Transcript Video From Hypothermia to Temperature Control < Back to Summit23 Cracks in the Ice From Hypothermia to Temperature Control Presented by Professor Fabio Silvio Taccone So now it's my pleasure to make you a little history on uh hypothermia, how we move from hypothermia concept to temperature control? And these are my conflict of interest. So you heard about this um how complex is the pathophysiology of brain injury? This is a slide only looking on neuro inflammation. So imagine if you add on top of these apoptosis, cellular damage changes in brain Amos. How complex is the pathophysiology, brain injury? This is true for traumatic brain injury where you have a focal injury and it is of course, even worse if you consider a global injury that suffer for patients after characterized, this is how the concept of derm has been introduced in clinical practice. It is a little bit like steroids in the su you have an intervention that is able to potentially minimize all of these pathways. It's a kind of general neuroprotective intervention. And looking at a bunch of experimental investigation, we have learned that all these pathways can be controlled by temperature management and all these pathways are temperature dependent. So it's logical to manipulate temperature, aiming to protect the brain in this setting. Now, when you look at how cold and our intervention, lack of manipulating temperature exists in the medical history. We are back to 3500 before Christ is Pyros from Egypt where they describe use of cold as a therapy. And even in the School of Hippocrates, they described that they use cold therapy for tetanus treatment. So that's not new as you can see. And Gladius Galen is a very famous doctor in Ancient Greece described using cold to treat fever. Of course, it was very symptomatic intervention. But using this cold and basically ice was able to relieve some of the symptoms of the patients. I'd like to remind Girolamo Mercora, who is of course an Italian doctor who was treating himself with the cold immersion into cold water to treat a renal colic and apply this to other people apparently with very good results and a very nice experience of Philippe Pinel in France who used APO for mental illness and discovered this because a guy was a mental illness just escaped from his asylum. He was found in the Pyrenees in the forest hypothermic and apparently his mental status improved after being etheric. So that's why they started using EPO for mental illness. You probably all know Barron Larry is a part of the great army of Napoleon who described how he could perform Palin's amputation of a soldier during Napoleon's campaign. And then of course, William Osler, who was the first to report that that using athermic for defo fever, decreased mortality from 20 to 7%. And I think it's important for us to know that he is a neurologist and a neurosurgeon from us was the first to be described athermic to treat pain and tractable ba due to malignancy. Basically, he used a very simple intervention. He opened the door of the patients during winter and he cooled down these patients to 32 degrees and apparently pain was much improved. Of course, nurses complained that, you know, the quality of work was a little bit too complex. And this is the first image of a blanket used in the room of a patient to induce a global hypothermia and to provide relief from this pain related to malignancy. And he was also the first person who provide local hypothermia during the surgery to treat not only tumors but even CNS infection and sometimes trauma. And it is important to remind that he provided data in the third International Cancer Congress in 1938. And he submitted the data for publication and the paradox of history says that his work was taken from Nazi who applied. Unfortunately, this intervention in Takao. So this is sometimes the paradox of medical research. But you see how you know the history of cold in the medical field is from is there since five millennium. And then it evolved during time in the fifties and sixties to the clinical application. This is the only I have, it reminds us that in cardiac surgery with this immersion in cold eyes. And then in local athermic for neurosurgery, the use of apo theia was used to protect the heart and the body and the brain of these patients during these complicated surgeries. So these were the first period when hypothermia was applied in clinics in the control setting of the or and then when you move from the clinical application to our patients in the ICU, everyone reminds Peter so far he is considered as the father of resuscitation as the one that in 61 describing this very nice cartoon how we should take care of patients after cardiac arrest, which is as you can see basically a post suation care as we know it today. So he was a pioneer in the field and described that hypothermia should be start within 30 minutes. If no signs of recovery is observed, this was the who basically said we should cool down patients. And if you see the literature, he was not the first one who demonstrated that it might work, but it's the work in the John Hopkins in Baltimore, Williams and Spencer were the first one who applied apo theia in four patients with cardiac arrest. You see here is not the same that in a trial is respiratory arrest, stab wound, very shorter. So it's a different setting, different duration, deeper temperature, but they provided that it is applicable. And then for many years, we forgot how to use it because the applicability in terms of devices was very limited. And then with the evolution of knowledge people in Austria had of course the merit to say, well, we are interested in studying temperature after career arrest. We observed that when you arrive at the hospital you look at because you were close to that. But then if you do nothing, this is what happens like that Raymond showed you you will develop some fever and those patients with poor outcome, there is an association with persistent hypothermia and poor outcomes. So it is important for you to remind that the people in Austria were so interested in cardiac arrest. Then in the nineties where the median survival in cardiac arrest was stand to 15% all over, they 45% rate of favorable outcome. So they were the first groups in the world that really were dedicated to improving care of these patients. And in Japan first, this is a paper coming from 90 was applied athermic. You see how long did it take for the temperature to go down to 23 degrees? It was feasible. It was not complicated. They applied this in 15 patients. And after Japan, this was reproduced in Austria again with the same group with the a a group that showed that in 27 patients, they were able with a new system, the thermos suit to improve, to implement apo these patients bring out temperature 33 degrees. It was basically well tolerated with a lot of physiological parameters were collected and they were ready to go for clinical trials. And this is how we came back to New England in 2002. That's the whole history behind how we went up with two randomized clinical trials. You all know one in one in Australia with different methodology. But with the same idea, targeting patients with a higher probability of good outcome. Those we witnessed shock about rhythm and arrest and we applied a poor for 12 to 24 hours and they show that improved survival and improved survival with good neurological outcome. And it's important to remind that Peter Safar could of course write a very nice editorial accompanying this idea that he promoted, you know, more than 50 years before it was finally had the chance to see a play of function in a clinical trial. And a few months after the Il Cor provide this recommendation, you should cool to 3234 degrees, all patients with character arrest in initial shock rhythm. But basically such cooling should be may be beneficial for all the others. So we moved from a nice concept and application in clinical practice with two randomized clinical trials. And then we basically apply to everyone. I remember Keith Polman made a lot of presentation use this Nike slogan, just do it basically while it works in this population, it will work in all the others. And so we came back into the area of hypothermia as the intervention that we see life after card arrest. Of course, together with these great results which have started the modern area of post station care. There have been some questions. First, we observed that it was not implemented all over. Some countries have 30 to 40% of people who were treated and there were many barriers limiting the application of a term in the field. They were questioning about the methods. How can we improve the quality of the methods we use to provide a better therapy faster and to potentially better control temperature over time. We understood that the apo tomia phase was important but all the hours preceding and following the apo tomia phase was as important as that one and they should also be controlled. And some questions, some people also question do we have enough evidence to say that these interventions will be improved and will work everywhere? And this is why you know, the literature has moved to a consensus where in 2011 5 professional societies met some experts and provide us this panel. This cartoon. This cartoon is basically the the start of the changes from apo hermia as the only important phase of the intervention to this targeted temperature management, the induction phase, the main phase, the warming phase and the fever avoidance. All this part at different target temperatures are important to provide an adequate neuroprotection in these patients. Most of these recommendations came by physio and common sense. They were not supported by clinical practice, but they basically provide a new standard to care about these patients. And we came out with all new modern methods to improve abo hermia which were temperature feedback, were able to provide the more accurate control of temperature compared to the previous one, which have a lot of problems of implementing and provide adequate hypothermia. Of course, we have to remind that some people said, you know, we have the evidence that maybe adding all the existing studies, hypothermia might work, but we are still not sure. And we have only a few 100 patients that have been included in these randomized clinical trials. We should move maybe to another trial. And also we recognize that maybe we have not described sufficiently the risk which exists related to the use of a term in this patient. There are many physiological derangements that occur when manipulate temperature in these patients. And we should better describe those in a randomized clinical trial. And so we have basically came from the APO thema phase to the TM phase. But with many questions pending in the area of we had I think the chance because the knowledge evolves thanks to the research that people provide to move further and then say, are we stick to 32 degrees or can we provide different ranges of apo? This is the idea behind the TM one trial that has been basically supported by Lund but also was a European effort to study almost 1000 patients to do two different levels of hypothermia. And in that study, as you know, the two levels of epidemic provide similar effect in terms of outcome, mortality or neurological outcome. And this has brought the thereafter to the challenges of the national idea, can we replicate it is not exactly the same study, but can we replicate the idea of promoting the ACA trial in a larger population of cardiac arrest patients where we again will compare hypothermia as we have done until today to control normal. So we are still controlling the temperature, but we are not aiming at hypothermia but at normal levels, let's say keeping below 37.8 degrees. And you all know the results of the TTM study presented by Joseph Danic here in the TTM course, no difference in outcome, no difference in logical outcome, a significant increase of the proportion of patients with significant arrhythmias. And so this came to the new guidelines have been part of this. Bern botting has been part of this and other people, there were people involved who were at the same time, some of those who were believers, some of those who were not believers, some of those who were in the middle and we came out, I think with a reasonable recommendation that we need to monitor temperature, it is very important. But at the best that we know today, as a general message, we still, we still should actively prevent fever. I think the world is very important, actively. So we still be active proactive in doing this and keeping the temperature below 37.7. And we also said that this intervention should be at least 72 hours as recommended in the box trial was not published yet at that moment. And there is insufficient evidence to say which patients might benefit or might be harmed. Very importantly from having lower body temperature. So we left the door open for further research. And so we came into the area of temperature control. Now we understand that manipulating temperature is important, but we are trying to within, let's say normal values as the intervention, at least in cardiac arrest patients. And if I want to re summarize the literature, we moved from the first area where the only possibility was 32 to 34 and all the rest was bad. Then we enlarge our viability of temperature targets 33 to 36 and above 36 everything was bad. And then now we have a larger scale of temperature in which patients could be managed with. Still some questions about the future. Can we do another trial? Should we use devices? Can we tolerate our term in the setting? We still do not know. Of course, don't worry if you are still here talking about temperature. There are a lot of questions that we don't have the answer. We know that for example, the ACA trial and the Bernard trial provided effectiveness but in a very selective patients population, which of course is only a small part of all the card patients you will observe in your clinical practice and TT M two trial which provide neutral results was partially overlapping but not entirely the ACA and Bernard. So the two options are still possible. You will learn, you will hear about the AA in trial in France looking shock rhythms and the recent German trial of in hospital cardiac arrest. You see that all these studies have some overlap, they provide positive or negative or neutral results, but they not entirely give the results to the whole patient's population. And there are maybe a portion of patients where we do not have information clinical trials, whether hypothermia might be effective, which is very important to me because it leaves the door open for further research. Of course, you heard we still need to understand which is a high quality TTM. If I decide to give an intervention like antibiotics or surgery or whatever, I want to give it the best methods as possible. So we still need to understand how to define high quality tm and how high quality can influence the trajectories of our patients. And finally, which is to me today, the most important question, we need to revise the way that we include patients randomized clinical trials whenever cardiac arrest. Patients arrive in the hospital with ventricular fibrillation, one minute of CPR and immediate defibrillation, sedated by the ES system. How we stop sedation. These patients will wake up. These patients are too well to be studying the clinical trials and some others with a witness arrest with no shock about rhythm with prolonged resuscitation. They arrive at the hospital with already too severe brain damage, whatever you will do, you will not be able to change the history. What we miss today is the capacity to individualize, identify these middle risk patients in whom an intervention can, which can potentially provide neural protection should be studied to see whether it is effective. I think this is the way to go in the future. So my conclusions are that there are different pathways related to brain injury. I focused a lot on cardiac arrest where a lot of literature, but it's very similar to other forms of brain injury and all these pathways are temperature dependence. So it's quite logical to manipulate them to provide neuroprotection in these patients. There is a biological plausibility telling us that hypothermia is neuroprotective. I didn't discuss the experimental evidence, a lot of studies that show that it might be effective. But I think as a researcher, clinician and scientist, we need to stick with the evidence, we can discuss it, but we cannot ignore what is now in the literature. And there is at least a huge controversy on the efficacy and the fact of hypothermia in clinical practice, which does not mean that we have to abandon temperature management. What we recommend today is to control temperature be active keeping a patient's normothermic, as Raymond said is as complicated as keeping a patient's hypothermic. And we clearly need ongoing research. We do not have all the response to our questions on the selection of patients and how to define and implement high quality TT M. Thanks a lot. Created by
