Ketamine

How to use ketamine in practice

• Induction (IV): 1–2 mg/kg produces anaesthesia in ~30–60 s; duration ~10–20 min
  • Consider lower doses (0.5–1 mg/kg) in shocked/hypovolaemic patients; titrate to effect
  • Co-administer benzodiazepine (e.g. midazolam) to reduce emergence phenomena; consider anticholinergic if troublesome hypersalivation
• Analgesic/sub-anaesthetic dosing: 0.1–0.3 mg/kg IV bolus; infusion commonly 0.05–0.3 mg/kg/h (institution-dependent)
  • Useful as opioid-sparing adjunct in acute pain, perioperative analgesia, opioid tolerance, and some chronic pain states
  • Monitor for psychotomimetic effects; consider co-analgesics and sedation strategy
• Procedural sedation/ED: 0.5–1 mg/kg IV (or 4–5 mg/kg IM) with appropriate monitoring and airway readiness
  • Maintain vigilance for laryngospasm (rare), apnoea after rapid IV bolus, and vomiting during recovery
• RSI/haemodynamic instability: useful where maintenance of blood pressure is desirable; ensure adequate depth and consider co-induction agent/opioid depending on physiology
  • Sympathomimetic response depends on intact catecholamine stores; in severe sepsis/prolonged shock, direct myocardial depression may predominate
• Asthma/bronchospasm: bronchodilator properties can be helpful; treat secretions and ensure adequate ventilation strategy
  • Increased secretions may worsen airway reactivity in some; consider anticholinergic and suction readiness

When to avoid or use with caution

• Raised intracranial pressure/space-occupying lesion: avoid or use only with controlled ventilation and specialist context (evidence mixed; CO2 control is key)
  • Ketamine can increase cerebral blood flow/CMRO2 in some settings; hypercapnia and inadequate anaesthesia increase ICP risk
• Severe ischaemic heart disease, uncontrolled hypertension, aortic dissection: sympathomimetic effects may be harmful
  • Consider alternatives or blunt response with opioid/benzodiazepine/alpha-2 agonist as appropriate
• Psychiatric illness (e.g. schizophrenia/active psychosis): increased risk of dysphoria/hallucinations
  • Emergence reactions reduced by calm environment and benzodiazepine co-administration
• Raised intraocular pressure/open globe injury: traditionally avoided (IOP may rise transiently)
  • If used, avoid hypoventilation and coughing/straining; ensure adequate depth

Class, formulation, and chemistry

• Phencyclidine (PCP) derivative; arylcyclohexylamine producing dissociative anaesthesia (functional and electrophysiological dissociation between thalamocortical and limbic systems)
• Racemic mixture (R/S); S-ketamine is more potent (analgesia/anaesthesia) with potentially fewer psychotomimetic effects (availability varies)
• Presentation commonly 10 mg/mL or 50 mg/mL; acidic solution; preservative-containing vials exist (check local product)

Mechanism of action

• Primary: non-competitive NMDA receptor antagonism (PCP site) → reduced excitatory glutamatergic transmission; key for analgesia and dissociation
• Additional actions: interaction with opioid receptors (μ, κ), monoaminergic pathways (inhibits reuptake of noradrenaline/serotonin), voltage-gated Ca2+ channels, HCN channels; local anaesthetic (Na+ channel) effects at higher concentrations
• Sympathomimetic effects largely indirect via central stimulation and inhibition of catecholamine reuptake; direct negative inotropy exists but is usually masked unless catecholamine-depleted

Pharmacokinetics

• Highly lipid soluble; rapid CNS uptake; onset IV ~30–60 s; IM onset ~3–5 min
• Distribution: large Vd; high protein binding (moderate); redistribution contributes to short clinical duration after bolus
• Metabolism: hepatic (CYP-mediated) N-demethylation to norketamine (active) then hydroxylation/conjugation; enterohepatic considerations minimal clinically
• Elimination: renal excretion of metabolites; context-sensitive half-time increases with prolonged infusion; terminal half-life often quoted ~2–3 h (product-dependent)
• Oral bioavailability low due to first-pass metabolism; intranasal/oral/transmucosal routes used in pain/psychiatry with different kinetics

Pharmacodynamics: CNS

• Produces dissociative anaesthesia: profound analgesia, amnesia, catalepsy; eyes may remain open with nystagmus; increased muscle tone; reflexes may be preserved
• EEG: increased high-frequency activity; BIS may be unreliable (can be higher than expected for depth)
• Emergence phenomena: vivid dreams, hallucinations, dysphoria; more common in adults, higher doses, rapid emergence, and anxious patients
  • Reduction strategies: benzodiazepine, alpha-2 agonist, adequate analgesia, quiet environment, slow titration
• Cerebral physiology: tends to increase CBF and CMRO2; may increase ICP especially with hypoventilation/hypercapnia; preserves airway reflexes but not reliably protective

Pharmacodynamics: respiratory

• Minimal respiratory depression compared with other induction agents; apnoea can occur with rapid IV bolus or with co-administered sedatives/opioids
• Airway: increased salivation/secretions; rare laryngospasm (notably in children/procedural sedation); bronchodilation via sympathetic and direct smooth muscle effects

Pharmacodynamics: cardiovascular

• Typically increases HR, BP, CO, and SVR (sympathomimetic); useful in haemodynamic compromise
• Direct myocardial depression (negative inotropy) may be unmasked in catecholamine-depleted states (septic shock, prolonged critical illness) → hypotension possible
• Increases myocardial oxygen demand; caution in severe CAD, tachyarrhythmias, pulmonary hypertension (may increase PVR variably)

Other system effects

• GI: nausea/vomiting can occur (often during recovery); consider antiemetic strategy for procedural sedation
• Eye: may increase IOP; nystagmus common; lacrimation increased
• Urology (chronic misuse): ulcerative cystitis and lower urinary tract symptoms; relevant in long-term recreational use history

Indications

• Induction/maintenance of anaesthesia where haemodynamic stability is required (trauma, hypovolaemia) and as part of TIVA/infusion techniques
• Analgesia: perioperative opioid-sparing, acute severe pain, opioid tolerance, burn dressings, trauma analgesia; adjunct in regional anaesthesia pathways
• Procedural sedation (ED, radiology, burns, paediatrics) with appropriate monitoring and airway capability
• Status asthmaticus/bronchospasm (adjunct) and refractory agitation requiring rapid control (specialist protocols)

Contraindications and cautions (exam framing)

• Relative: uncontrolled hypertension, severe IHD, aortic dissection, tachyarrhythmias, severe pulmonary hypertension
• Relative: raised ICP/space-occupying lesion, open globe injury, severe psychiatric illness/psychosis
• Caution with co-administered CNS depressants (opioids/benzodiazepines/propofol) → apnoea; caution in hepatic impairment (metabolism) and prolonged infusions

Adverse effects

• Psychotomimetic: emergence delirium, hallucinations, dysphoria; less with benzodiazepines/alpha-2 agonists and calm environment
• CV: hypertension, tachycardia, increased myocardial oxygen demand; hypotension in catecholamine-depleted states
• Respiratory/airway: hypersalivation, laryngospasm (rare), vomiting/aspiration risk if not fasted; apnoea with rapid bolus
• Neurological: increased muscle tone, involuntary movements; not a reliable marker of inadequate anaesthesia

Practical tips and comparisons

• Compared with propofol/thiopentone: better cardiovascular stability and analgesia, but more psychotomimetic effects and secretions; recovery can be less smooth
• Co-induction: small-dose ketamine with propofol can reduce propofol requirement and hypotension; balance against PONV/emergence and secretions
• Monitoring: depth monitors may mislead; rely on clinical signs, haemodynamics, and multimodal assessment