“Can I get a signature on this ECG, please?” you hear one of the techs ask as she walks over to the residents.
“You can do it; you just passed your ECG test.” You hear one of the seniors tell a newish second year resident as she hands it to him without talking a look.
“Ok, let me take a look.” He says as his eyes get big:
Rate: less than 30 beats per minute
Rhythm: Sinus brady
Axis: Left axis
Intervals: Narrow QRS, normal PR, QTc looks ok
Morphology: Overall, it’s slow but doesn’t look terrible
Final read: Sinus bradycardia, but the kind that gets your attention
“Uhhhh… I think I need a room for this patient and probably an attending!” you hear the second year resident say.
“You’re so dramatic! Look, if it’s a STEMI, just activate the cath lab. You don’t need to panic. Here. Give me that ECG and let me take a look,” she says taking it out of his hand.
You see the senior’s eyes get big as she runs over to the charge nurse’s desk with the ECG and second year. After some quick words, Shannon, the charge nurse, makes a call and you see the residents scamper off.
“Medical resuscitation coming to bed 6! Medical resuscitation coming to bed 6!” The hospital voice calls out. You hustle over to bed 6 and see the residents standing over a tearful teenager.
“What’s going on?” you ask.
“Hey Doc, let me catch you up,” Shannon says. “This is Jackie, she’s a 16-year-old female coming in after an overdose. She’s refusing to tell us what she took. Her parents are out of town and we can’t get in touch with them. Right now, all she’s complaining about is feeling a little weak and very tired. Her blood pressure looks a little soft in triage, 90/60, and respirations are 6-8ish per minute. She’s mentating ok, for now. No fevers, normal glucose. The residents were appropriately concerned about her ECG and asked me to get a room for her asap.”
“Wow, an unknown ingestion with bradycardia? Could be almost anything!” you say. “Shannon, can you give toxicology a call?”
“No need doc,” Shannon says, “He’s already standing over there with the EKG in his hand. He always seems to appear when he’s needed…” she says, gesturing to Dr. Boroughf.
“Hey, Dr. B. Thanks for coming by. I see you have met our patient’s EKG. Care to give us a breakdown of your thoughts on the matter?” the senior asks.
“Sure thing! Unless your patient is somehow a blue whale in disguise, I’d say we’ve got the perfect case for some classic toxic differential diagnosis teaching. Can you spare three minutes for the ABCs of tox bradycardia?”
“I think we’re mostly stable for the moment. The nurses will work on getting access and a crash cart near by, just in case. Let’s take a quick three minute pause! Here’s the teaching white board; Take it away!” you tell him.
When dealing with potential toxin-induced bradycardia, there are three things that you should pay attention to:
- Heart rate (obviously)
- Blood pressure
- Mental status.
The combination of these three things will get you most of the way through the ABCs of bradycardia, which will help you target your therapy most effectively and make you look like a rockstar in the process.
Let’s begin:
A: (central) Alpha-2 Adrenergic Agonists
These agents block the sympathetic outflow, meaning they result in a decrease of neuroexcitatory and cardioexcitatory amines. Because these receptors live presynaptically, stimulation/agonism results in the counterintuitive downstream inhibition of excitation. In other words, they are a sympatholytic, like “rest & digest” in a bottle.
As a side bonus, many also tickle the central mu opioid receptors, which can cause respiratory depression and even apnea that corrects with noxious stimulation. Thus, the clue triad of central Alpha-2 Adrenergic Agonists is bradycardia PLUS hypotension PLUS mental status depression, often with opioid-like features of apnea. Agents of concern include clonidine (and similar antihypertensives), tizanidine (a muscle “relaxer”)*, medetomidine (contaminating illicit fentanyl) and, importantly, OTC eye drops for “red eyes” (ie. Visine, containing tetrahydrozoline) which are potent, easily hidden and are often implicated in malicious poisoning and drug-facilitated sexual assault.
B: Beta Blockers
These are a bit self-explanatory. They block the cardiac beta-adrenergic receptors resulting in reduced chronotropy (decreased HR) and reduced inotropy (decreased contractility) leading to decreased cardiac output. Because blood pressure is dependent upon cardiac output, this will result in hypotension. However, mental status is largely preserved with the exception of propranolol, which is a dirty little drug that has all sorts of other effects including mental status depression, sodium channel blockade and seizures.
C: Calcium Channel Blockers
Obnoxious pharmacology classification alert! CCBs come in two flavors that have different hemodynamic effects that becomes increasingly more non-specific as the (over)dose increases.
Non-dihydropyridine CCBs (diltiazem and verapamil) cause bradycardia and reduced cardiac output by blocking central cardiac calcium channels. This, of course, causes secondary hypotension as a consequence. Mental status is usually preserved. Unexpected hyperglycemia offers a clue for diltiazem or verapamil overdose.
Dihydropyridines (amlodipine and other -dipines) block peripheral vascular calcium channels, leading to peripheral vasodilation (think dihydro = dilate) . These cause primary hypotension through vasoplegia, which is especially bad when combined with ARBs (ie valsartan). This hypotension often accompanied by a compensatory increased heart rate early in the course. Mental status is also usually preserved.
However, when doses increase, these agents become non-selective, which can lead to severe shock due to both reduced cardiac output and reduced SVR regardless of the agent. This can be accompanied by impaired mental status not from the drug itself, but due simply to poor CNS perfusion. Things can get very challenging very quickly, but that’s a topic for a later discussion.
D: Digoxin and cardiac glycoside-containing plants
Digoxin’s toxic calling card is bradycardia combined with cardiac irritability. Additional symptoms may include GI symptoms, confusion and mental status depression at higher concentrations (especially with chronic toxicity). Hypotension can be present, but is often secondary to significant GI losses or severely decreased cardiac output. Fortunately, clues can be found on the EKG (atrial dysthymias, bidirectional ventricular tachycardia, or characteristic ST segment morphology [“scooped” ST segments, pictured below]) or through lab testing (ie. serum digoxin level), which can make diagnosis more straightforward. Note that cardiac glycoside-containing plants (classically foxglove, but also oleander and lily of the valley) cause similar symptoms and will variably react with serum digoxin assays.
So, there you have it, the ABCD’s of toxic bradycardia. Each of these agents could fill their own lecture, but everything above will get you started in the right direction.
For my visual learners:
And for my non-tabular visual learners:
“So, what do we think our friend got into?”
“Well, let’s see…” you say. “Bradycardia? Check. Hypotension? Check. Mental status depression? Sorta-check. Could be anything except a dihydropyridine. Let’s look further. EKG looks (slowly) normal, so probably not propranolol. Blood glucose is also normal, so probably not a non-dihydropyradine. No GI symptoms or cardiac irritability, so digoxin is probably unlikely (we can also send a level). So, we’re left with central alpha-2 adrenergic agonists and beta blockers. With that, the slow respirations really stand out and make beta blockers less likely. Looks like we’re dealing with something like clonidine or tizanidine or something similar!” you exclaim.
“Well done, my tox padawans (padawanes?). Seems like you’ve got a handle on the ABCs of Tox Bradycardia,” says Dr. B.
“Awesome. Uh…now what do we do?” you ask.
“Ah, yes,” says Dr. B, “well that’s a whole different talk…”
*Side note: muscle “relaxer” is a bogus term. The only true muscle relaxers are paralytics. Everything else is just some sort of CNS depressant that reduces excitatory neurotransmitter release. Keep this in mind when considering the side-effects (and toxic potential) of the various agents and please, for the love of Willie Nelson and Beers, don’t prescribe any of these to the aged.
Recap:
- With an unknown bradycardic ingestion, think about the ABCD
- Alpha-2 Adrenergic Agonists
- Beta Blockers
- Calcium Channel Blockers
- Digoxin and cardiac glycoside-containing plants
- For Alpha-2 Adrenergic Agonists, think bradycardia PLUS hypotension PLUS mental status depression
- For Beta Blockers, think bradycardia PLUS hypotension but often mental status PRESERVED
- Except Propranolol, that can cause mental status depression
- For Calcium Channel Blockers bradycardia PLUS hypotension but often mental status PRESERVED
- Remember, CCBs often cause hyperglycemia, helping to differentiate them from BBs
- For Digoxin, think bradycardia PLUS mental status depression BUT normo-tensive
- Also look for those “scooped” ST segments
- As always, a HUGE thank you to Dr. Bill Boroughf for sharing his cases and expertise with us
- Check out his Substack, The Thing About Poison
Hit me up with any questions,
Lloyd
