#56 Tales from the ICU: BRASH Syndrome

What is BRASH Syndrome? The most important toxidrome you’ve never heard of

• BRASH is a synergistic, self-perpetuating toxicologic spiral of

• Bradycardia

• Renal failure (often acute-on-chronic)

• AV-nodal blocker exposure (usually a β-blocker or non-DHP calcium channel blocker)

• Shock

• Hyperkalemia.

The defining physiology is that mild hyperkalemia plus therapeutic AV-node blockade can produce profound bradycardia, worsening renal perfusion and potassium clearance, which then further amplifies hyperkalemia and AV-nodal blocking effect.

Why it matters

• BRASH Syndrome is frequently under-recognized and mislabeled as “just hyperkalemia” or “pure β-blocker/CCB overdose,” which can delay proper treatment.

• Typical patients are older adults with CKD on AV-nodal agents; common precipitants include hypovolemia, up-titration of AV-nodal drugs, and co-medications that worsen renal function or potassium (e.g., ACEi/ARB, potassium-sparing diuretics, etc).

BRASH Pathophysiology: A viscious spiral

1. AV-node blocker + even mild ↑K⁺ ⇒ marked bradycardia (synergy).

2. Bradycardia ⇒ ↓cardiac output ⇒ renal hypoperfusion ⇒ worsening AKI.

3. AKI ⇒ ↓K⁺ excretion & possible drug accumulation (esp. renally cleared β-blockers like atenolol/nadolol).

4. ↑K⁺ + higher AV-nodal blocker levels ⇒ more bradycardia ⇒ shock.

Presentation & Clinical Clues

• History: CKD, recent illness/dehydration, new or up-titrated AV-nodal drugs, or recent addition of a nephrotoxic/hyperkalemia-promoting medication

• Bradycardia out of proportion to the degree of hyperkalemia (often K⁺ ~5.3–6.5 mEq/L). ECG often lacks the classic findigns seen in severe hyperkalemia findings (no big T-waves, QRS widening, etc).

• Bradycardia with only mild hyperkalemia strongly suggests synergy (BRASH) rather than isolated hyperkalemia or large single-agent overdose.

• Shock or malperfusion (cool extremities, low urine output) may be present even with “normal” blood pressure (bradycardia with cryptic shock).

• Limited rreatment response: Standard ACLS bradycardia algorithms alone (e.g., repeating atropine) often fail in BRASH unless you simultaneously fix hyperkalemia and hypoperfusion.

Management: sequence & dosing pearls

Big picture: Treat the entire syndrome (bradycardia and hyperkalemia and perfusion) rather than any single component alone.

1. Hold AV-nodal blockers and hyperkalemia-promoting drugs. Begin volume resuscitation tailored to pH:

   • If acidemic (HCO₃⁻ <22 mEq/L): consider isotonic bicarbonate.

   • If not acidemic: balanced crystalloids (LR/Plasma-Lyte). Avoid large normal-saline loads (hyperchloremic acidosis can worsen K⁺).

2. Stabilize myocardium (first-line for bradycardia in BRASH): IV calcium

   • Calcium chloride 1 g IV (central line preferred in non-crash), or calcium gluconate 3 g IV (peripheral-safe). May repeat for persistent instability (effect lasts ~30–60 min).

   • (Many general references list 1 g Ca-gluconate; in severe cases many experts favor 3 g Ca-gluconate or 1 g Ca-chloride up front.)

3. Shift potassium intracellularly

   • Regular insulin 5–10 units IV + dextrose (e.g., 25–50 g), with frequent glucose checks (30–60 min, then hourly for 4–6 h).

   • High-dose albuterol 10–20 mg neb (continuous or stacked nebs).

   • If acidemic: isotonic bicarbonate as above can aid K⁺ movement.

4. Restore perfusion / rate

   • Epinephrine infusion (e.g., ~2–10 mcg/min, titrate) provides β-1 chronotropy/inotropy and β-2–mediated K⁺ shift; isoproterenol is an alternative where available (strong chronotrope without vasoconstriction).

   • Atropine is often ineffective because the bradycardia isn’t vagally mediated.

   • Watch for occult bradycardic shock (cool, oliguric, “normal” BP) — consider isoproterenol or dobutamine to raise cardiac output.

5. Remove potassium

   • Kaliuresis if making urine (loop ± thiazide ± acetazolamide; replace urine losses with appropriate crystalloid).

   • Consider sodium zirconium cyclosilicate as adjunct.

   • Dialysis if refractory hyperkalemia, severe AKI/ESRD, or failed medical therapy.

6. Temporary pacing

   • Requires in on the minority of patients with refractory instability after aggressive calcium + β-agonist therapy; most BRASH cases respond to medical therapy and do not need transvenous pacing wires.

• Clinical Trials Discussed

• Related Episodes

  Undifferentiated Shock

• References

  Farkas JD, Long B, Koyfman A, Menson K. BRASH Syndrome. J Emerg Med. 2020

  The EMCrit/IBCC: BRASH syndrome — practical, stepwise review of BRASH with comprehensive info on dosing

  Arif AW, et al. BRASH Syndrome with Hyperkalemia. Methodist DeBakey Cardiovasc J. 2020.

  Shah P, et al. Clinical characteristics of BRASH syndrome: systematic scoping review. Eur J Intern Med. 2022.