Monograph: |
Ketamine Hydrochloride
Indications: Anesthesia, adjunct; Anesthesia, general
SPECIAL NOTE
EMERGENCE REACTIONS HAVE OCCURRED IN APPROXIMATELY 12 % OF PATIENTS.
The psychological manifestations vary in severity between pleasant dream-like states, vivid imagery, hallucinations, and emergence delirium. In some cases these states have been accompanied by confusion, excitement, and irrational behavior which a few patients recall as an unpleasant experience. The duration ordinarily is no more than a few hours; in a few cases, however, recurrences have taken place up to 24 hours postoperatively. No residual psychological effects are known to have resulted from use of ketamine HCl.
The incidence of these emergence phenomena is least in the young (15 years of age or less) and elderly (over 65 years of age) patient. Also, they are less frequent when the drug is given intramuscularly and the incidence is reduced as experience with the drug is gained.
The incidence of psychological manifestations during emergence, particularly dream-like observations and emergence delirium, may be reduced by using lower recommended dosages of ketamine hcl in conjunction with intravenous diazepam during induction and maintenance of anesthesia. (See DOSAGE AND ADMINISTRATION.) Also, these reactions may be reduced if verbal, tactile and visual stimulation of the patient is minimized during the recovery period. THIS DOES NOT PRECLUDE THE MONITORING OF VITAL SIGNS.
IN ORDER TO TERMINATE A SEVERE EMERGENCE REACTION THE USE OF A SMALL HYPNOTIC DOSE OF A SHORT-ACTING OR ULTRASHORT-ACTING BARBITURATE MAY BE REQUIRED.
WHEN KETAMINE HCL IS USED ON AN OUTPATIENT BASIS, THE PATIENT SHOULD NOT BE RELEASED UNTIL RECOVERY FROM ANESTHESIA IS COMPLETE AND THEN SHOULD BE ACCOMPANIED BY A RESPONSIBLE ADULT.
DESCRIPTION:
Ketamine HCl is a nonbarbiturate anesthetic chemically designated dl 2-(o-chlorophenyl)-2-(methylamino) cyclohexanone hydrochloride. It is formulated as a slightly acid (pH 3.5-5.5) sterile solution for intravenous or intramuscular injection in concentrations containing the equivalent of either 10, 50, or 100 mg ketamine base per milliliter and contains not more than 0.1 mg/ml Phemerol (benzethonium chloride) added as a preservative. The 10 mg/ml solution has been made isotonic with sodium chloride.
CLINICAL PHARMACOLOGY:
Ketamine HCl is a rapid-acting general anesthetic producing an anesthetic state characterized by profound analgesia, normal pharyngeal-laryngeal reflexes, normal or slightly enhanced skeletal muscle tone, cardiovascular and respiratory stimulation, and occasionally a transient and minimal respiratory depression.
A patient airway is maintained partly by virtue of unimpaired pharyngeal and laryngeal reflexes. See WARNINGS and PRECAUTIONS.
The biotransformation of ketamine HCl includes N-dealkylation (metabolite I), hydroxylation of the cyclohexone ring (metabolites III and IV), conjugation with glucuronic acid and dehydration of the hydroxylated metabolites to form the cyclohexene derivative (metabolite II).
Following intravenous administration, the ketamine concentration has an initial slope (alpha phase) lasting about 45 minutes with a half-life of 10 to 15 minutes. This first phase corresponds clinically to the anesthetic effect of the drug. The anesthetic action is terminated by a combination of redistribution from the CNS to slower equilibrating peripheral tissues and by hepatic biotransformation to metabolite I. This metabolite is about as active as ketamine in reducing halothane requirements (MAC) of the rat. The later half-life of ketamine (beta phase) is 2.5 hours.
The anesthetic state produced by ketamine HCl has been termed "dissociative anesthesia" in that it appears to selectively interrupt association pathways of the brain before producing somesthetic sensory blockade. It may selectively depress the thalamoneocortical system before significantly obtunding the more ancient cerebral centers and pathways (reticular-activating and limbic systems).
Elevation of blood pressure begins shortly after injection, reaches a maximum within a few minutes and usually returns to preanesthetic values within 15 minutes after injection. In the majority of cases, the
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