Torsade de pointes and prolonged QT interval from surreptitious use of sotalol: use of drug levels in diagnosis.

Torsade de pointes is a well-established toxic effect of sotalol hydrochloride. In a patient presenting with torsade de pointes and a long QTc interval of unknown cause, a serum sotalol level was used to secure an otherwise difficult diagnosis.

Sotalol poisoning associated with asystole.

Sotalol overdose has special features because this beta-blocker has the potential to lengthen the Q-T interval and to initiate severe arrhythmias such as ventricular tachycardia or fibrillation. We describe the case of a 70-year-old woman who ingested 6.72 g sotalol with suicide attempt. Despite administration of activated charcoal, glucagon, atropine and isoprenaline, two episodes of asystole occurred, requiring cardiopulmonary resuscitation. Further treatment included ventricular pacing and dopamine. The patient recovered without neurologic nor cardiac sequelae.

Class III antiarrhythmics in overdose. Presenting features and management principles.

Class III (Vaughan-Williams classification) antiarrhythmic drugs prolong the cardiac action potential without affecting depolarisation. The 3 class III drugs currently in general use are amiodarone, sotalol and bretylium. The presenting features of acute toxicity are different for each agent and are, therefore, discussed separately. Several new class III antiarrhythmic agents are under development, including dofetilide and d-sotalol, but specific data on overdoses of these potent class III drugs are not yet available. Amiodarone toxicity following acute overdose is rare because poor bioavailability and a large volume of distribution limit the peak serum concentration. Toxicity is low even if high serum concentrations are reached. The major risks from acute overdose are hypotension (intravenous administration only) and arrhythmia if other factors, such as hypokalaemia or additional antiarrhythmic agents are present. Management is chiefly directed at reducing absorption with activated charcoal or cholestyramine, and monitoring for arrhythmia. Sotalol is a beta-blocker with additional class III activity. Oral bioavailability is high, and overdosed patients can present with bradycardia, hypotension and major haemodynamic collapse. The combination of bradycardia and prolongation of the QT interval is associated with malignant arrhythmias such as torsade de pointes. Management principles include observation and correction of bradycardia with endocardial pacing, intravenous adrenergic drugs and glucagon. The risk of arrhythmia can be substantially reduced by intravenous potassium and magnesium supplements. d-Sotalol is a potent class III drug devoid of beta-blocking activity and may be expected to share the proarrhythmic affects of the racemic mixture in overdose, without pronounced hypotension and bradycardia. Intravenous bretylium in overdose causes an initial hypertensive effect, followed by profound hypotension from systemic vasodilation. Management is directed at controlling hypotension with volume expansion and norepinephrine (noradrenaline).

Poisoning with anti-hypertensive drugs: beta-adrenoceptor blocker drugs.

The effects of poisoning with beta-blockers may be serious, but are usually self-limiting provided adequate support is given. If there is no evidence of toxicity and the degree of overdose is small, clinical observation may be all that is required. This review examines the cases of overdosage with beta-blockers reported in the literature, the presenting symptoms and possible strategems of management for such patients.

Torsade de pointes with sotalol overdose treated successfully with lidocaine.

Torsade de pointes is a polymorphic ventricular tachyarrhythmia associated with a long QT interval. The prognosis is excellent if torsade is recognized early. In the acquired long QT syndrome, measures should be taken quickly to identify and correct all predisposing conditions and to treat or prevent torsade. Established treatments of acquired torsade are magnesium bolus, electrolyte replacement, isoproterenol infusion and cardiac pacing. Sotalol overdose causing torsade is reported in which lidocaine appears to have suppressed an episode of torsade as well as prevented further episodes. Current understanding of the electrophysiological mechanisms of torsade and lidocaine, a review of the literature and the author's experience indicate that lidocaine is a potentially useful therapy in torsade.

Sotalol induced torsade de pointes.

Torsade de pointes is an uncommon ventricular tachyarrhythmia precipitated by a variety of metabolic and pharmacological conditions and requiring unconventional antiarrhythmic therapy. A case is presented demonstrating the occurrence of torsade de pointes following sotalol overdosage and specific features enabling recognition and treatment of this life-threatening arrhythmia are discussed.

Massive ingestion of cardiac drugs: toxicokinetic aspects of digoxin and sotalol during hemofiltration.

CASE: We present the case of a 75-year-old patient admitted to the emergency department after ingesting a large amount of several cardiac drugs, among which were digoxin and sotalol. Because of renal insufficiency, cardiogenic shock, and high serum digoxin levels, the patient received continuous venovenous hemofiltration (CVVH) and digoxin-specific Fab fragments. Digoxin and the digoxin-specific Fab fragments are normally cleared by the kidneys. METHODS: Serum-free and total digoxin and serum sotalol concentrations were monitored for several days. RESULTS: Less than 10% of the estimated ingested dose of digoxin was cleared by CVVH within 5 days. CONCLUSION: CVVH has little influence on the clearance of Fab-bound digoxin from the body. In contrast, sotalol is efficiently cleared by CVVH.

Severe poisoning with sotalol and verapamil. Recovery after 4 h of normothermic CPR followed by extra corporeal heart lung assist.

In acute poisoning with beta-blocking drugs and calcium-channel blockers patients may present with serious symptoms. We present a case of life-threatening sotalol and verapamil intoxication in a 29-year-old female suffering from depression. She was admitted to our hospital a few hours after she had taken 3.6 g verapamil and 4.8 g sotalol. On being found the patient was breathing and had a palpable pulse. On admission the patient experienced a cardiovascular collapse and CPR was started. Echocardiography confirmed cardiac standstill. After 4 h of normothermic CPR, extra corporeal heart lung assist (ECHLA) was established. Vasoactive drugs could be stopped after 2 days with ECHLA, and after 5 days the patient was extubated. The patient experienced several complications (intestinal bleeding, transient nerve paralysis, and renal failure due to rhabdomyolysis) but made a complete recovery and started working 6 months after the poisoning. She was no longer depressed.

A case of sotalol poisoning with fatal outcome.

The case of a 58 year old woman who died after ingestion of 14.4 g of sotalol and 50 mg of triazolam is described. Despite medical treatment, intracardiac pacing and hemodialysis, cardiovascular failure persisted and became irreversible. High sotalol concentrations were observed in plasma (65 micrograms/ml) and in post mortem tissues samples. Tissue to plasma ratios ranged from 2.5 to 6. The high drug concentration found in heart tissue (104.4 micrograms/g) explains the difficulties experienced in the sotalol poisoning.

Sotalol intoxication, two patients with concentration-effect relationships.

Two adult patients ingested an overdose of 2.4 g and 8.0 g of sotalol hydrochloride, respectively, i.e. 7-25 times the mean daily dose. Certain signs as bradycardia and hypotension were similar to those described for other beta-blocking agents. In addition to these, however, both patients had severe cardiac tachyarrhythmias and a considerably prolonged QT-interval in their electrocardiogram. The decline of serum sotalol concentrations followed first-order kinetics with the elimination half-life of 13-15 hours. There was a good correlation between the serum sotalol concentration and the prolongation of the QT-interval. Sotalol differs from other beta-blocking agents in its effects on the action potential of the ventricular muscle and Purkinje fibers of the heart. This is likely to explain the different symptoms and findings of sotalol intoxication compared to those seen in connection with other beta-blocking agents.

Fatal sotalol poisoning.

Sotalol [4-(2-isopropylamino-1-hydroxyethyl)-methane-sulfonanilide hydrochloride] is a beta-adrenergic blocking agent. Despite the widespread use of these drugs, poisonings are not frequent. In this report the authors describe the first recorded case of fatal sotalol overdosage to their knowledge. The results of toxicological analysis, performed by a specially developed method, are presented, and compared with findings in fatal intoxications with other beta-adrenergic blocking agents.

Clinical course, serum concentrations and elimination rate in a case of massive sotalol intoxication.

A young woman had been on antiarrhythmic treatment with sotalol 80-160 mg daily for three years because of ventricular tachycardia. After a quarrel she ingested an overdose of sotalol, estimated to be 13-14 g, and was immediately brought to hospital, where the first ECG was taken 25 minutes after the ingestion. The clinical course, including the relationship over time between pronounced bradycardia, QT prolongation and malignant ventricular tachyarrhythmias is described. Serum concentrations were obtained regularly between 11 and 54 hours after the ingestion. After initially very high levels, the concentrations decreased in a strictly exponential manner to arrive at therapeutic concentrations 39 hours after the ingestion. Calculations revealed that over 12 g of sotalol was absorbed into the circulation, while the half life was 9.2 h and the oral clearance 294 mg min-1. The heart rate normalized about 24 hours after the repolarization variables, which supports the opinion that the class III action of sotalol is unrelated to the beta-blockade. In sotalol intoxication, malignant tachyarrhythmias appearing during excessive prolongation of the QT interval, most often in combination with hypokalemia, ethanol intoxication or concomitant antiarrhythmic treatment, may need emergency defibrillation but seem to disappear within a few hours. Thus, while massive sotalol intoxication may be fatal, early treatment promotes a successful outcome even when very high doses have been ingested.

Pharmacokinetic evaluation of a case of massive sotalol intoxication.

OBJECTIVE: To describe serum concentrations and clearance of sotalol after a massive overdose. CASE SUMMARY: A 37-year-old white man took 11.2 g of sotalol hydrochloride tablets in a suicide attempt. The first serum d,l-sotalol concentration 3 hours after taking the first tablet was 20.6 mg/L and the last measured concentration 59 hours later was 1.8 mg/L. Logarithmic transformation of the concentration data indicated two separate monoexponential phases in the elimination curve, with half-lives of 30.1 and 11.6 hours. DISCUSSION: The shorter serum half-life in the later phase is comparable with that in four previously reported sotalol intoxications and within the normal range. The elimination rate increased in a temporal manner with an increase in systolic blood pressure about 30 hours after the patient was admitted. Since the sotalol elimination rate depends principally on renal function, we believe the initially slow elimination is due to a temporary reduction of the renal function caused by the systolic hypotension. CONCLUSIONS: An initial phase of slow sotalol elimination may occur after severe overdoses. In our patient this was probably due to hypotension. Thus, blood pressure should be monitored carefully.

Overdrive pacing as treatment of sotalol-induced ventricular tachyarrhythmias (torsade de pointes).

Four patients with ventricular arrhythmias due to sotalol intoxication were successfully treated with overdrive pacing. In three patients the reason for sotalol overdose was a suicidal attempt and in the fourth patient the reason was unknown. In all cases a prolongation of the Q-T interval was seen, which is a typical feature of sotalol overdose. Other features of beta-blocker intoxication like bradycardia were found in all patients and hypotension in two patients. Three of four patients received lidocaine, but with no effect on multiple ventricular premature beats (VPB) or ventricular tachycardia (VT) of "torsade de pointes"-type. Overdrive pacing abolished immediately VPBs and VTs in three patients, and in the fourth patient there was apparent decrease in dysrhythmia. Temporary overdrive pacing is suggested as treatment of ventricular arrhythmias in association with prolonged Q-T interval caused by overdose of sotalol.

[Intoxication by beta-blockers in children and adolescents (author's transl)]. / Vergiftungen mit beta-rezeptorenblockern bei Kindern und Jugendlichen.

After ingestion of beta-blocking agents 20 out of 77 children and adolescents developed clinical symptoms. 11 cases resulted from suicidal attempts. A 15 year old girl died. Neurological signs (12) predominated. Cardiovascular signs (10) were especially seen after suicidal ingestion of beta-blocking agents. Infants frequently showed hypoglycemia or symptoms based on hypoglycemia (6). After elimination from the gastrointestinal tract patients require intensive monitoring as well as symptomatic treatment. Treatment with atropin often gave insufficient results. However, treatment with glucagon was successful. Secondary detoxication generally is not required and must be evaluated after pharmacokinetic data. Forced diuresis is not indicated.

Prolonged Q-T interval and severe tachyarrhythmias, common features of sotalol intoxication.

The findings in six patients admitted to hospital 0.5-4.5 h after the ingestion of an overdose of 2.4-8 g sotalol are described. In addition to bradycardia and hypotension, all patients had a considerably prolonged corrected Q-T interval, up to 172 +/- 8% of normal. Severe ventricular tachyarrhythmias occurred in five of the six patients, the risk was greatest up to 20 h after the ingestion of sotalol. The long Q-T interval returned to normal over 3 to 4 days, which is consistent with the long half-life of sotalol. In addition to its beta-blocking action, sotalol has marked electrophysiological properties of a Class III antiarrhythmic drugs, which are likely to be able to account for its observed effects. Special attention should be paid to the risk of severe ventricular arrhythmias in sotalol intoxications.

Relative toxicity of beta blockers in overdose.

OBJECTIVE: To compare the toxicity of beta blockers in overdose and to identify clinical features predictive of serious toxicity. DESIGN: Comparison of clinical data collected prospectively on a relational database of subjects presenting to hospital with self-poisoning, coroner's data and prescription data. SETTING: Newcastle and Lake Macquarie, Australia, 1987-1995. MAIN OUTCOME MEASURES: Death, seizure, cardiovascular collapse, hypoglycemia, coma and respiratory depression. SUBJECTS: Fifty-eight self-poisonings with beta blockers and two deaths investigated by the coroner with evidence of propranolol poisoning. RESULTS: All patients who developed toxicity did so within six hours of ingestion. The use of ipecac was temporally associated with cardiorespiratory arrest in one patient. Propranolol was the only beta blocker associated with seizure; of those who ingested more than 2 g of propranolol, two thirds had a seizure. There was a significant association between a QRS duration of > 100 ms and risk of seizures. Propranolol was over represented in beta blocker poisoning when prescription data were also examined. Propranolol was the only beta blocker associated with death. Propranolol was taken by a younger age group. CONCLUSIONS: Propranolol should be avoided in patients at risk of self-poisoning. Propranolol poisonings should be observed closely for the first six hours post ingestion. Syrup of ipecac should not be used to decontaminate the gastrointestinal tract after beta blocker overdose.

[Intoxication with beta-receptor blockers (author's transl)]. / Intoxikation mit Beta-Rezeptorenblockern.

Beta-blockers are increasingly often used with suicidal intent, but are also sometimes swallowed accidentally by small children. Beta-blockers available in the Federal Republic of Germany differ in their pharmacodynamics and pharmacokinetics. After analysing 49 cases of intoxication, no certain relationship was found between the different substances and specific symptoms. Cardiovascular signs such as sinus bradycardia, arrhythmia, hypotension (30 cases), as well as dizziness and drowziness (17) were the most frequent ones. Loss of consciousness and hallucination (13), as well as seizures (3), also occurred frequently. Hypoglycaemia or symptoms due to it (12) were noted especially in young children. In addition to primary removal of the drug, repeated administration of charcoal and sodium sulphate are recommended with most of the drugs for interrupting the enterohepatic circulation. Administration of atropine for bradycardia and hypotension was usually not effective. Dopamine is recommended; glucagon for definite signs of shock. Haemodialysis is indicated only in exceptional instances and is effective for only a few of the drugs. Forced diuresis should not be practised.