Transcript
Speaker: Welcome to Critical Matters, a sound podcast covering a broad range of topics related to the practice of intensive care medicine.
Speaker: Sound provides comprehensive critical care programs to hospitals across the country.
Speaker: To learn more about our programs and career opportunities, visit www.soundphysicians.com.
Speaker: And now your host, Dr. Sergio Zanotti.
Speaker: The administration of vasopressors as part of our hemodynamic support strategy is common in patients with septic shock and other types of shock.
Speaker: Historically, we have required the use of central venous catheters for administration of vasopressors in our ICUs.
Speaker: In today's episode of the podcast, we will discuss administration of vasopressor agents through peripheral intravenous lines, or what we refer to as peripheral vasopressors.
Speaker: Our guest is Dr. Elizabeth Monroe, a practicing pulmonary critical care physician.
Speaker: Dr. Monroe completed her pulmonary and critical care fellowship and a master's in healthcare research at the University of Michigan.
Speaker: Dr. Monroe is currently an assistant professor of pulmonary and critical care at Intermountain Health in Salt Lake City, Utah.
Speaker: Her research interests include evidence-based resuscitation practices in early sepsis and septic shock,
Speaker: vasopressor administration practices, peripheral vasopressor use, and clinical trials, particularly novel pragmatic clinical trial designs.
Speaker: Elizabeth, welcome to Critical Matters.
Speaker: Thank you.
Speaker: Thanks so much for having me.
Speaker: I would like to start with a simple question.
Speaker: Why do you think this topic of peripheral vasopressors should be of interest or important to our listeners?
Speaker: Yeah, this is such a practical topic as we were just talking about before we came on air.
Speaker: I think that this is something that affects us all in our daily practice.
Speaker: We're all using vasopressors.
Speaker: And I came from a residency where they had to be given centrally and didn't even think about giving them peripherally.
Speaker: And then when I got to fellowship, we were allowed to give them peripherally.
Speaker: And it opened up a lot of doors and started to cascade and change some of my other practices in terms of
Speaker: how much fluid I was giving, how quickly I was moving patients to the ICU, and really, I think, draws attention to how this pretty practical choice of what route that you give a vasopressor through actually can cascade and affect other clinical decisions and is something that we may not be thinking about, but that at least affects our practice on a daily basis.
Speaker: Perfect.
Speaker: And I'm a little bit older, so I really come from the era where I remember the first surviving sexist guidelines were almost like mandatory.
Speaker: You have to have a central line, right, to measure this, to do this, to give the vasopressors.
Speaker: And I would like to maybe talk a little bit about the history and the rationale behind all this.
Speaker: Why were vasopressors traditionally restricted to central venous catheters?
Speaker: Yeah, that's a great question.
Speaker: It stems primarily from these case reports of catastrophic events happening when vasopressors were infused peripherally.
Speaker: That was back mainly in the 1950s and 60s.
Speaker: So the actual label itself, for example, norepinephrine, says to give it through a large...
Speaker: vein or like a central vein, but it doesn't say that it has to be given through a central vein.
Speaker: But in the 50s and 60s, they were giving vasopressors peripherally and saw a lot of really severe tissue necrosis and even to amputation.
Speaker: I think a lot of things as we'll kind of talk about have changed since the 50s and 60s in terms of the way that we administer medications.
Speaker: So back then they weren't giving medications on pumps.
Speaker: So they were just kind of freely dripping in the vasopressor.
Speaker: Also, a lot of those cases were in the lower extremity, were in the leg.
Speaker: So I think a lot about how we've administered medications has changed since then.
Speaker: But that's where the practice really stems from.
Speaker: And then as you mentioned, the early goal-directed therapy, the other advantage of a central line is that it allows you to measure hemodynamics.
Speaker: And so that does play a role if you're going to be measuring hemodynamics and putting in a central line, then central access is probably the safest way to give vasopressors.
Speaker: But as we've shifted kind of away from that towards wanting to give earlier vasopressors, maybe not needing invasive hemodynamics in every patient,
Speaker: that's when we're starting to see people kind of circle back to this question that hadn't really been addressed in many years of why did we have to give it centrally and is that still the case today?
Speaker: And it's also interesting that when you look at guidelines like the surviving septic guidelines that we discussed on the podcast and previous episodes, from the first guidelines where central lines were almost mandatory and they were highly encouraged because of early goal-directed therapy and other reasons,
Speaker: the latest guideline in 21 are encouraging people to not delay vasopressors and to initiate through a peripheral line if needed to make sure that people get that therapy in a timely fashion.
Speaker: Today, I presume we're gonna talk a little bit even further about what it really means
Speaker: to give vasopressors through peripheral lines.
Speaker: But as we talk about the shift in the paradigm, can you talk about some of the other issues that might have moved this forward?
Speaker: And what I really wanted to hear about is also there seems to be a growing aversion to central lines because of collapses, right?
Speaker: All hospitals going in
Speaker: crazy with central line utilization.
Speaker: And maybe we even go too far on that pendulum and now are not giving central lines to people who probably would benefit from them, but also would want to hear from your thoughts on, did COVID have any impact on this?
Speaker: Yeah, that's a good question.
Speaker: I think it's kind of multiple factors all at once, because certainly we saw people using peripheral vasopressors even before Clovers.
Speaker: Some of the early studies came out, some of the early case theories, and then Dr. Cardenas-Garcia's study in 2015 was obviously pre-COVID.
Speaker: But I do think that COVID and the need...
Speaker: I don't know.
Speaker: I've seen it go both ways.
Speaker: And I don't I don't think there's I haven't seen good data or study on it.
Speaker: But I, I in my practice personally saw it actually go the opposite way where we were a hospital that was using a lot of peripheral vasopressors.
Speaker: And we kind of shifted towards central because the nurses wanted more secure access.
Speaker: But I also could imagine, depending on your practice setting, that it might be an opportunity to shift more towards peripheral vasopressors to minimize time in the room, placing a central line, especially if you think the patient's going to come off of the vasopressor soon.
Speaker: So I think it was likely, like everything, changed our practice to some degree, which direction, I'm not sure.
Speaker: I think it probably just kind of continued to push forward change that was already happening in terms of the shift towards, like you said,
Speaker: Moving away from needing central invasive hemodynamics, being more cognizant of the bad effects, the side effects of central lines, CLABSIs, and other downsides to central access, and kind of this recognition that peripheral vasopressors may not be this really scary thing that used to be.
Speaker: So it's probably a combination of all those factors that were already pushing us towards peripheral, which may or may not have gotten accelerated through COVID and the different needs in those settings.
Speaker: And there's no question that over the last several years, whether it's, I don't know, it's five, seven, I think 10 is too much, but probably between five and seven years in my estimation, that there's been an increased focus or interest in peripheral vasopressors to the point where this is actively discussed at different ICUs and people have thought about protocols.
Speaker: And really, it's grown.
Speaker: And the goal today is to review this from a more evidence-based perspective, but also to try to give our audience some tips on how to do it the right way and for which patients, which ultimately is the most important aspect of any therapy, right?
Speaker: Making sure that we're doing it for the right patients.
Speaker: Yeah.
Speaker: Elizabeth, could you talk a little bit about the initial studies, safety studies, and how this whole field or the literature on this field has evolved?
Speaker: Yeah.
Speaker: So as I mentioned, it didn't really get much attention besides those original case reports of kind of catastrophic tissue injury back in the day.
Speaker: There was a study by Lubani et al.
Speaker: that was in 2015, I believe, that was kind of a conglomeration of all of these prior case studies of extravasation and tissue injury.
Speaker: But obviously that's biased because you're just collecting studies.
Speaker: negative outcomes that occurred in the literature.
Speaker: It wasn't until about 2015 when we started to see Cardenas Garcia and Dr. Mayo and his group use a protocol for peripheral vasopressors in their ICU and prospectively evaluate it.
Speaker: And that was really one of the earliest safety studies.
Speaker: Since then, we've seen a lot more.
Speaker: There were a couple of meta-analyses and systemic reviews in 2020 and 2021 of several more studies.
Speaker: And even since then, we've seen a lot more studies.
Speaker: They're usually single-centered or just a few centered studies where providers, ICU leadership, will implement a protocol in their ICU to utilize peripheral vasopressors.
Speaker: And either they'll look retrospectively at what happened to the patients who got peripheral vasopressors at their institution, or they'll implement that protocol and evaluate it prospectively or moving forward and look particularly at those adverse events that
Speaker: And then secondarily at how many central lines they saved, getting to your point about the concerns about CLABSI and trying to minimize central lines.
Speaker: So that's really what the field has looked like in terms of many kind of smaller single centered studies focused primarily on that safety component.
Speaker: Are we seeing tissue injury?
Speaker: Are we seeing extravasations?
Speaker: Those kind of things.
Speaker: And as you mentioned, one of the big limitations of a lot of these initial studies is just size, right?
Speaker: You have all these small studies, and it's very hard with small numbers to really make any definitive or any solid conclusions.
Speaker: And to that effect, we were talking before we started recording that the Clover trial, which you were part of,
Speaker: which we discussed earlier with Dr. Shapiro on the podcast in another episode, really, from my perspective, caught my attention because there was, I think, one slide hidden in the supplemental material about the number of peripheral IVs that were utilized during the trial.
Speaker: And that was one of the largest...
Speaker: prospective groups of patients who actually had vasopressors administered through peripheral IVs.
Speaker: So maybe you could tell us about the Clover trial just as a refresher at a high level, the hypothesis, the design, and what were the key findings?
Speaker: Yeah, absolutely.
Speaker: So, um,
Speaker: It was a multi-center trial in the United States, 60 hospitals, over 1,500 patients.
Speaker: And it was looking, those patients were primarily adults with suspected or confirmed sepsis and hypotension.
Speaker: They'd all gotten at least a liter of fluid, but not more than three liters.
Speaker: So it was kind of looking at this very early stage of presentation with sepsis and hypotension.
Speaker: The intervention, well, it was kind of two intervention arms, but the technical intervention arm was restrictive fluid, which was that they took a strategy of after you got that initial fluid, you were enrolled in the trial.
Speaker: and you were still hypotensive, they started early vasopressors.
Speaker: So they kind of favored vasopressors as a means to supporting blood pressure and managing hypotension and really saved fluid for very restrictive reasons, like MAP less than 50.
Speaker: So very much discouraging additional fluid resuscitation in that restrictive arm.
Speaker: The opposite arm was the fluid liberal arm.
Speaker: So in that arm, after the patient was enrolled, if they remained hypotensive, they were given additional fluid up to five liters with vasopressors reserved for very specific, again, very restrictive reasons.
Speaker: So you had this, these kind of management strategies looking at giving very early upfront vasopressors and restricting additional fluid versus this kind of much more liberal fluid approach where you're managing the hypotension with continued fluid boluses.
Speaker: Okay.
Speaker: And they looked at the effect of those kind of two approaches to fluid and vasopressor management on the primary outcome of mortality.
Speaker: Also looked at several secondary outcomes like renal replacement therapy, intubation, adverse events, etc.
Speaker: The main goal was to look at whether these two different strategies or two different approaches to managing hypotension using our tools of fluids and vasopressors led to differences in mortality, which they did not find any difference in mortality with the two different strategies.
Speaker: And can you talk a little bit about the interest in peripheral vasopressors that originated or that the insight that you had, and then we can move to the JAMA paper that you were the lead author.
Speaker: Yeah, so in Clovers, one of the interesting things is as they were designing this, and this was back, the study ran from 2018 to 2022, but as it was being designed, the issue of how you're going to administer early vasopressors became a really important one because you don't want this to be a trial of kind of who's getting, you know, vasopressors preferably.
Speaker: You want to have kind of a uniform approach and...
Speaker: At that time, it wasn't as commonly accepted to use peripheral vasopressors, but they wanted that restrictive fluid early vasopressor arm.
Speaker: They wanted those patients to be getting early vasopressors and not experiencing delays in initiating vasopressors.
Speaker: So,
Speaker: From the beginning and the conception of the trial, which was before my time, but I've had the opportunity to talk to the trial team about how they thought about this.
Speaker: Peripheral vasopressors were really an important component of the protocol.
Speaker: It was actually included in the consent that patients would be consenting to get a peripheral vasopressor.
Speaker: because they didn't want these delays for someone to get randomized to the restricted fluid arm, and then there to be huge delays in actually getting restricted fluids and starting vasopressors because they were sitting around waiting for the team to place a central line.
Speaker: So it's a very pragmatic and practical consideration, even for the trial team.
Speaker: But because of that, they gathered data on peripheral vasopressor use,
Speaker: which is where we were able to do this secondary analysis from is kind of they thought ahead about, hey, this is a novel practice that we're kind of going to be encouraging and promoting.
Speaker: Let's use this trial as an opportunity to understand the safety and the effects of that practice.
Speaker: So peripheral vasopressor use in early steps and induced hypotension was the title of that follow-up or secondary study that you led as lead author.
Speaker: Could you tell us more details about this particular study so we can start with the objective of the study and then go into how it was designed, the setting, and who was part of that study?
Speaker: Yeah, so this was a secondary analysis of the Clovers trial.
Speaker: So we included patients in the Clovers trial.
Speaker: We can talk about the inclusion criteria in a minute, but basically patients who were enrolled in the Clovers trial.
Speaker: And we had two main goals.
Speaker: We wanted to look at which of those patients were getting peripheral vasopressors.
Speaker: We'll talk about, I'm sure as we get into this, that there's a lot of variation in practice.
Speaker: And so kind of understanding using this multicenter group of patients, what were the factors that were predicted that they would get peripheral vasopressors versus central vasopressors.
Speaker: And then the other primary aim was to look at the association of peripheral vasopressors with both adverse events and then mortality.
Speaker: to look at whether that practice of using vasopressors peripherally has any effect on adverse events that we need to pay attention to.
Speaker: And also, is it affecting other elements of our practice that may be through indirect mechanisms, like shortening the duration of shock,
Speaker: or making us pay less attention to patients because we're running them peripherally, which is an argument some people make.
Speaker: But some kind of, is it affecting mortality through these kind of other practices that go along with it?
Speaker: So those were our two primary goals.
Speaker: In terms of main outcomes, what were the main outcomes and measures that you followed?
Speaker: Yeah, so the primary outcome was that mortality.
Speaker: We also looked at a couple of secondary clinical outcomes, different time points of mortality earlier and in hospital, intubation, renal replacement therapy, et cetera.
Speaker: But our primary outcome was mortality, like in the Clovers parent trial.
Speaker: Yeah, absolutely.
Speaker: Let's talk about the results.
Speaker: What were the main findings?
Speaker: And also, what was a finding that surprised you?
Speaker: Oh, that's a good question.
Speaker: So the main findings is kind of thinking about overall peripheral vasopressor use, that peripheral vasopressors were fairly common.
Speaker: 84% of patients were started on vasopressors peripherally in the trial.
Speaker: And this is among patients who received vasopressors in the first 24 hours who we knew their route of access.
Speaker: So that's kind of why the population is a little bit smaller than the main trial is we only took those who were getting vasopressors and where we knew what the access was.
Speaker: And so a majority of those patients getting vasopressors were getting them preferably.
Speaker: There were no patient level factors that actually predicted whether you would get a peripheral vasopressor or not.
Speaker: That surprised me that we've seen this across other studies.
Speaker: I'd say initially I was surprised by that result, but we've seen it kind of again and again that it's less about the patient in front of you, whether you're going to do a peripheral vasopressor and much more about where you're practicing.
Speaker: So the hospital level variation was quite large, even within this trial that said, hey, give vasopressors peripherally.
Speaker: You're allowed to do it.
Speaker: The patient's consented for it.
Speaker: We still saw huge variation in the use.
Speaker: And that was much, that kind of dwarfed any patient level factors that were driving use of peripheral vasopressors.
Speaker: And then there was no association with mortality, which was in line with kind of what I expected.
Speaker: So I think that the thing that surprised me is how important hospital or where you practice is much more than the patients in front of you.
Speaker: And then the other thing that was interesting is just that I really expected, as we kind of talked about, like how long has this been going on?
Speaker: probably the last five to seven years we've started to see more and more peripheral vasopressors at least that's what I've kind of seen in practice and yet from the beginning from 2018 the rate of peripheral vasopressor use both starting and then continuing peripheral vasopressors was very similar across trial years which really surprised me and kind of suggested to me that this is
Speaker: probably been happening in the background more than we think.
Speaker: And we're just now kind of looking at how it's happening and why it's happening.
Speaker: And like you said, the variation among the different hospitals that were participating in this study suggests that really it's more of a style of practice as opposed to something that is, oh, this is an ideal patient for peripheral, for whatever reason, and people would start the peripherals there.
Speaker: And it's true.
Speaker: I've also seen in different ICUs now across time, obviously, but
Speaker: In some ICUs, we had the very dogmatic about central lines, right?
Speaker: And you would put a central line in all these patients.
Speaker: And in other ICUs, you're seeing more and more of the use of these peripheral vasopressor administrations.
Speaker: Could you talk a little bit on the findings related to complications associated with the line specifically?
Speaker: Because as you mentioned earlier in the early years, a lot of these case reports, very dramatic case reports of tissue necrosis and all sorts of bad outcomes associated with
Speaker: peripheral vasopressors really guided our use of central lines.
Speaker: But you actually had a fair amount of patients that you followed.
Speaker: And what I found remarkable was that the safety profile seemed to be quite robust.
Speaker: Yeah, it really was.
Speaker: So in the study, it was 490 patients received peripheral vasopressors and three had an adverse event.
Speaker: So that's a 0.6% event rate.
Speaker: And they were all low grade.
Speaker: So one of the grade one is an asymptomatic extravasation and there were two of those.
Speaker: And then grade two is an extravasation requiring quote, non urgent intervention.
Speaker: That would be something like an ice pack, maybe fentolamine injection.
Speaker: And there was only one of those.
Speaker: So I think this just kind of highlights that with modern administration techniques, peripheral vasopressors are fairly safe.
Speaker: I will note that those rates are a little bit, is much lower than the rates that are in a lot of those other single center studies that I was talking about earlier and those systematic reviews.
Speaker: which seemed to suggest that extravasations, and we'll call it the real world, but kind of across these different single center studies, were on the order of 3% to 5%, but no cases of tissue injury.
Speaker: So I think my takeaway from that is that we may have in Clovers kind of underestimated the rate of complications because this was collected by unblinded study coordinators.
Speaker: So they knew a patient was given a peripheral vasopressor and they were instructed to look back at the
Speaker: day 28 they were instructed look back in the record do you see any documentation of any sort of complication and i think a lot of the other studies are just looking for any extravasation and you know talking to the bedside nurses there's a specific reporting system where they may be catching even small extravasations small leaks things that really didn't affect the patient whereas in this study it was really looking at chart review looking back 28 days so we're probably missing
Speaker: complications, but those are almost certainly very minor complications.
Speaker: So to me, that's extremely reassuring that this peripheral complication rate is low, and that we're not seeing any major complications, because those would have definitely been picked up by this kind of approach to looking at complications.
Speaker: And the other side of that coin regarding complications is the central lines.
Speaker: Could you comment on that?
Speaker: Yeah, so in the study, they also collected central line complications.
Speaker: So in Clovers, for any central line that was placed within the first 72 hours of the study, they, again, they had the study coordinators say at day 28, look back, and is there any documentation of a potential line complication?
Speaker: And so there were, of the 322 patients who had a central line, 12 of them, which was about 3.7%, had a complication.
Speaker: And two of those patients had two complications.
Speaker: And most of those were atrial arrhythmias.
Speaker: There were some ventricular arrhythmias, deep vein thrombosis, hematoma.
Speaker: Yeah.
Speaker: There was no nemothorax and actually no CLABSI, although, again, probably depending on how you're, if you're looking at just documentation, we document CLABSIs in certain ways because of hospital requirements.
Speaker: So we may have underestimated some of those complications, but we're certainly seeing that there were a fair number of central line complications.
Speaker: Yeah.
Speaker: And that's on the order of what prior studies, there's like a systematic review by Perinetti et al.
Speaker: And then a more recent one by Dr. Teja that quote this kind of similar rate around 3% of central lines will have a complication, which really fits with what we were seeing in clovers.
Speaker: So what's the take home message from the JAMA study?
Speaker: Yeah, so I think the take-home message for me is that peripheral vasopressor use is common, is safe.
Speaker: We'll talk about within what context, but is generally safe.
Speaker: And it's faster.
Speaker: It's not associated with increased mortality.
Speaker: So it's a valid approach to take to initiate vasopressors peripherally and perhaps even continue them.
Speaker: Although, as we mentioned in the article, I
Speaker: And I think kind of more broadly, we don't have a good sense of the threshold to kind of go to a central line.
Speaker: But in general, this practice of I need to start a vasopressor to manage shock, I can start it now through a peripheral IV and figure out the central line later seems to be a very valid and safe approach.
Speaker: Any limitations on the study that you want to mention?
Speaker: Yeah, I think the main one is just as a secondary analysis.
Speaker: Obviously, there's risk for residual confounding, meaning that we weren't randomizing patients to get a peripheral versus central line.
Speaker: So we did our best to account for differences in patients who might get peripheral versus central vasopressors, but it's never perfect.
Speaker: So I think kind of interpreting the results with that in mind.
Speaker: And then the fact that we also, with Clovers, they didn't collect, I think the other big one to keep in mind is that they didn't collect details about what each hospital's protocol was.
Speaker: So they said, use peripheral vasopressors, but we don't know how the hospitals were using them.
Speaker: So when I tell you peripheral vasopressors are broadly used and safe, the caveat there is I don't know what each of these hospitals was doing to make sure the administration of peripheral vasopressors was safe.
Speaker: those would be probably the biggest limitations in my mind.
Speaker: And to reemphasize, what I see as a super strength is that you had almost 500 patients, and that is a significantly larger group of patients than any of the previously published studies.
Speaker: Yeah, and definitely the perspective nature of it.
Speaker: There was a study that came out around the same time by Dr. Hsu and Dr. Pendleton at Minnesota looking at 9,000 patients retrospectively at their hospital systems, which is great.
Speaker: It's in ANALS, ATS, if you want to go look at it, which is the biggest one to date and is a fantastic addition to the literature.
Speaker: But I think the advantage here, as you mentioned, is the perspective nature and the fact that it was built into this study design
Speaker: to look at peripheral vasopressors from the beginning.
Speaker: So we have this collection of adverse events.
Speaker: We kind of have this built into the approach to managing septic shock in the trial across 60 hospitals.
Speaker: So a really good opportunity to look at this practice in more detail.
Speaker: Let's talk about
Speaker: Practical considerations.
Speaker: How do we actually do this in a safe way based on what we've learned from this and other studies and based on your own clinical experience?
Speaker: So in terms of peripheral vasopressors, the first question I have is why?
Speaker: Why would you even consider this?
Speaker: Yeah.
Speaker: So I think when I'm thinking about why, how to start a vasopressor, the why to me is the patient doesn't have central access and I want to start vasopressors quickly, which is what we see, you know, in Clovers, it was two hours faster to start peripheral vasopressors than it was to do, to start vasopressors through a central line.
Speaker: So it's that kind of practical.
Speaker: I want, need to start vasopressors now.
Speaker: I don't have central access to,
Speaker: Can I do it peripherally?
Speaker: That's the population who this is really, which is many of our patients, who this is really where I'm considering peripheral vis suppressors.
Speaker: Is there an ideal patient?
Speaker: You did mention that in the study you didn't see any relationship to patients, but in your mind at the bedside, do you have ideal patients?
Speaker: So obviously on one hand, I guess if you wanted to start it in a time-sensitive manner, there is no ideal patient, but there might be patients who you might think that you could avoid a central line perhaps.
Speaker: Yeah, I guess that's the ideal.
Speaker: So kind of, I guess I would split it into initiation and continuation.
Speaker: So initiation, I'm kind of thinking about that.
Speaker: You know, I need a vasopressor and I need it now.
Speaker: And all I have is a peripheral access, great, do it.
Speaker: I think the continuation of like, okay, now that I've started the peripheral vasopressor, I've maybe transferred them to the ICU.
Speaker: They're a little more stable.
Speaker: Am I going to put in a central line or am I going to continue that vasopressor peripherally?
Speaker: I think there's more of an ideal patient there in that I'm more likely to continue it if I think that the patient, and there's not a really good way to tell, but if they're on a low dose of vasopressor, I think they're going to turn around quickly.
Speaker: For example, recently I serviced someone with pyelonephritis who was on the way down to IR to get a pergnephrostomy tube.
Speaker: That's someone who I expect to
Speaker: May get a little bit worse during the procedure, but would hopefully, once I have source control, be turning around and maybe be off of pressers by the next day.
Speaker: So maybe is that patient who can avoid a central line.
Speaker: So I think the ideal patient to start a vasopressor peripherally is probably any patient who needs a vasopressor now and has at least some degree of stable peripheral access, which we can talk about.
Speaker: But the ideal patient to continue is that patient who is probably, in your best guess, going to turn around quickly and may be able to avoid that central line.
Speaker: Let's talk about line selection, size, location, and other aspects of the line that you would consider important for initiation, but also for continuation.
Speaker: Yeah, that's been an interesting thing and something that's been...
Speaker: A challenge in this literature is that each of those safety studies that I mentioned uses different cutoffs for size for how the IV was placed.
Speaker: For example, didn't need to be ultrasound guided placed, ultrasound guided confirmation.
Speaker: So we don't have really great.
Speaker: guidelines or, you know, I can't point to one study or even several studies to say this is the size you should have.
Speaker: This is the location it should be.
Speaker: This is how you should confirm its placement, because I think we've been all over the map with the studies to date.
Speaker: And for example, in Clovers, we don't even know they said a large IV, but we don't even know what they were actually doing.
Speaker: So practically kind of knowing all that literature and talking a lot to people who've developed different protocols, I generally think you need a larger IV.
Speaker: It needs to be in a secure location, so not the hand or the wrist or the foot, ideally on the forearm.
Speaker: Or actually, in the original study by Cardenas Garcia, it was the upper arm.
Speaker: There's debate about the antecubital fossa.
Speaker: And I think to me, that depends on if the patient is moving or not, because there's some concern that if it's in the antecubital fossa, that's a great vein in a lot of patients.
Speaker: But if they're awake and moving around, it may fall out.
Speaker: And so...
Speaker: Dr. DeCardena Garcia's study, they allowed it in the antecubital fossa, but others haven't.
Speaker: So I've seen that debate go both ways.
Speaker: I'm generally avoiding that unless they're like really intubated and sedated.
Speaker: But in general, I'm looking for a good IV that works well, flushes, draws back, is in a forearm or an upper arm, and
Speaker: At our institution, we're required to ultrasound them.
Speaker: That was part of the original protocol with Cardenas-Garcia.
Speaker: So we have to kind of throw a probe on just to make sure that the IV is within the vein and isn't taking up more than half the space.
Speaker: So for me, that's a checkpoint, although I don't know if that's broadly necessary because I know a lot of places that don't have routine access to ultrasound are
Speaker: do just fine with peripheral vasopressors.
Speaker: So my big summary of all of that is I think if you have a large, stable IV that you trust, that you can monitor and you can see, that's an okay IV for a peripheral vasopressor.
Speaker: Do these IVs require dedicated use to vasopressors?
Speaker: Not necessarily.
Speaker: You know, I think that when I've talked to our nursing colleagues who are much more versed in these kind of questions about access and how to use IVs about this question, I think the main thing that they point out is that they want to be able to visually monitor it.
Speaker: So they need to know which line it is going through.
Speaker: Yeah.
Speaker: Different vasopressors are compatible with different other drips and infusions.
Speaker: And so at our institution, and I haven't seen much written about people needing to just have the line for the vasopressor.
Speaker: But I do think that if you start to add other medications, you start to maybe change the rate of flow through the IV, which may increase the risk of extravasation or...
Speaker: or the IV quote unquote blowing.
Speaker: The other consideration that we always keep in mind is that if that IV stops, you need another IV where you can switch to.
Speaker: Otherwise, you're going to lose your vasopressor and your patient's going to go into worsening shock.
Speaker: So it's
Speaker: from what I know, evidence-based, there's not something that says you have to only use that IV dedicated for a vasopressor, but I think there are considerations in terms of what else you're tying with it to make sure you're not increasing the risk of the IV blowing or extravasating.
Speaker: And then also keeping in mind that I think it's a wise practice.
Speaker: While it hasn't been written up explicitly, I think it's a wise practice to always have a second IV ready to go in case something goes wrong with
Speaker: the first IV.
Speaker: What about agents?
Speaker: Are there particular agents that you're more inclined to accept for continuation than not?
Speaker: Obviously, if you're talking initiation, I would imagine that the vast majority is going to be norepinephrine, right?
Speaker: Just by our practice patterns.
Speaker: But in terms of agents, is there like more than one agent is a problem?
Speaker: Are there doses that make you think, okay, I need to move on?
Speaker: How do you handle that aspect?
Speaker: Yeah.
Speaker: Yeah, I think that's a great question because it comes up a lot.
Speaker: And I think that we're finally catching, people are finally catching up to the field.
Speaker: But some of the initial studies of peripheral vasopressors before Cardenas-Gracias, some of the other smaller studies were phenylephrine and dopamine.
Speaker: So I've had many people come up to me and tell me, but you shouldn't use norepinephrine.
Speaker: You should only use phenylephrine or only use dopamine peripherally.
Speaker: But actually, in the more recent years, especially with Clovers, a majority of these patients were getting norepinephrine.
Speaker: There's been other studies of just specifically peripheral norepinephrine.
Speaker: For example, in chest by Yerke and colleagues last year, we now have much more data on norepinephrine than any other vasopressor.
Speaker: So I think that in general, any sort of vasopressor is probably equal risk of causing damage.
Speaker: If it were to extravasate
Speaker: I think the distinction that's more important to make is catecholamine versus not, because the major way we have to address or manage extravasation is to inject an antidote, most commonly fentolamine, sometimes topical nitroglycerin.
Speaker: but fentolamine is only going to counteract the effects of a catecholamine.
Speaker: So I think vasopressin, there's an ongoing trial, the VASPR trial that will allow peripheral vasopressin.
Speaker: So that will be very interesting to see because to date, there's not much, most people seem afraid to use peripheral vasopressin.
Speaker: So for me, I'd say any catecholamine is probably equal to
Speaker: If it were to extravasate, it would probably cause equal risk of tissue damage, but you can counteract it with fentolamine.
Speaker: Norepinephrine is our first line.
Speaker: It's also, by now, the best studied peripheral.
Speaker: So that's definitely my code to where I'm most comfortable running peripherally.
Speaker: I do get uncomfortable running more than one vasopressor peripherally, although I know, like I said, this trial is coming out where they're doing vasopressin on top of norepinephrine, and they're running the vasopressin peripherally.
Speaker: But in my kind of practice, that's where I kind of start to get worried because for me, it's mainly not necessarily that there's two agents, but more this patient is in severe enough shock that if I, what will happen if I lost that IV, it's going to be beginning to get kind of more catastrophic if that IV blows.
Speaker: And I'm probably not turning this around quickly.
Speaker: I'm probably going to need central access to kind of maintain this level of support.
Speaker: So that's my kind of,
Speaker: very pragmatic approach that's somewhat evidence-based, but you'll see in all the different safety studies, different cutoffs of norepinephrine dosing, different other limitations.
Speaker: But I think practically it's that, for me, it's that trigger of, okay, I'm adding a second phasopressor, the patient's getting worse, we need to get secure, get control of the situation, get secure access.
Speaker: An important aspect, as you mentioned, is not only the amount that's going in, but what would be the consequence if I lose that IV, right?
Speaker: Yes.
Speaker: And I agree.
Speaker: I'm not sure that a lot of clinicians think about that frequently.
Speaker: Now, do you have a dose by which you say, you know what, we just need a central line?
Speaker: Yeah, that's my, again, my pragmatic dose is 0.2 of micrograms per kilogram per minute of norepinephrine, because that's when I typically add basopressin.
Speaker: And that's when I typically add stress dose steroids based on kind of interpretation from the approaches trial and the VAS trial.
Speaker: So for me, it's kind of when we're getting to 0.2 of norepinephrine and we're not turning around, like it's not like, oh,
Speaker: They just need a little more fluid or, you know, they just came back from the OR, they're settling out.
Speaker: It's, hey, they're really on point two.
Speaker: That's when I say, all right, let's add the vasopressin.
Speaker: We don't already have a central line.
Speaker: Let's go get that in.
Speaker: We're reaching a point where we're just going to need more support and we just need a more secure way to give that.
Speaker: But I'd say that's mainly a practical approach.
Speaker: I think you'll see people have lower, usually not a higher threshold, although in the literature, we've seen up to like 0.7 micrograms per kilogram per minute peak doses of norepinephrine given peripherally.
Speaker: I think you'll see most people and most protocols kind of are more around that 0.15 to 0.3 micrograms per kilogram per minute of norepinephrine is kind of where you start to see the line get drawn.
Speaker: So you mentioned that adding a second vasopressor, you mentioned obviously increasing doses, which usually leads to a second vasopressor.
Speaker: You mentioned if you have a need to measure other things like hemodynamics, those will all be indications for central venous access.
Speaker: Is there a timeframe by what you say, you know what, we're just going to have to move to a central line?
Speaker: Yeah, I think that's the timeframe aspect was so, when you look at the literature, it's so important early on, and I think it's really kind of changed.
Speaker: So, for example, the study I mentioned by Yerke and colleagues last year in CHEST, they did a protocol where they initially said, we're only going to allow this to run for 48 hours, preferably.
Speaker: And then they saw so few adverse events and people liked it so much that they ended up in the middle expanding it and saying there's no duration limit.
Speaker: Um, and most of their extravasations happen in the first 24 hours.
Speaker: It's kind of like, if you have a bad IV, it's going to go bad early.
Speaker: Um, so as long as you're kind of, and we should talk about this, but as long as you're monitoring that IV and it's a good IV and it's reliable and it's staying reliable, I think duration is probably less important.
Speaker: Although certainly, and this may be a fact of the fact that our hospital has, you have to reevaluate every 24 hours, but I definitely, if we're continuing to need it after 2448, I'm typically kind of like, why are we needing this?
Speaker: Should we put in a central line, secure central access, you know, to is how long term is this going to be?
Speaker: So I think the duration piece has been all over the map in different studies and is probably less important than having a secure IV that you're able to monitor that, you know, works.
Speaker: I think we get.
Speaker: duration was originally a point of concern because as IVs get older, they work less well, et cetera.
Speaker: So I think if you're going to do longer durations, just really paying attention to, is that IV still a good IV?
Speaker: Does the nurse, bedside nurse still trust that IV?
Speaker: Do I still trust that IV?
Speaker: Is probably the more important question to ask than how long.
Speaker: Excellent.
Speaker: And in terms of complications, I would like to talk about monitoring for complications and treatment.
Speaker: And one of the complications that I wasn't really thinking of till talking with you, but now would be first and foremost in my mind, would be losing the IV.
Speaker: Yeah.
Speaker: I never thought about that that way, but I think that would be complication number one.
Speaker: And the way you monitor that is to make sure the IV works, and the way you mitigate that is by making sure you have IV access, right?
Speaker: Yes.
Speaker: So that's complication number one.
Speaker: Now, the complication that everybody talks about is extravasation.
Speaker: Could you talk more about how you monitor and how you treat that when it happens?
Speaker: Yeah, so extravasation is the big, you know,
Speaker: point or complication of concern, meaning that if the medication leaks out, it leaking out itself is not a problem, but because vasopressors cause vasoconstriction, it can cause tissue damage.
Speaker: So in my mind, it's kind of tissue necrosis and tissue ischemia are kind of the complications that we're worried about.
Speaker: Extravations are
Speaker: opportunities to intervene to prevent those more serious complications because we know that all peripheral IVs are going to extravasate at some point.
Speaker: I think we can pretty much tell from this literature as well as other nursing literature about extravasations that it's kind of about 3% to 5%.
Speaker: So I always tell my teams, I'm like, you're running a peripheral vasopressor.
Speaker: There is a 3% to 5% chance that that IV is going to leak or extravasate, go bad, whatever it is.
Speaker: So we need to be prepared in the case that that happens.
Speaker: We need to be prepared to run the vasopressor somewhere else, like you said.
Speaker: And we need to be prepared to address that leakage to get that vasopressor out of the system so that, like I mentioned, our hospital has, and it's pretty typical, we inject fentolamine and we use nitroglycerin topical if it's severe.
Speaker: And we want to be able to catch when that happens.
Speaker: So I think one of the dangerous things and places people can get into with peripheral vasopressors is a set it and forget it.
Speaker: Oh, you can just start a peripheral vasopressor and put them in the corner room and not come back.
Speaker: And I think that's actually probably the least safe thing to do.
Speaker: If you're going to be putting a patient in a corner room, you might want a central line because you don't have to monitor that as closely.
Speaker: Versus peripheral vasopressors, our teams, and this comes out of a lot of these studies, are monitoring every two hours of
Speaker: Um, just like they do any other IV, but they're paying close attention and you can monitor in two ways, visually just inspecting the IV to make sure it's not, um, you know, leaking.
Speaker: There's no, uh, puffiness around it.
Speaker: It's not showing signs of extravasation and, or aspirating blood back.
Speaker: Um, which means you have to pause the vasopressor briefly, um,
Speaker: Different hospitals require different things.
Speaker: I think in general, in my mind, it's as long as you have some protocol for the bedside nursing team to be looking at that IV carefully.
Speaker: And they may be already doing that because they may have that similar protocols for all IVs.
Speaker: But that's how you catch that extravasation that we know is going to happen in three to 5% of patients.
Speaker: And that's how you address it and stop it from becoming that terrible tissue injury.
Speaker: And I think the evolution of this increased attention to monitoring and training and extravasation management protocols, access to fentolamine, nurses ready to act and respond to an extravasation, is what has taken us from these terrible tissue injuries to the point of we have extravasations, but it's exceedingly rare to have tissue injury problems.
Speaker: to that degree anymore.
Speaker: And I think that's somewhat attributable to improvements in how we're being more cognizant of which IVs we're using, which medications, what doses, et cetera.
Speaker: But I think more importantly is attributable to improved monitoring and training in the management of extravasation kind of more broadly, but specifically for vasopressors.
Speaker: Before we summarize, I just wonder, what is your use of IOs, intraosseous lines?
Speaker: The first time I put an intraosseous line in a cardiac arrest that had no IV access, I thought, oh my God, this is so cool.
Speaker: I'm going to be using this all the time.
Speaker: And I use it here and there, but I don't think that it picked up as I expected it to.
Speaker: Yes.
Speaker: I mean, I've used IOs here and there.
Speaker: I think they're great in a code situation, but they are not great in any patient with any sort of feeling because they're extremely painful.
Speaker: So, yes, if I were to lose a peripheral IV running a lot of vasopressors, IO would be something I would think about.
Speaker: But I probably most of the patients are at least somewhat awake.
Speaker: So that limits that as an option.
Speaker: So.
Speaker: Yeah, I think that certainly a crash line has its role still, as does an IO, but those come with complications.
Speaker: IOs come with pain, crash lines come with possible breaches of sterility and other issues.
Speaker: So as long as the patient has a peripheral IV, and certainly I've done that if they have a terrible peripheral IV, but as long as they have a peripheral IV that somewhat works,
Speaker: We start the vasopressor there, stabilize them, and then get a sanitary, sterile environment, get the line in, get them settled, and don't have to have this kind of rush to get access.
Speaker: Like, I feel like I had to before when I didn't use peripheral vasopressors.
Speaker: Perfect.
Speaker: So in summary, could you give us, Elizabeth, some common pitfalls to avoid and then some pearls for success as we use peripheral IVs for our vasopressors in our ICUs?
Speaker: Yeah, I think common pitfalls are, well, hopefully they're not too common, but is not monitoring the IV, like we mentioned, not knowing what to do if it extravasates, really just kind of setting it and forgetting it, not thinking, like we talked about, not thinking about needing that second IV available in case the first one goes bad.
Speaker: So I think that the biggest pitfall is not recognizing that an extravasation –
Speaker: will happen to you if you do peripheral visor presses regularly you will have an extravasation again three to five percent of the time definitely had my my share of them um so i think a pitfall is thinking oh i'm going to do this it's safe nothing happens it's it's it's safe extravasation happens but i have to know what to do when that happens and that probably leads into the pearls for success is is just making this a practice that's not just kind of done randomly in the background and
Speaker: that we're not acknowledging and that we're doing against protocol, but is something that we are talking about that we're doing thoughtfully as the team, getting input from our nursing colleagues about what, with their expertise for IV management, getting input from the rest of the team, leadership, that this is something that we know is practical,
Speaker: It's fast.
Speaker: We're all going to do it.
Speaker: Our research has shown we're all doing it.
Speaker: So how do we kind of do it safely and do it together in a way that makes sense for our patients and our unit, I think, is the key to doing this successfully.
Speaker: Perfect.
Speaker: Elizabeth, we'd like to close the podcast with a couple of questions that are unrelated to the clinical topic.
Speaker: Would that be okay?
Speaker: Okay.
Speaker: The first question relates to books.
Speaker: Is there a book or books that have influenced you significantly or a book that you have often gifted to other people?
Speaker: Yeah, it's funny that you asked this question because I just moved, as you mentioned, from Michigan to Utah.
Speaker: And as I was unpacking, I came across this book that I had totally forgotten about, but I've just started rereading again.
Speaker: And I'm totally, it's going to turn into a book that I gift, Ending Medical Reversal, which is by Dr. Prasad and Dr. Sifu, who is one of my professors in medical school, that talks about how practices that were convinced work in medicine.
Speaker: can be and are often later shown to be ineffective or potentially even harmful and kind of what is the thinking and uh way we kind of get in how does that happen to us um and it's a it's a great book and like i said i just pulled it out and i was like oh man uh this is something that um i need to revisit and and is probably going to be a book that i'm giving away frequently after this so um that's that's the one that comes to mind
Speaker: We'll definitely link it in the show notes.
Speaker: The second question is related to changing your mind.
Speaker: Could you share something you changed your mind about over the last few years?
Speaker: Yeah, actually, peripheral vasopressors.
Speaker: Of course.
Speaker: It's funny that you ask, because like I said, I came from a residency.
Speaker: I think it was both time and also the place I practiced where we weren't not allowed to use them.
Speaker: And then I landed at a fellowship where it was common practice.
Speaker: And I was really hesitant at first.
Speaker: And I think kind of as I got used to
Speaker: I wish I had had someone tell me kind of like, we've talked about today, how do you approach this?
Speaker: Because I just kind of dove into it and I was like, this seems unsafe, guys.
Speaker: Are we sure we should be doing this?
Speaker: And really ended up changing my mind and becoming an area of interest in research for me.
Speaker: So that is something medically that I've changed my mind on recently.
Speaker: And it's an important aspect of practice that we don't pay enough attention to is what do I need to change the way I think about a clinical issue?
Speaker: Yes, exactly.
Speaker: you start seeing, okay, maybe there's a different side to this that I had not seen.
Speaker: So that's, I think it's almost touche, right?
Speaker: But perfect for this conversation.
Speaker: Yes, exactly.
Speaker: Perfect.
Speaker: And to close, what would you want every listener to know?
Speaker: It could be a thought or a quote.
Speaker: Yeah, I think it kind of ties into exactly what you just said is that, um,
Speaker: is to really have humility, be rigorous in your approach to data, but have humility and open-mindedness.
Speaker: I mean, I've been surprised by how many of the things that I thought we had to do in practice or in life, but what we think we have to do actually turns out to be the wrong answer or to maybe not be what you have to do.
Speaker: And so I've learned the most from being open-minded to new practices, new studies, learning from my colleagues, learning from
Speaker: trainees, people around me.
Speaker: So that would be what I would, what I would close with.
Speaker: Perfect place to close.
Speaker: Be curious.
Speaker: Ask questions.
Speaker: Right.
Speaker: So Elizabeth, thank you for the wonderful work that you've done on this topic and for sharing your expertise with us today.
Speaker: I definitely look forward to having you back on the podcast soon.
Speaker: Thank you so much.
Speaker: This is great.
Speaker: Thank you for listening to Critical Matters, a sound podcast.
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Speaker: Sound's transforming the way critical care is provided in hospitals across the country.
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