Palliative Care Part 1

1. Palliative CarePart 1 Dr Christine Hirsch School of Pharmacy, Aston University, Birmingham B4 7ET

2. What is Palliative Care? “Palliative care is an approach that improves quality of life of patients and their families facing the problems associated with life threatening illness, through prevention & relief of suffering by means of early identification, impeccable assessment and treatment of pain and other problems physical, psychosocial and spiritual.” WHO 2004 www.who.int

3. Team Approach

4. Symptom prevalence patients with advanced cancerC. Faull and R. Woof .Palliative Care 2002 Oxford University Press

5. Objectives Part 1- Pain • Develop an individualised, safe, rational and stepwise approach to pain management in palliative care • Be able to advise on management of breakthrough pain • Be able to ‘convert with confidence’ • Understand the appropriate use of adjuvant analgesics

6. Part 1 Patient 1 • Mr S is a 78 year old man with advanced prostate cancer and bone metastases. • He has been admitted via casualty drowsy and confused. • He has a supply of paracetamol 1g qds and tramadol 100mg qds which were his own medications brought with him on admission. • The label on the tramadol indicates that it had been dispensed three days earlier.

7. Assessment of pain • An unpleasant sensory and emotional experience • Is what the patient says it is • Location – underlying pathology (related to cancer? Treatment?) • Duration and timing • Intensity and nature • What if anything eases it or makes it go away.

8. Pain management in cancer patients • Visceral pain - usually opioid sensitive “deep ache”, “pressure”, “throbbing” • Bone pain – localised, “aching” variable response to opioids, traditionally NSAID sensitive, radiotherapy or bisphosphonates may be appropriate • Neuropathic pain – difficult to describe, dysaesthesia, may respond poorly to opioids, adjuvant analgesics may be helpful • Incident pain - episodic

9. Pain due to cancer • 30% do not develop pain • Pain may be: • cancer related • treatment related • related to consequent disability • due to concurrent disorder • may be controlled in 80% of patients

10. Tramadol • Opioid and non-opioid action • Metabolised to M1(O-desmethyltramadol) in liver, • 2-4 x more potent than tramadol via CYP2D6 • 5-10% caucasians lack CYP2D6 • Much lower affinity for opioid receptors than morphine • Inhibits re-uptake of noradrenaline and serotonin • Drug interactions • Analgesic effect reduced by ondansetron • Warfarin - may prolong INR

11. WHO three-step analgesic ladder Opioid for moderate to severe pain +/- non-opioid +/-adjuvant e.g Paracetamol NSAIDs Opioid for mild to moderate pain +/- non-opioid +/- adjuvant Non-opioids +/- adjuvant/s e.g. Morphine Diamorphine Fentanyl Oxycodone Hydromorphone Methadone e.g. Codeine Dihydrocodeine Tramadol 1 2 3

12. Analgesia in advanced cancer • Where possible give analgesia: • Regularly • By mouth • By the WHO analgesic ladder

13. Initiating morphine as a ‘strong opioid’ • If previously on weak opioid give 10mg morphine 4-hourly or mr 20-30mg bd • If frail or elderly 5mg morphine 4-hourly • In reduced renal function reduce dose or lengthen dose interval or both. • If two or more prn doses taken in 24 hours increase by 30-50% every 2-3 days as long as pain is opioid responsive. • If using mr morphine also provide ‘immediate release’ morphine liquid or tablets • Goal: pain free, mentally alert

14. Anticipate – ‘Rescue’ doses • Choose opioid prescribed for regular medication (exceptions may be fentanyl & methadone) • Dose = up to 1/6 of 24 hour dose of baseline analgesia

15. PHYSICAL TOTAL PAIN SPIRITUAL SOCIAL PSYCHOLOGICAL

16. Alternative opioids • When would you use ? • Which would you use?

17. Patient 2 part 1 Mrs. B. A65 year old lady with advanced ovarian carcinoma has had her pain controlled previously on Zomorph 60mg bd. • Very unwell • vomiting for 3 days • severe abdominal pain • Unable to take her usual modified release morphine because of the vomiting

18. Alternative Step 3 opioid analgesics: • Fentanyl - (transdermal patch – reservoir & matrix, transmucosal lozenge/ sl, buccal, alfentanil injection-sc infusion) • Hydromorphone – (normal release capsules, modified release capsules,‘Special’ – injectable) • Oxycodone – (normal release caps and liquid, modified release tabs, injection) • Methadone - (liquid, caps/tabs, injection) - specialist use only. • Transdermal buprenorphine- (place in palliative pain control still not determined)

19. ‘Converting’ doses of opioid • Refer to tables- as guidance only • NB : Opioid metabolism varies between individuals • Titrate to individual requirements • NB: Compromised renal or hepatic function and concomitant drugs.

20. Episodic pain • Breakthrough pain – (exacerbations against a background on controlled pain or occurring before next opioid dose is due). • Spontaneous pain - ‘idiopathic pain’ unpredictable • Incident pain – (predictable) related to specific actions e.g. movement, dressing change, coughing • End-of-dose failure ‘Any acute transient pain that is severe and has an intensity that flares over the baseline’ EAPC working group 2002

21. Patient 3 – Part 1 • A 72 year-old man • Prostate cancer, diagnosed 2002 • Bone secondaries, March 2007 • Spinal cord compression recently • His assessment – ’20 year-old, locked in an old body’ • Problems: mobility, pain, constipation

22. Drug history on admission • Co-codamol 8/500 2 qds (not taken) • Diethylstilbestrol 1mg od • Lansoprazole 30mg od • Dexamethasone 8mg bd • Cyclizine 50mg tds • Aspirin 150mg od • Lactulose 10ml bd

23. Adjuvant analgesics • Corticosteroids • Antidepressants • Antiepileptics • Bisphosphonates • MNDA receptor blockade • Antispasmodics • Muscle relaxants • TENS / Acupuncture • Radiotherapy

24. Patient 4 Part 1 - BS 49 year old female • Bilateral carcinoma of breast • Long standing back pain • Severe pain • Straining to pass urine • Pain lower abdomen • Numbness in hands • NIDDM

25. Prescribed drugs • Zomorph 60mg bd • Paracetamol 1g qds • Lansoprazole 30mg od • Co-danthramer 2 nocte • Diclofenac 75mg MR bd • Sodium clodronate 1600mg od • Gabapentin 300mg tds • Dexamethasone 2mg od • Gliclazide 40mg od plus BM measurement. • Temazepam 10mg prn • Hyoscine Hydrobromide 400mcg prn • Midazolam 2.5mg prn • Levomepromazine 6mg po prn/ 5mg sc • Oromorph 20mg prn • Diamorphine 5mg sc prn

26. Gold Standards Framework • Communication • Co-ordination • Control of symptoms • Continuity out of hours • Continued learning • Carer support • Care in the dying phase

27. Availability of drugs in the community • Anticipation • In-hours availability • Out of hours availability Gold Standards Framework Liverpool Care Pathway • Communication

28. References: • West Midlands Palliative Care Physicians - Guidelines for the use of drugs in symptom control 4th Ed 2007. • Faull C, Carter Y,Daniels, 2005 Handbook of Palliative Care Blackwells Oxford. • Twycross R, Wilcock A. Palliative Care Formulary 3rd Ed. 2007. • Dickman A,Schneider J, Varga J. The syringe driver in palliative care.2nd Ed, 2005 Oxford University Press. Oxford. • Dickman A. Basics of managing breakthrough cancer pain. The Pharmaceutical Journal 2009;283,21

29. References cntd: • Fallon M, Hanks G. ABC of Palliative Care. 2nd Ed 2006. Blackwell Publishing. • Dickman A. Chronic pain management: advances. Pharm J. 2007;279:354-356. • Palliative drugs website: www.palliativedrugs.com • Scottish intercollegiate guidelines network website www.sign.ac.uk

30. Palliative CarePart 2 Dr Christine Hirsch School of Pharmacy, Aston University, Birmingham B4 7ET

31. Objectives Part 2 • To advise on aspects of symptom control other than pain • To understand the place of the syringe driver in symptom control in palliative care • Pain • Nausea • Agitation • Secretions

32. Pathway for care of the dying Integrated care pathway e.g. Liverpool Care Pathway • Initial assessment • Ongoing care • Care after death

33. When should a syringe driver be started? • Persistent nausea & vomiting • Difficulty swallowing • Poor alimentary absorption • Intestinal obstruction • Unconscious or profoundly weak

34. Opioids via syringe driver willNOTgive better analgesiaunless there is a problem withabsorption or administration

35. Patient 1 Part 2 Mrs BS 49 year old female • Bilateral carcinoma of breast • Long standing back pain • Severe pain • Straining to pass urine • Pain lower abdomen • Numbness in hands • NIDDM

36. Prescribed drugs • Zomorph 60mg bd • Paracetamol 1g qds • Lansoprazole 30mg od • Co-danthramer 2 nocte • Diclofenac 75mg MR bd • Sodium clodronate 1600mg od • Gabapentin 300mg tds • Dexamethasone 2mg od • Gliclazide 40mg od plus BM measurement. • Temazepam 10mg prn • Hyoscine Hydrobromide 400mcg prn • Midazolam 2.5mg prn • Levomepromazine 6mg po prn/ 5mg sc • Oromorph 20mg prn • Diamorphine 5mg sc prn

37. Data on drug compatibility and stability is limited: • Generally dilute with water - unless 0.9% saline is specified – debate! • Avoid mixing more than two drugs in a syringe, unless stability data is available

38. Analgesia - usually diamorphine • Alternatives: Morphine, Oxycodone, Hydromorphone, Alfentanil • Dose conversions – consult local palliative care guidelines • Consider, renal failure, liver failure, stable pain • Timing

39. Antiemetics • First line agent - based on underlying cause: haloperidol, metoclopramide, cyclizine • Second line, add another first line or change to ‘broad spectrum e.g. Levomepromazine • Third line, if other agents not controlling try 3 days 5HT3 receptor antagonist

40. Antiemetics - in syringe drivers • Cyclizine & levomepromazine (Nozinan) - irritation at infusion site. • Try saline as diluent for levomepromazine • Do not use saline to dilute cyclizine • Cyclizine / diamorphine mixture may precipitate if cyclizine conc >10mg/ml or either drug > 25mg/ml. Use larger volume • Do not mix cyclizine and oxycodone

41. Agitation and delirium • Consider causes; e.g. drugs (opioids), biochemistry (e.g. calcium) infection, constipation • Delirium/psychosis: Haloperidol Levomepromazine

42. Restlessness & agitation Where agitation & anxiety are predominant features: • Midazolam • Levomepromazine

43. Myoclonic jerking May be exacerbated by drugs, rapid escalation of opioid dose and anticholinergics • Midazolam • Clonazepam (specialist use only)

44. Terminal respiratory secretions • Positioning • Reassurance • Hyoscine hydrobromide -crosses blood brain barrier, absorbed transdermally, paradoxical agitation, sedation. • Hyoscine butylbromide - for colic with intestinal obstruction, may be used to control secretions. Does not cross blood brain barrier. • Glycopyrronium - for excessive respiratory secretions and bowel colic. Does not cross blood brain barrier. Unstable above pH6, avoid mixing with dexamethasone.

45. Prescribed drugs • Zomorph 60mg bd • Paracetamol 1g qds • Lansoprazole 30mg od • Co-danthramer 2 nocte • Diclofenac 75mg MR bd • Sodium clodronate 1600mg od • Gabapentin 300mg tds • Dexamethasone 2mg od • Gliclazide 40mg od plus BM measurement. • Temazepam 10mg prn • Hyoscine Hydrobromide 400mcg prn • Midazolam 2.5mg prn • Levomepromazine 6mg po prn/ 5mg sc • Oromorph 20mg prn • Diamorphine 5mg sc prn

46. BS syringe driver • Diamorphine 40mg over 24 hours • Cyclizine 150mg over 24 hours Increased by 10mg diamorphine after 3 days and to 60mg diamorphine after further 3 days.

47. High gastric output, obstruction, fistulae: • Opioids, regular or continuous • Octreotide 0.1-0.6mg per day (may be given as continuous infusion.)

48. Dyspnoea • Diazepam 2.5-10mg • Lorazepam 0.5mg sublingually • Midazolam 2.5-5mg 4 hourly subcutaneously • Opioids, 2.5-5mg diamorphine 4 hourly s.c. for opioid naïve patients • Levomepromazine 25-50mg 6-8 hourly if extreme agitation

49. Other symptoms: Mouth Care • Water sips, ice chips, mouth swabs • Emollients, paraffin jelly • Artificial saliva - not glycerin • Candidiasis • Benzydamine

50. Use of drugs beyond licence- • ‘a legitimate aspect of clinical practice’ • ‘currently both necessary and common’ • ‘..professionals should inform, change & monitor……… in light of evidence from audit and published research.’ Association for Palliative Medicine and the Pain Society – position statement 2001.