Ketamine

Ketamine is an N-methyl-D-aspartate receptor antagonist producing dissociative anaesthesia, profound analgesia and amnesia with relative preservation of airway reflexes, ventilation and blood pressure. It is used for induction, sedation, analgesia and anaesthesia, especially in shock, asthma and settings with limited monitoring. It causes emergence phenomena and raises blood pressure and heart rate.

Class. Intravenous general anaesthetic and analgesic (NMDA receptor antagonist).

Mechanism. Non-competitive antagonism of the NMDA receptor, with additional actions at opioid, monoaminergic and muscarinic receptors, and sodium channels. It produces sympathetic stimulation by inhibiting catecholamine reuptake.

Pharmacokinetics. Intravenous onset 30 to 60 seconds, duration 10 to 20 minutes for anaesthesia; analgesia lasts longer. Intramuscular onset 3 to 5 minutes, duration 20 to 30 minutes. Intranasal onset 5 to 10 minutes. Protein binding low (about 25%). Half-life 2.5 hours. Hepatic metabolism (CYP3A4, CYP2B6) to norketamine (about one third as potent), renal excretion.

Indications are induction and maintenance of anaesthesia (particularly in haemodynamic instability), procedural sedation and analgesia, analgesia in trauma and burns, status asthmaticus (adjunct), and low-dose analgesic adjunct for severe pain.

Adults

• Induction: 1 to 2 mg/kg intravenously over 60 seconds; 0.5 to 1 mg/kg in shock. Intramuscular 4 to 10 mg/kg.
• Rapid sequence induction: 1 to 2 mg/kg intravenously (0.5 to 1 mg/kg in shock).
• Maintenance: bolus 0.5 to 1 mg/kg every 10 to 15 minutes, or infusion 0.6 to 2.7 mg/kg/hour (10 to 45 micrograms/kg/minute).
• Procedural sedation: 1 to 2 mg/kg intravenously (slowly), with repeat boluses of 0.5 mg/kg; intramuscular 4 to 5 mg/kg.
• Sub-dissociative analgesia: 0.1 to 0.3 mg/kg intravenously over 10 to 15 minutes; infusion 0.1 to 0.5 mg/kg/hour (lower in older adults).
• Intranasal analgesia: 0.5 to 1 mg/kg (up to 1.5 mg/kg in some labels), maximum volume 1 mL in each nostril.

Children over 3 months

• Induction: 1 to 2 mg/kg intravenously; intramuscular 4 to 5 mg/kg (procedural sedation) or up to 10 mg/kg (anaesthesia).
• Sedation: 1 to 2 mg/kg intravenously over 1 to 2 minutes.
• Intranasal: 1 to 1.5 mg/kg.
• Under 3 months: avoid in most settings.

Premedication to reduce adverse effects. Midazolam 0.03 to 0.05 mg/kg intravenously reduces emergence reactions in adults. Glycopyrronium 5 micrograms/kg (maximum 0.2 mg) reduces salivation if required.

Contraindications. Eclampsia, pre-eclampsia or uncontrolled hypertension; recent myocardial infarction or unstable angina; raised intracranial pressure from space-occupying lesion (relative; evidence is mixed); raised intraocular pressure or open globe injury (relative); active psychosis (relative); porphyria; hypersensitivity; thyrotoxicosis (relative).

Boxed-warning-level risks. None formally labelled for anaesthetic use. Emergence phenomena (vivid dreams, hallucinations, agitation); airway complications (laryngospasm) in children and with airway stimulation; long-term use is associated with uropathy (cystitis) and liver injury.

Adverse effects. Common: hypertension, tachycardia, increased secretions, nystagmus, nausea, vomiting. Serious: emergence delirium, laryngospasm, apnoea after rapid bolus, raised intracranial and intraocular pressure, increased myocardial oxygen demand, cystitis and hepatotoxicity with chronic use, abuse and dependence.

Interactions. Thyroid hormones and sympathomimetics add hypertension and tachycardia. Benzodiazepines blunt emergence reactions. Opioids and barbiturates add respiratory depression. CYP3A4 inhibitors raise levels. Theophylline can lower seizure threshold.

Common prescribing errors. Giving in a patient with uncontrolled hypertension or severe cardiac disease; rapid intravenous bolus causing apnoea; using too high a dose for analgesia; omitting airway equipment; forgetting that ketamine does not abolish the need for monitoring.

Special groups

• Pregnancy: used for caesarean section in selected cases; avoid in pre-eclampsia; neonatal depression with high doses.
• Breastfeeding: compatible after recovery.
• Older adults: reduce dose by 30 to 50%; higher risk of delirium.
• Kidney impairment: no adjustment for single doses.
• Liver impairment: reduce repeat dosing; avoid prolonged infusion in severe disease.
• Regional: ketamine is often one of the few anaesthetic agents available in district settings, so its use does not remove the need for oxygen, suction, airway equipment and a clinician trained in airway rescue.

Formulations. Injection 10, 50 and 100 mg/mL (racemic) and 5 mg/mL for the S-enantiomer in some markets; intranasal formulations.

Administration. Give intravenous doses slowly over 60 seconds. Dilute to 10 mg/mL for intravenous use. For infusion, dilute in 0.9% sodium chloride or 5% glucose to 1 to 2 mg/mL. Intramuscular injections are given into a large muscle.

Baseline. Airway assessment, blood pressure, cardiac history, psychiatric history, pregnancy status, intracranial or intraocular pathology and weight.

Monitoring. Continuous electrocardiogram, blood pressure, oxygen saturation and capnography. Level of consciousness. Recovery observed in a quiet area to reduce emergence reactions.

Therapeutic drug monitoring. Not used.

Dose reduction and stopping thresholds. Reduce or stop for severe hypertension, tachyarrhythmia, laryngospasm, apnoea or severe emergence agitation. Avoid repeated use over weeks without review of bladder and liver symptoms.

Referral and escalation. Laryngospasm needs oxygen, jaw thrust and, if persistent, a small dose of suxamethonium (0.25 to 0.5 mg/kg intravenously). Severe emergence agitation needs a benzodiazepine and reassurance. Chronic users with haematuria or abdominal pain need urological and hepatic review.