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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