And right now, we're gonna start with Bhumesh Patel. He is an Assistant Professor of Anesthesiology and the Co-Director of the Yale Adult ECMO Program. He's the Associate Program Director for the Adult Cardiothoracic Anesthesia Fellowship in the Division of Cardiac Anesthesiology at the Yale University School of Medicine. And thank you for speaking, Bhumesh. Perfect. Thank you, John, for the introduction. Good morning, everyone. It's a pleasure to be here with you today. I'll get started. No disclosure from my end. Objectives, we'll briefly discuss top critical care trials from 2023. We'll start with the device trial, which looked at video versus DL in critically ill patient. Hypothesis was the use of video lingoscopy would lead to a higher incidence on first attempt. Design was a pragmatic multi-center, 17 centers, primarily in the ICUs and ED. Primary outcomes were successful intubation on the first attempt, with some secondary outcomes for severe complications. Patient characteristics, pretty similar across the groups. Just wanted to point out that 70% of those, these were done in the ED, but about 30% in the ICU. And same level of difficulty in intubation amongst the group. Now, the interesting thing here was the operators. Here's where 70% of them were ER docs, followed by 25% of ICU physicians. And the level of trainings were actually surprisingly, 70% were residents, followed by 20, 25% of fellows. As expected, had a better view, grade one view with video lingoscopy. Primary outcomes did indeed confirm the hypothesis of higher success of first attempt with video lingoscopy, which was significant. And in terms of secondary outcomes, there was no major difference between severe complication amongst the group. So key takeaway here, we do know that video lingoscopy has been increasing, especially outside of the perioperative realm. And what's important here is the people in the ED and intensive care non-anesthesiologist still will need proper training of video lingoscopy. The next steps, we will see an increase in this use of technology across board. And our job as anesthesiologists is here to make sure we help our training of our colleagues to make sure they're competent in video lingoscopy. That includes ED physicians, as well as pulmonologists. The next trial is the SELECT-2 trial, which looked at thrombectomy for larger ischemic strokes. This is important because mostly patients with large stroke have been excluded from thrombectomy trials and guidelines. The question here was, does thrombectomy within 24 hour leads to better outcomes? And the design was international across multiple countries in 31 sites. The primary outcome here that was looked at was modified ranking scale at 90 days, along with some functional out secondary outcomes. Intervention was one-to-one thrombectomy versus standard medical care. Patient characteristics pretty similar. Just wanted to point out, surprisingly, only 20% in each group had received thrombolysis and had about the same stroke score, as well as the same level of core infarct on imaging between the groups. Primary outcomes did indeed confirm that patients in thrombectomy group have a lower median ranking scale of four compared to five in medical care. And just for reference, a score of five is severe disability where patients are strictly bedridden and require constant care. So very meaningful response here from the intervention. Secondary outcomes as well showed better functional independence at 90 days in the thrombectomy group. Given it was an intervention, safety outcomes luckily did not show any major adverse events from the intervention itself, specifically intravenous hemorrhage and or any death from the intervention group. So key takeaway here, specifically, this applies to all ICUs where I think people with large ischemic strokes, hopefully will be given opportunity for thrombectomies in the future. And especially since there was no major complication from the intervention. And in my opinion, I think this could be a practice changing going forward. It's already happening in certain institutions, especially if it makes into the new guidelines. A big limitation was here, it was actually terminated early for efficacy. So this potentially could have led to overestimation of the thrombectomy group. The next is the DCD trial with heart transplantation. The problem remains that we don't have enough hearts in the country for our patients. And the question here was, does DCD transplantation have a non-inferior outcomes compared to DBD transplantation? Design was 15 centered across US, a multi-center randomized trial. Primary outcomes was survival at six months after transplantation and some key secondary outcomes, specifically PGD and primary graft failure in these patients. Patient characteristics pretty similar across the group, except as you look down on the allocation status, a sicker patient were two and a half times more likely to get a DBD heart status, especially status one and two. Primary outcomes did indeed show no difference for non-inferiority between the groups, adjusted for patient and donor characteristics, as well as in the unadjusted primary analysis. Similar for graft survival at one year. In terms of safety outcomes, this is where patients in DCD did indeed have a moderate severe PGD compared to DBD group. However, importantly, there was no severe adverse events from graft related issues, and more importantly, no primary graft failure leading to re-transplantation. So I think a key takeaway here would be, I think DCD is here to stay and it will definitely help improve access for these patients. A big limitations indeed remains that, it's obvious that the imbalance between the allocation definitely led to contribute to the success of the trial. And the next step, again, I think this safely will be expanding care and access to this lifesaving therapy. The next, you know, it's pretty controversial study, especially early ECPR outside hospital arrest, and a big problem remains that, you know, especially the two trials preceded this were stopped early. One showed superiority and the second was futility. Hence the trial came about. The question here was, does early ECPR improve survival with favorable neurological outcomes compared to standard care? Designed mainly in Netherlands across 10 centers are randomized multi-center study. Primary outcomes was survival with favorable neurological outcome at 30 days and some secondary outcomes. In terms of patient characteristics, the common things, you know, were similar between the groups, specifically age, shockable rhythm, and more importantly, the witness arrest aspect. In terms of the intervention and timing, had similar time from arrest to EMS arrival as well as from arrest to ROSC. Primary outcomes did not show any difference between the subgroups for neurological outcomes. And a key conclusion here, and I think most of us are dealing here, you know, it's not simple. You know, there's no significant difference here, and it's not as easy to replicate outcomes that's been published from certain centers. And just the next step would be a word of caution for people who are considering expanding their ECPR programs to outside of hospital arrest. We really thoroughly need to examine our criterias, which are institution specific and truly look at how efficacious this therapy is. The next is the Clover trial. I personally welcomed this trial because of my personal practice, but looked at early restrictive and liberal fluid management in septic shock patients. And the problem remains that fluid and vasopressors, you know, are common therapy, however, how much and when remains to be answered. The hypothesis here was, does restrictive therapy within the first 24 hours leads to lower mortality at discharge by 90 days? A design was 60 centers around the US multicenter randomized trial. Primary outcomes was death by any cause by day 90 and secondary outcomes was a 28 day measure. Intervention was very criticalized. And here, once a patient was in septic shock, received fluid, patient was randomized to either restrictive which meant vasopressors were preferred and then rescue fluids were secondary compared to liberal strategy where an additional two liters were given followed by a vasopressor. And in terms of patient characteristics, pretty similar, specifically, you know, similar in heart failure as well as end-stage renal disease, including SOFA score, mean blood pressure, as well as lactate levels. Therapy did indeed follow protocol. And as you can see, significant difference between fluid administration, 1.2 in the restricted compared to 3.4 liters in the liberal subgroup. And the primary outcomes here did indeed not show any difference between either group. However, the secondary outcomes as well did not show any difference between the groups, specifically, the incidence of renal replacement therapy here. And a key takeaway here, you know, I was glad what it showed. And I think a key takeaway is restrictive strategy after initial resuscitation does not lead to higher mortality in these patients. And early vasopressor is safe to use. And the next step, I think obviously we need better studies with protocol using volume responsiveness and perhaps include POCUS-guided resuscitation in those studies. The next is the STRESS-L trial, which looked at beta blocker in septic shock. We know tachycardia is common in septic shock despite vasopressors, and there's uncertainty in terms of beta blocker use. So the question here was, does beta blocker improve SOFA scores in patients with tachycardia and septic shock on Lebofed? And the design was open-label 40 centers across the United Kingdom. Primary outcome was mean SOFA score. Over 14 days. And the second outcome was mortality at 28 and 90 days. Intervention was once a patient was in septic shock on Lebofed tachycardia, they were randomized to either a beta blocker using Lendiolo or standard care. Initially, the trial had planned for 340 participants. However, trial was terminated early from an advice from independent data monitoring committee that demonstrated unlikely benefit. And more importantly, there was a signal toward possible harm in these patients. Patient characteristics pretty similar between the groups in terms of steroids use, mean lactate, mean blood pressure, and heart rate. And primary outcome did not show any difference here. However, the secondary outcomes did point towards higher incidence of mortality at 28 and 98 days. Hence the trial was stopped early. And especially you can see higher lactate level and increased use of vasopressor in these groups. So conclusion, I think we can adequately say the routine use of beta blocker should not be a standard therapy in patients in tachycardia and septic shock. But big limitation of the trial was obviously the cardiac output monitoring was left as their discretion and that was not in the protocol. So next step perhaps, I personally very restrictively use beta blocker and one patient population I use it is patients on VV ECMO with ARDS and trying to decrease the shunting from ECMO. So perhaps I would personally welcome those study to see whether or not it's causing harm in those patient population as well. The next is AMI shock and ECMO. We all know ECMO has been increasingly used despite lack of evidence of its mortality. The hypothesis here was early ECMO prior to PCI would lead to improved survival. Design was specifically in Germany and Slovenia, 44 centers, multi-center trial, randomized trial. The primary outcome was mortality at 30 days. Intervention was one-to-one, ECLS preferably prior to PCI in patients in shock. Pretty similar characteristics between the subgroups in terms of AMI shock, median lactate levels and the sky stages. The treatment groups, just wanted to point out a couple of things where 17 patients in intervention group did not receive ECLS and patients in control group did receive 20% of them had some sort of LVAD balloon pump or Impella support, which is part of medical therapy now. And then about 28 patients did indeed cross over to ECMO. And there was no difference in terms of primary outcomes between the subgroups. Secondary outcomes as well, no major difference. And as expected, there was higher incidence of complications of bleeding and peripheral ischemia in the ECMO subgroup. So a conclusion here, I think, it's pretty straightforward via ECMO. There's no benefit of early VA ECMO in patients who can be stabilized with medical care. And perhaps obviously there continues to be a role for rescue VA ECMO in patients who are refractory to medical care and potentially can be bridged to transplantation or a VAD. Limitations that we talked about, significant amount of crossover and a lot of these patients indeed had a high incidence of cardiac arrest prior to randomization. And again, the next step, we know that ECMO is not an answer for all kinds of cardiogenic shock and perhaps future study needs to personalize MCS based on type of cardiogenic shock. The last and my favorite trial of last year is the motive trial. And the reason being one is in the perioperative space and advancement in medicine are only as good if it can reach most patients in the world. The problem remains that postpartum hemorrhage continues to be the leading cause of maternal complication and death worldwide. Question here was, does a multi-competent strategy of early detection as well as a treatment bundle leads to better outcomes? Design, again, international trial cluster randomized in four countries in Africa, Kenya, Nigeria, South Africa and Tanzania across 80 centers. The primary outcome was a composite measure of severe bleeding, laparotomy and maternal death and some key secondary outcomes. Intervention here, as you can see, was early detection using just calibrated drapes which trigger lines at 300 and 500 followed by a bundle that we are all familiar with. And both of this was done in parallel. And patient characteristics be similar across the groups in terms of age and prior deliveries. Primary outcomes did indeed show decreased incidence of composite outcomes between the subgroups which was significant. And key secondary implementation, as you can see, significantly high detection of postpartum hemorrhage and adherence to the treatment bundle. And here's the difference. In this study, there was a seven month baseline period and then transition phase where patients in the hospitals, sorry, the hospitals had an education time followed by implementation phase. And as you can see, there was a clear benefit here. And the conclusion here is, early detection remains very important. You can't fix a problem if you don't recognize it. And that in conjunction in parallel leads to better outcomes. And the scalability of trials is important as well because it can be applied to lower resource facilities. The next step remains that we need to be better at wider adaptation and implementation. And I think this is where our role as anesthesiologists become very important and critical. And we need to be better globally. And I think it's our job to train anesthesiologists and non-anesthesia physicians across the world and more importantly in lower resource country and truly be global in our outreach. And there's no doubt with more mothers, the world will be a better place. And that's all I have. Thank you very much. Thank you.

critical care trials

video laryngoscopy

thrombectomy

heart transplants

septic shock