Chloral Hydrate Toxicity

Case

#1 A 4 year old girl was prescribed chloral hydrate to be taken at home prior to a procedure by her dentist. After a successful procedure, she was monitored for 1 hour, at which point she was described as tired but rousable and she was discharged home. Three hours later her mother finds her unresponsive and calls 911. Paramedics arrive to find a child in respiratory arrest and quickly package her up for the 5 minute drive to your small community hospital… (Nordt 2014)

#2 Later that evening, a 21 old man is transported from a local bar unresponsive after drinking a beer. The monitor reveals a wide complex tachycardia. There is a faint odor of pears on his breath, which triggers a vague recollection from medical trivia night. You have a nurse talk to his friends, and sure enough, they admit to slipping him a “Micky Finn” as a prank…

My approach

Although I usually jump right into management, chloral hydrate is used pretty rarely these days, so many of us aren’t that familiar with its presentation. Chloral hydrate is metabolized into trichloroethanol, which binds to GABA receptors, resulting in CNS depression. (Gussow 2014) Ataxia is also possible. It can cause hypotension and myocardial depression, but the most important cardiovascular side effects are tachydysrhythmias because of catecholamine hypersensitivity. (Nordt 2014) Gastrointestinal complications are common, including erosive gastritis, GI bleeding, and vomiting. (Nordt 2014) Chloral hydrate is also directly nephrotoxic and can cause hepatitis. A fruity or pear like smell on the breath is classic.

The first steps in management should focus on the basics of resuscitation: ensuring the patient has a patent airway and adequate ventilation while monitors and IV access are initiated. Significant CNS depression may require intubation and mechanical ventilation, but basic airway maneuvers are often enough during the first 10 minutes of stabilizing the patient.

After rapidly assessing the ABCs, and remembering to check a sugar in this patient with altered mental status, you can turn your attention to the toxicology. Always consider co-ingestants. The patient might benefit from one of the “universal antidotes” (dextrose, oxygen, naloxone, or thiamine), but probably not. There is no specific antidote for chloral hydrate, but there has been a case report of reversal with flumazenil. (Nordt 2014) In mixed or unknown overdoses, I would not use flumazenil. However, if it is a pediatric patient not on other medications for whom the chloral hydrate was used as a single sedation agent, an empiric trial of flumazenil might make sense before intubation.

Decontamination is always a consideration with overdose patients, but doesn’t really have a role here. Charcoal should not be used as chloral hydrate is very rapidly absorbed and can cause significant mucosal corrosive injury.

Ventricular arrhythmias, including torsades de pointes

Immediately cardioversion is appropriate for any unstable patient with a wide complex tachycardia (or defibrillation in the absence of a pulse). However, in the presence of chloral hydrate, dysrhythmias are very likely to recur. Antiarrhythmics such as lidocaine are unlikely to be helpful. (Zahedi 2014; Gussow 2014) The treatment of choice in this case is a beta-blocker, and in particular something short acting and easily titratable, such as esmolol. (Nordt 2014; Gussow 2014) Torsades de pointes should be treated as usual, with magnesium and overdrive pacing as necessary, but the beta-blocker should still be your first priority. (Gussow 2014)

Hypotension

Management of hypotension should focus primarily on ruling out arrhythmias and providing fluid boluses. Catecholamines should be avoided if possible, because of the increased chance of dysrhythmias. (Gussow 2014)

Hemodialysis and hemoperfusion

Trichloroethanol (the active metabolite of chloral hydrate) has a long half life, a large molecular weight, and low plasma protein binding. This makes it a good candidate for dialysis, so if the patient is sick, get on the phone with a toxicologist and a nephrologist for further guidance. (Nordt 2014; Zahedi 2014)

Notes

Maybe the most important note is this quote from the Nordt paper: “Chloral hydrate is an older medication, which in our opinion should no longer be used for procedural sedation in patients of any age.” (Nordt 2014) [emphasis added]

The “Mickey Finn” – a classic laced drink given to someone to incapacitate them – is a combination of ethanol and chloral hydrate. (Gussow 2014)

The half-life of trichloroethanol is 8-12 hours, but can be as long as 35 hours in acute overdoses. (Nordt 2014)

Chloral hydrate is a halogenated hydrocarbon. The life threatening dysrhythmias seen are the result of increased sensitivity to endogenous catecholamines, much like we see in patients abusing inhaled hydrocarbons. (Nordt 2014; Zahedi 2014) Potentially lethal dysrhythmias can occur at doses very close to therapeutic doses.

Chloral hydrate is more rapidly absorbed in a non-fasted state. (Nordt 2014)

Although I have no confirmatory sources, there are a number of famous individuals who have apparently used (or misused) chloral hydrate. Marilyn Monroe had chloral hydrate in her system at the time of her death. Anna Nicole Smith died of an overdose when chloral hydrate was combined with a number of benzodiazepines, and some other drugs. Oliver Sacks and Friedrich Nietzsche were both reported to have abused the drug. Finally, chloral hydrate was one of the ingredients in the famous ‘kool-aid’ used in the mass suicides in Jonestown.

Find this post helpful? Check out the other First10EM toxicology posts.

Other FOAMed Resources for Chloral Hydrate

EMCases Best Case Ever Series: Chloral Hydrate Poisoning and Cardiac Arrest

Chloral hydrate overdose on Life in the Fastlane

Overdose and death from pediatric chloral hydrate sedation on The Poison Review

References

Gussow L and Carlson A. Chapter 165. Sedative Hypnotics. In: Marx JA et al. eds. Rosen’s Emergency Medicine, 8e. Philadelphia: Elsevier Saunders; 2014.

Nordt SP, Rangan C, Hardmaslani M, Clark RF, Wendler C, Valente M. Pediatric chloral hydrate poisonings and death following outpatient procedural sedation. Journal of medical toxicology : official journal of the American College of Medical Toxicology. 10(2):219-22. 2014. [pubmed]

Zahedi A, Grant MH, Wong DT. Successful treatment of chloral hydrate cardiac toxicity with propranolol. The American journal of emergency medicine. 17(5):490-1. 1999. [pubmed]