Chloral Hydrate

Chloral hydrate is used in paediatrics undergoing procedures. It was withdrawn from the adult arena due to the narrow therapeutic index. In overdue it causes rapid CNS depression, cardiac dysrhythmias and these are lethal without prompt intervention.Chloral hydrate comes in 200ml bottles, 1g/10ml

Toxic Mechanism:

In brief the mechanism is unclear. Cardiac dysrhythmias are thought to be caused by sensitisation of the myocardium to circulating catecholamines.

Toxicokinetics: 

• Rapid absorption following oral administration
• Converted to its active metabolite trichloroethanal (TCE) by hepatic alcohol dehydrogenase. TCE conjugates with glucuronic acid and is then excreted in the urine and to a small extent the bile.
• Chloral hydrate has an elimination half-life of 4-5 minutes, TCE 8-12 hours but in overdose this extends up to 35+ hours.

Resuscitation:

• CNS depression:
  • At the first signs of CNS depression or cardiovascular toxicity the patient requires intubation and ventilation.
• Tachydysrhythmias:
  • Beta Blockers are recommended (one of the few times in toxicology and even treated Tornado de pointes) to suppress the catecholamine surge.
  • Propranolol 0.5 – 1 mg or
  • Metoprolol 5mg (0.1 mg/kg in children) by slow IV and repeat after 5 mins until adequate response
  • An esmolol infusion can then commence at a concentration of 10 mg/ml in 5% dextrose. Commence rate at 0.05 mg/kg/minute (20ml/hour in a 70kg adult). Titrate to response.
• Hypotension:
  • 20ml/kg of crystalloid.
  • Catecholamines are contraindicated in chloral hydrate toxicity.

Risk Assessment

• >100mg/kg, i.e. twice the upper limit of therapeutic dosing is associated with coma and cardiac dysrhythmias.
• In overdose the patient will have life-threatening toxicity within 30 mins
• CNS:
  • Drowsiness, lightheadedness, ataxia followed rapidly by coma and respiratory depression
• Cardiovascular:
  • Multifocal premature ventricular ectopics
  • Atrial fibrillation
  • Supra ventricular tachycardia
  • Ventricular tachycardia
  • Ventricular Fibrillation
  • Torsades de pointes (in this case rarely responds to magnesium or overdrive pacing – needs beta-blockers)
  • Asystole
• Hypotension
• Hypothermia
• Gastrointestinal
  • Corrosive injury including necrosis or perforation leading to permanent stricture formation.

Supportive Care

• General supportive measures (i.e. IV fluids only if dehydrated), monitor for urinary output.
• If intubated see FASTHUGSINBED for further supportive care.

Investigations

• Screening: 12 lead ECG, BSL, Paracetamol level
• Specific:
  • Continued ECG monitoring to look for dysrhythmias
  • TCE levels can be done but are usually returned in retrospect, can be used in forensic cases.
  • Gastroscopy maybe indicated if there are GI symptoms.

Decontamination:

• Activated charcoal maybe given once the patient is intubated but should never take precedence over resuscitation. If there is a suspected corrosive injury then it should be avoided.

Enhanced Elimination

• TCE can be eliminated via haemodialysis but the above interventions usually stabilise the patient rendering haemodialysis unnecessary. Can be considered if the above interventions fail.

Antidote

• Not clinically useful

Disposition

• All ingestions require assessment and observation in hospital with close cardiac monitoring for at least 2 hours.
• Patients who develop CNS depression, cardiac instability require an admission to intensive care (usually intubated).

References and Additional Resources:

Additional Resources:

• Tox conundrum on Chloral hydrate

References:

• Graham SR, Day RO, Lee R et al. Overdose with chloral hydrate: a pharmacological and therapeutic review. Medical Journal of Australia 1988; 149:686-688
• Murray L et al. Toxicology Handbook 3rd Edition. Elsevier Australia 2015. ISBN 9780729542241
• Perched J, Palminsano P, Nicholas M. Chloral Hydrate: the good and the bad. Paediatric Emergency Care. 1999; 15:432-435
• Sing K, Ericsson T, Amitai Y et al. Chloral hydrate toxicity from oral and intravenous administration. Journal of Toxicology – Clinical Toxicology 1996; 34:101-106
• Zahedq A, Grant MH, Wong DT. Successful treatment of chloral hydrate cardiac toxicity with propranolol. American Journal of Emergency Medicine 1999; 17(5):490-491

Wikipedia list of some famous users

• The Jonestown mass suicides, which involved the communal drinking of Flavor Aid poisoned with Valium, chloral hydrate, cyanide, and Phenergan
• Anna Nicole Smith (1967–2007) who died of an accidental combination of chloral hydrate with four benzodiazepines and several other drugs, as announced by forensic pathologist Dr. Joshua Perper on 26 March 2007. Chloral hydrate was the major factor, but it was unclear if any of these drugs would have been sufficient by itself to cause her death.
• Marilyn Monroe had chloral hydrate in her system at her death.
• Hank Williams came under the spell of a man calling himself “Doctor” Toby Marshall (actually a paroled forger), who often supplied him with prescriptions and injections of chloral hydrate, which Marshall claimed was a pain reliever, to deal with the pain from Williams’ lifelong severe back problems.
• Friedrich Nietzsche regularly used chloral hydrate in the years leading up to his nervous breakdown, according to Lou Salome and other associates. Whether the drug contributed to his insanity is a point of controversy.
• Oliver Sacks abused chloral hydrate in 1965 as a depressed insomniac. He found himself taking fifteen times the usual dose of chloral hydrate every night before he eventually ran out, causing violent withdrawal symptoms.