KETAMINE UNLOCKED: MECHANISMS, DOSING & CLINICAL PEARLS │ EP71

Ketamine is a dissociative anesthetic that provides powerful analgesia while preserving spontaneous ventilation, airway reflexes, and sympathetic tone, which makes it especially valuable in trauma, bronchospasm, difficult airways, and in patients with high opioid tolerance. As a phencyclidine derivative with a chiral center, it exists as two enantiomers, with S-ketamine roughly twice as potent as R-ketamine and associated with fewer unpleasant emergence reactions, while its pKa and balanced water–lipid solubility allow rapid CNS penetration and redistribution-limited offset. Its multimodal mechanism centers on noncompetitive NMDA antagonism but also includes opioid receptor modulation, catecholamine reuptake inhibition, AMPA receptor effects, ion channel blockade, muscarinic antagonism, and anti-inflammatory actions, all of which underpin clinical dosing strategies for induction, maintenance, procedural sedation, and analgesic infusions as well as key considerations around emergence delirium, secretions, cardiovascular status, and ICP.

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