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Medications and Therapies in the ICU
Medications and Therapies in the ICU
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everybody. So we're gonna start with visual imagery. Imagine walking into a world where there's no intensivist program, there are two competing pulmonary groups fighting over patients, there are no multidisciplinary rounds, there are no pharmacists doing antibiotic stewardship, and that was the world I walked into three years ago. So what we did, I was hired specifically to start an intensivist program. So initially we targeted all the things you would normally target with an intensivist program, but about a year into it we decided we need to start targeting carbapenem usage because we were using twice the national average of maripenem than anybody else in our system or in the southeast. So specifically I am the director of the intensivist program and Division of Critical Care at Mobile Infirmary and I have nothing to disclose. And the objective of the study was to assess the impact of not only an antibiotic stewardship program but also combined with a new intensivist program on carbapenem utilization in the ICU at a large, mostly non-academic hospital that recently started at residence. As everybody knows, carbapenems are broad-spectrum bacterial cidal beta-lactam antibiotics with broad coverage against gram-negatives, anaerobes, and some gram- positive coverage. Efficacy against extended-spectrum beta-lactamase isolates, but as we also know there's been a developing carbapenem resistance pattern that has become quite worrisome, and in particular carbapenem-resistant Enterobacter such as Acinobacter, or also Acinobacter, become two of the urgent threats according to the Infectious Disease Society of America. And so we were targeting the utilization of carbapenems hopefully to reduce that particular pattern in our ICU. And again it is a worsening problem of carbapenem resistance, 13,000 cases in 2017 with 1,100 deaths, and obviously increased expense to health care. So what is an antibiotic stewardship program? And it can really be summed up as the right drug, the right dose, the right duration, and the right route of administration. So you want to optimize the treatment of the infections while reducing the adverse events associated with antibiotic usage, and in particular you don't want to use an antibiotic you don't have to use when a lesser or a lower level antibiotic would work, and you also want to make sure you stop it as soon as you can when it's no longer needed. The CDC recommends with any antibiotic stewardship program that there's actually co-leadership with physicians and pharmacists, and we'll get a little glimpse as to why that's helpful in a minute. We all know about intensivist programs. What we did was we started one with board-certified critical care physicians. Our primary goals were to improve mortality, reduce length of stay, ventilator days, improve patient safety and satisfaction, reduce costs. In a previous study presented at ATS, we showed that we actually did impact all those things. This is the hospital that we work at. It's a 669 licensed bed with 70 critical care beds. We started by taking over first the surgical and medical ICU, and now we also run both the neuro ICU, so we currently run 58 of the 70 beds. The study design was a retrospective chart review. All patients admitted to surgical and medical ICU were the ones we looked at for this study, and the formulary carbapenem that was used is meripenem. We studied the year before the intensivist program, the year after the intensivist program, and these six months after we started to do both the intensivist program and the antibiotic stewardship program. And so you can see here, before we started any of this, the institution's usage of meripenems was far double the national average for our region, the southeast, and for the national average. We were using upwards of 40 to 50 percent carbapenems on patients in the ICU, where the average is closer to 20 percent. I think what happened was just the reflex was, well they're sick, I'm just going to start the biggest thing I can, make sure they get better, without a lot of thought into it. The primary endpoints that we looked at were carbapenem utilization pre- intensivist, intensivist alone, and intensivist with the stewardship program. And I will put a little plug in here to say the first year we were not really looking at carbapenem usage because we were trying to fix everything else at first, but when we did start looking at it, you can see there's a pretty big impact. So even though we weren't looking at it a lot the first year that we took over, there was a reduce, a reduction in carbapenem usage of about 2%. But once we actually started to look at the antibiotic stewardship, the reduction with the intensivist combined with pharmacy and the program was 50%. We used an interdisciplinary team approach, antibiotic stewardship, and decreased risk of multi-drug resistant bacteria, and specifically the multidisciplinary rounds. As the director of the program, I told our physicians and the pharmacists, I wanted the pharmacists to challenge us every day to stop or de-escalate antibiotics, and it led to some very interesting exchanges on rounds as to when we should lower the antibiotics or stop them or de-escalate them. But as you can tell, the results were really good, and I want to point out that our mortality rates at the same time actually declined in the ICU. I'm not going to say that's because of the stewardship, because that was also a reflection of the intensivist program and some of the changes we brought in, but the biggest take-home was we reduced the maripenem usage with no impact on mortality, and if anything mortality got better. So a couple of things I wanted to point out. Everybody that's on this research project, with the exception of me, has been out of training for five years. So I did click the box for young research presentation. I clicked it for everybody but me. As you can tell, I'm not a young researcher, and that's basically what we have, and if you have any questions, please let me know. So I would welcome Dr. Daisuke to do the next talk. Over to you. Good morning. My name is Daisuke Hasegawa. I'm one of the internal medicine residents at Mount Sinai Base Israel. I'm going to talk about my topic is beta-blocker use for patients with refractory ventricular fibrillation and pulseless ventricular tachycardia. There is no conflict of interest to disclose. So refractory ventricular fibrillation and pulseless VT, which does not have definition, may be a result of excessive endogenous and exogenous catecholamines, and there is a growing interest to use beta-blockers for this population, because blocking beta activity could be potentially beneficial for resuscitation. But the use of beta-blocker in the setting of VT has not been specifically addressed in the current ACLS guideline due to the lack of high-quality data. So in order to address this topic, we aimed to summarize the current available evidence regarding the effect of beta-blockers in this population through meta-analysis. So a thorough search of MEDLINE was conducted about one year ago, using keywords including ventricular tachycardia, V-fib, cardiac arrest, cardiopulmonary resuscitation, beta-blocker, beta-antagonist, and S-module. And two authors independently evaluated the following inclusion criteria. One, study design being interventional or observational or before and after studies. And two, patient population being adults with refractory V-fib or pulseless VT, defined by persistent V-fib or VT after three defibrillations. And intervention was beta-blocker use. And we excluded studies examining the effect of beta-blockers in patients with VT who had a pulse. And the primary outcome was sustained return of spontaneous circulation, ROSC, defined by ROSC for more than 20 minutes or pre-hospital ROSC. And also short-term survival, defined by survival less than 30 days or in-hospital survival. And the polled odds ratio and 95% CI were calculated using random effect model. And I-squared static with 95% CI were used to assess heterogeneity. So our search initially identified 1,413 articles as a primary search. And of these, 25 studies appeared to be relevant. And we carefully reviewed the full text. And we finally identified three studies included in this meta-analysis. And this is the three studies. The first one is Patrick et al. in 2022 conducted in the United States. The sample size was 124 single center retrospective before and after study. And they used Esmeral 500 mic per kick as a bolus for those who had always out-of-hospital cardiac arrest and requiring three or more defibrillations. And the second article was Lee et al. in 2016 conducted in Korea. And the sample size was 41. This was also single center retrospective cohort study. And they also used Esmeral 500 mic per kick as a bolus, followed by 0 to 100 gamma continuous infusions. And the inclusion criteria was similar. And the last one was Driver et al. in 2014 conducted also in the United States. The sample size was 25. And the infusion intervention was the same with Dr. Lee's study. And this is the main result of our meta-analysis. The use of Esmeral was significantly associated with higher chance of sustained ROSC, with odds ratio 2.95, with p-value 0.007, and i-squared was like less than 40 or 50%. But the use of Esmeral was not associated with better short-term survival. Even though the odds ratio favored the use of Esmeral, the CI crossed 1, meaning not statistically significant, with p-value 0.20. So basically, the conclusion discussion. In this meta-analysis, we found that Esmeral was associated with significantly higher chance of sustained ROSC in patients with refractory V-fib and PT. So this study suggested the potentially important role of beta-blocking to control refractory V-fib and VT. Potentially, this is because fibrillating myocardium has increased oxygen consumption, which can exacerbate further myocardial damage. So given the epinephrine can increase oxygen demand of the myocardium, beta-blocker may be a reasonable choice for a shockable reason, with persistent V-fib and VT. And on the other hand, despite the building attention to the use of beta-blockers, included studies in this meta-analysis were all small size and respective, and also all single center studies. So therefore, this study is still hypothesis gathering in nature, and should trigger further discussion and warrant further research projects regarding the use of beta-blockers and refractory V-fib and VT. This slide concludes my presentation. Thank you very much. Thank you, Dr. Zaisky. So our next presenter is Dr. Barney, who will talk about potentially inappropriate discharge medications in survivors of acute respiratory failure. Over to Dr. Barney. Good morning. My name's Patrick, and today I'll be talking about our assessment of potentially inappropriate discharge medications in survivors of acute respiratory failure. My name's Patrick Barney. I'm a third year internal medicine resident at Vanderbilt University Medical Center, and I do not have anything to disclose. I want to start off by highlighting two conclusions from previous research that informed our study. We know, based on prior studies, that medications prescribed to patients in the ICU can impact their post-hospital outcomes. And from the original assessing post-intensive care syndrome study, APICS-01, of which our investigation is a sub-study, we know that unmet medication needs are common among survivors of acute respiratory failure, even after discharge home. So in our study, we sought to determine whether medications prescribed to survivors of acute respiratory failure can impact specifically their post-discharge morbidity and mortality. We used the same cohort that was used in the original APICS-01 study, and some of the inclusion and exclusion criteria are listed here. Briefly, folks who were in the ICU for respiratory failure for greater than 24 hours and were discharged home alive were included. Some exclusion criteria to point out would be being in the ICU less than 24 hours, having a baseline need for mechanical ventilation, having a life expectancy less than six months, or having a greater than mild degree of dementia at baseline. This left us with an original cohort of 200 survivors of acute respiratory failure requiring ICU-level care. And through evaluating follow-up, looking at whether or not they were actually discharged home with new medications, and evaluating their discharge summaries for completeness to allow our group to adequately adjudicate their medications, we landed with 169 patients in our cohort. So our multidisciplinary team included myself, a third-year medicine resident, two intensivist attendings, and a medical ICU pharmacist who went through the process of assessing and adjudicating each medication that each patient in our cohort was discharged home with. To do this, we first categorized all of the medications into classes, so things like antihypertensives, antibiotics, antihistamines, and designated each class as low-impact or high-impact based on our group's perception of their ability to impact the patient's post-hospital outcomes. Finally, we looked at each individual medication that each patient was prescribed, each of the high-impact medications, and adjudicated them as appropriate or potentially inappropriate for the patient based on the discharge summary and their comorbidities. And we assessed medication as potentially inappropriate if we perceived that it posed a greater than acceptable risk to the patient at the time of discharge home. Our primary exposure in the study was prescription of a high-impact, potentially inappropriate medication, and the primary outcome was 90-day readmission or death after hospital discharge. And our statistical analysis method is listed at the bottom of the slide. Some demographic characteristics to point out about our study cohort was a median age of 55, a small female predominance, the majority of patients at the time of enrollment requiring invasive mechanical ventilation for their respiratory failure, and a median hospital length of stay of 14 days. First looking at our primary exposure, so prescription of potentially inappropriate high-impact medications, the chart at the top shows the median number of new medications split into low-impact and high-impact that each patient was discharged home with. So five was the median of new medications, and three high-impact medications was the median for each patient. That left us with 154 of our original 169 patients being prescribed one or more high-impact medications at the time of discharge, and 31 patients being prescribed a high-impact medication that was adjudicated as potentially inappropriate. So this was our exposed group. This is a bar chart showing the high-impact medication classes on the x-axis and the number of medications prescribed in each class on the y-axis. The red portion of each bar is the portion of these medication classes whose individual medications were adjudicated as potentially inappropriate, and the blue portion of each bar represents the portion that was adjudicated as appropriate. And what I want to draw your attention to is about two-thirds of the way down the x-axis, you see antipsychotics, antihistamines, and anxiolytics, and these were the three medication classes whose medications had the highest proportion of being adjudicated as potentially inappropriate at the time of discharge. Looking at our primary outcome, we had 154 patients who were prescribed a high-impact medication at the time of discharge. Forty-six of these patients met the primary outcome, and the majority met that through readmission rather than death at 90 days. Looking at our primary exposure and our primary outcome, we did not find an association between prescription of a potentially inappropriate high-impact medication and 90-day readmission or death, and that was true both for the composite primary outcome and both for the individual components of readmission or death. So to summarize, we found that survivors of acute respiratory failure are at risk for being prescribed high-impact, potentially inappropriate medications. Twenty percent of patients in our cohort met this criteria. We found that the medication classes most likely to be adjudicated by a multidisciplinary team were antihistamines, antipsychotics, and anxiolytics, and we did not find an association between the exposure of a high-impact, potentially inappropriate medication at discharge and 90-day hospital readmission or death. Some questions we had moving forward were whether or not an increased number of transitions of care for a patient during a single hospitalization would increase their risk of being prescribed potentially inappropriate medications, whether or not some of these specific medication classes that were adjudicated more frequently as potentially inappropriate affect outcomes more than others, and then from a resident's perspective, whether an educational intervention could be developed and implemented during training to decrease the risk of exposing patients to high-impact, potentially inappropriate medications, learning more about transitions of care and medication reconciliation. I want to give a really big thank you to all the faculty members who allowed me to participate in this study with them. First and foremost, Dr. Carla Steven, who was my primary mentor at Vanderbilt, Dr. Joanna is CIVA Protocol versus Phenobarbital and Managing Severe Alcohol Withdrawal at a Tertiary Care Teaching Hospitals, a Retrospective Comparative Data Analysis. I'm Sushant Gupta. I am one of the resident and in Department of Internal Medicine at Carl Foundation Hospital in Champaign, Illinois, and I don't have anything to disclose. So just briefly summarizing why we did this study. We understand the CIVA is very commonly followed for alcohol withdrawal in the hospital, but there have been studies that have shown phenobarbital mild therapies might be safer and more effective in managing patients with severe alcohol withdrawal. However, CIVA, one can understand that the outcomes may vary with the experience of the hospital in managing such patients, and also the previous studies that were done with phenobarbital had a smaller sample size that kind of limited the extrapolation of the data. So the primary objective of our study was to compare the standard of care treatment with CIVA-triggered benzodiazepine administration, comparing it with phenobarbital infusion in patients with severe alcohol withdrawal in the intensive care unit. So this is going briefly about the phenobarbital dosing protocol at our hospital. Every patient who we decide to initiate phenobarbital therapy receives one-time dose of 10 milligrams per gigs of phenobarbital, after which, for first 24 hours, the patient can receive 2.5 milligram per gigs based upon any of those mentioned criteria for a period of 24 hours, maximizing for two doses, after which we go on 2.5 milligram per gigs every three hours as needed, moving forward. So this was a retrospective data analysis study using SlicerDicer, which is a self-service cohort exploration tool that's embedded in Epic. We carried out the data analysis study for a period of five years, from February 15, 2018 to February 15, 2022, in the intensive care unit of a Midwest tertiary care teaching hospital. Based on our total population, we divided patients into two groups, one that received CIVA therapy, another that received phenobarbital therapy, and we looked at the overall length of ICU stay, the need for invasive ventilation, and the use of adjunct pharmacotherapy. We did, for statistical analysis, we clustered the data into, and they were expressed in absolute values, and we used chi-square test for the strength of association. Let's go over the results. So we had 326 patients in the CIVA group as compared to 54 in the phenobarbital group, which suggests that there's alcohol problem in Midwest. And we had around, if you look, most of our age group of our patients was between 27 to 82 in both the groups, predominantly in males, and we had a higher proportion of Caucasian population in our population group. In terms of comorbid conditions, we had, interestingly, we did not have any significant difference in terms of prior psychiatric conditions, substance abuse, or seizure problems in both the groups, though there was a significantly higher chances of phenobarbital therapy being prescribed if a patient has an underlying liver disease. There was no statistical significant difference in patients with history of complicated withdrawal in both the groups. So this was our primary outcome. Interestingly, we had a significantly higher proportion of patients with benzodiazepine-based CIVA therapy with a total ICU length of stay less than five days. We had a lower proportion of patients with CIVA therapy needing intubation. However, this was not statistically significant. We also had a lower proportion of patients with CIVA therapy needing dexmedetomidine infusion, which was statistically significant, and the use of gabapentin or other antipsychotic medications was similar in both the groups. So let's compare the data that has already been published from what we are proposing. So just briefly summarizing, ours was a retrospective comparative data analysis with 326 patients in the CIVA group and 54 in phenobarbital, and we found that there was significantly lesser proportion of patients in the CIVA protocol with a hospital ICU length of stay less than five days and fewer with dexmedetomidine infusion, and there was no difference in adjunct medications or need for intubation in both the groups. Now, this is a study that was published by Al-Waqeel et al, and they found there were 51 patients in both the groups. This was unlike our results. They did find that the median ICU length of stay was lower in the phenobarbital group, so was the adjunct use of medication and need for intubation. Contrary to this, this study, which was done in Cleveland Clinic, they found that length of ICU stay was similar in both the groups. Three patients in the phenobarbital group actually required mechanical ventilation, which is very close to what our study found. Contrary to that, this was another study. This was a meta-analysis that was done, which found no significant difference in terms of the length of ICU stay in both the control and the comparative arm, although they did find that there was some statistical significant difference in terms of intubation, but there was considerable heterogeneity in terms of the data that was compared in the studies. Moving again, contrary to that, there was another study that was published in American Journal of Critical Care, which proved that phenobarbital patients had lower ICU length of stay. The incidence of mechanical ventilation was lower in phenobarbital group, and use of adjunct medication were also lower in phenobarbital group. One of the reason why I have such a wayward presentation of discussion is to suggest that there's a lot of heterogeneity in terms of what the data has to say in terms of which is better, phenobarbital or CIVA therapy. But our study has certain limitations. One, again, is definitely a smaller sample size. It's a retrospective design. And one thing that can really contribute to the data is also the confounding that some of the patients might have received CIVA therapy prior to their ICU admissions. And also, we did not do a full safety analysis in terms of if there were other side effects of the medications that were used. Moving forward, there's a scope of doing more prospective studies. One that I could find being registered with CTRI was a phenomenal trial that would be a prospective trial comparing phenobarbital with CIVA therapy, which would give us more answers in terms of which one is better, which one is not. Concluding, severe alcohol withdrawal management in ICU benzodiazepine-based CIVA therapy may actually be non-inferior to phenobarbital therapy. And the decision of which therapy to use should be guided by individual's expertise and hospital protocols. And at the end, alcohol kills. Thank you. This is Dr. Jackson, who will talk about the effect of ketamine infusion on BIS in paralyzed, critically ill patients. Thank you, Dr. Jackson. Hi, everyone. Thanks for joining. My presentation is titled Evaluating the Effect of Ketamine Infusion on Bispectral Index in Paralyzed, Critically Ill Patients. I wanna thank all of my co-authors listed here for all of their hard work in putting together the presentation. My name's Ian Jackson. I'm a second year pulmonary and critical care fellow at Creighton University in Omaha, Nebraska. And as the title implies, we're gonna look at the effect of ketamine on bispectral index in patients that are under the effects of neuromuscular blockade in the ICU. And our group and myself personally have no financial disclosures. So I'm gonna start by talking a little bit about sedation in general. As I'm sure many people in this room have experienced, titrating sedation in ICU patients is not always an easy task. We rely heavily on use of scoring systems, such as a Richmond Agitation Sedation Scale to accurately assess our patient's level of sedation and then titrate medications accordingly. And the RAS scale varies from agitated and combative to our target, which is where they are kind of comfortable but open eyes to stimuli and are responsive all the way to unresponsive to stimuli. Of course, all of these and the scaling of the RAS system in general requires the motor function to be intact in patients. And so in patients that are under the effect of neuromuscular blockade, our kind of most tried and true method of evaluating sedation is not able to be used. And so we have to rely on alternative options, such as the Bispectral Index. So the Bispectral Index is essentially a processed electroencephalogram or EEG that involves the application of four electrodes across the forehead and then monitors the effect of hypnotic sedative medications on the brain activity. It was originally designed to be used in the operating room in the 1990s, but since then has expanded significantly in its use. And it can be used in the cases of status epilepticus to guide birth suppression therapy. There's some data that's come out recently to suggest that it could be used in neuroprognostication after TBI or cardiac arrest. But by far the most common use is what our patient population in this study is looking at, which is paralyzed patients in the ICU. And the Bispectral Index ranges is from zero to 100 with zero being cortical silence or a flatline EEG. And 100 being awake. For general anesthesia, we typically target 40 to 60, and that's what we target in our ICU population as well. In a perfect world, it portrays only the patient's level of sedation and is unaffected by other variables. But of course, we don't live in a perfect world. And there are a number of other variables that kind of artificially skew the BIS score one way or the other. So some of those are listed here, medications like nitrous oxide, certain states such as hypothermia or baseline intellectual disability can all skew the score one way or the other independent of the level of sedation. And so that's kind of where our study comes in looking at ketamine, which has seen kind of a resurgence in recent years as use of a sedative medication in the ICU. And obviously that causes it to overlap pretty frequently with patients that are also under the effects of neuromuscular blockade. There's not a lot of data on the effects of ketamine in Bispectral Index, but what data is out there suggests that it may, like the variables listed in the last slide, artificially elevate the Bispectral Index score independent of the level of sedation. And the exact underlying mechanism is unclear. It's been, you know, plenty of theories have looked at it, whether it's interaction with the NMDA receptor or its role as kind of a dissociative anesthetic have all been theorized, but no clear underlying answer. Regardless, our study looked to just kind of add further data to this idea that ketamine may artificially skew the Bispectral Index. And so we set up a retrospective analysis using our electronic health record. We looked at patients within our ICUs from January 2017 to December 2020 that were under the effects of neuromuscular blockade, had ketamine used at sedative doses, which for us was 0.5 to 4.5 milligrams per kilogram per hour, and then also had Bispectral Index scores that were measured hourly, both before and during ketamine infusion. And we, for statistical methods, use a linear mixed effects model to look at our time in hours, Bispectral Index score, and then the use of ketamine infusion, and then look to see if there was an interaction between these three variables, with our primary endpoint being the effect of ketamine use on Bispectral Index score. So in total, we identified 10 patients that fit our inclusion criteria. Their demographics are shown on the right here. They were split 50-50, male and female, average age of 54, average APACHE-2 score of 20. The ICU length of stay was 13 days, hospital length of stay was 20 days, and we had two patients that passed away in the ICU, giving us a 20% mortality. The average number of Bispectral Index measurements, not the measurement itself, was 65. So it ranged from 21 for patients that only required short-term paralysis to 213 in patients that required a longer course. Our results show that, on average, the Bispectral Index score increased through the first 24 hours after ketamine was initiated, and then gradually decreased thereafter. And most importantly, we found that the Bispectral Index score increased by an average of 6.1 points after ketamine infusion was initiated. And this had a p-value of less than 0.001. So this graph shows our data for the 10 patients that were included and their Bispectral Index score charted over time, with hours on the x-axis of zero being the time of ketamine infusion, and then following them up to 72 hours on the far right side of the graph. You can see that trend that I mentioned where it initially increased and then gradually decreased after. So overall, our results suggest that there is an association between ketamine use and increased Bispectral Index scores. And this, of course, has implications that we could potentially be over-sedating patients when we use ketamine in this population. It obviously has the opposite effect of what you would expect when you add an additional sedative medication. You'd expect the level of sedation and not just the Bispectral Index score to also decrease. But in this case, we saw an increase, and similar studies on the topic have also seen that increase as well. And so this could obviously lead to us increasing sedation kind of inappropriately. There are obviously limitations to our study. It was a small sample size. It was retrospective. There's always the potential for incomplete data. The Bispectral Index was never initially designed to be used in this population, although that's sort of its most widespread use currently. And then in our study, we also had patients not on just ketamine infusions, but other sedative medications as well that potentially could act as confounding variables in our data. However, the bottom line is that our results sort of add to this growing pool of evidence that ketamine may increase the Bispectral Index scores. And then knowing everything that we do about the morbidity and mortality associated with over-sedation of ICU patients, we propose that ketamine should be used with caution in this patient population, and that additional studies are needed to kind of fully explore this relationship. Thank you. Hello, everyone. I'm Mohamed Rahadi. I'm a medical doctor in training from University of Tripoli in Libya. I'm going to present today, evaluating the impact of mesenchymal stromal cell therapy on mortality and safety in acute respiratory disease syndrome caused by COVID-19 amid analysis of our clinical trials. So I have nothing to disclose. So as you know, acute respiratory distress syndrome is a severe lung condition causing respiratory failure, often require mechanical ventilation. There was some association between ARDS and COVID-19 as it's life-threatening complication for COVID-19 and can lead to high morbidity and mortality rates. So there was some needs for new treatment. Current treatment offer limited relief. Therefore, there is urgent need for innovative therapeutic strategies. ARDS has a lot of complications, such as fluid accumulation in the lungs or reduced oxygenation to the bloodstream, organ failure potentials, et cetera. So there are many supportive therapies such as oxygen therapy, mechanical ventilation. However, there is no definitive cure available. What about the mesenchymal stromal cells? They are multipotent cells found in virus organs and can differentiate into variety of cell types. It has an immunomodulatory function, so it can regulate immune response. Also, it has a regenerative ability, so it can promote tissue repair. So there's some potentials and using them in ARDS as they can modulate lung inflammation and enhance repair of the lung injury. So the objective of the study was to systematically assess the roles of mesenchymal therapy cells in ARDS outcome in COVID-19 patients based on the available RCTs, randomized clinical trials. So we searched Bob Med and Bayes Cochrane up to December 2022. We included only RCTs that compared mesenchymal therapy to standard care or placebo, mainly placebo, which we were focused on. And we focus only on patients who has ARDS from COVID only. So we used risk of bias by Cochrane to utilize and to evaluate the risk of bias. We focused mainly on all-cause mortality rates and adverse effects occurrence. We used R version 4 and employed metaphor and meta-packages to do the analysis. So we included about 10 trials comprising about 576 patients with the two groups. We have about 300 mesenchymal therapy patients and about 278 patients in control group. Most of these have used umbilical cord as a source of mesenchymal cell. Few of them have used other sources. Regarding the quality assessment of the included studies, as you can see, the majority of the study exhibited low quality of the studies. Majority of the study exhibited low risk of bias in the randomization process and measurement of outcomes. However, some concern were mainly in deviation from intended intervention and missing outcome domains. So the main outcomes, the mortality. We observed that it used a significant reduction in mortality in the mesenchymal group compared to placebo groups with a risk ratio of 0.78. However, it was slightly decreased. As you can see, the confidence interval reached about 0.96. However, the variability for I-squares was 1%, which is good. In terms of adverse events, there was no significant difference in terms of adverse event between the two groups, the mesenchymal and the control group, with a risk ratio of about 1.1. So mesenchymal therapy appeared to be promising for COVID-19-inducing ARDS. It has significant reduction in mortality, but no increase in adverse events, or maybe there was no significant difference between the both, so there is no adverse event possibly associated with mesenchymal therapy. However, as you can see, we have small number of trials with small sample size, so there is a need for more extensive RCTs to establish optimal therapy for mesenchymal administration protocols. Also, we need to determine the optimal dosage, how to explore, maybe further, a way of administration, and assessing the long-term effects of this therapy. Thank you very much. Thank you.
Video Summary
The video transcript discusses the impact of implementing an intensivist program and antibiotic stewardship program on carbapenem utilization in an ICU. The speaker highlights the high usage of carbapenems in their hospital and the need to target this in order to reduce the development of carbapenem-resistant bacteria. By implementing an intensivist program and antibiotic stewardship program, they were able to significantly reduce carbapenem utilization by 50%. This reduction in carbapenem usage did not negatively impact patient mortality rates and may have even improved mortality outcomes. The speaker emphasizes the importance of antibiotic stewardship in optimizing treatment while reducing adverse events and costs. They mention the need for co-leadership between physicians and pharmacists in antibiotic stewardship programs. Another speaker discusses the use of beta blockers in patients with refractory ventricular fibrillation and pulseless ventricular tachycardia. They conducted a meta-analysis to assess the effect of beta blockers on sustained return of spontaneous circulation and short-term survival. The results showed that the use of beta blockers was significantly associated with a higher chance of sustained return of spontaneous circulation, but not with short-term survival. The speakers emphasize the potential role of beta blockers in controlling refractory ventricular fibrillation and ventricular tachycardia and the need for further research in this area. Lastly, a speaker presents a study evaluating the impact of ketamine infusion on bispectral index in paralyzed, critically ill patients. The results suggest that ketamine use is associated with an increase in bispectral index scores, indicating potential over-sedation of patients. The speaker suggests caution in using ketamine in this patient population and the need for further studies to explore this relationship.
Meta Tag
Category
Critical Care
Session ID
4026
Speaker
Patrick Barney
Speaker
Muhammed Elhadi
Speaker
Sushan Gupta
Speaker
Daisuke Hasegawa
Speaker
Stephen Toth
Speaker
Michael Wilson
Track
Critical Care
Keywords
intensivist program
antibiotic stewardship program
carbapenem utilization
beta blockers
refractory ventricular fibrillation
pulseless ventricular tachycardia
bispectral index
over-sedation
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