Anaes · Intravenous induction agents

Ketamine

Also known as NMDA receptor antagonist · Dissociative anaesthetic · Phencyclidine derivative · Aryl-cyclohexylamine · Racemic ketamine · S-ketamine (esketamine) · Ketalar

Ketamine is the only intravenous induction agent whose pharmacology is built on NMDA-receptor antagonism rather than GABA-A modulation, and that single mechanistic difference explains every property that makes it the induction agent of choice for the hypovolaemic, the bronchospastic and the patient in refractory status asthmaticus. The framework rests on four exam-critical ideas: it is a non-competitive, use-dependent NMDA-receptor antagonist that binds inside the open ion channel and blocks calcium and sodium influx, a mechanism fundamentally different from the GABA-A positive allosteric modulation of propofol and thiopental; its dissociative state, profound sub-anaesthetic analgesia, bronchodilation and sympathomimetic pressor response make it unique among induction agents; the critical caveat that in the catecholamine-depleted heart the direct negative inotropic effect is unmasked and the expected pressor response can become a severe hypotension; and esketamine, the S-enantiomer, is about four times more potent at the NMDA receptor with fewer psychotomimetic effects and is the basis of the licensed intranasal treatment for treatment-resistant depression. Built on the foundational CI-581 human pharmacology (Domino 1965), the Lancet ketamine review (Dundee 1970), the NMDA pharmacokinetic and pharmacodynamic analysis (Niesters 2012), the opioid-sparing systematic reviews (Subramaniam 2004, Laskowski 2011), the status-asthmaticus review (Goyal 2013), the chirality review (Andrade 2017), the ketamine-metabolite antidepressant programme (Zanos Nature 2016, Molecular Psychiatry 2018, Pharmacological Reviews 2018), and the contemporary perioperative, trauma, prehospital, RSI and psychiatric-emergencies literature (Al Subhi 2026, Tanaka 2026, Rav 2026, Ayazbekova 2026, Duclos 2026, Mills 2026, Sheridan 2026, Chilingarashvili 2026).

high18 referencesUpdated 26 July 202636 min readVerification in progress

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In the catecholamine-depleted heart (severe prolonged shock, chronic severe heart failure, late sepsis) the expected sympathomimetic pressor response fails and ketamine's DIRECT negative inotropic effect is unmasked, producing severe hypotension rather than the expected rise in blood pressure. The profoundly shocked patient still needs concurrent vasopressor support ready and running — ketamine is not a pressor in its own right.Ketamine historically carried a relative contraindication in raised intracranial pressure and traumatic brain injury, on the grounds that it increases cerebral blood flow, cerebral metabolic rate and intracranial pressure. The modern reassessment is more nuanced: with controlled normocapnic ventilation and a suppressed cough, ketamine does not adversely raise ICP and may preserve cerebral perfusion pressure through its sympathomimetic effect, and it is increasingly accepted for neurotrauma RSI.Ketamine increases the intraocular pressure and the extraocular muscle tone — caution in the open-eye or globe injury, where a sudden rise in intraocular pressure can extrude intraocular contents.Emergence phenomena — vivid hallucinations, nightmares and delirium on emergence — are common after a large bolus, especially in adults. Reduce them with benzodiazepine pretreatment or by using a low-dose infusion rather than a bolus; avoid ketamine where postoperative delirium is particularly undesirable.Hypersalivation is prominent, especially in children, and combined with preserved airway reflexes can precipitate laryngospasm — give an antisialagogue (glycopyrrolate or atropine).Ketamine preserves airway reflexes and the respiratory drive better than other induction agents BUT a large or rapid bolus still causes transient apnoea and airway loss — equipment for airway control and ventilation must always be immediately available; it is not a licence for unmonitored sedation.Ketamine is a drug of misuse and potential dependence. Repeated or prolonged administration in the chronic-pain and palliative populations can produce tolerance, dependence, and the hepatobiliary and lower-urinary-tract toxicity (ulcerative cystitis) of chronic use. Prescribing must follow institutional and regulatory controls.

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[1]

Meet the patient

A 24-year-old is dragged from a wrecked car — cold, pale, systolic of 70 — and the trauma team is calling for a rapid-sequence induction. This is the ketamine stem: the agent you reach for precisely because it holds the blood pressure up where propofol and thiopental would drop it.[5]

Two questions frame every ketamine viva: why does it raise the blood pressure when every other induction agent lowers it? and when does that pressor response betray you? Hold those two and the whole drug arranges itself around them.[7]

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References18Show ledger

[1]Al Subhi M, et al. Effect of Perioperative Ketamine and Esketamine on Postoperative Fatigue: A Systematic Review and Meta-Analysis of Randomized Controlled Trials Medicina (Kaunas), 2026.PMID 42356168
[2]Tanaka M, et al. Synaptic Plasticity-Intrinsic Excitability and Antidepressant Discovery Biomedicines, 2026.PMID 42351693
[3]Rav E, et al. Topical Amitriptyline, Ketamine, and Lidocaine Cream for Neuropathic Pain Control in Pediatric Oncology Patients J Pain Symptom Manage, 2026.PMID 42362167
[4]Ayazbekova A, et al. Role of Opioid-Free Anesthesia Versus Opioid-Based Anesthesia in Postoperative Pain and Opioid Consumption: A Systematic Review and Meta-Analysis J Clin Med, 2026.PMID 42355728
[5]Duclos G, et al. Ketamine Low dOse Evaluation on morphine consumption in traumatic patients: study protocol for a randomized, double-blind, placebo-controlled trial (KLOE-Trial) Scand J Trauma Resusc Emerg Med, 2026.PMID 42310772
[6]Mills J, et al. Ketamine Versus Propofol for Sedation in Acute Psychiatric Emergencies During Aeromedical Retrieval: A Randomized Clinical Trial Prehosp Emerg Care, 2026.PMID 42307216
[7]Sheridan B, et al. Maintenance of prehospital anaesthesia using an intermittent bolus regime in blunt trauma patients with a high GCS and hemodynamic reserve: a retrospective cohort study Scand J Trauma Resusc Emerg Med, 2026.PMID 42351216
[8]Chilingarashvili G, et al. Ketamine Versus Etomidate for Rapid Sequence Intubation in Critically Ill Adults: A Comprehensive Systematic Review and Meta-Analysis Cureus, 2026.PMID 42011475
[9]Domino EF, Chodoff P, Corssen G. PHARMACOLOGIC EFFECTS OF CI-581, A NEW DISSOCIATIVE ANESTHETIC, IN MAN Clin Pharmacol Ther, 1965.PMID 14296024
[10]Dundee JW, Bovill J Ketamine Lancet, 1970.PMID 4194382
[11]Niesters M, Dahan A Pharmacokinetic and pharmacodynamic considerations for NMDA receptor antagonists in the treatment of chronic neuropathic pain Expert Opin Drug Metab Toxicol, 2012.PMID 22871026
[12]Subramaniam K, Subramaniam B, Steinbrook RA. Ketamine as adjuvant analgesic to opioids: a quantitative and qualitative systematic review Anesth Analg, 2004.PMID 15271729
[13]Laskowski K, Stirling A, McKay WP, Lim HJ. A systematic review of intravenous ketamine for postoperative analgesia Can J Anaesth, 2011.PMID 21773855
[14]Goyal S, Agrawal A. Ketamine in status asthmaticus: A review Indian J Crit Care Med, 2013.PMID 24082612
[15]Andrade C. Ketamine for Depression, 3: Does Chirality Matter? J Clin Psychiatry, 2017.PMID 28682536
[16]Zanos P, Moaddel R, Morris PJ, et al. NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature, 2016.PMID 27144355
[17]Zanos P, Gould TD. Mechanisms of ketamine action as an antidepressant Mol Psychiatry, 2018.PMID 29532791
[18]Zanos P, Moaddel R, Morris PJ, et al. Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms Pharmacol Rev, 2018.PMID 29945898

Ketamine

Also known as NMDA receptor antagonist · Dissociative anaesthetic · Phencyclidine derivative · Aryl-cyclohexylamine · Racemic ketamine · S-ketamine (esketamine) · Ketalar

high18 referencesUpdated 26 July 202636 min readVerification in progress

Practise this topic

10 MCQs

Meet the patient

Anaesthesia Pro

You have read the opening of this topic. The complete unit — every section and its primary-source references — is part of the Anaesthesia fellowship atlas.

References18Show ledger

[1]Al Subhi M, et al. Effect of Perioperative Ketamine and Esketamine on Postoperative Fatigue: A Systematic Review and Meta-Analysis of Randomized Controlled Trials Medicina (Kaunas), 2026.PMID 42356168
[2]Tanaka M, et al. Synaptic Plasticity-Intrinsic Excitability and Antidepressant Discovery Biomedicines, 2026.PMID 42351693
[3]Rav E, et al. Topical Amitriptyline, Ketamine, and Lidocaine Cream for Neuropathic Pain Control in Pediatric Oncology Patients J Pain Symptom Manage, 2026.PMID 42362167
[4]Ayazbekova A, et al. Role of Opioid-Free Anesthesia Versus Opioid-Based Anesthesia in Postoperative Pain and Opioid Consumption: A Systematic Review and Meta-Analysis J Clin Med, 2026.PMID 42355728
[5]Duclos G, et al. Ketamine Low dOse Evaluation on morphine consumption in traumatic patients: study protocol for a randomized, double-blind, placebo-controlled trial (KLOE-Trial) Scand J Trauma Resusc Emerg Med, 2026.PMID 42310772
[6]Mills J, et al. Ketamine Versus Propofol for Sedation in Acute Psychiatric Emergencies During Aeromedical Retrieval: A Randomized Clinical Trial Prehosp Emerg Care, 2026.PMID 42307216
[7]Sheridan B, et al. Maintenance of prehospital anaesthesia using an intermittent bolus regime in blunt trauma patients with a high GCS and hemodynamic reserve: a retrospective cohort study Scand J Trauma Resusc Emerg Med, 2026.PMID 42351216
[8]Chilingarashvili G, et al. Ketamine Versus Etomidate for Rapid Sequence Intubation in Critically Ill Adults: A Comprehensive Systematic Review and Meta-Analysis Cureus, 2026.PMID 42011475
[9]Domino EF, Chodoff P, Corssen G. PHARMACOLOGIC EFFECTS OF CI-581, A NEW DISSOCIATIVE ANESTHETIC, IN MAN Clin Pharmacol Ther, 1965.PMID 14296024
[10]Dundee JW, Bovill J Ketamine Lancet, 1970.PMID 4194382
[11]Niesters M, Dahan A Pharmacokinetic and pharmacodynamic considerations for NMDA receptor antagonists in the treatment of chronic neuropathic pain Expert Opin Drug Metab Toxicol, 2012.PMID 22871026
[12]Subramaniam K, Subramaniam B, Steinbrook RA. Ketamine as adjuvant analgesic to opioids: a quantitative and qualitative systematic review Anesth Analg, 2004.PMID 15271729
[13]Laskowski K, Stirling A, McKay WP, Lim HJ. A systematic review of intravenous ketamine for postoperative analgesia Can J Anaesth, 2011.PMID 21773855
[14]Goyal S, Agrawal A. Ketamine in status asthmaticus: A review Indian J Crit Care Med, 2013.PMID 24082612
[15]Andrade C. Ketamine for Depression, 3: Does Chirality Matter? J Clin Psychiatry, 2017.PMID 28682536
[16]Zanos P, Moaddel R, Morris PJ, et al. NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature, 2016.PMID 27144355
[17]Zanos P, Gould TD. Mechanisms of ketamine action as an antidepressant Mol Psychiatry, 2018.PMID 29532791
[18]Zanos P, Moaddel R, Morris PJ, et al. Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms Pharmacol Rev, 2018.PMID 29945898