1. Focus on pain: An introduction to pain management For Romford VTS trainees Nov 08 Dr Corinna Midgley Medical Director Saint Francis Hospice

2. Pain A common problem –In the cancer context about 3/4 will experience pain: 1/4 do not –A potentially complex problem with 1/3 of those in pain experiencing at least 3 different kinds of pain whether through cancer, treatment, debility or concurrent disorder Ref: Twycross: Symptom management in advanced cancer 2nd ed 1997

3. Patients with non cancer diseases are as likely as patients with cancer to suffer pain in the last year of life (94 vs 96%) CVAs: –In the last week of life 42% experienced pain Heart failure, COPD, cirrhosis: –level of pain experienced 3 days pre death was the same as that of cancer patients Addington-Hall J et al. Stroke 26:2242-8 Skillbeck J et al. Pal Med 12 (1998) 245-54 Motor Neurone Disease: –73% have pain due to stiffness, spasm or immobility/skin pressure Oliver D. Pal Med 1998; 12:113-115

4. The elderly: –40-60% of elderly in institutions are in pain Almost 1/2 of those dying of cancer are over 75 yrs old Ferrel BA. Pain evaluation and management in the nursing home.Ann Int Med 1995; 123:6681-687 Lefebvre-Chapiro S et al. Evaluating Pain in the Elderly. EJPC, 2001; 8(5) 191-194 –Indicators of poor pain management (NEJM 1995) include being aged over 70 being female having a dementia not having cancer pain

5. And in the dying? –Studies confirm that people are more likely to suffer pain in the last week of their life (77 vs 67%) Regional Study for Care of the Dying –even in a hospice population with generally well controlled pain, pain resurges for a proportion in their last 3 days of life (26% in hospice IPU population) EJPC 2000 7(3)

6. We do need to anticipate pain And assess, explore, and record in an effort to objectify, approach and monitor a subjective phenomenon

7. Constructing a management plan The best way of treating pain is to remove the cause. If cause is unremovable…we need to manage the pain in a way that the patient can manage

8. Pain can be complex, with physical, emotional and spiritual dimensions >> PAIN if Scared Suffering Suppressed Depressed Unconfident Vulnerable << PAIN if Safe Controlled and in control Able/allowed to talk On top of emotions Confident of care Confident team

9. Not all treatments are drug treatments but a methodical safe, effective approach to medicating is crucial

10. A medicines plan for pain: –The WHO analgesic step ladder approach to pain –By the clock regular pain needs regular analgesia –By the mouth most people’s preferred route-as effective as s/c, if absorbing –By the ladder If it still hurts-step UP the ladder An effective treatment plan: safe - but effective

11. The WHO Analgesic Step Ladder Paracetamol +/- NSAID +/- adjuvant STEP 1 STEP 2 Weak opioid+/- NSAID +/- adjuvant STEP 3 Strong opioid +/- NSAID +/- adjuvant Mild-mod pain Moderate pain Severe pain If pain is unrelieved on lower step, then progress up the ladder

12. Aims to build confidence in: Pain management for people with advancing life-limiting disease Knowledge about and skill in using a syringe driver: suitable drugs conversion of drugs from oral dosage to syringe driver, ‘either IV or subcutaneous’.

13. Scenario A 38 year old woman with known glioblastoma stage 4 Recently underwent radiotherapy and is on a reducing course of dexamethasone She comes to see you with headaches –What do you want to know?

14. She has tried paracetamol up to 4 x daily –What do you want to know? It is of no help –What do you do?

15. She is given cocodamol 8/500 2 qds –No help She is tried on codydramol 2 tabs qds –No help She then is given dihydrocodeine 30-60mg qds –No help She is tried on solpadol 2 tabs qds –No help She then tries tylex 2 tabs qds –No help

16. The commonest cause of poor pain control in adults with advanced life-limiting illness is reluctance to step up the analgesic pain ladder to an opioid

17. So…if someone needs an opioid what is the best one to start with? Oramorph –Cheap, safe if used safely, suits most people, works well for most people –The challenge is-how much does this lady need?

18. QUIZ: What is the usual starting dose of oramorph? –The norm is 10mg orally, but this dependent on previous exposure to weak opioids. With no exposure to step 2’s and especially if elderly/frail start at 5mg Will she definitely take it? If not-why not? –Patients often fear starting morphine as much as doctors do-the end is near, it will hasten death, it will make me a zombie, there will be nothing left at the end Any thing you should routinely advise on, or even co- prescribe? –Yes –warn re constipation. Supply a laxative to start if one missed BO –Warn re nausea/vomiting - affects 1/3 of those starting morphine. Note its transience-enough to cover week one, just in case, should be enough

19. QUIZ ctd You give her some oramorph to supplement her regular cocodamol 30/500 2 tabs qds. –When do you plan to revisit symptom control? How? She has taken 10mg oramorph 4 x in the last 24 hours –What next? –Was it helpful? –Any side effects? –Any toxicity symptoms? Now she is on MST 30mg bd. What just in case dose of oramorph should she be on? –Convention-safe and effective in practice-is that the immediate release drug should be tried for breakthrough pain at a dose of 1/6th of the total daily dose of morphine –In this case-oramorph 10mg o prn

20. Toxicity symptoms include Somnolence Hallucinations Confusion Respiratory depression Side effects include Nausea Constipation Dry mouth transient sleepiness

21. QUIZ: Now she is on MST 300mg bd. What just in case dose of oramorph should she be on? –Convention-safe and effective in practice-is that the immediate release drug should be tried for breakthrough pain at a dose of 1/6th of the total daily dose of morphine –In this case-oramorph 100mg o prn How did she get from 30mg bd to 300mg bd? –By constant review and reflection on effectiveness of prns in last 24 hours any emergent toxicity symptoms Seek help if you feel out of your depth –and titration up if no emerging toxicity break through medicine is effective

22. Issues for concern: –Rapid escalation of pain (and opioid dose) –It is not clear whether the morphine is effective or not –There are symptoms/signs of toxicity –You as GPs and/or district nurses feel unsafe or in any way out of your depth What to do if your patient deteriorates and can no longer manage oral medication? –A syringe driver is invaluable –Diamorphine is our 1st drug of choice –Add up total amount of oral morphine taken in the last 24 hours- and divide by 3 for 24 hour diamorphine dose –In this case it will be diamorphine 200mg/24 hours s/c

23. QUIZ ctd You have a patient who is clearly dying. He is unable to manage oral medicine but in fact was on no analgesia. He is uncomfortable Where do you start? –What about a SD with diamorphine 10-15mg/24 hours-a safe and sensible start dose. Plus prn diamorphine 2.5mg if pain What if he had been comfortable? –you don’t need to give analgesia unless discomfort breaks through. But-just in case do ensure that prn injectable medication and authorisation is in the house: diamorphine 2.5mg sc prn. What if he had been on 30mg MST bd? –you need to make sure he continues on the equivalent: MST 30mg bd = 60mg orally /24 hours Diamorphine equivalent = 1/3 of 60mg =20mg/24 hours Plus prn diamorphine 5mg s/c (1/6th daily dose)

24. Most pain will be fully responsive to the WHO ladder But what if it isn’t? note ‘ +/- NSAIDS, +/- adjuvants’. What about a.Other analgesics e.g. NSAIDS b.Adjuvants c.Steroids d.Non pharmaco-physical interventions e. Other opioids

25. In the dying patient opioids can often seem the only option for analgesia because of difficulty in managing oral medicines Why might we use another opioid when oral morphine and s/c diamorphine are so good? There is still pain-but there is also toxicity The patient has severe renal failure The patient was on different oral opioids and you are carrying on in the same vein

26. Alternative oral opioids 1. OXYCODONE An excellent and easy oral alternative to morphine. –Includes oral IR liquid and capsules (oxynorm); SR capsules (oxycontin), (also inj oxycodone) –Oxycodone o is twice as potent as morphine o oramorph 10mg 4 hrly = oxynorm 5mg 4 hrly MST 30mg bd = oxycontin 15mg bd Provides an alternative to morphine if the patient is in pain, but toxic with morphine Pros: An equally good analgesic, which can suit when morphine hasn’t. Cons: watch for drug errors. It is getting a street reputation, and it is more expensive. Is available, as oxycodone inj, into a syringe driver

27. E.g. A 67year old man with locally advanced rectal cancer is really troubled by aching in his bottom. The pain dulls with MST, and oramorph is very helpful-reducing it from 7/10 to 2/10, but over the last few weeks he has had to increase his MST from 30mg bd to 300mg bd and since his last increase is feeling muggy, dreaming vividly and has started to twitch.

28. Switch to oxycodone highly successful with better pain control and abolition of dreaminess etc. MST 300mg bd orally –= 600mg oral morphine/24 hours –(prn dose = 1/6 th daily dose, 100mg oramorph as needed) This is equivalent in potency to 300mg oxycodone orally/24 hours (as it is about 2 x as strong) –(prn dose = 1/6 th daily dose, 50mg oxynorm as needed) Great! But if a syringe driver is needed later on-it’s complex. –300mg oxycodone orally/24 hours = 150mg oxycodone inj/24 hours (with 1/6 th - 25mg – sc prn) –This = 15 x 1ml ampoules in SD, plus a prn which = 2.5mls…..

29. Alternative oral opioids 2. METHADONE Complex to titrate, but ultimately this is a simple oral alternative to morphine. –In liquid and tablet form. Also available as injectable. Pros: An equally good analgesic, which can suit when morphine hasn’t BUT Con: Despite being cheap and effective, difficult to titrate as no fixed conversion. No idea what dose your patient will emerge with. Usually conversion is done in the hospice, over 6-7 days. But can be done at home. Is available, as methadone inj into a syringe driver.

30. E.g. A 76 year old woman with a painful chest wall underlying fungating breast cancer. She is on oxycodone, gabapentin to 900mg tds, amitriptyline 25mg nocte, clonazepam 1mg nocte, diclofenac 50mg tds and paracetamol 1g qds. The pain is building again; oxynorm dulls it but she has developed hallucinations and twitches. She fell x 2 yesterday and is scared.

31. FENTANYL A very fast acting strong opioid –Key advantages:Is an alternative to morphine - it works on different receptor sites. So that it can be used when the patient is toxic but in pain with morphine Is available for use via a variety of non oral routes Is not reliant on renal excretion, so is the maintenance drug of choice in patients with severe renal failure –Key disadvantages: it does not sustain for long it is not available as an oral preparation as it is poorly absorbed from the GI tract

32. FENTANYL PATCH Pros: Patch only needs renewal every 72 hours, so can feel liberating to the patient –(note 1/5 th pts do need more frequent change) Less constipating than morphine Cons: Conversion from other opioids requires a table, and what prn should be used? (usually oramorph, with oxynorm the usual 2 nd line)

33. FENTANYL PATCH DANGER DANGER ***!the preparation MOST LIKELY TO LEAD TO TOXICITY*** The patch makes the fentanyl lie in a depot under the skin so nothing will change rapidly when a fentanyl patch is adjusted..: –Absorption continues for up to 24 hours after a patch is removed –When a patch dose is changed it can take a good 16 hours to show increased effect. So it should not be used in patients with rapidly changing analgesic needs Can often feel complex when on a dying patient

34. ALFENTANIL and FENTANYL The patch makes the preparation slow to build and slow to leave the body. When NOT in this preparation, fentanyl normally is rapidly absorbed, distributed and broken down. Thus its value in Incident Pain -fentanyl lollies absorb rapidly and provide a boost of pain relief for 15-20minutes -alfentanil inj’s provide fast short lived relief A syringe driver -alfentanil = our 2nd line subcutaneous driver drug of choice

35. 79 years, End stage renal failure. Dialysis abandoned. Hiccuping and sleepy, and in pain from diabetic peripheral neuropathy. Unable to manage oral meds. SD of diamorphine? Or… alfentanil. Diamorphine 10mg=alfentanil 1mg.

36. 61 year old lady. Advanced rectal cancer, with colostomy. Switched from morphine because of ? vestibulitis, to oxycodone orally, but tablets appearing in the stoma bag with increased pain control. Dose: 150mg o bd. So… switched to sc oxycodone. As pain escalated volume rapidly unmanageable. Switched to alfentanil. Now on 180mg alfentanil/day. No toxicity and reasonable pain control-but alfentanil not available any more. What to do?

37. 43 year old lady. Advanced abdominal disease. Increasing pain. Was on a 50mcg fentanyl patch-but-now needing up to 4 doses of extra analgesia a day. Struggling to manage oral meds. What to do?

38. BUPRENORPHINE Includes transdermal patches Similar to fentanyl transdermal, but start at a lower dose range, and the patches can be cut-allowing tiny doses to be given. Same limiting probs of time needed to reach an equilibrium, and what to do if rapidly changing needs, and, at dying-to supplement or substitute?

39. References The invaluable BNF-ALWAYS LOOK! –Excellent palliative care section at the beginning –Always look up drugs that you do not feel completely familiar with Symptom Management in Advanced Cancer: Robert Twycross ISBN 1857755103 Your local hospice will have protocols/guidelines on the analgesic step ladder and all of the opioids, and some common symptoms. If your patient is ever on a drug you do not understand please do contact your palliative care team or local hospice to discuss. You can ask for a copy of the protocol for that drug.

40. Pain in the dying phase Is usually simple to manage. Note the simplicity of the LCP guidance on pain management

41. The terminal phase ‘… is not simply a continuation of all that has gone before-there may be new causes of suffering for both the dying person and the relatives.. ’ Oxford textbook of Palliative Medicine 3rd ed Ch 18 The terminal phase ‘In the end all the kind care that had been given along the way went out of the window-because she died the way she died...’ A patient’s husband after she had died- a quote recalled by Dr John Ellershaw, LCP conference, 2005 and one inspiration for developing the LCP.

42. The cost of care The concept of a ‘just in case’ box –The aim is to be prepared for common problems and avoid delays in helpful care Cost for supplier? –Prescription writing time –Authorisation writing time –Pharmacist time –Pick up time –Storage care –Careful and appropriate disposal

43. Financial cost of just in case drugs –For pain: 10 x ampoules of x opioid - enough for several prns and a days worth of a syringe driver… variable e.g. diamorphine:10mg x 10 amps = £13.60 (for pt prev on MST 90mg bd + oramorph 30mg o prn) 30mg x 10amps = £16.20 (for pt prev on MST 270mg bd + oramorph 90mg o prn) oxycodone injectable: 10mg x 10 amps = £14.00 note volume of stat = 1ml (this would ‘cover’ pt prev on 60mg oxycontin bd + oxynorm 20mg prn) alfentanil: problematic for stats as very short acting. (for interest alfentanil 5mg-equiv to 50mg diamorphine costs £2.65 )

44. Costs continued –For nausea: 5 x ampoules of e.g. cyclizine (50mg / amp) - enough for a syringe driver for a day plus 2 prns … = £3.50 5 x ampoules of levomepromazine (25mg/amp) - enough for a syringe driver for at least one day plus probably 4 prns… = £10.68

45. Costs continued –For restlessness: 5 x ampoules of e.g. midazolam (10mg/amp) - enough for a syringe driver for a day plus usually at least 3 stat doses … = £3.95 (more complex restlessness already covered by levomepromazine) –for breathlessness: already covered by opioid plus benzodiazepine –for retained secretions: 5 x ampoules of hyoscine hydrobromide (400mcg/amp) - enough for syringe driver set up plus 1-2 stat doses = £13.55

46. Average total cost of just in case meds: Diamorphine + Cyclizine + Levomepromazine + Midazolam + Hyoscine + Water for injections = £46.60

47. Average cost of continuing with supplying medicines without reflection on their value and appropriateness for the changing patient High.

48. Many thanks for coming.