Synthesised by Justin Liebig in 1832
chloral hydrate is one of the oldest synthetic agents. Since 1869 it has been in use for
hypnotic or
sedative purposes.
Chloral hydrate was used a lot from the end of the 19th century to the middle of the 20th century. Since then
chloral hydrate has been less frequently in use as a
hypnotic. In the 1990's, the principal use of
chloral hydrate in pediatrics was the sedation of children for
minor surgery during dental or diagnostic procedures. In general practice, it is an
analgesia found in topical preparations. It was known as safe and easy to use. Now it is shown to be potentially dangerous (risk of death in case of intoxication) and there is doubt about genotoxicity and carcinogenecity. The pharmacological property was known in 1948 when Butler discovered the principal active metabolite,
trichloroethanol. The gastro-intestinal tract rapidly absorbs
chloral hydrate after oral or rectal use. The
sedative and hypnotic effects appear in 20 to 60 minutes. The main metabolites [
trichloroethanol (TCE) and
trichloroacetic acid (TCA)] are formed by hepatocytes and erythrocytes. The half-life of
chloral hydrate is short (a few minutes), the half lives of the metabolics are longer, 8 to 12 hours for TCE and 67 hours for TCA. The affinity for
lipids is high. It is eliminated principally by the kidneys. Its mechanism of action is unknown. It is a depressor of the SNC, and the sedation is attributed to
chloral hydrate and the
hypnotic effect to TCE. The interactions appear with: alcohol,
anticoagulants,
amitriptyline and
furosemide. The use of
flumazenil (a
gaba antagonist), in case of intoxication, indicates a possible action of
GABA. The posology is usually between 0.5 to 2 g per day.
Chloral hydrate is taken during meals to prevent gastric irritation. The main side effects are digestive, cardiologic (risk of rhythm disorder), dermatologic, neuropsychiatric (withdrawn, delusions,
hallucination, dependence) and ophthalmologic. Death occurs after absorption of doses of around 10 g of
hydrate chloral, some cases were reported with 5 g. The use of
hydrate chloral is contra-indicated in cases of
gastric ulcers,
hepatic insufficiency, porphyry,
respiratory insufficiency, association with
anticoagulants and hyper sensibility. Nowadays should we be using
chloral hydrate in cases of
insomnia in adult and older people? A recent preclinical working group of the French Agency for evaluation of medicinal products reassessed the benefit/risk ratio of
chloral hydrate. Many references are found about genotoxicity and carcinogenicity in recent literature. In France, since the end of 2000,
chloral hydrate has been withdrawn from many medications for external use in dermatology and in
stomatology.
Chloral hydrate can be used as a pediatric
sedative only once in a lifetime. The psychiatric indication for
insomnia is no longer justified and especially in older people.