The EMS Lighthouse Project

LHP - E89 IM Epi in OHCA
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[00:00:00] Welcome to the EMS Lighthouse Project Podcast, illuminating the darkness of current EMS clinical practice with the bright light of science. Here's your host, Dr. Jeff Jarvis. Howdy y'all. I'm Dr. Jeff Jarvis. Welcome back to the EMS Lighthouse Project Podcast, where we shine the bright light of science on the darkness of EMS clinical practice.

So I brought up Paramedic 2 before. Let's quickly review that, shall we? This was a large, well done trial in the UK. It randomized adult non traumatic arrests to standard dose epinephrine or placebo. Now this is the best evidence to date on epinephrine, but it really highlights what we don't know. For example, it tells us nothing about the potential impact of smaller doses or different routes of administration.

Prior trials convincingly demonstrated that higher [00:01:00] doses did not improve functional survival despite increasing ROSC. As I like to say, with enough epinephrine, I can get a pulse back on a table, but at the end of the day, it's still a table. It's not a functioning human being. And because of a limitation of the study, Paramedic 2 also did not tell us anything about early administration of epinephrine.

It turns out that the median time from call to first epinephrine was 21 minutes in Paramedic 2. Now part of that time was because their protocol said to make one attempt at IV access before moving on to IO. Now, given the known challenges of starting an IV and cardiac arrest, going straight to an IO likely would have been faster.

And we have a pretty clear signal for some observational studies. Most of them from the Japan registry. [00:02:00] We have a signal that faster epinephrine is likely to be better than slower epi, but the question remains Well one question anyway, could alternative delivery routes be faster, better, stronger, to paraphrase Steve Austin, the astronaut, not the wrestler, just in case you're wondering.

So that brings me to the paper for this episode. The title is early. I am adrenaline administration is associated with improved survival from out of hospital cardiac arrest. The title gives the topic away. We're talking. I am Epi here in cardiac arrest. This was published in, uh, 2024 and resuscitation. The lead author was Helen Palinitis.

Co authors included Austin Johnson, Henry Wang, Yeme Horay, and Dr. Horay, I am absolutely positive I massacred your name. Please forgive me. And the principal [00:03:00] investigator, the senior author was Dr. Scott Youngquist. This group is out of Salt Lake City. Now, we talked about a similar study from this group in episode 80.

That one was a much smaller feasibility study looking at IM epinephrine in out of hospital cardiac arrest. So the rationale for this was that IM is faster and they found, not surprisingly, that it That I am epinephrine was both feasible and resulted in administering the epinephrine three minutes faster.

Now, because that was a feasibility study, a small study, it was underpowered to show significant changes in survival. The current paper, however, the one published this year in resuscitation, it's bigger, it's better. It's better powered to look at the impact of survival, which is exactly what it does. Thank you very much.

Let's get into the meat of it. This was a before and after observational study evaluating the impact [00:04:00] of a protocol change. Salt Lake City Fire Department changed their practice in 2019 and they started giving five milligrams of im epinephrine in the lateral thigh. While other team members were attempting to gain IV or IO access.

Now, they typically have at least six clinicians on scene. So limited manpower isn't a problem for them. So why five milligrams? Great question. Like most things we do in EMS, turns out this was for a pragmatic reason. The maximum recommended volume for injection into the site is five milliliters, and the concentration they have was one milligram per milliliter of epinephrine.

5 milliliters, 5 milligrams. That meant the dose would be 5 milligrams. Pragmatic reason, that's what they had. Now, the authors do [00:05:00] reference some pharmacokinetic evidence that suggests 5 milligrams of IMEPI is roughly equivalent to 5 milliliters. To 0. 5 milligrams of IV or IO epinephrine. Therefore, this study is actually looking at both early epinephrine and slightly less epinephrine.

Now that first dose given IM while the IV or IO is being started, all subsequent epidosis were given as one milligram IV IO, and they did that every three to five minutes, no max. So this was really a study of standard ACLS versus standard ACLS plus IAM EPI. So who do they include? All adult non traumatic arrest who received any epinephrine.

That means they excluded trauma, they excluded children, and they excluded the one shock wonders who got ROSC. before any epinephrine was given. Now, their [00:06:00] before or control group was from 2010 to 2019. The after or intervention group was from 2019 to 2024. Like so many of us who made changes to our epi protocols after paramedic two, they had the piss poor fortune to implement their changes right before COVID.

We know that national survival took a huge hit after COVID, so we should assume that their IM EPI group, solely because of the timing, would have lower survival regardless of the impact of IM EPI. So just think about that. We're going to have two groups, one group now because of the COVID. we would suspect would have lower survival, blunting any impact of IAMAPI.

All right, so what's the primary outcome? That is survival to hospital discharge. Secondary outcomes include neurologically intact [00:07:00] survival, functional survival, again, the thing that patients care about. Now they used multivariable logistic regression to calculate the odds ratio for the association between IM EPI and the outcomes, that is functional survival, survival to hospital discharge, and they adjusted for all the usual Utstein covariates, age and sex, witness duress, shockable rhythm, all the things.

They also did some, what I think are pretty appropriate sensitivity analyses, but I'm going to skip over these because I don't think it really changes the clinical takeaway message. And that's what I want to focus on. Now, overall, they included 1, 405 patients that had roughly similar baseline characteristics.

There was one exception, and that is that the IV group, had slightly more bystander CPR, 70 percent versus 55 percent and were slightly younger, 57 percent versus [00:08:00] 60%. Both differences were included in the regression as confounders, meaning their analysis likely was able to appropriately control for these relatively small differences in baseline characteristics.

Now, their overall survival across both groups was 8. 2%. And as a reminder, lest you want to beat up on Salt Lake City's survival, remember that 8. 2%? That was both overall survival, including unwitnessed arrest, and And they had already excluded patients that were most likely to survive. That is the ones who got ROSC after a single defibrillation and before they could give any epi.

So already we're talking about a group that's going to have lower survival. Now the median time from 911 call to the first epi was significantly faster in the IM group. How much faster? 3. 5 minutes. It was 7. 8 minutes in the IVIO [00:09:00] group and 4. 3 minutes in the early IM group. Survival to discharge and functional survival.

Here's the bottom line. Both outcomes, both survival outcomes, including functional survival, significantly higher in the IM group in both raw and adjusted differences. Okay, let's go ahead and hit some of the numbers, but that's the big point here. Survival to discharge was 7 percent in the I M I O group and 11 percent in the I M group with an absolute increase of 4%.

The adjusted odds ratio is 1. 73 with a confidence interval from 1. 1 to 2. 71. That is a 73 percent increase in the odds of survival to hospital discharge. That seems important to me. What's even more important to me is functional neurologic survival. And more importantly, that's what's important to patients.

It [00:10:00] increased by an absolute 3. 6 percent from 6. 2 with IVIO to 9. 8 with IM. The adjusted odds ratio there 1. 7 to 95 percent confidence interval from 1. 07 to 2. 7. Six Again, I just want to iterate that is a 72% increased odds of neurologically intact survival with early epi via I am and that is despite the covid.

So I am epi seems to be having a benefit. I love this concept, y'all. I love it. Despite being completely surprised that any I am epi at all. made it to the central circulation during cardiac arrest. So let's face it, cardiac arrest is about as low a low output state as you're going to get. I was certainly taught, and I think [00:11:00] y'all were too, that IM drugs don't hit central circulation in low output states.

Well, turns out we give it an anaphylaxis all the time, an anaphylactic shock, shock, low output. I don't know, I don't know, but it seems like something's getting in there. It's getting in there faster and it seems to be working. Again, early evidence, not randomized control, but it does look good. Now, if this does work, it is a poster child for the pragmatic types of innovation that EMS is known for.

As a reminder, Paramedic 2 had a median time to first epi of 21 minutes. This trial was faster, it had 15 minutes, even in the IV IO group. And IM EPI shaved off another three minutes. Prior observational studies have estimated that each additional minute of delay to the first EPI is associated with 4. 6 percent [00:12:00] decreased odds of infection.

This suggests that getting epi three minutes faster might be associated with 12 to 15 percent higher odds of survival. Now, obviously they found a smaller effect size here. This may be because there was less epi making it to the heart via the IM route. Compared to IV or just as likely the estimated benefits seen in the observational studies just wasn't terribly accurate to really get an accurate estimate.

We need a prospective randomized control trial. Why? Well, because RCTs, when well done, are the best way to control for baseline differences like say covid or Unmeasured confounders. Now, having said that, we need an RCT. I want to talk about whether we should consider making a change in our practice before an RCT based only on this paper.

I've been thinking about this a lot lately. I've [00:13:00] been talking about this a lot lately. I think, I think the issue of when to adopt. A new intervention comes down to several factors. So certainty of evidence, the ease and expense of implementation and potential risks and potential benefits. In general, I think that the level of certainty of evidence I need to make a change.

is proportional to expense, logistical challenges, and risk. And I think it's inversely related to potential benefit. That means the more expensive, the harder to implement, or the higher the risks of harm to the patient, the higher level of certainty I need. Conversely, the higher the potential benefit, the lower level of certainty I need.

In this case, my gestalt, is that the price both in dollars and opportunity cost is reasonably low. Now one [00:14:00] thing we do have to worry about is the potential mix up between IM EPI for cardiac arrest, that is 5 mg, and the dose of IM EPI for anaphylaxis, which is 0. 5 mg. A tenfold increase in the EPI dose for anaphylactic shock could be Welcome.

So we don't want to do that. So we do need to have a balancing measure. We do need to look out for this, but maybe we can overcome this with proper labeling storage, something like that. I think the increase that we're seeing here is probably worth that risk. Now, because many of our BLS units in the U S are already credentialed to give I am Epi and anaphylaxis implementing this really shouldn't be all that challenging dosing.

Notwithstanding a 4 percent absolute increase in functional survival seems meaningful to me. Seems [00:15:00] meaningful to patients. And I think the risk of a single dose of I am Epi in cardiac arrest while waiting for standard care. That seems pretty low to me. So put together, I think this paper, I think it's enough to consider, for me anyway, adding this intervention to my system.

And that's even before we see an RCT. I would of course love to participate in a multi center trial, you know, just in case Scott or Henry happened to be listening and considering such a trial. Remember me in Fort Worth. We would love to help solve this problem. I think our patients can benefit from such a trial.

Now, these authors showed that a three minute time savings by giving EPI while other clinicians are getting access. It seems that even more time could be saved, potentially increasing survival further. If we were to give that first dose of epi even [00:16:00] before the first ambulance arrived. Dr. Youngquist didn't do that in this study because he was being cautious in the way that he's studying this.

The epi was given at the same time the ALS providers were starting an IV or IO. Think about that. Epinephrine on a BLS engine, getting that first dose in again, whether it's an engine company or, or hear me out, perhaps a police officer. I would love to have an officer with an AED, maybe a tourniquet and a large dose epinephrine auto injector respond to every arrest in my city.

I think, I think this could make a real difference. With this early intervention. Interestingly, I was talking about this at EMS Expo in Las Vegas. Just got back from a huge conference. I think this is the biggest Expo I've seen. [00:17:00] Very successful. I was very pleased with it. Thank you to the Expo folks. Thank you for NAMT for co sponsoring this conference.

Amazing thing. And by the way, as a proud Papa moment, if you don't mind me saying this, my daughter, Sydney Jarvis presented her first poster abstract at a research event as the primary author. I'm proud of you, Sid. Great, great work. Can't wait to see the manuscript. You're right. Well, as I was at Expo, we were discussing this with other medical directors, and they reminded me that.

I understand there is a formulation of intranasal epinephrine coming out marketed at the anaphylaxis group. Think about if we change the dose of that and allow intranasal epinephrine In cardiac arrest, that is something police officers could certainly do. It's something that perhaps we put in our fire extinguisher box [00:18:00] with the AED, the tourniquet with Narcan and now epinephrine.

Wouldn't that be great? I think that'd be great. All right. Bottom line here. I am at the clearly feasible. It's faster. It's unlikely to be harmful. clear suggestion of meaningful benefit. It fits with what we know already about epinephrine, which is that the earlier it's given the better. Again, that's probably one of the few things we do know.

And because of that, I'm going to be adding it to my protocols at some point. Now there are some obvious operational challenges that we have to address first, but I think the balance on my decision making matrix favors adoption. As always, y'all, I'm Interested in what you think about it. Is this something you'll be adopting?

Is this something you want to see in your practice? Let me know, hit me up in the comments on YouTube where all of these podcasts live on Twitter. I'm at dr. Jeff Jarvis, or you can email me [00:19:00] at jeff. jarvisatflightbridgeed. com. Thank y'all for listening and thank you for what you do for your communities every single day.

Take care of y'all. You've been listening to the EMS Lighthouse Project podcast, a proud member of the FlightBridgeEd podcast family and a FireDog production. Visit FlightBridgeEd. com for more information.