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. This use is outside the UK marketing authorisation.
(NB - Will need indication for use on prescription e.g. ‘for nerve pain’)
Used by subcutaneous injection/ infusion.
Specialists occasionally give ketamine IV – see below
Ketamine oral solution
50mg/5ml (unlicensed specials medicine)
(This is the preferred strength but other options are available)
Injection may be given orally
Ketamine is a Schedule 2 CD (Controlled Drug), 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).
- 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, 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.
- Use 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
- Do not use ketamine if patient has raised intracranial pressure; uncontrolled hypertension, delirium or recent seizures; history of psychosis.
- Ketamine 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.
- 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).
Dose and Administration
- Ketamine is started on the recommendation of a palliative medicine consultant. This is usually done in an in-patient setting.
- Very 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, community nurse, and unscheduled care service.
- 24 hour palliative medicine advice will be available.
- Patients starting ketamine will be taking a regular opioid. Ketamine may restore the patient’s 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 (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.
- Give haloperidol oral 500 micrograms to 1mg twice daily or SC 1mg to 2mg once daily. Midazolam SC 2mg as needed can also be used.
- 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 & 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 four times daily.
- Increase dose in 5 to 10mg increments.
- Usual dose range: 10mg to 60mg four times daily.
Dose & Administration - 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).
- 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 – refer to CME T34 syringe pump ketamine compatibility table in guidelines/on website.
- Dispose of the ketamine vial in accordance with the local policy.
- 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 if possible and/or add a maximum of 1 mg of dexamethasone injection to the ketamine infusion.
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 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.
Dose & Administration - parenteral ketamine
- Palliative medicine consultants or anaesthetists occasionally administer SC or IV ketamine as single or ‘pulsed’ doses for severe pain or to cover painful procedures.
- Specialists have used IV ketamine infusions to manage ischaemic limb pain.
- 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 to 4 hourly 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.
- Check 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.
- Record 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.
- 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 <85%, patient cyanosed
- Naloxone should not be given in large bolus doses as it can precipitate an acute opioid withdrawal reaction. See: Naloxone guideline
Dysphoria, hallucinations, vivid dreams
Assess patient daily until ketamine dose is stable; then stop any regular haloperidol or midazolam.
Patient & carer advice points
There can be a delay of several days in obtaining further supplies of ketamine. Patients are advised to ensure new supplies are requested in adequate time.
The taste of ketamine can be unpleasantly bitter. Patients can suck or chew on something sweeter after taking. Other flavours can also be requested.