Pain Control in Advanced Cancer

1. Pain Control in Advanced Cancer Dr Nial McCarron Specialist Registrar Palliative Medicine

2. Outline Background Classification of pain Assessment Case History, including; principles of WHO ladder principles of prescribing analgesia for different sorts of pain principles of prescribing opioids

3. Extent of the problem 80% advanced cancer patients get pain Reasonable pain control possible in around 90%. Pain control problematic in around 10% 1/3 have one pain 1/3 two pains 1/3 three or more pains Pain often progressive

4. Total Pain Physical Spiritual Psychological Social (Cicely Saunders, 1964)

5. Classification of pain in advanced cancer Temporality Acute/ Chronic Aetiology Visceral/ Somatic/ Neuropathic Periodicity Background/ Breakthrough/ Incident

6. This might link in with what they have already learned about pain. The significance of cancer pain � reminding of mortality could link into �total pain�. Pain is part of the body's defense system, triggering mental and physical behavior to end the painful experience. It promotes learning so that repetition of the painful situation will be less likely. Chronic pain, in which the pain becomes pathological rather than beneficial, may be an exception to the idea that pain is helpful to survival This might link in with what they have already learned about pain. The significance of cancer pain � reminding of mortality could link into �total pain�. Pain is part of the body's defense system, triggering mental and physical behavior to end the painful experience. It promotes learning so that repetition of the painful situation will be less likely. Chronic pain, in which the pain becomes pathological rather than beneficial, may be an exception to the idea that pain is helpful to survival

7. Aetiology- Visceral Pain Constant Aching Poorly localised Referred Abdominal organ pathology e.g. Ca pancreas Mediastinal/ para-aortic nodes Biliary tree Ca Kidney

8. Aetiology- Somatic Pain Aching, often constant May be dull or sharp Often worse with movement Well localised Musculo-skeletal e.g. bone metastases arthritis muscle sprain fracture

9. Aetiology- Neuropathic Pain �Pain arising as a consequence of a disturbance of function or pathological change in a nerve or the nervous system�. International Association for the Study of Pain (IASP, Pain 1986;Suppl.3:216-21) Often occurs in an area of abnormal sensation Often occurs in an area of abnormal sensation

10. allodynia, pain due to a stimulus which does not normally provoke pain, hyperalgesia, an increased response to a stimulus which is normally painful Phantom limb pain - deafferent pain allodynia, pain due to a stimulus which does not normally provoke pain, hyperalgesia, an increased response to a stimulus which is normally painful Phantom limb pain - deafferent pain

11. Periodicity Background Constant/ unremitting Controlled by constant dosing Breakthrough Intermittent Use additional medication prn Incident

12. Incident Pain Pain precipitated by movement/ activity Often difficult to treat as may be severe but short lived Analgesics may help but of prolonged duration OR Usual analgesics don�t work quickly enough to help Newer fast onset/offset analgesics (e.g. buccal/sublingual fentanyl) may increasingly have a role here Anticipatory medication

13. Assessment Take a pain history to elucidate cause of pain, e.g. �Socrates� Site, Onset Character Radiation Associated symptoms Timing Exacerbating/Relieving Factors Severity Site, onset, character � how will that help elucidate the cause of pain. Use appendicitis as an example. Can be hard for people to describe their painSite, onset, character � how will that help elucidate the cause of pain. Use appendicitis as an example. Can be hard for people to describe their pain

14. Also severity. More meaningful to describe pain in terms of functionAlso severity. More meaningful to describe pain in terms of function

15. Knowing what has/hasn�t already worked will help you decide on the next treatment Dose Compliance Side effects Suitable route Duration Exacerbating/relieving factorsExacerbating/relieving factors

16. Holistic Issues Don�t forget to consider and address �Total Pain� including questions such as: What is the meaning of the pain to the patient? What are the patient�s hopes/expectations? Context: cultural, social, spiritual, emotional factors? Describe a patient � mother unable to pick up children, man unable to play the guitar, pain at night � scared of dying. People�s experience of pain dependent upon the context in which it occurs.Describe a patient � mother unable to pick up children, man unable to play the guitar, pain at night � scared of dying. People�s experience of pain dependent upon the context in which it occurs.

17. Case -Introduction Mr S comes to see you in surgery. 74 yr, retired policeman Presenting Complaint Back pain PMH Acute MI 5 years ago, doing well Prostate cancer, on hormone therapy Keen gardener, won 1st prize for tallest sunflower

18. Case continued Mr S tells you he has an aching back pain more on left It is keeping him awake at night. He doesn�t believe in taking pain killers. He uses paracetamol �now and then� but thinks they�re �no use�. What sort of pain do you think Mr S might have? What other questions do you want to ask him? What might else might you do at this stage? What do you suggest for analgesia? To check whether students have picked up on important points of assessment earlier in the presentation and are thinking about joining it to the next step � i.e. diagnosing the cause of the pain Any analgesics you think may not be helpful? Aim: - to see what classes of drugs they know about eg neuropathic pain. To see if they recognise that simple analgesics eg paracetomol continue to be useful. To check whether students have picked up on important points of assessment earlier in the presentation and are thinking about joining it to the next step � i.e. diagnosing the cause of the pain Any analgesics you think may not be helpful? Aim: - to see what classes of drugs they know about eg neuropathic pain. To see if they recognise that simple analgesics eg paracetomol continue to be useful.

19. Differential diagnosis Back strain Arthritis Bone metastases Constipation UTI Spinal cord compression - Beware To labour point that in patients with cancer, can have cancer and non related cancer pain.To labour point that in patients with cancer, can have cancer and non related cancer pain.

20. Principles of Prescribing for Pain Treat the underlying cause if possible Visceral pain often opioid sensitive Bone pain may be opioid sensitive often NSAID sensitive Neuropathic pain usually only partially opioid sensitive anticonvulsants/antidepressants are useful

21. Pain Management- WHO Analgesic Ladder Strong Opioid + Paracetamol +/- adjuvant Weak Opioid + Paracetamol +/- adjuvant Paracetamol +/- adjuvant adjuvant drug - not designed to provide analgesia adjuvant drug - not designed to provide analgesia

22. WHO Analgesic Ladder Step 1 Paracetamol Not to be underestimated as an important analgesic Step 2 Codeine Dihydrocodeine Tramadol Limited doses � one or options only

23. WHO Analgesic Ladder Step 3 Morphine Diamorphine Oxycodone Fentanyl Doses depend upon: the patient previous opioid history

24. Case continued Previously you advised Mr S to take regular co-codamol 30/500 2 tablets qds. He returns for review two weeks later. He is sleeping better but his pain is still bad when he is up and about. What else might you do now? Think about imaging at this point i.e. bone scan. Might need to take history and examine for signs of SCCThink about imaging at this point i.e. bone scan. Might need to take history and examine for signs of SCC

25. Prescribing Opioids Morphine is standard - cost, effectiveness No ceiling dose for strong opioids Only side effects prevent escalation of dose if analgesic effect continuing To regain pain control � increase dose by 1/3 -1/2 Aim for constant blood level Give by mouth if possible

26. Opioid Doses 10mg oral morphine is equivalent to: 100mg Dihydrocodeine 100mg Codeine 100mg (?) Tramadol (Fentanyl patch 25micrograms/hr is about 90mg of oral morphine/24hrs) Palliative Care Formulary 3rd edition (revised)

27. Case Investigations confirm bone metastases and you inform his oncologist. You decide to start Mr S on morphine as his pain continues. You talk through how to start morphine. What else should you tell him about? See whether students know and side effects, driving advice, guidance on how to take etc.See whether students know and side effects, driving advice, guidance on how to take etc.

28. Case continued How much morphine might you give Mr S? What else should he take? How might the morphine be given? Think about imaging at this point i.e. bone scan. Might need to take history and examine for signs of SCCThink about imaging at this point i.e. bone scan. Might need to take history and examine for signs of SCC

29. Oral Morphine Sulphate Immediate release: Oramorph Sevredol Rapid onset 20 - 30 minutes Duration 4 hrs Slow release: MST Zomorph Given every 12 hours

30. Breakthrough Pain Pain which occurs despite regular doses of (modified release) morphine Treated using a �breakthrough� or �interval� dose of immediate release morphine Usually calculated as 1/6th of total daily (24hr) morphine requirements

31. Breakthrough doses For example MST 30mg bd Total daily dose = 60mg Breakthrough dose = 10mg short acting morphine MST 120mg bd Total daily dose = 240mg bd Breakthrough dose = 40mg short acting morphine

32. Side Effects of Opioids Constipation Nausea Sedation Vomiting Miosis Dry mouth Confusion Itching Euphoria Respiratory depression* Dependence /Addiction* *Do not tend to occur in patient receiving opioid for cancer related pain

33. Side effects Constipation Co prescribe laxative permanently Nausea Co prescribe anti-emetic prn first 5 -7days Drowsiness Assess � may pass / reduce

34. Case Mr S has some other worries about starting on morphine. What might they be? Addiction, equated with dying, won�t be able to driveAddiction, equated with dying, won�t be able to drive

36. Different Definitions Tolerance A normal physiological phenomenon in which increasing doses are required to produce the same effect Physical Dependence A normal physiological phenomenon in which a withdrawal syndrome occurs when an opioid is abruptly discontinued Psychological Dependence A pattern of drug use characterised by a continued craving for an opioid which is manifest as compulsive drug seeking behaviour leading to an overwhelming involvement in the use and procurement of the drug

37. Case For a few months Mr S� back pain is well controlled on MST 40mg bd. He comes back to see you, accompanied by his wife. On questioning he admits that the pain is not so well controlled, particularly when he is up and about. What would you consider now? Time to think about introducing a NSAID?Time to think about introducing a NSAID?

38. Bone pain Not always responsive to morphine NSAIDS Caution: H/O ulcer, on warfarin, high dose steroids, renal failure, (asthma) Radiotherapy Bisphosphonates

39. Case One morning during surgery, Mrs S phones asking for a home visit. Mr S has been poorly with nausea and vomiting and has started �talking jibberish�. What do you think might be going on? What would you look for to confirm this on examination? What would you do next? Think about hypercalcemia, renal failure etc. Should this patient be admitted? What are his wishes about place of care? Think about hypercalcemia, renal failure etc. Should this patient be admitted? What are his wishes about place of care?

40. Opioid Toxicity Intractable Nausea Hallucinations Drowsiness Jerks Pinpoint pupils (Depressed respiration) Remember metabolites of morphine accumulate in renal failure leading to toxicity What do we do? i.e reduce/stop What do we not do? i.e give naloxone except in profound respiratory depression What do we do? i.e reduce/stop What do we not do? i.e give naloxone except in profound respiratory depression

41. Case You decide Mr S should be admitted to hospital where he is found to be hypercalcaemic with renal impairment. His NSAID is stopped. The medical team are worried about him remaining on MST given his renal impairment. He feels fed up with having to take so many medications. What might they consider for analgesia now? Thinking about other routes for opioidsThinking about other routes for opioids

42. Analgesic Patches In general, should only be used in stable pain Indications for analgesic patches include: Difficulty taking medication orally Compliance Reduce medication load Side effect profile Always use conversion chart to work out breakthrough doses/ equivalence to other opioids

43. Fentanyl Patches Fentanyl 25mcg/hr patch equivalent to 90-100mg oral morphine /day Less constipation, better with poor renal function cf morphine Take 12-72 hrs to reach full strength on first application Take approx 24 hrs to wash out of system Breakthrough doses are oral e.g. morphine � charts used to calculate correct dose.

45. Buprenorphine Patches Trade name: Butrans, Transtec. Partial agonist at mu receptors Similar potency to Fentanyl when used as a patch. i.e. 25mcg/hour Buprenorphine Equivalent to 25 mcg/hr Fentanyl

46. Case Mr S has found the patch helpful but is now starting to get sharp pain in his hip radiating down his thigh. It is burning and occasionally has a shooting quality. His breakthrough doses of morphine are not helping and neither does increasing the patch. What sort of pain could this be? What do you suggest?

47. Neuropathic pain management Antidepressant e.g. amitriptyline low dose Anti- epileptic e.g. gabapentin, pregabalin, clonazapam, carbamazepine sodium valproate Anti depressant plus anti epileptic Other specialist options may include: NMDA antagonists e.g. ketamine/ methadone nerve blocks ?steroids

48. Antidepressants / antiepileptics Need to be titrated Take several days for each new dose to be effective Side effects: Antidepressants Antimuscarinic effects � dry mouth, nausea/ blurred vision/ drowsiness Anti-epileptics Drowsiness ++, nausea, constipation

49. Case Mr S continues to feel nauseated and occasionally vomits. He is fed up with going in and out of hospital. You see that he is clearly deteriorating. Both he and his wife would like him to remain at home if possible. What could you do now?

50. Syringe Drivers Graseby MS16A McKinley T34

51. Indications for a using the subcutaneous route Persistent nausea & vomiting Difficulty swallowing Irreversible confusion, agitation Fatigue or unrousable Malabsorption

52. Drugs used in a syringe driver Can be used in combination but need to check compatibility Are more potent than those used orally, e.g. 30mg oral morphine is equivalent to 15 mg subcutaneous morphine or 10mg diamorphine Doses of commonly used drugs can be found in the front of the BNF Can take four hours to reach optimal serum concentration

53. Summary Assessment is the key to good pain management in palliative care Patients may have more than one pain Use the pain ladder to guide management Morphine is safe when titrated correctly, with no ceiling dose Always prescribe appropriate dose of breakthrough analgesia Always co prescribe a laxative and anti-emetic Consider bone and nerve pain and use adjuvants accordingly Consider alternative routes, such as a syringe driver

54. References Coyle, N., et al. (2004) In their own words: seven advanced cancer patients describe their experience with pain and the use of opioid drugs. Journal of Pain and Symptom Management. 27: 300-309 Palliative Care Formulary 3rd Edition, Twycross and Wilcox (eds) If you register on the site (free), this book can accessed in the formulary section at www.palliativedrugs.com