INTRODUCTION

This guideline presents recommendations for management of pain in adult patients with life- threatening illness like cancer.

ASSESSMENT

• Perform comprehensive pain assessment prior to pain management (refer to the Guideline – Pain Assessment).
• Assess the aetiology of pain and manage the reversible causes.
• Routinely assess and re-assess pain using validated assessment tools.
• Document serial pain assessment on standardised forms.

RECOMMENDATIONS

• Assess the patient to identify the different components of pain and suffering to make specific goals of pain management and use appropriate pain management strategies.
• As a team along with patient and family develop a management/care plan incorporating the assessment findings and the goals.
• WHO analgesic ladder should be used as the mainstay in the pharmacological management of pain.
• Analgesics should be titrated to maximize the benefits and minimize the adverse effects, such as:
• The oral route should be the preferred route of administration of medications. Alternative routes can be considered when the oral route is not possible (e.g. vomiting, confusion etc.).
• Use analgesics on a regular basis, based on the half-life, bio-availability and duration of action of individual drugs and NOT on an “as and when required basis”.
• Rescue medications should be prescribed for breakthrough/ incident pain.
• The choice of drugs should depend on the severity of pain and the WHO analgesic ladder (non-opioids, opioids, adjuvants).
• The opioid of choice for severe cancer pain is oral morphine.
• Occasionally when patients present themselves with very severe pain, needing urgent pain relief and analgesia titration, morphine could be used in the subcutaneous route.
• The potency ratio of oral to subcutaneous morphine is 2:1.
• Transdermal fentanyl or buprenorphine should be reserved for patients with stable pain, when they are unable to swallow, poor tolerance to oral morphine, poor compliance.
• Buprenorphine is a safe opioid in renal failure.
• Opioid switching (depending on availability in India) could be considered to improve pain relief, in cases of poor drug tolerability.
• Assess for any contraindications before prescribing any group of analgesics (e.g. prior GI bleed, renal impairment in case of NSAIDs, use caution with renal, hepatic failure in case of opioids).
• Other adjuvant drugs are chosen based on the type and cause of pain.
• Consider other treatment interventions along with pharmacological management of pain as appropriate:
• Non-pharmacological interventions – TENS, physiotherapy, acupuncture, relaxation therapy, immobilization, breathing exercises, hot and cold application.
• Cancer treatment – surgery, chemotherapy, radiotherapy.
• Psychological interventions.
• When pain relief is inadequate with opioids/ adjuvants, the use of ketamine, spinal analgesia, and nerve blocks can be considered as appropriate.
• Explain to the patient and primary caregiver about the pain and the management care plan.
• Explain the anticipated side-effects and motivate compliance for good pain relief. Clarify any concerns regarding the medications used (especially opioids, addiction, adverse effects, tolerance, fears).
• Explain and educate the caregiver and family to look out for and report immediately if there are signs of opioid toxicity like excessive sleep or drowsiness, jerks, reduced rate of respiration.
• Provide verbal and written information about medications including dosing, route of administration and analgesics for breakthrough pain.
• Advise the patient and caregiver to swallow extended release tablets whole; not to break, crush, dissolve or chew.
• Advise caution when driving or using tools while on strong opioids.
• Higher doses of opioids may be required in patients with history of regular alcohol intake and substance abuse.
• Provide follow up plan to reassess pain.

MANAGEMENT

WHO Ladder Step 1 – Mild pain (<3 score on NPRS)
NSAIDS/ Paracetamol	Non-steroidal anti-inflammatory drugs (NSAIDs)*	± Adjuvant analgesics
Step 2 – Mild to moderate Pain (3-6 score on NPRS)
Weak opioids**	± NSAIDs Or Paracetamol	± Adjuvant analgesics
Step 3 – Moderate to severe Pain (>6 on NPRS)
Strong opioids**	± NSAIDs Or Paracetamol	± Adjuvant analgesics
NPRS- Numerical Pain Rating Scale *Add gastro-protectors along with NSAIDs **Consider prescribing stimulant laxatives and anti-emetics along with opioids to prevent constipation, nausea respectively.

Opioid titration

• Titration of oral morphine is essential to identify the right dose for a patient, which provides adequate pain relief with acceptable side effects.
• Immediate release morphine is useful during the titration and for rescue doses.
• The rescue dose is usually 1/6^th of the total daily dose of morphine. Assess pain relief 60 minutes after the rescue dose, and repeat another rescue dose if pain is not relieved.
• Consider increasing the regular dose of morphine if there is a need for >2-3 rescue doses/day.
• When increasing the dose of regular morphine, the number of rescue doses should be taken into account/ the dose can be increased by 30-50%.
• When the pain relief is stable, convert immediate-release morphine to modified release.
• Prescribe half the 24-hour dose of immediate-release morphine as modified-release morphine q12h. Continue to use an appropriate dose of immediate -release morphine for the rescue dose (1/6^th of the 24 hour dose).

Analgesics commonly used for cancer pain
Mild Pain	Opioids for Mild to Moderate Pain	Opioids for Moderate to Severe Pain
Paracetamol Celecoxib	Codeine Sulphate	Morphine Sulphate Tapentadol
Diclofenac Sodium Ibuprofen Naproxen	Tramadol HCl	Fentanyl Buprenorphine Methadone

Adjuvant analgesics commonly used for cancer pain
Corticosteroids (Dexamethasone)	Raised intracranial pressure Soft tissue infiltration Spinal cord/ nerve compression Hepatomegaly
Anti-depressants (Amitriptyline, Nortriptyline) Anticonvulsants (Gabapentin, Pregabalin)	Nerve Compression Nerve infiltration Para-neoplastic neuropathy
Bisphosphonates (Zoledronic Acid)	Bone pain

Symptoms of opioid toxicity

• Increasing drowsiness, sedation
• Delirium with hallucinations
• Multifocal muscle twitching, myoclonic jerks
• Whole body allodynia or hyperalgesia
• Respiratory depression (rare)

Management of opioid toxicity

• If the patient’s pain is controlled reduce opioid dose by one third.
• Ensure patient is well hydrated.
• Check renal function.
• Consider changing opioids (refer to the Guideline – Opioids).
• Respiratory depression -Seek a palliative care specialist’s advice. Naloxone, an opioid antagonist should be used if there are symptoms of respiratory depression.

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REFERENCES

• Branford, R., Wighton, E., Ross, J. (2015). Principles of drug therapy: focus on opioids. Oxford Textbook of Palliative Medicine (pp. 493-505)
• Fallon, M., Hanks, G., Cherny, N. (2006). The principles of control of cancer pain. ABC of Palliative Care (pp. 4-7)
• Rayment, C. and Bennett, M.I. (2015). Definition and assessment of chronic pain in advanced disease. Oxford Textbook of Palliative Medicine (pp. 519-524)
• Sjogren, P., Elsner, F., Kaasa, S. (2015). Non-opioid analgesics. Oxford Textbook of Palliative Medicine (pp. 567-576)
• Twycross, R., Wilcock, A., Howard, P. (2014). Analgesics. Palliative Care Formulary 5 (pp.385-581)