Lithium-induced sinus node disease at therapeutic concentrations: Linking lithium-induced blockade of sodium channels to impaired pacemaker activity

Abstract

W e describe a 64-year-old man with a history of bipolar depression who was maintained on 1200 mg of lithium carbonate for 11 years, and presented with prolonged presyncope (45 min) associated with bradycardia and hypotension (blood pressure of 85/55 mmHg). He was not taking any atrioventricular (AV) node-blocking drugs. The 12-lead electrocardiogram showed sinus node arrest ( Figure 1) with an idioventricular escape rhythm at 35 beats/min to 40 beats/min. He was treated with intravenous fluids and intravenous atropine, and his rhythm reverted to a normal sinus rhythm (Figure 2). His serum lithium was 0.72 mM, which was within the therapeutic range (0.5 mM to 1.5 mM). There was no known personal or family history of cardiovascular disease, syncope or sudden cardiac death. Levels of plasma creatine kinase (muscle-brain), troponin I, plasma electrolytes (including calcium), as well as renal function, were within normal limits. Thyroid function tests showed normal thyroid-stimulating hormone levels and free triiodothyronine and L-thyroxine levels. Chest x-ray was normal. An exercise Cardiolite (BristolMyers Squibb Medical Imaging, Inc, USA) stress test was performed to assess sinus and AV nodal response to exercise and to screen for coronary artery disease. The patient's heart rhythm at the start of the test was normal, as shown in Figure 2. During the stress test, the sinus rate increased appropriately to 140 beats/min with an exercise time of 12 min.There were no diagnostic electrocardiographical changes, and myocardial perfusion was normal at rest and with exercise. A transthoracic echocardiogram showed normal left ventricular systolic function with normal aortic and mitral valvular function. A diagnosis of lithium-induced sinus node dysfunction was made based on the absence of other competing diagnoses and the similarity of indications in this case to those in other documented case reports, although the role of modifying factors (such as age-related changes in the sinoatrial [SA] node or high vagal tone) could not be ruled out. The patient has had suicidal ideation and previous suicide attempts associated with a reduced dose of lithium, which precluded us from withdrawing his lithium therapy. Given the high likelihood of a reoccurrence of the bradyarrhythmia, a rate-modulated ventricular pacemaker was implanted, and the patient was discharged on his preadmission dose of lithium carbonate. DISCUSSIONLithium salts were introduced for psychiatric use approximately 55 years ago to treat mania. Their use for this purpose was delayed until 1970, in part due to the uncontrolled use of lithium as a salt substitute and instances of toxicity in patients with cardiac disease (see below). Subsequently, the safety and efficacy of lithium salts for the treatment of mania and major depression associated with bipolar illness became CASE REPORT ©2007 Pulsus Group Inc. All rights reserved GY Oudit, V Korley, PH Backx, P Dorian. Lithium-induced sinus node disease at therapeutic concentrations: Linking lithium-induced blockade of ...

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