December 2023 Literature Review Series

Speaker 30s - 186.8s

This episode of Pharmacy to Dose, the Critical Care ORG podcast, is proudly sponsored by Ki-A-Z. KIAZ ORG is a family-owned, researched-focused, sustainable pharmaceutical company accredited with both B-Corp ORG and a benefit corporation status. Kiezi ORG is making global changes that benefits patients, providers, and health care organizations with forward-looking and impactful initiatives. Kiyazi ORG appreciates the integral role that clinical pharmacists play inpatient care and are proudto support this community. To learn more, visit KIAZ.farmacetyidose.com. Again, that's C-H-I-E-S-I-Farmacetytose.com. The critical care PRN ORG is dedicated to fostering the role of critical care pharmacists as essential members of the multidisciplinary patient care team. The critical care PRN ORG's goal is to optimize drug therapy outcomes by promoting excellenceand innovation in clinical pharmacy practice, research, and education. For more information, including how to become a member, go to critprn.acCP.com. Again, that website is critprn. dot acCP.com Welcome to Pharmacy to dose the Critical Care podcast, a partner of the ACC Critical Care PRN ORG. And I'm your host, Nick Peters PERSON. And wherever you are and whoever you are listening, thank you. And this is the December 2020 literature review series. And two special guests helping highlightthe best articles published in December are Hannah Millard and Jenna Self PERSON. So the Literature Review series episode starts off with our featured studies where today we highlight six of the most noteworthy and potentially practice-changing publications. Then the discussion shifts to articles in cardiology, heem ID, a little popery section, and sepsis. Followed by the category featuring articles voted on by you, Friends of the Pod,in the pharmacist featured section, aka the front of the fridge. So if you want to vote in future episodes, be sure to follow on Twitter or Instagram at Pharmacy 2 dose ORG. Then the episode closes, of course, with our non-clinical section, Sweet Emotion ORG. There's a really great one highlighting some effortsof clinical pharmacists in Tokyo GPE. Now, let's not wait anymore so excited because the December 2023 Literature Review ORG series starts right now. Very lucky to be joined by Hannah Millard and Jenna Self PERSON.Now, Hannah is the PGI2 Critical Care Pharmacy resident at Trinity Health in Ann Arbor, Michigan GPE. And Jenna is the PGY2 Critical Care Pharmacy resident at the University of Kansas Health System ORG. Jenna, Hannah PERSON, welcome. How are you both doing today? Doing great, Nick PERSON.

Speaker 1186.86s - 192.1s

Thank you. Yeah, doing well. Thanks. All right.

Speaker 3192.18s - 211.54s

Let's check in. We're recording this mid-April. So we are in peak, peak senioritis season. It is spreading like wildfire. So on a scale from zero to 10, Hannah PERSON will start with you.What would you rate your senioritis as right now? I'm going to have to go at 12 out of 10.

Speaker 0211.58s - 222.8s

Yeah. Yep. This Michigan GPE weather, it's warming up a little bit too. I need out of the basement of the pharmacy. Yeah. Jenna PERSON, what about you?

Speaker 3223.94s - 225.14s

Yeah, I would have to agree.

Speaker 1225.26s - 229.8s

I'm a good 10 out of 10. Still having fun, but very ready to be done.

Speaker 3230.44s - 232.24s

79 days, if that told you anything.

Speaker 1234.62s - 236.04s

79, but who's counting?

Speaker 3236.16s - 281.36s

That's such a specific number. I love it. Yeah, this is, I remember feeling like mid to late April is like you're so close, but it also feels still fairly far away. You're so close, though. You're so close.Now, let's get into it our literature review series. And December was filled with some great articles to help end 2023 on a high note. And let's talk through them, starting, of course, with our featured articles. And today we have a six pack of studies. So Jenna PERSON's going to lead off our discussion looking at the ability to deprescribe a commonly used medication in our LVAD patients.

Speaker 1284.02s - 605.24s

Some of the best medicine is no medicine at all. So very excited to share the aspirin and hemocompatibility events with a left ventricular assist device in advanced heart failure which was published in jama two of the major complications from left ventricular assist devices or elvads are pump thrombosis and bleeding the most widely available elvad is the fully magnetically levitated Heartmate 3 PRODUCT, which has demonstrated improved long-term survival by decreasing pump thrombosis and disabling strokes, but only modestly influence bleeding complications. A common LVAD antithromotic regimen includes an aspirin at a dose of 325 milligrams in combination with the vitamin K antagonist due to the risk of device-related thrombolic complications. However, studies have shown the type and generation of LVAD PRODUCT can influence the thrombotic risk. Previous devices, such as the heartwear LVAD,has been removed from distribution due to its high stroke and pump malfunction risk. When studied in the heartware al-Bads, the use of lower dose aspirin at 81 milligrams daily was associated with increased pump thrombosis and stroke. An analysis from the Momentum 3 study in HeartMate 3 LVAD patients suggested that suggested that low dose 81 milligram aspirin is associated with similar hemocompatibility-related outcomes as compared to the higher 325 milligram doses. An observational research suggests that aspirin withdrawal after bleeding events with the Heartmate 3-LVAD PRODUCT reducessubsequent bleeds without an increase in thrombosis-related outcomes. So the question for this study is, can aspirin be safely avoided as part of an antithrombotic regimen, including a vitamin K antagonist with the fully magnetically levitated LVAD? And does this approach reduce residual risk of non-surgical bleeding complications? This was a multi-center placebo-controlled double-blind study at 51 sites in North America LOC, Europe, Kazakhstan, and Australia from July 2020 through September 2022. Patients were randomized one-to-one to placebo or aspirin in combination with a vitamin K antagonist, targeting an INR of 2 to 3 in patients with advanced heart failure withthe Heartmate 3 LVAD PRODUCT. The primary endpoint was a composite of survival-free of non-surgical major hemocompatibility-related adverse events at 12 months, specifically stroke, pump thrombosis, major non-surgical bleeding, and arterial thromboembolism. Patients with events occurring within 14 days after LVAT implantation were excluded to avoid counting surgical complications not attributed to the antithrombotic treatment. Secondary endpoint looked at first in recurrent events of non-surgical bleeding rates in theprimary population described as events per 100 patient years. To assess the safety of withholding aspirin therapy, they analyzed thrombotic events and survival. The final sample size was 589 in the primary analysis population, which met power for their primary endpoint. In the primary analysis population, 296 patients were assigned to placebo and 293 were assigned to the aspirin group. Baseline characteristics were similar. Majority of patients were white males in their late 50s receiving Elvad PRODUCT support as destination therapy. For the primary endpoint, more patients reached12 months alive and free of non-surgical major hemocompatibility-related adverse events in the placebo group than in the aspirin group, 74.1% versus 68.1, meeting that non-inferiority criteria, with the difference in the composite outcome driven by reduced bleeding events in the placebo group being 22.5 versus 28.2. When analyzed as a time-to-first event, fewer patients died or experienced a non-surgical major hemocompatibility-related adverse event in the placebo group than aspirin. It was estimated that for every hundred patients implanted with the study al-Vad PRODUCT,aspirin avoidance prevented 14.5 major bleeding events in the first year. Aspirin avoidance resulted in a reduction in major bleeding events without an increased risk for major thrombotic events, and there was no difference in thrombotic events component event components of the primary endpoint between the study groups. Both groups had zero-pon-thrombosis events, which provides further evidence of the safety of the Heartmate 3 LVADs PRODUCT overall. A couple considerations from the study. One is that patients deemed to need aspirin for other indications were excludedfrom the trial. However, some patients were included that had traditional indications for aspirin, such as prior PCI or cabbage, if the investigators felt comfortable with aspirin cessation. In the trial, a subgroup analysis of these patients demonstrated no increased risk of vascular complications with aspirin removal. However, given that this was a subgroup analysis and most patients deemed to need aspirin were excluded from the trial, there's still not enough evidence to support aspirin removal for patients with heartmate 3 el-badids PRODUCT and other indications for aspirin. Another consideration is aspirin avoidance was only studied after the LVat PRODUCT implementation,and so the effect of withdrawing aspirin in patients with the heartmate 3 PRODUCT elvads, who were initially started on it remains unclear. As well as these findings are specific to the heartmate 3 PRODUCT elvads and cannot be applied to others such as the heartwear or the heartmate 2 PRODUCT. So in conclusion, this study found that excluding aspirin from an antithrombotic regimen that includes a vitamin K antagonist and patients with advanced heart failure who received a fully magnetically levitated elvad is not inferior to an aspirin-containing regimenand is associated with a decrease of bleeding events while not increasing the risk of thromboembolic events. A really cool fun fact, KU ORG was a study site for this trial, and we have since implemented this study into our practice at KU ORG, and then we actually also allow further removal of aspirin from patient regimens who were initially started on it that do not have other indications for aspirin, so this has been a very relevant study to our practice. for aspirin. So this has been a very relevant study to our practice.

Speaker 3612.3s - 736.66s

Well, not only, what a great overview on the history of aspirin use in LVADs, but love that you got to highlight a study that you've gotten to see incorporated into your clinical practice firsthand. Wow, how cool is that? You know, you mentioned that your center has kind of maybe started peeling back a little bit or discontinuing aspirin in some of those patients. And that's where I'm curious where this is going to go and see if there's going to be a study looking at those who have already been on it for a certain period of time and looking what happens when that gets deprescribed. And I think even more, you know, they mentioned the whole theory behind it was because of the issues with bleeding and things.So I think that's, again, even going to be more of a consideration when you're combating those issues. Now, I try to use the dosing that our RCTs use. It's one of like my sticking points. Like if we're going to follow a study,we should use what they did. So a part of me hates the 100 milligram aspirin dose because I know that I'm not going to be able to use that. I think that's probably just me being a little type A, but that's always something that stands out when it's an international kind of study and you're using the different the 100 milligrams.This isn't even international. So what are we doing? But fun fact from the supplementary appendix, the different 100 milligrams. This isn't even international. So what are we doing? But fun fact from the supplementary appendix, the trial was designed with feedback from the US FDA ORG. I don't think you see that too often, but it makes sense that they would do that in tandemwith an FDA ORG approved device. Another note from the supplementary material for the listeners' cure is E-figure 15, but the time and therapeutic range from an I&R perspective, but Jenna highlighted their goal was two to three. And the groups were therapeutic between 55 to 60% of the time. Both groups were the same, similar for those experimental and control arms.Always something we think about, right, when we have the rare vitamin K antagonist indication. Now let's stay in the anti-platelet realm with Hannah PERSON reviewing a study looking at dual anti-platelet initiation in a specific neurocritical care population.

Speaker 0738.32s - 1046.56s

Yes, so this is the inspires trial and you may possibly be inspired about the initiation of DAPT after this. So a little bit of background. In acute mild ischemic strokes or TIAs, there's a 5 to 10 percent risk of recurrent stroke within 90 days. Guidelines recommend initiating DAPT with aspirin and clopidigril within 24 hours to reduce risk of recurrence. And then post hoc analyses of large randomized controlled trials like the Point and Thales trial suggest a benefit of adapt over aspirin when it started within 24 hours. But this time frame may have limitations for patients who present later than this.The author set out to determine if patients would have a similar benefit of reduced stroke recurrence if this time was extended up to 72 hours. Of note, the results presented in this study focus on the anti-platelet results of the Inspires trial, which was a two-by-two factorial trial, which also investigated statin therapy initiation timing. For their methods, this was a Chinese multi-center double-blind randomized placebo-controlled two-by-two factorial trial. They're at 2222 sites in China from September 2018 to October 22.Patients aged 35 to 80 years old, presenting within 72 hours of ischemic stroke symptom onset, were included. These patients had a mild ischemic stroke with an NIHSS score of 5 or less, or a high-risk TIA with a score of five or higher on the ABCD scale, a stroke risk calculator. Patients were excluded if they received thrombolysis endovascular therapy or had an NIHSS of less than or equal to three after the 2019 HAA ORG guideline update. Participants were randomly assigned one-to-one to receive clopidigrille plus aspirin or placebo plus aspirin for 90 days. So getting into dosing again, like we mentioned the previous trial, patients in this treatmentarm received a 300 milligram clopidigral loading dose, which was given on day one, then followed by 75 milligrams. And then a 100 to 300 milligram aspirin loading dose on day one, followed by, again, that 100 milligram daily dose for 21 days. And then the patients in the monotherapy aspirin group had the same loading dose of aspirin on day one, followed by that 100 milligram dose for days 2 through 90. Aspirin dosing in both groups was made by the treating physician. The primary efficacy outcome was any new stroke, eschemic, or hemorrhagic within 90 days. The primary safety outcome being moderate tosevere bleeding, according to the gusto criteria. So 6,100 patients underwent randomization with 3,050 assigned to the DAPT group and 3,050 to the aspirin group. 6 to 8% of patients in each group were excluded in the per protocol analysis. Baseline characteristics were similar between groups. Of note, a majority of patients were Han Chinese NORP, which makes sense since this took place in 200 Chinese NORP hospitals.The median age was 65 years old, about 36% of patients were women, 87% of patients were randomized between that 24 to 72-hour after symptom onset time, and about 76% of patients in each group had an NIHSS score of three or less and enrolled prior to the changing guidelines in the inclusion criteria. They found that DAPT treatment significantly reduced the primary outcome of any new stroke within 90 days, 7.3% of patients compared to 9.2% in the aspirin monotherapy group with a hazardratio of 0.79. The primary safety outcome was moderate to severe bleeding, which was significantly higher in the DAPT group, 0.9% compared to 0.4%, with a hazard ratio just above two. While the study wasn't power to allow for definitive conclusions from their subgroups, figure three is a forest plot that it would direct you to. It shows the hazard ratios for stroke and their pre-specified subgroups. So this shows potential hypothesis driving benefit for DAPT for patients less than 65 years of age, male sex, SBP, greater than are equal to140, and possibly acute multiple in VARCs, to name a few. As far as their conclusions, the authors concluded that in patients with acute mild stroke or high-risk TIA with a presumed atherosclerotic origin, DAPT with the culprit of growth in aspirin reduces the risk of stroke recurrence when initiated within 72 hours of symptom onset. The study expands upon the results of the trans in point trials, which found recurrent stroke risk reduction with DAPT initiated within 24 hours. The risk of moderate to sphero bleeding was alone in each group, but higher in the DAPT group. It would still be interesting to see this trial repeated in the U.S. patient population to ensure generalizability of these results is 98.5% of the patients were Han Chinese NORP. This population doeshave a higher risk of incidence of intracranial artery stenosis and likely would benefit from DAPT. And then just to conclude more, but it's still important to initiate DAPT as soon as feasible within 24 hours of symptom onset, but the findings in this trial may provide additional benefit for patients who may present later than this by extending that window up to 72 hours.

Speaker 31048.72s - 1376.86s

That's a really good point about the Chinese versus U.S. GPE population consideration. Definitely something we need to keep in mind. And the protocol, as part of the supplementary materials, it does an awesome job. I think when you have a topic like dual anti-platelet therapy and stroke, trying to feel like you understand the literature can be probably overwhelming at times. And the supplementary materials do a great job of giving you background.So you can go more in depth into the chance to point the Socrates, those kind of trials. You also mentioned it, rinse and repeat with my aspirin dosing grievance. Same problem in inspires as what we just talked about. You know, this study kind of highlights the question we're constantly balancing, right? Especially in the neuro world, right?Completed roll in aspirin reduced the primary outcome of a new stroke, but it also doubled the incidence of major bleeding. So stay tuned. I'm certain there's more to come in this arena. Now let's shift gears. We're going to stay in our neurocritical care world.And as Beyonce says, this ain't Texas GPE. It's Tex AIS ORG. That's exactly right. Treatment with exenotide in acute ischemic stroke. So as we get into this new article, the authors highlight three studies in the introduction that you describe as probably negative studies with regard to hyperglycemia treatment in neurocritical care.So just briefly, just UK 2007 underpowered study, but found that patients presenting within 24 hours of symptoms, they were randomized to a glucose potassium insulin infusion. You heard that correctly. Targeting a blood glucose between 72 and 126, no difference in outcomes. The 2012 French NORP single center insulin-farked study researched if IV insulinwith intensive control compared to that usual care with sub-Q insulin, improved your infarct volume at three-month MRI. And what they found was the exact opposite, that those in the intensive arm, they had reduced blood glucose, of course, but they actually had an increase in their infarct size on MRI. And then most recently, the 2019 JAMA Shine trial, a US GPE RCT in patients with acuteischemic stroke presenting within 12 hours of that symptom onset. In over 1,100 patients, IV insulin with the computerized decision support tool, targeting lower blood glucose 80 to 130, did not improve functional outcomes at 90 days. So this arm, of course, had improved blood glucose values, but had an increased risk of severe hypoglycemia. So one thing, all these studies, and most of our inpatient hyperglycemia management studies, share the focus is all on insulin. And one of the biggest risks with insulin, of course, is hypoglycemia.Let's talk about exenotide, right? GLP1, receptor agonist. It was doing this long before it was cool. Like everyone's kind of doing it now. Exenotide's been on it for a minute, but it stimulates the release of insulin, suppresses the release of glucagon.And that's how we arrived here to the management of post-stroke hyperglycemia, the results of the Tex AISRCT published in stroke. So phase two international prospective randomized, open label, blinded endpoint trial took place in 12 hospitals in Australia, New Zealand, and Finland GPE. So adult patients with acute ischemic stroke, presenting within nine hours of symptom onset, they had a pre-stroke MRS score of less than or equal to two and a presentation bloodglucose greater than 72. Those were the enrolled key exclusion criteria at Craddening Clearance less than 30. And they were randomized to exenotide five mic subcute twice daily or matching placebo treatment for five days or until hospital discharge. The primary outcome was the proportion of patients with major neurologic improvement at seven days. What does that mean? Mensure NIH SS was either zero or one or you you had a greater than you're equal to eight point improvement.So they defined hyperglycemia as greater than 126, hypoglycemia is less than 72, severe hypoglycemia at less than 54. The weird numbers are because it's technically in millimoles. We did the weird conversion. So whenever possible continuous glucose monitoring was used. Now, of course, COVID interfered with enrollment and the trial was stopped early, but theydid enroll 350 patients between April 2016 and June 2021, but of course missing their pre-planned sample size estimation. It's around 55% of these patients got reperfusion therapy and the median baseline NIHSS was about four median blood glucose of 120. And there was no difference in that primary outcome of major neurologic improvement at seven days between either arms. But also no difference in the rate of severe hypoglycemia.Now exenitide treatment was associated with nausea and vomiting despite scheduled anti-medic medications. But there was five patients in the group. So kind of keep that in mind. And with the boom of the GLP1 agonists, I definitely don't think this is going to be the last study we see looking at this drug class and using them in specific in patients.And if you're a Texas GPE longhorn listening, pull the supplementary appendix to see the logo for the Tex AIS ORG study. I think you'll love it. We're going to leave it at that, hook them horns, right? All right. So from neurocritical care to pulmonary critical care, let's highlight a study researchingif patient positioning can actually improve outcomes in ECMO. So Jenna PERSON, take it away.

Speaker 11378.12s - 1686.96s

So in ARDS, we're prone to think of proning, but now we'll look at early proning and severe ARDS for patients on ECMO in this prone-ecmo trial. So this is prone positioning during extracorporeal membrane oxygenation and patients with severe ARDS that was published in JAMA ORG. Among patients with acute respiratory distress syndrome or ARDS, ARDS, prone ventilation provided for at least 16 hours per day, significantly reduced 90-day mortality in the Proceiva PRODUCT trial. Frone positioning may also improve hemodynamics and promote overall ventilation profusion matchingand causes decreased levels of lung stress and strain. And in the 2023 American Therastic Society Guideline Update on the Management of Adult Patients with ARDS, they recommend prone positioning for greater than 12 hours per day in patients with severe ARDS. ECMO has traditionally been used as a last line therapy for ARDS, and supine therapy has generally been the standard. During the COVID-19 pandemic, prone positioning during venovenous extracorporeal membrane oxygenation or VV ECMO, increased in ECMO centers, but evidencesupporting prone positioning during VVECMO remains low quality, coming from retrospective observational studies. The intent of the prone trial was to determine the effect of early prone positioning during VV ECMO versus supine positioning on time to successful ECMO weaning in patients with severe ARDS. This is a French NORP investigator-initiated open label parallel group, multi-center randomized clinical trial, conducted in 14 French NORP hospitals between March2021 and December 2021. Patients initiated on VV ECMO that had been supported for less than 48 hours were eligible. Initiation of VV. ECMO was at the discretion of the treatment team, however, use of the OLEA trial inclusion criteria were recommended. Patients were randomized one-to-one to either prone positioning while undergoing ECMO or supine positioning. During the first four days, at least four prone position sessions of 16 hours were performed. Use of continuous neuromuscular blockade was recommended, but was left up to the physician's discretion.For patients in the supine group, prone positioning while undergoing ECMO was not allowed before day 60, but physicians could place patients in prone position as rescue therapy in cases of refractory hypoxemia during ECMO was not allowed before day 60, but physicians could place patients in prone position as rescue therapy in cases of refractory hypoxemia during ECMO. Both groups received similar protocolized treatment, including sedation, anticoagulation, ECMO, and circuit management. The primary outcome was timed to successful ECMO weaning within 60 days following randomization, and it was considered successful only if a patient survived without ECMO or lung transplant for 30 days after ECMO discontinuation.Secondary outcomes included ECMO and mechanical ventilation-free days, ICU and hospital length of stay, skin pressure injuries, serious adverse events, and all caused mortality at 90 days' follow-up. 170 patients were included in the trial, and the trial did meet power for their primary endpoint. Baseline characteristics were similar between the two treatment arms, and the median age was 51 years old and were primarily male, and the median P to F ratio was 66.The leading cause of ARDS was COVID-19 pneumonia. Patients underwent cannulation after a median of four days after intubation, and prior to initiation of ECMO, over 90% of patients in days after intubation, and prior to initiation of ECMO, over 90% of patients in each group had been in prone positioning prior to ECMO canulation. The primary outcome of successful ECMO weaning within 60 days of randomization was not significantly different between prone and supine positioning, occurring in 44.2% in the prone group and 44.0% in thesupine group. Of the patients with ECMO weaning failure, 10 were weaned but died,% in the prone group and 44.0% in the supine group. Of the patients with ECMO weaning failure, 10 were weaned but died, 8 in the prone and 2 in the SUPine group, and two patients needed a second ECMO run within 30 days after ECMO separation. At day 60, 7 patients in the prone group and 13 in the SUPINE ORG group were still undergoing ECMO. No significant differences were present in any of the pre-sessified secondary endpoints they found. As far as adverse events, the rate of cardiac arrest was significantlygreater in patients in the supine ECMO group compared with those in the prone group, 11.1% versus 3.5%. So this trial found in patients with severe ARDS, receiving VV ECMO, early prone positioning during ECMO, was not associated with a shorter time to successful ECMO weaning. This trial did not see similar findings of better outcomes in the prone group, as described in previous observational studies for a few possible reasons. A majority of the patients were prone prior to ECMO.A majority of patients had COVID-19 related ARDS, likely with a greater degree of pulmonary injury, which makes it hard to determine if they would have found like the same results in non-COV ARDS, and so would a different ARDS phenotype see a benefit? It's kind of hard to say. Consideration of trials, about 40% of the patients were enrolled at a single center, which may have potentially made the prone group look better as the center has more experienced treating patients with ECMO. Another consideration of something that study didn't include but may have been helpful is information on the various treatments received for both ARDS and COVID-19. The protocols are in the supplementary material, but no details on what the patients actually received. But in conclusion, among patients with severe ARDS, supported by VV ECMO PRODUCT,prone positioning during ECMO did not significantly reduce time to successful waning of ECMO.

Speaker 31689.16s - 1796.06s

Yeah, it's kind of notable that there will also be kind of another study looking at the impact of prone positioning on some of those biomarkers, right, IL6 or MCP1, so we're thinking of phenotypes. I also, you know, would there have been a difference if these patients were prone for more than four days? Unclear. And you may be wondering, why did they stop at four?Well, e-table three in the supplementary appendix describes all of the team members that are needed and all that's happening to safely prone a patient who's also concomitantly receiving VV ECMO. So they all have a responsibility. If you've never seen it done in practice,that kind of gives you a realistic view of what that looks like. And then a couple, you know, you mentioned you would have liked to see some of the COVID-19 specific treatments. And I agree the two treatments that they did talk about that patients received about 94% continuous neuromuscular blockade with cestricurium. And they used unfractionated heparin or as it's referred to in the supplementarymaterials, non-fractionated heparin, which may be my new favorite way to describe that. They targeted an APTT of 55 or an anti-10A between 0.2 to 0.4. They increased that goal in COVID-19 associated ARDS, which in this study, as Jenna PERSON mentioned, was our most common indication. Now, normally articles on Pharmaceted Dose are focusing on pharmacotherapy, but Hannah PERSON's going to highlight our next incredibly intriguing study researching a novel temperature management device in neurocritical care.

Speaker 01798.06s - 2069.98s

Yes, and we have to give a big shout out to pharmacist Michael Armaheiser from the University of Maryland as the second author on this study. So exciting to see pharmacists getting involved in this as well. So to start with some background, shivering is an adverse outcome for maintaining normal thermia. It can lead to metabolic stress, possible ICP elevations, and poor outcomes. Plus, the pharmacologic interventions like neuromuscular blocking agents to prevent shivering can have negative effects like prolonged mechanical ventilation and ICU outcomes. Plus, the pharmacologic interventions like neuromuscular blocking agents to prevent shivering can have negative effects like prolonged mechanical ventilation and ICU stay.You can refer to the TTM episode on the podcast for more of a breakdown on the consequences of cooling, but this study is specific to febrile neurocritical care patients, not just cardiac or acts patients. So traditionally, temperature modulating devices or TMDs achieve and maintain normothermia through surface, intravascular, or esophageal cooling. A classic example is the Arctic Sun PRODUCT, which is a non-invasive device that continuously monitors a patient's temperature and uses feedback to cool, rewarm, and maintain temperature via a water reservoir and heater. Water can then becirculated through the gel pads or blankets that are attached to the patient. So moving into our study, this was a prospective multi-center case control clinical trial that aimed to compare the shiver burden between a novel trans nasal temperature modulating device and the traditional surface cooling temperature modulating devices like the Arctic Sun. This occurred during the first 24 hours of targeted normothermia, which they defined as less than equal to 37.5 degrees Celsius and mechanically ventilated febrile neurocritical care patients.So the transnasal device that they used in the study, the cool stat PRODUCT, uses high flow room temperature air delivered through the nose, using a nasal mask to achieve normothermia through evaporative cooling. The adult neurocritical care patients require mechanical ventilation with a refractory fever and being admitted with a diagnosis of subarachnine hemorrhage, intracuribral hemorrhage, acute exchemic stroke or seizures were enrolled between August 2019 to December 2021. Refractory fevers were defined as a temperature of greater than or equal to 38.3 degrees Celsius and remained above this for two hours after administration of a Cidamine of M. Key exclusion criteria included quagalopathy and hemodynamic instability.They retrospectively included control patients who received chart TTM and a single center of neurocritical care unit between January 2019 and July 2021 in a three to one ratio of control to case patients. These patients were matched based on factors associated with shivering like age, sex, and body surface area. Shivering was assessed with the bedside shivering assessment scale score. Fuse for around 30 milligrams every 6 to 8 hours was utilized for shivering prophylaxis, and they also utilized institution-specific shivering management protocols.For their outcomes, they ended up including 10 patients in the trans nasal group and 30 in their control surface cooling group, and baseline characteristics were similar between the groups. Their primary outcome was timed to normothermia and temperature burden above that 37.5 degrees Celsius ranged during the 24-hour period, which they found no difference in between the groups. It took about 1.8 hours in the trans nasal group first 2.9 hours in the control to reach normothermia. They also assessed safety of the devices and adverse events were reported relatedto cooling devices in the control group. One patient of note in the trans nasal group didn't achieve normothermia. They did have a BMI of 38 and then another had cooling suspended at 20 hours after developing a pressure sore related to the device. As far as secondary outcomes, they assess the need for pharmacologic intervention to control for shivering. They're significantly higher in the control group, 67% versus 20%. And the number of patients requiring intervention was higher in the control group as well. Proportion of time spent with a bedside-Sherven assessment scale score over zero wasalso higher in the control group, 28% versus 4% in intervention. So a couple of limitations of this, the authors reported that the device has a possible risk of rebound temperature increases when it's discontinued, which could possibly limit its utility. And then additionally, control patients were selected from one institution while intervention were for multiple. There were there differences in standards of care. But one of the positives of this study is that it did look at targeting normothermia, which is being recommended in guidelines such as the spontaneous ICH guidelines. And the study showed overall no difference in time to normothermia, but it was exciting to see that this device had significantly less shiver burden,which could lead to better outcomes in neurocritical care patients.

Speaker 32077.24s - 2358.64s

Yeah, researching a device that may limit one of our most common rate limiting adverse effects. Ooh, say that five times fast. Shivering, right? And in this study, the thing is the treatment arm actually received less pharmacotherapy along with less shivering. So of course, hypothesis generating findings at this point, but we all know there is no perfect surface cooling device. So I think it's encouraging to see research happening in this field.Closing out our featured articles the same way a nice restaurant does with a mint. What type of mint you may ask? The myocardial ischemia and transfusion trial, aka the mint study. So beginning with the trick trial, numerous studies, they've shown the benefit of that restrictive transfusion goal, but one of the big populations that are excluded is ACS, right, acute coronarysyndrome patients. Now, pool data in a met analysis shows an increased ACS risk in the restrictive treatment arm and the 2015 UK Titer 2 trial showed an increase in 90-day mortality when they researched a restrictive transfusion goal targeting a hemoglobin of less than 7.5, and patients undergoing non-emergent cardiac surgery. And that leads us to our study today published in the New England Journal of Medicine ORG, the restrictive or liberal transfusion strategy in myocardial infarction and anemia.So international, open label, randomized clinical trial, and it randomized patients to a liberal or restrictive transfusion strategy. An open label or non-blinded meant the treatment team knew the assigned goal, right? Because they're acting on a lab value, of course. So 144 sites in the U.S., Canada, France, Brazil, New Zealand, and Australia GPE all over the place.Man, hitting some fun spots there. So adult ACS patients with a stemmy or N-stemi and a hemoglobin of less than 10 were enrolled. So key exclusion criteria, uncontrolled active bleeding, or a scheduled cardiac surgery, that same admission.So patients in their restrictive arm, they were permitted to receive a transfusion when their hemoglobin was less than eight, and it was strongly recommended when it was less than seven, because you'll see in the text less than seven to eight, and that's kind of the explanation why. Now, if angina symptoms were suspected to be caused by anemia, transfusion was permitted inthe research study. Now, the protocol states that the reason they allowed the higher transfusion is discussions with many cardiologists suggested that many clinicians are not comfortable with a threshold as low as seven. And that's kind of where the eight comes in. That's from the supplementary materials. And then patients in the liberal strategy arm, they had instantly raised their hemoglobin to greater than 10.They transfused packed red blood cells one unit at a time to keep it above 10. And the protocol, whatever you were randomized to is paused if active bleeding was suspected. So the primary composite outcome was 30-day all-cause mortality and myocardial infarction. So just over 3,500 patients enrolled and met that pre-specified sample size calculation. And they were enrolled between April 2017 and April 2023. So about 80% of these patients had an N-SemI, a mean hemoglobin about 8.6, and about 50% of thepatients were in the ICU at study enrollment. And out of all those countries, we named the U.S. sites enrolled 60% of these patients when thinking about that external validity. Now, there was no difference in the primary outcome between the restrictive and liberal transfusion arm. However, it just missed difference in the primary outcome between the restrictive and liberal transfusion arm. However, it just missed significance for the restrictive strategy actually increasing your risk of 30-day all-cause mortality and MI, that composite outcome.And the restrictive arm increased the risk of cardiac death with a relative risk of 1.74. So it's kind of a great trial showing that less isn't always more, especially as it relates to hemoglobin targets in acute coronary syndrome. So despite showing the possible benefits with a liberal transfusion goal, there's certainly hypothesis generating most of those were some secondary outcomes.Now let's kind of keep standing on that cardiology corner as we move from our featured articles. Jenna PERSON has some great studies to highlight as we try to avoid breaking any hearts. And our section begins with a study looking to modify a well-known scoring system that has some well-known imperfections. So Jenna PERSON, let's throw some teas on it. Yes, thank you.

Speaker 12358.64s - 2460.7s

So this study published in the Journal of Cardiothoracic and Vascular anesthesia is a modified 4 PRODUCTT score for Heparin-induced thrombocytopinia in the mechanical circulatory support population. Mechanical circulatory support devices innately caused platelet destruction and by definition patients undergoing MCS support will score zero points in the 4 PRODUCTT's other causes of thromocytopinia section. Thereby reducing MCS patients to a maximum of six out of eight points, and potentially reducing the diagnostic accuracy of the 4 PRODUCTT score in this patient population.This complicates hit diagnosis and cardiac surgery patients, which is a population already at an increased risk of hit. Patients who underwent cardiac surgery between May of 2008 and December of 2016 at Stanford University Medical Center were included in this retrospective cohort study. They stratified patients into three groups, control groups, those with normal platelet counts, thrombocytopinia with a negative hit test, and thrombocytopinia with a positive hit test. Patients were not matched or well-balanced between the three treatment arms.A comparison of diagnostic accuracy between the 4 PRODUCTT and the proposed 4T MCS score was performed. The suggested modified 4T score for use in the MCS population includes the same first three categories of thrombocytopenia, timing, and thrombosis, but the fourth category was replaced by type of mechanical circulatory support, with one point for each device, intra-aortic balloon pump, ECmo, or VAD support within 100 days with the maximum of two points. The study found that when using the guideline recommended score cutoff of greater than or equal to four, the 4 PRODUCTT MCS score had higher sensitivity than the traditional 4T score and may allow for more accurate screening and treatment of hit in the MCS population.

Speaker 32463.44s - 2503.24s

Yeah, interestingly, right, deep vein thrombosis, morbid obesity, and chronic kidney disease were all pre-op predictors of post-cardiac surgery hit. What a great research idea in a population with more than one risk, fact, risk for inaccuracy in that 4-T PRODUCT's predictive scoring system. So let's kind of stay in this cardiac surgery world and review a research study determining of time and location of vasoplasia treatment impacts those patient outcomes.And we know everyone loves a good B12 energy boost.

Speaker 12503.24s - 2599.86s

So this is the intraoperative versus postoperative hydroxycopalman for vasoplasic shock in cardiothoracic surgery. It was published in the Journal of Cardiothoracic and Fascular anesthesia Journal ORG. And hydroxicalbalamin is a highly bioavailable form of B12 that binds to and scavenges both nitric oxide synthase and nitric oxide, attenuated basodilation that can be induced by cardiopulmonary bypass use.Hydroxycopalamine is commonly used in the setting of basoplegic shock after cardiopulmonary bypass, but the timing of using it interoperatively versus post-op is not well elucidated. This is a retrospective cohort single center study that included adult patients who underwent cardiac surgery using cardiopulmonary bypass and who received hydroxycopalamine as a five gram bolus over 15 minutes for vasopplegic shock, either intraoperatively 37 patients or post-op, 75 patients. This is from June 2018 through October of 2018. The study found that althoughthe interoperative patients were sicker and required more frequent use of other hemodynamic rescue agents, hydroxycobalamin produced a greater increase in map when used intraoperatively. There was no difference in the primary outcome of vasopressor-free days in the first 14 days post-surgery. After adjusting for covariates, there were no differences found in any of the secondary outcomes. The study is not able to show a difference between intraoperative and postoperative hydroxycobalamine use,although challenges in the evaluation include selection bias and a high patient acuity, evidenced by the rate of ECMO use in both groups.

Speaker 32602.82s - 2657.7s

That's a really good point about the patient acuity. And the pharmacist authors, the first and senior author of this article, they note that the hydroxycobolament always comes from the central pharmacy. And whenever pharmacists are with me advice, I always tell them, if you want to get a way to help ingratiate yourself with the team, one of the best ways to do it is when they need something fast,you're the one to get it and you just mix it kind of quickly at bedside. You get to be hands-on. Obviously, make sure you're not breaking any institutional rules or things, but, you know, the treatment typically gets given in a more timely fashion. We're talking about this drug specifically. Don't be proud. Always wear gloves.These stains are a no joke. So always wear the gloves. But from a different research group in the same health system as our previous article, Jenna PERSON, close out these cardiac featured articles with a study researching how our choice of post-arrest vasopressor can impact patient outcomes.

Speaker 12660.76s - 2754.68s

Gladly and very happy to share another pharmacist-led study. So this was the risk of arrhythmia in post-resuscitative shock after out-of-hospital cardiac arrest with epinephrine versus norepinephrine, and it was published in the American Journal of Emergency Medicine ORG. So the optimal management for post-resuscitative shock after cardiac arrest remains unclear, and the American Heart Association ORG guidelines for post-arrest care make no recommendation of a preferred vasopressor for post-ROSC resuscitation. This was a retrospective multi-site cohort study of adult patients presenting to emergency departments at Mayo Clinic Hospitals and Health Systems in four different states in the U.S.Patients were included if they had an out-of-hospital cardiac arrest, achieve ROSC, and required either epinephrine or norepinephrine continuous infusions within the first six hours. 221 patients were enrolled from May of 2018 through January of 2022, with 70 patients in the epinephrine group and 151 in the norepinephrine group. For the primary outcome of clinically significant tachyarhythmias, this study found no statistical difference between the two groups. The study also found that patients whoreceived epinephrine infusion for post-out-of-hospital cardiac arrest shock had significantly higher in-hospital mortality of 90% versus 54.3% and were also significantly more likely to re-arrest during hospital admission, 39 versus 17.1%. These results add to the literature suggesting norapinephrine may be the vasopresser of choice and post out of hospital cardiac arrest patients with shock after ROSC. However, it's hard to say as patients in the epinephrine group appear to have been more sick.

Speaker 32757.36s - 3230.4s

Another shock subsection, another positive study for norepinephrine. The hits keep coming for everyone's favorite vasopressor and a really kind of great research idea from those Mayo Health Clinic ORG colleagues. That's kind of a perfect transition. Let's highlight a few notable cardiac arrest trials.So batting lead off, it's a resuscitation pilot study researching epinephrine pharmacokinetics in cardiac arrest patients. So this was a Norwegian NORP pre-hospital study. So just let me just set the scene and picture how incredible these paramedics are. They're doing chest compressions. They're intubating.Making sure everything's okay. And then they're ensuring labs are drawn appropriately for this study. So everyone got baseline labs. Patients were given one milligram IV push epinephrine, and then blood was drawn every minute for five minutes. So what the researchers did, they were researching peak concentrations and duration.So that peak was achieved one minute post-administration, and concentrations remained elevated at five minutes. Now remember, so to administer epinephrine every three to five minutes, but we all know if it's five seconds past three minutes, someone's yelling, it's time for epi. So we know that that's being given way more frequently.And the other thing that was notable was their significant variability, peaks and valleys of those epinephrine levels, rather than more steady levels, right? That would be the argument for maybe a continuous infusion. So kind of adds to the literature that more epinephrine levels rather than more steady levels, right? That would be the argument for maybe a continuous infusion. So it kind of adds to the literature that more epinephrine and cardiac arrest doesn't necessarily mean improved outcomes.Now, staying in that pre-hospital cardiac arrest setting and researching an intervention that's actually had previous positive results, but never adapted into clinical practice. And that's the use of methyl prednisalone. So the Stereoka PRODUCT, what a great trial name. It was published in intensive care medicine, investigator initiated, randomized multi-center,blinded, placebo-controlled phase two trial. Enrolled 137 adult comatose out-of-hospital cardiac arrest patients who achieved ROSC for more than five minutes in two Denmark hospitals. And they randomized them to 250 milligrams of methyl prednisolone given IV push over five minutes once or placebo.If you're wondering like I did, where did this dose come from? The only thing I can figure out is it appears that this dose was given because it's the highest dose that you can give IV push in Denmark GPE. But this was more of a biomarker study actually, right? Mentioned it was a phase two trial. And that's because the primary outcome was the reduction of IL6 and NSE levels with methylpred compared to placebo.And what they found was that one of the biomarkers, IL6, was significantly reduced, but no difference in those NSE levels. Hypothesis generating, but remember, this is kind of a little more into that phenotype researchthat we may continue seeing. And then last, but certainly not least, it's an article reviewing what happens when your heart actually does break. And it's an expert reviewon hypothermic circulatory arrest. So specifically the article focuses on aortic arch surgery, but many of the principles, it applies to more procedures. Shout out to figure one for a visual on what's happening with aortic arch surgery. And then the article highlights the effects of hypothermia on common drugs given in the OR via anesthesiologist. So it's a really good review in thatjournal of cardiothoracic and vascular anesthesia. Don't worry. Stars of the episode, our favorite guest host, will return shortly. But let's dive into a crowd favorite section here. That's right, the Popery PERSON section. And Ryan Feldman highlighted his systematic review of Fennibute withdrawal in the 2023 NACCT ORG FarmD Abstract episode.But his research is now available in a PDF in the journal Clinical Toxicology. I'm not going to go into too much detail. We kind of did a deep dive into it on there. But wanted to put it on everyone's radar. Ryan PERSON is a must download when he gets those things out in print. Now, previous episodes have highlighted the limitationwith standard coagulopathy labs in our patients with cirrhosis. So researchers from Cleveland GPE created a retrospective propensity match study to assess the safety and efficacy of their pre-procedural tag-directed transfusion strategy correcting coagulopathy in cirrhosis prior to tunneled central venous access. And I was in critical care exploration.So 82 patients were matched with a tag-guided strategy compared to a conventional lab strategy. And so baseline I and R about 1.9, platelet count of 75,000. I mean, patients with tag guided correction received less FFP, less platelets, and more cryo, with no difference in post-procedure bleeding or thrombosis. The viscoelisitography guidedprotocol actually led to a cost savings. You know, the funny memes, when you see Ben Affleck PERSON smoking a heater or you see Meredith Gray PERSON looking so distraught, one of my favorites versions of that is when it says someone ordered vitamin K or PCC to bring down our serotics I&R. And it's that look. Everyone knows that, that look and that feeling. So I had to bring that up into this critical care explorations article.Now, staying in the anticoagulation and heme world, pharmacotherapy has an excellent review featuring a fantastic pharmacist author list, reviewing antiquagulation considerations in ECMO. And of course, table one is what you'd expect in pharmacotherapy, a table describing studies researching antiquagulation strategies in ECLS.A must-save fantastic review article. Now, our next study, it's a CID clinical infectious diseases article, is describing the rationale for the 2022 changes in PIPTASO breakpoints. And the reason I'm highlighting this is sometimes your lab can't adapt their MICs at the same rate as maybe CLSI ORG or other governing bodies. And so it's helpful to know when and why they change those breakpoints so that you canapply them to your patients if they're not the most up to date. So you can go in depth into those changes in one of our most commonly used antibiotics. And closing out our Poperi section, our pharmacist colleagues in West Virginia published a study in the Journal of Antimicrobial Chemotherapy ORG, comparing atypical coverage for severe cap, zithromycin versus doxycycline. And doxy is the underrated drug. So I love that we're researching this. Prospective observational study enrolled 149patients from March 2020 through July 2022. Yeah, so we just classically enrolled through the straight global pandemic. So shout out to West Virginia GPE. And no difference in the composite primary outcome of in hospital and 30 day mortality between these two agents.The authors make the argument to include Doxy PRODUCT as an alternate agent for severe cap. And I agree. This episode of Pharmacyididosis is proudly sponsored by KCezy ORG, providing innovative pharmacologic therapies for over 85 years. KCeZ ORG is committed to supporting the clinical pharmacist community and the patients you serve. To learn more, visit kiazzi.farmacetadose.com.We've been working up to our sepsis section most of the episode and there are three fantastic articles to highlight because I'm feeling under pressure. So we kick off our sepsis section with a meta analysis focusing on one question. Hannah PERSON, help us out. Do we need flugia cortisone in septic shock? with a meta analysis focusing on one question. Hannah PERSON, help us out. Do we need flugrechortosone in septic shock?

Speaker 03233.86s - 3325.26s

Yeah, so this was published in critical care medicine, but it's an updated review and analysis looking at hydrochortizone and fluidic cortisone. So the authors reviewed the mechanisms and proposed benefits of adding fludricorone to hydrochrotazone in adult patients with septic shock. This is a systemic review of Bayesian network meta-analysis, including 19 studies, in over 95,000 patients. They included randomized controlled trials, as well as observational studies using target trial emulation. Their primary outcome was short-term mortality to find as 28-day or 30-day mortality,which the authors conclude was reduced in the hydrochortazone plus fluidicrhodocortoan group when compared to placebo alone. This significance was not maintained, though, when compared to hydrochortizone monotherapy. Odds ratios and probability rankings of short-term mortality improvement are shown in figure two, which I direct you to as some forest plots and then figure three, some rancograms. And the number needed to treat for primary outcome reduction with hydrochortisone plus fludercortizone was 21, but with a low certainty of evidence. Adverseeffects of therapy, as we know, could include gastrodoadnal bleeding, superinfection, and then hyperglycemia was analyzed. Their findings suggest that hydrochortizone plus phlogerogorotone may increase risk of hyperglycemia when compared to placebo. I thought this was a helpful review of current therapy and they called for a need for a possible large placebo-controlled randomized controlled trials just on the efficacy and safety of utilizing that hydrochortisone plus fluidic cortisone for septic shock.

Speaker 33327s - 3364.06s

Yeah, interesting data pooling all the RCTs to try and answer this question. You know, to be honest, you know, the, you know, the author said a large, well-powered RCTs needed. There's so much conflicting evidence. I'm not sure that would convince everybody, even if we had a large RCT, but we'll see this certainly is notgoing to be the last we've heard of this question. Now, some might have considered the Clover ORG's trial a negative study since a restrictive fluid strategy didn't necessarily improve the all-cause mortality primary outcome. However, can we blame this on the kidneys?

Speaker 03366.18s - 3456.32s

Yeah, so moving into an editorial in the American Journal of Respiratory and Critical Care Medicine. So fluid resuscitation techniques and sepsis associated A.K.I. Or unknown, this was a letter to the editor. The authors reported a secondary analysis of the Clover ORG's trial. Just a reminder, Clover's randomized patients to restrictive, prioritized early vasopressors, or liberal fluid resuscitation for sepsis-induced hypotension,with no difference being seen in either treatment strategy with regards to all-cause mortality. But this analysis looked to determine if the presence of AKI at randomization changed the incidence of renal replacement therapy or RRT between treatment strategies. Primary outcome was 28-day incidence of renal replacement therapy or RRT between treatment strategies. Primary outcome was 28-day incidence of RRT.So out of the 1,455 patients 913 or 63% had A.K.I. at randomization. The liberal group received a mean about 3,800 M.L.s of IVB fluids versus about 1,900 amels in the restrictive fluid group during the 24-hour protocol. They found no significant difference in the primary outcome, both in patients with and without A.KI.And the authors concluded that A.K.I status at randomization did not modify 28-day incidence of R.R.T. They also found no significant difference in mechanical ventilation or 28-day mortality in the treatment groups. So authors stated that these findings suggest an average about two-liter difference in fluids may not be a large enough difference to influence clinical outcomes. And the lower rates of ROT seen in the Clover ORG's trial may influence these secondaryanalysis findings.

Speaker 33458.56s - 3486.98s

Yeah, great research theory, but it certainly feels like it's back to the drawing board, right? It makes sense that we would look to see if kidney function affected it. It did not. I'll be curious. This feels like we're going to see some more coming from the Clovers PRODUCT trial data set with just the sheer number of patients they had enrolled.Now, our last sepsis article, it's looking at the use of a specific vasopressor in patients with shock and difficulty breathing. So Hannah PERSON, close us out. Yeah.

Speaker 03487.16s - 3585.68s

So looking at one of our new pressers, angiotensin-2, and what kind of an impact it might have in patients with ARDS. So this was published in the analysis of intensive care. And this was a post hoc subgroup analysis of the Aethos-3 trial, which studied Andrew-Tensin-2 in PRODUCT catacolamine refractory vasodilatory shock, aiming to determine whether Andrew Tenson 2 treatment was associated with improved oxygenation.So this analysis includes patients that met modified Berlin ORG criteria for ARDS at enrollment. 81 patients are about 25% of the original study cohort were included. 34 received Andrew and Tin 2 and 47 placebo, with a baseline PF ratio of about 150. Their primary outcome was PF ratio at 48 hours, adjusted for baseline PF ratio.The main PF ratio increased from 155 to 265 in the angiotensin 2 group compared to a minimal increase from 148 to 164 in the placebo group. And this change was not due to catacolamine dose or ventilator management. The authors reported out that this subset of ARDS patients still met the primary efficacy end point of the 8th dose 3 trial, which had been a limitation before. I thought their discussion section was interesting. They listed some possible mechanisms for their findings.One suggestion was that Andrew Tenson II PRODUCT offers possible anti-inflammatory benefits. And it'll be interesting to see additional studies on this to show significance of this outcome and possibly determine what the underlying mechanism is. But the use of Andrew Tenson 2 PRODUCT in shock with confident ARDS, appears safe and possibly effective in improving auctionation.

Speaker 33587.36s - 4100.08s

Yeah, some cool exploratory findings as we're still working, I think, to find that ideal patient population that we can use the little bit of a higher cost vasopressor angiotensin 2. So we've arrived to the front of the fridge, aka the pharmacist featured articles where you, the listener,gets to vote on the three articles discussed in this section on each literature of you series episode. So at Pharmacy to Dose, Tio to Dose on Twitter X or Instagram ORG, if you want to vote as well. And the winner of the first vote features two RSI guideline panel members.So this international research team created a cross-sectional survey on the use of peripheral vasopressor infusions in critical care, published in a journal of critical care. Now, they disseminated this survey in four countries, US, UK, Canada, and Australia GPE.So electronic survey from April to July of 2022, and it included 132 responses. So a few highlights. So 86% of the surveyed institutions allow peripheral noraphenephyran administration. However, 52% prefer an alternate vasopressor to norapinephrine. And you get to see some international preferences with dopamine and metametaminal,being preferred alternate first-line agents to norepinephrine. Over 50% use a 4 milligram in 250 or some would say maybe diluted concentration for its use. So overall, a really great article providing contemporary evidence on how peripheral vasopressers are being utilized in international practice. And it shows there's some big variability, right, across countries and centers with what we're doing here.So continuing on the clinical practice side of things is an annals of pharmacotherapy article from New Hampshire GPE researching a novel DCA treatment protocol. So they're researching the use of a two bag DKA protocol, also known as a fixed insulin dosing protocol. So the two bag method lets you titrate the dexterous fluids while keeping insulin and electrolyte infusions constant or fixed. And this hospital or group shifted to this approach as a way to help reduce their time to DCA resolution.So what did they find in this kind of retrospective before-after study? So the before or the pre-proticle cohort, they had data collected from January through August 2021, with the post or after protocol cohort being August 2021 through February 22. To avoid confounding, they excluded outside hospital transfers. So 143 patients were enrolled. And the before cohort had a significantly higher starting glucose and beta-hydroxybutrate level.Those are the two significant differences in those baseline characteristics. And the two-bag D-K.A. treatment actually significantly reduced the primary outcome, time-to-an-gap closure and or beta-hydroxybutylate normalization, so aka acidosis resolution. And they reduced not only time to anion gap closure, but also the normalization of that beta-hydroxybutyrate. So it worked on both.And the more rapid time to normalization, it didn't translate to other outcomes like length of hospitalization or duration of insulin infusion. But a hypothesis generating from the single center retrospective study, great results kind of supporting the use of a two bag or fixed insulin dosing DCA protocol. And rounding out our front of the fridge,the award for the most creative study design goes to our New Jersey GPE pharmacy colleagues, publishing a simulation article in the American Journal of Emergency Medicine ORG. So most of us have had to make a vasopressor, continuous infusion, or even whip up a push-dose vasopressor in the ED or the ICU. And this was actually a crossover simulation looking at total prep and administration time it takes to make both push- push dose vasopressers and continuousinfusion vasopressers. And they looked at epinephrine and phenolephrine, but they also looked at major errors. So it was about 50-50 split between ED and ICU pharmacists out of the 16. So some interesting results. The first thing, as we would expect, the administration of push-dose phasopressers was much out of the 16. So some interesting results. The first thing, as we would expect, the administration of push-dose phasopresserswas much faster than the administration of continuous infusion phase-upressers, about five times faster. But the push-dose vasopressers had significantly more preparation and administration errors.So benefit to bedside administration, but have to keep in mind the safety concerns, double checks, remembering the concentrations that we're using. And this paper from multiple pharmacists did just that, thinking about the benefit and the safety concerns. So awesome job from these authors. And two fantastic clinical articles close out our 2023 literature review series.Now, a JAMA Internal Medicine article highlights a trainee-led intervention to motivate resident physician voter registration. So the author specifically note this took place in North Texas LOC, right? So a place where voting rights are certainly needed. And the resident physicians, they created a five-step process to implement their initiative, prepare, organize, engage, measure, and sustain.And this led to a 99% voter registration. Important discussion in a presidential election year. Everyone makes sure they're registered to vote. Oh, this was such a cool study kind of showing what you can do, right, the power of one. And then one of my favorite articles maybe of the year is a JACCP article entitled Clinical Pharmacy Services at the Tokyo Olympic and Paralympic Games WORK_OF_ART. All right.This is so cool. So sports pharmacists, which I didn't even know was a newer area of clinical pharmacy. I'm telling you what, 10 years ago, Nick PERSON, when he graduated, is very jealous of this. But the article details all they did in the 2020, in the 2020 Tokyo Olympics to help us understand the role of this specialty a little bit better so they mentioned that there were 37 pharmacists and this was a volunteer role so shout them out and the article gives us the tea which I'm always grateful forthey detail which prohibited medications or prescriptions were written and for which event the athletes were participating in. They even highlight a great case involving a pharmacist, helping with the treatment of an athlete with epileptic seizures. So pharmacists doing awesome things, love highlighting this, great work to our sports pharmacist friends in Japan GPE.And we've made it the end of the December 2023 literature review series. Wow. A huge, huge thanks to Hannah and Jenna PERSON could not have had such a great episode without both of your help, hard work, and incredible puns. Greatly appreciate you both. Thank you all so much.Thanks again to Jenna and Hannah PERSON. Let them know how great they were. Let me know what feedback or comments you may have at Pharmacy to Dose ORG on social media. Send me an email, Pharmacy ORG to Dose at gmail.com or visit Pharmacy to Dose.com the website. Well, you'll find the reference list that has all the articles from the December 2023 literature reviewers, as well as the research we discussed in those review summaries.You can also find that in the podcast episode description as a clickable link. But until next time, I'm Nick Peters and this is Pharmacy to Dose, the Critical Care ORG podcast. and this is Pharmacy to Dose ORG, the Critical Care Podcast. The Critical Care PRN optimizes drug therapy outcomes by promoting excellence and innovation in clinical pharmacy practice, research, and education. For more information, go to critprn.acCP.com.

Speaker 24100.2s - 4138.82s

Again, that is critprn.acep.com. The podcast provides general information only does not offer individualized medical or professional health care services, including pharmaceutical advice. The contents and materials in the podcast are not intended to be a substitute for in-patient-farmac-scoldeat diagnosis or treatment. Use of the content and materials on the podcast does not constitute a pharmacist patient relationship. As a result, the information in and materials linked to this podcast are applied at the user or patient's-in-patient or applied at the user-in-patient or patient to consult their physician-of-patient or personal-care professional. The user-spation should not ignore delay seeking care professional care professional.In case, in an emergency case, the user-pment should not be contacted or those of the host and guests and should not be interpreted to reflect the official- they heard on this podcast. In case of an emergency, the user patient should contact their physician, call 911 ORG or go to the nearest medical emergency facility. The views and savings expressed on this podcast are those of the host and guests should not be interpreted to reflect the official or policy of the critical care PRN. ACP and the critical care PRN ORG, disclaim any in all liability or responsibility for any indirect, incidental, special, or any other damages, including without limitation, loss, profits arising out of any use of reference to reliance on or inability to use the podcast, its contents and materials.