Ketamin

Pharmacokinetics
ABSORPTION
Ketamine is administered intravenously or intramuscularly (Table 87). Peak plasma
levels are usually achieved within 1015 min after intramuscular injection.

DISTRIBUTION
Ketamine is more lipid soluble and less protein bound than thiopental; it is equally
ionized at physiological pH.
These characteristics, along with a ketamine-induced increase in cerebral blood flow and
cardiac output, lead to rapid brain uptake and subsequent / yang kemudian di redistribution
(the distribution half-life is 1015 min).
Once again, awakening is due to redistribution to peripheral compartments.

BIOTRANSFORMATION
Ketamine is biotransformed in the liver to several metabolites, some of which (eg,
norketamine) retain anesthetic activity.
Induction of hepatic enzymes may partially explain the development of tolerance in patients
who receive multiple doses of ketamine.
Extensive hepatic uptake (hepatic extraction ratio of 0.9) explains ketamine's relatively short
elimination half-life (2 h).

EXCRETION
End products of biotransformation are excreted renally.
Effects on Organ Systems
CARDIOVASCULAR
In sharp contrast to other anesthetic agents, ketamine increases arterial blood pressure, heart
rate, and cardiac output (Table 88).
These indirect cardiovascular effects are due to
1. central stimulation of the sympathetic nervous system
2. and inhibition of the reuptake of norepinephrine.
Accompanying these changes are increases in pulmonary artery pressure and myocardial work.
For these reasons, ketamine should be avoided in patients with
1. coronary artery disease,
2. uncontrolled hypertension,
3. congestive heart failure,
4. and arterial aneurysms.
The direct myocardial depressant effects of large doses of ketamine, probably due to inhibition
of calcium transients, are unmasked by sympathetic blockade (eg, spinal cord transection) or
exhaustion of catecholamine stores (eg, severe end-stage shock).
On the other hand, ketamine's indirect stimulatory effects are often beneficial to patients with
acute hypovolemic shock.
RESPIRATORY
Ventilatory drive is minimally affected by the customary induction doses of ketamine,
although rapid intravenous bolus administration or pretreatment with opioids occasionally
produces apnea.
Ketamine is a potent bronchodilator, making it a good induction agent for asthmatic patients.
Although upper airway reflexes remain largely intact, patients at increased risk for aspiration
pneumonia should be intubated (see Case Discussion, Chapter 15).
The increased salivation associated with ketamine can be attenuated by premedication with an
anticholinergic agent.
CEREBRAL
Consistent with its cardiovascular effects, ketamine increases cerebral oxygen
consumption, cerebral blood flow, and intracranial pressure.
These effects preclude its use in patients with space-occupying intracranial lesions. Myoclonic
activity is associated with increased subcortical electrical activity, which is not apparent on
surface EEG.
Undesirable psychotomimetic side effects (eg, illusions, disturbing dreams, and delirium)
during emergence and recovery are less common in children and in patients premedicated
with benzodiazepines.
Of the nonvolatile agents, ketamine may be the closest to being a "complete" anesthetic as it
induces
1. analgesia,
2. amnesia,
3. and unconsciousness.
Drug Interactions
Nondepolarizing neuromuscular blocking agents are potentiated by ketamine (see
Chapter 9).
The combination of theophylline and ketamine may predispose patients to seizures.
Diazepam attenuates ketamine's cardiostimulatory effects and prolongs its elimination half-life.
Propranolol, phenoxybenzamine, and other sympathetic antagonists unmask the direct
myocardial depressant effects of ketamine.
Ketamine produces myocardial depression when given to patients anesthetized with halothane
or, to a lesser extent, other volatile anesthetics. Lithium may prolong the duration of action of
ketamine.