Bradycardia, Renal Failure, Atrioventricular Nodal Blockade, Shock and Hyperkalemia (BRASH) Syndrome in the Setting of Amiodarone Use

Introduction Bradycardia, renal failure, atrioventricular (AV) nodal blockade, shock, and hyperkalemia (BRASH) is a syndrome resulting from the synergistic effect of profound hyperkalemia and AV nodal blockade, resulting in a cyclic pattern of bradycardia, and worsening renal function, in turn exacerbating hyperkalemia. This syndrome is classically defined with beta-blockers (BB) and calcium channel blockers (CCB). We present a case of BRASH syndrome in the setting of amiodarone - class III antiarrhythmic with alpha- and beta-blocking properties. Case Presentation 58-year-old obese male presents with dyspnea, and lower extremity swelling. Medical history is notable for hypothyroidism, atrial fibrillation, and recent hospitalization for novel coronavirus-2019 (COVID-19) complicated by acute renal failure requiring temporary hemodialysis. Active medications include levothyroxine, amiodarone, and apixaban. Patient is afebrile, with pulse 49 beats per minute (bpm), blood pressure 85/54mmHg, and respiratory rate 32 breaths per minute. On exam, respirations are non-labored, with bibasilar rales, jugular venous distention, and anasarca. Electrocardiogram shows sinus bradycardia (pulse 53bpm), with first-degree AV block and PR interval of 240ms. Basic metabolic panel: blood urea nitrogen 73 mmol/L, creatinine 2.3 mg/dL, sodium 125 mmol/L, chloride 93 mmol/L, and potassium 5.9 mEq/L. TSH is elevated (7.34 mIU/L) with normal free T4 level (1.2 ng/dL). A formal transthoracic echocardiography suggests normal systolic and diastolic function. Baseline cortisol level could not be ascertained;nevertheless, 60-minutes post-cosyntropin administration, cortisol level is 71.8 ug/dL. Repeat testing 96-hours later was not suggestive of adrenal insufficiency. Discussion The diagnosis of BRASH syndrome requires bradycardia in the setting of synergistic effect of hyperkalemia and AV nodal blockade with underlying renal insufficiency, in turn exacerbating hyperkalemia. There is a paucity of literature delineating the pathophysiology of BRASH. Unlike most reported cases classically involving BB or CCB, in our patient, the AV nodal blocking medication implicated is amiodarone. Amiodarone is a class III antiarrhythmic with alpha- and beta-blocking properties which prolongs the action potential and refractory period in myocardial tissue, thereby decreasing AV conduction and sinus node function. The anti-sympathetic action, calcium, and potassium channel blockade are responsible for the negative chronotropic effects as seen in BB and CCB. There has been one reported case linking BRASH and amiodarone. However, multiple doses of diltiazem and metoprolol were also cited. Our patient received no additional AV nodal blocking agents. Conclusion Patients taking amiodarone can present in renal failure as part of BRASH syndrome. With the wide use of amiodarone, this case deserves attention from clinicians.