Ketamine

Quick Answer

Ketamine is a phencyclidine (PCP) derivative dissociative anaesthetic producing analgesia, amnesia, and unconsciousness while preserving airway reflexes and cardiovascular stability. Mechanism: Non-competitive antagonist at NMDA (N-methyl-D-aspartate) glutamate receptors (primary anaesthetic effect); also acts at opioid receptors (analgesia), muscarinic receptors (emergence reactions), and voltage-gated sodium channels (local anaesthetic properties). Structure: Arylcyclohexylamine; chiral molecule; S-ketamine (esketamine) twice as potent as racemic mixture, available as nasal spray for depression. Pharmacokinetics: Lipophilic (logP 3.3), rapid onset IV 30-60 seconds, IM 3-5 minutes; distribution half-life 11-17 minutes, elimination half-life 2-3 hours; hepatic metabolism (CYP3A4, CYP2B6, CYP2C9) to norketamine (active metabolite, 1/3 potency) then dehydronorketamine (inactive); renal excretion of metabolites. Dosing: Induction IV 1-2 mg/kg, IM 5-10 mg/kg, infusion 0.1-0.5 mg/kg/hour (analgesia/low-dose), intranasal 3-6 mg/kg, oral 6-10 mg/kg. Effects: Dissociative anaesthesia (patient appears awake but disconnected from environment, eyes open, nystagmus, protective reflexes intact), potent analgesia (subanaesthetic doses 0.1-0.3 mg/kg provide significant pain relief), bronchodilation (sympathomimetic, useful in asthma), cardiovascular stimulation (increased BP, HR, CO via sympathetic activation—direct myocardial depressant masked by sympathetic stimulation), preserved airway reflexes (less aspiration risk than other agents), increases CMRO2, CBF, ICP (contraindicated in severe head injury/space-occupying lesions). Side effects: Emergence delirium (vivid dreams, hallucinations, confusion, 10-20% incidence in adults, reduce with benzodiazepines, avoid in adults with psychiatric history), increased secretions (antisialagogue required), laryngospasm (rare, 0.3-1%, usually with excessive secretions or airway manipulation), hypertension, tachycardia (sympathetic stimulation), increased ICP (cerebral vasodilation), nystagmus, myoclonus. Contraindications: Increased ICP (relative, avoid if severe), severe hypertension, severe cardiovascular disease (may precipitate ischaemia), psychiatric disorders (precipitate psychosis), raised intraocular pressure (glaucoma), upper airway infection (increased laryngospasm risk in children). Clinical uses: Emergency/induction in hypovolaemic/trauma patients (cardiovascular stability), paediatric induction (IM route if no IV), procedural sedation (ED, burns dressing changes), chronic pain (low-dose infusions, resistant depression), status asthmaticus (bronchodilation). Indigenous considerations: Higher rates of trauma and hypovolaemia make ketamine valuable; higher psychiatric illness rates require caution with emergence reactions; good agent for remote/retrieval settings. [1-10]