"Ketamine breaks every rule of the induction trolley: it raises the blood pressure, keeps the patient breathing, opens the bronchi and relieves pain. It is the drug for the crashing patient — bought at the price of a strange, dissociated awakening."
Tanya's notes, triangulated with Miller's Anesthesia; Morgan & Mikhail's Clinical Anesthesiology; Stoelting's Pharmacology.An NMDA antagonist that dissociates the brain
Ketamine is a non-competitive NMDA-receptor antagonist (binds the phencyclidine/PCP site). It is a partially water-soluble white crystalline salt with lipid solubility 5–10× that of thiopentone. Marketed as a racemate; the S(+) enantiomer is more potent as an analgesic, has faster clearance/recovery and fewer psychomimetic effects.
Many routes, one active metabolite
| Parameter | Value |
|---|---|
| Routes | IV, IM, SC, oral, nasal, rectal, intrathecal/epidural (preservative-free) |
| Onset (IV) | 30–60 s (IM ~2–4 min) |
| Distribution t½ | 11–16 min |
| Duration (single dose) | 10–15 min |
| Elimination t½ | 2–3 h |
Hepatic N-demethylation
Metabolised by hepatic microsomal enzymes → norketamine (an active metabolite, 20–30% of ketamine's activity) — prolongs the analgesia.
Hydroxylation & conjugation
→ hydroxynorketamine → water-soluble glucuronides → renal excretion. Total body clearance ≈ hepatic blood flow (flow-limited).
Receptors, dissociation, and a rise in ICP
Beyond NMDA antagonism (cortex, hippocampus, basal ganglia, brainstem, spinal cord), ketamine engages several systems:
| Target | Effect |
|---|---|
| NMDA receptor | Dissociation, analgesia, amnesia; inhibits central sensitisation (opioid-induced hyperalgesia) |
| Monoaminergic receptors | Antidepressant effect |
| Opioid receptors (brain & cord) | Analgesia; at high concentration acts at the σ receptor (dysphoria) |
| Cholinergic receptors | Purposeless movements; ↑ secretions |
| Thalamo-cortical/limbic dissociation | Unconsciousness + spinal analgesia; preserved corneal, cough & swallow reflexes |
Ketamine ↑ CMRO₂, ↑ CBF and ↑ ICP (antagonised by thiopentone/diazepam). Amnesia is weaker than a benzodiazepine. It also has an anti-apoptotic (neuroprotective) action and depresses auditory/visual relay nuclei.
Vivid dreams, a sense of floating out of the body, and illusions — more with women > men, large doses, and rapid administration. Treat/prevent with a benzodiazepine. A sub-anaesthetic dose (~0.5 mg/kg over 40 min) gives an antidepressant mood change lasting 3–12 days.
The airway-sparing bronchodilator
- Minimal effect on respiratory drive at usual doses (unusually large or rapid doses → apnoea).
- Bronchial smooth-muscle relaxant — a role in status asthmaticus (antagonises the spasmogenic effects of carbachol and histamine).
- ↑ Secretions & salivation — pre-treat with an antisialagogue (e.g. glycopyrrolate).
The sympathomimetic induction agent
- Blunt the sympathetic surge with a benzodiazepine, volatile agent or propofol if undesirable.
- In the catecholamine-depleted patient (prolonged shock, critical illness) the direct myocardial depressant effect is unmasked → cardiodepression.
- In congenital heart disease it does not change shunt fractions; PVR rises > SVR.
From shock induction to chronic-pain infusions
| Indication | Dose |
|---|---|
| Induction | 0.5–2 mg/kg IV, or 4–10 mg/kg IM |
| Maintenance | 15–45 µg/kg/min (up to 30–90 µg/kg/min with N₂O) |
| Sedation / premed (with an antisialagogue) | 0.2–0.8 mg/kg IV or 2–4 mg/kg IM |
| Analgesia — epidural/caudal (preservative-free) | 0.5–1 mg/kg |
| Pre-emptive analgesia | 0.15–0.25 mg/kg IV |
| Antidepressant | ~0.5 mg/kg IV over ~40 min |
- Induction of choice in shock: hypovolaemia, haemorrhagic and septic shock, cardiac tamponade — maintains BP.
- Reactive airway disease / status asthmaticus (bronchodilator).
- Multimodal analgesia — opioid-sparing (↓ PONV); chronic low-back, cancer, neuropathic/phantom/ischaemic-limb pain, fibromyalgia, CRPS, migraine, and opioid-induced hyperalgesia/tolerance.
- Day-care/NORA procedures and paediatric sedation.
Where ketamine is the wrong choice
- ↑ ICP — caution where intracranial pressure is already a concern.
- ↑ IOP — contraindicated in open-eye injury / ophthalmic disorders.
- ↑ MVO₂ — not used as a sole anaesthetic in ischaemic heart disease.
- Apnoea with large/rapid doses; emergence reactions and post-operative delirium.
- Psychiatric disease — caution in schizophrenia (may exacerbate).
- Preservatives (chlorobutanol/benzethonium chloride) are neurotoxic → use preservative-free ketamine for epidural/intrathecal use.
- Hepatic & renal toxicity with chronic/repeated exposure (e.g. long-term pain or misuse).
High-yield one-liners
Q: Mechanism & state produced?
NMDA antagonist at the PCP site → dissociative anaesthesia.
Q: Active metabolite?
Norketamine (20–30% activity) — prolongs analgesia.
Q: Why does BP rise?
Central sympathetic activation: ↑ catecholamines, vagal inhibition, ↓ noradrenaline re-uptake.
Q: When does it depress the heart instead?
When endogenous catecholamine stores are depleted (prolonged shock/critical illness).
Q: Classic contraindications?
Open-globe eye injury (↑ IOP), raised ICP, and IHD as a sole agent (↑ MVO₂).
References
- Dr. Tanya. Induction Agents — handwritten viva notes (primary source for this node).
- Gropper MA, Cohen NH, Eriksson LI, et al. (eds). Miller's Anesthesia. 9th ed. Elsevier; 2020.
- Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail's Clinical Anesthesiology. 7th ed. McGraw-Hill; 2022.
- Flood P, Rathmell JP, Urman RD. Stoelting's Pharmacology & Physiology in Anesthetic Practice. 6th ed. Wolters Kluwer; 2022.