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Chapter: Modern Medical Toxicology: Neurotoxic Poisons: Anaesthetics and Muscle Relaxants

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Ketamine - Intravenous Anaesthetics

Ketamine is a phencyclidine derivative chemically related to cyclohexamine.

Ketamine

Ketamine is a phencyclidine derivative chemically related to cyclohexamine.

Uses

·     Ketamine is a general anaesthetic that is rapid acting, producing profound analgesia with normal laryngeal-phar-yngeal reflexes, skeletal muscle tone, and cardiovascular and respiratory stimulation. When given intravenously, it induces sedation associated with immobility, amnesia, and analgesia (dissociative anaesthesia).

·     Ketamine is popular as an anaesthetic in cases of trauma and emergency surgical procedures.

·     It is also frequently used for short-term sedation during clinical procedures; most frequently in the paediatric population.

Toxicokinetics

·              Onset of effects after IV administration is 30 to 40 seconds, and after IM administration, 3 to 8 minutes. The duration of unconsciousness following the usual anaesthetic dose (vide infra) is about 40 to 60 minutes.

·              Ketamine undergoes first-pass metabolism by the liver necessitating higher doses when taken by the oral or rectal route. It undergoes N-demethylation by the cytochrome P450 system to form norketamine. Norketamine is an active metabolite with an anaesthetic potency one-third that of ketamine.

Adverse Effects

·              During the period of unconsciousness, patients are usually noncommunicative though the eyes may be open and they appear to be awake. Skeletal muscle spasm is often present.

·              Following usual anaesthetic doses, side effects include significant transient increases in blood pressure and heart rate, respiratory depression, airway obstruction, apnoea, muscular hypertonus, psychomotor, psychomimetic, and acute dystonic reactions.

·              Ketamine elevates intracranial and intraocular pressure.

·              Mydriasis and nystagmus may occur.

·       Emergence phenomena are also commonly reported char- acterised by vivid dreams, nightmares, hallucinations, screaming, crying, disorientation, and delirium. They can be minimised by concomitant administration of a benzodi-azepine. Nightmares following ketamine use sometimes lastfor several days to weeks. Children and the elderly seem less sensitive to these effects.

·              Ketamine must not be used for anaesthetic purposes in alcoholics since exaggerated psychotomimetic effects are commonly precipitated in such individuals during the recovery phase.

Clinical (Toxic) Features

Overdose is associated with convulsions, hypertension, tachy-cardia, and respiratory depression. The usual anaesthetic dose of ketamine is 2 mg/kg IV or 5 to 10 mg/kg IM.

Usual Fatal Dose

·              The minimal toxic or lethal dose is not well established in the literature. Deaths have been reported in adults following doses of 900 to 1000 mg.

Treatment

·      Treatment of the adverse and toxic effects of ketamine involves mainly symptomatic and supportive measures. Plasma ketamine levels are not clinically useful. Airway control and ventilatory support are essential.

·      Seizures and panic attacks must be treated with benzodi-azepines; dystonic reactions respond to diphenhydramine (5 to 50 mg IV over 2 minutes) or benztropine.

·      Droperidol intravenous administration as a pre-anaesthetic agent in doses of 75 mcg/kg has been reported to be effec-tive in reducing the incidence of psychotomimetic and circulatory side effects of ketamine. However, based on cases of QT prolongation and/or torsades de pointes in patients receiving droperidol at doses at or below recom-mended dosing, it should be reserved for use in patients who fail to show an acceptable response to other agents.

·      Alpha and beta blocking agents, benzodiazepines, and vera-pamil have been shown to block cardiovascular stimulation. Pulmonary hypertension and pulmonary oedema may be reversed by fentanyl.

·      There is evidence to suggest that 4-aminopyridine reverses most of the effects of ketamine toxicity.

·      Atropine or glycopyrrolate can help in reducing tracheo-bronchial secretions.

·              Physostigmine has been suggested in the management of phencyclidine overdose, but there is little evidence that indicates physostigmine is of value in the treatment of ketamine overdose and it is NOT recommended.

Forensic Issues

·              Ketamine is increasingly gaining popularity as a recre- ational drug and is employed in “rave” parties for its disso- ciative hallucinatory effects. It is usually taken intranasally or by inhalation, but may also be injected (IM or IV). It is |most commonly taken in powdered form and either mixed in a drink or snorted.

·              Slang names: K, Kay, K-amine, Special K, Vitamin K, Ketaset, Green, Jet, Mauve, Purple, Special LA coke, Super acid, Super C.

·              Ketamine has become popular in the teen and young adult culture because of its unique combination of hypnotic, analgesic and amnesic effects with limited respiratory depression. It can produce a "dissociative" effect which is characterised by analgesia and amnesia without causing a loss of consciousness. Users describe the effects of ketamine as an “out of body” experience or “near death”, characterised by exhilarating sensations of immobility and a disregard for death.

·              Other common effects include tachycardia, altered mental status, anxiety, palpitations, slurred speech, hallucinations, nystagmus, mydriasis, mild hypertension, and chest pain. Ketamine may produce bronchodilation and increased salivary and tracheobronchial secretions. Confusion, vomiting and memory loss are less common. Rarely seizures, polyneuropathy, or respiratory arrest may occur. Epistaxis and anosmia (loss of sense of smell) have been reported following chronic snorting of ketamine. Death is rare following ketamine abuse or overdose.

·     Ketamine crosses the placenta. Severe adverse effects on the infant, including respiratory depression, have been reported following ketamine use for obstetric analgesia.

 

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