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5th January 2024

Pain

Pain is a common symptom in end-of-life care. There are many pharmacological and non-pharmacological management options.

Types of Pain

Pain at the end of life can be broadly categorised into nociceptive or neuropathic pain. Nociceptive pain can be somatic, emanating from skin, soft tissue or bones, or visceral, originating from internal organs. Neuropathic pain emerges from damage to the peripheral or central nervous system. It can be described as a burning, shooting or shocking sensation. Pain is also heavily influenced by psychosocial and spiritual components, and for this reason, a holistic approach to pain management is vital at the end of life. It is important to understand the aetiology of pain in order to help guide appropriate management.

Assessing Pain

Pain can be continuous or intermittent at the end of life. It may be a background pain, best treated with long-acting analgesics, or breakthrough pain, indicating the need for PRN (as required) immediate-release analgesia. Pain can also be incidental, where a clear precipitant can be established. Examples of precipitants include certain movements, the changing of dressings or coughing. Pain may also be due to ‘end-of-dose failure’ when long-acting analgesics wear off sooner than expected. End-of-dose failure is not a breakthrough pain but instead indicates a failure of adequate management of the background pain. Pain can be assessed with history taking, the monitoring of medication charts for frequent use of PRNs, as well as numerical or visual tools.

MRCP Part 1 - Assessing Pain

Source: Created by Dr Tasneem Wadee. Watson M, Campbell R, Vallath N, Ward S, Wells J, editors. Oxford Handbook of Palliative Care. 3rd ed. Oxford: Oxford University Press; 2019. p. 249, 274, 296-297, 306-309

WHO Analgesic Ladder

In 1986, the World Health Organisation (WHO) created a ladder for cancer pain management. It set out three stages of pain: mild, mild-moderate and moderate-severe. Options for pain management were recommended, with mild pain being treated with non-opioids, mild-moderate with weak opioids and moderate-severe with strong opioids. Adjuvant medications were recommended for use alongside every stage.

No single opioid has been proven to be more efficacious than the others. In common practice, morphine is the first opioid medication of choice. In renal disease, oxycodone may be used instead (or alfentanil, following specialist advice).

The mainstay of management in constant background pain, according to WHO, is that analgesia should be given “by the mouth” (orally), “by the clock” (at regular intervals) and “by the ladder” (using the WHO analgesic ladder in a stepwise manner).

Morphine Titration

When commencing morphine, the total dose taken in the first 24 hours can be used to calculate the total morphine requirement. Morphine may be titrated using 4-hourly immediate-release preparations or a mixture of modified-release preparations (starting at 2mg – 5mg) with immediate-release opioid breakthrough doses. Choice of medication is dependent on the patient’s preference, co-morbidities, age, severity of pain and their level of monitoring. Morphine should not be up-titrated by more than 33-50% every 24 hours.

Breakthrough doses are one-tenth to one-sixth of the 24-hour dose and can be given every 2-4 hours or up to one hourly if needed. If more than 3 doses are taken in 24 hours, this indicates the need to assess the patient’s pain and consider further up-titrating the dose of morphine or the use of a different analgesic.

Opioid Dose Equivalence

If patients become unable to swallow, oral preparations of morphine can be switched to the subcutaneous route and are often given through a syringe driver.

From To Calculation
Oral codeine Oral morphine Divide by 10
Oral tramadol Oral morphine Divide by 10
Oral morphine Subcutaneous morphine Divide by 2
Oral morphine Intravenous or subcutaneous diamorphine Divide by 3
Oral morphine Oral oxycodone Divide by 2
Oral oxycodone Subcutaneous oxycodone Divide by 2

Source: adapted from Scottish Palliative Care Guidelines. Choosing and Changing Opioids [Internet]. [cited 2023 Jul 16]. Available from: https://www.palliativecareguidelines.scot.nhs.uk/guidelines/pain/choosing-and-changing-opioids.aspx

Common Opioid Adverse Effects

Drowsiness

Drowsiness is a common but transient adverse effect when starting or increasing a dose of opioid medications. It usually settles after 2-3 days, and if it doesn’t, reducing the dose may be indicated.

Nausea and Vomiting

This is also a transient issue that usually passes after the first week. Ongoing symptoms can be managed with an antiemetic.

Constipation

Constipation is an ongoing and common adverse effect of opioids. NICE suggests co-prescribing a stimulant and softener laxative to help manage this effect. In cases resistant to usual constipation management, naloxegol may be indicated. Naloxegol is a peripherally-acting opioid receptor antagonist that can manage constipation without altering opioid pain management.

Dry Mouth

Many common medications have anticholinergic activity that can also lead to dry mouth. It is worth considering de-prescribing medications appropriately to help alleviate this issue. Non-pharmacological management in the form of ice lollies, boiled sweets and small sips of fluid can all help manage dry mouth.

Opioid Toxicity

Features of Opioid Toxicity

  • Hallucinations
  • Confusion
  • Extreme drowsiness
  • Myoclonus
  • Respiratory depression

Interestingly, opioids can increase the end tidal volume, so a reduction in respiratory rate does not always correlate with a decrease in oxygen saturation. Features of opioid toxicity requiring immediate reversal in the palliative patient are a respiratory rate of 8 or less, abnormal oxygen saturations, or any signs of cyanosis. In the palliative care setting, naloxone is not indicated for use in drowsiness that is not life-threatening.

Naloxone

If opioid reversal is indicated, 400 micrograms of the reversal agent naloxone should be diluted and given as a slow IV bolus at 80 micrograms at a time. It is rare that the full dose will need to be used.

Naloxone should be used cautiously to help prevent immediate return of pain. When too high a dose is given in patients who are established on opioids, it can also lead to significant acute withdrawal reactions that can cause life-threatening tachycardia, arrhythmia, hypertension and arrest.

Non-Opioid Medications

Neuropathic Agents

It is important to first assess the patient to ascertain if there is a treatable cause of neuropathic pain. This could include nerve compression from bone or soft tissue disease that could be managed with corticosteroids, radiotherapy, or surgery. First-line management of neuropathic pain is with either a tricyclic antidepressant, pregabalin or gabapentin.

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

NSAIDs can be used to treat inflammatory pain from soft tissue, as well as bone pain. Examples include non-selective NSAIDs that inhibit COX-1 and COX-2, such as ibuprofen, naproxen and diclofenac, or COX-2 specific medications, such as celecoxib.

Corticosteroids

Corticosteroids include dexamethasone and methylprednisolone and can be used to manage inflammation, oedema and compression-associated pain. They are used in the management of raised intracranial pressure, bone pain, nerve compression and liver capsule pain.

It is important to be aware that steroids have a large side effect profile. They are a potential cause of new-onset agitation or delirium in the palliative patient. Some side effects, such as insomnia and increased appetite, can be used to the patient’s advantage, and steroids may be prescribed solely if a patient wishes to be more alert or to eat more.

Muscle Relaxants

Muscle spasm can be a cause of significant pain at the end of life. This can be treated with muscle relaxants such as benzodiazepines or baclofen. Non-pharmacological management, such as heat pads, massage or transcutaneous electrical nerve stimulation (TENS), may also be used.

Non-Pharmacological Management of Pain

Nerve Blocks

Local nerve blocks can be used to help manage pain and can reduce the need for large opioid doses. Examples include coeliac plexus blocks for upper abdominal pain and saddle blocks for perineal or perianal pain. Spinal or epidural nerve blocks may also be used for difficult-to-manage pain.

Radiotherapy

Radiotherapy can be used to manage localised bone pain alongside analgesia, steroids and bisphosphonates. This can be completed as a single fraction, requiring one visit, or in multiple fractions, requiring multiple visits. The patient’s prognosis and personal choice should be taken into account when deciding between single and multiple-fraction radiotherapy.

Surgery

This can include prophylactic fixation of long bones with lytic metastases, vertebroplasties for unstable vertebral fractures and debulking of tumours causing problems due to compression.

Complementary, Psychosocial and Spiritual Care

Pain can be significantly affected by psychosocial and spiritual components. A multidisciplinary team approach and a holistic view of managing pain can help to reduce medication use and allow for an individual approach to pain management. Psychosocial management strategies include, but are not limited to:

  • Heat pads
  • Cool pads
  • Occupational therapy
  • Complementary therapy
    • Acupuncture
    • Reflexology
    • Massage
  • Creative therapies
  • Psychological therapies
    • Hypnotherapy
    • Meditation
    • Counselling
    • CBT
  • Patient and family education

References

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