Transcript Video When is Extended TTM Required in My Protocol?Prof. Guoyi Gao < Back to Boundaries of Temperature Session 4: Limits When is Extended TTM Required in My Protocol? Presented by Professor Guoyi Gao now we are going again virtually and it's a great pleasure for me to introduce the next speaker. Next speaker is coming from shanghai in china. I can already see him on the screen and now he is visible for all of us. So welcome professor. So he is Professor Gao is the professor of the department of neurosurgery at the university hospital in shanghai and china. He did a lot of research on traumatic brain injury and hypothermia and he's a member of the neuro trauma pathological committee of the World Federation of neurosurgical Societies. So welcome Professor Gao to our meeting here in Berlin. You. The title of your talk is when is extended T. T. M. Required in my protocol. Please welcome professor. Thank you sir for your nice introduction. Good morning dear colleagues. It is my yeah it's my great pleasure to be invited to the Uh 2022. And also I'm sorry for not being able to attend in Berlin. Uh this is a disclaimer on my presentation. The topic I would like to present today focuses on the duration of cooling therapy on T. B. I patients. I appreciate the title chosen by the organizing committee when extended the T. T. M. Required in the protocol. It is truly a question for many intensive days when initiating cooling therapy. Especially on T. B. I patients. The importance of temperature control and the fever prevention in neuro critical care was stated by Aristotle in the 4th century BC. The men's superior intelligence depends on the fact that his larger brain is capable of keeping the cool enough for optimal mental activity. almost 20 years later, another chapter in the our regions of therapeutic hypothermia and its potential in neuro critical care and resuscitation is discovered, Charles phillips. A neurosurgeon wrote in 1897 that applying the escap was beneficial in traumatic brain injury. 2nd in efficacy only to traffic nation in the modern area early clues To the potential efficacy of therapeutic hypothermia was suggested by remarkable recoveries in neurosurgery. Dr. Lundberg described that hypothermia was induced and at rectal temperature of 26 degree and a partial resection of the continues the right temporal lobe was carried out In 2009. Dr. Bushman suggested the term targeted temperature management to describe the scope and approach to the potential use of therapeutic hypothermia and the temperature regulation across the field of critical care. T. T. M in its current form may represent represent a nobel concept namely ultra mild hypothermia. Ultra mild hypothermia could ultimately lead to a pharmacological substitute for therapeutic. These are exciting new avenues for the therapeutic cap astronomy research applications for neuro critical care and beyond personally. I respect the statement from another neurosurgeon dr coach, a neck in Pittsburgh, we believe that hypothermia is a complex therapy, not appeal and our understanding of how to optimize it. It's far from complete the pathological mechanisms underlying severe T. B. I are complex and often involves focal and diffuse change. The pathology. Ical mechanisms associated with T. B. I. Uh temperature sensitive, so in animal models of T. B. I, beneficial effects of therapeutic hypothermia have been shown repeatedly. This inspires the enthusiasm of clinical implementation. However, current have failed to yield the success in translating neuro protective, both adults and the Children in the variety of strategies. Over the last 30 years, numerous clinical trials conducted to assess the effects of induced hypothermia in severe traumatic brain injury. Most high level trials suggested week or no evidence for the use of therapeutic hypothermia. Following T. B. I. Reviews have suggested countless explanations for these failures, usually placing the blame on issues related to clinical trial. Heterogeneity of patients lack of accurate injury, Panel typing, uh inadequate outcome assessment, truth or sub optimal treating intensities. Uh, just as it said in the poem from the chinese Tang dynasty, many barriers went to the front line to fight but seldom comes back home successfully. This describes the current situation of trials of hypothermia on T. B. I. World widely does N. A. P. I intend to fight negative results. The facts are that the Eurozone study in road 387 patients as seven at 47 centers in 18 countries from november 2009 to october 2014 found that in patients with an intracranial pressure of more than 20 millimeter mercury after traumatic brain therapeutic hypothermia. Plus standard care to reduce intracranial pressure did not result in outcome better than those with standard care alone. The polar trial in road to 66 patients for about seven years. The final results showed that no fighting's about the use of early prophylactic hypothermia for patients with severe traumatic brain injury. The hope trial aimed to determine whether early induction and maintenance of hypothermia in patients with acute subdural hematoma will lead to decrease ischemia, re perfusion injury and improve global neurologic outcomes. 32 patients uh 16 in each group were analyzed. The favorable six months G. O. S. C. Outcomes were not statistically significant. Different between hypothermia was as normal for me in groups it can be assumed that the high inter study variability in the statistical and clinical designs of the trials which were included in some of the meta analysis and a different study selection protocols were responsible for the contradictory results. Thus Hungary group took a no well approach to determine the efficacy of therapeutic hypothermia. In T. B. I, they introduced the cooling index an integrated matter of therapeutic hypothermia calculated from three different cooling parameters including target cooling temperature, cooling duration and the speed of rewarming. The cooling index represents the area between the body temperature curve of cooled patients. The author concluded that milder longer cooling and the slower reforming are the most important to improve the outcome of severe T. B. I. They introduced the cooling index to assess the overall extent of cooling. They discussed that the therapeutic hypothermia is beneficial in severe T. B. I. Only if the cooling index is sufficiently high. These conclusions encourage us to revisit the cooling duration which is a major of arrival in the calculation of the cooling index in different trials. The early report on the positive results of hypothermic therapy on severe traumatic brain injury patients, the new England Journal of Medicine and the protocol they took in the study was uh to cool the patient and uh rectal temperature reached the 33 degree. It was kept between 32 and a 33 degree for 24 hours. In patients with coma. Score 5 to 7 hypothermia was a short aged with significantly improved the outcome at three and six months In the recently published the study results. The crew kids study could pediatric patient for 48- 72 hours. The Eurozone study suggests that the the study centers to cu patients at at least 48 hours And the power study will could patients at least 72 hours. Obviously the difference, including duration exists among studies currently we could not find for the cooling duration on hypothermia treatment on TB patients in Eastern countries such as china and japan. Maybe neurosurgeons tend to cool the patients for a longer duration. Our group published observation of cooling the patient cooling the TB patients for either two days or five days. Those patients are severe TB patients. It is very interesting to see that the phenomenon of I. C. P. Rebound in the group of two days cooling. We did not see this I. C. P. Rebound in the group Of five days cooling. This manuscript reflects the reflects reflects the root of clinical exploration in terms of cooling duration and also this the result of this manuscript also encouraged centers in china to continue with the protocol for longer uh cooling duration. Or to say it formally extended A. T. T. M. Protocol in 2021. The long term hypothermia. One that is long are th one study group analyze the data from three about 300 chinese patients enrolled into the trial with a unique cooling period to five days And the target temperature of uh 30 34-5 degree. The result of this study indicated that there was no difference in favorable outcome and in mortality between groups. But In patients with an initial I. c. p. higher than 30 hypothermic treatment significantly increased the favorable outcome over the normal semi a group. So to to interpret the results into clinical scenarios. The hypothermia may benefit the patients with refractory intracranial hypertension. If the cooling period is not 25 days. The scene of our working in the in the new neurosurgical iCU can can tell a lot of stories of long term cooling syrupy on Tv. I patients this is a patient who suffered a severe injury when falling down from running vehicle. He was alert upon sending to the local hospital. He wondered entering he entering a the compressive operation when he was found unconsciousness with progressive intracranial ations. Six hours after admission. But the operation did not relieve the status of the patient with the one side pupil still dilated after surgery. So the patient was transferred to a higher level T. B. I. Center and received the second decompression. The initial I. C. P. Before surgery. Maybe you can see from the chart. The initial I. c. p. before surgery was about 70 and I. C. P. In ICU. After the second surgery was higher than 50. So the neurosurgeons decided to cool the patients with surface cooling equipment and the sedative sedative agents combined with neuromuscular blockades. The I. C. P. Dropped to 20 But rebound to about 30. When the neurosurgeons try to treat the temperature slightly higher than 33 degree. Then the decision was to target the I. C. P. As a marker of cooling effectiveness. Thus the patient was good for 10 days. The patient was cool too for 10 days till the I. C. B. Curve got stable. So in many centers in china neurosurgeons have various experiences with longer cooling period towards an optimal I. C. P. On Tv. I. Especially severe TBI patient personally I agree that a more extended cooling period can cover a comprehensive acute disease trajectory. Does exert a protective and modify multiple physiological processes. Also maintaining I. C. P. And awarding rebound I. C. P. Of course. On the other hand we could not draw a clear conclusion yet for the unknown side effect of longer cooling. The huge work pardon on the bedside and the harm of over dosage of the sedatives and neuromuscular block case agents using during the longer cooling period. So for the for the reasons above I hesitate I hesitate to re recommend extended T. T. M. For every center and on every Tv patient neither could I point out the future of extended T. T. M. From my view however the progress of neuro intensive care has brought forward many aspects on the table. We certainly could not expect a fixed protocol to cure to cure a population which needs individualize the therapy with the progress of multi modality monitoring at the bedside. The heterogeneity of TB. I will finally exhibit the precise target to treatment including including treatment also to eat an elephant bite by bite. We need to focus on proper endpoint such as I. C. P. E. G. CPP oxygen for any therapy including hypothesis. In conclusion the extent extended GTM protocol still have space to stay and to be further investigated at at the end of my presentation. Please allow me apologize to old attendance from my inability to join you in Berlin for the covid control policy in shanghai also. I hope we can meet in the near future and welcome everybody to shanghai china. Thank you Created by
