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Bradycardia, Renal Failure, Atrioventricular Nodal Blockade, Shock, and Hyperkalemia (BRASH) Syndrome is a rare medical phenomenon with approximately only 70 reported cases carrying a mortality of 5.7%. 1,2 Presentation is variable but can range from asymptomatic bradycardia to multisystem organ failure. 3 The unique pathophysiology of BRASH syndrome involves synergy between Atrioventricular (AV) Nodal blocking agents and hyperkalemia leading to severe bradycardia and renal malperfusion. Here we present a case of a 66-year-old female who was found to fit the clinical picture of BRASH Syndrome in which the prompt diagnosis and intervention led to a positive outcome. Bradycardia, Renal Failure, Atrioventricular Nodal Blockade, Shock, and Hyperkalemia (BRASH) Syndrome is a rare medical phenomenon with approximately only 70 reported cases carrying a mortality of 5.7%. 1,2 Presentation is variable but can range from asymptomatic bradycardia to multisystem organ failure. 3 The unique pathophysiology of BRASH syndrome involves synergy between Atrioventricular (AV) Nodal blocking agents and hyperkalemia leading to severe bradycardia and renal malperfusion. Here we present a case of a 66-year-old female who was found to fit the clinical picture of BRASH Syndrome in which the prompt diagnosis and intervention led to a positive outcome. A 66-year-old female presented with a chief complaint of fatigue and was found unresponsive by her son who reported her being obtunded and incontinent earlier that day. However, prior to that day she was functioning well and hydrating adequately. The patient has a complex medical history with the most pertinent including heart failure with preserved ejection fraction (HFpEF), moderate aortic stenosis, permanent atrial fibrillation, and chronic kidney disease 3a (CKD). The patient was being treated medically with apixaban 5 mg bid, diltiazem ER 360 mg qd, and metoprolol tartrate 50 mg bid. A transthoracic echocardiogram obtained 3 months prior revealed a left ventricular ejection fraction of 50%, severely dilated left atrium, severely calcified aortic leaflets with moderate to severe stenosis, mild to moderate mitral regurgitation, and moderate tricuspid regurgitation. The patient had also been prescribed potassium chloride 10 mEq daily for hypokalemia and furosemide 40 mg twice daily for peripheral edema. En route to the emergency department (ED) the patient was found to be in 3rd degree heart block with a heart rate of 20, prompting EMS to begin transcutaneous pacing (rate 80, current of 80 mA). In the ED, epinephrine 2 mcg/min was given and transcutaneous pacing (rate 80, current 200 mA) was continued. (Figure 1) Epinephrine was raised to 4 mcg/min and transvenous pacing through her right internal jugular vein was started, greatly improving the patient's mental status. Patient's vital signs were stable at this time. Her labs were notable for hyperkalemia (8.1 mmol/L), so she was given calcium, insulin, glucose, and albuterol. The patient was also found to have an elevated creatinine (221 μmol/L). CT scan of the abdomen was performed showing no acute findings. Epinephrine was able to be weaned off two hours after arrival to the ED. Transvenous pacing was temporarily stopped before being restarted due to two, brief episodes of asystole while paused. The following day her potassium was reduced to 5.2 mmol/L and she no longer required pacing with a heart rate of 70, though she had atrial fibrillation with narrow QRS complexes. Over the next 24-hour period the patient had heart rates ranging 100-130 bpm; however, no pharmacological intervention occurred. The patient's other vital signs including blood pressure were within normal limits during this time. Upon review of prior EKGs, she was diagnosed with tachy-brady syndrome and scheduled for placement of a leadless pacemaker. The patient underwent a leadless pacemaker implantation without complications. An LSP112V AVEIR leadless pacemaker was used due to its utility in cases of bradycardia and irregular heart rhythms, both of which were seen in this patient. The pacemaker was set to a VVI setting with a backup rate of 60 bpm and chest x-ray confirmed stable right ventricular placement. On discharge her potassium (3.9 mmol/L) and creatinine (102 μmol/L) normalized. She was scheduled for a follow-up and slowly started on metoprolol succinate extended-release 75 mg qd and diltiazem 240 mg qd. At the follow-up, the patient had no complaints. Additionally, her device's parameters were all within normal limits and showed no significant high rate episodes. The patient's complex medical history includes over 5 comorbidities, a finding seen in 14.3% of BRASH syndrome patients. 2Majeed H. Khan U. Khan A.M. Khalid S.N. Farook S. Gangu K. Sagheer S. Sheikh A.B. BRASH Syndrome: A Systematic Review of Reported Cases.Curr Probl Cardiol. 2023 Jun; 48 (Epub 2023 Feb 24. PMID: 36842470)101663https://doi.org/10.1016/j.cpcardiol.2023.101663Crossref Scopus (2) Google Scholar Among these reported cases, 18.6% were taking a combination of nondihydropyridine calcium channel blockers (non-DHP CCBs) and beta blockers. 2Majeed H. Khan U. Khan A.M. Khalid S.N. Farook S. Gangu K. Sagheer S. Sheikh A.B. BRASH Syndrome: A Systematic Review of Reported Cases.Curr Probl Cardiol. 2023 Jun; 48 (Epub 2023 Feb 24. PMID: 36842470)101663https://doi.org/10.1016/j.cpcardiol.2023.101663Crossref Scopus (2) Google Scholar Bradycardia in these patients can present superimposed on a variety of arrhythmias including junctional escape rhythm (50%), sinus bradycardia (17.1%), and complete heart block (12.9%). 2Majeed H. Khan U. Khan A.M. Khalid S.N. Farook S. Gangu K. Sagheer S. Sheikh A.B. BRASH Syndrome: A Systematic Review of Reported Cases.Curr Probl Cardiol. 2023 Jun; 48 (Epub 2023 Feb 24. PMID: 36842470)101663https://doi.org/10.1016/j.cpcardiol.2023.101663Crossref Scopus (2) Google Scholar Hyperkalemia severity can vary. This patient's hyperkalemia may have been multifactorial due to CKD, Diabetes, and potassium supplementation. Our patient presented with bradycardia in the setting of complete heart block, severe hyperkalemia, and a medication list including diltiazem (non-DHP CCB) ER 360 mg qd and metoprolol tartrate (beta blocker) 50 mg bid. The cycle that defines BRASH syndrome includes bradycardia, which can lead to renal malperfusion, acute kidney injury, and thus hyperkalemia. This hyperkalemia can then worsen bradycardia in these patients, which will decrease renal perfusion further, completing the cycle. This cycle is usually initiated by severe AV nodal blockade or acute kidney injury, and patients can continue to deteriorate into multiorgan failure without proper intervention. The exact trigger for this patient is unclear. There are plausible explanations for both hyperkalemia and heart block being the trigger. The severe hyperkalemia could have been caused by the overuse of the patient's potassium supplements or an acute kidney injury caused by her nitrofurantoin. Heart block could have been caused by the concurrent use of beta blockers and calcium channel blockers. The Naranjo scale provided a score of 6 when used to evaluate the relationship between the patient's heart block and CCBs and beta blockers, meaning that these medications were a 'probable' cause of heart block in this patient. 4LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Adverse Drug Reaction Probability Scale (Naranjo) in Drug Induced Liver Injury. Updated 2019 May 4. Available from: https://www.ncbi.nlm.nih.gov/books/NBK548069/Google Scholar] Despite not knowing the trigger-the clinical cyclic syndrome of BRASH was still present. Though most patients presenting with this clinical syndrome have favorable outcomes with minimally invasive treatment, they have the potential to rapidly progress to multiorgan failure with a 5.7% mortality rate. 2Majeed H. Khan U. Khan A.M. Khalid S.N. Farook S. Gangu K. Sagheer S. Sheikh A.B. BRASH Syndrome: A Systematic Review of Reported Cases.Curr Probl Cardiol. 2023 Jun; 48 (Epub 2023 Feb 24. PMID: 36842470)101663https://doi.org/10.1016/j.cpcardiol.2023.101663Crossref Scopus (2) Google Scholar Treatment requires addressing the various parts of this cycle simultaneously. Bradycardia can be managed using positive inotropic and chronotropic agents (Epinephrine, Isoproterenol, etc.). In regards to hyperkalemia, intravenous calcium (calcium gluconate or calcium chloride), insulin, and dextrose should be given to stabilize the myocardium and move potassium into the cell. In addition, our patient was given nebulized albuterol to promote rapid intracellular shift of potassium, but its use has never been reported in other reported cases of BRASH. If the hyperkalemia persists, kaliuresis with potassium-wasting diuretics and fluid resuscitation using Ringer's lactate in addition to potassium binders should be explored. This patient did not require these. Additionally, upon correction of the hyperkalemia the patient's AV conduction did initially improve favoring BRASH syndrome. Fluid status can vary in these patients as hypovolemia can be a contributing factor to the onset of this syndrome, but renal failure can lead to fluid overload. 1Farkas J.D. Long B. Koyfman A. Menson K. BRASH Syndrome: Bradycardia, Renal Failure, AV Blockade, Shock, and Hyperkalemia.J Emerg Med. 2020 Aug; 59 (Epub 2020 Jun 18. PMID: 32565167): 216-223https://doi.org/10.1016/j.jemermed.2020.05.001Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar Additional interventions needed in severe cases include transvenous pacing to maintain perfusion, dialysis for kidney failure, and reversal agents like lipid emulsion, glucagon, and high-dose insulin infusion in the case of beta blocker or calcium channel blocker toxicity. 1Farkas J.D. Long B. Koyfman A. Menson K. BRASH Syndrome: Bradycardia, Renal Failure, AV Blockade, Shock, and Hyperkalemia.J Emerg Med. 2020 Aug; 59 (Epub 2020 Jun 18. PMID: 32565167): 216-223https://doi.org/10.1016/j.jemermed.2020.05.001Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar BRASH Syndrome patients (∼32.9% ) typically requires transvenous or transcutaneous pacing, with no patients undergoing placement of a permanent pacemaker. 2Majeed H. Khan U. Khan A.M. Khalid S.N. Farook S. Gangu K. Sagheer S. Sheikh A.B. BRASH Syndrome: A Systematic Review of Reported Cases.Curr Probl Cardiol. 2023 Jun; 48 (Epub 2023 Feb 24. PMID: 36842470)101663https://doi.org/10.1016/j.cpcardiol.2023.101663Crossref Scopus (2) Google Scholar Our patient showed a high propensity for tachycardia and bradycardia, which would only worsen after the necessary reinitiation of AV nodal blocking agents for her atrial fibrillation. Due to the multiple failed trials of rate control during her initial hospitalization, permanent pacemaker implantation was recommended. Leadless pacemaker placement was chosen out of operator preference. There is currently no data regarding restarting AV nodal blocking agents after BRASH syndrome. Literature review suggests a shared decision-making conversation between providers and patients regarding the risks and benefits in restarting beta-blocker or non-dihydropyridine calcium channel blocker therapy. 5Martinez A. Shah N. Kim A. Watat K. Banga S. Beta-Blocker and Calcium Channel Blocker Toxicity With BRASH Syndrome: A Case Report.Cureus. 2023; 15 (Published 2023 Jan 9)e33544https://doi.org/10.7759/cureus.33544Crossref Google Scholar,6Sarkar S. Rapista N. Rout A. Chaudhary R. BRASH: Case Report and Review of Literature.Hearts. 2021; 2: 302-306https://doi.org/10.3390/hearts2030025Crossref Google Scholar This patient's home regimen AV nodal blocking agent therapy of metoprolol and diltiazem resumed after pacemaker placement. This was considered appropriate considering the significant difficulty in rate control of atrial fibrillation noted in her past medical history, as well as stabilization of electrolytes and improvement in kidney function. The patient's heart rates were controlled through the remainder of her hospitalization. At 2-week device check and follow-up, the patient's vital signs were within normal limits and her device interrogation showed no significant high rate episodes. Although the development of other arrhythmias is not extensively reported in cases of BRASH syndrome, this patient shows that the development of BRASH syndrome may indicate a propensity for irregular heart rhythms. Thus, evaluation for other irregular heart rhythms should be conducted in these patients and placement of permanent pacemakers should be considered. This case reminds us of the identification and management of BRASH Syndrome.●The prompt identification and treatment of BRASH Syndrome can lead to better patient outcomes●BRASH Syndrome mimics many other common etiologies seen by hospitalists and emergency room physicians-being able to distinguish BRASH syndrome is a skillset●BRASH syndrome is a clinical diagnosis defined by the cycle of bradycardia → renal impairment → hyperkalemia → bradycardia.●BRASH syndrome should be managed by simultaneously treating bradycardia with inotropes/chronotropes, hyperkalemia with kaluresis or agents that shift potassium intracellularly, and varying fluid status with the necessary intervention.●Though the goal of treatment is stabilization of the patient through minimally invasive measures, our case highlights the importance of evaluating them for future arrhythmias and the benefits of permanent pacemaker implantation in these cases. None None
Roma et al. (Tue,) studied this question.