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PAIN MANAGEMENT IN CHILDREN WITH CANCER

PAIN MANAGEMENT IN CHILDREN WITH CANCER. Dr. John J. Collins AM, MB BS, PhD, FFPMANZCA, FRACP Head of Department Pain Medicine & Palliative Care The Children’s Hospital at Westmead Sydney, Australia. OBJECTIVES. DISCUSS: The symptoms of children with cancer

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PAIN MANAGEMENT IN CHILDREN WITH CANCER

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  1. PAIN MANAGEMENT IN CHILDREN WITH CANCER Dr. John J. Collins AM, MB BS, PhD, FFPMANZCA, FRACP Head of Department Pain Medicine & Palliative Care The Children’s Hospital at Westmead Sydney, Australia

  2. OBJECTIVES DISCUSS: • The symptoms of children with cancer • Standards for cancer pain management • Clinical and translational research • Analgesic prescription at end of life • Strategies for the management of intractable pain in children

  3. PREVALENCE AND CHARACTERISTICS OF SYMPTOMS IN CHILDREN WITH CANCER AGED 10-18 (n=159) • Degree when symptom was present • Overall Intensity Frequency Distress • Symptom prevalence (%) Mod-V Sev (%)* A lot-AA (%)† QB-VM (%)‡ • Lack of energy 49.7 61.6 40.9 21.4 • Pain 49.1 80.8 35.9 39.1 • Feeling drowsy 48.4 64.0 34.6 18.6 • Nausea 44.7 65.9 23.0 36.6 • Cough 40.9 47.7 23.0 16.3 • Lack of appetite 39.6 66.3 39.7 35.8 • Feeling sad 35.8 59.6 17.5 39.5 • Feeling nervous 35.8 56.1 28.1 23.7 • Worrying 35.4 66.1 28.6 27.2 • Feeling irritable 34.6 63.6 30.9 34.7 • Percentage moderate to very severe; †Percentage a lot to almost always; ‡ Percentage quite a bit to very much. • NE, not evaluated

  4. 1998 WHO monograph: Establishing universal standards, irrespective of cancer treatment options 2011 WHO monograph: “The pharmacological management of children with persisting pain due to medical illness” EXPECTED STANDARDS OF PAEDIATRIC CANCERPAIN MANAGEMENT

  5. EXPECTED STANDARDS FOR ACUTE PAIN MANAGEMENT ASSOC. PAEDIATRIC ANAESTHETISTS GREAT BRITAIN & IRELAND: www.apagbi.org.uk/docs/APA_Guidelines_on_Pain_Management.pdf AMERICAN PAIN SOCIETY: http://www.ampainsoc.org/advocacy/pediatric2.htm AUST. NZ COLLEGE OF ANAESTHETISTS & NHMRC: www.anzca.edu.au/resources/books_and_publications/acutepain_update.pdf

  6. EXPECTED INTERNATIONAL & NATIONAL STANDARDS for PROVIDING PALLIATIVE CARE *American Academy of Pediatrics Pediatrics 106 (2): 351-357, 2000 *www.palliativecare.org.au * Eur J Pall Care, 2007; 14 (3), 109-111

  7. CLINICAL RESEARCH & PAEDIATRIC CANCER PAIN MANAGEMENT

  8. TRANSLATIONAL RESEARCH: PAEDIATRIC CANCER PAIN MANAGEMENT • Basic sciences have shown cancer induced bone pain (CIBP) is distinct from other chronic pain states, such as inflammatory or neuropathic pain *A. Delaney, S. M. Fleetwood-Walker, L. A. Colvin, M. Fallon. British Journal of Anaesthesia 2008 101(1):87-94 • A translational medicine approach may allow improved understanding of the underlying mechanisms of CIBP to improve cancer pain management in children

  9. TRANSLATIONAL RESEARCH: PAEDIATRIC CANCER PAIN MANAGEMENT MECHANISMS of CIBP: Tumour type, site & extent of bony destruction may influence the mechanisms of CIBP 1. PERIPHERAL FACTORS Direct effects: -pressure/compression nerves -sensitization periosteal afferents -peripheral nerve sensitisation due to cytokines -osteoblast inflammatory response →cytokines → ↑osteoclast activity → nerve injury → PAIN

  10. TRANSLATIONAL RESEARCH: PAEDIATRIC CANCER PAIN MANAGEMENT MECHANISMS of CIBP: 2. CENTRAL EFFECTS • Changes in the endogenous opioid system: ↓ mu opioid receptors in DRG + higher doses of opioid needed • Sensitisation of Wide Dynamic Range (WDR) neurones in the spinal cord with ↑responsiveness to mechanical & thermal stimuli

  11. COMBINATION ANALGESIC THERAPY A combination analgesic therapeutic approach to cancer pain management, may be the most appropriate approach Gordon-Williams, R.M., Dickenson, A.H. Central neuronal mechanisms in cancer-induced bone pain. Curr Opin Support Palliat Care 1:6-10; 2007

  12. ANALGESIC PRESCRIPTION AT THE END OF LIFE IN CHILDREN WITH CANCER, 1996 • “Conventional” analgesic doses and routes is achievable for the majority of children with cancer • Approx. 6% of these patients required “massive” doses of an opioid infusion • Half required “extraordinary” analgesic measures, such as sedation or subarachnoid infusions • Regional anaesthetic techniques are infrequent in treating pain at end-of-life for children with cancer** *Collins JJ, Grier HE, Kinney HC, Berde CB. Control of severe pain in terminal pediatric malignancy. Journal of Pediatrics 1995; 126(4):653-657 **Collins JJ, Grier HE, Sethna NF, Berde CB. Regional anesthesia for pain associated with terminal malignancy. Pain 1996; 65:63-69

  13. CHANGING MANAGEMENT OF INTRACTABLE PAIN IN CHILDREN WITH CANCER Practice has become more sophisticated, greater understanding of: 1. Management of the paediatric pain crisis 2. Calculation of opioid “rescue” dosing and dose escalation 3. Opioid switching 4. Management of opioid side-effects 5. NMDA antagonists as new therapeutic options 6. Combination analgesic chemotherapy 6. Invasive approaches to pain management in children Fewer children may need to be sedated to reduce conscious awareness of intractable symptoms

  14. THE PAEDIATRIC PAIN CRISIS • Emergency • Make a diagnosis • Titrate incremental intravenous opioid doses every 10-15 minutes until analgesia effective • Analgesic effect of opioids increase in a log-linear function, with incremental opioid dosing required until either analgesia is achieved or somnolence occurs • Total amount of opioid administered is the opioid loading dose • A continuous infusion of opioid may need to be commenced to maintain this level of analgesia *Cherny NI, Foley KM. Nonopioid and opioid analgesic pharmacotherapy of cancer pain. In: Cherny NI, Foley KM, editors. Hematol Oncol Clin North Amer. 1996: 79-102

  15. BREAKTHROUGH CANCER PAIN IN CHILDREN • Breakthough cancer pain in children is*: - severe - sudden in onset - short-lived • Unclear what is the “best” breakthrough dose. This is probably better determined by the nature of the pain being treated. • Role of oral opioids?? *Friedrichsdorf, S, Collins JJ. Breakthrough pain in children with cancer. 2007;34(2):209-216.Journal of Pain and Symptom Management

  16. OPIOID SWITCHING • Indication is dose-limiting opioid side-effects preventing opioid dose escalation • Changing opioids is often accompanied by change in ratio between analgesia and side-effects*,** • Following a prolonged period of regular dosing with one opioid, equivalent analgesia may be attained with a dose of a second opioid that is smaller than that calculated from an equianalgesic table *Galer BS, Coyle N, Pasternak GW, et al. Individual variability in the response to different opioids: report of five cases. Pain 1992; 49:87-91 **Portenoy RK. Opioid tolerance and responsiveness: research findings and clinical observations. In: Gebhart GF, Hammond DI, Jensen TS, editors. Progress in Pain Research and Management. Seattle: IASP Press, 1994: 615-619

  17. OPIOID SWITCHING: PAEDIATRIC DATA Review of opioid prescriptions in the Oncology Unit, Children’s Hospital at Westmead* 14% children (n=11) had 30 opioid rotations Indications: - opioid side-effects with adequate analgesia • opioid side-effects with inadequate analgesia Outcome: Opioid side-effects resolved in 90% cases *Drake R, Longworth J, Collins JJ. Opioid rotation in children with cancer. Journal of Palliative Medicine 2004; 7(3):419-42

  18. NMDA RECEPTOR ANTAGONISTS • NMDA- receptor antagonists depress central sensitisation* • Dextromethorphan, dextrorphan, ketamine, memantine and amantadine have been shown to have NMDA-receptor antagonist activities** • Clinical usefulness is compromised by an adverse effect to side effect ratio • No data of their utility in paediatrics, other than procedural pain management • Clinical usage is increasing, particularly in the setting of severe neuropathic pain and rapid opioid dose escalation and perceived tolerance *Eide PK, Jorum E, Stubhaug A, et a. Relief of post-herpetic neuralgia with the N-methyl-D-aspartic acid receptor antagonist ketamine: a double-blind cross-over comparison with morphine and placebo. Pain 1994; 58:347-354 **Persson J, Axelsson G, Hallin RG, et a. Beneficial effects of ketamine in a chronic pain state with allodynia. Pain 1995; 60:217-222 **Nelson KA, Park KM, Robinovitz E, et al. High dose dextromethorphan versus placebo in painful diabetic neuropathy and postherpetic neuralgia. Neurology 1997; 48:1212-1218 **Eisenberg E, Pud D. Can patients with chronic neuropathic pain be cured by acute administration of the NMDA-receptor antagonist amantadine? Pain 1994; 74:37-39

  19. INVASIVE APPROACHES TO INTRACTABLE PAEDIATRIC CANCER PAIN Anaesthetic approaches • Experience of regional anaesthesia for children with intractable pain is limited • Regional anaesthesia may be appropriate in a highly select subset of children* • The indications for regional anaesthesia related to either dose-limiting side-effects of opioids or opioid unresponsiveness in patients where pain was confined to one region of the body • Rapid intravenous opioid dose reduction was required in some cases *Collins JJ, Grier HE, Sethna NF, Berde CB. Regional anesthesia for pain associated with terminal malignancy. Pain 1996; 65:63-69

  20. SEDATION AS A THERAPEUTIC MODALITY FOR REFRACTORY PAIN • Sedation assumes therapies beyond the conventional have been utilised and there is no acceptable means of providing analgesia without compromising consciousness • Trade-off between sedation and inadequate pain relief requires the consideration of the wishes of the child and his or her family • Ethical issues include the principle of double effect • Continuation of high-dose opioid infusions in these circumstances is recommended • A variety of drugs have been used in this setting, including barbiturates, benzodiazepines, and phenothiazines

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