BRASH syndrome is a clinical entity with a convoluted pathophysiology and clinical picture. Although the pathophysiology underlying BRASH syndrome has been established for a longer time, its recognition as a specific entity is very recent and little is known regarding its true epidemiology (2). The initiation of the vicious cycle of BRASH syndrome (bradycardia, renal failure, atrioventricular nodal blockade, shock, and hyperkalemia) follows several pathways. Identified triggers include mostly hypovolemia and dehydration, acute kidney injury, the potentiated effect of medications, or generally any event promoting hyperkalemia or renal failure (1, 2, 4). Older patients with multiple comorbidities, mainly cardiac and renal diseases may be at higher risk of developing BRASH, especially if their medications include multiple different AV-nodal blocking medications (2). The symptomatology of BRASH is rather complicated. Patients usually present with a variety of signs and symptoms, but the most common presentation is symptomatic bradycardia. Patients may also present with other complaints, including syncope, generalized weakness, altered mental status, dyspnea or dizziness/lightheadedness, and others (1). Differential diagnosis of a patient presenting with any BRASH syndrome signs and symptoms can naturally be very long. However, early recognition and diagnosis are critical to avoid multiorgan failure and adverse outcomes (2).
Our patient was transferred to the ED by EMS with a complex of symptoms, which were evaluated by EMS and neurologist as a possible stroke event, given the patient's complaints, clinical presentation, and personal history. Bradycardia was initially identified and the treatment by atropine was attempted, however, it was initially assigned to a potential complex of stroke symptoms (suspected Cushing reflex). After the suspicion of a stroke was rejected by CT imaging, the team was prompted to look into differential diagnoses to explain her complex symptomatology. Laboratory findings uncovered mild hyperkalemia, elevated BUN, creatinine, and serum bicarbonate with concomitant hypoglycemia.
We can speculate that neurologic symptomatology and altered mental status were present due to the low-flow stage causing brain hypoperfusion and the manifestation of the brain's “locus minoris resistentiae” in combination with acute renal failure and subsequent uremia. Hypoglycemia and decreased brain perfusion may very well imitate stroke symptoms too, but her glycemia was repeatedly measured by the EMS crew on the scene and she was not severely hypoglycemic at that time. Patients with advanced chronic kidney disease and insulin use have a higher risk for serious hypoglycemic events (5). Metabolism and the effect of insulins and other medications used to treat diabetes mellitus during BRASH cascade are not well understood. Though the first measurement on the scene could not be classified as hypoglycemia, the repeated measurement confirmed very low values, which can cause neurological impairment. As a severe diabetes patient, she was on numerous hypoglycemic medications. The patient denied overuse of medications or improper dosing protocols. We can speculate if acute renal failure in combination with bradycardia, hypoperfusion, and accumulation of medications and their metabolites can cause synergic effects and subsequently reinforce hypoglycemic effects of antidiabetic medications even without overdose or wrong dosing, as seen in this particular case.
Hyperkalemia may precipitate cardiac rhythm changes including bradycardia or even heart block, asystole, and ventricular tachycardia/ventricular fibrillation. However, these changes usually occur with more severe hyperkalemia ((K+) > 7.0 mmol/L), though the exact level of hyperkalemia which can cause these changes varies considerably (3). Severe hyperkalemia often has additional ECG findings, such as QRS widening and typical changes to the morphology of the P and T-waves, which are often absent in BRASH syndrome (2). ECG and rhythm abnormalities that are disproportionate to the degree of hyperkalemia should suggest other possible factors, which may be influencing and accentuating the effects of mildly elevated potassium levels (6).
The treatment of BRASH syndrome is primarily focused on resuscitation and stabilization of vital functions, mostly with vasopressors and fluids, with careful treatment of other conditions as well. One of the common errors in managing BRASH syndrome is focusing only on a single component of the syndrome, rather than approaching it from its complex perspective (2, 7). This may happen when BRASH is not recognized (e.g. we are treating the patient only within the silo of one of its specific symptoms) or one particular symptom seems to be more dangerous than another, which is often ignored in the emergency care phase (e.g. profound bradycardia).
Our patient's hemodynamic status was managed by atropine, dopamine, and fluids, however, due to concomitant hypoglycemia, we were not able to manage hyperkalemia with insulin, only by calcium gluconate for cardiac protection. We stabilized vital functions, replaced fluids, and supported diuresis through furosemide and this treatment mode was reinforced and continued in the ICU. On such treatment, she continued to improve and was ultimately discharged with altered chronic medication to decrease the risk of future recurrence.
To date, there were several case studies of BRASH syndrome reported (1). Only a few complex articles and reviews broadly analyzed the condition, its epidemiology, and treatment. Such complex presentation of BRASH syndrome complicated by altered mental status, suspected stroke, and hypoglycemia (due to accumulation and potentiation of antidiabetic medications) was not reported.
Ultimately, BRASH syndrome remains an under-recognized clinical diagnosis (1, 6). Improving understanding of diverse presenting signs and symptoms and the influence of other acute and chronic conditions can help healthcare workers in faster recognition and better management of this syndrome, ultimately improving survival and patient outcomes. Further research is needed to create and establish effective triaging tools, consistent diagnostic criteria, and therapeutic guidelines to reduce the time until appropriate treatment, unnecessary interventions, and complications related to its complicated pathophysiology and presentation.