BRASH Part 2: A BRASH with Death

Co-Authors: Esteban Davila, Hemil Chauhan

This is part 2 of a 2-part series focusing on BRASH. Part 1 can be found here.

Patient Presentation

A 70-year-old male with a past medical history of diabetes, hypertension, and chronic kidney disease (baseline creatinine 2-3 mg/dL) is brought in by EMS after being found unresponsive. EMS reports bradycardia to 20/min, blood glucose level 480 mg/dL, and they placed the patient on oxygen. On arrival to the ED, the patient is unresponsive to verbal or tactile stimuli and has agonal respirations. The heart rate is 20-40/min, respiratory rate 16/min, blood pressure 86/50 mm Hg, and pulse oximetry 75% on room air. The examination is notable for decreased responsiveness, S1 and S2, lungs clear to auscultation, cool extremities, and palpable bounding pulses. The ED providers begin assisted ventilation with a bag-valve-mask, place transcutaneous pacemaker pads, and administer 2 liters of normal saline by rapid bolus. Before administering atropine, this ECG is obtained: 

ECG Interpretation: Wide complex bradycardia at 20/min with no p waves consistent with ventricular escape rhythm; axis is normal; QTc is 87 msec by the Bazett formula; T wave inversions V1-V3. 

The ECG

A ventricular escape rhythm is characterized by rate less than 50/min, lack of preceding p waves, and wide QRS. As the rate increases from 50 to 130/min, the rhythm is called accelerated idioventricular rhythm. As pacemakers more proximal in the cardiac conduction system fail to generate impulses that are conducted to the ventricles, a focus in the ventricle, typically in the Purkinje system, assumes the role of the pacemaker. Common causes of ventricular escape rhythm include sino-atrial exit block, high-grade second-degree AV block, third-degree AV block, hyperkalemia, and drug toxicity such as beta-blockers, calcium-channel blockers, and digoxin.[1] 

Figure 1: On the left, note the lack of p waves, likely indicating sino-atrial arrest with ventricular escape. On the right, note the consistent p waves that march out without ventricular capture, indicating complete heart block. (Sources: https://litfl.com/ventricular-escape-rhythm-ecg-library/, https://litfl.com/av-block-3rd-degree-complete-heart-block/)

One mg of Atropine increases the heart rate to the 60s, though there is no change in the mental status. The ED providers decide to resuscitate with more IV fluids before proceeding to intubation. The pH is 7.23, bicarbonate 10 mEq/L, potassium 6.8 mEq/L, and creatinine of > 6 mg/dL. A quick chart check reveals a medication list that includes metoprolol and lisinopril. Having just evaluated the patient in Part I, you confidently diagnose this patient with BRASH. Now let’s discuss the treatment.

Treatment 

As discussed before, the pathophysiology of BRASH includes synergism between hyperkalemia and AV nodal blockers as well as any other underlying triggers contributing to the presentation. For that reason, fixating on and addressing just one of the pathologies may result in under-resuscitation.[2] 

General treatment: This may be a case of CAB instead of ABC first. In BRASH, the etiology of respiratory insufficiency is central due to shock (bradycardia and hypotension); therefore, early use of medications that increase chronotropy and vasoconstriction, such as push-dose epinephrine, should be administered before deciding upon intubation. As noted in our prior BRASH post, a “normal” blood pressure should not be 100% reassuring, as blood pressure is dependent on the degree of peripheral vasodilation or vasoconstriction; patients with “normal” blood pressure may still be under-perfusing their kidneys. Patients presenting with hypovolemia should receive IV fluids, and those with severe uremic acidosis and hyperkalemia could theoretically benefit from isotonic bicarbonate.[2] 

Hyperkalemia 

Treatment for hyperkalemia in BRASH mirrors that of general hyperkalemia treatment, with the caveat that the threshold K level to treat should be lower. 

Stabilize the Cardiac Membrane

Calcium, either 3 g of calcium gluconate or 1 g of calcium chloride, should be administered to stabilize the cardiac cell membrane to prevent malignant dysrhythmia. Repeat doses should be given within 5 to 10 minutes if there is no normalization of the ECG.[3]

Shift Potassium Intracellularly 

IV insulin, generally at a dose of 5 to 10 units, stimulates the Na-K ATPase, causing intracellular shifts of the extracellular potassium.[4] To avoid iatrogenic hypoglycemia, 25 to 50 g of glucose should be administered as 50 to 100 mL of D50W.[5] For patients with acute kidney injury, chronic kidney disease, or ESRD, two retrospective studies demonstrated a similar efficacy of 5 units of IV insulin compared to 10 units with a lower incidence of hypoglycemia.[6,7] Beta-adrenergic agonists such as Albuterol 10 to 20 mg nebulized, increases the activity of the Na-K ATP-ase as well as induces mild hyperglycemia, making simultaneous administration with IV insulin ideal.[8] Sodium bicarbonate, previously recommended for treatment of hyperkalemia, does not significantly decrease potassium in those with a normal pH, though there may be a small benefit in patients with metabolic acidemia.[9]

Eliminate Potassium from the Body 

There are 3 methods of elimination for potassium in the body: from the urine, stool, or blood. 

For urinary excretion, loop diuretics, such as furosemide, can produce renal excretion of potassium. The addition of additional loop diuretics such as thiazides and acetazolamide may bolster this effect, though special attention should be paid to over-diuresis or significant electrolyte depletion.[9] Additionally, the patient needs to be able to make urine, taking this method off the table if the patient has severe kidney injury and remains anuric. In patients with acute kidney injury from dehydration however, fluid repletion could induce kaliuresis (excreting potassium in the urine), and diuretics should be avoided until after volume repletion. 

For excretion in the stool, options include patiromer and sodium zirconium cyclosilicate, though these medications are unlikely to lower potassium levels in the acute setting. A prior study demonstrated potassium-lowering effects of Sodium Zirconium Cyclosilicate as quickly as one hour,[10] however, the ENERGIZE RCT did not demonstrate a significant decrease in potassium concentration at four hours when compared to placebo.[11] Sodium Polystyrene Sulfonate is generally not recommended given the lack of proven effectiveness and concerns for significant GI adverse effects.[9] 

For elimination from the blood, dialysis should be considered when the patient has compromised renal function and cannot “kaliurese”, and the hyperkalemia is refractory to medical treatments. Patients with baseline ESRD will require dialysis.[3] Dialysis is the most effective way of lowering potassium, though this requires significant coordination of resources and potentially invasive procedures. 

Back to the Patient

The ED providers administer 3 g of calcium gluconate, and as the team prepares to treat the hyperkalemia and intubate, bradycardia to the 20s recurs. The providers administer Atropine a second time without response, and the patient becomes pulseless. After five rounds of CPR, 1 mg of epinephrine, and 4 grams of calcium gluconate, there is a return of spontaneous circulation. After intubation, the team administers norepinephrine and vasopressin drips for refractory shock. 

The team administers 10 mg of albuterol through the endotracheal tube, 5 units of insulin, and another 2 g of calcium gluconate to treat hyperkalemia. To elevate the heart rate, transcutaneous pacing has limited success with only intermittent capture. At this point, the team prepares for transvenous pacemaker placement. However, you wonder: would this be effective in BRASH? Unfortunately, there are very few studies on patients with BRASH, with the majority being case reports and series, meaning all recommendations are extrapolated from patients with bradycardia or hyperkalemia. Therefore, BRASH treatment requires physician judgment. 

Bradycardia

The general management of significant bradycardia includes increasing the ventricular rate, followed by identification and reversal of any reversible causes. For patients with BRASH, the etiology of bradycardia is both AV blocker toxicity and hyperkalemia. ACLS does not specifically address BRASH, so treatments below are examined with the pathophysiology and prior evidence, or lack thereof, in mind. 

Pharmacologic

Given the underlying hyperkalemia, first-line pharmacologic treatment should include calcium.[2,12] Though ACLS recommends atropine (1 mg bolus every 3 to 5 minutes as needed, maximum 3 mg) as a first-line therapy for unstable bradycardia,[13] multiple case reports have demonstrated decreased efficacy of atropine for the treatment of BRASH.[14,16] As an antimuscarinic, Atropine acts as a vagolytic at the SA and AV nodes.[16] The combination of hyperkalemia and AV node blockade, poor circulation from hypotension and bradycardia, and Atropine’s short half-life may explain why it may be less effective for BRASH. 

ACLS recommends either dopamine (5 to 20 mcg/kg/min) or epinephrine infusion (2 to 10 mcg/min) next, though as mentioned before, epinephrine should be prioritized, not only for its effect on heart rate and cardiac output, but also its temporary effect of shifting potassium intracellularly.[2] Alternative medications include isoproterenol, a beta-1 and beta-2 adrenergic agonist useful for its positive chronotropic effect, though financial costs may be prohibitive.[17,18]

Adjuvant Medications

Digoxin Fab antibody fragment is recommended if digoxin toxicity is suspected. Both glucagon and high-dose insulin therapy are options if the bradycardia is deemed to be secondary to beta-blocker or calcium channel overdose, though both treatment modalities have low-quality evidence and have not proven effective for BRASH syndrome; therefore they cannot be recommended.[12,19] 

Mechanical 

While initiating pharmacological options, place transcutaneous pads on the patient if emergent pacing is required. Patients refractory to initial pharmacotherapy may require transcutaneous pacing, with one randomized feasibility prehospital study demonstrating similar effectiveness between transcutaneous pacing and dopamine infusion.[20] The 2018 ACC/AHA/HRS guidelines for bradycardia recommend transcutaneous pacing in patients with severe symptoms or hemodynamic compromise and transvenous pacing if initial medical therapy modalities fail.[12] Notably, the strength of recommendation for these treatments is moderate to weak with limited data, and BRASH patients were not the primary studied population.

Multiple case reports have reported varying levels of successful capture using transcutaneous and transvenous pacing in patients with BRASH.[14,21,22,23] Lack of capture may stem from changes to the cardiac membrane by hyperkalemia. Prior studies on patients with pacemakers and hyperkalemia show a widening of the paced QRS from delayed intraventricular conduction velocity, increased atrial and ventricular pacing thresholds, and increased delays from the pacemaker stimulus to the onset of depolarization, with potential immediate amelioration of these effects with the administration of calcium.[24,25] 

Figure 2: Acute Pacing Algorithm.[12]

Back to the Patient

The ED team places a transvenous pacemaker with improvement of the heart rate to 70/min and blood pressure to 110/70 mm Hg. Later, the blood pressure again begins to drop, and a quick evaluation of the patient and cardiac monitor reveals pacer spikes with no capture, and the pulse is palpated to be in the 20s. It is possible that the cardiac monitor showed pacing artifacts that may have been misinterpreted as electrical capture.[26] A quick review of the chest X-ray reveals the transvenous pacemaker wire looped near the tricuspid valve (note, this view can also be seen with point-of-care ultrasonography). As the team prepares to adjust the pacemaker wire, the patient has another cardiac arrest. After 2 rounds of CPR and 1 g of calcium chloride, ROSC again is achieved, and the team adjusts the pacemaker wire until there is capture. 

At this time, the potassium has dropped from 7.0 to 6.2. Head CT is normal, and the patient is transferred to the medical intensive care unit. 

After 24 hours of sodium bicarbonate and insulin infusions and furosemide, the patient’s mental status and kidney function begin to improve, and the hyperkalemia resolves. The heart rate improves, normal sinus rhythm resumes, and the transvenous pacemaker is removed. The patient is eventually discharged home with discontinuation of metoprolol and ACE inhibitor, which are both common triggers of BRASH.[2,19] 

Take Home Points: 

• Since BRASH is a constellation of pathologies, management entails targeting several problems at once: hyperkalemia and bradycardia/hypotension 
• Calcium is the first-line treatment for both hyperkalemia and bradycardia 
• Consider epinephrine infusion early
• Transcutaneous and transvenous pacing has limited evidence though it has been successful in some cases; beware that hyperkalemia may prevent capture