The one induction agent that supports blood pressure instead of dropping it — with a reputation that often precedes the pharmacology.
Ketamine occupies a strange place in the drug cupboard — simultaneously a first-line trauma induction agent, a legitimate analgesic infusion, a treatment-resistant depression therapy, a battlefield and disaster-medicine staple, and a drug carrying enough reputation from misuse that many patients (and some clinicians) are wary of it before understanding what it actually does. Nearly everything unusual about ketamine, good and bad, traces back to a single fact: it works by a completely different receptor mechanism than every other induction agent in routine use. Here is what matters about it, from the receptor up to the bedside.
Ketamine is a phencyclidine derivative and the prototypical NMDA (N-methyl-D-aspartate) receptor antagonist used in clinical anaesthesia. Where propofol and the benzodiazepines work by potentiating inhibitory GABA-A signalling, ketamine works by blocking excitatory glutamate transmission — a fundamentally different lever, which explains why its clinical footprint looks so unlike the other induction agents.
NMDA receptor (non-competitive antagonism, phencyclidine site): ketamine binds inside the NMDA ion channel and blocks glutamate-mediated excitatory transmission at cortical and subcortical sites. This produces "dissociative anaesthesia" — functional and electrophysiological dissociation between the thalamo-neocortical and limbic systems, rather than the generalised cortical depression produced by GABAergic agents. The patient can appear to have their eyes open, exhibit spontaneous movement, and yet be fully amnestic and unresponsive to surgical stimulus.
Opioid receptors (mu, kappa, sigma): ketamine has weak affinity at opioid receptors, contributing modestly to its analgesic profile independent of the NMDA effect.
Monoaminergic system: ketamine inhibits reuptake of noradrenaline, dopamine, and serotonin at central and peripheral synapses. This is the mechanism behind its signature sympathomimetic cardiovascular profile — a rise, not a fall, in heart rate and blood pressure — and it is also the mechanism increasingly implicated in ketamine's rapid antidepressant effect via downstream synaptic plasticity changes.
Direct myocardial and central effects: in isolated tissue, ketamine is actually a direct myocardial depressant and central sympathetic depressant. In the intact, catecholamine-replete patient, the indirect sympathomimetic effect from monoamine reuptake inhibition dominates and wins out — but in a catecholamine-depleted patient (prolonged critical illness, exhausted sympathetic reserve), the direct depressant effect can unmask itself, and blood pressure may fall instead of rise. This is one of the most important and most frequently missed pharmacological subtleties of the drug.
Ketamine does not produce anaesthesia on the same spectrum as propofol or the volatiles, where deeper dosing simply produces a deeper version of the same unconscious state. Instead it produces a distinct dissociative state — analgesia, amnesia, and a trance-like catalepsy — that exists somewhat orthogonally to the sedation-to-unconsciousness continuum most anaesthetists are trained to think in. This is precisely why airway reflexes, spontaneous ventilation, and even purposeful-looking movement can persist throughout a technically adequate ketamine anaesthetic, and why depth-of-anaesthesia monitors calibrated to GABAergic agents do not reliably apply to it.
Ketamine is highly lipophilic — five to ten times more so than thiopental — which underlies its rapid onset via prompt penetration of the blood-brain barrier. It is metabolised in the liver to a genuinely active metabolite, which is unusual among induction agents and clinically relevant for repeated or prolonged dosing.
| Parameter | Value | Clinical relevance |
|---|---|---|
| Onset (IV) | 30–60 sec | Comparable to propofol; suitable for rapid-sequence use |
| Onset (IM) | 3–5 min | Valuable when IV access is difficult or absent — combative or paediatric patients |
| Duration (single IV dose) | 10–15 min (dissociation) | Terminated by redistribution, like propofol; full reorientation takes longer |
| Elimination half-life | ~2–3 hours | Longer than the "wears off fast" bedside impression from redistribution alone |
| Active metabolite | Norketamine (~⅓ potency of parent) | Contributes to prolonged analgesia and sedation, especially with repeated dosing or infusion |
| Protein binding | ~20–30% | Relatively low compared with propofol or dexmedetomidine |
| Metabolism | Hepatic (CYP3A4, CYP2B6) — N-demethylation | Reduce dose in significant hepatic impairment; watch for drug interactions via CYP3A4 |
| Bioavailability | IV/IM ~100%; oral/intranasal considerably lower with first-pass effect | Oral and intranasal routes exist for analgesia/sedation but require higher doses |
The defining feature. Expect a rise in heart rate, blood pressure, and cardiac output from centrally and peripherally mediated sympathetic stimulation — the opposite of every other IV induction agent in common use. This makes ketamine a genuinely useful choice in hypovolaemic, haemorrhaging, or septic patients where haemodynamic support rather than further depression is needed at induction. The important caveat: in patients with exhausted or maximally stimulated endogenous catecholamine stores (prolonged shock, catecholamine-depleted critical illness), ketamine's intrinsic direct myocardial depressant effect can dominate instead, producing hypotension rather than the expected pressor response — the single most important exception to keep in mind.
Relatively preserved respiratory drive at analgesic and dissociative doses compared with other induction agents — apnoea is uncommon as a sole agent at standard doses, though it can still occur, particularly with rapid administration or co-administered sedatives/opioids. Ketamine is also a genuine bronchodilator, through both direct smooth muscle relaxation and catecholamine release, making it a favoured induction agent in patients with reactive airway disease or status asthmaticus. Airway reflexes are relatively preserved, though this should never be relied upon as protection against aspiration — patients are not considered to have an intact, protected airway simply because they are on ketamine.
Increases cerebral metabolic rate, cerebral blood flow, and — in spontaneously ventilating patients without controlled normocapnia — intracranial pressure; this classic teaching has been substantially revisited in the literature, and in mechanically ventilated, normocapnic patients ketamine's ICP effect appears far more modest than once taught, but caution and individualised judgement in raised-ICP states remains reasonable practice. Produces the dissociative state described above along with potent analgesia and amnesia. Emergence phenomena — vivid dreaming, hallucinations, or frank dysphoria on emergence — are the most clinically troublesome CNS effect and are discussed further below.
Increases salivary and bronchial secretions, which is why an antisialagogue (glycopyrrolate) is frequently co-administered, particularly in children. Preserves airway muscle tone better than propofol. Does not reliably trigger malignant hyperthermia. Analgesic effects at sub-dissociative ("low") doses are genuinely distinct from and additive to its anaesthetic effects — this is the basis of ketamine's expanding role in acute and chronic pain medicine.
Ketamine's unusual combination of haemodynamic support, preserved respiratory drive, bronchodilation, and potent analgesia has earned it a genuinely broad clinical footprint, from the trauma bay to the chronic pain clinic.
A commonly favoured induction agent in trauma, hypovolaemia, and septic shock, where the pressor effect can help rather than compound an already compromised circulation — though the response is patient-dependent and not guaranteed in every case.
IM availability, wide safety margin, preserved airway reflexes, and analgesic potency make it a mainstay where monitoring and rescue resources are limited.
Widely used in emergency departments and paediatric settings for fracture reduction, laceration repair, and burns dressing changes — a genuine strength given the analgesic-plus-sedative combination in one drug.
Bronchodilator properties make it a favoured induction and sedation agent when mechanical ventilation is required for severe reactive airway disease.
Low-dose IV ketamine infusion is an established opioid-sparing analgesic strategy for acute pain, including in the emergency department and postoperatively.
Ketamine infusions are used for complex regional pain syndrome and other refractory chronic pain states, typically in specialised pain-service settings with careful monitoring.
Used as an opioid- and sedative-sparing adjunct in mechanically ventilated ICU patients, particularly where haemodynamic instability limits other agents.
Sub-anaesthetic IV ketamine (and its S-enantiomer, esketamine, as an approved intranasal formulation) has a genuine, rapid-onset antidepressant effect in treatment-resistant depression — administered in monitored psychiatric settings distinct from anaesthetic use.
| Indication | Dose | Notes |
|---|---|---|
| Induction (IV) | 1–2 mg/kg IV | Give over 60 seconds; titrate to clinical effect — lower doses are often appropriate in profoundly haemodynamically compromised or catecholamine-depleted patients, where the full 2 mg/kg dose is not automatically required |
| Induction (IM) | 6.5–13 mg/kg IM | Labelled range for induction of anaesthesia as a sole agent; useful when IV access is not yet secured — combative, paediatric, or prehospital settings. Distinct from the lower IM doses used for procedural sedation below |
| Procedural sedation (IV) | 0.5–1 mg/kg IV, repeat 0.25–0.5 mg/kg as needed | Titrate to effect; co-administer antisialagogue where secretions are a concern |
| Procedural sedation (IM) | 3–4 mg/kg IM | Common in paediatric ED settings without IV access |
| Sub-dissociative analgesia (IV infusion) | 0.1–0.3 mg/kg/h, or small serial boluses of 0.1–0.2 mg/kg | Opioid-sparing adjunct for acute pain; monitor for dissociative side effects even at "low" dose |
| ICU sedation adjunct | 0.1–0.5 mg/kg/h infusion | Typically combined with a primary sedative rather than used alone |
| Paediatric procedural sedation | IV 0.5–1 mg/kg; IM 3–4 mg/kg | Co-administer glycopyrrolate to reduce secretions; monitor emergence closely |
Doses are illustrative and drawn from commonly cited ranges in the anaesthesia and emergency medicine literature. Always confirm against your institution's protocol and current product labelling — dosing in this table is not a substitute for local guidelines.
Ketamine is taught as the induction agent that "protects" blood pressure, and in the well-resourced, catecholamine-replete patient that is usually true. But in a patient whose sympathetic reserve is already exhausted — prolonged septic shock, late-stage haemorrhage, or profound critical illness — the direct myocardial and central depressant properties of the drug can dominate instead, and blood pressure can fall rather than rise. Treat the "ketamine will support the pressure" teaching as a strong tendency, not a guarantee, and be ready to support the circulation regardless of which agent is chosen. This is also why the induction dose itself should be titrated rather than reflexively pushed to the higher end in an unstable patient — a full dissociative dose landing on top of an unmasked direct depressant effect is a genuine risk, not a theoretical one.
Vivid dreaming, out-of-body sensations, and frank hallucinations or dysphoria can occur as the dissociative state resolves, most notably in adults and with rapid IV administration. Risk is reduced by administering the drug in a calm, quiet environment, minimising unnecessary stimulation during emergence, and co-administering a benzodiazepine, which reliably lowers the incidence and severity of these reactions. There is no reversal agent for ketamine — management of a significant emergence reaction is supportive: a calm environment, reassurance, and a small dose of benzodiazepine if the reaction is distressing rather than mild.
Ketamine has a long and well-established track record in paediatric anaesthesia and emergency procedural sedation, valued for its wide safety margin and IM availability in a population where IV access is often the limiting step.
The textbook version of ketamine induction is a fast, haemodynamically supportive slide into dissociation, ideal for the unstable patient who cannot tolerate another drop in blood pressure. The bedside version has more texture than that.
The first thing worth watching is that the eyes often stay open. A patient who is fully dissociated, amnestic, and unresponsive to a surgical incision can still have open, roving eyes and even spontaneous limb movement — which is disconcerting to anyone in the room unfamiliar with ketamine's particular brand of "unconscious." Explaining this to the surgical team and any observers before it happens avoids a moment of unnecessary alarm mid-procedure.
The second thing is that the secretions are real and can genuinely interfere with airway management if not anticipated. A dry field for laryngoscopy or fibreoptic work can become considerably less dry within minutes of a ketamine dose, particularly in children — glycopyrrolate given ahead of time, rather than reached for after the fact, makes a meaningful difference to how the airway actually looks when it matters.
The third thing, and the one most likely to be underappreciated by someone using ketamine for the first time outside a controlled OR setting, is the emergence period. A patient who tolerated the procedure itself without apparent distress can still surface into a genuinely unpleasant dissociative afterimage — vivid, sometimes frightening dreams, disorientation, or tearfulness — minutes to tens of minutes later, in a recovery bay that is loud, bright, and full of unfamiliar faces. A quiet, dim, unhurried emergence environment does more for the patient's actual experience of the drug than almost any other single intervention available.
Ketamine's reputation as "the safe one" for unstable patients is well earned, but it is not a universal exemption from haemodynamic vigilance. The drug supports blood pressure through an indirect, catecholamine-dependent mechanism — which means it works best precisely in the patients who still have sympathetic reserve to draw on, and can behave unpredictably in those who don't. Know which patient is in front of you before assuming the pressor effect will show up on cue, and be ready to titrate the induction dose down rather than up when that reserve is in doubt.
Ketamine carries more stigma into the room than almost any other anaesthetic drug, largely disconnected from its actual clinical profile — a reputation shaped by recreational misuse rather than its behaviour at clinical doses under monitored conditions. That stigma can influence decisions more than the pharmacology does, sometimes leading to an appropriate choice being avoided or a patient being under-prepared for what emergence will feel like. The drug is best evaluated on what it actually does, not on what it is assumed to represent.
This content is intended for educational reflection and discussion among clinicians and trainees. Dosing information reflects commonly cited ranges in the anaesthesia and emergency medicine literature and is not a substitute for institutional protocols, current product labelling, or independent clinical judgment. The views expressed are the author's own and do not represent any institution, employer, or training program.