Sotalol, unlike the other beta‐blockers, increases the QTcinterval and risk of torsades de pointes ventricular tachycardia in severe poisonings

Dear Editor, We read with great interest the original article "Clinical Toxicology of Beta-Blocker Overdose in Adults" by Michael Lauterbach in BCPT.1 This explorative analysis, based on the Mainz Poison Center/Germany database, was focused on the poisonings caused by different beta-blockers and it included 31 sotalol cases, too.1 Symptoms did not differ substantially between different beta-blocking agents, except more seizures were reported with propranolol and more CNS depression/vomiting with sotalol. Unfortunately, concentrations of the beta-blockers and of other drugs had not been measured, that is the ingestion and absorption of suspected drugs could not be confirmed. We wonder why there were no comments on possible prolongation of the QTc interval and/or ventricular tachycardias of torsade de pointes type after sotalol overdoses. Sotalol differs from other generally used beta-blocking agents by having additional class III (Vaughan-Williams classification) antiarrhythmic properties. This "amiodarone-like" effect remained clinically unrecognized for several years until reported in 1979 in association of sotalol intoxications in two patients, after the doses of 2.4 g and 8.0 g, respectively.2, 3 Both of these patients had, in addition to bradycardia and hypotension, a concentration-dependent QTc prolongation and severe cardiac tachyarrhythmias. In a later report, all the six sotalol intoxication patients had developed QTc interval, up to 172% ± 8% of normal.4 The QT intervals were at their longest 4-15 hours after sotalol ingestion. Severe ventricular tachyarrhythmias occurred in five of the six patients, the risk of tachyarrhythmias was greatest up to 20 hours. The QTc interval returned to normal over 3-4 days. Similar time courses of the QTc prolongation and malignant tachyarrhythmias have been described in many later case reports. The QTc-prolonging effect of (racemic) sotalol has been shown to correlate with its serum concentrations, both in the patients with acute sotalol overdose 2-5 and when its high daily doses have been used therapeutically.6, 7 Hypokalaemia and hypomagnesaemia increase the risk of malignant ventricular arrhythmias, such as torsades de pointes. The correlation between the serum sotalol concentration and QTc prolongation suggests that the QTc interval could be used as an index of the sotalol poisoning severity. In most patients, serum sotalol concentrations higher than 3 mg/L are associated with a prolongation of QT interval of 50-150 ms or more.6 It can be estimated that 1.6-3.2 g of sotalol, that is about 5-10 times its usual daily dose (FDA), ingested at once would elevate serum peak sotalol levels to over 10 mg/L and markedly increase the QT interval and the risk of arrhythmias (3, 4). Thus, one could assume that at least the 6 patients with the highest Poison Severity Scores (two in PSS2 and four in PSS3) in the Lauterbach study should have had a markedly prolonged QTc interval, provided that their symptoms were caused by sotalol.1 The high incidence of tachycardias in the sotalol group (30% of the symptomatic cases), unlike in the all other beta-blocker groups (5% or less), could be related to the class III intrinsic property of sotalol which is independent of its beta-blocking effect.7 Therefore, we want to underline that the sotalol poisonings are "different" and need special attention. Besides hypotension and bradycardia, which are usual in all beta-blocker poisonings, prolonged QTc and malignant tachyarrhythmias are common after high sotalol doses and may need careful follow-up and specific treatment, at least up to 24 hours after ingestion.4, 8, 9 Activated charcoal (single dose 50 g) binds effectively that fraction of the sotalol dose, which is still in the stomach at the time of charcoal administration.10 However, the antidotal efficacy of charcoal and of other gastrointestinal decontamination methods is limited in typical intoxication cases in which the treatment can be started not earlier than several hours after sotalol ingestion. Given in repeated doses from 6 hours after sotalol ingestion, charcoal can only slightly increase sotalol elimination.10 As the excretion into urine is the main route of sotalol elimination, adequate blood pressure and urine flow are important to its clearance.10, 11 None.