Transcript Video Which is the Target: Temperature or ICP? < Back to Summit23 Brain Injury Management Which is the Target: Temperature or ICP? Presented by Professor Chiara Robba So I think it's, it's 10 o'clock. So it's time to start this session. We call neuro session. Uh So I think we move a little bit from Carrere and uh discussing more, more acute non anoxic brain injury patients. So I'm fit a from Brussels and I will share the session and I will immediately call for the first speaker. Kra Robba is associate professor at the University of Genova San Martin Hospital. Uh Ciara is uh done so much in the field of uh care of brain injured patients. He just finished the mandate as the chair of the new intensive care section of I have one more year. I thought I hope for you that with the, with the finish. No, one year more so. Ok, great. So it's better than you can give the lecture which is the target temperature or IC py, please? Ok. Uh Fabio. OK, I can just use this microphone, I think. Ok, thank you very much for being here and thank you for the title because it's very tricky which is the target temperature or, or it's gonna be challenging because there are many things that we don't know about this topic. So I will start from what we know, which is already a good beginning. We know that fever is very common and that it has to be treated because fever in brain injured patients can worsen the outcomes. We know that fever in brain injured patients is not just infectious. Of course, the first thing that we have to do is to exclude that fever is related to an infection. But we also have to consider that what is called unexplained fever. And now we know it's called neurogenic fever can be 28% of the cases that we face in our neuro critical care units. And it's the brain injury itself that is associated with the risk of fever. And among all the types of brain injuries, subac noid hemorrhage is the one which is associated with a higher risk of developing fever. So let's keep in mind always the pathophysiology. So from one point of view, of course, micro organism can cause a release of pyrogenic cytokines. And this is a general mechanism. But let's keep in mind that circulating cytokines can affect the release of prostaglandins in the hypothalamus. So at the end, what happens is that there is a upward shift to the set of the temperature and the temperature just goes up. This is the mechanism. But regardless the mechanism, the risk of words out is consistent. This is a study which is a huge meta analysis including 39 studies with 14,000 of patients and more TBI and cerebrovascular disease. And as you can see the risk of mortality but also of neurological outcome and length of stay is importantly related to the development of fever during the. So why temperature control matters so much in this population? Because as we discussed just a few minutes ago, what we have to treat in neuro critical care is the secondary brain damage. Every time you have a patient who arrives in your I, you look at the first city and there is a part of the brain which is lost, this is the primary damage. There isn't anything that we can do against this. And as I always say, we can do anything about this, but we can do a lot about this. So everything which happens in the following cities might be our fault might be related to our treatment. And this is the part where we really have to work in order to reduce mortality and improve outcomes. Now, how can we, why do we have to care about temperature? First of all, because temperature is importantly related to the cerebral metabolism. If you change the temperature of the brain, you have a huge change. It's a logarithmic change in the metabolism, the integrity and the function of the brain. And then there is as mentioned before, the other problem that is related to brain injured patients. So the intracranial pressure, if you have fever, you have an increase of the metabolism which can cause initially a vasodilation to increase cerebral blood flow. But this increases the cerebral blood volume and you have an increase of. But when mechanism are exhausted, these cause ischemic areas which can further increase the intracranial pressure. But it's much more complex than this. I love the physiological studies and the NINOS with his group did many physiological studies on this. This is a small group of patients, 18 patients with acute brain injury, but with multimodal neuromonitoring micro dialysis data, cerebral oxygenation and arterial venous different of the oxygen concept. Here in this brain injured patients when fever occurred in this population CP didn't go very much hike. But the concept is that the cerebral metabolism might worsen might be impaired. But this happens especially if you do have a compensation of a substrate. If you maintain the cerebral oxygenation, the effect of the cerebral metabolism on the ALP ratio is much lower. So we need to be precise. This is the first message in brain injured patients. But to be precise, we have to know not just which is the core temperature. The optimal would be to know the brain temperature because there is an important difference between the systemic and the cerebral temperature. The brain is a bit hotter than the body you see here, this is the mean temperature core and this is the mean temperature in the brain. There is at least a delta of 0.5 degrees which can become one degrees or even two degrees when the temperature goes up. So it's basically, it's basically a lot and the changes of intracranial pressure, which are shown in these studies are more correlated to the changes of the brain temperature, respect to the changes of the core temperature. So this should be eventually our target. So in the general population, this is a recent editorial which basically provides some information regarding the fact that less is more in the treatment of fever. This editorial is basically telling us that sometimes we can avoid to treat fever as long as there is not a sign of organ dysfunction. Well, I think that less is more in brain injured patients cannot really be applied. We have to be probably more aggressive regarding the treatment of the temperature. These are the first recommendations published by Andrea Lavino. It's a consensus on cerebrovascular disease and basically one of the recommendations is that regardless because of fever, neurogenic, non neurogenic infections, non infection, the target of temperature should be this and not be related to. We cannot be as permissive as in the general population. So, no hyperthermia, this is what we know. So we have to go down with the temperature but how low and let's come to the second part of of of the title of the question temperature of our CP does hypothermia reduce CP? So these are the preliminary data of the Euro term trial. This is a randomized control trial where patients were randomized after a stage one therapy. So probably quite early in hypothermia and the standard of care. And if you see there is a nice reduction in the hypothermia group of intracranial pressure compared to the control. So probably yes, hypothermia does reduce the intracranial pressure. But which is the target and how deep is the effect on in this study, which is old. But it's a very nice physiological study. If you see here, the reduction of intracranial pressure is very clear, you go from 39 to 36 to 35 degrees. And then there is a plateau, just 31 patients with TBI. But it seems that until 35 degrees, there is a clear effect and then there is a sort of plateau. And at the same time, this is another very nice physiological study from the group of Cambridge. This is the cerebral oxygenation and this is the arterial oxygenation. You see again, when you have a reduction below 35 degrees, you have a reduction in the oxygenation. Despite you might improve the systemic arterial oxygenation, here comes different factors of the metabolism, the diffusion, the utilization of the oxygen, the shift of the association curve of hemoglobin. So let's come to clinical studies. These are very, very heterogeneous, especially in terms of of a methodology. This is a study randomized control trial where patients were randomized to 35 to 33 degrees. Lack of effect of induction of hypothermia after acute brain injury pay attention because in this study, patients were randomized in aggressive treatments, hyperventilation, barbiturates or aggressive treatments, hyperventilation, barbiturates and hypothermia. As additional. The other very important and very famous randomized control trial is the euro term study. The euro term study, randomized patients in hypothermia versus normothermia and the effect were scaring because patients randomized to a group of hypothermia at the worst outcome and a higher risk of complications. But I am not surprised about this because if you look at the structure of this study, these were patients who arrived in the ICU and they underwent just stage one treatment, mechanical ventilation, sedation. And then if they had an increase of they were randomized to go to hypothermia 33 degrees or to receive man or hypertonic saline. So I'm personally not surprised that what we see is the price to pay oversize effect. And this is the polar study, negative study which basically explore the effect of a prophylactic hypothermia on the effect on outcome, no effect on outcome. So not to be used as prophylactic strategy. So the result and the heterogeneity of these results, in my opinion, are really related to the fact of when we use the hypothermia and also to the target of hypothermia. Because when we use strategies which have a side effect like hypothermia, we have to pay a price and this price are the side effect. This is a sub analysis of study done by Carolina Yago from Milan. And if you look here, the use itself of aggressive treatment can increase the risk of complication, like the risk of va increase the risk of tracheostomy and increase the days of mechanical ventilation. And we all know that when we use hypothermia, we take risks which are importantly related on how low we go with the temperature and are related to important side effect which can eventually worsen the patient's outcome, respiratory cardiac how to cardiovascular effect. The problem of on coagulations. So it's the right patient which can benefit of this, but especially it's the right timing. And what about the duration? This is a randomized control trial. In this case, patients were patients with increased ICP. First arm were treated for two days, second arm were treated for five days. And basically the result is that the two versus five days, no difference in the side effect and better neurological outcomes for the patients were cooled for a prolonged time. So for these two time frames, probably we don't see much different in terms of consequences. But the concept is that we have to treat hypothermia with hypothermia. If we use it as long as the brain needs it, not just for a couple of days, we need to follow the changes and the behavior of intracranial pressure. So you will find in the literature, a lot of studies, you will find very contrasting studies. This is a me analysis where basically, which basically says that in some studies, hypothermia as I showed you or did not work or might increase the mortality and the neurological outcome in some groups of TB. But when doing the subgroups analysis, it's probably here where we see, which is the clinical reasoning patients with, when we select only studies with patients where hypothermia was used for increased CP, we can see a benefit on this. We cannot see a benefit if we use hypothermia as a prevention. So if you use that prevention yesterday, you have learned to understand that the vis square here, if it crosses the one line, it means that it's not significant and you can have a fever when hypothermia is used as just a treatment. So, Fabio did a wonderful figure which is the ghost cup and it's a very nice acronym. It means that first of all, when we treat our patients, we have to start from the physiology and from being a good general intensivist. And among all the factors that we have to take into account, one must be the temperature but not hypothermia. In this phase, we just avoid the fever. And then only after we fail with the initial strategies for CP control, we can try tier one where we have sedation changes in co two hypertonic saline man. Then if this doesn't work, you can try to modulate a bit more hypercapnia. You can use neuromuscular paralysis, you can do a map challenge. And then only if all these factors have failed, you can try aggressive treatment, the tier three treatments which are the compressive gray pentobarbital or, and mild hypothermia. We have a target of 3536. This is what the guideline says. So what do clinicians do in the clinical practice? We are still far from following the guidelines. Look, this is a survey where it was asked to the physicians, which type of tier three therapies are you generally using and look just looking at the colors. There is a huge heterogeneity in the use of these strategies, especially for the use of hypothermia. And of course, this also depends on the type of unit that you consider. Here, we standardized the use of the therapies according to the high or low income countries level. And this is quite important because look in low countries centers, they mainly use the compressive craniotomy as a tier three therapies and nobody uses hypothermia probably because if you want to do a good hypothermic, have a good hypothermic effect, you have to use feedback devices which might have a cost and for low income countries, this might be a problem. However, the good news is that at least hypothermia is more frequently used when patients have an monitoring inserted and less when patients are not neuromonitoring. This to me means that at least clinicians target the temperature according to ventral pressure. But we are still a bit far from the staircase approach. These are real data on what people do. These are treatment, mild, moderate and these are the extreme treatments including hypothermia. You see what I would like to see is a staircase here, but it's not, this is still, this is very alive. So this means that we have to work more, much more on helping clinicians to understand that how our approach has to be less and then eventually more aggressive. And this is a summary of this. You arrive at the tears, you arrive at the tier three therapies. And here if you have persistent intra hypertension, you decide one of the tier trees that can be used. And there are not indications in the guidelines about what to use first or afterwards. But here it is where you have to start to think about the physiology, the metabolism, everything that we have discussed. If a patient has a potential good neurological outcome, you might go for the compressive craniotomy. Otherwise you can consider to use mild hypothermia or to use it as a bridge before going to the compressive craniotomy. But also look at the images. This is another very nice figure done by Fabio Tacon. If you have a patient with subarachnoid hemorrhage blood or with hematoma and the Peric contusional area, well, hypothermia might work probably better because it affects and it works on the metabolism on the peral area. And then there is the last point which is the phase of warming So we use hypothermia to treat high CP ok. But we have to be careful because the degree of hypothermia when we start to rearm, the patient is associated with the risk of rebound of intracranial pressure. This is a very delic delicate phase because you might have a shivering, but you can have a rebound in the intracranial pressure. And here neuromonitoring can help you transcranial doctor and changes in the cerebral blood flow can really help you to understand whether the warming is associated with huge changes of cerebral blood flow and intracranial volume. So be careful about the flow and keep extreme control to the co two, especially in this phase. The summary is that we have to be good and provide a good quality of the temperature. This is a low quality treatment where you don't use a specific target when you don't know which is the specific target where you use just intermittent evaluation of the temperature continuous is obviously more accurate surface and endovascular methods. Temperature feedback device are all factors which make us more precise in the management of temperature and the development of protocols which can implement a good temperature control are fundamental in this context. Everything I told you is what is going to be implemented in the next recommendations. These are the pictures of the face to face meeting organized by Dr Lavino. And in the next talk, I think it is going to present you the results of this consensus which are based on the pathophysiology issues that I just described you. So in conclusion, hypothermia can decrease intracranial pressure. We for sure have to treat the temperature. But we also obviously have to treat the intracranial pressure, intracranial pressure. We have to avoid hyperthermia. It seems that no benefits can be found in profound hypothermia. My hypothermia can have a role but with this target 3536 degrees and only as tier three treatments for the management of intracranial pressure. So to answer to your initial question, both temperature and IC P are the target but not only this, everything is the target. Even the cerebral oxygenation, multi molar neuromonitoring can help you to understand how to deal with temperature in brain injured patients. Thank you. Thanks. We'll have the questions at the end. We have a planning session at the end. So thanks for this. So we then. Created by
