Ketamine
Ketamine is a phencyclidine derivative used for induction, sedation, analgesia, and as a bronchodilator in severe asthma.
Ketamine acts via:
- Non-competitive antagonist of NMDA and glutamate receptors in the CNS
- Reduces presynaptic glutamate release
- Sodium channel inhibition
Local anaesthetic-like effect. - Potential monoaminergic, muscarinic, and nicotinic antagonism
| Property | Action |
|---|---|
| Class | Phencyclidine derivative |
| Uses | Induction of anaesthesia, sedation, analgesia, asthma |
| Presentation | Clear, colourless solution forming an acidic solution (pH 3.5-5.5) |
| Isomerism | Racemic mixture or the single S(+) enantiomer, which is 2-3x as potent as the R(-) enantiomer but has less bronchodilatory properties |
| Route of Administration | IV, IM, PO, PR, PN, via epidural (with preservative-free solution) |
| Dosing | Induction: 1-2mg.kg-1 IV, 5-10mg.kg-1 IM, Sedation: 0.2-0.5mg.kg-1 IV |
| Distribution | 25% protein bound. t1/2α 10-15 minutes |
| Metabolism | Hepatic metabolism to active norketamine by CYP450 and then to inactive metabolites, t1/2β 2-4 hours |
| Elimination | Renal elimination of inactive metabolites. Action of norketamine prolonged in renal failure. |
| Resp | Bronchodilation, tachypnea, relative preservation of laryngeal reflexes. Apnoea with rapid injection. Preserved central response to CO2. |
| CVS | ↑ Sympathetic outflow: ↑ HR, ↑ BP, ↑ SVR, ↑ MVO2. Acts directly as a myocardial depressant - beware maximally stimulated patient. Depresses baroreceptor reflex. |
| CNS | Dissociation, analgesia, emergence phenomena (hallucinations, delirium) reduced by concurrent BDZ administration (increasing risk with higher doses and rapid administration). Produces dissociative anaesthesia within 90 seconds by dissociating thalamocortical and limbic systems on EEG. Purposeful movements unrelated to stimulus may occur even during surgical anaesthesia. ↑ IOP. |
| Renal | Cystitis with long-term, high-dose use |
| GIT | N/V |
References
- Peck TE, Hill SA. Pharmacology for Anaesthesia and Intensive Care. 4th Ed. Cambridge University Press. 2014.
- Smith S, Scarth E, Sasada M. Drugs in Anaesthesia and Intensive Care. 4th Ed. Oxford University Press. 2011.
- CICM July/Sept 2007
- Lupton T, Pratt O. Intravenous drugs used for the induction of anaesthesia.