Ketamine Dr Kirsty Lowe - PowerPoint Presentation

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Ketamine

Dr Kirsty LoweST6 in Palliative MedicineNHS Grampian

Overview

Case studyWhat is ketamine?Indications

Cautions, contraindications, interactionsSide effectsDose and administrationMonitoring

Questions

Case study

Tom is a 40 year old man with metastatic renal cancer Bone metastasis in R hip causing neuropathic pain down R leg.Allodynia over R thigh. Reduced mobility due to pain.

Current analgesia: MST 60mg BD, oramorph

20mg PRN (doesn’t help much)

Amitriptyline

50mg

nocte

Pregabalin

200mg BDDexamethasone 6mg ODPrevious radiotherapy to R hip metastasis – no effect.

What now?

What is Ketamine

?Anaesthetic agent used with specialist supervision as a third line analgesic to manage complex pain. It

is an N-methyl-D-aspartate (NMDA) receptor inhibitor. Ketamine

is a Schedule 2

CD therefore

all prescriptions must satisfy CD prescription requirements to be valid and include details of the dose, form, strength, directions for use and total quantity (in both words and figures).

NMDA receptor

The antagonism of the NMDA receptor is responsible for:AmnesicPsychosensory

Analgesic effects of ketamineNMDA receptors are present on nearly all the cells of the CNS especially those involved with

nociception

.

When resting membrane potential is changed, as a result of prolonged excitation, the NMDA channel unblocks.

Neuronal

hyperexcitability

develops causing hyperalgesia/ allodynia and a reduction in opioid responsiveness.Ketamine

:

decreases the NMDA channel opening time

decreases the amplification of the response to a repeated stimulus (wind-up)

binds to a second site to reduce the frequency of the channel opening.

More fun facts about ketamine

!Ketamine also has actions away from the NMDA receptor:

Calcium and Na channelsDopamine receptorsCholinergic transmissionNoradrenergic and

serotinergic

re-uptake

90% excreted in the urine (conjugated,

hydroxylated

metabolites).

Oral ketamine undergoes extensive first-pass hepatic metabolism to Norketamine via CYP3A4.Norketamine is also an NMDA receptor blocker

Equipotent analgesic but not anaesthetic agent

Ketamine

causes hepatic enzyme induction and enhances its own metabolism

Indications

Neuropathic pain poorly responsive to titrated opioids and oral adjuvant analgesics (e.g. antidepressant and/or anticonvulsant) particularly when there is abnormal pain sensitivity

– allodynia or hyperalgesia

.

Complex

ischaemic

limb pain or phantom limb pain.

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

Complex visceral / abdominal neuropathic pain.

Cautions, contraindications, interactions

CautionsUse low doses, carefully monitored, in cardiac failure, cerebrovascular

disease, ischaemic heart disease.If used for over 3 weeks and there is a need to stop treatment, discontinue

ketamine

gradually.

Consider dose reduction in severe hepatic impairment

Contraindications

Do not use

ketamine if patient has raised intracranial pressure; uncontrolled hypertension, delirium or recent seizures; history of psychosis. Drug interactionsKetamine interacts with theophylline

(tachycardia, seizures) and

levothyroxine

(monitor for hypertension, tachycardia).

Diazepam increases the plasma concentration of

ketamine

.

See relevant BNF section for further information

.

Inhibitors and inducers

Side effects

Hallucinations, dysphoria and vivid dreams.Hypertension, tachycardia, raised intracranial pressure.Sedation at higher doses.

Erythema and pain at infusion site.Urinary tract symptoms e.g. frequency, urgency, urge incontinence, dysuria

and

haematuria

(where is there no evidence of bacterial infection consider discontinuing

ketamine

and seeking urology advice

).Hepatotoxicity

Starting ketamine

Ketamine is started on the recommendation of a palliative medicine consultant. This is usually done in an in-patient setting.

Occasionally a patient may need to start ketamine in the community. The route of choice is generally oral ketamine

. The palliative medicine consultant will liaise closely with the

GP.

24 hour palliative medicine advice will be available.

Patients starting

ketamine

are usually taking a regular opioid. Ketamine may restore the patient’s opioid sensitivity and lead to opioid toxicity.

Monitor

closely for signs of

opioid

toxicity (e.g. 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

. Haloperidol can be helpful.

Preventing

ketamine

dysphoria

– consider oral 

haloperidol

 500 micrograms to 1mg daily when starting

ketamine

. It can be stopped when the patient’s

ketamine dose is stable.

Dose and Administration

Oral ketamine:Ketamine

can be started using the oral route or patients may be changed from a subcutaneous infusion when pain is controlled.Starting dose: 5 to 10mg QDS.

Increase dose in 5 to 10mg increments.

Usual dose range: 10mg to 60mg

QDS, can go up to 100mg QDS.

Subcutaneous

ketamine

infusion:Starting dose: 50 to 150mg/24 hours.Review daily; increase dose in 50 to 100mg increments.Usual dose range: 50mg to 600mg/24 hours (higher doses are occasionally used in specialist units).

Converting

from SC to oral ketamineOral ketamine is more potent than SC

ketamine (due to liver metabolism). Many patients require a dose reduction when changing to oral

ketamine

.

Prescribe the oral

ketamine

in divided doses - four times daily.

Titrate dose in 5 to 10mg increments.Some specialists stop the SC infusion when the first dose of oral ketamine is given. Others gradually reduce the infusion dose as the oral dose is increased.

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 for the first 24 hours.All patients should be medically 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 pressureCheck BP is normal or well controlled before starting ketamine. Record a baseline BP.Check BP an hour after the first dose of oral ketamine or starting a SC infusion.

Check BP 24 hours after the first dose of

ketamine

, then daily.

If blood pressure increases 20 mmHg above baseline inform the patient’s doctor.

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

ketamine

and seek advice from a palliative medicine specialist.

Patient monitoring

PulseRecord a baseline pulse rate.Check pulse an hour after the first dose of

ketamine or starting SC infusion.Check pulse 24 hours after the first dose of

ketamine

, then daily.

If pulse rate increases 20bpm above baseline or rises above 100bpm inform the patient’s doctor.

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

Respiratory rate

Record a baseline respiratory rate.If respiratory rate falls to <10/min seek medical advice.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 <85%, patient cyanosed

Naloxone

should not be given in large bolus doses as it can precipitate an acute

opioid

withdrawal reaction.

Case study

Tom is commenced on oral ketamine 10mg QDS and this is titrated over the next few days to 20mg QDS.Tom’s pain improves markedly! However...

Tom starts to become drowsy, myoclonic and tells you there are spiders crawling over his bed..

What should you do?

Any questions?