Transcript Video Infectious Fever and the TemperaturistProf. Ricard Ferrer < Back to Boundaries of Temperature Session 5: Control Infectious Fever and the Temperaturist Presented by Professor Ricard Ferrer we come to professor regard for her. He is uh infection biologist probably an intensive ist is head of the intensive care department at Valle de bron Hospital in Barcelona spain. He is head of the Saudi research group, diverse research networks and his publishing in the field of sepsis with numerous original articles, reviews and book check tres on on those topic and he's for sure, very competent speaker for the topic infectious fever and the temporary ist. So thank you. Thank you very much for the introduction. Thank you very much for inviting me to be here with you. This fantastic meeting in today's. So I'm going to discuss about fever and and T. T. M. Sepsis infection is always in the list of potential use of of DTM But I have to say that in the last edition of the service campaign there is no mention uh to fever temperature, any treatment related with that. So we have to look a little bit in which information we have about the rationale and which which trials have been published about that. Knowing that there is not any recommendation in the high line for this specific topic. So what is sepsis sepsis is a condition that has been recognized many years ago and is related to some patients that do not die because of the infection because of the bacterial load because of the viral load patients are dying because of the host response to this infection. This is the old definition and the diagnostic criteria include in the in the first um criteria published but roger born on co workers more than 30 years ago that sepsis infection plus systemic inflammation and systemic inflammation of course include fever and hypothermia. On on the definition. The modern definition of the modern diagnostic criteria defined sepsis as an organ dysfunction because of this regulated whole response to to an infection. So the six criteria have disappear from this definition and this is quite conflicting because many, many intensive ist or many infect ology is considered that since criteria are very sensitive and this definition is less sensitive. So some patients are missing when you're looking for septic patients using using this definition. So the streets criteria have been abandoned in this definition. But many, many clinicians still believe that they have a role in sepsis recognition regarding the path of physiology. You know that the microorganisms express some some pumps that are recognized by the immune system that generate a systemic inflammation that at the same time activate them totally. Um with the production of nitric oxide activation of coagulation, decreasing in the free analyzes and alteration in the micro circulation tissue and organ failure. This is the path of physiology and this is there is a feedback from the dams coming from the host. So the idea that we can manipulate that. It's also very old is more than 40 years ago that roger bone treat to modulate this systemic inflammation. And the rationale for using T. TM. Or controlling fever in this scenario is because because maybe we can reduce the amount of inflammatory mediators because we can maybe we can reduce the bezel dilatation and also because maybe we can control tissue dissection. So the hypothesis of the different trials have target this this this potential targets in the cascade of sepsis. But we have to recognize that this is a very broad scenario. Sepsis include patients with different immune response according the genetic background, according the phenotype, according to different microorganisms that are generating these steps this episode and also the micro Beom and different environmental factors play a role. So there is not specific systemic response for an infection, It's general that the patients are quite dynamic and in the 1st, 1st day can be completely different from patients in the second day. If we try to establish which is the relationship between body temperature and prognosis, you can see in the left that those patients in the ICU with infection hypothermia is related with higher risk of death. But not fever, fever is not related in this in this study to high risk of death. It seems that fever is adaptive and it's completely different. The results in patients without infection that if they have fever, the risk of death is higher this study and others were put it together in this meta regression, showing again this trend in this case, in patients with sepsis. And you can see that hypothermia is related to high mortality but not but not fever, but in fever there is an important variability because this heterogeneous city of our septic patients. So it seems that fever is adapted it which is the treatment of sepsis, which is the early treatment of sepsis. The campaign put the emphasis in infection control but also in correcting tissue tissue, profusion tissue destruction using fluids and early early. So this box is playing a very important role. And also we know that we can manipulate vital signs and it makes sense not to manipulate vital signs, which are normal and maybe when they are compensatory. But when they are in the extreme, maybe physicians may consider to manipulate vital signs because they can reduce for temperatures that can reduce tachycardia. They can reduce budget dilatation. They can reduce the loss of water and electrolytes and also reduce patient discomfort and also maybe can manipulate the inflammatory response. So, in fact in this survey, coming from the group mainly in France, you can see that physicians, in patients with septic shock, in patients with sepsis or in patients with infection. Most of the clinicians street street fever always or most of the time. So, as clinicians, we are treating this condition in patients with infection sepsis or septic shock. So this is the this is the reality if we move from sepsis to septic shock. I also want to remind you that the current definition. After this analysis, my manu shankar Harry uh include patients with hypertension need of a suppressor but also tissue. These are tissue the success included in the definition in the current definition of septic shock. Because as you can see in this graph, those are the patients with the higher mortality. So this is a more homogeneous with Harry immortality. What what this tissue is actually probably all of you in the room. Know this concept because it's an old concept is a physiological concept. This is a study done with healthy volunteers and healthy volunteers, investigators reduce the carry the oxygen delivery using beta blockers using lower moldavian using low oxygen. And they were able to find a critical point where if the oxygen delivery is decreased below this critical point, there is a decrease in oxygen consumption. So the original part of the of the chart, it's uh it's a safe zone. In fact, we can increase oxygen extraction radio and compensate a decrease in oxygen delivery. But after this critical point, there is a decrease in oxygen consumption. So that that means that the metabolic demands of the cells are are Are decreased because the law because mainly because of the low flow in Sepsis, this is a little bit different because the oxygen demand is higher. But also because the oxygen extraction from the tissue is affected by sepsis. And in the previous night, I show in healthy volunteers a cut off of 10 mls per minute and per kilo. But for sepsis maybe it's around 15. So 50 50% higher this court of point. And this is very old information showing that those patients probably need higher oxygen delivery because they are able to extract lex oxygen and because they have higher oxygen demands. So if we put together the two graphs, you can see here the critical point for healthy volunteers and here the critical point for patients with. So it shifts to the right and at the same time, the level of oxygen consumption is higher. So the area of dependence of dependent of oxygen delivery is higher. So the risk of having tissue perfusion is higher in patients with sepsis. So those patients level of high lactate levels as a marker as a market of the oxygen depth of the oxygen deficit per time. So we have several markers. I'm not going to discuss about that. I'm going to select lactate because it's related to mortality in patients with shock in patients without shock. When we interviewed the patients and we try to balance oxygen consumption with oxygen delivery, lactate is a good marker because most of the studies have shown that if you normalize like the levels the patients will do better. So it's a good it's a good matter of tissue of tissue perfusion. So the first strategy in sepsis is to increase oxygen delivery if the patient has tissue perfusion. So this is this is clear we move the patient to this situation and then we have a balance between oxygen delivery and oxygen consumption and we have to try to avoid super resuscitation to pay this debt because we know that this is harmful and increase mortality which tools we have for that? It's clear we have fluids, we have suppressors, we have we have oxygen and we have a model of it. So this is we can combine according different algorithms, these different treatments and we will improve oxygen delivery and we if you use lactate or we use now capitally refill time whatever you use you can achieve this in some patients you can achieve this balance between oxygen delivery and an oxygen consumption. But the other potential strategy that I'm going to discuss now is to decrease oxygen oxygen consumption. So how we can decrease oxygen consumption and to achieve this again, balanced situation between oxygen delivery and oxygen consumption. We can do it of course treating infection. We can of course giving the patient analgesia. And also I want to discuss a little bit about mechanical ventilation because I think it's part of the management of the patients in shock, not only in septic shock in shock because again this is an all physiological study showing comparing patients in so without support with patients in mechanical ventilation or in patients on mechanical ventilation. My master or muscle relaxation and all of them of course are critically ill patients. You will see here that the percentage of oxygen consumption by the respiratory muscles in patients critically ill patients represent 20% of the oxygen consumption. So just with supporting the patient with mechanical ventilation, non invasive mechanical ventilation, how flown as a can of any type of support that you consider according to risk benefit ratio can reduce Up to 20% of the oxygen consumption. So that can help. And this is part of the strategy. Of course I reduced those medications like the vitamin that is able to increase the oxygen consumption and cooling which is the topic for today. Those are 12 patients and that have been cool using cooling blankets you can see in the left, that is possible, you can using cooling planted, you increase the temperature but at the same time you reduce the oxygen consumption. So it seems that it works. Some patients of those 12 patients, seven patients in fact have a swan Ganz catheter and then demonstrate that they can reduce oxygen consumption and they can't um decrease the cardiac output, meaning that the patient needs less oxygen delivery because they have less oxygen consumption so they can download the effort down by the heart using that. So let's see different therapeutic approach. And I think the next speakers are going to cover part of this though, this is a randomized clinical trial in patients with substance not with So I'm going to discuss that with the population and intervention of all these trials. Those patients patients in the ICU with sepsis, some of them have fever, have not had fever and patients received placebo or even profit. So you can see that patients who receive ibuprofen. Eight doses there is a reduction in body temperature, there's a reduction in heart rate. There is a reduction in the minute in a minute ventilation. Very interesting. There is a reduction in oxygen consumption. There is a reduction in lactic level. So it goes in the adequate reduction what we are looking, what we are looking for based in the physiology. But there is not a reduction in organ dysfunction or immortality. Okay, so it seems it's a adequate way. Maybe the population is not. Maybe we can think in a study enriching enriching this population. But this is what we have with ibuprofen for we have one trial in patients in the ICU with fever. So not in patients with sepsis with infection and patients received one g of paracetamol or placebo every six hours. So there is no benefit in terms of morbidity, no difference in terms of mortality. So this is not for today. And regarding external coding The patients included in this trial. They have septic shock. They are on mechanical ventilation, they receive fever controlled by external cooling and they compare to no no cooling. The intervention last for 48 hours. There is a good difference in temperature between the two groups. There is a nice reduction in the dose of Paso pressures that the patient that the patient needs. And also a significant reduction of early mortality at 14 at 14 days. So Frederick Shorthand and co workers make this post hoc analysis of the sexy school trial and try to understand from where is the benefit coming? Is because of the cooling during during these 48 hours. Or it's because of the reduction of the heart rate between these 48 hours of the of the intervention. So they they found that there is there are two cut off one for body temperature. So the patients who survive the best cut off for patients who survive best different between the patients who survived and the patients who don't survive is is cut off of 38.5, meaning that the patients that stay more time below this threshold have better survival that those patients that stay lower time between these uh Below this threshold and for the heart rate is 95. So the threshold 38.5 and 95 for the heart rate. And in the Multivariate analysis they identified that is in fact body temperature. The factor that explains the reduction in mortality they have in the clinical trial. This is the last trial I'm going to discuss. This is the the cast trial in this case again, are patients in septic shock, respiratory failure. And in this case the patients are treated by uh importer mia for 24 hours to 33 to 33 degrees. Um Nice different in temperature. However, the study was stopped at 75% of the recruitment because fertility, but in fact the trend is that the mortality is higher in the hypothermic group. In the group analysis, there is not a specific group of patients that have a different, different outcomes. So difficult to see differences between here. So now, in the field of sepsis. When we talk about in mono modulation or other treatments difference for control infections, there is a general sense that there is not a magic bullet. So we have to personalize a little bit of treatments. We have to to enrich the trials because one size does not fit fatal. And I think this is the example again of fever control in this in this setting. So my conclusions are that fever can be considered as an adaptive mechanism in the patients of infections as clinicians. We treat fever in most of the most of the cases and probably not non steroidal anti inflammatory drugs are useful in this setting for treating those patients with sepsis infection in the ICU and in patients with septic shock, mechanical ventilation with severe tissue dyslexia. We may consider external cooling to reduce tissue perfusion and stabilize those patients. So with that, thank you for your attention and I'm happy to take questions later Created by
