ketamine in pall care

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Palliative Care Guidelines: Ketamine

1 NHS Lothian Re-issue date: August 2010 Review date: August 2013

Ketamine in Palliative Care

Description

Anaesthetic agent used with specialist supervision as a third line analgesic to manage very

complex pain. It is an N-methyl-D-aspartate (NMDA) receptor inhibitor. This use is outside the UK

marketing authorisation and ketamine is ordered on a named patient basis.

Preparations

Ketamine injection Used by subcutaneous injection/ infusion.

Specialists occasionally give ketamine IV see below

Ketamine oral solution

50mg/5ml 500ml bottle Martindale Pharmaceuticals

A ketamine oral solution can be prepared by the pharmacist

from the injection preparation using puried water + avouring

to mask ketamines bitter taste. (Can be stored in a fridge for up

to 1 week.)

Indications

Neuropathic pain poorly responsive to titrated opioids and oral adjuvant analgesics

(eg. antidepressant and/or anticonvulsant) particularly when there is abnormal pain sensitivity -

allodynia, hyperalgesia or hyperpathia.

Complex ischaemic limb pain or phantom limb pain.

Poorly controlled incident bone pain (often has a neuropathic element).

Complex visceral / abdominal neuropathic pain.

Contraindications

Do not use ketamine if patient has raised intracranial pressure; uncontrolled hypertension,

delirium or recent seizures; history of psychosis.

Cautions

Use low doses, carefully monitored, in cardiac failure, cerebrovascular disease, ischaemic

heart disease.

If used for over 3 weeks, discontinue ketamine gradually.

Drug interactions

Ketamine interacts with theophylline (tachycardia, seizures) and levothyroxine (monitor for

hypertension, tachycardia).

Diazepam increases the plasma concentration of ketamine.

Side effects

Hallucinations, dysphoria and vivid dreams see p2.

Hypertension, tachycardia, raised intracranial pressure.

Sedation at higher doses.

Erythema and pain at infusion site.

Starting ketamine

Ketamine is started on the recommendation of a palliative medicine consultant. This is usually

done in an inpatient setting.

Very occasionally, a patient may need to start ketamine in the community. The route of choiceis generally oral ketamine. The palliative medicine consultant will liaise closely with the GP,

district nurse, and unscheduled care service.

24 hour palliative medicine advice will be available.


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2 Re-issue date: August 2010 Review date: August 2013 NHS Lothian

Dose & Administration

Patients starting ketamine will be taking a regular opioid. Ketamine may restore the patients

opioid sensitivity and lead to opioid toxicity.

The specialist may recommend changing to a short acting, regular opioid before starting

ketamine, particularly if the patient has side effects from the current opioid dose.

Monitor closely for signs of opioid toxicity (eg. sedation, confusion); reduce opioid dose

by one third if the patient is drowsy and seek advice.

Hallucinations/ dysphoria: if the patient is not drowsy this is more likely to be a ketamine side

effect than due to opioids.

Give haloperidol oral 0.5-1mg twice daily or SC 1mg-2.5mg once daily. Midazolam SC

2.5mg as needed can also be used.

Preventing ketamine dysphoria consider oral haloperidol 0.5-1mg daily when starting

ketamine. It can be stopped when the patient is stable.

Oral ketamine

Ketamine can be started using the oral route or patients may be changed from a subcutaneousinfusion when pain is controlled.

Starting dose: 5-10mg four times daily.

Increase dose in 5-10mg increments.

Usual dose range: 10mg-60mg four times daily.

Subcutaneous ketamine infusion

Starting dose: 50-150mg/24 hours.

Review daily; increase dose in 50-100mg increments.

Usual dose range: 50mg- 600mg/24 hours (higher doses are occasionally used in specialist units).

Administration Prepare a new syringe every 24 hours.

Dilute ketamine with sodium chloride 0.9%.

Check the syringe is not cloudy and protect it from light.

Ketamine stability and compatibility see table below.

Discard the ketamine vial immediately after preparing the syringe.

Rotate the subcutaneous infusion site daily to prevent site reactions. If these occur, increase

the volume of sodium chloride 0.9% used to dilute the ketamine and/or add dexamethasone

injection 1mg to the ketamine infusion. Only low dose dexamethasone can be mixed with

ketamine in this way.

Converting from a 24 hour SC ketamine infusion to oral ketamine Oral ketamine is more potent than SC ketamine (due to liver metabolism). Many patients

require a dose reduction of 25-50% when changing to oral ketamine.

Prescribe the oral ketamine in divided doses - four times daily.

Titrate dose in 5-10mg increments.

Some specialists stop the SC infusion when the rst dose of oral ketamine is given. Others

gradually reduce the infusion dose as the oral dose is increased.

Parenteral administrationPalliative medicine consultants or anaesthetists occasionally administer SC or IV ketamine as

single doses for severe pain or to cover painful procedures.

Specialists have used IV ketamine infusions to manage ischaemic limb pain.


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3 NHS Lothian Re-issue date: August 2010 Review date: August 2013

Patient monitoring

Patients who are at risk of hypertension, tachycardia, respiratory depression or opioid toxicity

should only start ketamine in a clinical area able to monitor them 2-4 hourly for the rst 24

hours.

All patients should be reviewed at least once daily until stable, and then weekly.

Once the pain is controlled, the palliative medicine specialist may recommend a gradual

reduction in the dose of opioid and /or ketamine.

Blood pressure

Check BP is normal or well controlled before starting ketamine. Record a baseline BP.

Check BP an hour after the rst dose of oral ketamine or starting a SC infusion.

Check BP 24 hours after the rst dose of ketamine, then daily.

If blood pressure increases 20 mmHg above baseline inform the patients doctor.

If blood pressure remains elevated 20mmHg above baseline on repeated measurement, stop

the ketamine and seek advice from a palliative medicine specialist.

Pulse

Record a baseline pulse rate.

Check pulse an hour after the rst dose of ketamine or starting SC infusion.

Check pulse 24 hours after the rst dose of ketamine, then daily.

If pulse rate increases 20bpm above baseline or rises above 100bpm inform the patients doctor.

If there is no other cause of tachycardia, seek advice from a palliative medicine specialist.

Respiratory rate

Record a baseline respiratory rate.

The palliative medicine specialist will advise on frequency of monitoring.

If respiratory rate decreases to 10 breaths/min inform medical staff. Seek advice from a

palliative medicine specialist.

Naloxone (in small titrated doses) is only required for reversal of life-threatening respiratory

depression due to opioid analgesics, indicated by

A low respiratory rate < 8 respirations/minute

Oxygen saturation


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4 Re-issue date: August 2010 Review date: August 2013 NHS Lothian

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Stability References Watson D, Lin M, Morton A et al. Compatibility and stability of dexamethasone sodium phosphate

and ketamine hydrochloride subcutaneous infusions in polypropylene syringes.Journal Pain &

Symptom Management2005; 30: 80-86

Twycross R and Wilcock A. Palliative Care Formulary(Third Edition). Palliativedrugs.com Ltd 2007.

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