BRASH

Co-Authors: Camilo Galeano Londono, Esteban Davila 

This is part 1 of a 2-part series focusing on BRASH Syndrome

The little black phone in the Cardiac Care Unit (CCU) room rings. The cardiology fellow is on the other end of the line informing you of a new admission. The patient is a 79-year-old female with a past medical history of Gastroesophageal Reflux Disease, Chronic Kidney Disease stage 2, and Heart Failure with Reduced Ejection Fraction on goal-directed medical therapy. She presented to the ED with progressive shortness of breath and fatigue. The patient had HR of 30-40/min and SBP of 70 mm Hg. On exam, the patient is in mild respiratory distress and is speaking in short sentences. There are rales bilaterally, halfway to the apices. Bilateral pitting edema is appreciated in both lower extremities extending to the abdominal wall.

This is the initial ECG: 

ECG interpretation: The rate is between 50-60/min. The rhythm is sinus bradycardia with intermittent junctional escape beats. There is right axis deviation and the QRS is low voltage. The intervals are normal. There is no ST-deviation.

The ECG

A junctional escape rhythm occurs when the SA node is no longer working properly and, therefore, unable to suppress the other pacemaker cells in the heart. Classically, this is seen with SA node block or failure.[1] Other cardiac cells with automaticity, or the ability to generate spontaneous, rhythmic action potentials, include the AV node and His-Purkinje system, although all heart regions can develop automaticity during pathological circumstances such as heart failure and hypertrophy.[2] 

When the SA node fails to conduct, the cardiac tissue with the next fastest intrinsic rate will take over pacemaking. The intrinsic pacemaker rate decreases as you move distally from the SA node to the AV node and then to the His-Purkinje system. The SA node is the fastest, usually pacing at 60-100/min, and receives input from both the sympathetic (adrenergic) and parasympathetic (cholinergic) nervous system.[3] The AV node/junction has a pacemaker rate of 40-60/min, while the ventricles are 20-30/min. 

In this ECG, the lack of consistent p-waves suggests that the pacemaker is intermittently below the atria; however, the narrow QRS indicates that the escape impulses originate from a site above the bundle branches. This indicates that this patient’s electrical rhythm is intermittently initiated at the AV node/His bundle, as pictured in the figure below. 

Figure 1: Mechanism of junctional rhythm [4] 

Back to the Patient

In light of the hypotension and bradycardia, the team places transcutaneous pacer pads and initiates peripheral norepinephrine. The potassium returns at 6.4 and BUN/creatinine is 68/3.4. Looking at this constellation of hyperkalemia, bradycardia, and hypertension, you consider a diagnosis of “BRASH” syndrome. BRASH is an acronym that refers to: Bradycardia, Renal failure, AV nodal blockade, Shock, and Hyperkalemia. Let’s take a deep dive into this.

Figure 2: Illustration of BRASH (source: https://emcrit.org/ibcc/brash/)  

Pathophysiology

The pathophysiology of BRASH is based upon the synergistic effect of AV nodal blockade and hyperkalemia causing bradycardia and decreased cardiac output. AV nodal blockers, in this case beta blockers, slow depolarization of the heart’s primary pacemakers causing prolongation of the sinus node cycle length, AV conduction, and AV refractory period primarily through competitive blockade of B1 receptors.[5] Calcium channel blockers cause bradycardia by slowing cardiac conduction at the SA and AV node by blockade of L-type voltage-gated calcium channels.[6] 

Hyperkalemia exerts changes in cardiac physiology through alterations in the cardiac membrane gradient. The resting membrane potential of cardiac myocytes is formed by the concentration gradient of high intracellular potassium and high extracellular sodium, meticulously maintained by the Na-Potassium ATPase pump. More about the cardiac cycle can be found here.

Figure 3: Normal action potential (dark line) and action potential with hyperkalemia (dotted line).[7]

Increased extracellular potassium decreases the resting membrane potential of cardiac myocytes, causing slowed sodium influx. Phase 0 of the action potential, when Na channels open and a large influx of Na enters the cardiac myocyte, is dependent on the resting membrane gradient established by extracellular potassium. As extracellular potassium increases, the membrane potential becomes closer to 0, which decreases the percentage of sodium channels available and decreases the magnitude of the sodium influx; this prolongs the PR, QRS, and QT intervals.[7] 

Common ECG manifestations include peaked T waves, prolonged PR interval, prolonged QRS interval, shortening of the QT interval, decreased P wave amplitude, and at its worst, the sine-wave ventricular rhythm. Common rhythm changes include bradycardia, atrial fibrillation with slow ventricular response, and junctional rhythms.[8] More discussion of hyperkalemic ECG changes can be found here. 

Commonly, the synergism of both the effects of AV nodal blockers and hyperkalemia are greater than the sum of their parts. In other words, patients with BRASH rarely present from an overdose of their AV nodal blocker and the hyperkalemia is usually not severe. Therefore, it is possible to have an ECG without many of the typical findings of hyperkalemia.[9] Clinical history is often the best means to differentiate BRASH from hyperkalemia or AV nodal blocker toxicity alone. Furthermore, renal hypoperfusion and injury can occur because AV nodal blockade and hyperkalemia can result in bradycardia and decreased cardiac output. This may exacerbate the underlying hyperkalemia, as total body potassium levels are maintained by the kidneys.[10] 

Triggers

History-taking should focus on potential triggers, particularly causes of new renal failure. Common triggers include dehydration, recent up-titration of AV nodal blockers, and initiation of medications known to cause renal failure or hyperkalemia. Common culprit nephrotoxic medications include angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, spironolactone, non-steroidal anti-inflammatory drugs, digoxin, cyclosporine, tacrolimus, and trimethoprim.[10] A systematic review of BRASH by Shah et al (n=42) reported precipitating agents below. Important baseline demographics included 26.2% of patients with CKD3, 9.5% of patients with CKD4, and 4.8% of patients with CKD5 or ESRD on hemodialysis.[11] 

Figure 4: Precipitating Agents and Treatments in patients with BRASH[11]

Presentation

Patients may present along a spectrum from asymptomatic to severe multiorgan failure. Presenting symptoms may include dizziness or lightheadedness, presyncope or syncope, shortness of breath, fatigue, or altered mental status from cerebral hypoperfusion.[11,12] Physical exam should focus on hemodynamic stability and include vital signs and assessment of end-organ perfusion. Blood pressure may be variable and dependent on the degree of peripheral vasodilation or vasoconstriction. Keep in mind that although patients may have a “normal” mental status, they may still be underperfusing their kidneys.

Figure 5: Determinants of Cardiac Output and Blood Pressure. (Source: https://emcrit.org/ibcc/bradycardia/#top) 

Back to the Patient

You return to your patient with the diagnosis of BRASH. Upon reevaluation, you confirm with the patient a recent increase in their metoprolol dose. You deduce that this dosing change may have caused a decrease in cardiac output with subsequent renal failure, in turn, causing hyperkalemia.[9] You begin thinking of treatment options when you get another call on the CCU phone . . . 

Stay tuned for part 2 where we will discuss another case and treatment.

Take Home Points:  

- Consider BRASH in patients who present with bradycardia, hyperkalemia, hypotension, and acute kidney injury.  

- Look for underlying triggers: dehydration, AV nodal blocker up-titration, and medications that can increase potassium