Acta Med Scand 201: 227-230, 1977

Cardiac Arrhythmias in Chloral Hydrate Poisoning

Arne Gustafson, Sven-Eric Svensson and Lars Ugander

From the Intensive Care Unit, Department of Internal Medicine, University Hospital, Lund, Sweden

ABSTRACT. In three patients admitted to hospital after ingestion of an overdose of chloral hydrate, the ECG showed supraventricular and ventricular tachyarrhythmias. The possible mechanism for the arrhythmias may be an enhanced automaticity of supraventricular and ventricular pacemaker cells caused by metabolites of chloral hydrate. The ven- tricular arrhythmia responded to i.v. treatment with lignocaine in one patient, and to phenytoin in another in whom lignocaine failed to restore a normal sinus rhythm.

Chloral hydrate, which has been used for more than a century ( l ) , is considered t o b e a relatively non- toxic hypnotic drug, and fatalities f rom overdosage are rare (16). T h e toxic oral dose in adults is approx- imately 10 g, although fatal poisoning has occurred after ingestion of 4 g (15). On the other hand, doses up to 25 g during 20 hours have formerly been used in obstetric therapy, apparently without adverse ef- fects (6).

T h e toxic effects of an overdose of chloralhy- drate are characterized by respiratory depression and hypotension. Hypotension may be caused b y depressed contractility of the myocardium. Unto- ward cardiac effects may occur in particular in pa- tients with heart disease (15).

T h e aim of the present report is t o describe three patients without previous heart disease w h o showed cardiac arrhythmias after a n overdose of chloral hydrate. To our knowledge only a few cases with this complication have hitherto been reported ( 3 , 4 , 9 , 10).

P A T I E N T S A N D METHODS The observations were made on three patients who were admitted to our Intensive Care Unit after an overdose of

chloral hydrate. All three had taken Ansopal" tablets and no other drugs. One tablet of Ansopal contains 0.5 g chloral hydrate as acetylglycineamide-chloral hydrate. Acetylglycineamide is said to be pharmacologically inac- tive (5 ) .

A 12-lead ECG was taken on admission and the re- cording was then repeated daily, or more often when re- quired. Heart rhythm was monitored continuously. Rou- tine laboratory examinations, including serum electrolytes and blood gases, were performed.

C A S E R E P O R T S

Case 1 A 39-year-old woman was admitted eight hours after in- gestion of about 60 tablets of Ansopal. Only a small amount of tablet remnants was recovered by gastric lav- age. On admission she was comatose but responsive to pain. The respiratory rate was 16/min and analysis of an arterial blood sample showed pH 7.33, PaCO, 5.3 kPa (40 mmHg), PaO, 9.7 kPa (73 mmHg), base excess -5.0 mmol/l. Serum electrolytes were normal. The rectal temperature was 37.0"C and BP 105/75 mmHg. An en- dotracheal intubation was performed and treatment with forced diuresis was started. Frusemide, 20 mg i.v., was given six hours after admission and another dose of 40 mg was given after 13 hours.

An ECG on admission showed sinus rhythm with a rate of 120/min. Two hours after admission the continuous monitoring revealed occasional supraventricular and fre- quent ventricular premature beats of varying morphology in salvos (Fig. I ) . Lignocaine (Xylocain"), 50 mg i.v., was given as a bolus injection followed by an infusion of 2 mg/min. As no effect on the arrhythmia was noted after one hour, the infusion was discontinued. Phenytoin (Epanutin"), 150 mg i.v., was then administered at a rate of 25 mglmin. When 125 mg had been given, the ventricu- lar premature beats decreased in frequency and im- mediately after the injection the heart rhythm became regular. After half an hour an additional dose of 100 mg phenytoin was given and the rhythm remained normal except for short periods of ventricular bigeminy recorded at 7 and 21 hours after admission. A 12-lead ECG showed nothing abnormal except for slight flattening of the T waves. The patient recovered consciousness 12 hours af-

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228 A . Gustafson et al.

be extubated. He was discharged on the third day of admission.

Case 3 A 21-year-old woman was first admitted to a local hospital one hour after ingestion of about 40 tablets of Ansopal and some alcohol. After endotracheal intubation and gastric lavage, which yielded a large amount of tablet remnants, she was given mannitol and 40 mg frusemide. On arrival at the Intensive Care Unit in Lund two hours after ingestion of the tablets she was still comatose but responded to pain. The respiratory rate was 14/min and an arterial blood sample, taken when an oxygen-enriched air mix- ture was being administered, showed pH 7.35, PaCO2 4.9 Wa (37 mmHg) and PaO, 17.9 kPa (134 mmHg), standard bicarbonate 18.5 and base excess -7.0 mmol/l. The rectal temperature was 37.0"C. The ECG on admis- sion to the Intensive Care Unit showed runs of ventricular tachycardia with QRS complexes of varying morphology (Fig. 3). Shortly after recording of this arrhythmia the rhythm spontaneously converted to sinus rhythm with a rate of 15O/min. No antiarrhythmic therapy was given and the heart rate decreased to 120-100/min. Continuous monitoring revealed no arrhythmia during the subsequent course. The patient recovered consciousness one hour after admission and was then extubated. She was dis- charged on the second day of admission.

Fig. 1. Occasional supraventricular beats and frequent ventricular premature beats after ingestion of about 60 tablets of Ansopal' ten hours earlier. (Case 1.)

ter admission and was extubated 10 hours later. She was discharged on the fourth day of admission.

Case 2 A 51-year-old man was admitted about 8 hours after inges- tion of approximately 50 tablets of Ansopal (a gastric lavage yielded a large amount of tablet remnants). On admission he was comatose with no reaction to pain. The rectal temperature was 36.9"C. Respiration was shallow and analysis of an arterial blood sample showed pH 7.32, PaCO, 6.7 kPa (50 mmHg), PaO, 7.9 kPa (59 mmHg), standard bicarbonate 23.0 and base excess -1.5 mmol/l. Endotracheal intubation was performed and respirator therapy and treatment with forced diuresis were started. Frusemide, 20 mg i.v., was given 24 hours after admis- sion. On admission an ECG showed a supraventricular

rhythm with a rate of 75/min, interpreted as an accelerated AV junctional rhythm since no P waves were identified. The heart rate was about 200/min 15 min later. The ECG showed broad QRS complexes interrupted by occasional normal complexes and fusion beats (Fig. 2). On the diagnosis of ventricular tachycardia lignocaine was given as an i.v. bolus injection of 70 mg. The ECG was recorded continuously during the injection and when 40 mg had been given, a supraventricular rhythm with a rate of 150/min appeared. The P waves were initially inverted in leads I1 and 111, but after a few beats they became upright, indicating sinus rhythm. Ventricular premature beats with QRS complexes of the same morphology as during the tachycardia appeared during the first minute after conver- sion, followed by regular sinus rhythm. Systolic BP de- creased to 50 mmHg during the tachycardia but increased immediately after the episode to 80 mmHg. Lignocaine was given continuously at a rate of 2 mglmin during the next 30 hours. Continuous monitoring revealed no further arrhythmias and the subsequent course was uneventful. A 12-lead ECG on the second day of admission was normal and so were the serum enzymes (S-ASAT and S-ALAT). Respirator therapy was discontinued 30 hours after admis- sion, and seven hours later the patient was alert and could

DISCUSSION

After absorption, a varying amount of chloral hydrate is oxidized to trichloroacetic acid and the rest of the drug is reduced to trichloroethanol (1, 8, 11). This metabolism is so rapid that no chloral hydrate could be detected in the blood after therapeutic doses in man (8, 14). It was detected in blood samples taken after 10 but not after 15 min when large doses were administered orally to dogs (8). The hypnotic effect is largely, if not entirely,

Fig. 2. Ventricular tachycardia with occasional su- praventricular and fusion beats after ingestion of 50 tablets of Ansopal" eight hours earlier. (Case 2.)

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Chloral hydrate-induced arrhythmias 229

Fig. 3. Runs of ventricular tachycardia with QRS com- plexes of varying morphology after ingestion of 40 tablets of Ansopal@ two hours earlier. (Case 3 . )

due to trichloroethanol, while trichloroacetic acid has no such effect (1, 8). The plasma half-lives of trichloroethanol and trichloroacetic acid have been estimated to be 8.2 and 67 hours, respectively (12, 13).

In four reports of cardiac arrhythmias after chloral hydrate the ECG showed supraventricular and/or ventricular tachyarrhythmias. Auricular fi- brillation with a high ventricular rate and ventricu- lar premature beats were observed in a patient 45 min after ingestion of 12 g chloral hydrate (9). Ten hours after ingestion of 18 g, ventricular tachy- cardia was observed in a 66-year-old woman. This rhythm reverted to sinus rhythm on procainamide therapy, but the arrhythmia recurred after three hours with runs of ventricular fibrillation which re- sponded to continued treatment with procainamide (4). Recurrent episodes of ventricular fibrillation, premature ventricular beats and bursts of su- praventricular and ventricular tachycardia were recorded in a patient with a history of myocardial infarction who had taken 18 g of the drug. The arrhythmias were refractory to lignocaine but re- sponded to alprenolol(3). In a 2-year-old child, who had ingested 1.5 g chloral hydrate, an ECG revealed multifocal premature beats. The arrhythmia disap- peared spontaneously after about two hours (10).

In the present patients, the arrhythmias were of the same type as those described in the above publications, in that they all had supraventricular tachycardia and ventricular premature beats in

salvos or ventricular tachycardia. The mechanism behind these arrhythmias was presumably an en- hanced automaticity of supraventricular and ven- tricular pacemaker cells. As the ECGs showed no signs of AV block or intraventricular block, a de- creased conductivity with re-entrant mechanism seemed to be a less plausible cause. The shortening of the refractory period of the myocardium, which has been observed after large doses of chloral hydrate (151, could also be of importance for the genesis of the arrhythmias.

Since chloral hydrate is metabolized so rapidly and the arrhythmias were observed hours after in- gestion of tablets, it is most likely that one of the metabolites was the causative factor. Trichloroace- tic acid has been proposed as being responsible for the tachycardia and vasodilatation following si- multaneous administration of chloral hydrate and alcohol (121, and administration of frusemide to pa- tients who had taken chloral hydrate (7). The re- lapse of the arrhythmias after several hours in some of the previously reported cases, and also in the present case 1, may be attributed to the long half- life of trichloroacetic acid.

In our patient 3, gastric aspiration was performed soon after ingestion of the tablets and the coma was of short duration, which indicates absorption of only a moderate amount of the drug, yet a period of arrhythmia occurred. An interaction of chloral hydrate and alcohol as well as frusemide, could have contributed to the origin of the arrhythmia in this case. In case 1, ventricular premature beats were observed one hour after administration of frusemide, but this arrhythmia also recurred later when no frusemide had been given. In case 2, no arrhythmia was recorded when frusemide was given 24 hours after admission.

Lignocaine has become the drug of choice in treatment of ventricular tachyarrhythmias. In case 2 of the present study the arrhythmia was abolished by lignocaine. In two patients unresponsive to lignocaine, regular sinus rhythm was restored by alprenolol in one (3), and by phenytoin in the other (our case 1).

The arrhythmias reported in the present study had a benign course, but their appearance was that of a potentially malignant ventricular tachyar- rhythmia. The practical consequence is that monitoring of the heart rhythm is indicated in patients admitted after an overdose of chloral hydrate.

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