Hello and welcome to Episode 89 of ER-Rx- a podcast tailored to your clinical needs. I’m your host, Adis Keric. This week, I wanted to talk about BRASH syndrome. This is one of those rare, obscure things that’s very in line with what I like to talk about on this podcast- but it isn’t a new topic. There are tons of great references that discuss it- like the one on the EmCrit blog which I referenced a ton for this episode. And although it’s been discussed a good amount, most of what we know about it comes from case reports and case series. But the article I’m specifically talking about today is the first of its kind- where the authors systematically looked at all reported cases to help us understand the most common clinical presentations of the syndrome and how patients were managed. I highly recommend reading this study, and I’ll have a link to it posted in the Show Notes, so full credit goes to the authors here.
BRASH syndrome stands for bradycardia, renal failure, AV nodal blockade, shock, and hyperkalemia. It happens to patients taking AV nodal blocking agents who develop cardiogenic shock in the setting of hyperkalemia and acute kidney injury (AKI). We don’t fully know why it happens, but the leading thought is that patients first develop some degree of AKI. As we know, this leads to hyperkalemia and reduced clearance of the AV nodal blocking agent. Hyperkalemia can itself cause bradycardia, and the beta or calcium-channel blocking agent was designed to. But importantly, the hyperkalemia works synergistically with the AV nodal blocker to cause the bradycardia we see here. All of this leads to a reduced cardiac output which in turn worsens kidney perfusion, causing even more kidney injury and even more accumulation of potassium and the AV nodal blocking agent. As a triple-whammy, some of these patients are also taking an ACE-Inhibitor or ARB, which can cause and worsen both renal failure and hyperkalemia. I know we use the term “vicious cycle” a ton in medicine- but this one really is vicious.
This cycle can lead to cardiogenic shock and complete cardiovascular collapse if not treated quickly and appropriately.
So, who are the patients that get BRASH? How do they present, and how are they managed?
Of the 70 patients included in the study, the average patient was almost 70 years old, with about a 50-50 male/female split. A large majority of patients had hypertension (71%) and about half had diabetes (48.5%), and CKD (44.3%).
About 3/4 (n=52; 74%) were on a beta-blocker and about 1/3 (n=22; 31%) were on a non-dihydropyridine calcium channel blocker- think verapamil or diltiazem. 19% (n=13) were on both a CCB and a beta-blocker and about 1/3 (n=26; 37%) were taking an ACE-I or an ARB.
About 75% (n= 52) of patients presented with fatigue, headache, encephalopathy, or syncope- credit to the hypoperfusion. Most patients presented with hypotension (with an average MAP of 62 mmHg) and bradycardia (with an average heart rate of only 36). On EKG, about 50% had junctional escape rhythms but only about 13% had complete heart block. And this is where it gets interesting and goes back to what I said about the synergistic effect of all of these concurrent issues; the average potassium level was only 5.2, and although about half (n=32; 46%) of the patients did have severe hyperkalemia, more importantly, the other half had either mild or moderate hyperkalemia. In the same vein, the average serum creatinine was 3.6 (range 1.3 – 13.5 mg/dL)- which is high, but isn’t that extreme.
And then we get into the interesting, pharmacy stuff. Patients were treated with IV fluids if they needed it (remember not all patients with BRASH are hypovolemic) and they were also given vasopressors. One of the keys to managing this syndrome is immediate treatment of the hyperkalemia if it exists. A majority of patients were shifted using calcium and insulin, but still ¼ (n=16; 23%) needed dialysis. For their bradycardia, 1/3 of patients got atropine, another third got inotropic agents, and another third needed pacing—but no one needed a permanent pacemaker. Only 4 patients, or about 6% died, 7 of them were intubated, and only 2 patients needed cardioversion.
In a nutshell, BRASH is a rare and under-recognized syndrome that can be easily missed. But thank to this study, we can keep a few things about the syndrome in mind to help us diagnose and manage it appropriately. It mostly affects older adults, who usually have comorbid conditions like hypertension. These patients are by definition on a beta-blocker, or sometimes a non-DHP CCB who also present with some degree of renal dysfunction. They usually have some level of CNS dysfunction along with obvious bradycardia, possible hypotension, and a high rate of junctional escape rhythms on EKG. They may or may not have severe hyperkalemia- so a normal potassium doesn’t necessarily rule it out.
As recommended in other published reports and blogs, goals are to manage the bradycardic shock, AKI, and hyperkalemia by giving IV calcium and shifting with IV insulin. Albuterol also seems like a good idea because it can both shift potassium and increase the heart rate. Patients will also need high doses of diuretics and as we saw in this study- potentially dialysis. If patients are still unstable, most recommend starting epinephrine or isoproterenol, but I’m sure if you’re in a bind norepinephrine is an option as well. But more importantly, these patients usually do NOT need to be treated like patients with pure beta-blocker or CCB intoxications- meaning no need for high-dose insulin or lipids.
Remember the thought that this syndrome is dependent on the synergistic effects of AKI, taking an AV-nodal blocker, and hyperkalemia—typically neither one of these by itself would cause the constellation of symptoms that we see. This is evidenced by ½ of all patients not having a severe hyperkalemia or a severe enough AKI to cause circulatory shock alone. It also doesn’t fit with pure AV-node blocker toxicity since patients report taking their meds as directed.
As always, thank you so much for your time, and thank you for wanting to learn more about pharmacotherapy. If you have any comments or anything you’d like to add to this episode, please give me a shout out on the @errxpodcast Instagram page, or reach out to me personally on errxpodcast.com- I’d love to respond to all comments and criticisms.
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