Ketamine The Hospice Waikato Perspective. Dr Tom Reid, Rachel Yang, Dr Gordon Giddings Hospice Waikato

Transcription

1 Ketamine The Hospice Waikato Perspective Dr Tom Reid, Rachel Yang, Dr Gordon Giddings Hospice Waikato

2 Presentation outline 1. Overview of ketamine 2. Recognised ketamine protocols in palliative care 3. Hospice Waikato case review 4. PHARMAC position on ketamine funding 5. Practicalities of community ketamine use Financial implications to Hospice costs Impact on patients 6. Summary and future directions

3 WHO Analgesic Ladder For Cancer Pain (1) Mild Pain [1-3] Aspirin NSAIDS Paracetamol Moderate Pain [4-6] Combined meds Codeine, Tramadol Increasing pain Severe Pain [7-10] Morphine Oxycodone Fentanyl Methadone

4 Modified WHO Ladder (2) Step 4 Nerve blocks (regional analgesia) Neuroaxial analgesia Surgical procedures Alpha 2 agonists Lidocaine

5 Modified WHO Ladder (2) Step 4 Nerve blocks (regional analgesia) Neuroaxial analgesia Surgical procedures Alpha 2 agonists Lidocaine Ketamine?

6 Ketamine: What is it? Dissociative anaesthetic agent (1963) Minimal negative effects on the cardiovascular system Analgesic properties in sub-anaesthetic (low) doses Use in pain management is off label

7 Ketamine: How does it work? Interacts with several receptor systems and ion-channels Non-competitive NMDA receptor antagonist (more selective at low dose) Thought to increase sensitivity to opioids. Thought to be effective in neuropathic and ischaemic pain (3)

8 Role For Ketamine In Palliative Care Third or fourth line co-analgesic, particularly in neuropathic pain syndromes (after TCA and/or AED) Prevent / reverse opioid tolerance and opioid toxicity Any pain syndrome with the triad of Allodynia Hyperalgesia Prolongation of pain response

9 Ketamine Administration in Palliative Care - New Zealand (4) Burst protocol Via CSCI Over 3-5 days Starting dose 100mg/24 hrs Incrementing daily by 100mg up to 500mg/24 hrs, according to effect. Continuous infusion Via a CSCI at doses of mg / 24hrs Treatment continued up to several months

10 Evidence base Limited evidence base. Disparate studies to date. Key paper: Variations in practice make drawing conclusions difficult. Recent review article remains positive :

11 Hospice Waikato Case Report

12 Mary Age 77 Diagnosis: Metastatic breast cancer - Lives with husband in Hamilton - 3 daughters (UK, US, North Island) - Son passed away 5 years ago - Minister with Spiritualist church - Enjoys creative crafts

13 Diagnosis Initial diagnosis 2002 Grade 2 infiltrating ductal Ca of R breast, 2/12 nodes involved, ER/PR positive Wide local excision with sentinel node biopsy and R axillary node dissection Did not have chemotherapy, radiation or hormonal treatment.

14 Intervening years 2008 local recurrence of R breast Ca, excision done in USA Dec 2009 R mastectomy with reconstructive surgery June 2010 symptomatic bony metastases Palliative radiotherapy: July 2010 T L ischium March 2012 L SI joint April 2012 C spine Sept 2013 Both femurs

15 December 2014 WPH admission Acute pain crisis L femur and hip area Restricting mobility CT showed extensive bony disease Destructive change around acetabulum Further radiotherapy Methadone conversion performed Struggling with sedation from high doses 50mg TDS + 20mg PRN

16 30 th January 2015 Day 0 Home visit Ongoing pain L thigh and leg Restricting mobility 8/10 Using more methadone sedation Complicated by # clavicle Plan: admission to IPU for symptom control

17 Day 1 - Trial of ketamine Commenced ketamine infusion 25mg/24hr via CSCI For emergence phenomena Lorazepam 1mg BD For breakthrough pain Fentanyl 25mcg subcut first line Methadone 15mg second line

18 Day 2 Pain reduced from 9/10 to 6/10 3/10 after single dose fentanyl More sedated, RR 8 Held off further ketamine increase Remained at 25mg/24hr Reduced lorazepam to 0.5mg BD

19 Next two weeks.. Day 3 ketamine 50mg/24h Single episode visual hallucination overnight day 2 Day 8 ketamine 75mg/24h No prn use, moving L leg Day 9 pain 0/10, converted to oral ketamine 10mg TDS = 100mg subcut Day 10 symptoms well controlled Tolerating oral meds, no pain, no prn use Day 11 discharge home

20 6 Months later PPS 40% Other concerns Recurrent UTIs Oedema Worsening mobility but still weight bearing for transfers Analgesia unchanged Ketamine 10mg TDS orally CSCI methadone and oxycodone Still at home and still attending creative therapy!

21 Expanding Experience in Hospice Waikato 4 cases in the last 2 years All have demonstrated subjective benefit to patient s symptoms Use of oral ketamine has allowed safe transfer home from hospice IPU on 2 occasions

22 Hospice Waikato Ketamine Continuous Infusion Practice *Loading Bolus Infusion Rate Comments Once Stable convert to oral Ketamine 5-10mg sc Start at 1-2mg/hr or 50mg/24hrs Reduce opioids by 25-50% 1/3 parenteral dose * If indicated Titrate Q24hrs Prophylaxis Bzd or Haldol 8 hourly dosing

23 Hospice Waikato Practice 50% of our SMO body bring a Canadian perspective Utilise a transition to oral ketamine (as per Ottawa protocol (7)) Reducing costs Allowing safe discharge Utilising lozenges to improve complience Uses a lower dose escalation - reducing side effect profile Incorporates prophylaxis against emergence phenomena Use oral ketamine as a long term coanalgesic option for discharged patients

24 Current PHARMAC Funding Situation PHARMAC sought clinical advice from its Pharmacology and Therapeutics Advisory Committee (PTAC) In 2011 PTAC recommended the application be declined on the basis of absence of evidence of benefit over placebo.(4) The Committee considered that the strength and quality of the available evidence was weak for burst ketamine and lacking for longer-term CSCI use. (4) The Committee considered that there was insufficient evidence to recommend funding ketamine in the community at this time. (4)

25 Ketamine Use In The Community -Impact on hospices Large funding implications to Hospice when patients discharged from hospital to IPU on ketamine Hospice expected to absorb costs 5 ampoules of ketamine 200mg/2ml cost: $325 usual brand Ketalar 3 patients tripled the monthly drug bills for Hospice Waikato on two occasions in last year.

26 Hospice Waikato Monthly Medication Costs NZ $

27 Ketamine Use In The Community - Impact on patients High costs to patients if subsequently discharged home Ethical considerations around discharge, leading to prolonged admissions Expectation of self-funded patients introduces lack of equity within healthcare at end of life

28 New perspective?

29 Summary Our experience and practice to date, has demonstrated good clinical benefit with ketamine in complex patients with resistant pain Managing symptoms Reducing opioid doses Enabling discharge from IPU to home Our local practice is different to the current Australasian literature Incorporating oral ketamine effectively There remains a lack of funding for ketamine in the community currently What is the experience of ketamine use throughout other New Zealand Hospices?

30 References: 1. World Health Organisation. WHO's cancer pain ladder for adults. [Internet]. Cited: 1/9/2016. vailable at: 2. Miguel R, Interventional treatment of cancer pain: the fourth step in the World Health Organisation analgesic ladder? Cancer Control. 2000;7(2): Gorlin AW, Rosenfeld DM, Ramakrishna H. Intravenous sub-anesthetic ketamine for perioperative analgesia. J Anaesthesiol Clin Pharmacol. 2016;32: Pharmac, Pharmaceutical Management Agency. Ketamine (community use) Ranked. [Internet] Cited: 1/9/2016. Available at: 5. Hardy J, Quinn S, Fazekas B, Plummer J, Eckermann S, Agar M et al. Randomized, Double-Blind, Placebo- Controlled Study to Assess the Efficacy and Toxicity of Subcutaneous Ketamine in the Management of Cancer Pain Journal of Clinical Oncology. 2012;30(29); Bredlau A, Thakur R, Korones D, Dworkin R: Ketamine for Pain in Adults and Children with Cancer: A Systematic Review and Synthesis of the Literature. Pain Medicine. 2013; 14: Fitzgibbon E, Hall P, Schroder C, Seely J, Viola R. Low Dose Ketamine as an Analgesic Adjuvant in Difficult Pain Syndromes: A Strategy For Conversion from Parenteral to Oral Ketamine.J Pain Symptom Manage ;23(2):

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