Ellen Pil, Dr. Asa Margolis, & Dr. Matt Levy: Diltiazem in EMS (9/6/24)

All right, welcome everybody. It's September 6th, Friday at 11am and we have a great presentation for you today. First, I'm going to introduce two of my good friends, Asa Margolis and Matt Levy, both from Hopkins. They're both in the EMS division, fellowship directors, critical care transport, et cetera. And they had a publication that I was very interested in hearing about. And so Matt and Asa, if you wouldn't mind introducing Ellen, you know, medical student, and then we'll get the conversation going. Thanks for joining us today.

Great.

Well, hey, thanks, Peter, and good morning. And it's good to see everybody virtually. You know, hands down, one of the best parts of our jobs being in academic medicine is getting to work with highly motivated, super bright and super energetic medical students, undergraduate students, residents and fellows. And Ellen is the quintessential example of that. Ellen is a medical student here at Johns Hopkins. She's currently a fourth year applying to residencies, but hands off, everybody. No, but, but she's applying to residencies and I'll. She'll tell her story a little bit more. But Ellen's also an EMT by background and has been doing stuff academically and programmatically with Asa and I really since, since a first year, including, you know, on, during her free time shadowing in the department with us and really getting involved. And this is, this is really the results of a project that we've been working on for some time. So, Asa, do you want to add anything to that?

No. You know, this was something that actually Ellen sort of came to us with a background and an interest in and, you know, we were just sort of along for the ride. Right. I mean, she came with everything from, you know, the idea to the development of the idea, and we just kind of mentored her through it. She presented this as part of her medical school scholarly work, scholarly project. And this is just a really nice opportunity for her to be able to talk to this great community. And I think it's a, it's a great thing and a great thing for her moving forward. So, Ellen, great work and we look forward to hearing what you have to say.

Thank you so much. All right, shall we get started?

Take it away. Yes.

All right, great. Hi. Good morning, everyone. As Dr. Levy and Dr. Margolis mentioned, my name is Ellen Pill. I'm a fourth year medical student at Johns Hopkins School of Medicine. I'm thrilled to be here, excited to be speaking with you today, and I'll be presenting to you on the efficacy and safety of pre hospital dilta ism.

See if we can get this to go. So a little bit of background. I'm sure most of you on this call are familiar with this. We'll just start by talking about rapid atrial fibrillation. So this is a cardiac tachy dysrhythmia. Atrial fibrillation is characterized by an irregularly irregular heartbeat. That rapid ventricular response can in turn impair diastolic filling. And this leads to patients presenting with symptoms such as palpitations, shortness of breath and chest pain. A quick note here that while atrial fibrillation and atrial flutter are distinct entities, for the purposes of this presentation I'll be discussing them together because in both our study and Maryland State protocols, these two dysrhythmias are treated identically. And in particular today we'll be talking about one of those treatments, which is a rate control agent called diltiazem.

So moving on to a little bit of epidemiology. Atrial fibrillation and atrial flutter are very common tachydysrhythmias affecting between 3 and 6 million people in the U.S. these are also common in both the ED and the pre hospital settings. So they account for nearly 600,000 ED visits every year. And according to NEMSIS data, almost 50,000 patients in the pre hospital setting who were given diltiazem by ems.

So to move on a little bit to diltiazem. Diltiazem is a non dihydropyridine calcium channel blocker, meaning that it slows conduction and prolongs the refractory period in the AV node. What this means for us is that this is what we call a rate control agent. It slows down the heart rate in these rapid tachy dysrhythmias. It's used to treat hemodynamically stable atrial fibrillation. The pre hospital setting. In particular, rhythm control is achieved by electrical cardioversion, which is reserved for hemodynamically unstable patients. Diltiazem can also precipitate shock by undermining compensatory mechanisms. A patient may have this underlying atrial fibrillation, but then the rapid part of that comes as compensation for an underlying pathology, for example, hemorrhage, sepsis, things like that. The major risks of diltiazem are its adverse events, namely hypotension and bradycardia, bradycardia being a result of its mechanism of action.

I want to talk just a little bit about the Maryland EMS system. The Maryland EMS system is made up of five regions. As you can see on the map on the right side of the screen. It has 28 different jurisdictions and transports half a million patients every year. The Maryland Institute for Emergency Medical Services Systems, or mims, develops mandatory statewide treatment protocols and administers a unified electronic medical record system. I emphasize this in particular because it forms the basis of the method and the query that we'll discuss in a minute and how we were able to get access to this data.

So I'd like to discuss the Maryland protocols during the study period, and I emphasize that during the study period because these protocols have changed. As I'll discuss later on in the presentation. Maryland protocols allowed for the use of diltiazem in hemodynamically stable adult patients who were symptomatic from atrial fibrillation or flutter. They had to have a rapid atrial fibrillation or flutter as defined by a heart rate of greater than 100 beats per minute and hemodynamic stability which was ensured by a systolic blood pressure of greater than 100 millimeters of mercury. Again, at the time of the.

The.

Dosing was prescribed as an IV Diltiazem Bolus which was given over two minutes as a weight based dosage of 0.25 mg per kg with a maximum dose of 20 mg. If there was inadequate response after 15 minutes, a second dose of 0.35 mg per kg could be administered again via slow IV push.

It's important to note that there's a caveat to this. The dosage describes that for patients who are older than the age of 50 having a borderline blood pressure known kidney failure or CHF, a smaller initial bolus of 5-10mg. Again recall that the initial bolus would have been 20mg for patients without these comorbidities was administered IV over 2 minutes as well.

The research question that we aimed to undertake was to find out whether or no diltiazem was a safe and or effective medication when given by pre hospital emergency medical services in the State of Maryland.

So to answer that question we did a retrospective chart review encompassing greater than three years of charts where we got every case of when EMS gave it diltiazem to an adult patient. We received this as de identified data from MIMS and in particular the variables that we requested and were given were the demographics, transport time, all of the vital signs that were taken on the patient, as well as lists of any procedures performed and medications administered by ems. We also got the number of individual diltiazem doses as well as the total amount of diltiazem that was administered to the patient during their encounter with ems.

When EMS sent us this Sorry. When MIMS sent us this query, they gave us almost 2,400 individual charts. Of these, about 94% of patients were included. Reasons why we excluded the criteria were an error. There was no diltiazem that was actually given by ems. They were missing vital signs which would impede our ability to assess our outcomes. Diltiazem was given outside of the protocol, so the systolic blood pressure was not over 100 or the heart rate was not over 100. There were other medications that were given that could potentially confound our results, namely amiodarone, verapamil and adenosine. There was anomalous or identical data or an inconsistent narrative and data set. The way that we assessed these was for patients with extreme results, for example a heart rate over 240. Both Dr. Margolis and Dr. Levy, who are on this call, independently reviewed the narratives for that chart as well as the data set and made a determination as to whether or not those patients would be included. We also excluded one patient who was non transported and one patient who was post arrest.

This left us with our final data set of 2,254 patients.

Looking at our outcome variables, we defined rate control as a heart rate of greater than 60 and less than 100 beats per minute, with the lower and upper bounds of that range being defined as bradycardia and tachycardia, respectively. We then defined clinical improvement as a non bradycardic heart rate that was at least 20% lower than the maximum heart rate. That was a standardized outcome that was initially used during the diltiazem approval studies done at the FDA and was subsequently adopted in other research on diltiazem conducted both in the hospital setting and in the pre hospital setting.

For safety outcomes. As I mentioned, there are two main adverse events, bradycardia, which we defined as a heart rate of less than 60, and hypotension, which is a systolic blood pressure of less than 90. We looked at these measures both at the time of hospital arrival as well as whether or not these patients required a rescue medication from EMS. For a heart rate of less than 60. We defined rescue medication procedure as atropine, epinephrine or external pacing for hypotension. We define this as using epinephrine or calcium chloride.

Just a little bit about our summary statistics. The median age of Our patient was 72 I think that this is especially important to acknowledge because as you recall earlier, there's a separate protocol for patients who are over the age of 50. As you can see, even the bottom end of our IQR is well above that age and it wound up being over 90% of our patients fell into that greater than 50 age range. Our average encounter length was 34 minutes and our maximum heart rate was almost 170 and our final heart rate is 120. That led to a decrease of about 27%. The maximum systolic blood pressures and final systolic blood pressures were 153 and 132, respectively. These patients received a total diliazem dose of 10mg and the IV fluid volume, the median was 0. This is obviously a right skew for that IV fluid.

Taking a closer look at our summary statistics, you can see the heart rate on the left side of the screen and the solid blood pressure on the right side of the screen. For the heart rate, you can see that our patient's final heart rate has substantially decreased from the initial, with some but not most patients falling into that rate control range and then and a handful following into that bradycardic range as well. Likewise with systolic blood pressure on the right side of the screen, you see that dashed line there representing 90 or the threshold for hypotension. Patients did have a substantial decrease in their systolic blood pressure as well, with some of them falling into that hypotensive range as we were concerned about from the risk of adverse events with this drug.

Looking more closely at efficacy, 3 in 5 patients, 63.8% had clinical improvement, again defined as that 20% decrease, but only 604. So less than half of those patients had rate control. There were also 802 patients who had neither clinical improvement nor rate control with this drug.

Looking more closely at the predictors of efficacy can see that age was a significant predictor of clinical improvement in that patients who were younger who were less than the age of 50 were more likely to have clinical improvement from diltiazem. A dose of between 10 and 20 milligrams was also significantly increased with higher odds of both clinical improvement and rate control. Utilize some data that suggested as well that a systolic blood pressure between 100 and 119 was associated with higher odds of clinical improvement and that between 160 and 179 was associated with lower odds of rate control.

Moving on to our safety events, 96.5% of our patients did not experience any adverse events from receiving diltiazem. Over three and a half of them did. I think that this is especially important to emphasize because these patients were hemodynamically stable. They came to us and by definition in the protocol, they could not receive this drug, should not receive this drug unless they were not hypotensive and were not bradycardic. However, these patients left the care of EMS or required rescue medications for hypotension and bradycardia. In 78 cases, there were 8 patients who had both hypotension and bradycardia, 40 who had hypotension only, and 30 who had bradycardia only.

In terms of predicting the adverse events, nitroglycerin. Concurrent use of nitroglycerin was a significant predictor of adverse events at an odds ratio of 3.68. I think that for most of us on this call, that's probably relatively intuitive given that the side effect profiles of these drugs overlap. A heart rate of less than120 was also associated with a higher rate of adverse events, as was a systolic blood pressure of less than 140.

We did a separate analysis of patients who received what we called an excessive dose of diltiazem. The way we measured this was we looked at all those patients who were over the age of 50 who received a higher initial diltiazem dose than recommended by MIMS protocol. Remember MIMS protocol being that 5 to 10 milligram initial bolus and 20 being the usual maximum weight based dosage? These patients who received that excessive dose of diltiazem were more likely to attain clinical improvement in rate control. But as is likely intuitive for most of us here, they were also much more likely to have an adverse event.

To briefly discuss some limitations, we had no time stamp on the diltiazem dose. That's why we used our maximum heart rate and maximum systolic blood pressure as a proxy, assuming that those would be markers from before diltiazem was given. However, without a timestamp on the diltiazem dose, we cannot verify whether or not that was true. We also did not have recorded or accurate weights on these patients, so we don't know whether the amount that they were given was actually an appropriate weight based dose. As I mentioned earlier, one of the major risks of diltiazem is that it can undermine a compensatory mechanism. And there's some evidence that suggests that diltiazem is associated with more adverse events in patients where their tachycardia is Secondary to underlying pathology, we were not able to stratify by an underlying illness or injury. We also were not able to link to downstream or in hospital outcomes. We can't look at markers like for example, 30D mortality. We did not independently verify the paramedics rhythm interpretation. So we assumed that when these patients were considered to have atrial fibrillation or atrial flutter, that that interpretation was correct.

As a result of our study, there was a protocol change in 2023 during an update which increased the heart rate threshold for diltiazem administration from 100 beats per minute to 130 beats per minute.

And then to quickly discuss some conclusions. So after receiving Pre Hospital Diltiasem, 3 in 5 patients had clinical improvement again that greater than 20% decrease from the maximum heart rate. But only 1 in 5 had recontrol. 1 in 30 patients experienced a serious adverse event. This is again important to emphasize because all 30 of these patients were hemodynamically stable at the start of their encounter with ems. We also found that diltiazem is less effective when it's given to patients over the age of 50. Again a very significant thing to note because the vast majority of patients who receive diltiazem do fall into that category. And adverse events are more common with systolic blood pressures of less than 140, heart rates of less than 120. So really, these patients who are falling on the margins of do we give this drug, do we not give this drug? When they're falling at those borderline thresholds, they're more likely to have adverse events as well as with concurrent nitroglycerin administration.

Be happy to answer any questions.

Wow, great presentation, Ellen. Thank you so much. Let me remove the spotlight. So there you go. All right, so I know we have. Let's go. I see Dr. Pepe, you have your hand raised. And then we're going to go to Tanner. Go ahead.

Can you see me okay?

Yes.

Yeah.

Listen, for doing this really good.

Piece of research, I mean it's really important and it's brought out stuff that I little fit fits my bias. You're going to probably go back and drill down on this a little bit more. But what I wanted to find, and I can't remember if you you gave these data, but what was the breakdown on a flutter and atrial fib? You'll see why I'm asking in just a second.

So we did not have that information on atrial flutter and atrial relation. And the reason why we didn't push for that is because it would have required independently verifying the rhythm strips of each patient.

Oh, wow. Okay. The reason I was asking is that first of all, almost the great majority of people who have atrial flutter specifically have underlying coronary artery disease. Okay. Whereas atrial fibrillation, which is probably actually more common, can come from so many things. You could get it because you had a drowning and there was pulmonary edema, you know, whatever, there's a left atrial stretch from this or whatever, or it'll be an acute incident in which you could be at a mountaintop, you know, and get atrial fibrillation. So I'll just. I just wanted to see if there was a difference between people who were had non cardiac reasons versus and that would be a good start right there. And it would be kind of cool to be able to break down some of the etiologies. But you know, if you want to pursue this further in other databases or whatever, it would be just kind of interesting to find that out. I think so.

Yeah, that would be fascinating. Yeah. Another good point for future directions here. Thank you.

Okay. A nice job.

Excellent job. Thanks, Paul, for the comment. Let's move over to Tanner.

First of all, I just want to say wonderful presentation. I also love that it drove a change in practice, a protocol change. Love to see that. It's fantastic. So just a couple comments, and I know you weren't able to link your data to in hospital records and kind of what the laboratory values and things seen in the emergency department and you may not have looked at this, but in terms of EMS clinician impressions just recorded in the pre hospital electronic health record, were these patients primarily, was their primary impression arrhythmia or did you see some of these other disease processes that we worry about, things like sepsis, et cetera. So that's one comment. Another one, and you noted this in the discussion, is that the proportion of patients who had clinical improvement and the proportion of patients who ended up actually having rate control was lower than what was seen in previous randomized controlled trials. Looking at the efficacy of dual TASM for AFIB and other dysrhythmias. And so do you think that maybe we should be looking at other drugs in the prehospital setting to treat this? Should we be looking at, you know, beta blockers, for instance, or some other classes of medications that can be used instead of calcium channel blockers? And then so finally, and this is a question, and I don't believe this is the case, but I don't believe it was specifically stated in the manuscript. Were there any patients who after administration of diltiazem had a pre hospital cardiac arrest?

Yeah, all great questions. I do not believe just the last one first. I do not believe that there were any patients who had a pre hospital cardiac arrest. As far as I'm wear associated with diltiazem. I think for your first question about the paramedic impressions, I did look at those. They were quite, quite varied. I don't remember the exact number off the top of my head. The majority of them were cardiac, but there were also a decent number that were traumatic actually in nature. And then there were many that were just categorized as something like sick person. So more or less nondescript and didn't really help us narrow down whether they were feeling ill because of their cardiac dysrhythmia or if the cardiac dysrhythmia was secondary to another pathology. As your question about is this a different drug or should we be looking at other things in the pre hospital setting? I, you know, I think that there is a reason why our efficacy rate is lower than in randomized controlled trials and why our adverse event rates are higher. I think, you know, these are when given in a randomized controlled setting, you know, they're doing things like these perfect weight based dosing, right. And they're really looking very closely.

Should I phrase this? They're looking at patients who don't have those other secondary underlying pathologies. Right. You're not going to have somebody show up and do a randomized control trial on them after they've been into a car accident, they're stabbed, they're septic, something like that. I think my inclination would love to have other thoughts on this as well. And I know Dr. Levy and Dr. Margolis also have some opinions on this, is that I am not particularly inclined to look for a better rate control agent in the pre hospital setting because these patients are hemodynamically stable. I think, you know, if we consider the role of EMS to largely be in stabilizing unstable patients or ideally keeping keeping patients who are stable stable until they can reach a higher level of care, I think that there's a lot of potential risk in, in introducing medications for hemodynamically stable patients with a side effect profile that includes hemodynamic instability, if that makes sense. I think that it is certainly something that should be addressed and included in protocols for agencies that may have longer transport times. But for patients where you have say a 10 minute ride to the hospital, I'm not sure that I feel Strongly that the resources that we have in EMS research should be dedicated towards trying to find other rate control agents for those patients.

Can I ask just one very quick question? I'm sorry about the pump in. I have to go somewhere and go to another session. But what I. One thing it is interesting is I know if there is a difference. For example, that was where I was kind of leading to before about the etiologies. Sometimes if someone has an acute event, it may be easier to convert them versus someone who's had a chronic atrial fibrillation condition that we're going to see. You know, that kind of thing. And was that. That wasn't easy to split out, I suspect. Right. Okay.

No, it's. Yeah.

For future directions. Right, of course. All right.

The next project. Go ahead.

I was going to. I was going to say quickly. So I think, Ellen, you know, you hit the nail on the head with respect to the EMS system. Right. As EMS medical directors, obviously we have to make these decisions based on what our EMS system looks like, including transport time. Honestly, rate control agents such as Dual Tyson give me a little bit of chest pain when I think about it, because I always waffle back and forth to whether or not we should even be treating somebody, especially with shorter transport times that have afib, when we really have no idea why they're in rvr. Right. What sort of compensatory mechanism is happening. And often when we see these people in the emergency department, we're not jumping all over them to treat them within the first 5, 10, 15, 20 minutes of arrival. Right. We're gathering data, we're obtaining labs, we're doing a volume exam. We're really assessing what is the potential downside of administration of these rate control agents. So really doing that off the bat again, gives me a little bit of concern. In wood with any sort of rate control agent, obviously, the treatment of these patients becomes much easier, whether in the field or in the hospital when they're critically unstable, because then we know what to do. Right. We give them electricity, but in that sort of, that group of, like, their rate is high, but they're not unstable. We don't really know why their rate is high. This is a very dangerous patient population to be potentially messing with if you don't have all of the data that you need.

Well said. I have a comment, but we have two other people want to come in. So let me go to Scott and then we're going to go to George next. Scott, go ahead.

Hey, good morning.

Great presentation. I apologize if I missed this. But does your protocol address anything such as onset of the afib? Some. Some EMIS protocols. Say, if it's been greater than, say, 48 hours, don't mess with it for fear of implus taking place. Does it address this, and did you see any complications related to something along those lines?

Thank you.

I do not believe that our protocol addresses the duration of the atrial fibrillation. So, no, we were not able to collect that data on the duration of their dysrhythmia.

And that is a great question, because what was the percentage of patients that actually converted out of afib? Ellen, you had mentioned it.

I don't. So we don't have hospital arrival data, so we can't confirm what their rhythm was at the time of hospital arrival. And so we can't tell how many of these patients necessarily had rhythm control. We really only looked at rate control and then the clinical improvement marker in this project.

Gotcha. Okay, let's go to George.

Hi. Great presentation, by the way. My question is this.

Of the.

And you may have covered this already.

Of the adverse effects that you saw, were they.

Was it able to be discerned if.

It was directly from the drug itself, or they just happen to have an adverse reaction that may have fit several different profiles and it just happened to.

Happen after giving the drug?

Yeah, we were not able to determine that based on it. You know, with the. You know, we were only able to request narratives for patients who. We had concerns about the validity of the data that was presented to us rather than narratives for all the patients in this data set. So that wasn't something that we were able to deter. And I do think that it raises an important question about confounders. You know, we are able to assess whether. And control for those somewhat in terms of, you know, eliminating potentially confounding medications like verapamil adenosine. But, you know, for example, with the concurrent use of nitroglycerin, I think it's very hard to say. For example, is, are they hypotensive because they got nitro, or are they hypotensive because they got dilt? I don't know that even if we had the narratives, we could answer that kind of question. But I think that it does raise important safety considerations about the patients who should and should not be receiving diltiazem and the potential comorbidities or concomitant use of other medications that may increase their risk for those adverse events.

Thank you.

Great question and a great answer. Let's go to Moshe.

Hey. Hello, all. Thank you for this presentation. I had a. A couple questions for you guys. I was surprised to see that the MIMS protocols actually has a minimum threshold of 100 for the rate. I can't remember giving diltiazem to someone who had a rate of 100 and afib. So that was an interesting point. So I'm glad that this study was able to move it. Now, the question. Second question is.

Which part of the study made you move it from 100 to 130? Was it the lack of improvement or was it the adverse effects that you saw? You know, I'll let Dr. Levy and Dr. Margolis take that one, because I know that they were more closely involved in the discussions and the decision to raise the threshold.

For us, it was more of the. The potential adverse effect. Right. Of treating somebody with a heart rate that we wouldn't ordinarily treat anyway. Right. I mean, typically, we're looking to treat heart rates as they're getting above, you know, 130, 140. And when they're sitting in the low 100s or 110s, we're usually letting the patients ride. So it's really because of the adverse. Potential adverse effect of dropping their heart rate too low or getting rid of their compensatory response. And the sequelae of that, that was a driving factor to make us raise that.

And we also try really hard to teach, both clinically, pre hospitally and in hospital, that when you see a tachycardia, your initial response should be that it's the symptom of another problem, not the primary problem itself. And if you can do it because a line and a protocol says you can do it, then we haven't really set this patient up for utmost success and safety. So as Dr. Margolis said, it was a bumper guard. And clinically, there's really very few reasons why you'd want to rate control someone in the 130s, but rather figure out the underlying cause first and foremost. And then exclusionarily, you can go to rate control if you've ruled out the life threat. But great question. Measure.

Thank you.

So I'm gonna. I'm just gonna play devil's advocate before we go to Charlie. So, Asa, you had mentioned earlier that this is not something that we should. We should even. Maybe we should not consider treating. So you have short transport times where you are. Why have it in your protocol?

Yeah, great question. So, you know, we are a statewide system, right? So while Matt and I in Howard county, you know, have you know, anywhere between five and 20, 25 minutes, maybe 30. There are other EMS jurisdictions, as Ellen showed in that map, that have much longer transport times. The western end of the state, the eastern shore, they have much longer transport times. And for those where you're going in excess of 30, 35 minutes, maybe longer, depending to the hospital, it may be something that you do want in your tool, in your toolbox, but certainly something I was thinking about, Peter, like, you know, why do we even need this medication? Why are we tempting ourselves with something that can potentially result in instability of a previously stable patient? And I still really think long and hard about it, and I'm still not totally convinced that this is always the right answer for us in ems.

Yeah, this really falls under the just because we can do it, should we do it, you know, approach to things. And I think we have to be very thoughtful and careful about that. The other issue is, as we all are struggling with wall time and dwell time, we know that just the time of transport to the hospital in a vacuum, in amongst itself only tells part of the story. It may actually be many, many minutes, if not hour later before that patient is actually seen by a prescriber, a provider who can actually order the treatment. So there are some patient centered reasons. But what we're most excited about the study is that when used properly with certain safety guards in place, it's relatively safe, as you can see here. And that's what this large analysis has shown us. We, I think, have given a lot more thought to the dosing and the parameters which are dosing, and we've hopefully made it safer for our patients without throwing out the proverbial baby with the bathwater.

Great, great answers, guys. Okay, let's go to Dr. Charlie Ingram.

Charlie, hi, good morning. So a couple of things. One, first a question where how did we land on rate control definition of being a hundred. And then also kind of to the the same point that you were just making, I think the next study here, like there are a lot of good ideas here. The next study is like, what's your ED length of stay for these treatments and these patients? Right? Because like, I agree, like if you're standing on the wall and Your heart rate's 140 versus you're standing on the wall and you're now like converted from afib to sinus, like, I bet you there's a difference there. And that becomes a now like patient centered difference, which I think is really important to link kind of all of our EMS studies too. So, but also really great Work and great presentation. So thanks.

Yeah, no, I. Absolutely. Sorry, your first question. I cut out for a second.

Oh, sorry. My wi fi is terrible. Why the. Why 100? So why is your, your heart rate goal 100 instead of like 110 or et cetera? Because I don't know that we have a reason for 100.

Yeah, I think the reason we really chose 100 is because the number that everyone chooses when you define tachycardia, it's also the number that's been historically used for rate control studies for atrial fibrillation, both within, without deltaize and with other agents as well. So when I was looking at things like the American Heart Association, American College of Cardiology, their thresholds, they pretty much universally used 100 as the threshold for tachycardia and 60 for bradycardia. And we did not want to call an adverse event rate control. Hence why we chose the 60 and then 100. Really? Because it was the commonly accepted and used threshold for the definition of tachycardia.

Hey, Charlie. We actually had that very discussion early in the planning phases about this because we all, I think as clinicians on the call, none of us are going to give somebody with a heart rate of 104diltiazem. But what we did is we tried to be pure to the legacy data and say, here's what other studies had used, but we very were very eyes wide open to that. So. So good catch on your part. For the sake of comparison and looking at the historical data. That's why we did it that way.

Yeah, I'd be interested to see like, if you, if you broke it to like 110 or 120, even like, I bet you your 1 in 5 now becomes like 3 or 4 and 5. Right? Like, there's a big difference there to.

We did play with it a little bit. We did look a little bit. Ellen, I don't remember the inflection point, but there was a bit of an inflection point.

You'd be including patients who, for example, never got above 110 to begin with. So that is to say, if a patient with a heart rate of 105 was given diltiazem, do we call that rate control? Because they would have been rate controlled to begin with. So I think that was our hesitancy about moving our threshold up when at the time of the study, the study protocols gave an indication of 100. So we said, I feel like if we're calling greater than 100 rapid atrial fibrillation, we can't Call a patient who at the time met the indication receiving the drug, considered that their initial vital sign to be emblematic of a positive outcome.

Interesting. Yeah.

But to Charlie's point, I was gonna say Charlie, to your point, you know, 3 and 5 did have clinical improvement. And so maybe that's the more, the more important variable. But go ahead. Sorry. Yeah.

My other question was, is the. Is, are IV fluids in the protocol right now? Right. So are they supposed to give IV fluids before giving drugs? Because I wonder like how many of these are just eliminated with some IV fluids? Because again, it's not the AFIB that's the problem, it's something else leading to the rapid afib. Right.

Yeah. So IV fluids are not in the protocol. Prior to the tiazem, we did include IV fluids as a variable in a multivariable model when we looked at the rates of efficacy and adverse events. Because we're also wondering, you know, does giving fluids in turn somewhat buffer that risk of, for example, hypotension? But we did not find that there was a significant difference in the amount of fluid given. I would also say that, you know, relative to a study done in a hospital in a randomized controlled trial, I think that our the recorded amount of fluids given is going to be more imprecise in the pre hospital setting.

Definitely.

Cool, thanks.

Awesome.

Great. Great conversation. Thanks, Charlie. Let's go to Lou. Lou, what's your question?

Actually a comment and a question. So the comment, historically I don't think average rated below 130 anyway. But it wasn't because the rate of 130, it's because they had some sort of distress. It's kind of like why we treat pain. No one is waiting at the door of the ER when we get there to give cortisone. It may be up to an hour, as the other doc mentioned. So we're trying to make the patient comfortable, just like we are with pain control. And the goal was never rate control, it was relief of the acute distress. So generally we got a rate in the one teens or so. That was good enough. And that's the time to stop. And that's the way I've always taught it. But my question.

Is, you had in there, if I saw it correctly, for hypotension, you gave calcium. It was hypotension induced by the cortisone. For bradycardia, you had atropine pacing and something else. It's like a two part question. Number one, if you have bradycardia without hypotension, then normotensive why would you even treat it? And number two, if you were going to, probably because they're hypotensive, is why wouldn't you titrate small amounts of calcium since it was the calcium channel blocker that caused it, rather than starting another path with atropine, other drugs, other treatments, et cetera.

Yeah, no, those are great questions. I think that's why we included the rescue medication to begin with, I think, as in our definition of adverse events, because there might be people who Normally sit at 59 beats per minute, and we didn't want to call that necessarily an adverse event. So we looked at really, what were they concerned enough about this to do something like atropine, epinephrine, external pacing? To your question about why wouldn't you just give calcium? At the time, protocol said something along the lines of for hypotension, give calcium chloride. And so because the protocol for diltiazem toxicity did not specify calcium chloride for bradycardia, we did not include that as a rescue medication for bradycardia. I did run the analysis separately, though, and there were no patients who had bradycardia, only who were given calcium chloride. So patients were not excluded from having an adverse event for that reason.

Thank you.

I tell you what, this is the first presentation where I feel like I'm sitting in the auditorium at namsp. It was a great presentation, and then you had a whole lot of people just coming in and giving some great questions and feedback. And this is really one of the reasons why having the authors of the paper describe their paper is so much better than just reading the paper. So just amazing stuff. I'm going to go over to Tanner, and then I'm going to let Ellen, Asa, and Matt finish us off. So, Tanner, any final comments before we go?

Yeah, again, just fantastic presentation. A topic that I think is of broad interest to the EMS community. And we appreciate that you've done the hard work to bring this to all of us. But before I let you finish it off, I also had one other quick question that came up while I was listening to everybody else talking. So, in terms of the temporality of the adverse events in comparison to diltiasm administration. So I know that for inclusion in this study, hypertension, and I believe it was heart rate less than 100, you excluded those patients that had that initially, and I believe you also recorded the maximum, minimum and final blood pressure and heart rates as well. So were you actually able to adjudicate, you know, the. The episode of hypertension was recorded post medication administration or was it just a hypertensive blood pressure measurement after the initial, and not necessarily after diltiazem administration?

Yeah, that's a great question. It's not something that we were able to determine because the diltiazem dose was not timestamped. I would hope that our providers were not giving diltiazem to a patient after they had been hypotensive, but in theory, yes, that's certainly possible, and we would not be able to discern that from the data set.

Fantastic. Thank you very much.

Great, great question. So I will. We really want to thank the three of you for coming on. I do always like to give you guys the last word. So, Ellen, we'll start with you and then we'll go to Ellen and Matt. Any final comments for our guests, for our attendees today?

No, I don't think so. Thank you so much for having me and I really appreciated talking with all of you.

Dr. Marcos, you did a wonderful job. Asa, Matt.

Yeah, I mean, obviously you guys can all see why we were so excited to have Ellen present this. You know, she did a better job than we could do and she's. She's wonderful to work with. Ellen, congratulations, Peter. Thank you for bringing everybody together. Really a great opportunity to share some work, get some feedback and have a great discussion.

Matt, now I. I would echo everyone's comments so far. Every time we tried to come off mute to answer a question, Ellen already had answered it and, and done a better job than we could have. So, Ellen, we're really proud of you. Congratulations and great work. Two plugs. One is.

One of my favorite mantras of the resuscitation academy is measure and improve. Measure and improve. We gotta measure, we gotta improve. If you're not measuring something in your system, start with measuring something and look to improve. It's how we get better. You don't have to do, you know, randomized double blind placebo controlled studies in EMS to do meaningful contributions to the body of knowledge. This was a retrospective review and I think was a great example of what you can do when someone has passion and motivation. The last thing I would say is that this was a study that we did. We bootstrapped it.

We, we don't.

We didn't get funded for it. We didn't have protective time for it. We did it out of passion and our love of ems. And I think we all are here for that same passion. So find something you're interested about and study it. That's all I got. Thank you guys. It's a privilege to be part of.

It because I don't want to be too rude to Dr. Pepe, but definitely seems like a very interesting comment there. The link for Eagle's webinar is in the chat. Tanner just posted it. Please join Dr. Pepe, which is in progress if you have the time to do so, and if not, we will see you next week. We have speakers booked out till January on this webinar, which is just insane. And if you know anyone or if you see a paper that you would love to hear from the authors, send it our way. Kenner and I would love to connect with those authors and bring you these types of episodes. So from Florida, signing off and we'll see you guys on the other side. Have a good weekend everybody.