Ketamine Hydrochloride Injection, USP
CIII
Rx only
SPECIAL NOTE
EMERGENCE REACTIONS HAVE OCCURRED IN APPROXIMATELY 12 PERCENT
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.
THE INCIDENCE OF THESE EMERGENCE PHENOMENA IS LEAST IN THE
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 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 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 hydrochloride is a nonbarbiturate anesthetic chemically
designated (±)-2-(o-Chlorophenyl)-2-(methylamino)
cyclohexanone hydrochloride. It is formulated as a slightly acid (pH 3.5 to
5.5) sterile solution for intravenous or intramuscular injection in concentrations
containing the equivalent of either 50 or 100 mg ketamine base per milliliter
and contains not more than 0.1 mg/mL benzethonium chloride added as a preservative.
Ketamine hydrochloride has a molecular formula of C13H16ClNO• HCl, a molecular weight of 274.19 and the following structural
formula:
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CLINICAL PHARMACOLOGY
Ketamine 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 patent airway is maintained partly by
virtue of unimpaired pharyngeal and laryngeal reflexes. (See WARNINGS and PRECAUTIONS.)
The
biotransformation of ketamine 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 1/3 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 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 systolic and diastolic blood pressure peaks from 10% to 50%
above preanesthetic levels shortly after induction of anesthesia, but the
elevation can be higher or longer in individual cases (see CONTRAINDICATIONS).
Ketamine has a wide margin of safety;
several instances of unintentional administration of overdoses of ketamine
(up to ten times that usually required) have been followed by prolonged butcomplete recovery.
Ketamine has been studied in over
12,000 operative and diagnostic procedures, involving over 10,000 patients
from 105 separate studies. During the course of these studies ketamine hydrochloride
was administered as the sole agent, as induction for other general agents,
or to supplement low-potency agents.
Specific areas
of application have included the following:
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debridement, painful dressings, and skin grafting in burn
patients, as well as other superficial surgical procedures.
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neurodiagnostic procedures such as pneumonencephalograms,
ventriculograms, myelograms, and lumbar punctures. See also PRECAUTION concerning increased intracranial pressure.
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diagnostic and operative procedures of the eye, ear, nose,
and mouth, including dental extractions.
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diagnostic and operative procedures of the pharynx, larynx,
or bronchial tree. NOTE: Muscle relaxants, with proper attention to respiration,
may be required (see PRECAUTIONS section).
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sigmoidoscopy and minor surgery of the anus and rectum, and
circumcision.
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extraperitoneal procedures used in gynecology such as dilatation
and curettage.
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orthopedic procedures such as closed reductions, manipulations,
femoral pinning, amputations, and biopsies.
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as an anesthetic in poor-risk patients with depression of
vital functions.
-
in procedures where the intramuscular route of administration
is preferred.
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in cardiac catheterization procedures.
In these studies, the anesthesia was rated either “excellent”
or “good” by the anesthesiologist and the surgeon at 90% and
93%, respectively; rated “fair” at 6% and 4%, respectively;
and rated “poor” at 4% and 3%, respectively. In a second method
of evaluation, the anesthesia was rated “adequate” in at least
90% and “inadequate” in 10% or less of the procedures.
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