Ketamine Palliative Continuing Care Guideline

Specialist Details Patient Identifier

Name: Name: Date of Birth: Location: NHS No: Address: Tel:

Ketamine is a short acting anaesthetic with analgesic properties at low doses. It is used particularly for neuropathic pain, ischaemic limb pain, refractory cancer pain and as an adjunct to opioid therapy. Ketamine may be given orally or by continuous subcutaneous infusion via syringe pump Introduction either as a sole agent or in combination with other agents. Ketamine should only be initiated and prescribed for adult patients by a Palliative Medicine Specialist. This guideline is therefore only valid for these patients. It is Mid Essex CCG policy that ketamine should not be used for patients with chronic pain. Ketamine is currently a schedule 2 controlled drug.

Dosage and Dose recommendation varies depending on oral or subcutaneous use and clinical response. Administration Conversion between oral and subcutaneous doses should be managed under specialist advice.

Oral Ketamine Usually standard 10mg/1mL preparation (see below): start at low doses e.g. 10mg TDS orally The dose can normally be increased in increments of 10mg TDS Cautions  Titrate slower in frail patients  The dose of opioid may need to be reduced when ketamine is initiated  Caution when calculating volume for administration: incidents have been reported as a result of confusion regarding the standard strength, particularly where lower doses are used and the dose is a small volume. For example a 10mg dose is 1mL of the 10mg/1mL oral solution, 25mg dose is 0.5mL of the 50mg/mL oral solution.  Ensure that patients are counselled on the measurement of the dose.

Subcutaneous Start with 50 – 100mg over 24 hours using a syringe pump and increase by 50mg increments every Ketamine 24 hours until benefit is achieved. It is unusual to require doses greater than 500mg per day.

Cautions  If frail start at 30mg/24hrs  Can be irritant to subcutaneous tissue: dilute with sodium chloride 0.9% to largest possible volume  Caution when calculating volume for administration: incidents have been reported as a result of confusion between the available preparations of ketamine injection  Consider the addition of either haloperidol 2.5mg or midazolam 5mg to try to prevent psychomimetic phenomena

 Ketamine normally mixes well with the following drugs: Compatibility in Morphine/oxycodone/haloperidol/metoclopramide/levomepromazine/midazolam Syringe Pumps  Ketamine is incompatible with cyclizine  Consider adding dexamethasone 1mg/24hr to syringe pump if too irritant to skin  If more than 2 drugs are to be mixed in the same syringe, seek specialist palliative care advice at Farleigh Hospice on 01245 455478

Available Oral ketamine solution: Available as 10mg/1ml (100ml) from Oxford Pharmacy Stores Preparations http://oxfordpharmacystore.co.uk/contact/ 01865 904141.

Subcutaneous ketamine injection: Available in the following strengths – 10mg/ml, 50mg/ml, 100mg/ml. As it is licensed it should be readily available from main wholesalers.

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A Palliative Medicine Specialist herein is defined as either a Specialist Palliative Medicine Physician or a Specialist Palliative Care Non-Medical Prescriber under a supplementary prescriber agreement.

 Assess appropriateness of ketamine use, considering any contraindications  Initiate and titrate the dosage regimen, assessing response and adverse effects  Check baseline observations and investigations: - Ensure knowledge of patient’s blood pressure (BP) history and check BP before initiation - Baseline liver function tests (LFTs), heart rate and urinalysis Palliative Medicine  Prescribe ketamine and arrange any on-going monitoring. This may include: Specialist - Arranging BP check 1 – 2 weeks into treatment and on dosage increases Responsibilities - For longer term treatment (> 1 month): arrange periodic LFTs and assess patients for symptoms suggestive of ulcerative cystitis when reviewed  Review patient’s response and continuing appropriateness of ketamine at specified intervals, sending a written summary to the GP following a review. This may be facilitated by the Community Specialist Palliative Care CNS Team.  Provide patient/family/carer with relevant information on use, adverse effects and need for monitoring  Provide GP, District Nurses, Community Pharmacist (as nominated by the patient) with - a copy of continuing care guideline - detailed patient summary on discharge - GP or pharmacist letter as appropriate (template attached)  Refer to district nursing team if patient requires a ketamine subcutaneous syringe pump  Ensure at least 14 days supply issued on discharge to ensure continuity of supply  Provide any other advice for GP and other relevant healthcare professionals as required  Stop treatment when no longer considered appropriate

Hospice Specialist Farleigh Hospice currently receive a pharmacy service on their Inpatient Unit from the Pharmacy Palliative Care Department at Mid Essex Hospital Trust (Broomfield Hospital). Pharmacist Ensure at least 14 days supply is issued on discharge and that prescription details are provided to Responsibilities the patient’s nominated Community Pharmacist with sufficient notice to ensure continuity of supply in the community  Provide on-going advice to Community Pharmacist e.g. regarding ordering further supplies

GP Responsibilities  Continue to review patient from a GP perspective to monitor all symptoms  Refer to specialist when symptoms fail to respond or when change in route of administration may be indicated  Consider the possibility of ulcerative cystitis if the patient develops significant urinary symptoms e.g. frequency, urgency, dysuria and haematuria which are not due to a bacterial infection. Discuss patient promptly with Palliative Medicine Specialist should this arise  Liaise with district and community specialist palliative care CNS team

District Nurse  Support BP monitoring in the community. BP frequency monitoring to be recommended by Responsibilities Palliative Medicine Consultant on an individual basis. E.g. 1 – 2 weeks into treatment, on dosage increases and periodically on treatment. If systolic BP is >150, please contact Farleigh Hospice (01245 455478) for further advice.  Refer to specialist when symptoms fail to respond or when change in route of administration may be indicated  Support the use of ketamine as a continuous subcutaneous infusion via a syringe pump which includes daily renewal of pump. It is at the discretion of the individual DN as to whether a second nurse is required at the time of renewal of syringe pump.

Adverse Effects  Most commonly: vivid dreams, hallucinations, excessive salivation/secretions, sedation, hypertension and tachycardia

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 Long term use: cases of ulcerative cystitis reported  Isolated cases of liver injury reported, especially at high doses  Rarely: psychosis. If patient experiences dysphoria or hallucinations, dose of ketamine should be reduced or midazolam (e.g. 2.5mg subcut) or haloperidol e.g. 2.5mg (oral or subcut) should be prescribed as an interim measure Contraindications  Absolute: intracranial hypertension and seizures  Relative: hypertension, cardiac failure, previous cardiac events and stroke Precautions  Precaution: patients on levothyroxine may be at increased risk of hypertension & tachycardia.  To avoid withdrawal after long term use, discontinue gradually

Common Drug  Plasma concentrations of ketamine may be increased by diazepam or grapefruit juice Interactions  Plasma concentrations of ketamine may be reduced by carbamazepine, phenytoin, phenobarbital or rifampicin  Concurrent use of ketamine and theophylline/aminophylline can reduce seizure threshold  Avoid concomitant use with memantine (increased risk of CNS toxicity) Communication For any queries relating to this patient’s treatment with octreotide, please contact the specialist named at the top of this document

Acknowledgements Interface Pharmacist Network Specialist Medicines (www.ipnsm.hscni.net)

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Appendix 1 - GP Template letter Farleigh Hospice Private and Confidential North Court Road

Chelmsford

Essex CM1 7FH Tel No: 01245 457300 Fax: 01245 457314

Dear

DOB: NHS Number: The above named patient has been an inpatient and is due for discharge on date:………. See attached discharge summary. They have been started on…………………… by our team. Prescribing responsibility is to remain with the palliative care team for this only. Please can you ensure that this is added to the patient record as outlined in the “Guideline on the recording of non GP prescribed medications on GP clinical systems” http://midessexccg.nhs.uk/your-health-services/medicines-optimisation/general-prescribing- guidance/1558-guidance-on-recording-non-gp-medications-in-clinical-systems-feb-2015/file

All other regular medications will need prescribing by yourself. They have been discharged with ……days of medication.

Yours sincerely

Private and Confidential c.c.

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Appendix 2 – Community Pharmacy Template Letter Farleigh Hospice North Court Road

Private and Confidential Chelmsford

Essex CM1 7FH Community pharmacist Tel No: 01245 457300 Address Fax: 01245 457314

Dear ……….(community pharmacist)

DOB: NHS Number: The above named patient has been an inpatient and is due for discharge on date: They have identified you as their regular pharmacist. Please inform us if this is not the case. See attached the discharge summary for the above named patient. Note the following changes to their regular prescription:

They have been discharged with ……days of medication. Medication will run out on……..

Yours sincerely

Private and Confidential c.c.

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Title Ketamine Continuing Care Guidelines Document reference KetamineContinuingCareGUI201811V2.0FINAL Author Dr Eva Lew, Lead Consultant in Palliative Medicine Natalie Prior, Senior Pharmacist, MECCG Approved by APC Date approved November 2018 Next review date November 2021

Previous version Key Changes - New guidance KetamineContinuingCareGUI201608 Change to inpatient pharmacy service now from the V1.0FINAL Pharmacy Department at Mid Essex Hospital Trust (Broomfield Hospital)

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