Sepsis Update I 2022

more than 30 years and Pulmonary and Critical Care Medicine and he is an associate professor at the University of Alabama in Birmingham and tonight he'll be giving us an update on sepsis but there will be another session on the 25th of August and that section will be at a different time of 9 30 so half an hour later in real time but whatever time that corresponds to yourselves just to let you know the advanced mechanical ventilation course will be conducted on August the 31st and September the 1st so please visit the event tab on the website for details about registration all educational sessions are available now under the top education of the website however you will need to be at least a silver supporter of our mission to be able to access them so we just recommend again that if you're not already a silver supporter that there's so many benefits included with being one and we really appreciate everyone who supports us at ICU reach so at night I'm going to pass over to Dr abhishala and let him take it away thank you very much thank you Grace and thank you Madison um I'm really uh excited to share this information with you um um talking about sepsis and septic shock is uh a passionate topic we see it very often in the ICU and a lot of you no matter what specialty you might be doing if you're not already working in the Intensive Care we'll be facing the different manifestation of sepsis um so with that I mean there there have been some issues uh I I'm gonna say it at the beginning and maybe say that the end is what we usually do in sepsis um so sepsick and and and in general but you know septic shock we like to keep things perfused we like to fill up the tank and we want to get the pressure up uh and you want to do all of these things at the same time concurrently and quickly um so everything we're going to talk about is how can we do that uh aseptic shock patients or somebody who's hyper perfused and hypotensive and you're dealing with those patients in various manifestations different phases of their Illness but that's sort of the bottom line so I'll come back to this and we're going to try to dissect how we can get all of these things done and how we can do it all at the same time so with this sepsis is not an easy disease to recognize it may be very clear to uh sometimes when you have the classic knowledge of having the patient infected having fever um and drivers and have a clear-cut pneumonia and they they gradually drop their blood pressure this may be a easy patient to identify but many times sepsis is a big masquerade of other illnesses and and sometimes we're not sure uh so you want to err on on making sure sepsis is in your differential diagnosis particularly in those patients that present atypically uh like those patients present only with ultimental status for example now how important is sepsis and how we manage it um here I'm trying to show you three different sort of scenarios if you happen to work in an emergency room and you see these uh different situations so one on the left is somebody who had a car accident he's alert and his blood pressure is 130 over 60. the next is a patient who's having chest pain he's 70 years old and he's having a stomach and the third one is a patient who's having cough and fever confused and his blood pressure what people call it these days soft these blood pressure is 88 over 50. now when you look at these patients you know how do you imagine is going to be seen first if you happen to be there and you know whether you're a nurse or a physician uh who's gonna you're gonna run to see first um I know we're not doing any polling here but you know if I were to bed very likely most people are going to go to either the patients on the left with a car accident or the patient with the stemi and the last person is to be seen is a patient who's having cough fever and a soft blood pressure uh and I'm not saying this is appropriate whenever appropriate but at the same time I want you to be aware that the mortality of these patients that person roughly about five percent a patient with stemi it's about 10 and that patients with pneumonia and sepsi and sepsis has a 30 mortality so that may should make you think differently in the future when you deal with that I'll and and it is urgent to manage sepsis as it is urgent to manage any of the other conditions and probably some time uh more important so with this um the reason for preventing this confusion is that they have published several guidelines and this is the history of the guidelines uh as you can see it here it started from 2001 uh it's usually published in both journals a critical care medicine and the Intensive Care Medicine so European and the North American journals tends to publish the guidelines simultaneously and as we can see here the guidelines been about every four years and then there were some updates so 2016 you see here different bundles and I'll mention to you why we use those bundles and then finally the last one was in 2021 and so we had in 2018 that was considered to be a supplement based on newer data I've been a lot of debates and con and and uh uh criticism for the one hour bundle then now we're back to the one hour and three hour bundles for managing uh patients with uh receptors so 2021 is the last guideline now the terminology of sepsis and and I think some of you have seen this sort of progression from what we call it sirs to sepsis to severe sepsis the septic shock that terminology was brought in from the time and I happened to attend some lectures Dr Roger bone he's one of the fathers of Care Medicine uh that was in 1992. uh and now the so the sepsis three sort of definition that was in 2018 decided to use two-tip Parts they said we only have sepsis or we have septic shock so they took the other terms and they dependent on definition of sepsis by using the Q so far the quick sofa score as you know so far is the organ dysfunction uh so if you had more than two out of the three we would use this and then if you have hypotension requiring vasopressors and the lactate after adequate fluid resuscitation you would call the patient having septic shock so that was the definition that was used uh since 2018 and now it looks like they changed their mind so 2021 they said oh we don't like the Quicksilver not anymore we're going to go back to serves so 2021 now and they came up with 93 new recommendations uh and do not worry I'm not gonna go over the 93 new recommendations or uh but they are sort of summarized in the first two to three pages of the sepsis campaign when I'm sure any one of you can Google it's available for free um so now we have three terms we have sirs which is sort of the pre uh sepsis stage where you have uh manifestations of inflammation uh you can have high low temperature tachycardia tachypnea or elevation or decreasing why count and then you have sepsis where you identify serves caused by infection and then you have septic shock and septic shock nowadays require that the patient has to be on vasopressors with elevated serum lactate uh so hypotension by so the patient need to require the the use of as oppressors so this is the new sort of agreement in the last 2021 guidelines now just to be clear uh we talk about hemodynamic instability I wanted to Define that because this is something we're going to deal with all the time when we manage sepsis is parameters and goals for management so hemodynamic stability has two parts one has to do with the blood pressure and the other one has to do with the perfusion uh so hypotension tachycardia unresponsive to treatment orthostasis patient has to have multiple fluid boluses to get the blood pressure or the use of vasopressors to maintain accurate blood pressure all of these would go in the category of what we call it BP related now parameters of inadequate perfusion is the other part that you can see the patient is hemodynamically unstable and that's a blood test could be lactic acid prolonged capillary refill time reduce urine output ultimental status or someone who has modeling and hypo perfused lower extremities in cold so as you can see here there there's part that has to do with things you can measure which is blood pressure and heart rate or these are things that you can do either as a blood test as a parameters of perfusion uh adequacy to regarding organ function now how do we do this on the bedside and this is oftenly missed and I think I'm noticing now our resident I've recognizing these things much better uh but feeling you know when you go inside the room you want to touch the patient's skin you want to feel their hands and they want to feel their feet and you want to look for modeling so having someone who has cold hand or cold extremities uh the tip of the fingers we do What's called the capillary refill time and then the modeling and I and I notice even in the most recent publication um that would present that were presented in Belfast they used Capital they used the modeling score to identify the severity of of hyper perfusion sepsis so this is where you look at it over the kneecap and how extensive is the area of modeling now if you want to get sophisticated on the right side you could do What's called the t-skin called t-central to peripheral simply if you put your hand on the patient's chest and you put your hand on the patient's hands and you can feel a difference in temperature that's a sign of hypoperfusion you can look at the oximeter itself the waveform on the finger can also give you an idea about the perfusion because it tends to be reduced the waveform tend to be more dampened and there are some more you know sophisticated near infrared spectrographies but I'm not sure these are available worldwide so with these parameters these are things you can walk in in the room touch the patient look at them and then tell whether are they having signs of hyperfusion how sick they are um now so this is a sign this is I'm trying to show you the biggest manifestation this is a patient who has significant modeling this would be almost grade five because we're going beyond the kneecap all the way up to the upper thigh and this is the same patient after adequate resuscitation you see how that skin looks beautiful pink and well perfused but this is uh but but this modeling is important to recognize and it sort of you can use your ways of resuscitation to monitor response of that patient now this has been done in a scientific way um so one of the papers that was published in the New England Journal medicine looked at capite refill time versus serum lactate and in a lot of places may you may not have the capacity to do you know see it on lactate every four hours particularly in some you know developing countries where lab limitation And Timely lab is difficult to do uh so you can do this very simply and this study looked at a resuscitated strategy targeting peripheral perfusion status versus serum lactate so you can do the finger check and you do Capital refill time you put a put amount of pressure they describe but the paper you do it for 20 seconds you make the finger tip Blanche and then you let it go and then you look at how long does it take to get the the tip of the finger to be pink again oh and and in general should be less than five seconds um so this is you know and the longer it takes the worse is the hypoperfusion so this study was called the Andromeda shock and they compared if we did this for patients every four hours and we looked at Capital refill time and actually you can do this every two hours if you want this is a bedside examination and then you look at is it as good as just keep measuring serum lactate every four or six hours and then correlate that with the outcome so this is what the study how the study was conducted comparing so you don't lactate serial measurements with a patient uh uh response to a resuscitation so if we look at it here the study had about 400 patients each about 200 in each group and the intervention was comparing capillary refill time with uh the patients doing serum lactate and if we look here at the outcome these are 28 icus five countries in South America uh the study shows that if you do this and you look at the cumulative mortality it appears that peripheral perfusion group did a little better but there was no statistical significance but again the mortality was 35 versus 43 so this is a very simple thing I always suggest that we should do this routinely uh nursing can be very helpful in in looking at that and saying you know vocabulary time it's not improving we need to do something else we may have to consider our method of resuscitation the amount of fluid the type of ionotrope and so forth but this is a very simple bedside measure has been scientifically proven to be as good if not better than serum lactic and I bet you it's under underused so here's a quick question before we move to the next uh which is um you know making that think which intervention directed to treat patient with septic shock has the strongest impact on Survival so early triage to a high volume Center early appropriate antimicrobial therapy starting corticosteroids and blood sugar control and again I don't think we're set up to do uh question answers or polls on on the system but the idea is if you see a septic patient do you feel the most important thing is to send them to a referral center as soon as possible or would you like to start on an antibiotic right away but do you think steroids would have the most impact or do I need to make sure his sugar is well controlled as we know almost most patients with sepsis uh and septic shock have uh hyperglycemia even if they're not related to um if they don't have any diabetes so the correct answer for this is going to be early appropriate antibiotics um and now we're going to talk about this later uh maybe in the part two I'm not sure how much time we will finish today to talk about initial resuscitation and infectionation so the the guidelines are divided into three parts uh one is related to how we should resuscitate patients and make and take care of the infection how do we provide hemodynamic support and adjunctive therapy is things that might be helpful like the discussion usually raised steroids vitamin C or crrt other methods uh that might be helpful to um in patients outcome and then and then you have other supportive therapy is sort of the the Optimal Care in the ICU so most of the the stuff that we will discuss in today's is going to be related to how we initially resuscitate patients and and manage infection issues so with this uh let me show you what is called the sepsis bundle and I'll tell you what's the background behind that bundle uh so the sepsis bundle is looked at these parameters uh uh which is measure serum lactate serially at least every six do blood cultures before antibiotics the yield of blood cultures doubles if you do it before uh but on there are some studies that show that if you give antibiotic don't discard the idea of doing blood country they're still helpful probably more that in the 20 range if you have somebody with bacteremia compared to about 40 range if you did it before antibiotics you want to give your antibiotics within one hour of the Ed that's the early sepsis bundle we're going to discuss that later because there's some modification now and then you want to do fluid resuscitation the recommendation based on the study that I will discuss next is 30 ml per kilogram for hypotension or lactate more than four use vasopressors for hypotension if they don't respond to fluid maintain adequate CBP methane adequate svo2 that's again taken from the early goal therapy uh study that that will discussed next and then keep measuring serum lactate so this is sort of the the initial bundle now when we look at that the reason I wanted to mention this paper because it is cited so many times and I'm sure what I did this there are a lot more exciting articles uh this is a study by Emmanuel River um mainly done in it was done in Detroit um and um they have a very large volume very large emergency rooms it wasn't in your study that looked at early goal directed therapy in the treatment of severe sepsis and septic shock um so this early goal therapy has sort of taken the practice of ICU after this publication to the point that is you know when we look at what happened afterward uh the culture have changed using what has been done but not every step of it so the study looked at intervention so if you have hypotension meaning systolic blood pressure is a 90. after initial fluid bolus your lactate more than four so you have septic shock and that's the inclusion criteria and these patients received fluid vasopressors and transfusions of the butamine depending on these parameters I will not dwell I'll go through the details for purposes of time they use the central line and they use a continuous oximetry through the central line to measurements between the saturation which is something we don't do these days and and then we can see uh so when they did the whole protocol the early goal director therapy managing them targeting fluid initial Bowlers followed by reaching High CVP giving them vasopressors for a map more than 65 and then targeting a mixed Venus more than 70 percent this patients did better they did quite much better that you can see here that the mortality reduced from 47 to 31 percent so this is almost uh uh 16 um difference that gives you an a number needed to treat of seven so there was a very astounding study that made all of us who were practicing at that time feel that we're compelled we have to follow this protocol but for some reason we didn't follow every product we protocol uh and then people start questioning do we need to do the whole six-packs or can we do a little bit of this can we modify it uh we always you know uh we always people are Rebels they don't follow exact guidelines but you know sepsis management did get better and this study have shown that there's a significant reduction in mortality if you follow the early goal therapy so after this it caused people questions and and if you look at our real practice we really never sort of did a mixed Venus continuous saturation Central lines we didn't some people did some people did not so the idea of targeting a hemoglobin of 10 which at that time we had studied to show that seven was adequate and then you know a titrating our cardiac output based on mixed VNS and then you know using dobutamine all of that was part of the bundle that was not used uh most of the time so these three studies the arise study the process study the promise study were very large randomized as you can see U.S UK and Australia looked at you know do we need every part of this protocol so they did what's called protocol-based standard therapy and they did protocol early gold therapy which is exactly how Emmanuel Revolt did his study and what it showed that there was no benefit as you can see here in the previous Slide the mortality was the same whether you use the protocol base which is early gold and doing exactly what was done in the Emanuel River study versus leaving the physician to do the usual management now we need to keep in mind that the culture have changed and people already done this fluid boluses they already started early inotropes so to be fair to the study uh now we're looking at it years later uh people changed their practice so people did look because all of these were well randomized studies and done at University Center so there was a prompt recognition for sepsis they did prompt IV fluid for hypotension people were resuscitated early and they gave them antibiotic very early in the course of early septic shock so in those settings it really after that it seems it doesn't matter if you do mixed Venus it doesn't matter if you target a hemoglobin of 10 if you use the butamine all of these issues would not be the most important uh to and and it did not show any difference in outcome so in 2021 we could say that we need to follow these three things because these are established early recognition prompt IV fluid and prompt IV antibiotic and we're going to show later the importance of each one of those so as you can see here these part of the bundles we still use we do want to measure serum lactate we wanted to re-measure it we want to do blood cultures we want to give antibiotic quickly we want to give fluid resuscitation we want to use vasopressors but we don't need to follow CVP we don't need to follow and explain this oxygen saturation now now I want to talk a little bit about for septic shock and using fluid now fluid is uh uh we have so many options when it comes to using fluid for patients that's became a little bit confusing and and so for this uh I wanted to say what would a fluid bolus do to the patients hemodynamic status when you say give the patients fluid bolus and in general I usually always discuss on rounds when I tell the resident if you want to resuscitate someone don't give them a continuous infusion because it's worthless continuous infusions for collecting electrolyte imbalances or maintaining the patient uh fluid status but if you want it challenge the patients if you want to improving or that you have to always use bonuses for that so a bonus in the range of 250 to 500 MLS is going to raise the stroke volume by about 10 to 15 percent uh but you know keep in mind that less than half the patient respond to fluid uh so the other so that's why you know most patients with septic shock end up in the ICU because otherwise we would not see them um so about 40 May respond to fluid and that's the end of it but about 60 or more will be requiring Castle pressures and coming to the ICU now with this that hemodynamic effect of fluid bolus is shortland we know fluid tends to dissipate in the interstitium and get out of the intravascular um uh tree so 15 of crystalloids remain intravascript it's about three three hours um and then if you do two aggressive fluid resuscitation it increases mortality so that's issue I will hopefully touch base on it uh as as you know there is a big talk about the resuscitation and being conservative in fluid management and I think there are some new information that came out recently in this uh that I will share with you today so with this if you look at the recommendations now about using IV fluid we see here that the initial fluid challenge usually is about a liter that's what the the guidelines recommend and they want you to use about 30 ml per kilogram of crystalloid in the first four to six hours so it used to be that it was a strong recommendation before in 2016 and 18 but now became weak recommendation so it's not like you have to give 30 ml per kilogram because you know based on review of the data and going back to the early bone therapy where this number came up is no longer felt to be a strong recommendation so it's a weak recommendation 2021 uh the recommendation continues to say use crystalloid as the initial fluid for resuscitation you could use albumin uh but it is a weak recommendation there was a point in time and the guidelines say don't use LPM because it was early trial that you know showed higher mortality and now we say no you can use it it's safe um and then we I don't think these are any more available there were several papers that showed worse outcome if you use these hydroxy uh ethyl starches with the high molecular weight so that's a strong recommendation not to use now the reason I wanted to share with you this paper and I think it's uh it was discussed in the uh Belfast meeting is you know why do we care about fluid um is uh and why the pharmacist is going to point to you and say you know uh um yeah why are you using albumin so if you look at the cost and this is a study that looked at the international comparison of the cost of fluid resuscitation therapies uh the normal saline this is the cost for about 100 ml normal saline costs about less than a dollar uh the what we call them the the other fluid the uh the electrolyte equivalent fluid uh is about three to four dollars per 100 MLS but albumin is about roughly about 59 to 60 per 100 ml so you can see and since fluid is the major management issue that gets done in hospitals so you can see how from a hospital Administration cost efficiency makes a huge difference if we use albumin for resuscitation versus normal saline versus other type of fluid but when it comes to outcome it's still also important and does it make a difference in outcome and mortality so here I wanted to compare you know what is normal saline and I think that a lot of people say there's nothing normal about normal saline because if we look comparing our plasma composition compared to the normal saline we see the sodium is higher the chloride is the major problem in normal saline is that it's very high in chloride because it doesn't have anything to buffer it uh and the osmonaut is a bit higher and it is acidic so ringus lactate seems to be closer to real plasma the sodium is a bit lower but the chloride is closer to the normal and it has lactate in it and that by the way is not usually a problem inducing more lactidemia in patients of a normal person should be able to metabolize the serial lactate and becomes bicarbonate uh the osmallowed is closer to normal so it's a little definitely more physiologic to use ringers lactate plasma light is sort of equivalent of plasma in many aspects as you can see here uh but it is a lot more less available and more expensive so now if you look at this this is called the balance fluid versus saline increasing ill this is looking at the evidence now there have been many peepers published looking at outcome if we resuscitate patients and these studies most of them were first not randomized to the included all critical L patients not specifically septic patients so if you look here this is a negative study no difference this is a negative studies called the split trial this is a smart trial which was positive in 2018 basic trial 2021 the plus 2022 and the meta-analysis here so these were various sort of looks at whether it makes a difference and I think the only true randomized trial in patients in general ICU patients were the smart trial published in New England Journal medicine 2018. this is the one that I will share a couple of slides on this one um and this one they compared balanced crystalloid versus saline so balanced crystalline could be plasmolite or it could be ringers lactate uh and this is called the smart investigator that was published in 2018 and this study if you look here and you dissect about the type of patients and whether they had sepsis yes or no and you look at the odds ratio comparing favoring balanced crystalloid versus saline we'll see that it is statistically better to give patients who have sepsis balance crystalloid them to give them normal saline with the odds ratio of 0.8 so almost like a 20 reduction in mortality uh based on the smart trial and that's probably so and the number of patients were quite good I mean you see here that those with sepsis 395 455 so it's a it's a good study to draw a conclusion from it and for that reason when I try to look at three commendations for example this is the anesthesical Care and Pain service look the choice of driving fluids for vascular filling into the L patient this is 2021 guidelines and the other question is inpatient with septic sepsis of septic shock does use a particular crystalloid solution help to reduce morbid or morbidity and mortality so their feeling is their recommendation is use balanced crystalloid for fluid resuscitation rather than normal saline and they give it a strong agreement and when I looked at the rationale it has to do with looking at that specific paper uh so I won't say that the evidence is the strongest but I think the prices is very close to each other and a lot of us practicing in the ICU now favor ringers lactate or balance solutions that they're available like plasma light over normal saline now the problem of fluid resuscitation is fluid over or there is no question that almost every patient we see with sepsis end up being fluid overloaded they swell up and that's what probably those of you who around and see family they always tell you why is my uh father or my mother are swollen up so much and that's one of the reasons the moment I walk in and sometime I had one patient who had the ring and I reminded the nurse you need to take the ring off because tomorrow you won't be able to take it off um so this is a problem you you swell the patients if it looked like that Michelin uh a man uh and that's quite common in substance so there's a principle uh I think it was published by Dr jean-mi vanson he called it the sosd concept that as initially in aseptic patients uh you initially when they're in the State of Shock you want to salvage them you want to keep keep them you know alive in a resuscitate them properly so that's where you use fluid vasopressors you know if you have somebody with uh pass upon the embolism from shock you you give them thermolytics it's called the Salvage stage and in this stage almost all patients get too much fluid the optimization phase in in the management of sepsis is where you want to get the patient to the right target that's what we start doing calculating real time say am I giving enough fluid am I giving enough uh vasopressors is there any should I optimize the antibiotics so it's called the optimization I got cultures back and then the stabilization phase is when you when you keep them from having organ dysfunction uh particularly you know are they waking up properly uh and these patients do they have renal fader do I have adequate perfusion to the kidneys do I need to dialyze and to remove fluid and so forth and then finally the de-escalation is where you start cutting down and when it comes to fluid is the time when you want to get rid of the extra fluid so sometimes you either dialyze or most of us would use diuretics when the kidneys still function so in this situation this sort of uh concept uh people talked about maybe we could avoid too much fluid so we don't have to go through this over resuscitation then de-resuscitation and that's that's a term that you'll see called the resuscitation uh in sepsis so this is one of the studies that looked recently published I believe it was also uh presented uh at the Belfast meeting through care reviews about publishing from the ignore general medicine is is restricting IV fluid in septic patients improves outcome so that was the question so the study was published here in the general medicine and these all were septic shock patients that were on vasopressors and had elevated and they called the classic trial group so this study looked at restrictive therapy and they had a large number of patients 770 almost in each group and those patients and I'll show you their protocol so if the patient get randomized to the restrictive Therapy Group these patients would get a bolus initially of 250 to 500 this is the one we discussed earlier and then you don't give them any flow you just give them vasopressors if you see signs of hypoperfusion and they Define it in their paper as having problem calculate refill time or they have modeling that is worsening then you give them more fluid but otherwise you don't you just give vasopressors and you give them limited amount of fluid initially before that and then if these patients can't be given so then you sort of give them whatever they need if you think they're dehydrated or you need to give them maintenance fluid to maintain their adequate fluid intake per day now in the liberal strategy or the standard therapy these patients had loan limitations so they could get whatever they want so 30 ml per kilogram they can continue to resuscitate with fluid based on hemodynamic parameters so they left it up to the position and the healthcare team to give more fluid uh and there was no limitation on that side so if you look at the death at 90 days this is looking at restrictive therapy where you only you basically use a lot more vasopressors and less and then the standard therapy and there was absolutely no difference in mortality between the two patient's outcome was the same so giving the patients seen that restrictive therapy is safe if you look at it either way if you are from the group that believe in restricting fluid you'll say well restricting fluid is good patient did not have excess mortality if you're one of those people who like to get more fluid in general you'll say well see I told you so you don't have to restrict patients fluid because the outcome is the same and giving them too much fluid is not uh detrimental to their outcome the problem with this study is the amount of fluid and again I always say culture change make people practice it's we've we've been talking about restricting fluid for so many years that these patients in the group did not get too much fluid in either group so the standard fluid group in in my mind and in many people that looked at the study felt that they were getting restricted fluid anyway so the difference between the two and the first day was 700 MLS and that's the the median or the mean difference between restrictive versus standard if you look after five days it was no difference if you look at 90 days 2 liters so I would say two liter is not going to make a difference in outcome in these patients uh what we've seen sometime in real practices patient who gets five or eight or ten leaders and the first day and these fishing get really blown up and then get very Intimates uh and that I feel that many times is inappropriate because people do not want to use enough vasopressors and so forth so I think this debate is at the paper says restricting fluid is equal to liberal or a traditional approach of giving fluid but I want to remind you from analyzing this paper that the difference was too small so I think both groups they did not get too much fluid um I think the best way to manage fluid is to look at Dynamic assessments and that's been recommended so that's one of the ways is to do stroke volume variation measurements a lot of the simple bedside equipment if you insert a material line which is recommended by the guidelines of sepsises in any patient required as oppressors put an arterial line so you can do invasive hemodynamic assessments and looking at the waveform of the arterial line particularly with those machines would help you to define whether they have stroke volume variation so this is one of the ways to look at it so if you look this is called the Frank Starling curve preload versus uh the patient's cardiac output you see that those patients who have significant stroke volume variation if you look at that arterial line you see significant fluctuation with breathing these patients are usually fluid responsive and giving them more fluid to bump their cardiac output and they it's called fluid responsive whereas as if the stroke volume variation that fluctuation blood pressure over time is less than 10 percent these patients are unlikely to respond to fluid and you should concentrate on just using vasopressors so that's actually the real way to do this or this is more accurate uh and it's not available to everybody uh but if you have an arterial line and you have very very simple equipment this is called Dynamic assessment now I want to move to a couple of things uh one about timing of antibiotics we will not discuss the antibiotic choices as it vary based on the patients cause of sepsis and most places have protocols based on their antimicrobial resistance but how fast do I need to give the antibiotic um so this is one of the early trials in 2006 is still being quoted that looked at timing of antibiotic and survival uh so if you look here over time uh this is zero to half and then as you move down over the longer the patient receive this study looked at appropriate antibiotic not just any antibiotic because in in hindsides you look back at the cultures so getting appropriate antibiotics the later that you give antibiotic particularly after that six hour window the mortality really becomes this one uh and the outcome is very poor now when we look at percent of patients receiving antibiotic it is you know shameful to say that about 50 percent of patients in septic shock at that time in 2006 receive antibiotic within six hours and they did have septic shock so with this I want to say that you know now that number here that you see sometime what people call it seven percent per hour is probably not accurate there are more data newer data uh that I may share with you in the part two that the real number is probably three to four percent so every hour delay in autobiotic would increase mortality by three to four percent so it matters when you give up so what happened is in the new guidelines in 2021 they sort of gave us a summary about how to deal with antibiotic timing now in 2018 I remember I mentioned to you they did the supplement to the guideline they did the one hour window they said you got to give antibiotic the first hour what did that make that made particularly Ed phys ically for the cause of fear of you know having the hospital being reviewed and not meeting the the proper criteria and government criteria because it became almost like a government mandate everybody that comes in hypotensive everybody with fever everybody was suspected substance were getting antibiotic and and that that led to overuse about the web so I think and there are some studies that show that you really don't have to give it in the first hour so now it's sort of dissected if the patient have shock is present or absent so if it's not absent it says give antimicrobial immediately ideally within one hour but you have up to three hours to give the antibiotic if your patient's not in shock So within three hours particularly if you're in the Ed where you have the capacity to do all the tests and the white count and the chest x-ray urine cultures and and so forth you should be able to figure out in three hours whether your patient is infected or not so three hours window is acceptable if you have shock they would like it to give that antibiotic within one hour of recognition and that's a Time window so now we have a sort of separation between shock present shock not present to give antibiotic time so now I know we have the the next uh 10 minutes I want to talk a little bit about hemodynamic support now when it comes to hemodynamic support uh I'll give this example here of a patient and see you know how we choose vasopressors one of the common things we hear from probably you know colleagues in in medicine is is that we can't tell the difference between vasopressors and I usually like to say it's it's really simple and I hope that I can explain it well in the next slide so if you have this patient who has septic shock somebody started a vasoactive drug and then this is the patient's numbers before and after the best active problem if you see here before chronic index 4.5 4.2 after the drug heart rate 115 110 Amino tear pressure 59 and increase is 65. so this is a vasective drug that worked and led to an increase in Minot air pressure what drug is it is it dopamine is it duputamine is it normal um so if you notice here so one of the things we look for because all of these have different effects they have Alpha Beta and sometimes neither um that's why you can look at heart rate there's no change there's no change in color index so this must be one of those drugs that have no impact doesn't have any beta stimulation so dopamine dobutamine have beta stimulation or if we have beta so the only drug that would fit that pattern would be vasopressor so I usually have this slide that I think I'm hoping that this will make things very easy for you oh so you start from isopraternal which is a pure beta and you go to the butamine mainly beta I would actually only beta the dopamine which has mixed depending on the dose epinephrine Alpha and beta norepi is predominantly Alpha but a little bit of beta so you do get some tachycardia and use high doses phenylephrine is a pure Alpha so a lot of time but however none of the guidelines in sepsis recommend that you use phenylephrine for management of septic shock the only way I can see it is the patients was getting severe severe tachycardia uh and then we can talk a little bit about this later but phenylephrine is one enough but it's the only pure Alpha now vasopressin on the other hand does cause laser constriction working on the VIP receptors without having any impact on a heart rate so with this the recommendation is to use nor Epi as a first choice this has not changed for any of the guidelines from 2016 till 2021 it always says strong recommendation not vasopressin is an adjunctive treatment 0.03 and there's a debate about when to add it uh I usually like to add it if I'm using a high dose of norepi my high dose is considered 0.3 mics and more some people think we should use it earlier there's a big debate so but it is a weak recommendation um now certainly if I'm using norepine I'm getting tachycardia then I would add vasopressin to minimize the dose now epinephrine would be the second line if you have a patient particularly when you have suspected secondary cardiogenic shock you can get cardiogenic shock from sepsis you can have cardiogenic shock when someone who has already pre-existing heart failure so Epi would be the next drug the problem with there'd be too many arrhythmias and a significant tachycard and I think all the guidelines throughout the years now strong evidence do not use dopamine and I think it's I haven't used dopamine for many many years now oh there are very very few reasons to use it uh people think that you can use it peripherally at low dosages but now we know that neuropathy can be the same the butamine is a tricky drug I've had more failure we're using dobutamine than benefits but supposedly when you have a low cardiac output particularly with patient pre-existing heart failure first you need to make sure it never started alone and never started at the beginning because you're going to make the patients more vasodilated it's a bit Agonist but it's a vasodilator so it is one of those to add on to norepi if you still have a low cardiac output parameters and hypoperfusion and you feel the patient's IV fluid status is adequate so uh now so if you notice here the term in the 2012 they always reminded us use vasopressors early uh you know in my early training say you can't use vasopressors until you give enough fluid now it says it's even when hypovolemia has not been resolved so you do it in conjunction remember the term I said in the first slide do all of these things fill up the tag get the flusher up and do it concurrently so you don't need to wait for all the volume the three liters that you wanted to give to the patient to say I'm not going to start vasopressors usually the holding factors for using early vasopressors is where the patient is located and whether it's available to you so if you are on the floor a new patient crashed and you don't have a central line many people will not stop as oppressors and I think that's probably going to change based on what we're learning these days so with this 2021 said that the same thing use it even when hypovolemia has not been now here I'm showing you this cartoon to explain why vasopressors would help you to reduce the amount of fluid needed so as we know in sepsis physiologically the veins get dilated so we have vino dilatation of vasoplegia so your capacity capacitance increase and your blood vessels get bigger so you need more volume to fill them and that's why you end up pumping fluid and sometimes imagine where is this 8-10 liters of fluid that I gave to the patient go through because now you have bigger vessels so in order not to give too much fluid to reach that tank to get the blood pressure out you can squeeze that blood vessel so it make it more constricted so now it goes back to the normal volume and I need a lot less fluid and that's a rationale of using uh vasopressors is sort of causing some degree of vasoconstriction so you don't need to use that much fluid and that's the idea of doing both at the same time in conjunction so you don't want to use norepi in someone who's hypovolemic that would be bad you don't want to use too much fluid without vasopressors because you don't end up drowning the patient so now what target blood pressure these are the two questions that come up to vasopressors and now here I'm trying to clear the debates and how soon should be used of as oppressor so timing and Target now the traditional target has been listed above 65. that's a number based on early trial that looked at outcome brain perfusion and renal perfusion uh and then I think that's been challenged with a large study uh that I feel it's sort of not well used called the 65 trial so the 65 trial is a study that talked about how to give less vasopressors to elderly shock patients so 65 meaning the patient had to be over 65. and had to have septic shock and they randomized these patients two called what they call the studies called effect of reduced exposure to vasopressors and 90-day mortality and they call it the 65 trial and this trial said okay instead of aiming for the traditional because anytime you tell the nurse I want blood pressure 65 and above that means she's going to aim for 65 to 70 or 70 higher so this study said we're going to aim for 60 to 65 versus 70 to 75. so this is how you can randomize a patient have enough difference to tell if there is any change so if you notice here the average patient in the trial that got the lower blood pressure was 66.7 and you see the range versus the other group that got a map of 73 average and this is the range of blood pressure here on that group so they did have a good separation between the two uh and I'll remind you a lot of these patients uh all of these patients went above 65 and a lot of them more than 40 percent had hypertension so when we look at the outcome of these patients there was no difference in mortality so they call this permissive hypotension versus usual care mortality was the same and actually there was about two percent less patients had a lot less need for vasopressors these patients had a lot less fluid received uh and uh and and and uh and they did the same they have the same mortality with and I wanted to say the third issues there was no increased renal failure between these patients with the permissive hypotension despite the presence of chronic hypertension so I think based on this study and I think now the guidelines have talked about it but not clearly but 65 is acceptable and I've you know I think we're working on changing our Target in blood pressure and using 60 to 65 in any patients who has septic shock or any State of Shock because that seems to be acceptable outcome with no with reduced needs of vasopressors now how soon you want to give your vasopressors and that's also a debatable issue uh been raised is you know should I give the fluid and stuff as oppressor should I do it very early um so in my previous presentation I was reminded by one of our uh former fellows about one of the papers that was published recently um so but before I go through the paper I want to tell you what the guidelines say so the guidelines tell us U is not Epi use a target of 65 now they're not saying higher than 65 so that's a 2021 now they're telling us you can use vasopressors peripherally and with peripherally there is sort of a mandate here and they we discovered recently that they have a typo in the guidelines uh so when using vasopressor periphery they should be administered only for a short period of time and in a vein should be distal not proximal to the anti-cubital fossa but that's a typo in the guidelines so meaning you can run a peripheral levofed in a patient uh and that's their recommendation that's the idea of using vasopressors early and then here they talk about so they wanted to use this in the first hour that's what the guideline recommends so after the guideline was published there's a peeper that caused a little bit of confusion this this is a Korean sepsis Alliance investigator and that looked at vasopressor initiation within one hour of fluid loading is associated with increased mortality and it can cause a problem it's published in the care journal in April but I want to remind you to stop a randomized trial this is a prospective multi-centered observational study so this is administrators looking at huge database and they cleaned it out and they said we're gonna do this propensity score and compare patients uh that have the same severity of illness and see with those who received vasopressors in the first hour because the decision The Physician felt he wants to give in the first hour versus those who received it later does that make a difference when you look at the study it appears that mortality was higher so if you look at the early vasopressors they have 48 mortality this is a Kappa Maya curve and this is 34 mortality in the late vasopressor so if you were to take this data and accept it you would say early vasopressors is detrimental we should not do this and they talk about their rationale and delaying fluid but I think I want to remind you of the same problem with propensity scores and first this is Administrative data this is someone who looked at it and they were forgetting the confounding factors and I think the simple factor is when the physician decide to give back a person that means he sees the patient on the bedside sicker the same thing happened with the PA catheter and years ago there was an editorial say PA catheters are killing people because they did this again propensity score so the patient had be a catheter more likely to die so people thought the pH catheter is killing them they were not dying from complication of the Pia catheter they were not dying because of Point reality of bacterial infections they were dying because the doctors thought they were sicker and that's why they got to be a catheter but that's not there it's hard to do when you don't do a true randomized study to do a propensity school so I don't think we should take that paper and say we should not use vasopressors in the first hour so with this I think I will I'll tell you that there are two papers that are or two randomized studies uh we're waiting on them to uh they started being recruiting patients this is called the arise fluid uh this is the same group that did the arise study so this is Australia New Zealand and this is the Eva study which is the UK uh and Ireland I believe they also started recruiting and this is looking at a randomized control study of using early vasopressors versus fluid so I'm excited to you know one day we can hear the result these will be the true prospective randomized trials meantime I would say we should continue to use vasopressors early um so um with this I think time is is uh we will uh go to the next slide here uh I'm gonna skip that these are the other supportive care that we're going to discuss in the uh in the next uh uh part two uh and I want to finish again with what we discussed before is is you know you want to keep things perfused I hope I tried to clarify how we measure signs of adequate uh organ perfusion from what we can do on the bedside examination and maybe some other Advanced testing that is available to us these days you want to fill up the tank so giving adequate fluid all the studies that I've showed you have given to patients at least two to three liters before they were entered in the trial so giving the patients enough fluid is always a Paramount importance and it should be done first uh and then get the pressure up and it seems that uh a map of 65 is adequate and shows as good outcome as higher Maps uh and do everything that I discussed before do it concurrently and quickly so with this I will stop today um and uh see if you have anything that came up any questions great thank you so much Dr abhishala that was very informative um chat tonight and it was both easy to understand but challenging at the same time and making us think more about the different studies um and also I was very glad to hear you mentioned Belfast a few times I'm joining you from Belfast right now so it's great to hear about um the different research that was presented there we have a question in the chat so far um I'm also going to ask if anyone asks us any questions either to put them in the chat or you can raise your hand um and unmute yourself and then ask them directly to Dr abhishala but the first question is from Dr Shafi and hello my name is Dr Shafi from Tanzania East Africa my question for you is how long should we keep patients on vasopressors when they have a per response um so let me say it again so the question is what do I do or uh or how low or um how long should we keep patients on visual pressers when they have a per response oh well I mean I think it's how long we continue the as oppressive they have a poor response I mean that the idea is sort of the escalation if we're talking about a patient not reaching the target blood pressure with my labor fed and I'm reaching a higher level and reaching as I mentioned maybe 0.3.4 Mike so this is what I add another as a presser now I think if if I'm reaching very high levels of uh of vasopressin the patient's not responding then I have to do more Dynamic assessment where maybe this patient does need more fluid maybe I have to use epinephrine so that's where the role of bedside echocardiography would be helpful uh to help us and then some people are quite advanced in in doing uh Echo measurements and be able to tell what things might be helpful to the patient uh um but but that's how I would use it use the other vasopressors and check for other parameters foreign I'm just looking through to see if anyone else has their hand up or wants to ask a question so another question that has just been asked um thank you for the very interesting lecture my question is have you ever used methylene blue in septic shock and that's from Dr Osama okay only one time uh I was seeing a patience and actually I've never I I don't know if there's any I heard there's a randomized trial but I haven't seen any publication that uh that was I was seeing a patient who was in septic shock and the cardiac ICU and I remember the cardiac intensivist would use methylene blue uh on that patients I think they use it for uh what they call vasoplegia and the patient had a good response uh but it was more of a post-op cardioplegia rather than septic shock so I'm not aware yet that there are any uh really studies in septic shock uh certainly would be interested of somebody I've seen a publication that feel that I didn't see it ever mentioned in the guidelines to be used oh but I've seen it in post-op cardiac patients and I've seen some traumatic results with it but I think it's more related to the vasoplegia that we see post cardiac surgery rather than septic shock thank you for asking or answering that question if you have another question with um Hassan who has their hand up so if you want to unmute yourself and ask yeah hi hi it's a comment rather than a question to hear you over the waves the excellent talk as ever thank you very much it's just to answer our colleague from uh Tanzania I mean further to what Dr abushala had said uh quite rightly this patient already into a refractory shock and here we have to consider any reversible cause as the turbisha was saying so you need to make sure that you filled up the tank maybe reach out to your echo or have advanced homodynamic monitoring device to check am I dealing with the pure distributive shock or is there an element of hypovolemia or more importantly and commonly at least an element of cardiogenic shock and here probably you need to add an inotropic agent in addition to your laser process the agents having said that the immortality is quite high once you reach to norepinephrine 0.6 marks per kg per minute uh associated with multi-organ failure state or a sofa score more than seven so there's some evidence to support this and the mortality goes above 90 percent so if we are in an area if you are in an area where it's a lower resource country then probably I would stop at that level keep pushing hard because I know my patient is not going to make it obviously this is not applicable to someone who is Young or thrum a patient or potentially reversible that probably more applicable to those who already have got comorbidities and you are thinking of giving them an ICU trial or something like that and then once you get to that level then you really have to stop on the other hand there's really in the literature there is no limit to how much uh vasopresses you give especially as I said in someone who doesn't have comorbidities and we have sealed or I I'm sure the wheel have seen I have seen uh people having their fingertips uh you know amputated the necrosis of their the note of the tip of the nose and they came back to the ICU walk into a last uh goodbye before they left the hospital so you need to take things into context but really once you've exceeded 0.6 marks per kg per minute leave of it and there's no reversible cause and the patient has got multi-organ failure State then that's the time I would stop thank you very much thank you for adding that comment for us um I'm going to pass over um Dr talal dehans with us tonight and he's got a question to ask you as well uh Elite and elegant presentation Dr abushala thank you so much um I wanted to to elaborate on a problem I think that we have in in critical care for a very long time I don't think we have defined sepsis well I think the trials have been either too specific or too sensitive to Define sepsis and based on that I still struggle with the outcomes that we look at in in clinical trials if we don't know how to Define sepsis well how can we apply therapeutic measures so I completely agree accused of a score was probably too liberal probably everybody who's critically ill will receive sepsis management at the same time looking at sirs as we know from the anzacs group back in 2015 We Are Gonna Miss at least a good portion of patients who have severe sepsis so I I don't know how do you feel about the latest recommendation on going back to Source criteria while really back in 2018 or so with sepsis redefinition we were too sensitive what is really the right definition that we should use oh I'm not sure I mean I can really add to it I mean I'm sure there are great great minds that are looking at this far beyond what I can think of to to find you know a better way to identify patients with sepsis uh my Approach is that if you think about it cover it but be bold enough later if you if the page is not septic to stop the antibiotic so I would earn more on you know I've seen quite a few patients that come well people think they had a cute Mi they had a PE or they had something else so they have ultimental status they had a stroke and there are things that don't match up and I think the patient may be septic on top of it and I usually ER on covering them uh but that would be a big caution is that doesn't mean you know you're gonna throw antibiotic on every patient that comes to you but anybody that you have this lightest suspicion uh I would not to miss these patients I I'd like them to be you know covered we know that the only difference is going to be is whether to add or not to add antibiotics and but you always have to be also cognizant that I'm going to stop antibiotic after 48 hours if I know this patient is not septic and that probably would be a defensive mechanism but what if you be careful if you make it more of a uh more uh guideline recommendations then people may abuse it so it it's it's I think the best thing is it's good training and and and uh and uh antibiotic de-escalation strategies and and so people can can even if Physicians would do this and then you know the de-escalation team would contact them and say okay I think that you don't need to do this then I think we'll we'll be able to catch most patients but I don't know if there are other parameters of cytokines or blood tests that are coming up uh in the future that would uh help us to identify these patients are thank you Dr Naveen um another geek session don't worry but what is the appropriate time to start arnotropes oh I think I've discussed that I think it should be started in the first hour if the patients after the patients you know an ambition doesn't have to finish their first leader of two leaders but I like to get it particularly with those patients that have a diastolic pressure less than 40. those patients are a lot of the papers recommend that we start them uh very early investopressors even if we we just started the IP course but if it does not like less than 40 and they don't look too bad at it you know that it's like a combination I look at that you know are they modeling are they hyper perfuse or do they look confused or are they I mean some patients come in hypotensive but they can still talk to you or look comfortable those patients I would hold off from as oppressor so it's a sort of a decision with bedside assessment okay thank you um I think we had another hand up from Ali uh yes but uh the question is answered thank you lovely thank you very much um okay the next question in the chat um if Andrew attention two is available would you use it before Nora I've been asking uh I'm sorry what say it again is it did you see a vasopressor sorry um Andrew tencent two yeah versus Nora Abby okay I think the Angiotensin II trials have not shown any additional benefit uh there's only I think one or two papers published uh when they were compared there was I think the cost is tremendously higher uh and I don't see any advantage of angiotensin too I think there's more data about adding vasopressin to levofed there is only a couple of papers and I don't see it's really widespread I don't think it's even available in most of the hospital I work at because of lack of data um so it has probably the same Advantage as a person not causing any tachycardia but I think as far as you know physiologically making or something in difference in outcome of patients and all the and see any advantage okay um do you have time to answer a few more or are you I think I might probably have to I had you have no idea how many pages I got and I know Dr Carolyn has been helping me uh um in in taking care of some of the Urgent issues so but I mean I think we can do some more um answering questions I'm hoping in the part two which is going to be next week so it won't be too far we look forward uh everybody who can attend next week well that's great there's some good questions remaining in the chats so if people can remember them and ask them again next week when we have a little bit more time that would be great um I want to see if uh uh Dr Kerala Dr talelo Dr Hassan wants to answer some of these questions you'll be uh feel free if you imagine you can decide okay um well thank you so much for joining us and hopefully which is all answered but we appreciate up the chat tonight and just so much work you put into those lectures so thank you and I'll see you again next week all right thank you thank you everyone

Channel: ICU REACH

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Id: 6QBGcfbanQA

Length: 72min 56sec (4376 seconds)

Published: Mon Jan 30 2023