Ketamine

Ketamine is phencyclidine derivative. Ketamine is the closest to being a "complete" anesthetic as it induces analgesia, amnesia, and unconsciousness.

Mechanisms of Action

· Ketamine functionally "dissociates" the thalamus from the limbic cortex .Thalamus relays sensory impulses from the reticular activating system to the cerebral cortex and limbic cortex is involved with the awareness of sensation.

· Ketamine produces dissociative anesthesia. The patient appear conscious (eg, eye opening, swallowing, muscle contracture) but unable to process or respond to sensory input and in a state of dissociation from surroundings.

· Ketamine is an N-methyl-D-aspartate receptor (a subtype of the glutamate receptor) antagonist.

· Ketamine blocks polysynaptic reflexes in the spinal cord and inhibits excitatory neurotransmitter effects in selected areas of the brain.

Pharmacokinetics

Absorption

Ketamine is administered intravenously or intramuscularly. Peak plasma levels are usually achieved within 10–15 min after intramuscular injection.

Distribution

Ketamine is more lipid soluble and less protein bound than thiopentone. Distribution half-life is 10–15 min. Awakening is due to redistribution.

Metabolism

Ketamine is metabolized in the liver; some of the metabolites (eg, norketamine) have anesthetic activity. Development of tolerance is seen which is due to hepatic enzyme induction. Elimination half-life is short 2 hours.

Extensive hepatic uptake (hepatic extraction ratio of 0.9) explains ketamine's relatively short .End products of biotransformation are excreted renally.

Effects on body Systems

Cardiovascular

1. Ketamine increases arterial blood pressure, heart rate, and cardiac output due to central sympathetic stimulation and inhibition of norepinephrine reuptake. So it is the induction agent of choice for patients in shock.

2. Ketamine is avoided in patients with coronary artery disease, uncontrolled hypertension, congestive heart failure and arterial aneurysms.

3. Direct action of ketamine is myocardial depressant at high doses.

Respiratory

1. Respiration is minimally affected by induction doses of ketamine.

2. Ketamine is a potent bronchodilator, making it a good induction agent for asthmatic patients. Although upper airway reflexes remain intact, But not sufficient to prevent aspiration pneumonia in high risk (like potentially full stomach) patients.

3. Salivation is increased with ketamine. Premedication with an anticholinergic agent (glycopyrolate or atropine) can prevent it.

Cerebral

1. Ketamine increases cerebral oxygen consumption, cerebral blood flow, and intracranial pressure.

2. Ketamine should be avoided in patients with space-occupying intracranial lesions.

3. Ketamine hallucination-

· Ketamine may cause psychotomimetic side effects (eg, illusions, disturbing dreams, and delirium) during emergence and recovery.

· Less common in children.

· Premedication with benzodiazepines can prevent it.