Symptoms 1

1. Symptoms 1 Pain – The essentials Module 3

2. Definition of Pain “Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage. Pain is always subjective.” Pain, 1979

3. Total Suffering = Pain PAIN + physical symptoms + psychological problems + social difficulties + cultural issues + spiritual concerns Total Suffering PhysicalSymptoms Spiritual Cultural Psychological Social Strang et al. 2004

4. Cancer Pain • Prevalence about 70% • Not everyone with cancer will experience pain • The 5th Vital Sign • Under-diagnosed • Under-treated • Many dying patients continue to suffer from unrelieved pain • Cleeland and colleagues suggest >50% Cleeland et al. 1994; Portenoy & Lesage 1999

5. Cancer Pain • About 80% will have more than one type of pain • About 80-90% of cancer pain can be relieved with relatively simple oral analgesics and adjuvant drugs • The remaining 10-20% can be ‘difficult’ • In advanced cancer about 2% is not responsive to traditional methods and classified as ‘intractable’ Sykes et al. 1997, Kay et al. 2007

6. Barriers to Pain Management • Three categories: • Patient • Reluctance to report, fatalism, fear side effects, addiction ‘opiophobia’, concern about ‘distracting’ physicians • Professional • Poor (lack of) pain assessment, lack of knowledge about pain management, fear of addiction or side effects • System • Problems of access to expertise, treatment, inadequate reimbursement, lack of time, restrictive drug regulation, low priority to cancer symptom treatment • Sun et al. 2007

7. Basic Principles • Thorough assessment of the patient and all the types of pain they are experiencing • Including history, examination and appropriate investigations • Treating each type of pain with individualised, type-specific (‘mechanistic’) interventions • Continuous reassessment of the patient, the pain(s) and efficacy of the management

8. Basic Pain Questions • Site: “Where is the pain, point it out for me?” • Onset: “When did it start?” • Intensity:“How severe is the pain?” eg. with visual analogue scale • Duration: “How long does it last?” • Quality: “How would describe the pain? eg. dull, aching, burning” • Radiation: “Does the pain move?” • Aggravating/Relieving Factors: “What makes it better / worse?”

9. More Basic Pain Questions • Associated symptoms eg. Nausea, anxiety, dyspnea • Always assess for other factors which may impact / contribute • E.g. intercurrent stressors, mood • Response to current / previous therapies • ? Complete / ? partial relief, adverse effects • Impact “How is the pain affecting you and your daily activities?” eg. sleep, appetite, mood, quality of life, mobility, interpersonal relationships

10. Psychological factors affecting pain response • Cultural differences • Observational learning (modelling) • Cognitive appraisal (meaning of pain) • Fear & anxiety • Neuroticism & extroversion • Perceived control of events • Coping style • Attention/distraction Cousins and Power 1999

11. Cautions • Do not make psychiatric or emotional assessments whilst pain remains uncontrolled • Always believe the patient “My mother was always accusing people of faking. Even when they died she’d still manage to look sceptical.” Tiger’s Eye by Inga Clendinnen, 2000

12. Aim to categorise the pain • Temporally • Acute (subacute, intermittent, episodic) • Chronic (pain persisting for > 3 months) • (both?) • Neurophysiologic • Somatic / nociceptive • Visceral • Neuropathic

13. Categorising pain • Nociceptive / Somatic eg. Arthritis, fracture, bony metastasis, cellulitis • Well localised, felt in cutaneous or deep musculoskeletal tissues • Visceral eg. Pancreatic pain, myocardial infarction, liver metastasis • Poorly localised, deep, squeezing, pressure, often associated with diaphoresis, nausea and vomiting. May be referred (eg, shoulder tip)

14. More pain categories • Neuropathic eg. Cord compression, peripheral neuropathies • Constant dull ache, pressure with superimposed spasms of shooting, burning, or stabbing • Other categories: • Raised intracranial pressure • Non-cancer eg. pressure areas, arthritis, urinary retention, oral thrush, fracture (which may require different approaches) • Non-physical causes (‘pain plus’ / ‘total pain’)

15. Basic management approach • Appropriate drug selection • For the mechanism of pain, for the individual • Appropriate starting dose and stepwise titration to effective dose • Discontinuing if ineffective after reasonable trial • Considering appropriate non-opioid analgesics and/or adjuvant analgesics

16. More basic management • Employ non-pharmacological techniques • Involve the multi-disciplinary team, consider: • Physical therapies, rehabilitation • Psychological and psychiatric interventions • Consider the role of: • Surgery • Radiotherapy • Chemotherapy • Nerve blocks / other anaesthetic techniques • Interventional radiology (eg. vertebroplasty)

17. Opioid Myths, and our duty to dispel them • Huge number • Amongst patients and doctors • Need to be dispelled because they are barriers to good pain relief, and good medical care • Reluctance to prescribe and manage acute pain may lead to chronic pain • Should be raised pro-actively when first prescribing opioids

18. Other opioid myths …. • MYTH: opioids cause premature death • Clinically significant respiratory depression is extremely rare when patients receive appropriate dosing, even when underlying respiratory illness is present. • MYTH: opioid use leads to addiction • None of 10,000 burns patients became addicted when prescribed opioids appropriately for pain management. Morita et al. 2001; Rurup et al. 2006; Fobes & Huxtable 2006; Perry & Heidrich, 1982

19. More myths … • MYTH: opioids should be reserved for the imminently dying / mean the ‘end is near’ • MYTH: opioids cause deep sedation • MYTH: you can’t drive on opioids • Stable doses do not significantly impair fitness to drive • MYTH: withdrawal is always a problem • Unusual if dose is proportionally and slowly reduced (and easily managed if it does arise) • MYTH: opioids always cause nausea Vainio et al. 1995

20. Still more myths… • MYTH: opioids should be avoided in older patients • MYTH: injectable opioids are required for really good analgesia • MYTH: pain management could be on an ‘as needs’ only basis • Good evidence for ‘round the clock’ analgesia • MYTH: codeine is an effective analgesic • Weak analgesic, severe constipation • 7% lack CYP2D6 activity (poor metabolisers) Auret & Schug 2005

21. Choosing an opioid • Need to consider: • Response to previous trials • Co-existing diseases • Preparation • Route • Acceptability ease of administration

22. Opioid Preparations • Short acting • Liquid (morphine, hydromorphone, oxycodone) • Tablets (morphine mixture, hydromorphone, oxycodone) • Transmucosal (fentanyl) • Long acting • Tablets (morphine, oxycodone) • Suspension (morphine) • Patches / transdermal (fentanyl, buprenorphine) • Methadone – in its’ own category!

23. More opioid preparations • Subcutaneous/parenteral options (for driver / breakthroughs) • Morphine • Hydromorphone • Fentanyl • Methadone • (Oxycodone)

24. Opioids – some tips • To rotate opioids • refer to an opioid conversion table • consider their relative pharmacokinetics • Dosing guide • Breakthrough dose usually 1/6th 24 hour requirement • To convert oral to parenteral morphine – divide by 2-3 • When doing an opioid rotation – usually reduce calculated equianalgesic dose by about 1/3rd • When titrating, using the total breakthroughs in the prior 24 hours as a guide

25. An example • Mary’s pain is well controlled on 30mg bd of Oxycontin SR (no breakthroughs in the last 24 hours) • She is unable to swallow her Oxycontin reliably • You decide to change her to a subcutaneous infusion • What drug, dose will you chart and when should is start?

26. The answer? • Assuming there is not allergy/insensitivity to morphine • 30mg morphine subcutaneously over 24 hours, to commence 12 hours after she last took an Oxycontin SR • 5mg subcutaneous morphine as a breakthrough should also be charted

27. Opioid prescribing tips • Appropriate route • In naive patient, use short acting for the first 24 hours to gauge dose requirements • If regularly > 3-4 break throughs are required, consider: • Re assessing the pain(s) • Increase baseline dose • Adding an adjuvant • Patient/family compliance • Vital to dispel myths (pro-actively)

28. More opioid prescribing tips • Adverse effects • Pre-warn (eg. Sedation, nausea, constipation, confusion) • Anticipate (eg. Commence aperients with opioid) • Overdose • Extremely rare to be clinically significant with appropriate dosing. Most commonly results in better analgesia and incr. drowsiness. Of concern if respiratory rate <10 and/or inability to protect their airway.

29. Therapeutic range concept

30. Adjuvant analgesics • Benefits • Usually added to an opioid regime that despite optimisation, is not adequate • A particular pain may respond very well to an adjuvant (because of its mechanism) • The adjuvants primary function may be useful for a concurrent symptom • Side effects • Polypharmacy and additive toxicities

31. Major classes of adjuvants • Antidepressants • Anticonvulsants • Corticosteroids • Benzodiazepines • Local anaesthetics • Radio-pharmaceuticals • Neuroleptics • Muscle relaxants • NMDA receptor anatagonists • Alpha-2 adrenergic antagonists • Osteoclast inhibitors Lussier & Portenoy 2005

32. Cancer Pain: Specific Strategies • Visceral Pain • May respond completely to opioids • Anticholinergics may be helpful • For liver capsular pain anti-inflammatories (NSAIDS/steroids) are particularly helpful • Somatic Pain • Usually opioid responsive • Bone pain often responds well to anti-inflammatories, consider XRT, bisphosphonate, stabilisation (surgery / vertebroplasty), calcitonin, strontium

33. More strategies • Neuropathic Pain • Often ‘difficult’ • Likely to be less opioid responsive and require adjuvant agents (eg. antidepressants, anticonvulsants) • Raised ICP • Often incomplete opioid response • Responds well to dexamethasone

34. Defining Difficult Pain • Opioid poorly responsive pain • inadequately relieved by doses that cause intolerable side effects (despite optimal measures to control them) • Opioid irrelevant pain

35. Some examples • Neuropathic pain • Existential pain • Opioid toxicity • Incident pain / breakthrough pain • Delirium coexisting with pain • Pain in patients unable to self report • Rectal and bladder pain … and many others

36. An approach • “Abandon the therapy not the patient” • Reassess the patient and their pain • Comprehensive evaluation of causes for worsening pain or altered pain perception • Factors influencing opioid responsiveness • Multidisciplinary team • “it’s good to talk” • Consider palliative care referral Twomey et al. 2006

37. Factors influencing Opioid Responsiveness • Pain mechanisms (e.g. neuropathic) • Temporal pattern of pain (e.g. incident pain) • Opioid tolerance • Progression of disease • Individual factors • Drug factors • Opioid metabolites (M3G and M6G) • Route of administration Mercandante & Portenoy 2001

38. Approach to opioid poorly responsive pain • Adjuvants with independent effects • Drugs that reduce opioid side effects • Drugs that enhance analgesia produced by opioids • Opioid rotation • Other measures • Radiotherapy, chemotherapy, surgery • Orthotics or physiotherapy • Interventional (anesthetic) techniques • Psychological intervention Mercandante and Portenoy, 2001

39. Opioid Induced Neurotoxicity • Syndrome: cognitive impairment, severe sedation, hallucinations, delirium, myoclonus, seizures, hyperalgesia and allodynia • Risk factors: • High doses opiates for prolonged periods • Renal failure / dehydration • Pre-existing cognitive impairment or delirium • Advanced age • Psychoactive drugs (BZD’s, TCA’s) • Angst & Clark 2006; Daeninck & Bruera 1999; Mercandante et al. 2003

40. Opioid Toxicity Management ACUTELY • Opioid rotation • Dose reduction or discontinuation • Hydration • Psychostimulants • Other meds - e.g. neuroleptics • Seek advice PREVENTION • Thorough assessment of pain (and the patient) • Assessment of risk factors, especially: • Delirium • Drug interaction • ‘Difficult’ pain • Substance abuse • Prevent dose escalation • Monitor for early signs Daeninck & Bruera, 1999

41. If pain persists … • There is (nearly) always something that can be done to provide some, even if not complete, relief. • Seek expert advice.

42. References • [No authors listed] Pain terms: a list with definitions and notes on usage. Recommended by the IASP Subcommittee on TaxonomyPain 1979;6(3):249 • Angst MS, Clark DJ Opioid-induced hyperalgesia: a qualitative systematic reviewAnesthesiology 2006;104:570-87 • Auret K, Schug SA Underutilisation of opioids in elderly patients with chronic pain: approaches to correcting the problem Drugs Ageing 2005;22(8):641-54 • Bruera E, Sala R, Rico MA, Moyana J, Centeno C, Willey J, Palmer JL Effects of parenteral hydration in terminally ill cancer patients: a preliminary studyJournal of Clinical Oncology 2005;23(10):2366-2371 • Cleeland CS, Gonin R, Hatfield AK, Edmonson JH, Blum RH, Stewart JA, Pandya KJ Pain and its treatment in outpatients with metastatic cancerNew England Journal of Medicine 1994;330(9):592-596 • Clendinnen IV 2000. Tiger’s eye: a memoir Melbourne: Text Pub. • Cousins M and Power I Acute and post operative pain In: Wall P, Melzack R eds. Textbook of pain 4th ed. Edinburgh Churchill Livingstone;1999:65 • Daeninck PJ & Bruera E Opioid use in cancer pain. Is a more liberal approach enhancing toxicity?Acta AnaesthesiologicaScandinavica 1999;43:924-938 • Fasinger R, Nekolaichuk C, Lawlor P & Neumann C Edmonton Classification System for Cancer Pain (ECS-CP) Administration Manual 2006 Available from URL: http://www.palliative.org/PC/ClinicalInfo/AssessmentTools/Edmonton%20Classification%20System%20for%20Cancer%20Pain%20(ECS-CP)%20Manual%2030%20Jan%2008.pdf

43. References • Forbes K and Huxtable R Clarifying the data on double effectPalliative Medicine 2006;20(4):395-6 • Kay S, Husbands E, Antrobus JH, Munday D Provision for advanced pain management techniques in adult palliative care: a national survey of anaesthetics pain specialistsPalliative Medicine 2007;21(4):279-84 • Lussier D and Portenoy RK Adjuvant analgesics in pain management IN Oxford Textbook of Palliative Medicine 3rd Edition Edited by Doyle D, Hanks G, Cherny N and Calman K 2005:349-378 • Mercandante S, Ferrera P, Villari P, Arcuri E Hyperalgesia: an emerging iatrogenic syndromeJournal of Pain and Symptom Management 2003;26(2):769-75 • Mercandante S and Portenoy RK Opioid poorly-responsive cancer pain. Part 1. Clinical considerationsJournal of Pain and Symptom Management 2001;21(2):144-150 • Mercandante S and Portenoy RK Opioid poorly-responsive cancer pain. Part 3. Clinical Strategies to improve opioid responsivenessJournal of Pain and Symptom Management 2001;21(4):338-254 • Morita T, Tsunoda J, Inoue S, Chihara S Effects of high dose opioids and sedatives on survival in terminally ill cancer patientsJournal of Pain and Symptom Management 2001;21(4):282-289 • Perry S and Heidrich G Management of pain during debridement: a survey of US burn units Pain 1982;13(3):267-280 • Portenoy RK & Lesage P Management of cancer painLancet 1999;353:1695-1700

44. References • Rurup ML, Onwuteaka-Philipsen BD, van der Heide A, van der Wal G, van der Maas PJ Trends in the agents used for euthanasia and the relationship with the number of notificationsNederlandsTijdschriftvoorGeneeskunde 2006;150:618-24 • Strang P, Strang S, Hultborn R, Arner S Existential Pain- an entity, a provocation or a challenge?Journal of Pain and Symptom Management 2004;27(3):241-250 • Sykes J, Johnson R and Hanks GW ABC of palliative care: difficult pain problemsBritish Medical Journal 1997;315:867-869 • Sun VC, Borneman Y, Ferrell B, Piper B, Koczywas M, Choi K Overcoming barriers to cancer pain management: an institutional change modelJournal of Pain and Symptom Management 2007;34(4):359-69 • Twomey F, Corcoran GD, Nash TP Collaboration in difficult pain control in palliative medicine – it’s good to talkJournal of Pain and Symptom Management 2006;31(6):483-4 • Vainio A, Ollila J, Matikainen E, Rosenberg P, Kalso E Driving ability in cancer patients receiving long-term morphine analgesiaLancet 1995;346(8976):667-670