Chloral hydrate (CH) is a hydrocarbon historically used as a sedative, hypnotic, and anxiolytic agent mainly in radiological imaging procedures.1–3 Cardiac arrhythmias have been reported even with therapeutic doses of CH with a risk of sudden death,4 which made CH less commonly used as sedative agents.5

The half-life of CH is 30–60 minutes, but its active metabolite trichloroethanol duration of action lasts for more than eight hours and up to 35 hours at higher doses.4,6

Acute poisoning with CH causes significant central nervous system (CNS) depression, respiratory failure, and tachyarrhythmias. The other reported side effects are gastric irritation and vomiting.7,8 The common cause of death due to CH toxicity is cardiac arrhythmia and unrecognized respiratory arrest due to CNS depression.7

CH induced cardiac arrhythmias are usually refractory, which are unresponsive to standard antiarrhythmic drugs including amiodarone and lidocaine.6,7,9,10 However, β-blockers have been reported to be an effective treatment of hydrocarbon-induced cardiotoxicity, including CH.11–13

We report a case of CH poisoning with cardiac arrest and complete recovery.

Case report

A 23-year-old woman, with no significant medical history, was brought to the emergency department after being found unresponsive at home. Her family found medication strips of paracetamol and diclofenac beside her. Her initial vital signs at presentation were as follows: pulse rate of 95 beats per minute; blood pressure of 109/83 mmHg; respiratory rate 25 breaths per minute; and a temperature of 37 oC. Her initial physical exam was unremarkable apart from a low Glasgow coma scale of 7/15 with normal size reactive pupils. Due to her CNS depression, she was intubated and mechanically ventilated.
A nasogastric tube was inserted, and gastric lavage was done with pinkish fluid and some particles coming out. Analysis of the contents of gastric lavage was not possible.

Electrocardiogram (ECG) at the time of presentation showed multiple premature ventricular contractions [Figure 1]. ECG repeated 30 minutes later showed prolonged QT interval [Figure 2]. Her arterial blood gas showed metabolic and respiratory acidosis with a pH = 7.16; pO2 = 82 mmHg; pCO2 = 53 mmHg; and bicarbonate = 16 mmol/L. The toxicology screening for tricyclic antidepressants, salicylates, benzodiazepines, acetaminophen, morphine, cocaine, marijuana, phencyclidines, amphetamines, methadone, and barbiturates were all negative. Brain computed tomography [Figure 3] and chest radiography were also unremarkable. All her laboratory investigations were normal apart from low bicarbonate (17 mmol/L) and elevated lactate (3.5 mmol/L).

Within nine hours of hospital presentation, she had multiple episodes of ventricular fibrillation (VF) requiring cardiopulmonary resuscitation. Her VF was refractory to the standard advanced cardiac life support protocol including epinephrine, amiodarone, and defibrillations. A clinical toxicologist was consulted, and due to the combination of cardiotoxicity and sedation, hydrocarbon poisoning was considered. Esmolol (β-blocker) infusion was started with a dose of 150 µg/kg/min following an intermittent bolus dose of 30 mg to a total bolus dose of 150 mg, and shortly after, she reverted to sinus rhythm.

She developed hypotension and was supported initially with intravenous fluid resuscitation and norepinephrine infusion, but following her cardiac arrest, it was changed to phenylephrine infusion. Later her sister brought the patient’s bag that had a bottle of water with pinkish fluid inside, smelling like CH. There was no toxicological test available for CH confirmation. Over the next 36 hours, the patient’s neurological and cardiac status had normalized, and she was extubated successfully and was weaned from phenylephrine and esmolol infusion. She was discharged from the hospital in good condition on day five after psychiatric review. She confirmed the ingestion of around 30–35 g of CH.

Discussion

This case represents significant lethal ingestion of CH causing cardiac arrest with a favorable outcome. Although the dose considered to be fatal for CH is about 10 g, fatalities have been documented with ingestion of as little as 4 g and the recovery of a patient following ingestion of 30 g CH was also reported.1,12 Table 1 shows reported cases of CH overdose.

CH overdose is known to cause tachy-arrhythmias.18,19 Our patient suffered significant cardiotoxicity ranging from sinus tachycardia, multiple atrial and ventricular ectopics, prolonged QT interval, and eventually VF. CH and its metabolites-induced cardiotoxicity could be explained by many mechanisms. One of the suggested effects is the reduced conduction velocity, which causes conduction defects like atrioventricular and intraventricular conduction delays, which can cause re-entrant arrhythmias.18 Other suggested effects are increased automaticity of the supraventricular and ventricular pacemaker cells and sensitization of the myocardium to the circulating catecholamine.9,20

CH induced VF in our patient did not respond to standard antiarrhythmic drugs but responded well to β-blockers. CH induced arrhythmias have been reported to be refractory to the standard antiarrhythmic medications.9,10 A failure to control CH induced arrhythmias with lidocaine was reported in two out of five patients with CH overdose.9 Others have reported partial response with lidocaine.10

A case series of CH overdose showed that VT control was achieved in more than 80% of patients by β-blockers where other antiarrhythmic drugs had failed.12 In general, β-blockers use for CH induced refractory arrhythmias has been reported to be effective.4,9,11–13,17,21 Esmolol infusion was very effective in controlling our patient’s tachyarrhythmias and was reported to be effective in other case reports.4,21

Paracetamol and diclofenac tablets found beside our patient were thought to be the culprit of her symptoms by her family. However, neither could explain her presentation especially with negative paracetamol levels and the presence of significant cardiac toxicity. The combination of CNS depression with refractory arrhythmias made hydrocarbon toxicity likely.

Of note, due to CH toxicity induced hypersensitivity to catecholamines, norepinephrine infusion was changed to phenylephrine, which is a selective α agonist.22 Fortunately, our patient did not develop any hepatotoxicity, which has been reported with CH overdose.23

Our patient survived a massive ingestion of CH and had an excellent outcome despite serious cardiotoxicity and cardiac arrest due to prompt recognition and good supportive and specific care.

Conclusion

CH toxicity usually presents with CNS depression and cardiac toxicity; hence, emergency physicians should have a high index of suspicion of possible hydrocarbon ingestion with such presentations. CH induced tachyarrhythmias are usually refractory to standard antiarrhythmic medications and usually respond well to β-blocker.

Disclosure

The authors declared no conflict of interest.

references

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