Archive | August 2012

Palliative Care Guidelines: Ketamine

Ketamine in Palliative Care

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.

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 purified water + flavouring
to mask ketamine’s bitter taste. (Can be stored in a fridge for up
to 1 week.)

• 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.

• Do not use ketamine if patient has raised intracranial pressure; uncontrolled hypertension,
delirium or recent seizures; history of psychosis.
• 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 choice
is 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.Palliative Care Guidelines: Ketamine

Dose & Administration
• 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 (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 subcutaneous
infusion 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).

• 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 first dose of oral ketamine is given. Others
gradually reduce the infusion dose as the oral dose is increased.

Parenteral administration
Palliative 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.Palliative Care Guidelines: Ketamine

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 first 24
• 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 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.

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 <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.

Further information
Specialist palliative care services/ Palliative medicine on-call advice service
Palliative Care Drug Information online: Care Guidelines: Ketamine




Refeeding syndrome


A syndrome consisting of metabolic disturbances that occur as a result of reintroduction of nutrition to patients who are starved or severely malnourished.

Patients who have had negligible nutrient intake for 5 consecutive days are at risk of refeeding syndrome.

  • occurs within four days of starting to feed.
  • Patients can develop fluid and electrolyte imbalances such as
  • hypophasphatemia
  • neurologic, pulmonary, cardiac, neuromuscular, and hematologic complications.


  Fig. 3.


  1. During prolonged fasting the body aims to conserve muscle and protein breakdown by switching to ketones derived from fatty acids as the main energy source.
  2. The liver decreases its rate of gluconeogenesis thus conserving muscle and protein.
  3. Many intracellular minerals become severely depleted during this period, although serum levels remain normal.
  4. Insulin secretion is suppressed in this fasted state and glugagon secretion is increased.
  5. During refeeding, insulin secretion resumes in response to increased glycemia; resulting in increased glycogen, fat and protein synthesis.
  6. This process requires phosphates, magnesium and potassium which are depleted.
  7. Remaining stores are rapidly used up.
  8. Formation of phosphorylated carbohydrate compounds in the liver and skeletal muscle depletes intracellular ATP and 2,3-diphosphoglycerate in the red blood cells, leading to cellular dysfunction and inadequate oxygen delivery to the body’s organs.
  9. Refeeding increases the body’s basal metabolic rate.
  10. Intracellular movement of electrolytes occurs along with a fall in the serum electrolytes including phosphate, potasium and magnesium.
  11. Glucose, and levels of the B vitamin thiamine may also fall.
  12. Cardiac arrhythmias are the most common cause of death from refeeding syndrome, with other significant risks including confusion, coma and convulsions and cardiac failure.

Assessment, treatment and management:

Refeeding syndrome can be fatal if not recognized and treated properly.

Refeeding syndrome occurs most commonly in those who have lost weight rapidly.
The electrolyte disturbances of the refeeding syndrome can occur within the first few days of refeeding, which can be undertaken through the oral or nasogastric or G tube routes.

Milk is often the refeeding food of choice in this early period as it is naturally high in phosphate and easily tolerated by those who have been starved.

If potassium, phosphate or magnesium are low then these deficiencies should be corrected with supplements.

Prescribing thiamine, vitamin B complex (strong) and a multivitamin and mineral is recommended.

Electrolytes/Biochemistry should be monitored regularly until it is stable.

Dietary intake should remain only 50-70% that of normally required for the first 3–5 days.

Patients who have been starved for some time often experience gastrointestinal disturbance during refeeding:

  • colicky abdominal pain
  • Reflux symptoms
  • Nausea
  • Early sensation of fullness


Pro-kinetic agents such as maxeran

Acid suppressants such as omeprazole