Ketamine
Class: anaesthetic – NMDA-receptor antagonist
Indications (NB some may be unlicensed): general anaesthesia (400 to 700 mg im), severe pain (at sub-anaesthetic doses), opioid tolerance reversal, neuropathic pain
Contraindications/cautions: hypertension, tendency to hallucinations, alcohol abuse, epilepsy; severe cardiac disease
Adverse reactions: common: hallucinations (see notes below), delirium, tachycardia, hypertension; nausea, vomiting, diplopia; less common: hypotension, bradycardia laryngospasm, respiratory depression
Metabolism/clearance: may be metabolised in the liver by CYP metabolising enzymes. Consider dose reduction in hepatic impairment. Active metabolite – norketamine
Interactions:
- additive CNS effects with other CNS depressants e.g. benzodiazepines (e.g. lorazepam), phenothiazines (e.g. chlorpromazine), tricyclic antidepressants (e.g. amitriptyline), opioids, alcohol
- Caution with drugs metabolised by CYP enzymes
| Dosing: | |
|---|---|
| oral: | injection has been given orally |
| subcut: | 100 to 500 mg in 24 hours as a ‘pulse’ over 5 days. Give a test dose of 10 mg before starting infusion |
| Subcut | Typically 10 to 25 mg prn; some use 2.5 to 5 mg (PCF8) – if necessary increase dose in steps of 25 to 33% |
| rectal: | not available |
Syringe driver: see syringe driver compatibility chart – ketamine is irritant; use largest volume possible; consider use of NaCl 0.9% as diluent. Start with 1 to 2.5 mg/kg/24 hours
- if necessary increase by 50 to 100 mg/24 hours. Usual maximum 500 mg/24 hours
Mechanism of action: in pain thought to act at NMDA receptors in the dorsal horn
Peak effect: iv: 10 to 15 minutes
Duration: iv: 15 to 30 minutes
Notes:
- may be useful in opioid tolerance/intolerance, in ‘wind-up’ (or rapidly escalating doses) and may allow a reduction in opioid dose
- may be useful in neuropathic pain although ‘pulse’ therapy has been shown to be no better than placebo in one study
- if hallucinations occur reduce the dose of ketamine and give a benzodiazepine (e.g. diazepam 5 mg orally, midazolam 5 mg subcutaneously) or haloperidol 2 to 5 mg orally or subcutaneously
- has been effective when used topically
- ‘Pulse’ therapy (increasing subcutaneous doses over 3 to 5 days) may be sufficient to ‘reset’ the NMDA/opioid receptors. Give 100 mg/24 hours then 200 mg/24 hours then 300 mg/24 hours for 3 days then consider discontinuation
- oral administration usually involves lower doses e.g. 25 to 50 mg 3 times a day as more norketamine is produced due to first pass metabolism. Norketamine is active and may be more potent than the parent ketamine
- oral formulations include the injection given orally either straight or made up into a syrup (see http://www.palliativedrugs.com for formula)
- sublingual use of the injection may also be effective
- may have a role treating severe depressive disorders