KETAMINE

Ketamine anesthesia is a valuable tool in medicine due to its unique properties and advantages, especially in certain clinical scenarios. Some of the key reasons for its importance include:

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1. Dissociative anesthesia: Ketamine provides a state of dissociative anesthesia, where the patient remains unconscious while maintaining some degree of spontaneous respiration. This is particularly useful in situations where intubation or mechanical ventilation is not feasible or desired.

2. Analgesia: Ketamine has strong analgesic properties, making it an effective pain reliever, even at sub-anesthetic doses. This can be beneficial in managing acute and chronic pain, as well as in procedures that require potent analgesia.

3. Hemodynamic stability: Ketamine has a unique effect on the cardiovascular system, causing an increase in blood pressure and heart rate. This can be advantageous in patients with hypotension or shock, where other anesthetic agents may worsen their condition.

4. Bronchodilation: Ketamine can induce bronchodilation, which can be beneficial in patients with asthma or other respiratory conditions. This property makes it a preferred anesthetic agent in patients with a history of bronchospasm or reactive airway disease.

5. Pediatric use: Ketamine is well-tolerated in children and is often used for sedation and anesthesia in pediatric cases. Its rapid onset and short duration of action make it suitable for various procedures in children.

6. Low-resource settings: Ketamine can be administered via several routes (intravenous, intramuscular, oral, and others), making it a versatile option in low-resource settings where advanced equipment may not be available.

7. Psychiatry: Research has shown that low doses of ketamine can provide rapid and effective relief from severe depression and suicidal ideation. This has led to an increased interest in its potential as a novel antidepressant agent.

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Here are the main steps in ketamine's mechanism of action:

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1. NMDA receptor antagonism: Ketamine acts as a noncompetitive antagonist at the NMDA receptor, which is a type of ionotropic glutamate receptor in the central nervous system. By blocking the NMDA receptor, ketamine inhibits the excitatory effects of glutamate, the primary excitatory neurotransmitter in the brain.

2. Disruption of neuronal communication: The antagonism of NMDA receptors by ketamine disrupts the normal flow of electrical signals between neurons. This leads to a dissociative state, characterized by a sense of detachment from the body and the environment, as well as altered perception and cognition.

3. Modulation of other neurotransmitter systems: In addition to NMDA receptor antagonism, ketamine also interacts with other neurotransmitter systems, including opioid, monoaminergic, and cholinergic systems. These interactions may contribute to ketamine's analgesic, sedative, and psychotomimetic effects.

4. Indirect effects on neuronal plasticity: Ketamine has been shown to increase the expression of brain-derived neurotrophic factor (BDNF) and other neurotrophic factors, which play a role in neuronal plasticity and survival. This effect has been linked to ketamine's rapid antidepressant properties observed in some clinical studies.

5. Analgesic effects: The exact mechanism of ketamine's analgesic effects is not fully understood but is believed to involve NMDA receptor antagonism, as well as its interaction with other neurotransmitter systems, such as the opioid and monoaminergic systems.

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                                                                                                         Key points about Ketamine

• Ketamine is a phencyclidine derivative.

• NMDA receptor antagonist.

• Ketamine is supplied as the racemic mixture of two optical isomers (enantiomers).

• Ketamine produces a dissociative state of anesthesia.

• It produces a catatonic state in which the patient appears conscious (eye opening, swallowing, muscle contracture) but unable to process and respond to sensory stimuli.

• May cause nystagmus and increased intraocular pressure.

• The patient maintains the cough, corneal, and swallow reflexes.

• Ketamine produces profound analgesia and amnesia.

• Ketamine has anti-inflammatory effects due to inhibition of tumor necrosis factor-alpha (TNF-alpha) and interlukin-6 (IL-6).

• The metabolite norketamine is approximately 20% to 30% of the activity of ketamine.

• Cerebral blood flow (CBF) and cerebral oxygen consumption (CMRO2) are increased by ketamine.

• Ketamine increases pulmonary compliance and decreases pulmonary resistance (potent bronchodilator).

• Good induction agent for asthmatic patients.

• Minimal effect on the central respiratory drive. Although, combination of ketamine with opioids may produce apnea.

• Stimulates the sympathetic nervous system and inhibits the reuptake of norepinephrine after release at nerve terminals.

• Ketamine increases arterial blood pressure, heart rate, and cardiac output.

• Increases lacrimation and salivation can increase the risk of laryngospasm. This attenuated by premedication with an anticholinergic agent such as glycopyrrolate.

• Ketamine is useful for intramuscular induction in children and uncooperative adults.

• Repeated doses of ketamine (daily changing of dressings on burns) can result in development of tolerance and induction of hepatic enzymes.

• Sympathetic blockade or depleted catecholamine stores may unmask the direct myocardial depressant effects of ketamine.

• Alpha-adrenergic and beta-adrenergic antagonists may unmask the direct myocardial depressant effects of ketamine.

• Undesirable psychotomimetic side effects disturbing dreams, delirium, and hallucinations) may occur.