Good morning everyone. Thank you for that very kind introduction. I'm going to be speaking about the surviving sepsis campaign contemporary research priorities and I'm really grateful to the European Society of Intensive Care Medicine and the Society of Critical Care for Medicine for giving me this opportunity. Before I start I'd like to state my disclosures. I have no financial disclosures, a conflict of interest, but I am a member of the surviving sepsis research committee and also a member of the surviving sepsis campaign 2025 guidelines committee and a steering committee member of the Asia-Pacific sepsis Alliance. I'd also like to thank Dr. Craig Cooper Smith for allowing me to for sharing some of his slides for this presentation. So I'm sure all of you have seen this paper which was published just two days ago on Friday, surviving sepsis campaign research priorities 2023. I hope all of you have read it. So I'm just going to give you a broad overview because I want to have more time for discussion. I want you to go back and read this paper so I'm just going to give you like a little teaser on what we have for this paper. So a little about the surviving sepsis research committee. Now this is a multi-professional group that you know which has representation from the European Society of Intensive Care Medicine and the Society of Critical Care Medicine and there are 16 members and I was very proud to be one of the members on this committee and I looked after the domain on resuscitation. So these 16 members, multi-professional group and of course we had two very dynamic past presidents who were co-chairs of this paper that from ESICM Daniel DeBacker and from SCCM Craig Cooper Smith both past presidents who were co-chairs and led this entire research committee. So just going a bit about the surviving sepsis priorities the entire process. So this 16 committee members represented SCCM and ESICM and they were chosen by the presidents of both the organizations and they decided to use include authors with expertise in a wide variety of topics related to sepsis and some of the authors were from the SSC previous iterations of the SSC guidelines some were not involved but basically what they wanted to us to cover you know a wide range of things that were not covered in the previous guidelines as well and of course various aspects of diversity were taken into consideration. And it was a very simple process actually that we followed and what each member was asked to do was to submit five research questions on any subject that they felt would be improved the understanding of sepsis. So all the members of the team would submit this and then the task force explicitly you know sort of told them to pick the topics that they felt were most important from the entire lot and this was again not restricted to any particular area or not restricted to you know the previous whatever was already covered or not covered by the previous guidelines and the expectation was that this kind of open-ended process would lead to research questions spanning over a broad spectrum or especially of unanswered essential questions related to sepsis. So this is the kind of flow diagram looks a little complicated but was a really simple process. There were 81 questions that were put together by this group and there were many overlaps so they were you know removed and finally there were 34 clinical questions and there were 10 basic science questions and then the members of the committee they voted and from these questions we got five top clinical questions and top five basic science questions and the remaining 34 questions were not considered as a top but they were also included in this in the research priorities but not as top priorities they were only five and five from the clinical questions as well as the basic research. So these were the top research priorities, five top clinical prior research priorities and five from basic sciences. I won't go through each of them but I'll just tell you the kind of the way in which they are described. So each of these you know the research priorities there is you know first we have described what is known about the topic and then we talk about what are the gaps in knowledge including a critique of whatever evidence that exists about this and future directions in which the research should progress and again they are listed not in order of the importance but in the order of you know the patient management. So I'll just put you through one of them not all the five because then I'll take a very long time and I want to have enough time for discussion. So the first clinical question was what is the best strategy for screening and identification of patients with sepsis and can predictive modeling be used in real time to assist recognition of sepsis. So what it's important to know what we know so far so in the 2021 iteration of surviving sepsis guidelines they recommended that healthcare systems have performance improvement programs for sepsis including screening. Identification is crucial since any delay in treatment is associated with what outcomes as we know and identification requires the recognition of infection the acute organ dysfunction and determination and also that this is due to a dysregulated host response. So it's really really important for us to know and we know that we have many screening tools that are available in our mentarium for predicting this kind of clinical deterioration you know and also for outcomes however many have utility and each is associated with they have some limitation or the other. So this was an important you know to know further about this and to do research. So the real gaps in the knowledge are the best screening tool for sepsis is still unknown and this is really important for us because we're going to manage it if we know what that this is sepsis in the first place and without standard diagnosing of infections sepsis or dysregulated host response or organs dysfunction both the adjunct both accurate and generalizable the it will be very difficult to create them and despite the interest and the growth in automated sepsis screening models we have many of them high quality evidence of the benefit or routine care is actually lacking. So a future directions would be of course that we need studies to determine whether these various sepsis algorithms that are generalizable to different especially this electronic health records have accurate sensitivity specificity and also positive predictive value to be incorporated in the clinical workflow and we need studies to test if these automated sepsis algorithms improve outcomes compared to routine care and these studies should not only be large-scale observation studies but it's important that we also do prospective randomized control trials to add value to the algorithm and what was recommended is that these RCTs should be designed as cluster randomized control trials and randomized you know units within the hospital to have both alert in live mode and silent mode and comparing these outcomes so that means including the patient related outcomes but also the impact of this on various health care systems. So based on this various you know recommendations for various questions that needed to be addressed were given that what defines a dysregulated host response how should sepsis algorithms be trained and what should be used as a gold standard how are automated sepsis screening best implemented into clinical workflow when implemented well can automated sepsis screening to algorithms actually improve care processes and also outcomes as compared to the usual care and more importantly how is sepsis screening best implemented in the low resource settings so this is just an example of how each clinical question and also the basic research questions was addressed I won't go through each of them but I'll just talk about the other four the important clinical ones the second question was what causes organ injury and dysregulated dysfunction in sepsis how should it be defined and how can it be detected and there were various there were three parts to this and the first part was what causes organ injury and dysfunction in sepsis then we had a second part that do we know how can we identify this organ dysfunction and the third mark was that can blood biomarkers various biomarkers that we have can they be used to improve our understanding of what is happening so if we could have something that could tell us real time about the effect of you know on the you know tissue cells and the tissues with this ongoing sepsis if we could know this real time that would really be useful and the way forward for research to progress in this area and this was the third question was on fluid resuscitation and this was the part that I was involved in and should it be individualized initially and beyond so the many many unanswered questions in this domain and 3a is what is the optimal fluid management not only in the first 24 hours but also going further and you know for these patients who present with hypotension and hyper perfusion and as we know in the even the last iteration of surviving sepsis guidelines we talk about giving 30 mils per kg of fluid for the initial resuscitation and this is based on one retrospective study so whether we can use this all one-size-fits-approach or we should have a more individualized approach what is the best hemodynamic tool should we look at fluid responsiveness to predict you know the requirement for fluid and individualize our care if we use flu-lose responsiveness there are various tests and which test which one is better over the others and you know which one can predict the fluid responsiveness better and which is the best fluid for the initial resuscitation we all use crystalloids but should we be using you know balance or solutions or should we you'll be using saline many many unanswered questions in terms of individualized resuscitation the fourth question was the best vasopressor approach for treating the different phases of shock even with vasopressors there are many unanswered questions what should be the target of the vasopressor therapy for example the mean arterial pressure or should it be organ specific special region pressure or should we be looking at the diastolic pressure and what are the strategies to optimize your vasopressor therapy to improve the outcomes so when should you initiate the vasopressor should you give fluids and then start the vasopressors if there's no response or co-administration of vasopressors and in what circumstances can the vasopressor be delivered peripherally and what is the role of epinephrine or adrenaline can you use adrenaline and this is an important question in resource limited settings where it's you know is cheaper and readily available and for patient with septic shock receiving norepinephrine and vasopressin which drug should be weaned off first should you stop your norepinephrine first or should you stop your vasopressin versus there but these are very important clinical questions for which we really don't know have the answer and the fifth top clinical question was that can a personalized precision medicine approach identify optimal therapies for improving patient outcomes and there were also top basic science priorities I'm not going to go through each of them but many looking at various aspects of sepsis how we can you know improve the animal models that we use and make them resemble as closely to humans because we're using them as surrogates for various therapies that we're using in humans aren't we and how can we you know outcomes be maximized correlation between the animal models and in sepsis and therefore use appropriate tools in both and various other you know points were identified and these were the five top basic research questions in addition to that there were many other clinical priorities the remaining 34 were also included and this has also been detailed I won't go into you know into this but should you have you know separate for immunocompromised patients should there be separate recommendations should we be used looking at you know sepsis outcomes in obese patients differently so there were very different perspectives that were given and more towards an individualized approach and not a one-size-fits-all approach towards sepsis so these have been identified you know outlined I won't go into details in the interest of time and there were also other basic science priorities that have been enlisted in these in this paper and if you look at the last iteration in 2018 we had a similar SSC research committee was formulated a joint committee by SICM and SCCM and also identified six clinical priorities that have been enumerated here in the 2018 guidelines that were published and if you look at the progress that has occurred since these 2018 there has been significant progress that has been made for each of these questions that have been enumerated however it's very interesting that four of the you know of the top five clinical priorities in the new surviving sepsis guidelines four of them are actually from the previous iteration of the 2018 guidelines and this is not really surprising because when you have multiple studies have been performed and this has you know changed the way we manage sepsis never nevertheless when you have use a concept of precision medicine it means you know there's with near certainty you can't have a one-size-fits-all approach and a sepsis of course as we know is a heterogeneous entity and continuing to ask the big picture questions will guide the future of sepsis and the care and this necessitates that every time you ask one question is answered this will follow with many other questions from the same domain so this these were the basic research questions that were asked in 2018 and although the few basic research questions have translated into improved outcomes the majority of the basic science priorities have changed from 2018 the question related to microbiome represents the only one that is repeated from 2018 to this iteration of the research priorities and this may be because the combination of chair questions has actually changed with the change in the committees and between the previous iterations of the guidelines so I'll just conclude by my last two slides so if you look at the general limitation of this kind of process of having the research priorities now of course you know one of the inherent limitations is there is subjectivity of course in the process and this panel was composed of intensivists so not all intensivists are they not the only ones who manage sepsis right there are non intensivists who manage sepsis but they were not included and some countries had higher representation sadly Africa was not represented and significantly less is known about sepsis management in resource limited settings though the kind of questions that were used were independent of the practice setting we know that there will be differences in high and low resource settings and this of course needs to be incorporated in the future you know iterations and most importantly that the committee did acknowledge that in order that some elements of the research agenda ultimately reach to the patient you know there are pragmatic elements in its success and therefore it's very important to include explicitly link the research performance to implementation science if you really want to get it at the bedside so I just like to summarize by saying that this surviving sepsis research priorities actually is designed to be a catalyst for the research that's required in sepsis and the knowledge that is advanced in the incorporation with various iterations of the surviving sepsis campaign guideline has actually allowed us to have evidence based recommendations for the management however we all acknowledge that there are such gaps and they remove and these are the you know the therefore we cannot have very strong recommendations and the priorities that have been identified represent a kind of roadmap for research in in sepsis and septic shock in the future and the hope really is that this document spurs international research on sepsis both to change clinical guidance in the near future and also to answer more basic questions that will hopefully spear the discovery and innovation and can be translated into fundamental breakthroughs in sepsis and with that I thank you very much for your attention

Sepsis Research

Precision Medicine

Critical Care

International Collaboration

Sepsis Management