I now have the privilege of introducing our third and last speaker, my co-moderator, Dr. Elizabeth Munro. She is, she had mentioned previously as a clinical instructor and research fellow at the University of Michigan where her research focuses on vasopressor administration and fluid resuscitation. And in particular, I think it's fair to say that even at this junior stage in her career, she probably is one of our leading experts on peripheral use of vasopressors. So we now have the privilege of listening to her speak on ditching the central line. When is a peripheral IV enough for vasopressor administration? Thank you. So I have no disclosures. And I wanna start by posing this question of how do you start vasopressors? Because there's several different approaches that have really been evolving over the past few years. The traditional approach is to place a central line and only administer a vasopressor centrally. And this stems from case reports in the 1950s and 60s of terrible catastrophic tissue injury that occurred when vasopressors leaked out of a peripheral IV or extravasated. This led central administration to really become the standard. However, central administration has a few disadvantages. No matter how fast you are at placing a central line, it will take you time. And that can lead to delays in vasopressor initiation which can be important as we move towards earlier vasopressors as Dr. Pelton discussed. Also central lines themselves have complications on the order of about 3%. So at the same time, there's been increasing safety data that supports that peripheral vasopressor use may be safe. It's based on that data that in 2021, the surviving sepsis campaign guidelines updated their guideline to say that you can start vasopressors peripherally to avoid delays, although they still recommend placing a central line as soon as possible. In practice, we've seen this taken one step further where you start vasopressors through a peripheral IV but only place a central line if you need it. For example, for high doses of vasopressors or another indication. So which of these approaches should we be taking? To answer that question, I wanna take a look at the newer peripheral vasopressor safety data that I mentioned. This is a summary of three systematic reviews and meta-analyses that have come out in the past few years. You can see it's a few thousand ERICU patients and several thousand more perioperative patients with adverse event rates ranging from 1.8 to 7%. And those adverse event rates were mostly minor. They were mostly extravasations and some local tissue erythema and phlebitis. But importantly, in all of these patients, there was zero cases of skin necrosis or limb ischemia. So I wanna walk you through a few of those larger studies to give you a sense of what their design was and what they tell us. So the largest study was a perioperative study. Retrospective, it included 14,000 patients at two hospitals in the Netherlands. These patients were receiving peripheral neuropinephrine for short durations perioperatively, so during and after surgery. And that extravasation rate was very low, 0.035%. But we all know that the operating room is very different from the intensive care unit. So what about in the ICU? So the largest ICU-based study we have is from Cardenas-Garcia in 2015. This was a well-designed single-center prospective study that enrolled 700 ICU patients who were on vasopressors and said that those vasopressors could be administered peripherally using strict safety protocols for up to 72 hours. The extravasation rate was 2.3%, but no tissue injury, which is great. And then only 13% of those patients ended up getting a central line, which is pretty impressive for patients on vasopressors for up to 72 hours. More recently, the study by Yerke et al. in CHESS in 2023 was a similarly designed single-center prospective study, 600 ICU patients, this time particularly on neuropinephrine. They also used strict safety protocols, and they allowed vasopressors to be run peripherally for 48 hours initially, although they extended that later in the study as they saw that it was safe. Extravasation rates were 5.5%, no tissue injury, and then about half of their patients avoided a central line. So in these studies, I've mentioned these strict safety protocols. I put this up here not to overwhelm you, but just to show you how detailed these protocols are. And we're gonna go through some of these elements in depth, but you can see that they're requiring certain vein sizes, certain IV sizes. These are very comprehensive protocols. So hopefully I've shown you that based on the data we have, that peripheral vasopressors appear to be safe. But the caveat is that's all in single-centered studies with strict safety protocols. So if we're using these vasopressors through peripheral IVs at our hospitals, do we have similar safety protocols in place? We asked this question by conducting a survey of hospitals in our HMS, which is our Michigan Hospital Medicine Safety Consortium. We had answers from 62 hospitals, of whom 52 or 83% had a policy. And those policies fell fairly evenly between central only, which means they required central lines for vasopressor administration, central preferred, meaning they recommended central lines, and peripheral friendly, which was more liberal and more explicitly allowed peripheral vasopressors. But even the hospitals that were allowing peripheral vasopressors put limits on their use. Those limits fell into two main categories, vasopressor-based limits, based on doses, duration, agent, and IV-based limits, size, location, ultrasound requirements. And so there were these broad categories that were similar, but the actual limits varied widely across these hospital policies. Which raises the question, if there's different safety protocols in all of these different studies and in each hospital, then what are the most important elements? What should you be taking back with you? So I would argue that they fall into three main categories, elements that are definitely needed, maybe needed, and not needed, potentially harmful. So definitely needed is monitoring and extravasation management plans. Why is that? So extravasation happens. I showed you that even in these well-done studies, it's happening two to 5% of the time. So in order to prevent tissue injury, we need to be able to catch it early. What does that monitoring look like? In the safety studies I've reviewed, that monitoring was every two hours, quote, for patency. At our Michigan hospitals, two-thirds of them had a monitoring protocol, although that should arguably be 100%. But what they're doing is they're looking every one to two hours at that IV, either visually and or by aspiration. I think the details are less important than the fact that you're keeping an eye on that IV while vasopressors are running through it. Similarly, because extravasation happens, we need to know what to do about it. So these studies have also included explicit extravasation management plans, where they have the antidotes to extravasation, pentolamine to counteract the catecholamine effects, and nitroglycerin to vasodilate. All of those are available in their omni cells on their units. They have nursing-driven response protocols, so the nurses don't have to wait for orders, and then broad education. So it's important that as you're using peripheral vasopressors that you're monitoring it, and you know what to do when extravasation happens, because it will. Now what about these other elements that potentially are needed? And I say they're potentially needed because these range widely across the studies and policies. So in terms of dose caps, there's a theoretical idea that the higher dose that you have of a vasopressor, the more likely it is to cause injury if it extravasates. At our hospitals, 45% of the Michigan hospitals had a dose limit, and the one they do, it was usually less than 0.3 micrograms per kilogram per minute of norepinephrine, or equivalent. And that fits in pretty closely with the safety studies that we have. So most studies are capping it at a dose of 0.15 to 0.3 norepinephrine equivalents, although I will say that the Cardenas-Garcia ICU study allowed much higher doses with a mean peak dose of 0.7, which is quite high peripheral, but it was safe in that study. So we don't know the exact right dose cutoff. I'll also say here that we also don't know the exact concentration. There are some people who advocate for more diluted norepinephrine, although the studies have mostly used standard concentration. So while there's a little bit of debate about the optimal dose, what we do know a little bit more is that all the studies have only studied so far a single vasopressor agent at a time, so you can't run two vasopressors at the same time in these studies through peripheral IV. And then vasopressin, which we just heard about, was not included in most studies because it doesn't have a specific antidote. It's not a catecholamine. So in general, in my practice, I'm worrying less about what the dose is and more following the guidance to place a central line when I'm adding that second vasopressor. What about duration limits? So the argument here is that longer duration increases the risk of extravasation. At our Michigan hospitals, we see that duration limits range from just until a central line all the way up to 48 hours or no limit. And in the studies, as I mentioned, those were much longer times, 48 to 72 hours. And they didn't really see a relationship between extravasation and time. So in general, it's less about duration and it's more about monitoring that IV and making sure that IV is working. As long as it's working and you're watching it, you can probably push out to these longer time limits. And finally, in this category is IV requirements. So the rationale here is that a large proximal IV is gonna be less likely to extravasate. Although from the nursing literature, they actually care more about the vein size than the IV. But taking what we've focused on in these studies is that they have used large IVs, 18 to 20 gauge, generally the forearm or the upper arm. There's some debate there, but in general, they're never using the hands and never using the legs. And these IVs are confirmed with ultrasound. Now we'll see that makes sense, that seems nice and easy, but there were tons of violations of this protocol within the Yerkes study and it was still safe. For example, 50% did not have their IVs confirmed by ultrasound. So it's a little bit unclear what you need to do. So with all of these different protocols and approaches, we wondered what do providers do and what do they care about? I led a randomized vignette study of 550 critical care providers where we asked the question, in a patient who's getting norepinephrine through an 18 gauge IV, when would you place a central line? And we randomized certain factors and saw how those factors impacted the decision to place a central line. So if we take a look here, vasopressor dose had a large impact. So at a low dose of 0.08 equivalents of norepinephrine, about 25% of respondents along the x-axis would place a central line versus when that dose gets to 0.5, you see about 80% of providers are placing a central line in these cases. Similarly, dosing trend is playing a role. So an increasing dose is triggering more providers to place a central line rather than a decreasing dose. Duration has a smaller effect with providers being more likely to place a central line at 24 hours. And then peripheral IV location between upper arm and forearm, which are arguably both good locations, didn't really make a difference. So to providers, this dose and dosing trend seems to be a key of when they're deciding to place central lines. Now, what about this final component of what is not needed or harmful? That's limitations on peripheral norepinephrine. So almost 25% of our Michigan hospitals prohibit peripheral norepinephrine. And we also see in practice at our Michigan hospitals that less norepinephrine is used peripherally, 84 versus 97%. And that's probably because of fears from these 1950s case reports where the vasopressor that extravasated in all of those pictures was norepinephrine. But the caveat is that was the primary vasopressor back in that time. And since then, peripheral norepinephrine has actually been the best study. So it's been used in over 16,000 patients in these safety studies, as well as Dr. Pelton mentioned, it was used in over 400 patients in the 2023 Clover's trial of early vasopressors. So I would argue that using peripheral access is not a reason to avoid norepinephrine, especially because the Surviving Sepsis Campaign recommends using norepinephrine as a first-line vasopressor, which is a rare, strong recommendation based on high-quality evidence. So I've shown you that there are key elements of peripheral vasopressor protocols, but our actual hospital policies vary. So what are we doing in practice? We took a look at this, again, through our HMS, through our Michigan hospitals, in a study where we had 594 patients with sepsis on vasopressors across 29 hospitals. We saw that peripheral initiation was the most common route, 67% of the patients had vasopressors started peripherally compared to 26% centrally. And those who had vasopressors started peripherally were started, on average, 30 minutes faster, which makes sense, and one in three of them avoided a central line, speaking, again, to the practical advantages of using a peripheral vasopressor. So what happened to those patients over time? They got started on vasopressors peripherally, but when were they getting a central line placed? So this is a Sankey diagram from that study, and you can see on the left side of the screen the initiation, and on the right side where they were at by day four. And I'll draw your attention to the dark blue, which is those patients who were started on vasopressors peripherally. You can see about a quarter of them died, a quarter of them were still on vasopressors on day four, but through a central line in orange there, a tiny percent, 2%, were still on vasopressors peripherally, and then the rest were alive and off of vasopressors. So we've seen in this study that peripheral vasopressor use is common and usually short-term, but that's not the full story. So what I didn't show you is that peripheral initiation actually varied widely across our hospitals. So across these 29 hospitals, their overall rate of peripheral initiation was 67%, but you can see along the x-axis we have hospital, and in the green bars we have the percent of peripheral vasopressor initiation. And that's ranging from 27% to 95%, depending on which hospital you're presenting to. So a lot of variation. And you may tell me that makes sense. You just told me they have different policies. So if a hospital has a central-only policy, of course they're gonna be using less peripheral vasopressors. But that's not actually true. So if we take that same graph and we rearrange it by hospital policy type, the central-only and central-preferred policy, peripheral-friendly, there was no correlation between policy and practice. So there's something else that's driving this variation here. So I've shown you that policies vary, practices vary, and then somewhat concerningly or problematically there's no relationship between policy and practice, which is problematic because if we're doing this already in practice and there's important things that we need to be doing to monitor these peripheral IVs and watch them and have management plans, we need to make sure that those two are correlating and that we know how to watch those peripheral IVs closely. So in conclusion, peripheral vasopressors I think can be used safely with the right protocols. It's not just a set it and forget it because extravasation will happen. So long you're monitoring and have a plan, you'll be able to hopefully prevent tissue injury. And while practice is varied, peripheral vasopressor use is common and that's probably because it has these practical advantages. It's easy to start, it's faster, and it may spare a central line. But we really need to make sure we're updating our policies to ensure that when we're using peripheral vasopressors, we're using them safely. With that, I'd like to thank you. Thank you.

peripheral vasopressor

central line administration

safety protocols

extravasation management

clinical practices