converted to a syringe driver due to difficulty swallowing.

Which of the following prescriptions would be most suitable for this patient?
a