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 (e.g. bone marrow biopsy) may often be worse than that of the disease. Such pain due to procedures should be aggressively treated.¹

Non-drug

• Pacifiers and sweet solutions such as sucrose and glucose are useful interventions in children.² Suckling at the breast may be a healthier option.³
• Immobilisation by splinting has traditionally been used for musculoskeletal injury, to alleviate pain and promote healing.⁴
• Play therapy can help to alleviate anxiety and provide a means of distraction from pain.⁵

Drugs

Use the stepwise World Health Organization (WHO) "analgesic ladder" to choose pain-relieving drugs, using the severity of a child's pain to determine the type and dose of analgesic.^6,7,8

• 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 (sublingual tablets not licensed for use in children under 6; injections not licensed for use in children under six months).^8,9

Non-opioids^8,10

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 and not be apparent for 4-6 days

• These are particularly useful where pain is associated with fever (especially in children over the age of five), dental pain and for control of pain in long-term inflammatory conditions.
• They do, however, cause more gastric irritation than paracetamol and, for mild-to-moderate pain, paracetamol is often preferred.
• 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.
• Inhaled nitrous oxide provides useful short-term analgesia for patients undergoing painful procedures and for those who have needle phobia.¹¹
• Ketamine is an effective analgesic in children and can be used orally, intravenously or via a caudal epidural.^12,13,14
• EMLA cream may be used to reduce the pain of venepuncture and has also been successfully used to reduce pain post-circumcision.¹⁵

Opioids^8,16

• These are useful for moderate-to-severe pain, particularly of visceral origin.
• Combining paracetamol with an opioid makes it difficult to titrate individual drugs and increases the risk of adverse effects and of toxicity. Combined preparations may, however, be of occasional use in palliative care.
• Long-term prescribing is most common 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 the British National Formulary for Children (BNFC) for for further details.⁸

Which opioid?

• Morphine:
  • This is most valuable for severe pain. Nausea and vomiting can occur, but one study suggests these side effects are less frequent than was once thought.¹⁷ 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 four 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.
  • It is licensed for intranasal use (diamorphine powder dissolved in sufficient Water for Injection) in 3-8 year olds for the treatment of acute pain in emergencies and short painful procedures.
• 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 make 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:
  • It is less constipating than morphine but less potent and the BNFC does not recommend its use in children.
• Tramadol:
  • This is used in older children for postoperative 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.
  • Injections are not licensed for use in children under the age of one.
• Dihydrocodeine:
  • This has an efficacy similar to codeine.
  • It can be given four-hourly.
  • Most preparations are not licensed for use in children under the age of four.
• Alfentanil, fentanyl and remifentanil:
  • These are used by injection for intraoperative analgesia.
  • Transdermal fentanyl has been used to good effect in paediatric patients with chronic pain. The manufacturers recommend its use only in opioid-tolerant patients due to the risk of respiratory depression. Patients with fever should be monitored as this can cause increased absorption.
  • Preliminary studies suggest intranasal fentanyl is effective, safe and well tolerated for use as an acute analgesic for children aged 1-3 years with moderate-to-severe pain.¹⁸

Procedures

Local and regional anaesthesia techniques are being increasingly used as the mainstay of analgesia for many surgical procedures and for post-operative pain control, e.g. caudal anaesthesia or femoral nerve block under ultrasound guidance.^19,20

Controlling pain in palliative care⁸

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 are also useful in controlling bone secondaries. Radiotherapy, bisphosphonates and radioactive isotopes of strontium can also be useful for pain due to bone metastases.
• If non-opioids are 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 a 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 WHO 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 four 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 four hours.
• Side-effects of opioids (e.g. constipation) should be anticipated, aggressively treated and regularly reassessed.
• Once the daily requirement is established, give total dose od or bd. Consult the BNFC for appropriate modified-release preparations. If required, increase the strength of dose, not frequency of administration. Give the first dose of modified-release preparation four hours after last oral dose.
• Adverse effects which are more common in children include urinary retention (which can be eased by carbachol or bethanechol). Opioid-induced pruritus is less common.
• If swallowing becomes difficult, give an injectable opioid. Diamorphine is to be preferred to morphine as it can be given in a smaller volume. It can be given IM or subcutaneously, approximately a third of the oral dose of morphine. In the case of the modified-release tablets, give half the total 24-hour dose (which is then divided into six portions to be given every four hours).
• Subcutaneous infusion of diamorphine via syringe driver is another option. Indications include difficulty or refusal to take medication by mouth, or malignant bowel obstruction (avoiding the need for an intravenous infusion or for insertion of a nasogastric tube). Other drugs can be combined to treat other symptoms (e.g. vomiting). For more details see the BNFC.⁸
• Substitute oral morphine if the child can resume taking medicines by mouth.
• Other options include rectal route (morphine suppositories), or transdermal route (fentanyl patches).
• Gastrointestinal pain - bowel colic pain may be reduced by loperamide, hyoscine hydrobromide sublingually at a dose of 10 micrograms/kg (maximum 300 micrograms) three 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; a TENS machine 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 healthcare professional, institutional and governmental organisation caring for children to support, educate and advocate for integration of these principles."²¹

Document references

1. Mishra S, Bhatnagar S, Singh M, et al; Pediatric cancer pain management at a regional cancer center: implementation of WHO Analgesic Ladder. Middle East J Anesthesiol. 2009 Jun;20(2):239-44. [abstract]
2. Carbajal R, Chauvet X, Couderc S, et al; Randomised trial of analgesic effects of sucrose, glucose, and pacifiers in term BMJ. 1999 Nov 27;319(7222):1393-7. [abstract]
3. Campbell C; Analgesic effects of sweet solutions and pacifiers in term neonates. Suckling at BMJ. 2000 Apr 8;320(7240):1002; author reply 1003-4.
4. Incavo SJ, Mogan JV, Hilfrank BC; Extension splinting of palmar plate avulsion injuries of the proximal J Hand Surg Am. 1989 Jul;14(4):659-61. [abstract]
5. Darnill S, Gamage B; The patient's journey: palliative care--a parent's view. BMJ. 2006 Jun 24;332(7556):1494-5.
6. Cancer Pain Relief and Palliative Care. Geneva, Switzerland; World Health Organization; 1990.
7. McGrath PA; Development of the World Health Organization Guidelines on Cancer Pain Relief and Palliative Care in Children. J Pain Symptom Manage. 1996 Aug;12(2):87-92. [abstract]
8. British National Formulary for Children; British Medical Association and Royal Pharmaceutical Society of Great Britain. London
9. Khan FA, Memon GA, Kamal RS; Effect of route of buprenorphine on recovery and postoperative analgesic requirement in paediatric patients. Paediatr Anaesth. 2002 Nov;12(9):786-90. [abstract]
10. Purssell E; Treating fever in children: paracetamol or ibuprofen? Br J Community Nurs. 2002 Jun;7(6):316-20. [abstract]
11. Williams V, Riley A, Rayner R, et al; Inhaled nitrous oxide during painful procedures: a satisfaction survey. Paediatr Nurs. 2006 Oct;18(8):31-3. [abstract]
12. Ugur F, Gulcu N, Boyaci A; Oral ketamine for pain relief in a child with abdominal malignancy. Pain Med. 2009 Jan;10(1):120-1. Epub 2008 Mar 11. [abstract]
13. Karapinar B, Yilmaz D, Demirag K, et al; Sedation with intravenous ketamine and midazolam for painful procedures in Pediatr Int. 2006 Apr;48(2):146-51. [abstract]
14. Nafiu OO, Kolawole IK, Salam RA, et al; Comparison of caudal ketamine with or without bupivacaine in pediatric J Natl Med Assoc. 2007 Jun;99(6):670-3. [abstract]
15. Choi WY, Irwin MG, Hui TW, et al; EMLA cream versus dorsal penile nerve block for postcircumcision analgesia in Anesth Analg. 2003 Feb;96(2):396-9, table of contents. [abstract]
16. Ozalevli M, Unlugenc H, Tuncer U, et al; Comparison of morphine and tramadol by patient-controlled analgesia for postoperative analgesia after tonsillectomy in children.; Paediatr Anaesth. 2005 Nov;15(11):979-84. [abstract]
17. Bradshaw M, Sen A; Use of a prophylactic antiemetic with morphine in acute pain: randomised Emerg Med J. 2006 Mar;23(3):210-3. [abstract]
18. Cole J, Shepherd M, Young P; Intranasal fentanyl in 1-3-year-olds: a prospective study of the effectiveness of intranasal fentanyl as acute analgesia. Emerg Med Australas. 2009 Oct;21(5):395-400. [abstract]
19. Ivani G, Mosseti V; Pediatric regional anesthesia. Minerva Anestesiol. 2009 Oct;75(10):577-83. [abstract]
20. Oberndorfer U, Marhofer P, Bosenberg A, et al; Ultrasonographic guidance for sciatic and femoral nerve blocks in children. Br J Anaesth. 2007 Jun;98(6):797-801. Epub 2007 Apr 21. [abstract]
21. Finkel JC, Finley A, Greco C, et al; Transdermal fentanyl in the management of children with chronic severe pain: results from an international study.; Cancer. 2005 Dec 15;104(12):2847-57. [abstract]

Internet and further reading

• Cancer Pain Management in Children; Texas Cancer Council 2009.; American site but with information of general relevance

Acknowledgements