Palliative Care Part 1 Dr Christine Hirsch School of Pharmacy, Aston University, Birmingham B4 7ET

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

Team Approach

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?

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

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.

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.

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

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

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).

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

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

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

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

PHYSICAL TOTAL PAIN SPIRITUAL SOCIAL PSYCHOLOGICAL

Alternative opioids When would you use ? Which would you use?

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

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.

‘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.

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

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

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

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

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

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?

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.

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

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

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

Palliative Care Part 2 Dr Christine Hirsch School of Pharmacy, Aston University, Birmingham B4 7ET

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

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

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

Opioids via syringe driver will NOT give better analgesia unless there is a problem with absorption or administration

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

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

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

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

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

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

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

Restlessness & agitation Where agitation & anxiety are predominant features: Midazolam Levomepromazine

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

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.

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

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.

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

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

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

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.

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.

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

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

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