CASE REPORT |
https://doi.org/10.5005/jp-journals-11006-0158 |
A Rare Case of BRASH Syndrome: Diagnostic and Therapeutic Challenges
1,5Department of Anesthesiology, Father Muller Medical College, Mangaluru, Karnataka, India
2Department of Anesthesiology and Critical Care Medicine, Father Muller Medical College, Mangaluru, Karnataka, India
3Department of Critical Care Medicine, Father Muller Medical College, Mangaluru, Karnataka, India
4Department of Internal Medicine, Father Muller Medical College, Mangaluru, Karnataka, India
Corresponding Author: Manoj Kumar R, Department of Anesthesiology and Critical Care Medicine, Father Muller Medical College, Mangaluru, Karnataka, India, Phone: +91 8072952625, e-mail: manovignes@gmail.com
Received: 16 December 2024; Accepted: 10 January 2025; Published on: 25 February 2025
ABSTRACT
Aim and background: BRASH syndrome (bradycardia, renal failure, AV-nodal blockade, shock, and hyperkalemia) is a rare and underrecognized clinical entity that poses significant diagnostic and therapeutic challenges.
Case description: We report the case of a 75-year-old female with multiple comorbidities presenting with symptomatic bradycardia and shock due to BRASH syndrome, triggered by AV nodal-blocking medications and sepsis-induced hypovolemia. Early recognition, prompt discontinuation of precipitating drugs, correction of hyperkalemia, and hemodynamic stabilization resulted in a favorable outcome.
Conclusion: This case underscores the importance of timely diagnosis and comprehensive management to prevent complications, reduce the need for invasive interventions, and improve overall patient outcomes in BRASH syndrome.
Clinical significance: In elderly patients with multiple comorbidities, combining calcium channel blockers (CCBs) and beta-blockers should be done with caution. Vigilant monitoring for BRASH features is essential, and even mild hyperkalemia must be treated promptly. Early recognition and tailored management can improve outcomes in BRASH syndrome.
Keywords: Acute kidney injury, Bradycardia, BRASH syndrome, Case report, Elderly, Hyperkalemia, Junctional rhythm
How to cite this article: Rench JH H, Kumar R M, Sundarsingh V, et al. A Rare Case of BRASH Syndrome: Diagnostic and Therapeutic Challenges. Indian J Crit Care Case Rep 2025;4(2):50–53.
Source of support: Nil
Conflict of interest: None
Patient consent statement: The author(s) have obtained written informed consent from the patient for publication of the case report details and related images.
INTRODUCTION
The BRASH (bradycardia, renal failure, AV-nodal blockade, shock, and hyperkalemia) syndrome is a rare and underrecognized condition that can lead to significant cardiovascular and systemic manifestations, resulting in morbidity and mortality.1 We report the case of a 75-year-old female with multiple comorbidities who presented with symptomatic bradycardia and shock. Timely diagnosis and management led to a favorable outcome, underscoring the importance of recognizing this complex syndrome.
CASE DESCRIPTION
A 75-year-old female presented with complaints of multiple swellings over both lower limbs for 10 days. She had a medical history of coronary artery disease with previous percutaneous coronary intervention to multiple vessels, chronic kidney disease (nonoliguric), type 2 diabetes mellitus, and hypertension. Her routine medications included insulin, amlodipine 5 mg once daily, a combination of metoprolol 50 mg and telmisartan 40 mg, and antiplatelets.
The lower limbs exhibited diffuse, warm, and tender swellings on examination, with the largest measuring 2 × 2 cm. Ultrasonography of the soft tissues revealed focal cellulitis in the left mid-thigh and right knee. She was diagnosed with bilateral lower limb pyoderma and started on intravenous cefotaxime 1 gm twice daily. The patient was admitted to the ward, and her telmisartan was withheld due to hyperkalemia and worsening renal function. Nifedipine 10 mg twice daily was added to her treatment regimen.
She developed generalized weakness, blurring of vision, and respiratory distress, necessitating a transfer to the intensive care unit (ICU). On ICU arrival, she was conscious, oriented to time, place, and person, and protecting her airway. Her respiratory rate was 24 breaths per minute, her heart rate was 38 beats per minute, and her blood pressure was 70/50 mm Hg, with cold extremities and a mean arterial pressure (MAP) of 56 mm Hg. She received two doses of atropine 0.6 mg, which transiently increased her heart rate to 45 beats per minute. An adrenaline infusion was initiated at 0.05 mcg/kg/minute to maintain her blood pressure. All antihypertensive medications were withheld due to the ongoing shock.
Her investigation trends are shown in Table 1. Arterial blood gas analysis revealed a pH of 7.38, pCO₂ of 31 mm Hg, HCO₃ of 18 mmol/L, potassium of 5.9 mmol/L, sodium of 129 mmol/L, and lactate of 2.2 mmol/L. The patient was found to be hypovolemic and was resuscitated with intravenous fluids. Hyperkalemia was managed with calcium gluconate, insulin with dextrose, and nebulized salbutamol. A 12-lead electrocardiogram (ECG) showed bradycardia with a junctional rhythm (Fig. 1). Bedside echocardiography revealed a left ventricular ejection fraction of 53%, with no regional wall motion abnormalities. Her chest X-ray was unremarkable.
| Parameters | Day 1 | Day 2 | At discharge |
|---|---|---|---|
| Urea (mg/dL) | 82 | 62 | 37 |
| Creatinine (mg/dL) | 2.4 | 2.3 | 1.1 |
| Sodium (mEq) | 131 | 131 | 131 |
| Potassium (mEq) | 6.1 | 5.2 | 4.1 |
| Chloride (mEq) | 100 | 99 | 103 |
| Hemoglobin (gm/dL) | 12.2 | 10.9 | 11.4 |
| Total leukocyte count (cells/mm3) | 17620 | 26590 | 11000 |
| Platelets (cells/mm3) | 297000 | 273000 | 302000 |
| C-reactive protein (mg/dL) | 161.9 | 104.6 | 46.9 |
| Whole blood troponin I quantitative | <0.01 ng/mL | ||
| Serum CK-MB activity | 8 IU/L |
Fig. 1: ECG of the patient showing bradycardia with junctional rhythm
A pus culture from the burst swelling on her left lower limb revealed the presence of methicillin-resistant Staphylococcus aureus (MRSA), treated with injection linezolid 600 mg twice daily.
A detailed differential diagnosis was considered in this case. Drug overdose was an unlikely cause of the patient’s presentation, as she was hospitalized and receiving only prescribed medications, but the Naranjo Adverse Drug Reaction Probability Scale2 shows a score of 6, indicating a possible drug reaction. Septic shock was considered due to focal cellulitis and bilateral lower limb pyoderma, elevated inflammatory markers, and positive blood cultures; however, the absence of fever, bradycardia, and cold peripheries, with narrow pulse pressure, made sepsis less likely to be the sole cause. The cardiogenic shock from myocardial infarction was ruled out as initial troponin levels were negative, echocardiography showed a normal ejection fraction with no regional wall motion abnormalities, and the ECG did not indicate ischemic changes. Hyperkalemia-induced bradycardia was another consideration, given the elevated potassium levels (5.9 mmol/L) and junctional rhythm on ECG; however, the lack of typical hyperkalemia-related ECG changes, such as peaked T-waves or QRS widening, made this an incomplete explanation for the degree of bradycardia observed.
Despite adequate fluid resuscitation, the patient’s hypotension persisted. Her blood pressure showed significant improvement only after an increase in heart rate, achieved through adrenaline infusion and discontinuation of AV nodal-blocking medications.
The most plausible explanation for her presentation involves the combined effects of AV nodal-blocking medications and sepsis-induced hypovolemia, which precipitated acute kidney injury (AKI) and hyperkalemia, leading to bradycardia and hypotension. This clinical picture is consistent with the BRASH syndrome.
Over the next 48 hours, her hyperkalemia resolved, AKI improved, and bradycardia resolved, with a return to sinus rhythm on ECG. The patient’s condition stabilized, and she was transferred back to the ward. Her antihypertensive medications were optimized. She was discharged on oral prazosin hydrochloride, amlodipine, and antiplatelets. A month after the event, the patient’s potassium levels and renal function remained stable, with an ECG showing a normal sinus rhythm.
DISCUSSION
Our patient presented with cellulitis associated with pyoderma and displayed features characteristic of BRASH syndrome, likely precipitated by the chronic use of AV nodal-blocking medications and sepsis-induced hypovolemia, which led to AKI and hyperkalemia. The elevated potassium levels exacerbated bradycardia by impairing cardiac conduction, resulting in persistent hypotension and circulatory shock.
The BRASH syndrome (bradycardia, renal failure, AV-nodal blockade, shock, and hyperkalemia) is a rare but clinically significant condition, first described by Dr Josh Farkas in 2016, where standard ACLS algorithms are less effective.3 Patients often respond poorly to atropine,4,5 as seen in our case. It involves a harmful interaction between AV-nodal-blocking agents, hyperkalemia, and renal dysfunction, characterized by severe bradycardia, hypotension, and metabolic abnormalities.
The BRASH syndrome is predominantly observed in elderly patients with multiple comorbidities, making them a vulnerable population. The average reported age is 69 years, with hypertension (71%), diabetes (48%), and chronic kidney disease (44%) being the most common associated conditions.6 Our patient had similar characteristics, which highlights the importance of recognizing this syndrome in similar high-risk individuals.
The BRASH syndrome is characterized by a vicious cycle7 in which bradycardia reduces renal perfusion, leading to AKI and subsequent hyperkalemia, which further exacerbates bradycardia. This cycle, if unaddressed, can rapidly progress to multiorgan failure. Beta-blockers and calcium channel blockers (CCBs) are commonly identified as the primary culprits in BRASH syndrome; angiotensin receptor blockers (ARBs) have also been implicated as contributing factors.6
In our case, the likely trigger was new-onset hyperkalemia combined with additional AV nodal blockade from metoprolol, nifedipine, and amlodipine, which contributed to BRASH syndrome. Using the Naranjo Adverse Drug Reaction Probability Scale,2 the patient received a score of 6, indicating that the heart block was ”probably” caused by CCBs and beta-blockers.
Patients with BRASH syndrome can present with a spectrum of symptoms, ranging from mild bradycardia to severe multiorgan failure. Despite significant derangements in vital signs and lab results, they may appear less ill than expected.
Several key features distinguish BRASH syndrome from isolated hyperkalemia and AV nodal blocker toxicity. In BRASH syndrome, bradycardia often occurs with moderate hyperkalemia and is synergistically exacerbated by therapeutic levels of AV nodal-blocking drugs rather than drug toxicity.3 Unlike isolated hyperkalemia, which usually requires severe potassium elevation (>7 mEq/L) to cause bradycardia, BRASH syndrome can occur at lower potassium levels (<6.5 mEq/L).5,7,9 Additionally, an ECG showing bradycardia without other typical hyperkalemia changes, with features like junctional escape rhythm (50%), sinus bradycardia (17.1%), and complete heart block (12.9%).6 In our case, the patient had moderate hyperkalemia (potassium 5.9 mEq/L) and was concurrently using AV-nodal-blocking agents (metoprolol, nifedipine, and amlodipine). The ECG revealed sinus bradycardia with a junctional rhythm.
Effective management of BRASH syndrome requires addressing all components of the syndrome rather than focusing on a single issue.1 The mainstays of treatment include:
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Stabilization of hemodynamics [volume expansion + inotropes ± pacing (temporary/permanent)].
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Rapid correction of hyperkalemia [calcium gluconate + insulin dextrose + nebulized salbutamol + sodium bicarbonate (if metabolic acidosis coexists) ± renal replacement therapy].
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Cessation of precipitating medications (AV nodal-blocking medications).
Outcomes in BRASH syndrome can vary widely, ranging from complete recovery to mortality. Some patients may require temporary or permanent pacemakers, while others may need emergent renal replacement therapies.10 In more severe cases, multiorgan dysfunction can occur, and mortality is also a potential outcome. The variability in outcomes highlights the importance of early diagnosis and intervention to improve prognosis and minimize the risk of complications.6
In our case, timely intervention resulted in rapid symptom resolution and stabilization, preventing the need for invasive treatments such as transvenous pacing (33%) or dialysis (20%).6
CONCLUSION
It is essential to maintain a high index of suspicion for BRASH syndrome in elderly patients who are on AV nodal-blocking medications, have AKI, and hyperkalemia, and present with bradycardia and hypotension. Early identification and prompt intervention, aimed at breaking the vicious cycle, can prevent complications and minimize the need for major treatments like pacemakers or hemodialysis, ultimately improving patient outcomes.
Clinical Significance
In elderly patients with multiple comorbidities, combining CCBs and beta-blockers should be done with caution. Vigilant monitoring for BRASH features is essential, and even mild hyperkalemia must be treated promptly. Early recognition and tailored management can improve outcomes in BRASH syndrome.
AVAILABILITY OF DATA AND MATERIALS
All data and materials available at request.
ORCID
Hari Rench JH https://orcid.org/0009-0004-9156-2187
Manoj Kumar R https://orcid.org/0000-0002-4990-3708
Vijay Sundarsingh https://orcid.org/0009-0009-3303-2328
Lishal A Misquith https://orcid.org/0009-0004-4065-2473
REFERENCES
1. Farkas JD, Long B, Koyfman A, et al. BRASH syndrome: bradycardia, renal failure, AV blockade, shock, and hyperkalemia. J Emerg Med 2020;59(2):216–223. DOI: 10.1016/j.jemermed.2020.05.001
2. Adverse drug reaction probability scale (Naranjo) in drug induced liver injury. In: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012. Available from: http://www.ncbi.nlm.nih.gov/books/NBK548069/.
3. Farkas J. PulmCrit-BRASH syndrome: bradycardia, renal failure, Av blocker, shock, hyperkalemia. EMCrit Project. 2016. Available from: https://emcrit.org/pulmcrit/brash-syndrome-bradycardia-renal-failure-av-blocker-shock-hyperkalemia/.
4. Srivastava S, Kemnic T, Hildebrandt KR. BRASH syndrome. BMJ Case Rep 2020;13(2):e233825. DOI: 10.1136/bcr-2019-233825
5. Habib A. BRASH syndrome: a rare but reversible cause of sinus node dysfunction. HeartRhythm Case Rep 2024;10(6):398–401. DOI: 10.1016/j.hrcr.2024.03.005
6. Majeed H, Khan U, Khan AM, et al. BRASH syndrome: a systematic review of reported cases. Curr Probl Cardiol 2023;48(6):101663. DOI: 10.1016/j.cpcardiol.2023.101663
7. Saini T, Reny J, Hennawi HA, et al. The vicious cycle of BRASH syndrome: a case report. Glob Cardiol Sci Pract 2023;2023(1):e202302. DOI: 10.21542/gcsp.2023.2
8. Shah P, Silangruz K, Lee E, et al. Two cases of BRASH syndrome: a diagnostic challenge. Eur J Case Rep Intern Med 2022;9(4):003314. DOI: 10.12890/2022_003314
9. Ghallab M, Noff NC, Sandhu J, et al. A case report of BRASH (bradycardia, renal failure, atrioventricular (AV) blockage, shock, and hyperkalemia) syndrome with a challenging diagnosis and management dilemma. Cureus 2023;15(10):e46413. DOI: 10.7759/cureus.46413
10. Imburgio S, Johal A, Udongwo N, et al. BRASH syndrome: a case report and literature review. J Integr Cardiol Open Access 2022;2022(3):1–4. DOI: 10.31487/j.JICOA.2022.03.05
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