E20: The vasopressor debate: Epinephrine or Norepinephrine after cardiac arrest

What happens after the pulse comes back?

In this episode, we dive into one of the most practical — and controversial — questions in post-cardiac arrest care: Which vasopressor should clinicians reach for first after ROSC? Epinephrine or norepinephrine?

Joining me is Dr. Nathalie Van Der Rijst, pulmonary and critical care physician from Philadelphia, for an energetic and evidence-driven debate exploring the physiology, pharmacology, real-world logistics, and limitations of current research surrounding post-cardiac arrest hypotension.

Together, we tackle:

• Why post-ROSC hypotension remains so deadly
• The physiologic argument for epinephrine vs. norepinephrine
• Myocardial stunning, vasoplegia, and recurrent arrest
• What observational studies and limited randomized data actually show
• Why prehospital realities matter when choosing vasopressors
• The challenges EMS agencies face with pumps, medications, and resources
• How ICU and emergency medicine perspectives sometimes differ — and where they align

Along the way, expect spirited Pittsburgh vs. Philadelphia banter, ICU vs. ER jabs, practical resuscitation pearls, and an honest discussion about the gap between ideal medicine and real-world medicine.

Whether you work in EMS, emergency medicine, critical care, anesthesia, or hospital medicine, this conversation will challenge the way you think about post-cardiac arrest shock and the critical minutes after ROSC.

As always, thank you for listening, sharing feedback, and helping grow this community focused on resuscitation, emergency medicine, critical care, and public health.

If you enjoy the episode, please share it with a colleague and send along topics you’d like covered in future episodes.

Transcript

Mohamed 0:01

Hello everyone. I know it's been a while since I last recorded an episode. Life has a way of pulling us in many different directions clinically, personally, and academically. And over the past few months, I simply haven't been able to record as consistently as I wanted to. But I've genuinely missed these conversations, and I'm excited to get back to doing this more regularly. Moving forward, my goal is to continue bringing you thoughtful, practical, and sometimes controversial discussions around resuscitation, emergency medicine, critical care, pre-hospital care, global health, and public health topics that impact the way you care for patients every single day. And honestly, some of the best episode ideas come directly from you. So if there's a topic you want covered, a debate you want explored, a paper you want discussed, or a clinical question you've been wrestling with, send it my way, please. I truly value your input, and many of these conversations are shaped by the feedback I receive from listeners around the world. Today's episode is one I think you're really going to enjoy. It's thoughtful, evidence-driven, practical, and yes, a little competitive. We're diving into the management of post-cardiac arrest hypotension and debating a question many clinicians face in the real world, epinephrine or norepinephrine as a first-line vasopressor after ROSC. And joining me is someone who brings an incredible critical care perspective. She's an ICU physician from Philadelphia, Which of course means that we also had to include a little Pittsburgh versus Philly rivalry along the way. I appreciate all of you for being here, for continuing to support the podcast and for growing this community with me. Let's get into it. Nathalie, I am so excited to have you here with me. I want you to tell our audience who you are and where you hail from.

Natalie 2:08

First of all, thank you. I'm so excited to be here. big fan of yours as well. I'm Dr. Nathalie Van Der Rijst. I am originally from the Netherlands, but now I am a practicing pulmonary and ICU physician in Philadelphia, which I love. I, to be fair, I love my job. I legitimately think I have the best job in the whole wide world. And I think if there's anything that you learn from me is that everybody should go into ICU, and that if you're not going into the ICU, then you should at least be living your life the best that you can. The best way to say it.

Mohamed 2:38

Now that you brought up Philadelphia, I have to ask you the most important questions. Two questions. Number one, which place you prefer to go and eat a Philly cheese steak in?

Natalie 2:52

I don't like Philly cheese. Are you really just like out in there on air like this? Wow. Thought we were friends. yeah. No, as a Dutch person, there's something fundamentally wrong about a cheese steak. Fundamentally wrong.

Mohamed 3:13

Oh my

Natalie 3:14

What is this plastic cheese?

Mohamed 3:16

Plastic cheese. Okay. So No. Are you a vegan?

Natalie 3:23

Oh, no. I love food. I love all food. except for plastic cheese. That's just a no.

Mohamed 3:29

I'll tell you like there are some places that do, make real beef meat, in, in Philadelphia, one of them is actually, Dalessandro's. It's in East Falls when I used to go there all the time. Not all the time. I would say like once in a week, Damn. Yes. Once weekly. That's all the time. with some friends. Okay. Are you a big philly sports fan.

Natalie 3:51

I'm so sorry to disappoint you. No, I'm a soccer girly. Again, the Dutch is strong within me. that being said, I have taken a more forward approach and conscientious approach to enjoying the sports more. So I went to my first Sixers game. I went to my first Go Birds. don't judge me. I can't remember what they're called. What's the football team called?

Mohamed 4:17

The Eagles

Natalie 4:18

Oh my God.

Mohamed 4:20

Eagle. Wow. I

Natalie 4:23

Don't judge.

Mohamed 4:25

I should be happy actually, as a Steelers fan, I probably should be happy to know that.

Natalie 4:30

supporting you here

Mohamed 4:32

Exactly. I feel supported by you completely dismissing the Eagles, which is it's

Natalie 4:37

but I the Super Bowl. Okay, that's all that matters.

Mohamed 4:43

I'm happy that you're actually representing Philadelphia. This is an interesting, episode that I'm trying to Make it fun yet competitive because as as an athlete, I like to be very competitive. and you being from Philadelphia, from Pittsburgh, we have this, beef, no pun intended. so I'm trying hard to make it as friendly as possible, but I might throw some jabs. Okay. Is that okay with you?

Natalie 5:07

That's totally fine. As long as I can jab back.

Mohamed 5:12

Okay. I can take it by the way.

Natalie 5:13

ICU and ER. Let's go.

Mohamed 5:15

Let's go.

Natalie 5:17

Yes, I just.

Mohamed 5:18

So really I think the topic is gonna be relevant to, a lot of us who practice emergency medicine, critical care, prehospital medicine, basically taking care of patients who sustained a cardiac arrest. Now they have post cardiac arrest hypotension. It's sadly and unsurprisingly very common, so anywhere between 50 to 70% of those who sustain ROSC become hypotensive and it has a very high in-hospital mortality up to 55%. That's crazy. the discussion we're having today is about which vasopressor. Should you start first, and I can expand this conversation to very other different agents, but I like to focus mostly on epinephrine and no epi. And being from Pittsburgh, I'm gonna pick epinephrine. it's muscular. There's a lot of pushups and can take a decent load. And I would tell you, you being from Philadelphia, norepinephrine to be a reasonable choice. But with many caveats. So I like to have this discussion. I'm gonna maybe split it in maybe three to four rounds. Is that okay with you?

Natalie 6:39

Okay.

Mohamed 6:40

Okay. I'm gonna start with my opening statement, and I'll tell you why I like epinephrine. So I like epinephrine for three important reasons. First, the pharmacology. This agent has an alpha properties as well as beta properties, so alpha one, beta one, beta two, so it helps with peripheral vasoconstriction. It can also help increase the diastolic pressure, improving coronary perfusion and also cerebral perfusion. And then the beta one properties can also help with inotropy and chronotropic. Which a distressed heart needs to provide good perfusion. And then the second reason for me is I love it because we're so familiar with it. Just epinephrine is so easily available in the pre-hospital setting. And I just have to say, I know you practice in a different setting in the ICU. Surrounded by plenty of food beds, naps, peaceful machines with, classical musics coming out of them. But I work in both the pre-hospital setting surrounded by emesis, stool urine, angry patients, and also work in the emergency department. The setting matters in this situation, depending on what we use more commonly. So epinephrine is very commonly used in a prehospital setting, and it's in the ACLS guidelines. Lastly, the evidence supporting either epi or norepi is lacking, is not very robust. So I would argue because of the numerous observational trials, EPI is easier to use, more effective and we should keep using it as a first line agent. Waiting for your jab.

Natalie 8:40

okay, I hear you. And I appreciate you admitting that the ER is the first place and then you bring them to the ICU in our calm and collected environment where we fix and patch up everything you just did. Just kidding.

Mohamed 8:56

I.

Natalie 8:57

ER is probably the only place that they could compare someone and say that the ICU is calm and collected, which I like, yeah, it's, here's my thoughts on it though, because yes, Levo(norepinephrine) is a superior choice and just because epi is the oldest and might be the easiest to use, does not mean it's the best. And I would like to work at a level where we give the best and only the best and nothing but the best, sir. So I do believe that EPI has an active resuscitation usage. Absolutely. Like epi, give epi, PEA, the whole shebang, but, when somebody is brought back to life AKA, we have achieved Rosc. The physiology is dramatically different, and I think that norepi should be the preferred vasopressor in the post cardiac period for the following reasons. One, to address the pharmacology that you mentioned. Post cardiac arrest. There is a lot of myocardial dysfunction. There is stunning vasodilation, cerebral hypoperfusion, all the reasons that you said epi could work. But epi stimulates both beta one and beta two, as you pointed out, which increases heart rate and myocardial oxygen demand, which. During cardiac arrest, trying to bring someone back is helpful, but post-op, the heart needs a chance to recover, to be like, whoa, I just died. I need to start beating again and actually getting blood to my heart so it can function appropriately again. So having levophed(norepinephrine) instead of epi because epi works on the beta receptors, therefore increasing your rate of tachy-arrhythmias, rearrest, and worsening myocardial injury versus levo or norepinephrine, which primarily acts as just an alpha one agonist with moderate beta one activity. It increases systemic vascular resistance, mean arterial pressure. but without the excessive myocardial stimulation that you get in epi use. plus if you actually look at the data and like I tell all my residents that if you wanna get any question right, in critical care, the answer is always because the study said so. So because the study said so, there's actually some decent data showing lower rearrest rates and improved survival with norepinephrine in the post ROSC population. So for those reasons, I still believe the norepinephrine is a safer and more physiologically appropriate vasopressor after ROSC.

Mohamed 11:29

Dr. Natalie, you raise very important points, and I take them with humility and respect, obviously, but I still have to stick with epinephrine in my argument because for the reasons you mentioned. a lot of the. Post cardiac arrest hearts are stunted, yet there is high risk of myocardial dysfunction. Correct? If I want to provide them with the best situation to recover, I think epi makes more sense to me because not only am raising their systemic, perfusion or systemic vasoconstriction, I'm also providing the heart itself with more perfusion by the alpha one and also augmenting the peripheral perfusion by the beta one simulation. Epinephrine also covers whole wider range of etiologies of cardiac arrest, and I'm thinking anaphylaxis, Natalie, are you ready for story time?

Natalie 12:33

I am ready.

Mohamed 12:34

Alright. Patient that I had not too long ago came in by EMS. It was as a transfer. It was an inter-facility transfer, and this is a critical care transport. So the patient was intubated, ROSC achieved by a community hospital, community emergency department, and during transport somehow, for some reason, the pressures and the alarms kept like going off, blowing off like crazy. With peak pressures, increased plateau pressures. So the critical care paramedic and nurse were like concerned what's going on? So they'll listen to the lungs. There's some wheezing. They gave some beta agonism. They noticed also hypotension. The patient was placed on norepinephrine. They went up by 0.05 micro kilo per minute times three doses. The map's still like 60 59, soft, and then it went down. So just they called for a consult. It's like what's happening? So I was like, what else are you seeing beside wheezing? Is there any signs of volume overload? Signs of cardiogenic shock? listen to the lungs, the moment they expose the chest area they saw this diffuse hives. So what did they do? Okay, maybe we should stop norepinephrine and start epinephrine for the beta two agonism to cover whatever that anaphylactic situation going on that might help with that. So it's again, for me as a first line undifferentiated post cardiac arrest. I don't know what's going on. Epi makes more sense because it can cover a wider range of etiologies. So is that convincing?

Natalie 14:15

As your ICU colleague, I have nothing but respect for ER and EMS and having now been in the planes for a while with too many, emergencies, which I know you work with planes so you can fully get this and fully understanding that when you have nothing at your disposal, you will use whatever you can. To me that is epi and post cardiac arrest patients. I appreciate the double usage. I appreciate throwing the entire kitchen sink at cutting a cucumber. But that being said, if we're talking about now that we have the choice of what you would like of picking the best one for all patients. Or as many patients included and not just the anaphylactic shock, which obviously like epi is a great choice and I love that story and I'm so glad you were able to save that patient. I still think that ultimately the degree of beta stimulation matters. For the following reasons that if we're gonna be talking about the different types of shock, one of the most common causes of cardiac arrest remains ischemic. So many people have heart attacks or something. So if you're telling me that you had a cardiac arrest or a patient had a cardiac arrest, their myocardium is not just ischemic from the cardiac arrest itself and metabolically stressed, but they already have small little blood vessels that aren't getting blood flow. So epi in this instance, can increase the heart rate, can increase the myocardial oxygen consumption has such an arrhythmogenic potential. So ultimately I think norepi is just better post ROSC, less tachy arrhythmias with less risk of recurrent cardiac arrest, which are the known complications or common next steps when you finally achieve Rosc. So Levo, AK, norepinephrine, I need to stop Calling. So norepinephrine, I truly believe, actually increases that vascular tone without excessively stimulating the heart. It gives the heart the blood that it wants without having all the side effects, which we get from Epi. there we go.

Mohamed 16:32

I really like your flex by stating these studies articles, even though you didn't really gimme the details, but I appreciate the initiative and the effort. So let's discuss some of your evidence, quote unquote. A lot of these studies are observational. I read and I'm sure you did also read the paramedic two trial, right? The paramedic two trial that found higher rates of Rosc and survival of 30 days with an unadjusted odd ratio of 1.39. and that was in a significant confidence interval. So Epi showed high rates of survival and ROSC, we know this, I know the only issue that we have between Norepi and Epi both did not show any improvement in neuro outcome and hospital discharge. So it's about the same, but the issues and the concerns that I have with the evidence you stated. They're based on observational data. And guess what? The devil is in the detail, when you look at who got epi, these are sicker patients with many comorbidities had longer CPR duration, baseline low blood pressure, lower than in norepi group. Higher lactate levels, which is a marker for poor perfusion in addition to worse acidosis and a severe, more severe baseline myocardial dysfunction. So basically we're studying two separate groups. Two different groups. you are giving epi to a sicker patient population than the norepinephrine, I'm sure the Norepinephrine group maybe were like, they just finished their manicure/pedicure and then they got norepi. I'm not sure what else they got. Maybe a fancy steak, I'm not sure. But different groups!

Natalie 18:27

Cheese on there.

Mohamed 18:28

yes. So yes, and that is my concern with these papers you listed, which to me, don't convince me that Norepi the answer.

Natalie 18:42

I truly do appreciate the fact that you put in the devils and the details and the patient population because such an important point that you always have to look at who the study's actually studying. so completely agree with you, the devil's in the details. However, if we're gonna then be mentioning that, I do think that using the lactate or having an increased lactate in epi is slightly misleading as epi epinephrine in and of itself can lead to an increase in lactate. so I personally was gonna ignore that part of it'cause I think that is a misleading fact, but. Even if the devil's in the details, even if you're going through observational studies, if you bring it all together, when you actually examine all of the clinical data and not just one style, there's several trials, several studies and ultimately meta-analysis that lead to me believing that levo(norepinephrine) is a superior choice, including a multicenter observational study of 766 patients with post Rosc shock, that found that patients treated with epinephrine post cardiac arrest had significantly worse outcomes. And yes, you are right, that is a sacred population, but it had a higher all cause mortality, higher cardiovascular mortality. Then there's a meta-analysis on top of that, which is a systemic review and a meta-analysis of six different studies, which overall included I what, 3,000. 3,458 patients, which showed that norepinephrine was associated with a 63% reduction in recurrent cardiac arrest. Yes, the devil's in the details, but if you bring all of this literature consistently showing that just in one study that was a sacred population, but then you show me a meta-analysis on top of that, including many different studies that show that there's a higher risk of mortality, at that point, you start thinking, is the devil in the details or is the details just the devil in this case?

Mohamed 20:56

Natalie, do you smell that? It smells very funky, I think smells like confounding bias to me. So again. They are not convincing to me and both you and I agree as clinicians and scientists that the ideal answer is a randomized trial, right? So we want to have a gold standard trial that tells us that. I know what the answer will be. Epi is better than Norepi, but there is a small, very small feasibility trial comparing norepi and EPI for post ROS shock. And interestingly, more patients in the EPI group achieved a target map and that I know. Don't get at me map number versus patient oriented outcome, the two different things. But yes, at least that what we have and that is the strongest evidence we have so far with this small feasibility randomized trial, all capital letters tells me that likely nor IP will take care of that post, ROSC shock, quickly. My issue with that trial itself is that it showed what, that you need to give a lot of epinephrine and I Now, this is when it comes to the point when I agree with you is that we already give a lot of epinephrine during cardiac arrest. So maybe the answer is not to give epi Q3 to four minutes, Q3 to five minutes, whatever that is. Maybe the answer is to give one dose Epi N actually focus on high quality. Compressions, ventilations, maybe reversing the underlying issue and then manage that post Ros shock with epinephrine so that the heart is not stressed with the frequent boluses of epinephrine. Maybe that's the answer, but I tell you, I am still in the undifferentiated situation. I'm still giving epinephrine first until I get more information.

Natalie 23:02

Okay. I hear you loud and clear. I am fully with you that randomized controlled trials are always the end all be all.'cause that's how we actually study things, but that being said it exactly like you said already. I agree with you this. The dosage that they used in that RCT, the epi was so much higher and so much higher than we would give at regular doses. And other randomized controlled trial for cardiogenic shock after myocardial infarction, which again we're gonna talk about in a second. That trial actually had to stop early because the refractory shock was so much more common in patients with epinephrine than it was with norepinephrine. So to answer your point in undifferentiated shock, while I do understand the benefits of epinephrine, and I think that it has great aspects, including the fact that it's great for, anaphylaxis, the fact that it's great for achieving Rosc in the first place. Ultimately, if I am at the point that a patient is back alive again, I will always choose levo(norepinephrine) because I firmly believe that at the end of the day, it will have a decreased risk of re death even an undifferentiated shock. In any shock, unless I see hives or I'm concerned for anaphylaxis, I would say that norepinephrine is still my preferred vasopressor post cardiac arrest.

Mohamed 24:35

Yeah, it's sad that, a lot of EMS agencies don't yet in the US don't yet have. Norepinephrine, that would be ideal because it would make more sense to give a vasopressor whatever that is as early as possible, that patient's home, that store, that, car situation happening. So as soon as possible, right. So we both agree that vasopressor initiation in post cardiac arrest shock is important. Now I sound like a politician. but I think given the current processes and systems that do exist in this country. In the United States, epinephrine is readily available, is pragmatic, is practical. A lot of EMS agencies and in hospital clinicians, emergency physicians are familiar with it. So I think for that reasons epi makes more sense until we get more data convincing me, convincing us that norepinephrine. Is as equal or maybe slightly superior, which I don't think is gonna happen soon'cause it's gonna be an issue with randomizing these patients. I know that we're seeing more and more data about vasopressin as another vasopressor of choice in these patients or even other medications specifically targeting these etiologies in cardiac arrest. My point is, and I wanna summarize my perspective, is that post ROSC shock is very complex and often involve vasoplegia and myocardial dysfunction. So epi for me is very pragmatic because it provides vasoconstriction, inotropic, and chronotropic support, which is ideal in those crucial early moments after gaining a pulse in a post cardiac arrest patient.

Natalie 26:33

I acknowledge the limitations of medicine and the limitations of not having anything, but to this date, there's never been an ER physician or an EMS person that I've spoken to that would not want to provide the best care if it was available. So just because Epi may be easier and may be well more known. Based on everything I know about my colleagues and your colleagues, I feel that norepinephrine remains the best choice. As discussed, it has a lot less adrenergic effects. It has a lot less cause for myocardial oxygen demand, a lot less risk for re-arrest arrhythmias. And there's enough observational data out there nowadays that suggests it is superior medication in our post cardiac arrest patients. So therefore me plus all of your colleagues. Would recommend it to be a first line vasopressor.

Mohamed 27:39

Wouldn't be nice for all EMS agencies in this country to have a pump.

Natalie 27:45

Yes. Oh my God, yes. Do you know that I was an EMS and like it took me so long to realize when I went through medical school and everything, that there was never a pump on the ambulance, which. And now with the surviving sepsis guidelines coming out, they're saying like, give antibiotics early. I'm like, have you given some of those an how are we What? I feel like it would be so nice. I feel like you and I can have a whole other conversation about all the equipment on EMS, on planes and so many other things that need to be fixed.

Mohamed 28:21

See, thank you for validating my point, because that is exactly the issue, right? EMS agencies are struggling to keep business, right? Are struggling to keep doors open and paying paramedics and EMTs. So the reality is right now. Many agencies don't carry an IV pump. So norepinephrine cannot be given as a bolus. Norepinephrine cannot be just given as wide open and run it. So that is an issue, right? That is a problem that we are having and more and more people because of that, that huge problem. Epi is more pragmatic and makes more sense'cause they can give it as a push dose of epinephrine. They can mix it in a hundred cc bag and like. do a little, little bolus. Little boluses. And yeah. So that is the reality, and thank you for realizing that because I agree with you. Every EMS agency, every patient that they take care of, deserves the best quality driven care. Regardless whether it's, norepi or epinephrine. However, the current reality is that not a lot of agencies are up to date with the equipment and the training. So based on that, epi makes more sense to me.

Natalie 29:41

In this case, I agree with you, which is why I think it's so important that we keep talking about this so that more agencies realize. this is so needed and that we are harming patients by not having the equipment that they need.

Mohamed 30:00

I think, having two different takes and two different perspectives from someone who works in the ICU and someone who works in a pre-hospital and the emergency department setting is very important. but I tell you, I think from my summary for this is we both agree that post cardiac arrest hypotension is lethal, right? That needs to be addressed quickly. We need to be more mindful of what caused that cardiac arrest and reverse some of the causes, whether it's, maybe a tension pneumothorax, pulmonary embolism or hypoxia. anaphylactic shock, septic shock. So it's important to start that early as soon as possible. Knowing your resources, I believe this is my conclusion that epi is ideal based on many pragmatic evidence that I've just listed to you, vasoconstriction, inotropic, and chronotropic support, and also the evidence that you and I just mentioned. unfortunately, it's very limited and it's based mostly on confounding observational data. And I do believe that is reasonable to start epi as a first choice as you investigate the other causes. And as we. Tuck patient in and make them ready for you to receive them in the ICU.

Natalie 31:16

I will admit that I see epi being at this point in time, a practical choice, even if it may not be the best one.

Mohamed 31:28

Thank you so much for providing us with your insight and perspective, and please allow me to invite you to the podcast in the future. And, maybe one of these days I'm gonna, I'm gonna convince you to, eat a Philly cheese steak from a reasonable and reliable, humane sources.

Natalie 31:46

This was amazing. Thank you so much. truly a pleasure to talk to you. I hope we do it again.