Ketamine (Guidelines)

Drug Interactions

Ketamine has known interactions with

• Theophylline (tachycardia, reduced seizure threshold with resulting seizures)
• Levothyroxine (hypotension, tachycardia)
• Diazepam (increased plasma concentrations of ketamine, consider reducing ketamine infusion dose)

Equipment

An Agilia PCA pump should be obtained. Use a luer lock 50ml syringe attached to an anti siphon line (which must be labelled as per NHS Highland guidelines) and a dedicated IV cannula.  Standard aseptic precautions should be deployed.

Dose and Drug Preparation

A new drug syringe should be prepared and discarded every 24 hours. Ketamine should be prepared to a concentration of 5mg/mL using these instructions:

• Obtain ketamine hydrochloride (Ketolar) at a concentration of 10mg/mL.
• Draw 20mL of ketamine into a 50mL syringe (20mL x 10mg = 200mg).  The addition of 20mL 0.9% saline gives a total of 40mL volume and a final concentration of 5mg/mL (200mg ketamine in 40mL = 5mg/mL).
• Infusions should be commenced at 1mL per hour (5mg/hour) and titrated to effect (see below for maximal infusion rates) or until side effects are experienced.
• In patients weighing more than 50kg the infusion rate should not be increased more frequently than hourly and should never exceed 5mL/25mg per hour.
• If weight less than 50kg the infusion rate should not be increased more frequently than hourly and should never exceed 3mL/15mg per hour.
• Consider an initial dosage of 0.5mL (2.5mg) per hour in the frail and elderly with cautious dose titration.

Loading doses are not recommended.

Ketamine undergoes renal excretion, however there is no requirement for dose adjustment in patients with renal dysfunction in the dose ranges suggested in this guideline.

Paracetamol and NSAIDS should be continued unless specifically contraindicated.

Concurrent prescription of adequate antiemetics should be available prior to starting the infusion to ameliorate any side effects.

A dedicated ketamine prescription chart must be used and can be obtained from the acute pain team. The prescription is not valid unless signed by the treating anaesthetist or acute pain service.

Ketamine infusions should ideally be commenced before 2pm allowing for close monitoring for side effects and toxicity within day time working hours.

Side effects

Side effects are minimal at the initial dosages in this guideline but may limit usage at higher doses. These include:

• Cardiovascular stimulation causing hypertension and tachycardia
• Hallucinations and dysphoria (may be alleviated with benzodiazepines under anaesthetic direction)
• Rise in intra-cranial pressure, cerebral metabolic rate and cerebral blood flow
• Excessive sedation

If the patient develops disturbing hallucinations or other concerning symptoms the infusion should be stopped and the acute pain service or on call anaesthetist out of hours should be notified urgently.

Respiratory depression and hypotension are not typical features of ketamine however consider the use of naloxone in compromised patients with concurrent opioid treatment.

Patient Observation

Patients should be nursed in a critical care environment such as an HDU or ICU only.  Ketamine infusions are not suitable for ward level care.  Patients may be mobilised with care.

Patients should have supplemental oxygen prescribed for the duration of the infusion. Increasing oxygen requirements should prompt medical review with particular focus on assessment for concurrent opioid toxicity.

Hypotension is unusual with ketamine due to its positive inotropic effects. Persistent hypotension should prompt urgent medical review and consideration of other potential causes eg sepsis, acute coronary syndromes, haemorrhage/ hypotension, post operative complications.

Respiratory depression is not a typical feature of ketamine however any respiratory depression should prompt an increase in monitoring of vital signs and urgent medical review. In the event of respiratory compromise the on call ward doctor should be contacted immediately if the respiratory rate drops below 9/minute and the infusion should be stopped. Administer high flow oxygen via a reservoir mask. If in doubt summon emergency help by calling 2222.

Naloxone has NO effect on ketamine however should be considered in any patient with significant respiratory depression or excessive sedation who is receiving concurrent opioids.

In the event of suspected opioid toxicity with resulting respiratory depression, respiratory rate of 8 or less and difficult to rouse, observe the following actions:

• Stop ketamine infusion and withhold further doses of opioids
• Ensure a clear airway and administer high flow, 15 litres per minute, oxygen using a reservoir face mask
• Contact the on call ward doctor, ICU anaesthetist and acute pain nurse
• Prepare naloxone, see Naloxone guidance
• DO NOT give further doses of ketamine or opioids until reviewed by the acute pain nurse or ICU anaesthetist

In the event of excessive sedation with ketamine alone WITHOUT respiratory compromise:

• Stop ketamine infusion and withhold further doses of opioids
• Ensure a clear airway and administer high flow, 10L per minute, oxygen using a reservoir face mask
• Contact the acute pain nurse or ICU anaesthetist out of hours to reassess analgesia

Nausea and vomiting should be treated with regular antiemetics with escalation to the anaesthetic team as detailed below.

Guidance for escalation to the acute pain service / on call anaesthetist in the event of:

• Ineffective pain relief
• Persistent nausea and vomiting despite regular antiemetics
• Seizures
• Acute agitation/dysphoria
• Acute change in vital signs, the acute pain service of on call anaesthetist out of hours should be notified urgently and the infusion stopped in the event of any of the following:
  • Drop in systolic blood pressure of 30%
  • Drop in respiratory rate to 8 or less
  • Profound sedation or difficulty in waking

Follow Up

Patients treated with ketamine infusion should be reviewed at least daily by the acute pain service or on-call anaesthetist out of hours. Discontinuation of the infusion will be guided by clinical response under the direction of the acute pain service/on call anaesthetist. Infusions lasting more than 72 hours require are by anaesthetic consultant discretion only following patient review.