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CDHB

Chronic/Persistent Pain in the Cancer/Palliative Setting

• It is important to establish the cause of pain in cancer patients, e.g., muscle spasm is treated differently from a bone metastasis or a pressure area.
• Cancer-induced pain is best controlled by specific anti-cancer treatment, e.g., irradiation of bone metastases in combination with analgesics.
• For moderate to severe pain, use morphine as first-line.
• Guidelines for starting morphine for palliative therapy:
  • Commence using either:
    • morphine elixir (1 mg/mL, 2 mg/mL, 5 mg/mL, or 10 mg/mL), or
    • Sevredol™ 10 mg or 20 mg tablets.
  • Starting dose: up to 10 mg 4 hourly, regularly throughout 24 hours. Extra doses must also be available for severe pain (maximum of hourly prn).
  • Gradually titrate dose to effect before converting to sustained release morphine.
  • Reduce dose and/or frequency in elderly (e.g., 6 hourly rather than 4 hourly).
  • Increase starting dose if already on regular codeine. Codeine, 60 mg, is equivalent to at least 5 mg oral morphine.
  • Give dose 6-8 hourly if impaired renal function (no need to change dosing interval for mild to moderate hepatic failure). It may be preferable to use oxycodone first line in mild-moderate renal impairment.
  • Patients maintained on morphine may develop tolerance. Therefore, there can be a need to titrate the dose up, to maintain efficacy.

  Starting sustained release morphine (morphine sulphate SR):

  • Currently available preparations:
    • m-Eslon™ (10 mg, 30 mg, 60 mg, and 100 mg).
    • LA Morph™ (10 mg, 30 mg, 60 mg, and 100 mg).
  • Add up morphine doses over 24 hours during which pain was controlled, and divide by 2 to get the 12 hourly m-Eslon or LA Morph dose given twice daily.
  • When stabilized on morphine sulphate SR, an appropriate dose of breakthrough morphine should be charted (15 - 20% of the total daily dose q3-4h as elixir or Sevredol™ tablets).
  • Continue to prescribe paracetamol and/or NSAID even when taking regular morphine.
  • Morphine is approximately twice as potent subcut as orally, and can be given both as a bolus injection and as a continuous infusion. Refer to the Palliative Care Guidelines, or refer to the Palliative Care Service 81473 (or page via the operator).

    Note: If commencing directly on morphine sulphate SR without prior dose titration with elixir or Sevredol™, caution is needed as a safe and effective starting dose is difficult to predict.

Breakthrough Pain:

• Morphine elixir 3 to 4 hourly, using doses of up to 1/6^th of total daily morphine dose.

  If several breakthrough doses needed per day, increase morphine sulphate SR dose.

Incident Pain:

• Use morphine elixir, 1/6^th of total daily morphine dose, before activity that causes pain. Adjustment of the morphine sulphate SR dose is generally not recommended.

Alternative Opioids to Morphine:

• Oxycodone. This is available in four formulations: Oxycodone CR tablets (controlled release), OxyNorm™ capsules and OxyNorm oral liquid™ (both immediate release), and oxycodone injection. For more details, refer to the Palliative Care Guidelines.
  • Oxycodone is an opioid analgesic and is approximately twice as strong as morphine when given orally.
  • There have recently been concerns relating to the inappropriate prescribing of oxycodone, its increasing availability in the community, and its high potential for abuse.
  • Oxycodone is similar to morphine in its action and has a similar side effect profile. This drug is more expensive than morphine and there is no clinical evidence to support its use first line. Morphine therefore remains the drug of first choice for acute and chronic persistent pain.
  • The main indications for the use of oxycodone are:
    • Persistent hallucinations or other signs of morphine neurotoxicity.
    • Evidence of morphine tolerance/intolerance.

      Note: It is renally cleared and should be used with caution in renal impairment.

  • See the Opioid Conversion Guide.
• Transdermal fentanyl.
• Methadone.

For advice regarding indications and prescribing, refer to the CDHB intranet under Clinical Information and Resources > Palliative Care Service and Guidelines. A referral to the Palliative Care Service is strongly recommended particularly if considering fentanyl or methadone - 81473 (or page via the operator).

Note: Pain is a physiological antagonist to morphine induced respiratory depression. Morphine doses can usually be increased until pain is controlled.

Opioid Conversion

Management of Opioid Side Effects

Nausea and vomiting

• Domperidone 10 - 20 mg PO QID before food.
• Metoclopramide 10 mg PO/subcut q4-8h (or QID before food).
• Haloperidol 0.5 mg PO/subcut q8h (can be given as a single nocte dose of 1.5-3 mg).
• Cyclizine 25-50 mg PO q8-12h. Can be given IV q8h or subcut. If prescribed subcut it must be given by infusion with a maximum dose of 150 mg/24 hours.

Nausea and vomiting due to opioids tends to subside over the first week. Therefore reassess need for antiemetics.

Metoclopramide has theoretical advantages in the presence of constipation as it stimulates peristalsis. However it is contraindicated if obstruction is likely. Domperidone has fewer side effects, and extrapyramidal reactions are very rare. Can only be given orally.

Methotrimeprazine is a broad-spectrum antiemetic and can be very effective in advanced disease states. Referral to the Palliative Care Service 81473 (or page via the operator) is recommended for persistent or intractable nausea.

Ondansetron 4-8 mg PO q12h or 4 mg IV q6h for severe nausea & vomiting which has not responded to the first line antiemetics. Caution: constipation is a side effect when used for more than a few days.

Dexamethasone 2-8 mg PO or via a continuous subcut infusion can also be effective for intractable nausea.

Constipation

• Regular stool softeners (e.g., docusate) with stimulants (e.g., bisacodyl, senna) or a combination laxative such as docusate and senna should be used routinely when taking opioids.
• Pinorax™ or Pinorax Forte™ daily is also a combination laxative and can be used in conjunction with docusate and senna. It is licensed for use in opioid-induced constipation but only for patients with advanced incurable disease.
• Movicol requires an application for a special authority number as it incurs a part charge in the community (SA0891 - Macrogol 3350). It is recommended for faecal impaction (up to 8 sachets per 24 hours) or can be used as chronic treatment (up to 3 sachets daily). See the Palliative Care Guidelines (online at http://cdhb.palliativecare.org.nz).

Opioid-induced Hyperalgesia

This is a clinical syndrome whereby a patient experiences increased pain, usually to touch, as a result of too high a dose of opioid (or where the opioid has been increased too rapidly) and which may improve on dose reduction.

Reference: Silverman SM. Opioid induced hyperalgesia: clinical implications for the pain practitioner. Pain Physician 2009; 12:679.

Adjuvant Analgesics

• Paracetamol or NSAIDs are effective for pain, especially for bone or soft tissue injury.
• Corticosteroids are useful for pain related to nerve compression or cerebral oedema.
• Tricyclic antidepressants, e.g., nortriptyline, and anticonvulsant agents, e.g., sodium valproate, gabapentin, are useful in neuropathic pain (burning, shooting).
• Gabapentin is an effective agent with limited adverse side-effects. A special authority application is required. The patient must have first tried and failed or been unable to tolerate treatment for pain with a tricyclic antidepressant. Initial approval is for 3 months. Subsequent approval, once proven effective, is for 2 years. Dose modification is required in renal impairment.
• Occasionally nerve blocks, transcutaneous nerve stimulation (TENS), or intraspinal catheter may be required.

For more information on adjuvant analgesics and neuropathic pain management in palliative care, see Palliative Care Guidelines.

For complex pain problems, it is suggested that advice be sought either from the Christchurch Hospital Palliative Care Service 81473 (Palliative Care is not just for patients with a cancer diagnosis), or the Pain Management Centre, Burwood Hospital.

Topic Code: 1575