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Chapter 15: Ketamine

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The principal mechanism of action of ketamine is best described as:

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(A) potentiation of GABA-mediated chloride currents

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(B) stimulation of μ- and κ-opioid receptors

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(C) stimulation of α2-adrenergic receptors

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(D) inhibition of NMDA receptors

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(E) blockade of CNS sodium channels

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The answer is D. While many intravenous anesthetics exert their effect by potentiating the effect of GABA, the principal analgesic and anesthetic mechanism of ketamine is blockade of the NMDA receptor. Ketamine is known to have effects on a wide variety of receptors, including AMPA, adenosine, μ-opioid, and cholinergic receptors, but the relative contribution of these players is substantially less significant than the NMDA inhibition.

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It is generally accepted that the main role of ketamine (when used in subhypnotic doses) is as an antihyperalgesic, antiallodynic drug, reducing the temporal summation of nociceptive afferent input that leads to central sensitization and windup.

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Ketamine is quite versatile in terms of its route of administration. It can be given via the intravenous, intramuscular, rectal, subcutaneous, transdermal, topical, oral, intranasal, sublingual, transmucosal, epidural, or intrathecal route. Ketamine has been gargled as a local throat analgesic, locally infiltrated, and used in intravenous regional anesthesia. The oral bioavailability of ketamine is low, and since so many other routes are available, this method is not particularly common. Intramuscular ketamine 4–5 mg/kg is very effective in the preoperative sedation in patients who are uncooperative.

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Ref: Miller RD. Miller's Anesthesia. 8th ed. Philadelphia, PA: Elsevier; 2015.

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The typical anesthetic state observed following an induction dose of ketamine is best characterized by which of the following?

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(A) catalepsy

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(B) miosis

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(C) hypoventilation

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(D) flaccid paralysis

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(E) ablation of protective reflexes

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The answer is A. Ketamine produces unconsciousness and analgesia in a dose-related manner. The anesthetic state produced by ketamine has been termed “dissociative anesthesia.” Rather than normal sleep, patients appear dissociated from their environment in an apparent cataleptic state. Patients may move, vocalize, and exhibit ocular tracking movements, but have profound analgesia and do not react to surgical stimuli or recall any of the events that occurred during the anesthetic. Amnesia, while part of the ketamine experience, is not as predictable as it is with benzodiazepines. Corneal, cough, and swallow reflexes may be present, but these should not be assumed to be protective. Skeletal muscle tone is also maintained and in some cases increased, ...

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