SCCM Pod-465 PCCM: Who’s Got the Right Dose?

Pediatric advanced life support (PALS) guidelines include weight-based epinephrine dosing recommendations of 0.01 mg/kg with a maximum of 1 mg, which corresponds to a weight of 100 kg. But what are the actual practice patterns? Elizabeth H. Mack, MD, MS, FCCM, is joined by Martha Kienzle, MD, to discuss the article “Weight-Based Versus Flat Dosing of Epinephrine During Cardiac Arrest in the PICU: A Multicenter Survey,” published in the October 2022 issue of Pediatric Critical Care Medicine (Kienzle M, et al. Pediatr Crit Care Med. 2022;23:e451-e455). Dr. Kienzle is an attending physician in the Department of Anesthesiology and Critical Care Medicine at Children's Hospital of Philadelphia.

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Category: PCCM Podcast

Transcript:

Dr. Mack: Hello and welcome to the Society of Critical Care Medicine Podcast. I’m your host, Dr. Elizabeth Mack. Today I’ll be speaking with Dr. Martha Kienzle. We’ll be talking about the article, “Weight-Based Versus Flat Dosing of Epinephrine During Cardiac Arrest in the Pediatric Intensive Care Unit: A Multicenter Survey,” published in Pediatric Critical Care Medicine. To access the full article, visit pccmjournal.org. Dr. Kienzle is an attending physician in the Department of Anesthesiology and Critical Care Medicine at Children’s Hospital of Philadelphia in Philadelphia, Pennsylvania. Welcome, Dr. Kienzle.

Dr. Kienzle: Thank you so much for having me.

Dr. Mack: Sure. Before we start, do you have any disclosures to report?

Dr. Kienzle: I do not.

Dr. Mack: Wonderful. I noticed so many amazing minds came together for this work. It’s really an interesting topic and an important contribution and, I think, something many of us grapple with. And it’s so timely. Many of us were forced to reconsider our dosing strategy as many of our PICUs cared for adults during the peak of COVID. I’m wondering, how did you guys all connect and where did the idea come from?

Dr. Kienzle: Yeah, definitely. Thanks for your kind words. The question of how to dose adolescents and larger kids had come up in one of our divisional cardiac arrest debriefs. We had brought the question to our resuscitation committee meeting as we were in the process of revamping our, quote, code book, which is the binder of emergency meds with dosages that is on all of our code carts throughout the hospital. At that time, the code book said to dose epinephrine by weight until 100 kilos, which would provide the adult dose of one milligram. But we wondered if that made sense, considering most adults weigh less than a hundred kilos. And we realized we really had no idea what intensivists at other institutions were doing. So we brought in collaborators from Cincinnati and Atlanta with whom we had worked on earlier projects, both to confirm that this topic was as much of a black box as we thought it was and also to have diversity of perspective among resuscitation experts in creating our survey questions. They agreed that it was a black box and that we should definitely ask everybody.

Dr. Mack: Awesome. Thanks for sharing that. Really an interesting story. I know that debriefing is really a strong suit there, and so glad that you guys brought this forward. Can you share with us a little bit about what you all found? Was there anything that you were surprised about?

Dr. Kienzle: We found that weight, and not age, was overwhelmingly the patient factor most used in code epinephrine dosing. The largest proportion of those respondents, about half, switched to flat dosing at the 50-to-60 kilogram weight range. PALS guidelines were fairly vague over the years. The 2020 version specifically says these guidelines refer to children less than 18 years of age. But the 2020 guidelines were not yet published at the time of the survey distribution, and this statement referred to the entire scope of the guidelines, not medication dosing specifically.

There’s more added confusion when you consider that BLS guidelines have historically recommended switching from pediatric to adult algorithms at signs of puberty, and this comes up not uncommonly in our divisional conferences as well. Someone will say, aren’t we supposed to switch to ACLS at puberty? So perhaps the cumulative effect of these consensus statements, as well as the fact that we increasingly care for chronically ill adults in PICUs, has led to a de-emphasis of age. So we were not surprised by there being overall heterogeneity in practice, but we were surprised that so many institutions were doing the same thing and not the thing that was most consistent with guidelines.

Dr. Mack: Thanks for sharing that. It’s totally clear as mud in the guidelines, it sounds like, and therefore variation in our practice. You all noted in the paper, as you said, that current PALS guidelines apply to patients less than 18 years of age, with an implicit recommendation that patients less than 100 kilos should receive weight-based epinephrine dosing; however, only about 9% of your respondents reported switching to flat dosing at 18 years, and 12% reported employing weight-based dosing up to 100 kilos. So I’m just curious, is your sense that this is related to computer-based code sheet generators or an intentional decision, or what did the author group think?

Dr. Kienzle: I think that it is an intentional decision because the more streamlined thing to do with our automatic code generation, which we use as well, would be to dose by weight for children less than 18 until the adult dose is reached, just like you do with many other drugs, and then automatically switch to adult doses when the patient is 18 or older. But it really doesn’t seem like many places are doing this. Other emergency meds reach adult dosing at much lower weights than 100 kilos. So doing something different than that with epinephrine, which people are clearly doing, actually seems like it could be the more error-prone strategy. But that being said, I was glad to see that most places standardize epinephrine dosing in some way and standardization should, in theory, reduce errors.

Dr. Mack: Awesome. Thanks for that. It is interesting to think that the same child admitted to a PICU versus an adult ICU would get different doses of epinephrine, or even the same child admitted to two different pediatric ICUs. In light of the fact that deviance from the PALS guidelines is prevalent, do you think that many intensivists have it wrong, or do you think that we should be revisiting the guidelines? Just wondering what are your thoughts on that related to the science and maybe what’s best for our coronaries.

Dr. Kienzle: I don’t think anybody is wrong, but I do think the guidelines could be more clear because intensivists have clearly chosen to dose epinephrine in many different ways, and I can’t tell if that phenomenon is a rejection of the guidelines or a perception that the guidelines are not clear, so people are doing what they think is best. There is no evidence that half a milligram, for example, for a 50-kilo child is more or less effective than a full milligram. But as far as toxicities go, a, quote, double dose for a 50-kilo child is still far from high-dose epinephrine, which was investigated with randomized control trials and is typically defined as 10 times the standard dose. That has had documented toxicities in human studies. So, considering the lack of data and really not approaching documented toxicity doses, it’s reasonable in my mind to use either strategy. We just don’t know which one is best.

An academic interest of mine and of my research group as a whole is how to provide personalized resuscitation care. We have seen in large animal studies at our institution that animals respond differently to intra-arrest vasopressor boluses. Some need more doses, some need fewer doses, and some don’t need any at all to achieve good hemodynamics and ROSC. There are likely patient- and disease-specific factors that determine the response to epinephrine. Like other drugs, there’s unlikely to be a dose that works for everyone. Hopefully we learn more about it over time.

I guess the recommendations have been written as they are based on the limited evidence that we have, which is totally appropriate. But that being said, the survey results, I think, show that there’s a disconnect between the recommendations and the implementation of the recommendations, and that, I think, should be addressed by the next writing group.

Dr. Mack: Awesome. Lots of work to do. Thank you so much. I’m curious about your thoughts on ideal body weight and the impact of that on dosing in both directions, since we take care of children and adults at the extremes of the ends of body habitus.

Dr. Kienzle: Absolutely. This, interestingly, is another example that I didn’t really delve into in the paper, but another example of how institutional practice deviates from the guidelines. The 2010 guidelines recommended against using ideal body weight despite the theoretical risks of using the actual body weight in obese patients, meaning providing an overdose of a medication. And they recommended against using ideal body weight because there’s not enough evidence to support using an ideal body weight. The 2015 guidelines did not readdress it, but the 2020 guidelines also cautioned against using ideal body weight. But despite this, almost half of respondents say that their institutions do use ideal body weight when dosing epinephrine for obese patients.

It would have been interesting to ask the opposite question. Do people use ideal body weight for, for example, the non-ambulatory, very thin cerebral palsy patient? I would guess that this is less common because overdosing a cachectic malnourished patient feels more harmful than underdosing an obese patient. But in the setting of cardiac arrest, who really knows? These are all big question marks and another example of people diverging from the recommendations, but just a paucity of evidence to guide us.

Dr. Mack: Thank you for that. I’m curious, what suggestions would you have if one of us were building a program from scratch and really intentionally developing dosing recommendations in our local institutions? I’m curious how you would recommend the dosing of the code-dose epi.

Dr. Kienzle: Yeah, I think that probably a hybrid recommendation is best. For children, epinephrine should be dosed by weight, at the dose that we all know, 0.01 milligrams per kilogram, while not exceeding the adult dose of one milligram. But for patients over, for example, 60 kilos, the code leader could consider providing an adult dose. Epinephrine is the only drug that’s universally recommended across all algorithms, even though, our institution included, we use a lot of things that are pointedly not recommended to be used routinely in cardiac arrest. But I think that, because it is kind of the drug, a little bit of nuance within institutional recommendations is appropriate, especially since the data to support a specific strategy are very limited.

The other side of the coin, which is the small adult, is murkier, I think. Anecdotally, at our hospital, code leaders would not even consider giving a milligram of epinephrine to a 35-kilo 20-year-old with chronic disease. But I’ve also seen a 70-kilo 20-year-old get weight-based dosing instead of a flat dose because they’re in a pediatric hospital and that’s what we do and that’s our workflow.

I think dosing policies could potentially address this too. They could say, adult patients should get 1 milligram. But if the adult patient is less than, for example, 40 kilos or child size, the code leader could consider a weight-based dose. This might be getting too nuanced and, frankly, that goes against the ACLS guidelines. I recommend 1 milligram for people 18 and over, but the preference for weight thresholds among pediatric institutions shows that this is basically what’s happening anyway. Like many under-researched areas of pediatric medicine, we use our best clinical judgment to cater to our patients’ differences. I do think we need to strike a better balance between what our professional societies say to do and what is actually being done.

Dr. Mack: Thank you for that. I think that’s very thoughtful and, like always, no black or white answers here. Anything else that you would like to share about your research or other thoughts on CPR and your work there?

Dr. Kienzle: No, I have nothing else to add. I think this sets up a lot of fascinating questions. My work moving forward will continue to understand this drug that we all use so much but understand so little about. It’s actually fascinating when you go back to the text and the recommendation for using epinephrine is not strong. The verbiage is, it is reasonable to give epinephrine, and yet we all do it. I think we need to understand its pharmacokinetics and dynamics and patient factors that influence the response to it. We’ll be able to take better care of people as a result.

Dr. Mack: Thank you so much. I really appreciate the work that you’ve done in this field that has led to this publication and others and all that you continue to do to try to understand this very high-stakes area. This concludes another addition of the Society of Critical Care Medicine podcast. For the Society of Critical Care Medicine podcast, I’m Elizabeth Mack.

Elizabeth H. Mack, MD, MS, FCCM, is a professor of pediatrics and chief of pediatric critical care at Medical University of South Carolina Children’s Health in Charleston, South Carolina.

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