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Chapter: Modern Medical Toxicology: Neurotoxic Poisons: Inebriants

Chloral Hydrate - Inebriant Neurotoxic Poisons

Chloral hydrate (2,2,2,-trichloroacetaldehyde) is rarely used as a hypnotic today, but is a common adulterant of illicit liquor to enhance its intoxicating effect (Mickey Finn or Knock-outdrops).

Chloral Hydrate

Chloral hydrate (2,2,2,-trichloroacetaldehyde) is rarely used as a hypnotic today, but is a common adulterant of illicit liquor to enhance its intoxicating effect (Mickey Finn or Knock-outdrops). It is a white crystalline substance soluble in water oralcohol with a pungent, pear-like odour and bitter taste.

Chloral hydrate is well absorbed on oral administration and is quickly metabolised to trichloroethanol in the liver by alcohol dehydrogenase. This is the active form which is later conjugated with glucuronic acid and excreted in the urine as urochloralic acid. Chlorobutanol is structurally related to trichloroethanol, and is used as a sedative/hypnotic in doses of 300 to 1200 mg/day.

Chloral hydrate overdose manifests as nausea, vomiting, gastric irritation, miosis, hypotension, renal and hepatic damage, and cardiac arrhythmias (ventricular fibrillation, ventricular tachycardia, and torsades de pointes), cardiac arrest, respiratory depression, and coma. Non-cardiogenic pulmonary oedema and aspiration pneumonitis have been reported after massive overdose. Renal tubular toxicity may occur between 2 and 5 days following ingestion. Pupils are usually miotic initially, but later may be dilated. Breath may have a pear-like odour.

The usual fatal dose is around 10 grams, but deaths have occured with doses as low as 4 grams.

Chronic use of chloral hydratecan lead to a dependency syndrome with a withdrawal state similar to delirium tremens (convulsions and psychosis).

Chloral hydrate tablets and capsules may be visualised by X-ray. A simple diagnostic test involves the instillation of a small amount of the suspected liquid in 10 ml of water, to which 2 ml of purified aniline and 4 ml of 20% sodium hydroxide are added and heated gently. The evolution of a foul odour (skunkodour) is indicative of a positive result, which also occurs withchloroform and carbon tetrachloride. The test can also be done on 10 ml of distillate. Chloral hydrate and trichloroethanol in plasma can be analysed by gas chromatography.

Institute continuous cardiac monitoring and obtain an ECG after significant overdose. Monitor pulse oximetry and/or arte-rial blood gases in patients with CNS or respiratory depres-sion. Emesis is not recommended. Chloral hydrate is rapidly absorbed, particularly after ingestion of liquid formulations. Gastric lavage is also unlikely to be of benefit in most cases. If performed, lavage should be done carefully because of the risk of perforation. In the case of liquid ingestions a small flexible tube may be indicated to prevent oesophageal damage.

Treatment should be mainly directed at the management of cardiac arrhythmias which are potentially life- threatening. Unfortunately the arrhythmias are usually non-responsive to conventional anti-arrhythmic drugs, and a beta-adrenergic antagonist (non-cardioselective or beta1-specific), or adren-ergic neurone blocking drug such as bretylium may have to be administered. Propranolol has been the most commonly used beta adrenergic blocker for chloral hydrate-induced arrhyth-mias. Dose: 1 mg/dose intravenously, administered no faster than 1 mg/min repeated every 5 minutes until desired response is seen, or a maximum of 5 mg has been given. Esmolol, a short-acting beta -blocker, may be preferable to propranolol since it has rapid onset and short duration of action, enabling rapid attenuation of adverse effects if the patient’s status deteriorates. Dose: Infuse 500 mcg/kg for one minute. Follow loading dose with infusion of 50 mcg/kg per minute for 4 minutes. If inadequate response to initial loading dose and 4 minute maintenance dose, repeat loading dose (infuse 500 mcg/kg for one minute), followed by a maintenance infusion of 100 mcg/kg /min for 4 minutes. Re-evaluate therapeutic effect. If response is inadequate, repeat loading dose, and increase the maintenance dose by increments of 50 mcg/ kg/min, administered as above. Arrhythmias refractory to propranolol or esmolol may respond to lignocaine. Torsades de pointes usually responds to magnesium sulfate or isopro-terenol or amiodarone.

For hypotension, infuse 10 to 20 ml/kg of isotonic fluid and place in Trendelenburg position. Consider central venous pressure monitoring to guide further fluid therapy. If hypotension persists consider administering dopamine or noradrenaline. Caution: Catecholamines may precipitate ventricular arrhythmias in patients with chloral hydrate overdose.

Flumazenil (200 micrograms followed by three additional 100-microgram doses, at one minute intervals) may produce dramatic improvement in chloral hydrate poisoning according to some investigators.

Haemodialysis and haemoperfusion have been advocated as beneficial, and may be useful in a patient unresponsive to normal supportive care, or in whom acid-base or fluid and electrolyte problems may become uncontrollable.

Sudden withdrawal from chronic chloral hydrate use can result in delirium and convulsions, which may have to be managed with barbiturates or other sedative-hypnotic drugs.

·              There are indications that chloral hydrate may be carci-nogenic.

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