1. Palliative Care Part 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

3. Team Approach

4. Symptom prevalence patients with advanced cancer C. Faull and R. Woof
Symptom prevalence patients with advanced cancer C. Faull and R. Woof .Palliative Care 2002 Oxford University Press
Symptom
% Cancer
Pain 60
Anorexia
Fatigue / weakness 50
Sleep disturbance
Constipation
Depression 45
Nausea or vomiting 40
Trouble breathing
Incontinence
Anxiety
Confusion 30
But which is most distressing for the patient?

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
Oral bioavailablity 75%
M1 = o desmethyltramadol
Ondansetron may block by blocking 5HT3 receptors on neurones in spinal horn (afferent).

11. WHO three-step analgesic ladder
Opioid for moderate to severe pain +/- non-opioid +/-adjuvant
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
Although the distinction between higher doses of weak opioids and lower doses of strong opioids is clear.
e.g Paracetamol NSAIDs 1 2 3

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

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. A 65 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
LISA

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)
Renal impairment
Buprenoprhine CYP3A4 induced by rifampicin. 7 Day vs 3 day patch.

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
Reluctant to use prn sevredol – need analgesia to rehab therefore increase Zomorph to 20mg bd from 10mg
BREAKTHROUGH PAIN

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
What would you put in the syringe driver?

26. Gold Standards Framework
Communication
Co-ordination
Control of symptoms
Continuity out of hours
Continued learning
Carer support
Care in the dying phase
The Seven C’s of the Gold Standards Framework developed by Dr Keri Thomas are designed to help primary care teams improve their delivery of palliative care.
Communication – Patients are recorded on a Practice register, regular meetings for information and sharing are held with team members. Patient information and patient held records are recommended.
Co-ordination – A nominated co-ordinator maintains the register, organises meetings and audit, education etc.
Control of symptoms – holistic patient centred management
Continuity out of hours – effective transfer of information to and from out-of-hours services. Access to drugs and equipment.
Continued learning – Audit, reflection, critical incident analysis.
Carer support – Practical, financial, emotional bereavement support
Care in the dying phase – Protocol driven care addressing spiritual emotional and physical needs. Care needs around and after death acted upon.

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
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 Blackwell Publishing.
Dickman A. Chronic pain management: advances. Pharm J. 2007;279:
Palliative drugs website:
Scottish intercollegiate guidelines network website

30. Palliative Care Part 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 will NOT give better analgesia unless there is a problem with absorption 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 mg 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 mg 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.

51. Gold Standards Framework
Communication
Co-ordination
Control of symptoms
Continuity out of hours
Continued learning
Carer support
Care in the dying phase
The Seven C’s of the Gold Standards Framework developed by Dr Keri Thomas are designed to help primary care teams improve their delivery of palliative care.
Communication – Patients are recorded on a Practice register, regular meetings for information and sharing are held with team members. Patient information and patient held records are recommended.
Co-ordination – A nominated co-ordinator maintains the register, organises meetings and audit, education etc.
Control of symptoms – holistic patient centred management
Continuity out of hours – effective transfer of information to and from out-of-hours services. Access to drugs and equipment.
Continued learning – Audit, reflection, critical incident analysis.
Carer support – Practical, financial, emotional bereavement support
Care in the dying phase – Protocol driven care addressing spiritual emotional and physical needs. Care needs around and after death acted upon.

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

53. 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
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

54. References cntd:
Fallon M, Hanks G. ABC of Palliative Care. 2nd Ed Blackwell Publishing.
Dickman A. Chronic pain management: advances. Pharm J. 2007;279:
Palliative drugs website:
Scottish intercollegiate guidelines network website