Pain Relief in Children

• Pain management should start when a child is first diagnosed and should continue throughout the illness.
• Childhood pain is often complex (particularly cancer pain) and ideally a multidisciplinary approach should be used.
• While providing analgesia, the underlying cause of the pain should be determined and treated if possible, remembering that the pain of both diagnostic and therapeutic procedures (eg bone marrow biopsy) may often be worse than that of the disease. Such pain due to procedures should be aggressively treated.
• Use the stepwise WHO "analgesic ladder" to choose pain-relieving drugs, using the severity of a child's pain to determine the type and dose of analgesic:^1,2,3
  • Step 1 - Mild pain - non-opioids: paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs).
  • Step 2 - Moderate pain - opiates step 1 non-opioids. If the effect of an opioid for mild to moderate pain at optimum dose is not adequate, move directly to step 3.
  • Step 3 - Moderate to severe pain - morphine, diamorphine step 1 non-opioids. Some use buprenorphine (unlicensed indication).⁴

Paracetamol

• Sugar-free preparation is appropriate for many children with mild to moderate pain
• Does not cause respiratory depression but overdose dangerous as it may cause hepatic damage not be apparent for 4-6 days

NSAIDs

• These are particularly useful where pain is associated with fever (especially in children over 5), dental pain, and for control of pain in long-term inflammatory conditions.
• They do however cause more gastric irritation than paracetamol.
• Warn asthmatic patients/parents taking NSAIDs for the first time to watch for worsening of bronchospasm
• Avoid aspirin in children under 16 due to risk of Reye's syndrome.
• Pain associated with acute problems of the oral mucosa (e.g. acute herpetic gingivostomatitis, erythema multiforme) may require benzydamine or topical anaesthetics until resolution, in addition to paracetamol or ibuprofen.

• These are useful for moderate to severe pain particularly of visceral origin.
• Long-term prescribing is commonest for malignant disease but also may be appropriate for chronic non-malignant conditions in conjunction with specialist advice.
• The main side effects of opioids as a class are nausea, vomiting, constipation, drowsiness. Respiratory depression and hypotension occur in larger doses. Neonates, particularly if pre-term, may be more susceptible.
• Doses may need to be adjusted individually according to the degree of analgesia and side-effects.
• The response to opioids varies widely, particularly in the neonatal period.
• Opioid doses should be calculated and checked with care.

See drug monographs for further details.

Which opioid?

• Morphine:
  • This is most valuable for severe pain, though nausea and vomiting are frequent. Additional beneficial effects afforded are detachment and euphoria.
  • Morphine is the first line oral medication for severe pain in palliative care. It should be given regularly every 4 hours (or every 12 or 24 hours as modified-release preparations).
• Diamorphine (heroin):
  • This may cause less nausea and hypotension than morphine.
  • Its greater solubility allows effective doses to be injected in smaller volumes and this is important in the emaciated patient.
• Buprenorphine:
  • This has opioid agonist and antagonist properties and may precipitate withdrawal symptoms, including pain, in children dependent on other opioids.
  • It has a longer duration of action than morphine and sublingually is an effective analgesic for 6 to 8 hours.
  • Vomiting may be a problem.
  • It is rarely used in children, but long duration of action, various application routes and metabolic independence from renal function makes it worthy of further consideration in management of cancer pain and postoperative pain.
• Methadone:
  • This is less sedating than morphine and acts for longer periods.
  • There is a risk of accumulation and overdose if administered more than twice a day long term.
  • It may be used instead of morphine when excitation (or exacerbation of pain) occurs with morphine.
• Pethidine:
  • This enables prompt analgesia, but short duration of action.
  • It is less constipating than morphine, but less potent.
  • It is not suitable for severe continuing pain.
  • It is used rarely in children, but sometimes given IV for short surgical procedures - eg. eye surgery.
• Tramadol:
  • This is used in older children for post-operative pain control and cancer pain.
  • It has an opioid effect and an enhancement of serotonergic and adrenergic pathways.
  • It has fewer of the typical opioid side-effects (notably, less respiratory depression, less constipation and less addiction potential).
  • Psychiatric reactions have been reported.
• Codeine:
  • This is effective for the relief of mild to moderate pain but is too constipating for long-term use.
• Dihydrocodeine:
  • This has an efficacy similar to codeine.
  • It can be given 4 hourly.
• Alfentanil, fentanyl and remifentanil:
  • These are used by injection for intra-operative analgesia.
  • Transdermal fentanyl has also been used to good effect in paediatric patients with chronic pain.

• Whilst the same principles apply to the palliative control of pain in children as for any other condition, additional considerations apply.
• Care should be comprehensive and address psychological, cultural, and spiritual needs. If so desired, this care should be provided at home.
• Remember factors such as the physical environment, attitudes, and behaviours can profoundly increase or decrease children's pain.
• Pain management therefore relies not only on the use of pain-relieving drugs but also on practical cognitive, behavioural, physical, and supportive therapies (many of these therapies can be provided by family members).

• Paracetamol or an NSAID given regularly will often make the use of opioids unnecessary. NSAIDs also useful in controlling bone secondaries. Radiotherapy, biphosphonates and radioactive isotopes of strontium also be useful for pain due to bone metastases.
• If non-opioids not sufficient substitute with (or combine with) adequate dosage of opioid such as codeine or dihydrocodeine. Step up to morphine, or fentanyl (to initiate, consider involving specialist in palliative care). Arrange for doses to be given at regular intervals - "by the clock", rather than "as required" using the oral route whenever possible. If oral administration is not tolerated, alternatives include intravenous, continuous subcutaneous, and transdermal opioid administration. Give an adequate dose which effectively relieves pain (children may require extremely large doses of opioids to obtain relief). Steep escalation of opioid doses (e.g., by 100 times or more) may be required, particularly among patients with spine or central nervous system metastatic tumours.
• The fear of opioid "addiction" is one of the main reasons children with severe cancer pain do not receive adequate analgesia. The World Health Organisation stresses this 'greatly exaggerated fear must be addressed and corrected' but remember when reducing or stopping opioids, doses should be tapered gradually to avoid causing severe pain flare or withdrawal symptoms.
• Morphine is given by mouth as an oral solution or as standard ('immediate release') tablets regularly every 4 hours, the initial dose depending largely on the patient's previous treatment. Increase next dose by 50% if the previous dose no more effective than preceding analgesic. Choose the lowest dose which prevents pain and consider adjuvant analgesics (e.g. NSAIDs). Titrate stepwise depending on response. Omit overnight dose if double the usual dose given at bedtime.
• Consider rescue doses for breakthrough pain and prophylactic doses 30 minutes before potentially painful procedure (e.g. dressing changes). Use oral morphine solution or standard tablets, about one-sixth of total daily dose every 4 hours.
• Side-effects of opioids (eg constipation) should be anticipated, aggressively treated, and regularly reassessed.
• Once the daily requirement established, give total dose od or bd. Consult BNF for appropriate modified-release preparations. If required, increase the strength of dose, not frequency of administration. Give the first dose of modified-release preparation 4 hours after last oral dose.
• Adverse effects commoner in children include urinary retention (which can be eased by carbachol or bethanechol). Opioid-induced pruritus is less common.
• If swallowing becomes difficult, give IM morphine, at half the oral solution dose. In the case of the modified-release tablets give half the total 24-hour dose (which is then divided into 6 portions to be given every 4 hours). Diamorphine can be given in a smaller volume, IM or subcutaneous, approximately a third of the oral dose of morphine. Subcutaneous infusion of diamorphine via syringe driver is another option. Substitute oral morphine if the child can resume taking medicines by mouth.
• Other options include rectal route (morphine suppositories), or transdermal route (fentanyl patches).
• Gastro-intestinal pain - bowel colic pain may be reduced by loperamide, hyoscine hydrobromide sublingually at a dose of 10 micrograms/kg (max. 300 micrograms) 3 times daily . Subcutaneous hyoscine can be given via a syringe driver.
• Gastric distension pain - consider an antacid antiflatulent (section 1.1.1) and domperidone before meals.
• Muscle spasm - consider a muscle relaxant such as diazepam or baclofen.
• Neuropathic pain - a tricyclic antidepressant, most commonly amitriptyline, may be useful. Other options are an anticonvulsant, most commonly carbamazepine. Gabapentin and pregabalin are licensed for neuropathic pain in adults, but check with specialist for unlicensed use in children.
• Nerve compression may be reduced by a corticosteroid such as dexamethasone, which reduces oedema around the tumour, thus reducing compression. Consider nerve blocks when pain is localised to a specific area; TENS is another option.

• Although children's understanding of death may vary at different times in their development, they often know when they are dying, their major concerns are frequently fear of abandonment and fear of suffering.
• Emphasise to such children that they will be kept comfortable and that the people they love will always be with them.
• "It is the responsibility of every health-care professional, institutional and governmental organization caring for children to support, educate, and advocate for integration of these principles."⁸