BRASH syndrome: a systematic review of clinical manifestations and associated risk factors

doi:10.5847/wjem.j.1920-8642.2025.107

Abstract

Abstract:

BACKGROUND: BRASH syndrome (Bradycardia, Renal failure, AV nodal blockade, Shock, and Hyperkalemia) is a recently described clinical entity characterized by synergistic interaction between AV nodal blocking medications and hyperkalemia. Despite increasing recognition, its clinical characteristics, risk factors, and outcomes remain poorly defined. The rationale of this review is to provide clinicians an up-to-date overview of the most commonly encountered risk factors, triggers, clinical pictures, usual lab values, complications and outcomes, via the systemic analysis of currently published cases.

METHODS: A systematic review was conducted using MEDLINE, Web of Science, and Cochrane Library databases through December 2024. Case reports, case series, and conference abstracts involving adult patients with BRASH syndrome were included. Data extraction focused on demographics, clinical presentations, laboratory findings, management strategies, and outcomes.

RESULTS: Analysis included 131 patients from 111 published cases. Mean age was (71±13) years, with female predominance (58.1%). Hypertension (77.0%), chronic kidney disease (48.4%), and diabetes mellitus (46.7%) were the most common comorbidities. Beta-blockers were the predominant medication (76.5%). Most common presenting symptoms were syncope (17.9%), generalized weakness (16.2%), and altered mental status (11.9%). Mean potassium level was 6.6 mEq/L, with more than half of cases presenting with non-severe hyperkalemia (<6.5 mEq/L). Management often required multimodal therapy, with 50.8% of patients requiring vasopressors and 31.6% requiring hemodialysis.

CONCLUSION: This systematic review provides the most comprehensive analysis of BRASH syndrome to date, demonstrating that while potentially serious, outcomes are generally favorable with appropriate recognition and management. The syndrome can develop even with modest hyperkalemia, particularly in elderly patients with multiple comorbidities. Early recognition and systematic management addressing all components of the syndrome appear crucial for optimal outcomes.

Key words: Bradycardia, Renal failure, AV nodal blockade, Shock, Hyperkalemia

Silviu-Andrei Tomulescu, Gaia Bavestrello Piccini, Ciprian Niță, Anca Stoian, Yaroslava Longhitano, Raymond Planinsic, Giorgia Caputo, Manfredi Tesauro, Antonio Voza, Christian Zanza. BRASH syndrome: a systematic review of clinical manifestations and associated risk factors[J]. World Journal of Emergency Medicine, 2025, 16(6): 521-531.

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Major outcomes	Mean ± SD (Event vs non-event)	t-value	P-value	Lower 95% CI	Upper 95% CI
Mortality
Age, years	75.5 ± 7.9 vs 71.6 ± 13.4	1.66	0.45	-2.05	9.88
Creatinine, μmol/dL	308 ± 173 vs 316 ± 226	0.11	0.91	-144.51	128.72
Mean blood pressure, mmHg	62.8 ± 9.1 vs 64.4 ± 8.9	0.57	0.57	-32.52	58.97
Systolic blood pressure, mmHg	86.1 ± 15.7 vs 88.5 ± 14.8	0.34	0.73	-48.86	69.66
Diastolic blood pressure, mmHg	51.7 ± 9.4 vs 53.2 ± 8.8	0.99	0.32	-22.52	68.79
Heart rate, beats/min	36.3 ± 7.2 vs 37.1 ± 6.8	0.09	0.93	-15.36	16.82
K⁺, mEq/L	6.6 ± 1.0 vs 5.9 ± 0.9	-0.72	0.47	-0.99	0.46
Need for vasopressors
Age, years	69.9 ± 8.3 vs 72.8 ± 9.5	-1.26	0.41	-7.48	1.67
Creatinine, μmol/dL	305 ± 185 vs 334 ± 201	-1.69	0.18	-166.23	14.48
Mean blood pressure, mmHg	62.8 ± 8.1 vs 64.4 ± 9.3	1.92	0.11	-166.23	14.48
Systolic blood pressure, mmHg	86.1 ± 15.7 vs 88.5 ± 14.8	1.77	0.15	-1.43	25.55
Diastolic blood pressure, mmHg	51.7 ± 9.4 vs 53.2 ± 8.8	2.19	0.06	0.79	16.91
Heart rate, beats/min	36.3 ± 7.2 vs 37.1 ± 6.8	0.18	1.72	-3.33	3.98
K⁺, mEq/L	6.6 ± 1.0 vs 5.8 ± 0.8	3.27	0.01	0.63	2.60
Need for hemodialysis
Age, years	75.1 ± 11.6 vs 68.1 ± 13.5	2.56	0.02	1.75	14.15
Creatinine, μmol/dL	612 ± 385 vs 321 ± 179	3.65	0.01	-100.41	-345.57
Mean blood pressure, mmHg	61.5 ± 10.8 vs 64.2 ± 8.9	0.14	1.78	-12.31	10.71
Systolic blood pressure, mmHg	86.4 ± 17.5 vs 88.9 ± 15.3	0.69	0.98	-19.15	9.38
Diastolic blood pressure, mmHg	50.6 ± 8.4 vs 53.2 ± 7.9	0.55	1.17	-7.33	12.80
Heart rate, beats/min	35.4 ± 6.5 vs 37.8 ± 7.1	1.16	0.49	-1.82	6.88
K⁺, mEq/L	4.6 ± 3.8 vs 6.6 ± 1.0	2.85	0.01	-3.54	-0.60

Variable associated with mortality	Odds ratio	Lower 95% CI	Upper 95% CI	Fisher’s exact test
Male sex	2.48	0.56	10.93	0.28
Chronic kidney disease	1.50	0.30	7.07	0.71
Hypertension	6.51	1.33	31.77	0.12
Heart failure	1.07	0.20	5.83	1.00
Atrial fibrillation	1.07	0.20	5.83	1.00
Beta-blocker	12.00	0.02	50.00	0.59
Non-dihydropyridine CCB	0.56	0.06	26.00	1.00
Diuretic	2.32	0.44	12.15	0.37
ACE/ARB	3.98	0.77	20.62	0.14
Beta-blocker or CCB	0.96	0.22	4.22	1.00
Conservative treatment	2.02	0.24	17.27	1.00
Vasopressors/Inotropes	1.14	0.27	4.80	1.00
Hemodialysis	0.29	0.04	2.44	0.10
Transvenous pacemaker	0.81	0.09	7.06	1.00

Variable associated with vasopressor use	Odds ratio	Lower 95% CI	Upper 95% CI	Fisher’s exact test
Sex	1.09	0.51	2.33	0.85
Chronic kidney disease	1.66	0.76	3.62	0.24
Hypertension	1.33	0.47	3.77	0.30
Heart failure	1.49	0.64	3.54	0.39
Atrial fibrillation	1.75	0.72	4.28	0.26
Beta-blocker	2.98	0.98	9.07	0.07
Non-dihydropyridine CCB	1.52	0.63	3.63	0.38
Diuretic	1.09	0.48	2.47	1.00
ACE/ARB	0.73	0.34	1.59	0.57
Beta-blocker or CCB	1.63	0.75	3.56	0.68

Variable associated with hemodialysis	Odds ratio	Lower 95% CI	Upper 95% CI	Fisher’s exact test
Sex	1.59	0.70	3.63	0.30
Chronic kidney disease	1.51	0.64	3.56	0.27
Hypertension	2.42	0.65	8.69	0.39
Heart failure	0.79	0.31	2.00	1.00
Atrial fibrillation	1.09	0.42	2.84	1.00
Beta blocker	1.02	0.33	3.16	1.00
Non-dihydropyridine CCB	0.88	0.34	2.24	1.00
Diuretic	1.15	0.47	2.81	0.82
ACE/ARB	0.77	0.34	1.76	0.68
Beta-blocker or CCB	1.14	0.48	2.67	0.83

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