Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CHAPTER 5 ANESTHETIC AGENTS
Pharmacokinetics
Ketamine rapidly crosses the blood–brain barrier to
induce anesthesia; however, the onset time is slower
than with thiopental. After intramuscular or subcutaneous
injection, 10–15 min elapse before sedation or anesthesia
develops. The duration of anesthesia is dose
dependent and lasts for 5–15 min after a single intravenous
dose. Termination of anesthesia is due to redistribution
from the brain and plasma to other tissue.
Ketamine is metabolized in the liver, producing a
number of metabolites. Some, e.g. norketamine, have
anesthetic activity. Induction of hepatic enzymes occurs
with chronic administration of ketamine and higher
doses may be required when it is given repeatedly.
Hepatic dysfunction can prolong the action of ketamine
and the drug should be used with caution in patients
with a hepatopathy.
Ketamine and its metabolites, including norketamine,
are excreted in urine. Despite this, diuresis does not
enhance elimination although a prolonged effect may be
seen in animals with renal insufficiency. Prolonged
recoveries may also occur after multiple doses, intramuscular
or subcutaneous administration and following
the concurrent use of other sedative and anesthetic
agents.
Adverse effects
Central nervous system effects
● Ketamine increases cerebral blood flow and thereby
raises intracranial pressure. Combination with a
benzodiazepine lessens the rise in ICP. The provision
of intermittent positive pressure ventilation (IPPV)
to prevent hypercapnia may also attenuate this
response.
● Ketamine can induce seizures, especially if used alone
in dogs. Seizures have also been reported following
the administration of atipamezole to dogs anesthetized
with a combination of an α 2 -agonist and
ketamine. It is possible that early reversal of the α 2 -
agonist leaves the ketamine action unopposed by a
suitable sedative. Although anticonvulsant effects
have also been documented it would seem sensible
to avoid ketamine in patients with epilepsy and those
undergoing myelography.
● Adverse emergence reactions with excitement,
hallucinatory behavior, ataxia and increased muscle
activity are occasionally seen during recovery from
ketamine, used alone or in combination with a
benzodiazepine. Sedative premedication reduces the
incidence and severity of such side effects.
Cardiovascular effects
Ketamine has a two-fold effect on the cardiovascular
system.
● It has a direct depressant effect on myocardial function
and an indirect stimulatory effect mediated
by increased sympathetic nervous system activity.
Normally the latter action dominates and heart rate,
cardiac output and arterial blood pressure all increase
slightly after ketamine administration. Peripheral
vascular resistance is usually unchanged. These stimulating
effects may be diminished or prevented by
the concurrent administration of other drugs. Of
these, the benzodiazepines have the least effect and
α 2 -agonists and halothane the greatest effect.
● Ketamine alone appears to have an antiarrhythmic
effect but concurrent administration of halothane
reduces the cardiac threshold for adrenaline
(epinephrine)-induced arrhythmias.
● Overall, ketamine appears to produce minimal cardiovascular
depression and can be administered to many
patients with cardiovascular disease. Occasionally
critically ill patients appear to decompensate when
ketamine is given. If catecholamine stores have been
depleted, e.g. patients in end-stage shock, further
increases in sympathetic activity are not possible and the
direct depressant effects of ketamine may be unmasked.
A similar phenomenon may occur if sympathetic antagonists
such as propranolol are given concurrently.
Respiratory effects
● Transient respiratory depression occurs and hypoxia
is possible in the animal breathing room air. The
severity of the respiratory depression is dependent on
the dose administered and the concurrent administration
of other sedative and anesthetic agents. The
benzodiazepines cause little additional respiratory
depression whereas the α 2 -agonists, opioids and
inhalational agents can cause greater depression.
● An apneustic respiratory pattern, whereby the patient
breath-holds on inspiration, has been described but
is not frequently seen in small animals.
Hepatic effects
● Ketamine appears to have no effect on hepatic
function.
● Ketamine is metabolized in the liver and hepatic
dysfunction can result in a prolonged action.
Renal effects
● Ketamine appears to have no direct effect on the
kidney but anesthetic-induced hypotension can
result in compromised renal function.
● Animals with renal or postrenal disease can have a
prolonged recovery time.
Skeletal muscle effects
● Ketamine alone can induce extreme muscle tone and
spontaneous movement that is reduced by the concurrent
use of a sedative.
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