?Pharmacokinetics and indications of Ketamine hydrochloride

Ketamine hydrochloride is a phencyclidine derivative and was introduced in 1965. It produces dissociative anaesthesia (via non-competitive antagonism at the NMDA receptor) rather than classical generalised depression of the CNS and is a useful adjunctive analgesic. Ketamine has no action at GABAA receptors.

Physical characteristics and presentation Ketamine has a single chiral centre and is usually presented as a racemic mixture of its R(−) and S(+) stereoisomers in water solutions at concentrations of 10, 50 and 100mgml −1 . The S(+) enantiomer has more potent analgesic effects (approximately fourfold), allowing lower doses to be used, with fewer adverse effects and a more rapid clinical recovery than the racemic mixture, but its pharmacokinetics are identical. The enantiopure formulation of S(+) ketamine is not currently available in the UK.

Pharmacokinetics 

Protein binding is lower than other i.v. agents. Redistribution after i.v. injection occurs more slowly than with other i.v. anaesthetic agents, and the elimination half-life is approximately 2.5h. Ketamine undergoes extensive hepatic metabolism by demethylation and hydroxylation of the cyclohexanone ring. Metabolites include norketamine, which is pharmacologically active (20%–30% of the activity of ketamine). Approximately 80% of the injected dose is excreted via the kidneys as glucuronides; only 2.5% is excreted unchanged. After i.m. injection, peak concentrations are achieved after approximately 20 min.

Specific indications 

The high-risk patient 

Ketamine is considered useful in the patient with shock because of maintenance of cardiovascular function, but arterial pressure decreases in the presence of hypovolaemia. High-risk patients often receive postoperative sedation in ICU which minimises the risk of emergence phenomena. 

Paediatric anaesthesia 

Children undergoing minor surgery, invasive investigations (e.g. cardiac catheterisation), ophthalmic examinations or radiotherapy may be managed successfully with ketamine administered orally or by i.m. or i.v. injection. 

Difficult locations and developing countries 

Ketamine has been used successfully on scene in trauma, for analgesia and anaesthesia in casualties of war and in resource-poor locations where there is limited equipment for inhalational anaesthesia and trained staff are in short supply. 

Analgesia and sedation 

Ketamine may be used in lower doses for its analgesic effects – such as for changing wound or burn dressings or positioning patients in pain before regional anaesthesia (e.g. fractured neck of femur).

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