Torsades de Pointes with Administration of High-Dose Intravenous d-Sotalol to a Patient with Congestive Heart Failure Stephen S. Gottlieb, M.D., Michelle Cines, R.N., and Joanne Marshall, R.’N. A patient with heart failure was administered d-sotalol3.0 mg/kg infused over 2 minutes. The patient had normal electrolytes and baseline QT. Six minutes after drug administration the QT prolonged to 600 msec, and the patient developed torsades de pointes and required electrical cardioversion. This emphasizes the need to consider both rate of administration and the dosage when evaluating the safety and efficacy of a new class zyxw 111 antiarrhythmic drug. (Pharmacotherapy 199 7; 1 7 (4) zyxwv : 830-83 1) zyxw i Although the clinical development of d-sotalol has terminated, other Vaughan Williams class I11 antiarrhythmic agents are still being evaluated for the treatment of arrhythmia in patients with congestive heart failure. One major problem is the development of torsades de pointes in some individuals after administration of these antiarrhythmic agents. However, it is difficult to predict the circumstances that lead to the disorder. Torsades de pointes developed in a patient with heart failure who was given a high dose of intravenous d-sotalol as an infusion over 2 minutes. This experience suggests that either rapid changes in the plasma concentration of the agent or very high concentrations may cause the development of this complication. zyxwvu Case Report As part of a study designed to evaluate the acute hemodynamic effects of d-sotalol in patients with heart failure1 and approved by the institutional review board, right heart catheterization was performed in a 69-year-old man with moderate congestive heart failure and no evidence of clinically important atrial or ventricular arrhythmias. He had an ejection fraction of 21% by nuclear ventriculography, New York Heart From the Division of Cardiology, Department of Medicine, University of Maryland School of Medicine, and the DVA Medical Center, Baltimore, Maryland (all authors). Supported by a grant from Bristol-Myers Squibb, Princeton, New Jersey. Address reprint requests to Stephen S. Gottlieb, M.D., Division of Cardiology, University of Maryland School of Medicine, 22 South Greene Street, Baltimore, MD 21201. Association class 111 symptoms, and no known ischemic heart disease. Hemodj?lamic assessment showed a cardiac index of 1.2 Uminute/m2, a pulmonary capillary wedge pressure of 25 mm Hg, a right atrial pressure of 8 mm Hg, a mean arterial pressure of 91 mm Hg, and a heart rate of 82 minute-’. He had not received angiotensin- converting enzyme inhibitors, long-acting nitrates, diuretics, or any other vasodilator for at least 24 hours before entry into the study. He was not receiving digoxin. Baseline electrolytes were normal, with a potassium of 4.7 mEq/L (normal 3.5-5.1 mEq/L) and a magnesium of 2.0 mEq/L (normal 1.6-2.5 MEq/L). Eighteen other patients in the study safely received d-sotalol 1.5 mg/kg or placebo. The protocol specified that the rest of the patients would receive either d-sotalol 3.0 mg/kg or placebo. All doses were administered by intravenous infusion over 2 minutes. Thus, after an overnight fast of more than 8 hours, a single intravenous dose of d-sotalol 3.0 mg/kg was given. Six minutes after the infusion this patient developed torsades de pointes. Electrical cardioversion restored normal sinus rhythm, but the man developed a cerebrovascular accident, with no residual paresis. Baseline QT was 356 msec, with a heart rate of 75 minute-’. Immediately after infusion, the heart rate had decreased to 65 minute-’ and the QT increased to 460 msec. Immediately before the onset of the torsades de pointes the QT interval was 600 msec. Since torsades de pointes developed in the first patient to have received a dose this high this quickly, the study protocol was revised so that