Transcript Video Is Fever Bad? < Back to Summit23 Cracks in the Ice Is Fever Bad? Presented by Professor Raimund Helbok So um I would like now to introduce the second speaker. Uh my friend Raymond Bu uh where I met him was in his Brook. Now he is responsible for the neurology department in Linz and also in the New IC U. And Raymond will talk about his fever bed. Is yours? Thank you very much, Fabian. It's great to see so many people here and I, I have to congratulate the organizers. It's uh it's fantastic to have a set up on uh temperature control and also the discussion about what it is from a diverse direction. And uh as you've heard, I'm neurologist and I'm neuro intensivist and you might hear some other thoughts because I'm, I'm think I'm trying to think what's happening in the brain on a cellular level and translate that into, into clinical practice. And when I went through the literature, just before preparing the talk, I came over this very nice review on what is temperature in the ICU. And it seems totally different if you look at surgical patients. Well, fever is a normal response after the operation, cardiac ICU patients. Well, you should check whether there is any infectious cause concerning the cardiac system, myocarditis, for example, or pericarditis in a mixed. I see. Well, there is, there's a lot of things we have to think about cardiac stuff or also a gastrointestinal. But the neurological IC U there is a recommendation you should treat fever and that's, that's interesting. Um It's, it's a very recently published review. So if we now look back and see what what happened in neural care, we have to, we can say that the outcome got better in the last decade. And there are several publications on that, that a specialized neuro actually improves outcome. And we have to think about why is that? I think one reason is because we understand that the physiology much better in different diseases. And we know that um certain diseases like traumatic brain injury or sah or ince hemorrhage or cardiac arrests, not every patient is the same and not every phase is the same where the patient is in which means that uh right after traumatic brain injury, the patient is totally different from a patient after uh at day three or day seven. And maybe we have to treat the patient differently. And we also know that there are several talks about precision medicine. So individualized treatment. So may maybe that's, that's where we should actually move towards in, in, in the next years to identify specific patients which are eligible for certain interventions. And there is one thing more. Um it's what we do in our IC U and I think that's, that's a critical situation. We have so many instruments on the patient, be side. Uh We have the patient in the middle. Sometimes we don't touch the patient because we have so many machines and we, we are so concentrated on, on all the machines which is going on. But as a human being, we can only concentrate on two or three variables and try to combine these two or three variables. But it's nearly impossible to get the information about how is oxygen temperature IP related to each other. And what we did, we implemented bundles bundles of control of fever, sugar, control, swallowing control. This is a nice study where nurses did the major work. So just implementation of such a bundle to control fever when temperature is above 37.5 degrees, regulate sugar and assess for swallowing. The patient population was not very sick. They were not only for 40% with malignant of ischemia, but uh there was an improvement in outcome by these interventions. So, fever was significantly decreased and also the swallowing assessment uh significantly improved the care management in the IC U. And this is the modified ranking scale. There was no difference in uh mortality as you see here um on the right side, but there was a significant improvement uh in overall patient outcome. And that's, that's quite interesting. It's a, it's a simple recipe as we have heard before. Uh So So give, give your nurses and your IC the recipe, how, how to manage things and temperature is one part of the puzzle. If we think that with temperature control, we can control everything and improve outcome. I'm not sure whether that's, that's correct. But there are so many other things which are important for our, our patients. So what about the neuro patients and non neurological patients? And this is, this is a study published in 2015 from FRED RCN. And you see that neurological patients, temperature matters. If they have fever, they have worse outcome. And that seems not to be the case for other patients. And this is also in a, in a large study replicated that even in neuro patients, CNS infections are different. Meaning that maybe in, in the infectious causes of fever, even in the neuro patients like meningitis, encephalitis fever is something good and something protective as well. So maybe we don't have to treat it that aggressively. But if you look at stroke patients or uh trauma patients, there's, there's the same signal that uh fever is actually associated with worse outcome. This is a very old and uh I think a very nice uh study in uh cardiac arrest patients. And uh what you can actually see these are untreated patients, uh that temperature increases in nearly all of these patients and the patients with a higher temperature. Um they had actually worse outcome and there were both signals the hypothermic patients, especially at the beginning with very low temperature had a signal for for worse outcome. And then later on, these were also the patients who are more likely to get increased temperatures. So very low, very high is very bad. In terms of, in terms of outcome. The question is always whether we control it, whether that actually improves outcome. And you have the um the three trials, the Haka trial TT M trial and TT M two trial, I will not go into detail because there are other um discussions about it and you see the temperature curves and in uh green, you see this is, this is between 37 and 38 degrees. So um if we control temperature and as you have heard in the previous talk, should we have a recipe to really target um the goal in terms of reaching 37 degrees or as you can see here, we have a large confidence interval in these patients. And even in the intervention group, there were some patients having fever at a certain time period. And so this is then 38 degrees and, and, and higher uh in all of these publications and what happens after 48 hours or after 40 hours, we don't know what happened to these patients. And if you, if you also look at the intervention groups, you see that um the temperature rises at a certain time and we know that rebound hypothermia is something which is bad for our patients. So we don't know even in the intervention group whether afterwards some episodes of fever occurred in these patients and these rebound hypothermia is associated with worse outcome. So maybe we have a wash out effect after, after an intervention, which is good for the for the early phase. And then later on, we actually wash out everything because the patient then comes into this feverish episodes. So what happened after the TT M trial when the TT M trial was published, you see that the use of therapeutic hypothermia significantly decreased and the temperature increased in the patient. And these were not temperature ranges uh very high in the in the fever state. So if you look at the median values between 35 and 36 degrees, this just shows that certain, I didn't follow that the target of 33 degrees again. But if you look at the fever incidences, you see that there were significantly increases in episodes of fever in this patient population. And although there is no direct correlation, it's only an association also mortality increase. This is this is the rate of mortality over years in cardiac arrest patients. And you see at a certain there's a certain stable phase stability, but it's actually not uh improving anymore. So what is fever? And I think you've heard something about how we define fever before. But still, there is a huge diversity of what everyone understands by having uh what, what fever means. And this is important because there are usually implications by that. Because if you say fever at 38 degrees, you will start treating fever at 38 degrees. And if you say, well, the critical value is already at 37.5 then the nurses will ask the doctor, well, this is maybe the time when we should start a certain treatment. And this is a survey among European ICUs. You see ICU intensive care medicine, 50% anesthesiology, 30% of replicants, more than 230 replicants and the definition of fever and the trigger to intervention was totally different compared to depending on whom you actually asked. So the question is uh is fever bad? And uh would I treat fever? And I can just give you my personal view as a neurologist and neuro intensivist why I would uh why I would recommend to treat fever in the patient population. So 1st, 1st of all, fever is associated with raised intracranial pressure. Is that how does that actually work? We know that that high b also increases metabolism and then at a certain degree vasodilation occurs and then intracranial pressure can increase. That's a, that's a very mechanistic view of thinking. Does that happen to you? No, of course not. Does that happen to all our patients? No, actually not. But to the critical ones who are just on the edge where a certain degree in the change of a physiologic variable metals. And in these patients, um temperature can be associated with uh raised intracranial pressure. And this is a publication we published a few years ago in um this is traumatic brain injury patients. The center, the TV, I study uh lots of patients but finally having brain temperature and body temperature only in 21 patients. But uh I'm monitoring time uh quite a lot and you know that uh we didn't discuss about brain temperature management, the brain temperature is usually higher than body temperature by how many degrees we we don't know 0.2 0.4 degrees. And in certain patients also, one degree difference is for certain episodes. And if we measure brain temperature, we usually reach the target of 38 quite fast in our patients. And the question is, should we treat that should actually that be the target? Where should, where we, where we should monitor our patients and treat our patients aggressively. In this study, we found that these episodes of high brain temperature and you see the brain temperature, the color yellow, yellow is already above 38 degrees in these different patients is associated with high CP and also with lower sober perfusion pressure. Is that a major effect? And as I discussed previously, no, it's not. It's around there is an association by increase in temperature above 38 degrees only by five millimeters of mercury or 3 to 5 millimeters of mercury in CP. Does it matter? Yeah. Yes. Well, I think it matters if you combine P and other variables together. And this is also what we see in these analysis. If uh temperature increases. CP also increases. If temperature decreases, then CP also decreases. So this is, this is a small part of what we do in ICU care. And there's one study also studying nomia where uh IC P significantly decreased. And so that's also the idea why no fia or why fever could be bad and no fia should actually the way to go. So we have uh two arguments, association with brain edema and association with raised intracranial pressure uh for the um the argument that fever might be bad. Another argument is cortical spreading depolarizations. And I think this is something where not every one of you may be aware of it. These cortical spreading depos are actually protective mechanisms of the brain to bring more energy to certain regions of the brain. And we have uh in, in the physiology of migraine in migraine auras, we have these Corts in the occipital area, having the aura and then some patients have hemiparesis or hemi plaia because these are slow moving waves over the cortex. The but they, and that's, that's what we, what we have learned in the last 10 years of research. They can be pathological, especially in patients with acute brain injury. And we are talking about trauma patients. We are talking about patients with inter hemorrhage, but also of cardiac arrest. And um the question is what is the trigger for these cortico depolarizations? Obviously, it's the lesion, it's hypoxia. So nearly every stroke patient has these, these and um the the the other point is potassium. So if there is free blood in the brain, potassium can also be triggered for these cortical spread and depolarizations. These are very slow moving waves and they need a lot of energy. And if you compare it to convulsions and epileptic seizures, it's eight times as much energy as as it is consumed during an epileptic seizures. And that's why these electrographic activity, what you see down there is then depressed afterwards. And it needs quite a long time for the brain to recover from these cortical sparing des. So what does that have to do with temperature? Um as I said, it's a very highly demanding metabolic um um uh part or injury mechanism of the brain. And we did one study and studied body temperature and brain temperature. And what we found is when these as these occur, the brain temperature goes up, which means that actually that that is associated with higher brain temperatures. And on the other hand, we found that those patients who are having higher body temperatures or or the brain temperature, they have a higher incidence of cortic Respa in conversation. So that there is an association between temperature and these phenomenon. Is that relevant or what is chicken in the neck. We don't know. Uh So could it be that these are the cause for that? Could it be the fever is then the cause for SD actually, we we don't know, but we know that these especially these coral depos are bad for the brain and they, they can cause DC these are typical these phenomenon in sah patients where, where we have these cortical infarcts and we don't see vasospasm, large vessel vasospasm in these patients. But still we see this brain injury and this is known. Now there, there are several studies that this is actually the cause caused by cortical de conversations. So what what can we do against it? Um And the problem is that these phenomenons, we can only uh monitor nowadays by invasive methods so that there is no non invasive method for monitoring of, of these co de conversations. That's why it's more a research tool. But what are the recommendations? Well, obviously based on that association, maybe we should control temperature to a level, not having fever to our patients. And obviously, there are some other studies like Ketamine trial in Denmark is now ongoing where we look at the PAPS concept because there are some, some evidence from animal studies that ketamine actually could work in this uh um in the depression of cortical spread and debation, which does not mean that everybody should get ketamine that. Uh but we need a study to prove that that's actually beneficial. And uh the problem also in these, the monitoring is that we know that that these repeated spreading debation are bad. But there are, there are some patients which only have one spreading dilation a day. And we don't know whether it's worth suppressing this one single spreading conversations. But once we have these clusters of SDS, we know that this is associated with brain injury. And that's why the message cannot be treat patients with, with ketamine. But maybe this is an argument for controlling, for measuring and controlling temperature, increased brain metabolism. I think you have heard a lot about that higher temperature is associated with more oxygen consumption. We have also some studies looking at brain metabolism using several micros. We see that that this metabolic derangement actually is associated with higher temperatures. And if you bring the patient to normal fia the metabolic signature is improved in these patients. This is another study from uh our group from, from Innsbruck where we looked at uh temperature changes in the center TBI study and uh looking at what's happened with brain oxygenation. And as you can see here on the right side that if brain, brain temperature increases body temperature, was it in this case, if body temperature increases, some patients have an increase in brain oxygen tension, some are stable and some have a decrease in brain oxygen tension. What we have seen and what we have learned that no patient actually is the same uh comparing one patient to another. I think that's an interesting information and the mechanism was always an association with blood pressure and then cerebral perfusion pressure. So, meaning what, what we see actually is changes in temperature associated with hemodynamic changes in, in, in the patients. And this is something what we know from our patients. You see here the curve of the temperature um and the temperature was high 38 degrees and, and at a certain time, we stabilize the patient and decrease the temperature. And you see these irregular waves and blood pressure, s systolic diastolic and medium blood pressure going up down. And also the heart rate before and after controlling the temperature of the patient is actually quite stable. And also when we analyzed a large data set on patients, the increase in brain temperature was directly associated with the increase in heart rate. And once stabilizing the temperature, the heart rate also went down. So there is some kind of hemodynamic instability in the patients when temperature increases. And it's reasonable as good clinical practice to control uh temperature to my mind in these patients. So this is from from a clinical point of view and also with scientific studies, the idea why I think fever is bad in these neuro care patients and fever should be controlled. So should we treat it aggressively in every patient and this fever bad in every patient? I think. Yes. But and there are so many many things now associated and I gonna discuss about some more things tomorrow in my talk. No, theia is the most difficult target. If you, if you wanna wanna control temperature to hypothermia, it's sometimes easy than controlling to normothermia. And if we now say treat aggressively and your goal is nother and you have many, many patients with shivering and there are so many other mechanisms which actually can counteract the benefit what you want. And with what are the methods to control? If you, if you think about pharmacological methods like non steroid anti inflammatory drugs, you know that the temperature decreases, but it will never go down to 37 degrees. And you will always have this, you have a certain decrease in temperature and then it goes up and goes and then you treat again and then you treat again and then you have actually a variability in temperature. And I gonna talk more about uh uh a potential approach to individualized therapy in temperature management uh tomorrow in this talk. So if you do TT M I think you should do it wisely. And you've seen that publication already of five corner I think high quality TT M means that you apply a new protocol, which is a huge investment for the ICU for your nurses. But I think it's absolutely worth approaching that. Thank you very much for your attention. Created by
