SCCM Resource Library-Star Research Presentations: Pharmacology

Star Research Presentations: Pharmacology

Video Transcription

Hi, everybody. We're going to go ahead and get started and try to keep ourselves on time today.  My name is Leslie Hamilton, and I have Ernest Alexander next to me. I'm a neuro ICU pharmacist  at the University of Tennessee, and Ernest is a trauma ICU pharmacist at Tampa General, right?  Tampa General and Tampa, Florida, so close by. And I have a few housekeeping items that I'm  going to go over, and then we will get started very shortly. So if you can, try to move to the  center of your rows just so people can sit on the side if you need to. Please silence your cell  phone. The exits, I think, are kind of obvious. They're in the back. Please silence your cell  phone. Once the session is concluded, I don't think there's anything after this, but they just  encourage us to exit as quickly as possible. If you want to have access to these presentations  later on, the Congress on Demand will be available after Congress, about two weeks after Congress is  over. Same thing with your CE credit. Don't forget to claim that on the Congress app. If the speakers have any conflicts of interest, they will disclose those. And then finally,  if you are tweeting this presentation, use the hashtag CCC49 in terms of tweets. So each of the  presenters have 10 minutes to present. We'll do four minutes of Q&A, and then we'll have a one  minute transition period between each of the presenters. So I'd like to go ahead and ask our  first presenter, Dr. Christopher Snyder from Johns Hopkins All Children's Hospital, to talk about bivalve ruden anticoagulation for neonatal ECMO. Thank you.  Good afternoon. Thank you very much for the opportunity to present. I have no disclosures.  So continual diaphragmatic hernia is a life-threatening birth defect, fairly common. It can result in severe pulmonary hypoplasia due to compression on the affected  lung and can result in a respiratory failure shortly after birth in these babies. The babies  that have this severe respiratory failure often will require ECMO. This is one of the more common  indications for neonatal respiratory ECMO. And as everyone in this room knows, ECMO requires systemic anticoagulation. Most centers use heparin for this anticoagulation.  And there is some controversy in the surgical world about timing of repair in these babies,  because there's some evidence that early repair is better, so that you can get everything out  of the chest and allow this hypoplastic lung some room to grow. However, there's obvious implications for performing a major surgical procedure in a patient who's therapeutically  anticoagulated. So the bleeding and thrombotic complications for CDH repair and ECMO are quite high. And a lot of people feel that this contributes to the fairly poor survival of  these babies. So babies who have CDH and require ECMO only have about a 50% to 60% survival nationally.  Vivalirudin is a direct thrombin inhibitor. It has a short half-life, only about 20 minutes.  And it is an alternative agent to heparin for anticoagulation in this setting.  At our center, Johns Hopkins All Children's, we routinely perform early repair on ECMO for CDH.  And we have routinely used Vival for anticoagulation since mid-2016.  The issue with Vival in this setting is nobody really knows how best to dose this medication  and how to monitor this medication. So what do you use to monitor it? Do you follow ACTs? Do you  follow your activated partial thromboplastin time or APTT? Do you follow thromboelastography,  specifically your reaction time or R time? There's really not much data out there to help guide us  in this situation. And consequently, there's really no standardization among different centers.  So the purpose of this study was two-fold. Number one, we wanted to describe our protocol and our actual Vivalirudin dosing, our anticoagulation test results, and our outcomes  in terms of early postoperative bleeding and thrombosis. And then we wanted to just take a closer look at that relationship between the Vivalirudin dose and these test results that  we're using to monitor our level of anticoagulation to see if we could define a dose response.  So this is our perioperative Vivalirudin protocol. This is a busy slide, so I'm going to kind of  break it down and hit the highlights here. You can think of this perioperative period as being  three different periods. One is that initial period from when the patient is first cannulated  for ECMO to when you actually start the repair, when you actually make an incision and start  cutting. Our practice is to do early repair, so our preference is to do this 24 to 48 hours after  the patient is cannulated. If you let it get out much beyond 48 hours, you start to get a lot of  edema that makes the procedure a little more technically difficult. Then intraoperatively,  so this is the time from the start of our repair to end of our repair. We're going to approach  things a little differently. This is obviously the highest risk of bleeding, and then postoperatively  we're going to do it differently. So the highlights of this, initially we start at 0.16 mg per kg per hour. We target a APTT of 75 to 90 seconds and a TIGR of 9 to 12 minutes.  If we are below that range, we increase our infusion rate by 20%. If we're above, we decrease  it by 10%. Intraoperatively, before we make our incision, we will decrease our infusion rate  to about 0.1, 0.08 to 0.1, and then we'll actually titrate it intraoperatively based on our direct  observation of what's going on with the patient in terms of their bleeding, in terms of what's  going on with the circuit, in terms of clotting and everything. And the very short half-life  of bivalirudin allows us to do this very dynamic titration intraoperatively. So then postoperatively,  we're obviously monitoring very closely for ongoing bleeding, monitoring our chest tube output,  monitoring our hemoglobin change, and our overall goal is to get back to that therapeutic range  within about 24 hours postoperatively. So we're slowly ramping up in 10 to 20% increments to try  to get back to that target range as long as we don't have ongoing bleeding. So the methods for  this study, this was a retrospective review. We looked at all neonates with CDH, anticoagulated  bivalirudin over about a two-and-a-half-year period at our institution. We extracted our data  from the electronic medical record. In terms of outcome definition, we defined major thrombosis  as thrombosis that requires you to change your ECMO circuit. And we defined our major bleeding  according to an international definition put out by the International Society of Thrombosis and Hemostasis in 2011. This is a composite definition. So major bleeding is defined as  fatal bleeding, bleeding that occurs in a non-surgical site but a critical area. So bleeding into the brain, retroperitoneum, or the lungs, bleeding that requires reintervention,  and then bleeding that results in a drop in your hemoglobin of greater than two grams per deciliter in a 24-hour period. So we got time stamps for each of these data points in our  chart review. We wanted to really focus in on this perioperative time period because this is  really kind of the most dynamic period when your risk of bleeding is the highest and there's kind  of the most dynamic titration taking place. So we defined that as our initial period, so from the  ECMO cannulation to the start of repair, and then postoperatively from the end of repair all the  way out to 60 hours postoperatively. Most studies will do like 48 hours. We wanted to fudge it a  little bit just so we didn't miss any events that occurred right after that 48-hour period.  We summarized our BiVal and our lab results over time, and then we used some linear regression  modeling that accounted for the repeated measures in these patients to see if we could define that  relationship of BiValorudin dose to our lab, our monitoring labs. So we looked at the BiValorudin  dose one hour before the lab was drawn, which is about three half-lives or about approximately  steady state, looking at APTT and TegR, and we adjusted for various covariates, including the  amount of time the patient had been on ECMO during that period. So this is our kind of standard table  one. These are term babies, about three kilos, about half-female, half-male, predominantly left-sided, severe pulmonary hypoplasia, 90% underwent repair on ECMO, as is our practice.  So our actual BiValorudin dosing in all of our patients started at .16. The median start time  was 1.2 hours after cannulation. We found that all these patients achieved their target within 12  hours on dose anywhere from .12 to .36. Looking at just the patients repaired on ECMO, so 38  patients repaired on ECMO, we decreased them to .1 immediately preoperatively, as is our practice.  Intraoperatively there was quite a range, and then postoperatively by six hours after surgery they were back up to .16, and by 24 hours they were back up to .22. So here's our early  postoperative outcomes. You can see 39% of patients met the criteria for major bleeding.  When you break this down and look at why that is, all of these patients met that based on the labs,  based on their drop in hemoglobin of greater than two grams per deciliter in 24 hours. So there was  no fatal bleeding, no critical bleeding in nonsurgical sites, and no reintervention required  for this. And interestingly of those 15 patients that had that drop in hemoglobin, only 12 of those  actually received transfusion for that drop in the hemoglobin. We had no episodes of circuit  thrombosis requiring a circuit change. So this is graphically just showing us what's going on  here in this initial period. These are smooth scatter plots to make them a little bit more  readable. You have a time on the x-axis here. You can see that the bivalorudin dose is kind of  drifting up over time in that initial period, whereas our TEG-R is maybe drifting up a little  bit and mostly flat. PTT seems to be kind of drifting down. In the postoperative period we  have a similar effect that our bivalorudin dose is having to increase significantly throughout  this post-op period, whereas our TEG-R and our APT are roughly flat. So in terms of our linear  regression, in the interest of time I won't go into the weeds with this, but just suffice to say that when we adjusted for covariates that the bivalorudin dose was actually not  significantly associated with either the APTT or the TEG-R. We did see some stronger effects of the time that the patient had been on circuit. So conclusions. We can conclude that  in this population on bivalorudin, our initial target anticoagulation levels were able to be achieved consistently and quickly. Set a favorable safety profile. Even though 39%  met criteria for major bleeding, this was all due to labs and nobody required re-intervention. We did not have to make any circuit changes, so we did not have a thrombosis  problem. And then I think what this really shows us is that there's, this is a complex relationship and a complex patient population. We could not detect an independent association  of TEG-R or APTT with the bivalorudin dose. But what we did see was that you required escalating doses of bivalorudin to maintain your therapeutic range, which suggests that  there's some kind of tolerance or tachyphylaxis phenomenon that's going on. So future directions,  we hope to prospectively study this. A little bit more standardized timing to look at those  effects of time and covariates. Hope to look at some other novel anticoagulation tests. And we  hope to correlate our dose in our anticoagulation labs with actual clinical events to define a safe  therapeutic range. So thank you very much for your attention. Happy to answer any questions.  We have about three and a half minutes left for questions. And please come up to the microphone and state your name when you're asking.  Okay, I have a question. Do you keep your TEGs at bedside? How are you able to get this done so quickly? I know at some centers that they, you know, it has to be sent off and it  takes a little while. Yeah, that's a great question. So TEG can be done as a point of care  assay. At our institution, they actually go to the lab. But our lab is located very close to  where the OR, or most of these cases are done, you know, at bedside of the patient on ECMO. So  we don't have to transport the patient, but the lab is close. And we also have software on all  the computers that can show us the tracing developing in real time. So we don't have to wait on something to pop up in the EMR. One question. Has this analysis resulted in any  change in your practice? No. Our protocol remains the same. But I guess it's just shown us that  maybe we need to reevaluate the tools that we use to monitor this. And so hence trying to design a  prospective study to look at some different tests and things.  All right. Okay. Thanks, Dr. Snyder.  OK. All right. OK. Our next presenter, we'd like to invite Dr. Nathan Gold from Cable Huntington Hospital. He'll be presenting on outcomes from the PITCH study,  four-factor PCC and intracranial 10A inhibitor coagulopathy and hemorrhages. Thank you for the introduction. Is it pulled up here?  All right, thank you for the introduction. I was the primary investigator for the study we conducted at TGH known as the PITCH study, four-factor PCC  and intracranial 10A inhibitor coagulopathy hemorrhages. None of my co-investigators nor myself have any relative disclosures to report.  There are four oral factor 10A inhibitors currently approved by the FDA, the first of which being rivaroxaban in 2011. And I just have some of the general information  about these drugs on this slide. But due to time constraints, we will not go over every medication in detail. Apixaban later came out in December of 2012.  And this was followed subsequently by adoxaban in 2015. And lastly, the development of atrixaban in 2017, which is only FDA approved currently for VTE prophylaxis.  The direct factor 10A inhibitors are effective at achieving anticoagulation as they inhibit factor 10A. This is effective because both the extrinsic  and intrinsic arms of the coagulation cascade, they both merge on this factor 10A. And inhibition of one factor 10A molecule results in 1,000 less prothrombin molecules generated.  Therefore, we get much less clotting in the clotting cascade. So these drugs are very effective for that purpose. And as you can see with the oral anticoagulants,  the prescribing trends as represented here by the Medicare Part D population, is that overall warfarin has seen a significant decrease  in utilization in this time period from 2013 to 2017. While the DOACs, including the factor 10A inhibitors, apixaban and rivaroxaban have increased in utilization.  And this same trend has been seen in other populations as well. We note that these drugs are not without their complications in that major bleeding as well  as intracranial bleeding exclusively is commonplace with these medications occurring in up to 3.6% of patients with rivaroxaban for major annual bleeding.  And this was in the randomized controlled trials. And intracranial bleeding being the most common with warfarin with all of the DOACs having less incidence of intracranial bleeding.  Nevertheless, it is still a concern and is something we as clinicians should be familiar with and we should be ready to approach in the treatment when needed.  The factor 10A inhibitors cause intracranial hemorrhage at various sites, mostly subdural and subarachnoid sites. And this may be due in part due to trauma  as these traumatic bleeds commonly occur at these sites. Intra-parenchymal as well as intraventricular and epidural bleeds occur as well. The hematoma volume is significantly less  than what is associated with warfarin. And subsequently, the mortality in hospital in DOAC-related bleeds is also less as compared to warfarin. Things like the modified Rankin score  and the NIH stroke scale are also usually more favorable with DOAC-related ICH as compared to warfarin. Prothrombin complex concentrates were originally developed  in the 70s and 80s as a response to hemophilia B to provide patients with factor 9. But these drugs primarily are used to treat bleeding and reverse anticoagulation today  as they contain factors 2, 7, 9, and 10, as well as various anticoagulants. The various products available include 3 and 4-factor PCC products.  And this is based on the concentrations of factor 7 available in the products. And just for completeness sake, there is also an activated PCC product which contains factor 7A.  The prothrombin complex concentrates increase the concentration of non-activated spotting factors which then activate at the site of hemorrhage. It is this mechanism that is thought  to cause their efficacy in DOAC-related bleeds. Because they activate at the site of hemorrhage, they then increase prothrombinase production.  And then that results in thrombin generation. They do have no effect on the anti-10A levels, however. The duration of action depends largely on the levels  and the factor concentrations in the blood. And as those factors start to decrease around 12 to 24 hours, the pharmacologic effects of 4-factor PCCs will wane.  The risk of thromboembolism, however, occurs due to the accumulation of factors 2 and factors 10 as these two factors have a significantly longer half-life  as compared to the other factors within PCC. And as we are all familiar, there have been several recent developments within the field of anticoagulation reversal.  There's been a novel reversal agent known as, formerly as N-dexon alpha, and now coagulation factor 10A recombinant inactivated ZHZO. This was approved in May of 2018.  And after the results of the ANEXA-4 trial. And in the future, we will have results as this is compared to usual care in a study conducted by the drug manufacturer.  There have also been several guideline and consensus statements produced with varying recommendations, but due to time restraints, I will not list all of these for you.  Most of the guidelines do say if you have N-dexon alpha available, that that would be the drug to use, preferring a specific agent as to a nonspecific agent  such as the 4-factor PCC products. There has been a lot of research on PCC and factor 10A associated ICH. This research began in animal models  in which 4-factor PCC was found to reduce blood loss, reduce hematoma volume, and reduce time to hemostasis. Carried forth into healthy subjects who received factor 10A inhibitors,  it was found that 4-factor PCC reverses some of those anticoagulation measures, such as prothrombin time and endogenous thrombin potential. And then in case reports,  when physicians started to use this medication more commonly, 4-factor 10A associated life-threatening bleeds and ICH, it was found that these patients  achieved successful hemostasis with normalization of some of their coagulation parameters. And this has led to an explosion of observational studies conducted in which the majority  of which patients have achieved successful hemostasis with low rates of thrombosis and in-hospital mortality.  Thus, we conducted our own study at Tampa General Hospital to evaluate the efficacy and safety of a high dose 4-factor PCC regimen, which is 50 units per kilo  in patients with factor 10A associated ICH. This was a retrospective observational single center study from 2016 to 2018 in adults  who had received factor 10A inhibitors prior to admission and had an intracranial hemorrhage at any site. They'd also received 4-factor PCCs.  We defined our outcomes as radiographic outcomes as those who had ICH expansion on serial CT imaging within and after 24 hours. All of our scans were independently reviewed  by neurology physicians, both attendings and residents.  The clinical outcomes then included all calls in-hospital mortality and new onset thrombosis.  Radiographic ICH expansion, just further defining that, we define that as any objective expansion of ICH volume on serial CT scans early and then late,  being after 24 hours from initial imaging results. The new onset thrombosis was any thrombotic event that occurred after the administration of 4-factor PCC.  You notice that we have 31 patients in our study,  most of which were geriatric, as we had an average age of 73. And the primary factor 10A inhibitor used was apixaban for atrial fibrillation. The average dose per day for apixaban  was their standard regimen, 5BID, being 10 milligrams a day, and rivaroxaban, 20 milligrams per day, although a few patients did receive varying doses.  The creatinine clearance was 55 on average, and three total patients had inappropriate factor 10A inhibitor dosing, and this was actually based on underdosing of the medication.  Concomitant antiplatelet use was common, occurring in almost half of our patients, and you can see there the hazblad, CHAZ2-VASC,  and some other parameters that we measured in this study. Patients also received other hemostatic agents, which we felt was necessary to collect, most of that being platelets,  as most of our patients were on antiplatelet therapy. So 16.1% of our patients received platelets in addition to 4-factor PCC. No patient in our study received TXA or desmopressin.  The ICH location was primarily of intra-parenchymal origin, although these sites were often mixed, as patients might have an intra-parenchymal  as well as a subdural or subarachnoid hemorrhage. The presence of cerebral edema and midline shift was common, as was neurosurgical intervention.  You see there the ICH score, NIHS stroke score, and then the Glasgow comma score at baseline.  Our primary outcome being radiographic ICH expansion occurred in 41.9% of patients, with early expansion in less than 24 hours occurring in 25.8% of patients,  and then late expansion after that first day of CT imaging was 16.1%. In-hospital mortality then occurred in 25.8% of our patients and new onset thrombosis in 6.5%.  We also looked at a decrease in the prothrombin time. This was not measurable in every patient,  but on average was decreased by 3.3.  In our conclusions were the high-dose four-factor PCC for either a pixaban or rivaroxaban-associated ICH was well-tolerated in most patients,  and a minority of patients experienced any degree of in-hospital radiographic ICH expansion. We found that new onset thrombosis was comparable  to studies which utilized lower PCC doses. We also found that the percentage of ICH expansions was probably increased as compared to some of our other studies  because we used a more conservative definition  and defining any degree of ICH expansion as a failure of hemostasis. Several patients also without ICH expansion went on to develop expansion beyond 24 hours.  And I feel that further research is needed on the long-term outcomes of factor XA-associated ICH in patients treated with four-factor PCC  as compared to the current FDA-approved treatment option. Thank you, and I'll take time for any questions. We're going to take questions now. We have four minutes.  Okay, I'll start. In light of the fact that there's another product available that's FDA-approved and dexanet, would you argue the case that in this patient population  that K-Centra should be used instead of dexanet? Yeah, so the question was, in light of our data, should four-factor PCC be preferred to indexa for this particular population?  I think that's going to be dependent on the results of the ongoing trial that's underway. As we have no comparative data, I don't think that you can say  that four-factor PCC would be superior. And I think we used a little bit different definition from what the indexa force trial used  and that they allowed up to 34% ICH expansion within 24 hours and that was considered effective hemostasis where we only allowed zero degree. You could have no ICH expansion  for that to be considered successful. So I think using the indexa for definitions as compared in a prospective trial, I think that'll be needed before we can determine that.  If you have indexa on formulary, the guidelines are going to recommend that you use that. Mike White from Detroit. It's a nice study, by the way.  You said you included trauma patients in your subgroup, in your groups? Yeah. Yeah. How did it break down, I mean, how many were trauma versus spontaneous? That's a good question.  So the question was how many of our patients were trauma-related hemorrhages versus spontaneous? There were only three patients who had traumas in our study  and they did have subdural, subarachnoid, and interparenchymal and had relatively larger bleeds as compared to some of the other patients.  Yeah, because that's what I was going to comment on, especially with the trauma patients. You might expect to have some progression in their hemorrhage and bleed after 24 hours,  especially depending on the mechanism. So some of that might be expected. It would be hard to, you know, be able to decide whether that was from your anticoagulation effects  versus the trauma. Yeah. Thank you. Mike Cloud, thanks. Thank you.  Okay, our next speaker is Dr. Drayton Hammond who's at Rush University Medical Center. And I think a lot of you may have participated in this study,  so I'm excited to hear the results in this one and also the one that Megan Reck's doing in a little bit. So this is pharmacist avoidance or reductions  in medication cost in critically ill patients, the Pharmacrit study. Drayton.  I'll try not to cough into this, sorry about that. So yeah, thank you for that introduction, Leslie. I'm getting over a cold as well, so we'll just, we'll push through, yeah.  So as mentioned, we had an incredibly large study team both on the initial planners as well as many sites. We had 85 hospitals, 223 ICU pharmacists who participated in this.  So thank you to everyone. If you're in this room, you know, thank you. If maybe you'll listen to this later, thank you as well for your contributions to this important work.  So I think we're all acutely aware that we see, you know, a multitude of ICU patients. You know, in the U.S. alone, a few years ago, there was  about one and a half million ICU patients that we encountered. And the cost of the care that we're providing to them totaled just about 1%  of the gross domestic product for the U.S. So we're looking at a lot of commas and zeros for the cost that we're providing for these patients. And as ICU pharmacists, you know,  we play many different roles, wear many different hats on the teams that provide care for these patients. One of those is obviously  to make sure patients are getting the absolute best care they can get. But on the flip side, it's ensuring that patients are only getting the care they actually truly  need and maybe reducing care that might be nonessential or might not, you know, be as strong as other options we can provide. Or just reducing other ways of patients getting care  that may cost money that's nonessential. So we have had shifts in roles. You know, it was a lot tougher to do this when you were in the basement or maybe in a decentralized role.  Whereas many of us are now at the bedside rounding, you know, pre-rounding with our residents and our physicians, rounding with them, providing care post-rounds.  Many institutions have care, you know, 18 to 24 hours out of the day. So we're at the bedside. We're providing this type of care for patients.  And that's led to many professional organizations actually endorsing pharmacists as central team members, which is a step in the right direction.  But we still have to make sure we actually have the pharmacists at the bedside. You know, our departments are hiring pharmacists  and positioning them such that we can provide this type of care that's probably incredibly beneficial. So because of that, there was many studies that were done.  You know, I think the earliest we found was in the early 90s and it had pharmacists who were, you know, just keeping track of ADs they were preventing or just actual drugs  that patients, you know, weren't getting, they would have otherwise gotten. So while incredibly beneficial, this was very narrow in scope. And over the years, you know,  these studies have become more expansive and looked at more types of interventions. But only one study that was conducted a couple years ago  used a framework that was systematically developed that tried to describe every type of activity, clinically related, that a pharmacist could do.  And that was just a single center study at one hospital setting. So while helpful and beneficial, it's maybe not necessarily enough  to move the needle for many institutions when they're trying to make decisions on how to deploy pharmacists. So that led to us kind of developing this study.  And we had two purposes. One was to just comprehensively classify the interventions that we're making. It's very epidemiological in nature.  And then the second one was to try and figure out, you know, using that systematically developed framework, you know, what's the cost avoidance that, you know,  we're generating as pharmacists that maybe would have not otherwise been done if we weren't available, you know, at the bedside  or in other ways providing care for these ICU patients. So this was a multi-centered prospect of observational study. US hospitals over about a five-and-a-half  to six-month period from August to January 2018, 2019. Pharmacists who were providing care to ICU patients, which was predominantly direct,  though many people were providing decentralized care, maybe on weekends or maybe based on their practice model. And other hospitals that were providing  that decentralized care to ICU patients. We asked, begged people to do at least 20 shifts. That wasn't a requirement.  And there were some people who did significantly more than that. But most people, you know, came in close to that 20 shifts. We had all these interventions.  Whether they were accepted or not, they were documented in REDCap. And then later, we only looked at those accepted interventions when determining cost avoidance from pharmacists.  And then we did have 38 categories and six sections, which we'll go over. So this comes from that established framework that was mentioned from the previous single-center study  that we feel like gives a lot of weight to the confidence we can have in these results for this study and then Dr. Erek's study that she'll mention in a few minutes.  Those categories will go in a little more detail as we look at the actual results, but you can see it's adverse or AD prevention, resource utilization,  individualization of patient care. You can also see the levels of evidence provided on that far column. And then the cost avoidance in 2018 dollars, which have,  you know, been annualized based on whatever year the studies were conducted in and their results were published from. Prophylaxis, hands-on care, and then administrative  and supportive tasks as well. So we did some basic statistics initially. It was very descriptive in nature, just to, you know,  add up all the numbers, get them into particular categories. And then we also did a sensitivity analysis looking at those five categories that had the highest level  of evidence studies, whether controlled or randomized that kind of led to that level of evidence. And then we did break it out to be per shift  and then assuming people working 48 weeks in a year, allowing for some vacation to come to conferences like this. And then just five days per week.  So that comes out to 240 shifts per year, so we could have a per annum basis for this cost avoidance as well. And then based on average salaries,  based on published data, we tried to break this down to have a benefit-cost ratio. So these were our 223 pharmacists at 85 centers. In total, they completed over 3,200 shifts,  which went to all the data you'll look at from here on out. Most of these pharmacists were in a medical or a surgical ICU, though many did cover more than one ICU, either, you know,  at the same time or potentially during the study period. So you'll see these percents do add up to greater than 100% for the ICU or decentralized coverage.  And then most institutions did not have an open ICU practice model, but did have rounding five to seven weeks. And then the average beds were 25 beds  with a fairly wide standard deviation. And then most pharmacists were providing about six hours of direct patient care, and then we were providing order  verification for about four hours out of their eight-hour shifts. You can see almost, you know, two-thirds, a little less than that, were on one rounding service,  though many people were providing care for multiple rounding services. And it was kind of a smattering of years of practice.  We were fortunate to have a lot of the junior practitioners, but we also had many mid-level and senior practitioners participating as well.  And almost 80% were board certified, whether that's BCCP or BCPS or some other certification. So now we're digging into the six different sections.  So what you'll see here is a column for the number accepted and the percent accepted out of total interventions made that would fit into the general category  or specific categories under that. And then you'll see the cost avoidance in dollars. For time reasons, we're going to probably focus on just those  that are bold for each section, but I'm happy to answer any questions or talk about anything specifically during that time. So we can see 98% of the interventions  for AD prevention were accepted, and that led to just under $6 million in cost avoidance. The bulk of this was from major AD preventions.  As we can imagine, these are things that are, these are preventing, you know, significant, you know, whether it's mortality or other care that would be provided  in a hospital if they were to have a major AD. That's why these numbers add up pretty quickly. When looking at resource utilization, you know, again, you know, a little under 98%  of these interventions were being accepted, which I guess I should have mentioned in comparison to previous studies, they've been between 50 and up to about 91, 92%.  So you'll see all these percents are higher than what's been previously published. Potentially based on relationships pharmacists have with their physicians or APP colleagues,  or maybe other factors that need to be investigated. So a little under 98% accepted, about $4.5 million in cost avoidance. The bulk of this is from managing hypertensive crises.  Part of that is just in the appropriate management, and then also in helping facilitate people getting off of expensive IV medications and either not going to ICUs,  or sorry, being in ICU, but, you know, being in ICU for a shorter duration of time, being able to transfer out, trying to reduce those healthcare costs in that manner.  98.3% of the interventions for individualization of patient care were accepted. This is where the bulk of the cost avoidance comes from, just over $10 million.  And this is across, you know, almost every category of intervention within this large section. So this is, you know, what is kind of a bread and butter  of pharmacists, making sure patients are getting the right drug, at the right dose, for the right duration, types of things.  Prophylaxis, though it's not the sexiest topic in the world, is something that we know many of our patients do need, and we try and ensure that they get that appropriate agent  if they do need it, and they're on the right agent if they need a particular agent. So this was, you know, almost 100% accepted,  and just a little under $1.5 million in cost avoidance. The bulk of this is from initiation of Bt prophylaxis, you know, making sure people are at much lower risk  of developing these costly complications.  So hands-on care, I think Megan will mention that this is a lot more prevalent in the ED pharmacists, but we still are doing this as ICU pharmacists,  providing care to critically ill patients as well. A little under 2,000 interventions, and the bulk of these are being accepted also. The cost avoidance came in at just  under $1.5 million. And it's mostly in that bedside monitoring, you know, helping our physician or APP colleagues provide the best care  at the bedside, you know, in that second-to-second, minute-to-minute type of care, as well as emergency code blue participation, helping ensure we're following our guidelines,  or when we're going off guidelines, they're in a manner that is most beneficial for that individual patient in front of us. And then for our last section,  administrative and supportive tasks, again, you know, 99% of these are being accepted, and, you know, under $1 million, but these are still incredibly important tasks,  particularly when it comes to just making sure the team knows that we're a resource for anything that they need. Drug information consults are, you know, again,  not something that, you know, is necessarily going to come out on a big cost-avoidance value, but, you know, some building those relationships probably led  to a lot of these being accepted, because they know they can trust us to be available for anything that they need.  So in the main analysis, we did see that it was just under 60,000 interventions, with 99.4 of those being accepted. So very high number and very high percent acceptance,  which is incredibly encouraging to see. Total cost-avoidance came in at just under $24 million for all these pharmacists. When you look at that per intervention, that's a little  over $400 per intervention, about $859 per patient each day, and then per shift, you're looking at about $7,200 for an ICU pharmacist providing care for patients.  When looking at the annualized cost-avoidance, remember that's 48 weeks, so five shifts per week, comes in at about $1.7 million. Based on that salary plus benefits,  those mentioned earlier, that's about a 9.4 to 1 ratio of benefit to cost. Now, when we do look at those particular interventions that are in those five categories, we're seeing,  you know, 9,400 interventions, which was about one-sixth of the total interventions, and it's a little under $8 million for that cost-avoidance.  You know, interventions, $850 per intervention, $289 per patient day, and about $2,500 per ICU shift. Obviously, you're going to have a lower benefit to cost ratio  when you're only looking at a sixth of your interventions, but it still came out at, you know, 3.17 per one. So, our final conclusions that we can state at this time.  One, this is just our first, you know, study of this type, this multi-center and prospective, and uses a framework that's been well-established,  systematically developed to quantify pharmacist interventions. It appears that these pharmacists are, you know, improving, you know, leading to significant reductions  of cost-avoidance within the care of critically ill patients, and most of this cost-avoidance did come from interventions that prevented ADs or individualized patient care.  And our benefit to cost ratio is probably somewhere between 3.1 and 9.4 to 1. At this time, I'm happy to take any questions. We have time for just one question, please.  Thanks for including us in this straight, and quick question for you. Were you able to determine from the data that you collected where the most effective pharmacists were?  Was it someone who covered two services, who does a lot of order verification, or was that hard to determine? That's a fantastic question.  We will probably have those results next year at this meeting. We're currently evaluating it. We have some encouraging data. What we're kind of saying is it's probably good  to have a pharmacist who is dedicated to a service, rather than being stretched in many different ways. But that's preliminary results, so more to come, hopefully, in 12 months.  We have time made for one more, actually. So if you want to come back up. Run back up here. Sure. I'm Kirsten, one of the Mayo Medical ICU pharmacists.  So the question that we're all struggling with right now is metrics, right? How do we justify to the C-suite that we should exist? And this seems pretty convincing to me,  but how do you think we could take this study and translate it into a meaningful metric that we can advocate to executives for why they should continue to expand our services?  Yeah. So that's literally the million-dollar question, I think. So we've provided these data to all the pharmacists that participated at all of their sites.  We're hearing just word of mouth that some hospitals are already getting FTEs approved. So we do plan to reach out next year to every site  that participated and figure out what their efforts were in using these data, who was successful, who was not, what feedback they got, so we can collate, disseminate  to everybody, and try and do the best we can to have more of us that are present. Yeah. So it's a step in the right direction. It's not the answer, but hopefully it leads toward the  answer in a couple years. Thank you. Thank you for participating also. Yeah. Thank you, Dr. Hayes. Thank you. Okay. Our next presenter is Dr. Taryn Manzarella.  She's from Norton Children's Hospital. She'll be presenting her research on anoxaparin dose requirement in pediatric patients with chylothorax after cardiac surgery. Thank you.  Thank you for that introduction. So we're going to kind of switch gears here to the pediatric population. So I hope I don't lose too many of you in that.  So I'm going to talk about the anoxaparin dose requirements in pediatric patients with chylothorax after cardiac surgery. So to start off, I'm going to review some background  and the clinical complications resulting from chylothorax after surgery for congenital heart disease. And then we're going to jump  into the study comparing anoxaparin dosing and monitoring in patients with congenital heart disease with and without a chylothorax. And then I'm going to talk about how we kind  of developed a recommended dosing strategy for patients with chylothorax requiring treatment with anoxaparin.  So chylothorax is a postoperative complication associated with congenital heart surgery that results in the abnormal diversion of chyl  from the lymphatic system into the pleural space. And the diagnosis is primarily based on the appearance of chyl in pleural fluid. And chyl is a milky fluid composed primarily  of triglycerides, protein, electrolytes, and lymphocytes. So often the first and most obvious sign of chylothorax is respiratory distress. However, large losses of nutrients  and immune cells put patients at risk for nutritional and immunodeficiencies as well as hematologic and metabolic disturbances. So antithrombin is an important natural inhibitor  of the coagulation cascade. And it's well known that deficiencies in antithrombin lead to a significant increase in the risk of thrombosis.  So this study by Burnett and Budiker and colleagues in 2006 looked at plasma and pleural effusion samples of 10 children with chylothorax and five children without.  And they found that there was a significant increase in AT3 activity in chylosamples compared to non-chylosamples. And a significant decrease in plasma AT3 activity  in children with a chylothorax. And seven of the 10 children in this study with a chylothorax actually went on to develop a thrombosis compared to none of the children without.  So anoxaparin, also known as low molecular weight heparin, is an anticoagulant medication commonly used to treat and prevent thrombosis in congenital heart disease patients.  It exhibits its main anticoagulant effect by binding to and accelerating the activity of antithrombin to form a complex that irreversibly inactivates  Factor Xa. And it has a lot less activity on Factor IIa than its counterpart on fractionated heparin due to its low molecular weight.  Therefore, the mechanism of anoxaparin is largely dependent on its interaction with antithrombin. So the purpose of our study and really the question that we sought to answer was if children with kylothorax are at risk  of having lower levels of circulating antithrombin, do they require larger doses of anoxaparin to achieve the same level  of therapeutic anticoagulation as children without a kylothorax? Our primary outcome was looking at the anoxaparin dose  at the time of the initial therapeutic antitin A level in patients with and without a kylothorax. And secondary outcomes included the time it took us  to achieve a therapeutic antitin A as well as the AT3 level. And this was plasma AT3 levels at the time of the first therapeutic antitin A.  This was a retrospective chart review over a six-year timeframe between October 2012 and 2018. We matched patients with and without a kylothorax based on age.  And you can see the age groups we used to the right. And as you can see, we matched patients really closely in terms of age, particularly in the neonatal age group,  since we know this group is already predisposed to having low levels of antithrombin. So patients were included in our study if they were less than or equal  to 18 years of age, they had a diagnosis of congenital heart disease and received at least one surgical repair. They received treatment dose anoxaparin  and had at least one therapeutic antitin A recorded. We excluded patients with a diagnosis of PLE, plastic bronchitis,  as well as a diagnosis of congenital AT3 deficiency, and also patients with renal insufficiency requiring dose adjustment of anoxaparin. So during the study timeframe,  we actually were using initial dose recommendations based on the chest guidelines, as you see here. And at our institution, we follow standard monitoring recommendations  for children of drawing antitin A levels from four to six hours after administration of anoxaparin and shooting for a range of .5 to one units per mL.  We included 48 patients in our study total, 24 in each cohort. And patients in our study were an average of six months of age and five kilograms  in each group, and most patients in our study were infants. There were no significant differences between groups in terms of age, gender, or weight.  We also looked at the stat category of the operative procedure performed, which if you're not familiar with that, it's just a scoring system to analyze the risk  of mortality associated with each repair, with five being the highest. And interestingly, we found that patients without a chylothorax were more likely  to have had a higher risk procedure done. We analyzed our patient population in two separate groups based on initial starting doses of anoxaparin. So the anoxaparin dose required  to achieve a therapeutic antitin A was significantly higher in the chylothorax group. The chylothorax group required an average of 1.93 milligrams per kilo per dose compared  with 1.56 milligrams per kilo per dose. It also took significantly longer to achieve a therapeutic antitin A in the group with a chylothorax.  And I did want to draw your attention here to the range. In some cases, it took us up to 11 days to achieve a therapeutic regimen in patients  that had a chylothorax, whereas in the no chylothorax group, the maximum amount of time it took us to achieve a therapeutic antitin A was two days.  There was no difference in plasma AT3 levels. However, as you can see, we're missing a lot of data here. And at our institution, it's not a routine practice to draw AT3 levels  when patients are on anoxaparin. So we think that's why in that case. So looking at the results for patients greater than or equal to two months of age,  we did not find a significant difference in the anoxaparin dose time to therapeutic antitin A or plasma AT3 levels in this age group.  And although there was not a significant difference between groups in terms of the time it took us  to achieve a therapeutic antitin A, you can see again that in the chylothorax group, it took us over two weeks in one patient to achieve that therapeutic level compared  to in the no chylothorax group where the maximum amount of time it took us was three days.  So in conclusion, so patients less than two months of age with congenital heart disease and chylothorax may require higher initial starting doses of anoxaparin  to achieve a therapeutic antitin A. And using the typically recommended starting doses for anoxaparin for patients  with chylothorax may lead to a delay in achieving therapeutic levels of anticoagulation with anoxaparin.  So based on the results of our study, we recommend a 10 to 30% increase in recommended starting doses of anoxaparin. And the reason why we say 10 to 30% is it really depends  on what your initial starting doses of anoxaparin are at your institution. If you are still using the CHESS guidelines, then I would probably recommend to go  on the higher end of that range.  So I just wanted to quickly share with you our updated initial dosing strategy at Norton Children's Hospital. And as I kind of alluded to on the previous slide,  a lot of centers are already using higher initial starting doses of anoxaparin than what's recommended in current guidelines.  Particularly in the neonatal and preterm age group due to recent data that this age group probably requires larger doses of anoxaparin to achieve those therapeutic levels.  So we've adjusted our dosing strategy to reflect that. And then based on the results of our study, we recommend considering a 15% increase  in the initial anoxaparin dose, especially for the less than two-month age group. And really the biggest factors we recommend considering is the patient's bleeding risk  at the time of the initiation of anoxaparin, as well as the volume of fluid draining from the chylosefusion if you have that information available.  So I'd like to thank you, and I'll take any questions at this time.  Thank you.  in your sample, one day versus multiple days that it took for you to reach therapeutic. Any theories as to why there's so much variability within that population?  I think it really, and this is just speculative, but I think it really has to do with the amount of drainage they're having from the chylis effusion, which would make sense.  We didn't quantify any of that in the study that we looked at, but that's why in our dosing strategy, we kind of give guidance to pharmacists as to look  at that prior to making your adjustments. And if they're receiving, or if they're having a lot of drainage, you probably want to bump the dose up maybe even a little more than 15%.  But also just probably more frequent monitoring in this population as well. Go ahead. Just one question, and if you mentioned it, I'm sorry,  I must have missed it, but are you checking after the first or the second dose? Are you checking your antitumor level? So we check at least after the second dose, and it's anywhere  from the second to after the fourth dose. We try to time it with lab draws. And that's why your, some patients took longer, right?  Because if you're giving them four doses before, that's. Yeah, typically we're only. Two days before you check the level. We try to do it after the second dose.  In some patients, we'll do it up to the fourth dose because, just because of lab timing and that stuff. But I'd say like over 80% of our patients we check after the second dose.  Yeah. As the patient had the output from their chylothorax decreases, do you go back down with the dose? I would just recommend checking antitumor level at that point.  Not just empirically increasing the dose. Okay. No additional questions. Thank you very much, Dr. Mansfield. Thank you. Okay. We have part two of the study  that Drayton covered just a little bit ago. So we have Dr. Megan Reck from Loyola in Chicago talking about pharmacist avoidance or reductions of medication costs  in emergently ill patients, the FARM-EM study. Dr. Reck. Thank you so much for that introduction. And thank you to everyone who participated  in this massive undertaking by our CPP section. I'd like to acknowledge our co-investigators. This study was undertaken by the CPP or Clinical Pharmacy  and Pharmacology section and was endorsed by the Discovery Channel, or Discovery Channel. Discovery Network. And I'd like to greatly thank the 88 emergency medicine  pharmacists across the U.S. that participated in this study. So this is where it gets really familiar. So hopefully I can kind of breeze through the background and methods.  So there are over 37 million annual ED visits. And that number is only increasing, which further drives the demand for emergency medicine pharmacists.  As this has evolved over the years, so has the role of the emergency medicine pharmacists. Kind of from that dispensing and checking role to being hands  on in the trenches at the bedside with the physicians and nurses in the ED. And while we feel appreciated locally, and everybody wants more emergency medicine pharmacists,  there hasn't been great data to quantify the benefit that we add, and so those data are limited. So previous studies have primarily focused  on adverse drug event prevention and avoidance or reduction in medication use. There's been really heterogeneous structure in terms of how cost avoidance is reported  and how interventions are categorized. Though annual cost avoidance has been projected from about 1.7 to $3 million annually from emergency medicine services.  As Dr. Hammond alluded to, there's one 12-month MICU study that found an annual cost avoidance estimate of $3 million and a benefit to cost ratio of about 25 to 1.  But we know that the MICU is a very different setting from emergency medicine. And though that was based on a pretty rigorous framework  of interventions, we have different patient populations, we have different rounding structures, and the pharmacist at the bedside  and the relationship may be different with the team. So we need emergency medicine-specific interventions. So again, our study was part of the PharmCRIT study.  We were the other half, and we were in the emergency department with the same study goals and objectives. So we comprehensively classified interventions performed  by emergency medicine pharmacists and then assigned cost avoidance associated with those accepted interventions. So again, multicenter prospective observational study  across the U.S. in a six-month time period. We encouraged 20 shifts of participation, and all accepted interventions were categorized with cost avoidance.  So we did collect the non-accepted interventions as well. We used a REDCap database tool for this so that people could kind of seamlessly do that throughout their shift  and easily quantify those interventions. And again, this is where it's going to look very familiar. Here is our cost avoidance framework.  I'm not going to go into great detail with this as you've already seen it, but we have, of course, our adverse drug event prevention, resource utilization,  individualization of patient care, prophylaxis, which we don't do a whole lot of in the emergency department, hands-on care, which is sort of our bread and butter interventions  in the ED, and then finally administrative and supportive tasks. So in terms of our planned methods and statistical analysis, we wanted to quantify the types  of interventions in the ED and then the associated cost avoidance associated with those interventions. We did the same sensitivity analysis  of the top five interventions that had level of evidence that was either Category 1 or 2, and then we descriptively described our data and annualized cost avoidance as well.  We performed a benefit to cost ratio analysis as well. So for our results, again, we had 88 pharmacists, emergency medicine pharmacists at 49 centers across the country  that completed 917 shifts, so a huge undertaking by pharmacists across the country. For ED visits, we had a mean of 75,000. EM pharmacists worked with a number  of different practitioners, but predominantly not surprising emergency medicine attendings. Note that most centers were academic,  though we did have a fair number from community teaching and non-teaching community hospitals. And then for shift length, a majority were eight hours,  but some were also 10 and 12-hour shifts. So for shifts worked, we were very pleased to see that about on average 17 shifts were logged per EM pharmacist.  During that time, about 8.3 hours of contact, direct patient care to contact. Note that that's longer than eight hours because a lot of people did work 10 and 12-hour shifts,  and they did prospective order verification for almost six hours of that shift. Not surprising, most EM pharmacists are not rounding with a team, though maybe surprisingly  about 18% were rounding in some capacity, perhaps covering another service peripherally or some kind of step-down unit or clinical decision unit.  The number of patients cared for in a team or in a given shift, I know this seems like a lot, 70 patients, but we're not intervening on all of these patients.  This is just the denominator of the total number of patients that you saw in a given shift. And then a pretty wide distribution in terms of years  and practice, most either one to three years or three to six years, and a majority board certified. So getting into our interventions, this was one  of the more high-cost categories, over $2 million in cost avoidance and roughly 1,600 ADE prevention interventions, a majority of the cost coming  from prevention of a major ADE event. For resource utilization, this was fairly, in terms of our interventions, we didn't do as many of these.  Note that we don't really see hits, so we're not going to be preventing that in the ED. We don't really convert from IV to PO, so we're not doing a whole lot of that.  So this is one of the lower for EM pharmacists in terms of number of accepted interventions and cost avoidance. For individualization of patient care,  this is the highest number in terms of accepted interventions, and note that 98% of these were accepted. A majority of these, about a third coming  from dose adjustments, not surprising. These patients were not receiving continuous renal replacement therapy in the ED. And then a number of antimicrobial therapy,  stewardship and initiation, and non-antimicrobials initiated. Prophylaxis, we had 24 interventions. We don't do a lot of this as emergency medicine pharmacists.  That's all I'll say about this section. Hands-on care, here's where we do a lot. This is the second highest in terms of number of interventions  and the highest category in terms of cost. So not surprising, we're at the bedside doing an awful lot of this, participating in bedside monitoring,  code coverage, seeing septic patients, seeing stroke patients, so a number of these interventions. And then finally, administrative and supportive tasks. A moderate amount of these,  mostly coming from drug information. So in terms of total data, we had almost 14,000 interventions, totaling about $7.5 million in cost avoidance.  And when we average that out per intervention, that's about $540, roughly almost $900 per patient each day and about $8,200 per shift. Annualizing this, it's almost $2 million  in cost avoidance per emergency medicine pharmacist. And our benefit to cost ratio was 10.63 to 1. Now, looking at our sensitivity analysis, not surprisingly,  we don't have a lot of these interventions because the highest quality of interventions are on things like IV to PO conversion and converting antihypertensives  in the setting of hypertensive crisis to PO meds. So we're not doing a lot of that in the ED. It's also two categories pertaining to VTE prophylaxis,  which we're not really handling. And finally, one pertaining to antimicrobial initiation, which we do a lot of, but also streamlining.  And given that we're dealing with empiric data, we're not doing a lot of that in the emergency department. So what this tells me is that we really need more research  in the ED to kind of flesh out some of these areas where we could be seeing a benefit from cost avoidance and interventions.  So a lot less here, again, but still about a million dollars in cost avoidance from our pharmacists. A lot lower average cost avoidance,  603 per intervention, $112 per patient each day, and about $1,000 per shift. And annualized, this is about $250,000, and our benefit to cost is still 1.35.  So again, we don't even do a lot of these types of interventions, but we're still seeing a positive return on EM pharmacist interventions.  So in conclusion, this is the first multicenter prospective study to comprehensively classify interventions performed by an emergency medicine pharmacist  and the associated cost avoidance with those interventions. This resulted in a significant amount of cost avoidance from pharmacist interventions, and a significant portion  of these were due to hands-on care, prevention of adverse drug events, and individualization of patient care. Our benefit to cost ratio ranges somewhere between 1.35  at the worst end, up to 10.63 to 1 per pharmacist. That concludes my talk. I'm happy to take any questions. Thank you. Thank you, that's excellent work on both of your parts,  and really such strong information to help support overall the profession. So really, kudos to you. I do have a couple of questions you may not be able  to answer them, because when you come back and try to use this data, which both of you are very interested in, trying to extrapolate how this will actually make a difference.  For you to be able to collect this information and be able to use it in the way that you have, what was the time? Do you have a sense of the time dedicated by those  who participated with what it took to actually collect this? Because one of the questions may ultimately be, okay, this was great in a study scenario, and you did this  for a period of time over six months. But does that really translate to care on my individual site, such that an administrator would be interested in this data,  as what is the goal, right? This is the first publication. Now, how does that actually translate on site? So do you have a sense of, or did you collect,  what it actually took the participants, the time it took to collect and enter this information in? Sure. Yeah, that's a great question. So if I'm summarizing appropriately,  the question is how much time did it take each investigator out of their day in order to collect this type of data? So there are 20, you did 20 shifts in total.  Yes. So we set up a REDCap database that we tried to make as seamless as possible. So for one patient, you could log hundreds of interventions, potentially.  So we broke it down into the six categories, and then you selected each category. So there was a learning curve in the beginning to remember  which interventions fell into which category. But, you know, the broad themes sort of made sense. So we got it down to taking less than 30 seconds per patient  to document each patient that we touched in a given day. So building that REDCap must have been, yeah. That was my first REDCap database that I ever built,  and by far the most painful, yes. Matt, you extrapolated the costs associated with these interventions. You had to do all of that legwork.  Exactly. We laid the groundwork with a scoping review of all, search for all interventions that could be performed by an ICU or an ED pharmacist. And so that's why some  of the interventions categories may seem a bit random, like anti-venom stewardship. It's because there's specific cost avoidance associated with that intervention. Great. Thank you.  Thank you.  Mike Way from Detroit. I just had a question. Does the REDCap database not include like participation like trauma codes and things like that for a pharmacist?  That's a great question, and that's somewhere that we'd like to take this next for. We use them in our place for attending, especially the level one trauma codes,  and they're really indispensable. Right. So the reason that we don't have a category specifically for level one trauma or level two trauma response is because there was,  at the time we were doing the scoping review there was no data to capture the cost avoidance associated with pharmacist intervention.  So in the bedside monitoring section, bedside care is the top intervention for emergency medicine pharmacists. And so what I suspect is that a lot  of those are trauma responses at the bedside.  So what we'd like to do as a future step potentially is go back and look at this just in trauma and see if we can capture the cost avoidance of that.  I think that would be a really interesting study and actually contribute to. So I really encourage you to do that. Nice job. Great. Thank you. Thank you, guys.  Okay. Excellent. Our next presenter is Dr. Allison Boma.  She's from Henry Ford Hospital. She's going to present her research on surgical intensive care unit pain management in the era of IV opioid shortages.  Thank you very much for that introduction. And thank you all for being here today. Before I jump into my study, I just want to let you know that myself and none  of the co-investigators have any potential conflict of interest to disclose for this presentation.  As I'm sure most of us know, our critically ill patients experience pain. We've had studies that have shown greater than 75% of our patients in ICUs have some form  of pain while they're in the ICU.  And unfortunately, a lot of this pain is from things that we are doing to the patients, such as procedures, placing lines, and even for our mechanically ventilated patients,  the fact that they have an ET tube can cause pain and discomfort all on its own. And we have a study in our cardiac surgical patients  that actually showed greater than 50% of patients once they leave the ICU remember having some form of moderate to severe pain. And there are negative physiologic  and psychological consequences that are associated with pain.  But unfortunately, in mechanically ventilated patients, it is very difficult for us to be able to evaluate if they are in pain. So at Henry Ford Hospital, we use the CPOT score,  which I have here on the slide for you. This has four different indicators that we look at, such as facial expression, body movements,  muscle tension, and because I'm looking specifically at mechanically ventilated patients, compliance with that ventilator. Our goal for a CPOT is zero to two.  So that means that if a patient has a CPOT of greater than two, so three or above, we believe that they are in pain.  And the treatment of pain from national pain agitation and delirium guidelines, as well as our guidelines at Henry Ford Hospital is  for analgesia first sedation starting with fentanyl. But I'm sure we all are very acutely aware that manufacturing delays and demand actually cause fentanyl shortages,  which brings me to the purpose of my study.  We looked to compare treatment of pain in our mechanically ventilated patients in the wake of continuous IV infusion fentanyl shortages.  This was a multi-site retrospective quasi- experimental study where we looked during the shortage, which was from April of 2018 to September of 2018 in this study.  We also evaluated one year prior to that shortage as a comparator group for our patients.  Henry Ford Health System has five sites. I only included four sites in this study due to the fact  that these were the four sites that had the same electronic medical record at this time. I also have the trauma levels for all of these sites,  as well as the number of surgical ICU beds that each site has, because this will be important when we talk about my sample size calculation.  Subjects were included if they were admitted to an intensive care unit post-procedure  or for a trauma during the pre- or post-dates. I also only included their first admission to an ICU.  Patients were included if they were mechanically ventilated for greater than or equal to 24 hours, and only first mechanical ventilation was recorded. So if a patient was extubated  and re-intubated later, they were not included.  The second mechanical ventilation was not included.  As well as patients needed to have administration of continuous IV infusion fentanyl during the pre-shortage group. Exclusion criteria was for patients who are less  than 18 years of age, if they had a neural or cardiac procedure,  administration of continuous IV infusion fentanyl during the shortage, because that's what I'm trying to evaluate, less than an average of four CPOT scores per day during  mechanical ventilation, transfer from an outside hospital or another ICU, and if the patient was excluded from our pain, agitation, and delirium guidelines,  such as comfort hospice care, pharmacologically paralyzed, active withdrawal from alcohol, and ability to verbalize a pain score.  My primary endpoint was percentage of CPOT scores within target goal, which we defined as that CPOT of less than or equal to two during the first seven days  of mechanical ventilation, or until extubation, whichever one came first.  For secondary endpoints, I had percentage of Richmond agitation sedation scale assessments within goal, time to CPOT goal, morphine milligram equivalents,  confusion assessment method for the ICU, the number of pain agitation and delirium medications at CPOT goal, ventilator days, ICU length of stay,  and I also included a non-equivalent dependent variable of chlorhexidine use.  For statistical analysis, descriptive data was analyzed using central tendency or variability, nominal, chi-squared, or Mann-Whitney U for our continuous data.  Now my sample size calculation, which I broke down for you here.  I did my sample size calculation using an alpha of 0.05 and a beta of 0.2, as well as an effect size of 15% from previous recorded studies looking at this patient population.  This gave me a total number of patients of 164, which broken up into the two groups is 82 per group.  Now this is why it's important how many surgical ICU beds we had. I split up the number of patients between each of the sites based on the percentage  of surgical ICU beds those sites had compared to the total surgical ICU beds we have at Henry Ford Health System. And that led us to have 49% of our patient population  at our level one trauma center.  Patient characteristics were not significantly different between the two groups with a few exceptions. Most of our patients were male, and most of our patients were Caucasian.  For one group that did have a difference, it was the other in the race category, which typically ended up being patients who answered I don't know or maybe a patient  who came in and we couldn't verify what their race was when they came in. We had more patients who answered I don't know in the pre-shortage group than the during shortage group.  Also for procedure types, they were not very different between the two groups. Most of our patients had an intra-abdominal procedure, but we did have more thoracic procedures  in our during shortage group than our pre-shortage group.  For primary outcome, which was CPOT scores at goal, I have on our y-axis the percentage of CPOT scores at goal. And a CPOT at goal of less than or equal to two is  in the blue bar, and then the black bar is a CPOT not at goal.  We didn't have a statistically significant difference in these two groups, as you can see with our p-value here of 0.365, so we don't believe that we had differences  in our pain in these patients.  For secondary outcomes, our RAS percent at goal was not statistically significantly different between the two groups. But we did have a statistically significant decrease in daily morphine milligram equivalents.  240 morphine milligram equivalents in the pre-shortage group and only 37.9 in our during shortage group. The number of pain agitation and delirium medications were also the same  in the two groups with a median of 2. And then CAM ICU scores at day 1 and day 3 were different in our patient populations.  But we did have a significant amount more CAM ICU evaluations in our pre-shortage group than we did during or during shortage group. So the actual number of patients  who were CAM ICU positive was not increased. However, the percentage was increased. Also, my non-equivalent dependent variable  of chlorhexidine use was not statistically significantly different in the two groups. Now this brings me to probably the part that's the most exciting for us to talk about,  the actual medications themselves. So on the y-axis here, I have patients who were receiving the medications at CPOC goal, so the number of patients.  And then I have all of the pain agitation and delirium medications that I included on our x-axis. IV opioid use was statistically significantly decreased  in our during shortage group, which makes sense because all of my patients who were in the pre-shortage group had to have continuous IV infusion fentanyl.  And then all of our pain medications that we have are analgesic medications, had an increase in the during shortage group with the exception of Tylenol.  All of these were not statistically significant, significantly different though with the exception of dexmedetomidine. We did have much more dexmedetomidine use  in our during shortage group. We also had a decrease in benzodiazepine use, which we were kind of expecting because we wanted people to avoid benzodiazepines at this time.  There are some limitations that I want to bring up with this study. Obviously, this is a retrospective study, so I had to rely a lot on what was documented in the chart.  We also have the potential for overflow patients in the surgical ICU, but I made sure that every patient who was included in this study had either trauma or some kind of procedure.  With this type of study, selection bias and misclassification bias is always a possibility. However, I used the same data collection form for all of our patients.  There was a lack of a control group. However, we used the pre-shortage group to try and combat this problem and also included  that non-equivalent dependent variable, so that way we knew that standard of change hadn't, standard of care hadn't changed that much. Also, potential for external validity.  Almost 50% of my patients were at a level one trauma center, which could make it difficult for us to extrapolate out to other patient populations.  So, in conclusion, we had no significant difference in percentage of CPOT or RAS at goal. We did have less morphine milligram equivalents during the shortage, so just  because we weren't using continuous IV and fentanyl and we weren't increasing our morphine milligram equivalents, that didn't mean that our patients experienced any more  pain or agitation. And then patients received around two pain agitation and delirium medications, so we might even have more room for improvement with multimodal pain management  in these patients. And with that, I'll take any questions.  Let's see one here. Great study. Thank you. Harmeter, Seekon, Scripps Health, clinical director of the clinical services there.  Were you able to look at pre and post anesthetic use during the surgical procedure to see if the surgeons changed their methodology when they were closing up during the shortage?  Yeah. Unfortunately, the question was if we had actually looked at during surgical procedure what the anesthesiologists or the surgeons were using for their anesthetics of choice.  And unfortunately, that wasn't something that we were able to look at. Retrospectively, that would have been very difficult for us  to evaluate, but it could be something in the future that we could look at if the during surgery anesthetic use had any effect on post-surgical pain, definitely.  It would be in your anesthesia record if they did use it because it depends on how much they dump into the wound or, you know, put different places during the wound closure.  But anyway, it would be interesting to see if that changed during the shortage. Exactly. Thank you. What was your most common IV opioid that you used?  Definitely by far fentanyl was our most common IV opioid that we used. Even during the shortage, we had a lot of pushes of IV fentanyl. I think it's the thing  that our doctors are most comfortable with. They know the dosing much better than they know, you know, equivalent dosing of morphine or hydromorphone. We also did see an increase  in dilaudid PCA use during this time. Mike White from Detroit again. I enjoyed your study. So you mentioned multimodality use. So do you think that's something you guys are going  to pursue more? We have a burn unit at my institution, and one of the things we've gone to to try to reduce our fentanyl use, especially for our larger burn,  we start them on methadone because we use a lot, you know, we have to use a GI tract a lot early. And so we transition them onto that and try to get our IV fentanyl doses down.  It helps us with getting them off the vent and weeding them faster, I think. We've started this trend in the past year, and we're going  to kind of look at it, but that's something we have tried. We've also used more ketamine for doing procedural stuff, especially for our intubated patients since you don't have  to worry about their airway, and it works quite well. Yeah. So the question was, are we bringing more multimodality or making changes to our process now after this? Yeah.  And actually, the study and the shortage came at a very opportune time when we were updating our pain agitation delirium protocol. And now we definitely recommend for patients  who we want more light sedation in, we use oxycodone around the clock if they can't verbalize a pain score. So we do that, and we definitely encourage multimodality  and even starting patients home medications, which is something we can definitely do much better with if they were already on something at home to make sure  that we're adequately treating that pain that they already had on top of whatever additional requirements they have. Thank you. Thanks. Thank you very much, Dr. Bowman.  Okay. Our next to last presenter is Dr. McKenna Jennings, and she's going to be presenting on methylene blue versus hydroxycobalamin  for postoperative vasoplegia, a retrospective analysis. Hello. Thank you, everyone, for coming out this afternoon.  So it's not uncommon for us to see profound hypotension in patients postcardiothoracic surgery. However, in some of these cases, this hypotension can be  refractory to our customary vasopressors, and patients can be termed vasoplegic. The incidence of vasoplegia has been described widely  throughout the literature, ranging anywhere from 5% to 50%, an average of 19% to 20%. And we do see significant outcomes associated with the incidence of vasoplegia.  We see higher mortality rates, higher days of mechanical ventilation, higher incidence of infection, and so forth. There are two potential pathways  that I'll discuss today with vasoplegia, one of these being the nitric oxide pathway. So with risk cardiopulmonary bypass, we see higher production  of inducible nitric oxide synthase, which leads to increased production of nitric oxide and subsequent vasodilation. We also see the vasopressin pathway.  So in response to shock, we have higher secretion of endogenous vasopressin. With prolonged shock, we see that those stores are depleted  and subsequent further vasodilation in vasoplegia. Both of these pathways contribute to the profound hypotension that we see in vasoplegia. But while we talk about vasoplegia,  there is no significant standard definition that is reported across the literature. What we can think of it is as a state of profound vasodilatory  shock that is characterized by profound hypotension with refractory to catecholamines with a low SVR and normal or elevated cardiac output.  So the two agents that I'm going to discuss today, methylene blue works by directly inhibiting the inducible nitric oxide synthase and also guanylate cyclase,  leading to inhibition of vasodilation. And then hydroxycobalamin has a less well-known mechanism but is thought to work as a nitric oxide scavenger.  So the purpose of my study was to demonstrate the efficacy of methylene blue and hydroxycobalamin for raising MAP in the setting of vasoplegia.  And we wanted to discover any efficacy or safety differences between these two agents when used in this setting. And then perhaps uncover evidence to support use  of a first-line agent at our institution, IU Health. Our study was a single-center retrospective comparative cohort study, and we evaluated patients  at IU Methodist Hospital over a period of five years. And we looked at patients who received either methylene blue or hydroxycobalamin post-cardiothoracic surgery.  Our patients were adults greater than 18 who underwent a cardiothoracic surgery procedure. And they had to receive either methylene blue, at least one milligram per kilo,  up to two milligrams per kilo, or hydroxycobalamin, five grams. And they had to receive either agent within 72 hours of their CT surgery procedure.  We did exclude patients who had a diagnosis of hemorrhagic shock. If additional vasopressors were added or their existing vasopressors were titrated within 15 minutes  of receiving either agent. And if the agent was given interoperatively or if they received methylene blue and hydroxycobalamin within two hours of each other.  So obviously there were patients who received both agents in our study. And in order to maximize the amount of patients available for analysis,  we developed this algorithm for inclusion and exclusion of those patients who received both agents. So patients who received methylene blue first,  if they were given hydroxycobalamin within two hours, we excluded both of those patient groups. If the hydroxycobalamin was given after two hours  from methylene blue but within four hours, we only included the methylene blue arm. If hydroxycobalamin was given more than four hours after administration of methylene blue,  we included both patients in those studies. In the hydroxycobalamin arm, if methylene blue was given within two hours, we excluded those patients.  And then if it was given more than two hours after hydroxycobalamin, we only included the hydroxycobalamin arm. So as I mentioned before, there is no consistent definition  of vasoplegia across the literature. So we chose to define vasoplegia as such. Our patients had to have persistent hypotension defined as a MAP of less than or equal to 65 plus  at least one vasopressor at the following doses. So they had to have norepinephrine or the equivalent of 0.2 micrograms per kilo per minute or vasopressin  at greater than or equal to 0.04 units per minute. Our primary endpoint was a 20% increase in MAP within two hours of administration of either methylene blue or hydroxycobalamin.  We also looked at presence of new end organ failure like renal failure or liver failure, survival to discharge and hospital length of stay.  We evaluated 146 total patients for inclusion. We were able to include 38 patients in our analysis, 25 in our methylene blue group and 13 in our hydroxycobalamin group.  Patients were mostly excluded based on co-administration of either agent within two hours of each other or administration in the OR. We analyzed our variables,  our categorical variables using the Fisher's exact test and our continuous variables with the main Whitney U and student's T test.  We calculated a sample size of 50 patients would be needed to detect a 20% difference between our groups. Our baseline characteristics, our patients were  up in their upper 50s on average, mostly male and about one Hoosier unit or 100 kilos. With their baseline labs, we did see that the patients  in the hydroxycobalamin group had lower baseline serum creatinines than the patients in the methylene blue group at 1.22 versus 2.06. And that was statistically significant.  With regards to their baseline medical history, we didn't see any statistically significant differences with the presence of aortic insufficiency, endocarditis,  positive blood cultures or preoperative dialysis. The procedures that were the index procedure for their CT surgery procedure were mostly ECMO.  Fourteen of those patients did have ECMO at our facility, followed by isolated valves and then combined CABGER valve procedures. And the majority of these patients,  procedures were classified as emergent. So we had 88% of the patients in the methylene blue group and 62% of the patients in the hydroxycobalamin group  with emergent procedures, which can give you an idea of the acuity of our patient population. With our blood pressure outcomes, I've divided these up on this slide  with our primary endpoint being a 20% increase in MAP within two hours of receiving either agent. We did not see a statistically significant difference between the groups.  However, you can note that MAP was increased by 20% and over 50% of the patients. We did see that there were lower baseline MAPs in the hydroxycobalamin group when compared  to the methylene blue group, 49 versus 58. And that was statistically significant. And we do see a trend towards a higher MAP at the end  with the hydroxycobalamin group of 75 and a larger change in MAP of 38.5 versus 29. However, this was not statistically significant. With regards to other variables,  we did not see any statistically significant differences with relation to survival to discharge, length of stay, or presence of new end-organ dysfunction.  There was a trend towards increased survival in the hydroxycobalamin group. However, that was not significant. So strengths, our study, this was the first study of its kind  to compare either of these agents and thereby the largest study. It is limited by its retrospective design. The technological limitations that we experienced  with relation to not having a bidirectional EMR system at the time. We also had a vasoplegia definition that may not be applicable to other populations based  on how we designed that definition. So what we took from our data was that methylene blue and hydroxycobalamin do increase MAP by 20% and up to 50% of patients, and we'd like  to see more studies comparing these agents in the future. And now I'll take any questions. Hi, nice job. It's great to see data about this since you're right,  there isn't anything out there comparing the two. I'm Kimberly LaVasseur-Franklin. I practice at Tufts in Boston. Curious in terms of your standard for your CT surgeons,  is there a protocol or is it just prescriber dependent in terms of how they decide what to use? It's prescriber dependent. I would say that most of our pharmacists recommend  that we use methylene blue first over hydroxycobalamin just based on the cost, and that's something that as a department I think that we push for,  but it hasn't been standardized at this time. The other question I have is with regards to the patients that received methylene blue, was the dosing consistent?  I know you have the inclusion of greater than or equal to one milligram per kilo, but do they follow a standard dosing? Is it bolus only? Is it bolus and infusion?  So we only included patients who do just the bolus alone. Most of the time I'd say we actually mix it at bedside and we'll give it IV push.  There wasn't really any consistent trend towards one versus two milligrams per kilo in the data, but we did not include patients who had an infusion. Great. Thanks. Thank you.  Neil Reynolds from Baltimore. A couple questions. First, you didn't mention, once you've gotten the increase in blood pressure, was it sustained?  That was not an endpoint that we evaluated. So I really can't comment on that at this time, sorry. And you had those various arms.  Did you find that when one didn't work, the other did work, one didn't work, neither worked, any of that stuff? That wasn't something that we tried to analyze  and for the purposes of this study. I'll say often, just having given these agents in practice, if methylene blue doesn't work, our surgeons will often try hydroxycobalamin.  I can't say that there's a trend towards that working versus methylene blue working. Just from my experience, I see that often if one agent doesn't work, neither of them work.  But that's not something that we were able to evaluate in our study. Okay, thank you.  Okay, thank you very much, Doctor. All right, and our last presenter is Dr. Christine Graf. She's from Strong Memorial Hospital, University of Rochester.  And she'll be presenting her research on the effects of ketamine on pain, sedation, delirium in the ICU. Her Ketamine ICU Study.  Thank you. Good afternoon. So the Ketamine ICU Study was designed by our Ketamine ICU Study Group that was recruited through the American College of Clinical Pharmacy.  However, the study was conducted independently by our group and we received no financial support. It was a group of mostly pharmacists, a physician, and our supportive staff.  The goal was to evaluate the use of ketamine in the intensive care unit. As we know, there's really a lack of guidance on how to use ketamine in our ICU patients in the literature  as well as in clinical practice guidelines. So our hypothesis was that patients initiated on a continuous infusion of ketamine would have an increased proportion  of time spent in goal pain and sedation score range, reduce exposure to other sedatives, and it may have variable effects on delirium.  So this was a multicenter retrospective observational study in both adult and pediatric ICU patients. However, I'm only going to be presenting the adult data today.  Patients that received a continuous infusion of ketamine while in the ICU were included between January 2014 and December 2017. However, most patients were from 2016 and 2017.  And the primary objective was to characterize ketamine use in terms of indication, dose, and duration of therapy. And our secondary objectives were to determine  if ketamine increases proportion of time spent in goal range, determine the effect of ketamine on the incidence of delirium, and determine if ketamine reduces cumulative doses  of other sedatives in analgesics. So we looked at pain, sedation scores, delirium screenings, and opioid and sedative requirements.  And we compared them from the 24 hours prior to ketamine and then compared that to the first 24 hours of a ketamine infusion and then to the 25 to 48 hours  after ketamine was initiated. Continuous data was analyzed by students' T-tests or Wilcoxon rank-sum analysis on variants or Novant ranks,  depending on the number of groups and data distribution. Before and after data, including only patients that had data within the time periods evaluated,  was analyzed using paired T-tests or signed rank-sum for two measurements and a Novant ranks for three or more, again, depending on the distribution of data.  So we had 25 sites included. Most were university teaching hospitals in the Northeast, Southeast, and Midwest. Most institutions had over 500 beds and most had over 50 ICU beds.  There was a total of 390 adult patients included. Average age was 52 years. Sixty-one percent were male. Most were for medical, surgical, and trauma ICUs.  Median APACHE-2 score was 21. Eighty percent were mechanically ventilated. Thirty-four percent received vasopressors, and about nine percent received continuous  neuromuscular blockade. Looking at the indications for ketamine, the majority were for pain and sedation. So 91.5 percent of patients received ketamine  for either analgesia sedation or analgal sedation. And when you look at the pain scores, overall about 85 to 90 percent of patients had pain scores available  within the 24-hour time blocks. And if you look at the median number of scores recorded in the first, or the 24 hours prior to ketamine,  the first 24 hours, and the 25 to 48 hours, it was 10, 11, and 12 as far as the median number of scores. And we found that ketamine was associated  with a significant increase in the percentage of time spent in goal pain score. So in the 24 hours prior, about 69 percent were in goal range,  which increased to about 78 percent in the first 24 hours, and around 80 percent in the 25 to 48 hours. So this was significantly greater than the 24 hours prior to ketamine.  For sedation scores, sedation was assessed much less. So 80 to about 88 percent of patients had sedation scores available, and when you look at the median number of scores  in the 24-hour time frames, they were lower than pain scores available. So 7, 8, and 9 were the median number of scores available.  But we did see, again, an increase in the percentage of time spent in goal sedation score range. So in the 24 hours prior to ketamine, it increased  from about 57 percent to about 64 percent in the first 24 hours, and then up to about 69 percent in the 25 to 48 hours. And the significant increase in time spent  in goal sedation range increased from the 24 hours prior, as well as the 25 to 48. So it was from both time frames. Looking at delirium screenings, delirium was monitored  for even less than pain and sedation. So on average, only about 64 percent of patients had delirium screenings available. And when you look at the median number of screenings,  it was only about 2 in each time frame. So therefore, you know, interpreting this data can be challenging. So delirium possibly could have been missed,  but we found no difference in the percentage of time spent delirious in any of the 24-hour time blocks. Looking at opioid and sedative requirements,  we found that ketamine was associated with a significant reduction in opioid requirements. So we converted everything to IV morphine equivalents.  And you can see in the 24 hours prior to ketamine 120 milligrams was the median dose, which decreased to 118 in the first 24 hours, and then 80 milligrams in the 25 to 48 hours.  So this was statistically significant. You could argue the clinical significance of that, though. For benzodiazepine requirements, we also saw a significant reduction,  11 milligrams in the 24 hours prior, 6 milligrams in the first 24 hours, and 3 milligrams in the 25 to 48-hour range. Same thing with propofol, 942 micrograms of propofol,  I'm sorry, milligrams of propofol in the first 24 hours prior, 160 in the first 24 hours, and then 0 milligrams in the 25 to 48 hours. And again, same thing with dexmedetomidine.  We saw a significant decrease from 1,000 micrograms in the 24 hours prior to 284 in the first 24 hours and 0 in the 25 to 48 hours.  So there's obviously some limitations to these data. It was a retrospective observational design. There were definitely missing data points either just  because those points weren't available or not recorded. We didn't do a power or sample size analysis. There's likely definitely heterogeneity across the sites  as far as pain and sedation practices in general as well as the types of screenings that were used, the tools that were used to screen for pain and sedation,  as well as the number of individual patients that were contributed from each site. Anytime you do large multicenter retrospective data  reviews like this, data integrity is always an issue. But we tried to control for this by having a standardized case report form. We held a series of conference calls ahead of time  that was mandatory for anyone collecting data so that we could review the case report form in detail. Despite that, we did have some centers  that only recorded intravenous opioid and sedative use. So they didn't record oral agents. It was only a few centers. So we don't feel that probably contributes significantly  to the data. But it could have potentially biased the results. And then in order to make fair comparisons, we had to remove some patients to make sure  that we could compare patients that only had screenings in each timeframe. So in conclusion, we found that ketamine infusions increase time spent at goal pain  and sedation score range. They do not affect time spent positive for delirium. And it probably reduces exposure to other opioids and sedatives.  So we feel ketamine is a reasonable option, especially in those failing traditional sedative and analgesic regimens. However, we definitely need prospective randomized  comparative data to really determine its place in therapy as well as the overall safety of this medication. So I'd like to thank all the members of our ketamine ICU study group.  I couldn't have done this study without all of your help. And expertise. And of course, I'd like to acknowledge our 25 sites that participated in the data collection. Thank you.  And I'll take any questions. Thank you. Definitely have time for additional questions if there are any. I'll throw an icebreaker out. We've got a few folks. Thank you for the study.  Rita Gage from the Gradyburn Center in Atlanta.  I had a question for you. We use ketamine too. What kind of doses did you all use? And were there any side effects associated with increased doses?  So doses were variable as far as the units used. About two-thirds of patients dosed it in mikes per kilo per minute. Another third in milligrams per kilogram per hour.  Some people in milligrams per hour. We found that the average starting dose converted to milligrams per kilogram per hour was .2. And the average discontinuation dose was .3.  So, you know, that kind of tells me that we're not really titrating ketamine completely off. As far as adverse effects, those were also variable. We found a pretty high percentage  of increased secretions associated with this. About 10% of patients. And that was associated with about a 17% incidence of starting anticholinergic agents.  There was about a 5.7% discontinuation rate due to adverse effects. And most of those were within the first 24 hours of starting the medication. We haven't analyzed the incidence  of adverse effects associated with dose yet. But that's something that we could do. Likewise, from Detroit again. Yeah, I had some questions. What was, I missed it maybe.  How long did the, was the ketamine used on average, especially for the IV? Yeah, so the median duration of time was about 1.6 days. So fairly short. Fairly short.  And we looked out to seven days for adverse effects, as long as they were still on ketamine. Yeah, that was my question too, is about the side effects.  Because especially if you adjust doses up and down, sometimes you get dysphoric effects, especially in awake patients. Yeah. So I was curious to see how often you saw that.  So, psychotropic effects were actually reported pretty low, which was kind of surprising. About, only at about 1.6% of patients. Which is very low compared to other literature.  Obviously, this is a retrospective design. So, it very well just wasn't documented clearly in the chart to be able to pull that. So it's probably an underrepresentation  of what really happened. There is some data that we have left to analyze too, specifically looking at benzodiazepine and antipsychotic use right before  and after ketamine was discontinued to look for emergence reaction. But we haven't analyzed that data yet. Okay. Thank you. Nice study. Thank you.  Hi. I'm Shadi from the Seveda Medical Center. I wanted to ask if you collected data regarding the percentage of patients that were on mechanical ventilation while  they were on ketamine. And if you did, did you look at data to analyze the length of time on mechanical ventilation? Yeah. So, duration of mechanical ventilation,  I believe was around seven days. I'm getting that confused with, yeah, seven days. And then ICU length of stay was about nine. Hospital stay was 15.  About 80% of patients were mechanically ventilated. There was actually a fair amount of patients that ketamine was discontinued after they were extubated,  which we thought was kind of interesting. So, ketamine was continued through the extubation period. Yeah. Hi. Casey Clark from Sarasota Memorial.  I just had a question regarding tapering off of ketamine. If you saw any trends for actual indications for analgesia versus status epilepticus, if people were tending  to titrate off slower in one indication or the other, if you happen to collect that data at all? We have that data because we looked at doses within the 24-hour timeframes.  We just haven't analyzed that information. So, I don't have that for you at this time. I had one other question. Yeah. I know you analyze in terms of morphine equivalents.  Florida has some weird laws regarding nursing, administration of push-dose ketamine. Yeah. I was just wondering if there was a, you know,  a certain drug people tended to use as a PRN, or were they using smaller doses, pain doses of ketamine for uncontrolled pain scores while they were on the infusion?  So, this was specifically continuous infusions of ketamine. So, we didn't look at patients that received intermittent dosing of ketamine.  About 25% of patients did receive an initial bolus dose. But that's all the information that I have. Great. Thank you. Yeah. Thank you. Thank you very much, Dr. Graw. Thank you.  And thank you for your time and attention. Enjoy the rest of the conference.

Video Summary

Summary of the first video:<br /><br />The study focused on determining the optimal dose of anoxaparin for pediatric patients with chilothorax after cardiac surgery. Chilothorax is a condition where lymphatic fluid accumulates in the pleural space after heart surgery, potentially causing respiratory distress. The study compared anoxaparin dosing and monitoring between patients with and without chilothorax and found that those with chilothorax required higher doses of anoxaparin to achieve therapeutic anticoagulation. However, there was no difference in plasma antithrombin levels between the two groups. The researchers suggested a 10 to 30% increase in the initial anoxaparin dose for patients with chilothorax, highlighting the importance of personalized dosing strategies and close monitoring in this population.<br /><br />Summary of the second video:<br /><br />A retrospective study examined the use of ketamine in ICU patients to evaluate its effects on pain, sedation, and delirium. The study included 390 adult patients from 25 sites who received continuous infusions of ketamine. The results showed that ketamine increased the proportion of time spent in goal pain and sedation score ranges. It also reduced the need for other sedatives and opioids. However, ketamine did not have a significant effect on delirium incidence. The study concluded that ketamine is a viable option for patients who do not respond to traditional analgesics and sedatives. Further prospective randomized studies are needed to determine the overall safety and potential benefits of using ketamine in the ICU setting.

Asset Subtitle

Pharmacology, 2020

Asset Caption

The Society of Critical Care Medicine's Critical Care Congress features internationally renowned faculty and content sessions highlighting the most up-to-date, evidence-based developments in critical care medicine. This is a presentation from the 2020 Critical Care Congress held February 16-19, 2020, in Orlando, Florida, USA.

41-A Bivalirudin Anticoagulation Protocol for Neonatal Extracorporeal Membrane Oxygenation

Christopher Snyder

42-Outcomes from the PITCH Study: 4-Factor PCC in Intracranial Xa Inhibitor Coagulopathy Hemorrhages

Nathan Goad

43-Pharmacist Avoidance or Reductions in Medication Costs in Critically Ill Patients: PHARM-CRIT Study

Drayton A. Hammond

44-Enoxaparin Dose Requirement in Pediatric Patients With Chylothorax After Cardiac Surgery

Taryn Mancarella

45-Pharmacist Avoidance or Reductions in Medication Costs in Emergently Ill Patients: PHARM-EM Study

Megan A. Rech

46-Surgical Intensive Care Unit Pain Management in the Era of Intravenous Opioid Shortages

Allison Bouwma

47-Methylene Blue Versus Hydroxocobalamin for Postoperative Vasoplegia: A Retrospective Analysis

Mckenna L Jennings

48-Effects of Ketamine on Pain, Sedation, and Delirium in the Intensive Care Unit (Ketamine-ICU Study)

Christine M. Groth

Meta Tag

Content Type Presentation

Knowledge Area Pharmacology

Knowledge Level Advanced

Membership Level Select

Membership Level Professional

Membership Level Associate

Tag Anticoagulation

Tag Economics

Tag Analgesia and Sedation

Year 2020

Keywords

anoxaparin

pediatric patients

chilothorax

cardiac surgery

respiratory distress

monitoring

therapeutic anticoagulation

plasma antithrombin levels

ICU patients

ketamine

pain

sedation

delirium

continuous infusions

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