Bühler, H.

Huynh-Do, U.

Keusch, G.

Sulzer, M.

Wahl, C.

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Nephrol Dial Transplant (1996) 11: 1153-1154Case ReportNephrologyDialysisTransplantationTorsade de pointes during low-dosage sotalol therapy in haemodialysispatientsU. Huynh-Do1'2, C. Wahl1-2, M. Sulzer2, H. Buhler2 and G. Keusch1'Division of Nephrology and 2Medical Clinic, City Hospital Waid, Zurich, SwitzerlandKey words: haemodialysis; sotalol; ventricular tachy-cardia; torsade de pointesIntroductionSotalol is the prototype class III agent that combines^-blocking properties with the propensity to prolongthe effective refractory period by lengthening the actionpotential duration. A review of clinical trials demon-strates that sotalol is an effective treatment for unsus-tained and sustained ventricular tachyarrhythmias. It isalso active against several supraventriculararrhythmias. Sotalol is safe and generally well toler-ated; most of the adverse effects experienced with itsuse are related to its /^-blocking activity. However,sotalol has been associated with life-threatening pro-arrhythmias, including torsade de pointes, althoughthe incidence of this adverse effect is low, varyingbetween 1.8 and 3% in the clinical trials conducted todate [1-3]. To our knowledge, the occurrence of sota-lol-induced torsade de pointes has never been reportedbefore in haemodialysis (HD) patients. We report herethree HD patients who underwent cardiopulmonaryresuscitation for torsade de pointes and cardiopulmon-ary arrest under low-dosage sotalol therapy.Case reportsCase 1. A 53-year-old female patient had had recurrentpulmonary infections because of bronchiectasis of thelower lobes from the age of 19. HD was started in1983 because of end-stage renal disease (ESRD) dueto secondary renal amyloidosis. In November 1992, aresection of the lingula was performed. Postoperativelysotalol was started in a low dosage of 2 x 40 mg/dayfor recurrent supraventricular tachyarrhythmias. Onthe second day, the patient underwent mechanicalcardiopulmonary resuscitation because of torsade depointes. The ECG showed a prolonged corrected QTcCorrespondence and offprint requests to: U. Huynh-Do, MD, Divisionof Nephrology and Medical Clinic, City Hospital Waid, Tiechestrasse99, CH-8037 Zurich, Switzerland.interval of 550 ms. Sotalol was stopped and magnesiumsulphate was given; the QTc interval normalized andthe patient remained in a stable sinus rhythm of 70/min.Case 2. A 78-year-old male patient with a knownhypertensive and coronary heart disease had been onHD since 1979 because of ischaemic nephropathy. InJuly 1995 he developed intermittent supraventriculartachyarrhythmias; because of digoxin incompatibility,sotalol was given in a dosage of 2 x 40 mg/day withoutsupplemental dosage after HD. One month later hewas hospitalized because of acute gastrointestinalbleeding under aspirin and indomethacin. During thefirst 3 days he needed daily blood transfusions andendoscopic haemostasis because of recurrent bleeding.On the third day, torsade de pointes with haemo-dynamic compromise occurred twice (Figure 1) butresponded promptly to cardioversion and magnesiumsulphate infusion. The ECG showed a bradycardia of50/min and a slightly prolonged QTc of 480 ms. Sotalolwas replaced by atenolol and the patient recovereduneventfully.Case 3. A 73-year-old female patient with hyperten-sive, valvular and coronary heart disease had been onCAPD, then HD since 1979 because of analgesic-associated nephropathy. In May 1995 she underwentparathyroidectomy for secondary hyperparathyroid-ism. Postoperatively acute atrial fibrillation occurred,but could be controlled with digoxin plus sotalol.Digoxin was discontinued after 1 more day, and thepatient remained on sotalol 2 x 40 mg/day. One weeklater, she had a cardiopulmonary arrest, which wassuccessfully managed by chest compression. TheECG immediately after cardiopulmonary resuscitationshowed a bradycardia of 44-52/min, with a QTc of540 ms. After sotalol was stopped, the heart rate andQTc interval normalized during the following 3 days.DiscussionThe side-effects of sotalol are related either to its /?-blocking properties or to its propensity to lengthen theQT interval. Adverse reactions due to /?-adrenergicreceptor blockade are similar to those associatedwith conventional /?-adrenergic antagonists. How-ever, aggravation of congestive heart failure by sotalol© 1996 European Dialysis and Transplant Association-European Renal Association1154 U. Huynh-Do et a/. Fig. 1. Electrocardiogram demonstrating torsade de pointes. It is readily apparent that a long pause precedes the sinus beat which triggers a run of polymorphic ventricular tachycardia. The tachycardia is characterized by periodic shifts in the QRS axis and in its amplitude. is less frequent than might be expected with a P- adrenergic antagonist. The most dangerous effect of antiarrhythmic drugs is aggravation of pre-existing arrhythmias or the pro- vocation of new arrhythmias. The drugs that prolong the action potential duration may cause torsade de pointes, a polymorphic ventricular tachycardia associ- ated with an exaggerated prolongation of the QT interval. Many cases of sotalol-induced torsade de pointes have been associated with drug overdose or predisposing factors, such as bradycardia, hypokalae- mia, or concomitant use of drugs that prolong repolar- ization [4-61. A recent review of data from controlled trials of sotalol in a total of 3257 patients reported proarrhythmic events in 141 (4.3%) patients. Of these, 78 (2.4%) had torsades de pointes, which were more prevalent in patients with congestive heart failure and low ejection fraction. Torsade de pointes were observed early in the course of the treatment and their occur- rence was related to. dose [I].  Most studies have reported control of arrhythmia with daily doses between 160 and 640 mg in patients with normal renal function. With doses ranging from 160 to 640 mg/d, the QT interval is prolonged by 40-100 ms. Exaggerated prolongation results in a predisposition to torsade de pointes. Although there are no data from controlled studies, the current recommendation is that sotalol therapy should be discontinued at a maximal QTc interval of 500 ms [7]. Oral administered sotalol is almost completely absorbed and does not undergo first-pass metabolism in the liver, resulting in a bioavailability of 90-100%; 85-90% of the drug is excreted unchanged in the urine, the mean elimination half-life being 8 + 3 h in patients with normal renal function. In ESRD the elimination half-life is increased to 41 h, so that a dose reduction to 25% of the normal dosage is recommended. However, sotalol is effectively removed by haemo- dialysis (HD), and a supplemental dose of 80 mg is currently recommended after each H D  [7,8]. Our three patients were all treated with 80 mg sotalol daily, without drug supplementation after HD, which implies a low dosage of sotalol. Nonetheless cardiopul- monary arrest occurred 1-14 days after the drug had been started. In all three patients, the QTc interval at the time of cardiopulmonary resuscitation was over 480 ms. Although torsade de pointes had been docu- mented in patients 1 and 2 only, the excessive bradycar- dia and prolongation of the QTc interval in patient 3 makes the same diagnosis very probable. All patients had normal electrolytes at the time of cardiopulmonary resuscitation, and none had concomitant therapy with any drug known to prolong cardiac repolarization. Patients 2 and 3, however, had a reduced cardiac ejection fraction. To our knowledge, this life-threatening complication of sotalol has never been reported before in H D  patients. Because of our own experience, we advise extreme caution in the indications and use of sotalol in that special patient population. A daily dose of 40 mg schould not be exceeded in the first days, and daily ECG controls are warranted in the acute titration phase in order to register a possible excessive prolonga- tion of the QTc interval, and stop sotalol medication on time. References 1. MacNeil DJ, Davies RO, Deitchman D. Clinical safety profile of sotalol in the treatment of arrhythmias. Am J Cardiol 1993; 72: 44A-50A 2. Kehoe RF, MacNeil DJ, Zheutlin TA et a/. Safety and efficacy of oral sotalol for sustained ventricular tachyarrhythmias refract- ory to other antiarrythmic agents. Am J Cardiol 1993; 72: 56A-66A 3. Singh BN, Kehoe R, Woolsley RL, Scheinman M, Quart B. Multicenter trial of sotalol compared with procainamide in the suppression of inducible ventricular tachycardia: a double-blind, randomized parallel evaluation. Sotalol Multicenter Study Group. Am Heart J 1995; 129: 87-97 4. Neuvonen PJ, Elonen E, Vuorenmaa T, Laakso M. Prolonged Q-T interval and severe tachyarrhythmias, common features of sotalol intoxication. Ertr J Clin Pliarmacol 1981; 20: 85-89 5. McKibbin JK, Pocock WA, Barlow JB, Millar RNS, Obel WP. Sotalol, hypokalaemia, syncope, and torsade de pointes. Br Heart J 1984; 51: 157-162 6. Krapf R, Gertsch M. Torsade de pointes induced by sotalol despite therapeutic plasma concentrations. Br Med J 1985; 290: 1784-1785 7. Hohnloser SH, Woosley RL. Drug therapy: Sotalol. N Engl J Med 1994; 331: 31-38 8. Bennett WM, Aronoff GR, Golper TA, Morrison G, Brater DC, Singer I. Drug Prescribing in Renal Failrrre. 3rd edn. ACP, Philadelphia, 1994; 45 Received for ptrblication: 27.11.95 Accepted in revised form: 7.2.96 Editor's note Please see also the Editorial Comment by BIhrle (pp. 944-946 in this issue). 

Torsade de pointes during low-dosage sotalol therapy in haemodialysis patients

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