Transcript Video What Happens When We Lose Control? Prof. Rainer Kollmar < Back to Boundaries of Temperature Session 1: The Temperaturist What Happens When We Lose Control? Presented by Professor Rainer Kollmar it is my great pleasure now to introduce the last not least speaker who is focusing on what happens when we lose control and this is related to temperature management I guess. And the next speaker is Professor Arena calma. He's chair of the department of neurology and neuro intensive care at the hospital in Darmstadt in Germany. This is where I was educated in medicine first in my life, it's one of the largest department of neurology in Germany. Um He was before he went to Darmstadt in Heidelberg in Germany there we met and his research folk er T. T. M stroke and trump back to me and hypothermia. I have found more than 130 publications in midland. So we are very much looking forward to your talk. Thank you very much for being here. Thank you very much for the kind invitation. I remember the time when you invited Peter Safar I think to Heidelberg, it was an incredible experience for me when I was just changing from the lab to the clinic and started ICU treatment and this was a beautiful experience. Thank you again for that. Um Well I was asked to have a topic about what happens when you lose control and going through the program. I was also asked to straightly point to neurological diseases since these are not so very well addressed in the program so far. So please forgive me if there are many things about neurological diseases. So I would start with some general effects that you probably all know up to 50% of all stroke patients develop fever within the first four or five days after stroke. And we know from many publications that fever worsens outcome after stroke. Therefore anti periodic treatment is recommended by different guidelines all over the world especially in europe. However there is not so good data on the topic that anti pirating treatment is improving the outcome of stroke patients. Um There's something missing. They're a little small here but it doesn't matter. Um fewer preventions plus a evidence after cardiac arrest. And um it is also recommended um in severe head trauma for the treatment of elevated I. C. P. And refractory I. C. P. What is even more important talking about temperature is what happens to brain temperature in correlation to fever and to body core temperature. This is um a study from Sharp metal from 1997. In patients with large systemic stocks showing that to inter pine humus temperature is about 1 to 2 degree higher than the body core temperature. In patients that are suffering from large stroke. The temperature initially is higher on the side of in fortune. And it's also influencing the side of non in farted brain increasing over time. What happens if you're treating fever or if you try to initiate hypothermia and come to uh degrees of 33°C. This is also from the same publication. Um the difference when this is over time and at 33°C. It's the same in the um in the brain and in the body core. So these modes of action is something that you all know from animal experiments, Also from clinical experiments, hypothermia is probably the gold standard for neural protection. It influences inflammation, decreases cerebral metabolic rate and so blood volume um it influences edema on this and it's also something that is influencing racist person in separate hemorrhage fever is doing the opposite and potentially also shivering is doing the opposite. So this is a sketch very often shown in neurology from the inaugural um showing what is happening after acute focal serval ischemia in animals. But the same certainly holds 22 patients after minutes. There are effects of excited toxicity. Perry in fact equalization and inflammation is increasing over time leading to apoptosis after several days. Hypothermia is known to decrease all these path a physiological process whereas fever increases all these processes. So what is the case if you're talking about a scenario of mass occupying stoke um for all for all patients that are suffering from Idema. Re bombing is a very critical period. This is also from an early publication from our department in Heidelberg Where patients were cooled down to 33°C for 2-3 days. And the re bombing phase was really critical and we lost some of these patients because of rebound um idioma. So what are temperature effects on the blood compartment which is very important for example, um severe head trauma. And also for this mass occupying stoke the bone um is surrounding brain server spinal fluid and the blood and hypothermia reduces to serve a blood volume giving space to the injured brain which is very important in these scenarios. I would go to the first topic starting with ischemic stroke. I consider there are different targets for stroke therapy that might be interesting for temperature management. Neural protection is certainly something that we all know from categories but also from animal experience and our experience should be done as fast as possible. Ischemic stroke has always something to do with occlusion and re perfusion and there is also something taking place as called re perfusion injury and therefore fast hypothermia and best before recognize ation can be recommended reduction of edema is something um more important for the super cute phase and many days after induction of stroke and reduction of secondary harm is something for fever prevention. So me and others tried to implement therapeutic, mild therapeutic hypothermia to the majority of patients in our stock units because we were convinced that this is a good idea. However, it was not because um In Europe we did a large trial that was originally designed for 1500 patients. Similar thing was done in the United States and um it was a very sad story because the european union lost some money and we were not able to cool these patients because they were in the wake status and it just could not stand um hypothermia, cold and shivering was too personal intensive and we were just not making any good of it. So we ended up in Not in 1000 500 patients but in 100 patients. And certainly there are no not even a sign of efficacy but we have severe side effects. What is now a game changer for ischemic stroke treatment after the randomized trials in 2015 is from back to me and I consider from back to me is maybe the classical case where we could use therapeutic hypothermia because it's something that we have as a model. Also. Please forgive me in the animal experiments we have here a very standardized scenario with an occlusion of a large vessel. And we obviously see that this vessel um is reopened and we can also calculate what would be um the in fact later on. So I think keep that in mind for the for the next slide that this is something that we could do. Um What is in the scenario of large ischemic stroke. This is certainly by many randomized trials, not an indication for hypothermic but for d compressive surgery, decompress of surgery is the gold standard. And colleagues in mind thought that maybe hypothermia would add something valuable to patients that are undergoing decompressing surgery, but it was not, we were conducting this death as a s trial and showing that there were no difference in the outcome. There were more side effects. So there was no add on beneficial effects for these patients. I personally could consider two scenarios. Um for hypothermia one would be kind of rescue therapy if patients have an M. C. A stroke plus something else. But this is not investigated so far. And if surgery is not an option there are some clinical trials especially from the asian neurologists that are investigating these things and are performing hypothermia in non craniectomy patients. I would go now to the second topic. Well I think I think the slides um they're a little mixed but it doesn't matter. The second topic in neurology would be intracranial hemorrhage. We all know that the size of the intracranial hemorrhage is the major determined of later outcomes for patients who have um bleeding of above 60 million. They have a really really bad outcome. About 90 they will probably die. So um there is also another factor contributing to the outcome which is called the perry hemorrhagic edema that is increasing over time. Um And we were thinking a few years ago that um Target temperature management for this case 35°. That would be something intelligent to do because we might freeze the oedema. And therefore we did a feasibility study including 25 patients and these are this is from the publications. What we can see here is that in our historic control group um the bleeding volume decreases over time. But the oedema increases tremendously over time. And as seen in the sketch before the perry hemorrhagic edema didn't didn't uh Didn't develop at all. So it was really frozen. Um we were applying hypothermic here for 10 days for 35°C and um the outcome was a little better. So they are really mixed here. Sorry for that. Coming to the next issue is up on the hemorrhage. There are certainly in severe subdural hemorrhage. There are three critical issues after the bleeding phase is I. C. P. Faces person anti led several in facts and there are no not so much so many good ways to fight against them. So this is from the theory group showing in their own population how hypothermia could influence their velocity in ultrasound as a surrogate parameter specimen. And this whole held true for the early phase of hypothermia. For the late phase of hypothermia. And even for the phase after hypothermia was finished. So this this might have been an indication that there is an effect on radio specimen In back in Ireland a few years ago we did a study on prophylactic hypothermia in these severe injured patients and we were treating them prophylactically 7-8 days by target temperature of 35°C and controlled rewarming and we were replicating similar things like that. Our surrogate parameter for Bezos person was controlled. So the frequencies de velocities were decreased during and after hypothermia. And there were science this is not a randomized study. Um This is against historical control. There were science that the patients were doing better and had less in fact compared to the control group. So what we're doing induction now is something not so prophylactic. It's more adapted to surrogate parameter S. I. C. P. And person. And if a patient develops I. C. P. And away. So specimen the patients transferred to the angiography get specimen lies is and will be cooled down and we are cooling the patients according to the search parameters. So it could be the case that patients are called up and down for 10-15 days in the individual case. So um others also replicated these things that we were seeing in Ellen and in search about effects of hypothermia and temperature on specimen. This is a study recently published that is showing that fever influences um the velocity in transcranial Doppler. So in fever is increasing and this correlates to a higher rate of S. A specimen. So this indirect surrogate parameter of ultrasound is something that we could use for our patients. So um I should have talked about losing control. I think for all of these all of these diseases you should have your own S. O. P. And you should not lose control because then you might harm the patient. Um There are many ways that you that you could lose control. Like you have an overshoot in terms of really hypothermia that you have an undulation during hypothermia which is also bad for the patient and please take care of free bombing. It shouldn't be too fast. We do it really really slow as um our colleagues does doing to maybe meet 0.5 degrees Celsius per hour or 0.1 degrees Celsius per hour and be aware of the temperature overshoot after you have finished um your therapeutic hypothermia. So we missed something. I will I will go through that without slides. No problem. Um This would have been my conclusion a white fever, tweet fever. If you do hypothermic control it control especially the side effects such as shivering and really really implement an S. A. P. On temperature control and take the chance for the session in the afternoon where you might go with some of us through different protocols um the slides are not on here but but it's not so much a problem. I would have talked about data on thrown back to me. So there are different scenarios. One is that there's observational data, what happens if a patient um undergoes thrown back to me and has fewer before and afterwards and there is conflicting data. Some are saying that um if patients have hypothermia they are doing worse. They have more side effects and other papers are saying if the hypothermic before come back to me and after thyroidectomy then a modified ranking outcome is better. So what we are doing right now as a small feasibility study in fiber that's a phase two trial hopefully will lead to a phase 23 trials is that we will combine third party to me in a way that we try to mimic things that we have learned um from myocardial infarction and also from our animal experiments. Like most of our patients for tom beck to me are going to be intubated and ventilated at least in my hometown. And therefore we have the chance to cool them before they get victimized. So we have this this tiny 30 minutes or something before trump ectomy takes place. And therefore we we implement a technique where we try to get the patient to 35 degree before reap refused and afterwards patients are intubated and ventilated, transferred to the ICU And will be cooled stable li for six hours to 35° sales and then slowly re want why are we going that doing that only for six hours where you might say you you showed the sketch of Leonardo showing that there is inflammation apoptosis Blah Blah Blah. So that's the best guess. And we have limited ICU resources. It's a feasibility study and we have made the experiments If we are cooling patients with lumpectomy. There were some studies before in our own department. If we are cooling these patients for 24 hours we have to load them with medications for example they might suffer from pneumonia. And there we have the patient that could normally maybe be exacerbated after coming back to me for many days on the I. C. U. And I think um that's not that's not a good way for the first study in this field, so thank you very much. I'm happy to take questions. Created by
