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Drug Reference

ketamine

NMDA receptor antagonist/anesthetic· Brands: Ketalar, Ketaset, Ketanest, KetajectIMIVPOSC

Mechanism of action
Ketamine is a non-competitive NMDA receptor antagonist. It blocks the ion channel in a use-dependent manner, inhibiting excitatory glutamate transmission. At subanaesthetic doses it produces dissociation and analgesia; at higher doses it produces general anaesthesia. It also interacts with opioid receptors, monoamine transporters and muscarinic receptors, contributing to its overall effects.
Pharmacokinetics
Ketamine is well absorbed after oral and parenteral administration, but undergoes extensive first-pass metabolism, reducing oral bioavailability to about 20%. It is highly lipid soluble and rapidly distributed to the brain. Metabolism is hepatic, principally via CYP3A4 and CYP2B6, to norketamine, which has some activity. The elimination half-life is approximately 2 to 3 hours. It is excreted mainly as metabolites in urine.
Indications & dosing

Induction of anaesthesia

For short procedures; may cause emergence phenomena.

  • adult · IV: 1–2 mg/kg single · For short procedures; may cause emergence phenomena.

Procedural sedation

Dissociative sedation; monitor airway and vitals.

  • adult · IV: 0.5–1 mg/kg single · Dissociative sedation; monitor airway and vitals.

Analgesia (subdissociative)

For acute pain; may be used as adjunct to opioids.

  • adult · IV: 0.1–0.5 mg/kg single · For acute pain; may be used as adjunct to opioids.

Procedural sedation

Commonly used in children for painful procedures.

  • pediatric · IM: 4–5 mg/kg single · Commonly used in children for painful procedures.

Treatment-resistant depressionoff-label

Off-label; infuse over 40 minutes.

  • adult · IV: 0.5 mg/kg twice weekly · Off-label; infuse over 40 minutes.
Contraindications & precautions
  • Uncontrolled or severe hypertension · Ketamine can increase blood pressure and heart rate, which may precipitate cardiovascular complications.
  • Severe coronary artery disease or recent myocardial infarction · Risk of myocardial ischemia due to increased myocardial oxygen demand.
  • Increased intracranial pressure (e.g. from mass lesion, hydrocephalus) · May cause further increase in ICP; use only if ventilation is adequately controlled and monitoring is available.
  • History of psychosis or schizophrenia · Ketamine can exacerbate psychiatric symptoms and cause hallucinations.
  • Monitor blood pressure, heart rate, respiratory rate and oxygenation during administration, especially in patients with cardiovascular or respiratory disease.
  • Use with caution in patients with seizures or a history of seizures, as ketamine may lower the seizure threshold.
  • Consider premedication with an anticholinergic (e.g. atropine) to reduce salivary secretions, and with a benzodiazepine to reduce emergence phenomena.
  • Avoid rapid intravenous administration, which may cause transient apnoea and severe hypertension.
  • Use only with appropriate airway equipment and suction available, as laryngospasm may occur.
Adverse effects
  • Emergence phenomena (hallucinations, vivid dreams, dissociative feelings)
  • Increase in heart rate and blood pressure
  • Nausea and vomiting
  • Airway secretions (salivation, bronchorrhoea)
  • Respiratory depression or apnoeaserious
  • Laryngospasmserious
  • Anaphylaxisserious
Renal & hepatic adjustment
  • eGFR 0+: No dose adjustment required. Caution in severe renal impairment as metabolites may accumulate.
  • Hepatic impairment (mild): Consider dose reduction; monitor for adverse effects.
  • Hepatic impairment (moderate): Reduce dose significantly; consider alternative agent.
  • Hepatic impairment (severe): Avoid use. (avoid)
Monitoring, pregnancy & toxicity
  • Blood pressure · Before and during administration
  • Heart rate · Before and during administration
  • Respiratory rate · Continuously during administration
  • Oxygen saturation · Continuously during administration
  • Mental status · During recovery
  • Liver function tests · Regularly with prolonged use
  • Pregnancy: Use only if potential benefit justifies risk to the fetus. Not recommended for routine use; consider alternatives.
  • Toxicity: Cardiovascular stimulation: tachycardia, hypertension. · Monitor vital signs. Administer beta-blockers if severe hypertension persists.
  • Toxicity: Respiratory depression and laryngospasm. · Maintain airway, provide oxygen, support ventilation; have suction and airway equipment available.
  • Toxicity: Emergence reactions: hallucinations, agitation, confusion. · Provide calm environment; administer benzodiazepines for severe agitation.
  • Toxicity: Increased intraocular pressure. · Avoid use in patients with raised intraocular pressure; monitor and treat accordingly.
Clinical notes
Ketamine is used for induction and maintenance of anaesthesia, for short procedures, and as an analgesic at subanaesthetic doses. It is valuable in emergency settings because it preserves airway reflexes and respiratory drive. It may be used for refractory depression and chronic pain. Adverse effects include emergence reactions, raised intracranial and intraocular pressure, and tachycardia. Contraindications include uncontrolled hypertension and severe cardiovascular disease. Prescribe per local protocols.

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BNF; local formulary