Oral theophylline corrects sinus node dysfunction in acute on chronic lithium toxicity: case report and systematic review of lithium-induced Sinus node dysfunction

Abstract

Introduction: Lithium is a well-known agent to cause systemic toxicity with its narrow therapeutic window. Toxic cardiac effects are known but seldomly reported and can manifest as sinus node dysfunction (SND) ranging from delayed conduction to sinus arrest with the potential to induce asystole. Theophylline a positive chronotropic agent has been previously used for correction of sinus node dysfunction but never been utilized for the correction of lithium-induced SND. We report the first successful use of Theophylline for rate/rhythm correction of SND in a patient presenting with acute lithium toxicity along with a review summarizing the clinical features of all published literature regarding lithium-induced SND.

Methods: Case report and systematic review of the literature are presented. Three independent scientific databases were queried for reports of lithium-induced SND. A clinical compendium was then generated detailing associated clinical data and descriptive statistics were performed.

Results: 1,117 reports were initially retrieved with full-text review yielding a cohort of 49 unique, independent studies. (61.4%) of patients presented with a supratherapeutic lithium level, 12 (21.1%) were normotherapeutic, and 11 (19.3%) were subtherapeutic. EKG findings varied but most commonly described sinus node dysfunction with a variable degree of sinoatrial block with sinus bradycardia (54.39%) and sinus arrest (29.82%) predominating. Twelve patients (21.1%) required inotrope or vasopressor support. 10 (17.5%) of patient required temporary pacing while 7 (12.3%) required permanent pacemaker implantation. In the majority of cases no significant permanent sequelae were reported as 50 (87.7%) patients recovered, 2 (3.5%) patients had persistent sinus node dysfunction, and 2 (3.5%) patients expired as a result of acute lithium toxicity.

Discussion & conclusion: In this review we report the most up-to-date and comprehensive clinical compendium of lithium-associated sinus node dysfunction along with describing a novel treatment methodology to rapidly correct lithium-induced cardiac toxicity in a patient with long-standing bipolar disorder on chronic lithium treatment. We have reviewed the available literature and provide a comprehensive summary detailing symptomatology of presentation, treatments utilized, electrocardiographic findings and patient prognoses. We have concluded that under the presumptive conditions that transient sinus node dysfunction will resolve with elimination of toxic concentrations of lithium, temporary chronotropic support provided by theophylline administration would be preferable to more invasive measures such as hemodialysis, temporary pacing, or implantation of a permanent pacemaker.

Keywords: arrythmia; hemodialysis; lithium; lithium toxicity; sick sinus syndrome; sinus bradycardia; sinus node dysfunction; temporary pacing.

Figure 1

(A) Initial EKG at obtained in the emergency department at time of patient presentation with evidence of junctional escape rhythm and noted absence of p-waves indicative of sinoatrial dysfunction in all but the last sinus complex. (B) Repeat EKG 30-minutes after administration of atropine showing normal sinus rhythm with emergence of p-waves and bigeminal premature atrial complexes indicative of sinus node and atrial conduction recovery. There is noted lead misplacement of V1 indicated by only positive deflection of QRS complexes not consistent with antecedent and subsequent studies. (C) Repeat EKG obtained 12-hours after atropine administration revealing complete dissipation of sinus node recovery with re-emergence junctional escape rhythm and noted absence of p-waves indicative. (D) Sequential progression of telemetry-capture approximately 12-hours after initial Theophylline dose revealing progressively shortening sinus pauses ranging from sinus arrest of 3.8 s to a briefer pause of 1.12 s to eventual complete resolution of SND with return to normal sinus rhythm. (E) EKG obtained approximately 24 h after theophylline administration with evidence of sustained normal sinus rhythm and regular p-waves with normal sinoatrial conduction pattern.

Figure 2

PRISMA diagram (14) of workflow for selection and retrieval of articles included in our literature review utilizing search engines pubMed, Web of science, and embase.

Figure 3

Timeline of monitoring for serial lithium levels potassium, and creatinine as a marker of renal function over the course of the patient's hospital admission.