The BRASH syndrome, a synergistic arrhythmia phenomenon

Abstract

BRASH syndrome is a relatively novel clinical entity with profound bradycardia secondary to simultaneous metabolic derangement and drug toxicity. The syndrome is a clinical pentad of bradycardia, acute kidney injury, use of atrioventricular nodal blocking agents, shock, and hyperkalemia. It is widely underrecognized with selectively few reports, mainly in the elderly population. We present a 43-year-old woman on two oral atrioventricular blocking agents who presented with 1 week of increasing lethargy with rapid deterioration into cardiac arrest with subsequent shock postresuscitation. She was found to have hyperkalemia, metabolic acidosis, and acute kidney injury on arrival. Her initial electrocardiogram was remarkable for sinus arrest and junctional bradycardia. She was treated with a temporary pacemaker, renal replacement therapy, and potassium-lowering agents, with subsequent improvement resulting in conversion to normal sinus rhythm.

BRASH syndrome is a rather novel and underdiagnosed clinical entity. It was first reported in 2016 by Josh Farkas. The syndrome is characterized by the clinical pentad of bradycardia, acute kidney injury (AKI), use of atrioventricular (AV) nodal blocking agents, shock, and hyperkalemia. Patients with BRASH syndrome have profound bradycardia, sinus arrest, and/or AV block that cannot be solely attributed to either their AV nodal medications or their hyperkalemia. ^{1 , 2}

CASE REPORT

A 43-year-old woman with nonalcoholic steatohepatitis cirrhosis, atrial fibrillation, hypertension, diabetes mellitus, and bipolar disorder presented to an outside hospital with 1 week of progressive lethargy and decreased oral intake. Her home medications included oral diltiazem 180 mg daily and oral metoprolol tartrate 50 mg twice daily for rate control of atrial fibrillation. Shortly after arrival to the emergency department, she became unresponsive and went into pulseless electrical activity arrest requiring cardiopulmonary resuscitation, intubation, and vasopressor initiation. After resuscitation, she had a temperature of 98.5°F, blood pressure of 109/42 mm Hg, heart rate of 35 beats per minute, and respiratory rate of 16 breaths per minute. An electrocardiogram at the outside hospital was reported as complete heart block. Initial laboratory workup revealed AKI (creatinine 2.75 mg/dL with baseline 0.7 mg/dL), hyperkalemia (potassium 7.6 mmol/L), and anion gap metabolic acidosis (pH 6.98, partial pressure of carbon dioxide 30 mm Hg, bicarbonate 8.4 mmol/L, lactate 12.5 mmol/L). Initial interventions included lactated Ringer’s fluid boluses, norepinephrine drip, insulin, dextrose, bicarbonate drip, calcium gluconate, broad-spectrum antibiotics, and transcutaneous pacer with subsequent transfer to our hospital.

Upon arrival, the initial chest x-ray demonstrated multifocal pneumonia, and the differential diagnosis included septic shock vs. cardiogenic shock vs. the combination. The transcutaneous pacemaker was switched to a transvenous pacemaker. As a result of the patient’s hyperkalemia and metabolic acidosis, emergent renal replacement therapy and bicarbonate infusion was initiated. Further review of the initial electrocardiogram was deemed sinus arrest with junctional bradycardia at 35 beats per minute (Figure 1a). Hyperkalemia resolved with initiation of renal replacement therapy, and the subsequent electrocardiogram revealed normal sinus rhythm (Figure 1b), allowing for pacemaker removal. Septic over cardiogenic shock was favored as the initial inciting factor due to improvement with antibiotics, steroids, and vasopressors without inotropic support.

Figure 1.

(a) Initial electrocardiogram depicting sinus arrest with junctional bradycardia. (b) Electrocardiogram after hyperkalemia correction depicting sinus rhythm.

DISCUSSION

BRASH syndrome is triggered by an inciting factor that results in renal compromise. In our patient, septic shock resulted in renal compromise with subsequent hyperkalemia. ³ Hyperkalemia with concurrent use of AV nodal blockers caused a profound bradycardia, ⁴ which hindered an adequate tachycardic response to hypovolemia and further reduced renal perfusion (Figure 2). ^{5 , 6}

Figure 2.

The process of an initial renal hypoperfusion insult causing hyperkalemia, which synergizes with AV nodal blockers to cause bradycardia and a subsequent repeating cascade.

The key pathophysiologic characteristic of this syndrome is the synergistic effect of hyperkalemia and AV nodal blockers in causing sinus bradycardia/arrest. In pure hyperkalemia, potassium levels tend to be much higher for patients to develop arrhythmias and electrocardiographic changes. Levels of 6.0 to 6.5 mEq/L typically are associated with tall peaked T waves, whereas severe sinus bradycardia/sinus arrest usually requires potassium >8 mEq/L. ⁷ In BRASH syndrome, potassium levels of 5 mEq/L have been reported for bradyarrhythmias. Also, parts of the Advanced Cardiovascular Life Support (ACLS) bradycardia algorithm do not perform well in BRASH syndrome. For example, atropine is useful in vagally mediated bradycardia by blocking the parasympathetic influence on the heart. ⁸ However, the pathophysiology of bradycardia in BRASH syndrome is unrelated to vagal tone. Thus, following the ACLS algorithm will lead to overutilization of transvenous pacing without actually correcting the underlining etiology. Management should consist of interventions preventing further renal compromise and addressing hyperkalemia: fluid resuscitation, vasopressors and/or inotropic agents, intravenous calcium, intravenous insulin and dextrose, intravenous bicarbonate, or a trial of dialysis.

In conclusion, patients with BRASH syndrome present with profound bradycardia, sinus arrest, or AV nodal block that cannot be solely attributed to medications or hyperkalemia but is caused by a combination of both entities. Aggressive correction of plasma potassium and appropriate fluid management will usually result in quick correction of the electrocardiographic abnormalities. Our case highlights the importance of considering BRASH syndrome in the differential diagnosis of patients presenting with bradycardia, hyperkalemia, and AKI, given the ubiquitous use of AV nodal blocking agents for a variety of conditions. Further, early recognition of BRASH syndrome as well as expeditious treatment of hyperkalemia and other metabolic derangements prevents unnecessary interventions such as pacemaker implantation, as well as adverse outcomes.