Ketamine

Why this drug is interesting

Ketamine is the drug that most clearly exposes the gap between a licence and a practice. The SmPC describes an anaesthetic induction agent given at 1–4.5 mg/kg intravenously.¹ The emergency physician's ketamine is a different drug at a different dose for a different purpose — 0.15 mg/kg for a fractured neck of femur, 1 mg/kg for a shoulder relocation in a child, 2 mg/kg for a shocked trauma patient needing intubation.

Its pharmacological distinctiveness is real, not marketing. Ketamine produces dissociation rather than a dose-dependent continuum of sedation: below a threshold the patient is awake with analgesia, above it they are dissociated, and there is no meaningful intermediate. Airway reflexes and respiratory drive are largely preserved. Sympathetic tone is maintained or increased. No other agent in the department does all three.

Pharmacology

Mechanism

Ketamine is a phencyclidine derivative and principally a non-competitive antagonist at the NMDA receptor, binding within the open channel pore. Blocking glutamatergic transmission at NMDA receptors uncouples the thalamocortical and limbic systems — the functional dissociation from which the clinical state takes its name.

It also acts at opioid receptors, monoaminergic receptors, muscarinic receptors and voltage-gated sodium channels, and inhibits catecholamine reuptake. That last action produces the characteristic indirect sympathomimetic effect: tachycardia, hypertension and preserved cardiac output.

Kinetics

Onset

IV within 30 seconds; IM 3–4 minutes to surgical anaesthesia

Distribution half-life

10–15 minutes — this, not elimination, governs the duration of anaesthesia (about 20 minutes)

Elimination half-life

Approximately 2–3 hours

Metabolism

Hepatic, CYP3A4/CYP2B6, to norketamine — active, roughly a third as potent, and responsible for prolonged mild effects

Excretion

Renal, as metabolites

The gap between a 10–15 minute distribution half-life and a 2–3 hour elimination half-life explains a common bedside observation: the patient re-orientates quickly but remains subtly off for considerably longer. That tail matters for discharge and driving advice, not for airway safety.

Racemate and S-ketamine

UK ketamine is the racemic mixture. S-ketamine (esketamine) has roughly twice the anaesthetic potency of the racemate, allowing lower volumes and possibly fewer psychotomimetic effects, but it is not the standard ED preparation in the UK — check which your department stocks before assuming a dose.

Licensed dosing

The licensed indication is as an anaesthetic agent for diagnostic and surgical procedures, in children and adults — by IV or IM injection for short procedures, or with additional doses or infusion for longer ones.¹ Named applications include burns debridement and dressings, neurodiagnostic and ophthalmic/ENT procedures, orthopaedic procedures, and anaesthesia in poor-risk patients and asthmatics.

Antisialagogue premedication

The SmPC recommends premedication with an antimuscarinic — atropine, hyoscine or glycopyrronium — to reduce hypersalivation. Modern practice has largely abandoned routine co-administration, since the evidence suggests it does not reduce airway adverse events and adds side effects. Reserve it for the patient in whom secretions are actually a problem, and know that this is a deliberate departure from the label.

Off-label use in the emergency department

Dissociative procedural sedation

The commonest ED use, particularly in children — fracture manipulation, joint relocation, laceration repair in the distressed child, foreign body removal.

• IV: approximately 1 mg/kg, given slowly over 60 seconds, with further increments of 0.25–0.5 mg/kg as required
• IM: 2.5–4 mg/kg where IV access is impractical — slower onset and slower offset, but avoids cannulation in a distressed child
• Dissociation is a threshold phenomenon: increments beyond the dissociative dose prolong recovery without deepening sedation
• Follow RCEM and local safe sedation standards — trained staff, monitoring, capnography, recovery area and a practitioner whose sole responsibility is the patient

Sub-dissociative analgesia

Low-dose ketamine as an analgesic, typically 0.1–0.3 mg/kg IV given slowly or as a short infusion, is increasingly used for acute severe pain — particularly where opioids are undesirable, ineffective or already maximal. Giving it as a brief infusion rather than a bolus substantially reduces the dysphoria that otherwise limits its acceptability.

Induction for RSI

Ketamine at 1–2 mg/kg is a common induction agent in the haemodynamically compromised patient, precisely because of the preserved sympathetic tone. Reduce the dose in shock — often substantially, to 0.5–1 mg/kg — recognising both the smaller volume of distribution and the catecholamine-depletion caveat above.

Other established uses

• Severe asthma — bronchodilator properties; the SmPC itself names asthmatic patients among suitable anaesthesia candidates
• Agitated delirium and acute behavioural disturbance — rapid IM control where other agents have failed; see the ABD algorithm for governance
• Analgesia for extrication and prehospital care — where an intact airway and preserved blood pressure are at a premium

Contraindications and the intracranial pressure question

SmPC contraindications

• Hypersensitivity to ketamine or excipients
• Patients in whom an elevation of blood pressure would constitute a serious hazard
• Eclampsia or pre-eclampsia
• Severe coronary or myocardial disease
• Cerebrovascular accident or cerebral trauma

Cautions worth knowing

• Raised intraocular pressure and globe injury — the SmPC specifically warns that IOP may rise significantly after a single dose
• Mild-to-moderate hypertension — blood pressure rises shortly after injection, peaking within minutes at a median 20–25% above baseline
• Airway reflexes are preserved but not guaranteed — the SmPC advises avoiding mechanical stimulation of the pharynx unless muscle relaxants and airway control are in place. Preserved reflexes are not the same as a protected airway
• Psychiatric history — relative caution; emergence phenomena may be more distressing, though this should not become a blanket exclusion

Adverse effects

Emergence phenomena

The characteristic adverse effect: pleasant dream-like states through to vivid imagery, hallucinations, nightmares and emergence delirium. The SmPC notes these may be reduced if verbal and tactile stimulation is minimised during recovery — which translates directly into a quiet, dimly lit recovery space and hands off the patient unless clinically necessary.

Emergence phenomena are markedly less common and less severe in children, which is one reason paediatric ED sedation practice adopted ketamine so readily. In adults, forewarning the patient and co-administering a small benzodiazepine are both used, though the evidence for routine prophylactic benzodiazepine is not strong and it prolongs recovery.

Airway and respiratory

• Hypersalivation — troublesome mainly in small children
• Laryngospasm — uncommon but the most feared complication of paediatric ketamine sedation; usually responds to airway repositioning and positive pressure
• Transient apnoea — chiefly a consequence of rapid administration or high dose
• Vomiting — common enough to matter, generally late in recovery

Cardiovascular and other

• Tachycardia and hypertension — usually desirable, occasionally not
• Random purposeless movements and nystagmus — normal features of dissociation, frequently mistaken by observers for inadequate sedation. Resist the urge to top up for movement alone
• Increased muscle tone
• Ketamine-induced uropathy — ulcerative cystitis and upper tract damage with chronic recreational use; not a single-dose concern but relevant to the patient population and to counselling

Practical and governance points

Controlled drug status

Ketamine was reclassified from Class C to Class B under the Misuse of Drugs Act on 10 June 2014, and is in Schedule 2 of the Misuse of Drugs Regulations.⁵ It therefore carries full controlled-drug requirements — safe custody, CD register entries, witnessed administration and destruction — in line with your trust's CD policy.

Documentation for off-label use

For procedural sedation and analgesic dosing, record that the use is off-label, the indication, the consent discussion, and the local guideline relied upon. This is straightforward when done contemporaneously and awkward to reconstruct afterwards.

Critical appraisal

1. The licence is the weakest part of this drug's story. The SmPC describes 1970s anaesthetic practice; the evidence base for ED procedural sedation and sub-dissociative analgesia is now large, and RCEM guidance is well established. Practice has justifiably moved, but every clinician using ketamine should be able to say which parts of their use are licensed and which are not.
2. The ICP evidence is reassuring but not definitive for the ED context. Most reassuring data come from ventilated patients with controlled ventilation and monitored ICP — not from a spontaneously breathing patient in resus. Extrapolate with that in mind.
3. "Cardiostable" is over-taught. The haemodynamic benefit depends on endogenous catecholamines, and the direct myocardial depressant effect is real. In the profoundly shocked patient ketamine is the least bad induction agent, not a harmless one.
4. Comparative analgesia evidence is genuinely encouraging but heterogeneous. Sub-dissociative ketamine performs comparably to morphine in several trials, with more minor psychoperceptual effects and less respiratory depression — but dosing, infusion rates and outcome measures vary widely between studies, which limits how precisely the optimal regimen can be stated.
5. Recreational-use harms should not be projected onto single therapeutic doses. Ketamine-induced uropathy follows sustained heavy use. Conflating the two misleads patients who need a single dose for a painful procedure.

References

1. 1
   Ketalar 50 mg/ml Injection — Summary of Product Characteristics. electronic Medicines Compendium. Sections 4.1–4.4, 5.2. Verified 20 Aug 2026.
2. 2
   Ketamine — dosing and safety monograph. BNF, NICE. bnf.nice.org.uk
3. 3
   Royal College of Emergency Medicine. Safe Sedation of Adults in the Emergency Department and Ketamine Procedural Sedation for Children in the Emergency Department — RCEM best practice guidance. rcem.ac.uk
4. 4
   Green SM, Roback MG, Kennedy RM, Krauss B. Clinical practice guideline for emergency department ketamine dissociative sedation: 2011 update. Ann Emerg Med 2011;57(5):449–61.
5. 5
   The Misuse of Drugs Act 1971 (Amendment) Order 2014, SI 2014/1106 — reclassification of ketamine to Class B, in force 10 June 2014. legislation.gov.uk. See also the House of Commons Library briefing on ketamine. commonslibrary.parliament.uk
6. 6
   Cohen L, Athaide V, Wickham ME, et al. The effect of ketamine on intracranial and cerebral perfusion pressure and health outcomes: a systematic review. Ann Emerg Med 2015;65(1):43–51.
7. 7
   Zietlow J, Berns K, Jenkins D, Zietlow S. Prehospital use of ketamine: effectiveness in critically ill and injured patients. Mil Med 2019;184(Suppl 1):542–44.