It's my pleasure to welcome to the podium my friend and colleague from Italy, Franco Servadai, who is not only a distinguished neurosurgeon and researcher in neurotrauma, but is currently the president of the World Federation of Neurological Surgeons. Franco is going to talk to us about TBI. Time for a change? Franco, thank you. Good afternoon, and I will try to discuss with you the experience that I have in producing guidelines. I was, you will see the picture, deeply involved in the process of producing guidelines from the beginning, and the problems we have now in dealing with the guidelines for traumatic brain injury, which we have to remember were the first guidelines ever published in neurosurgery. When we did this, the first publication in 1996 of the Brain Trauma Foundation, WNS, and CNS joint section, it was by far, because the other guidelines which arrived was six years later, was by far the first guidelines published in neurosurgery and in neurointensive care, we would say. So, this is me 20 years ago, actually 24, and this was an American-European meeting with Germans, Italians, Dutch, and Randy Cessna, Jane Gagiar, and Graham Tisdell, meeting for the first European presentation of the American guidelines, and it was actually the first one was done in my country, in Italy, was presented in 1996. So, first, what we have learned from the guidelines, we have learned a method which is still valid. We have to check the papers who are published, we have to score the paper and grade the papers according to class one, two, and three, which at that time was not obvious at all. Then, combining the level of the publication that we see in the evidence-based medicine, we produce what we call at that time standard guidelines and options. Standard was produced by class one and two, guidelines by class two and three, options only by class three. It seems easy, but it wasn't easy. The first set of guidelines which was published were received by the neurosurgical community. They were translated in seven languages with a different system, which we will see it's still valid now. Some of the countries, like the Spanish translation for Spain and Latin America, just took the set of guidelines and translated. Some other countries, like my country, tried to adapt the guidelines to the local situation to make them easier to be used. A third part, which was done by the European Consortium, was applying, taking the guidelines with an addition of some expert opinion. These three sets of environment are still very much important now. What about the first set of guidelines? Fourteen topics, only four standards, all negative. Don't do hypotension, avoid hyperventilation, avoid glucocorticoids, avoid prophylactic anti-epileptic drugs. These are the list of topics. As you see, they were revised in 2007, but that's not the issue. I am talking now about the limit of the process. We can realize guidelines are taken as a Bible. The Bible is still there 2,000 years afterwards. The guidelines may be wrong. The first set of guidelines may be wrong, and actually we were wrong. The cerebral perfusion pressure should not be maintained over 70. This was wrong. We realized a few years later, that's not good. It's enough 50 or between 50 and 70. Second, when we produce, I was one of the authors of the surgical guidelines. When we produced the surgical guidelines, basically we didn't find any good paper at that time. We only found class three papers, but we operate traumatic brain injury every night. Every one of you who is in this room is called in the night to operate. We operate without standards because we didn't publish standards. How can you randomize this patient and say to non-operation? It's impossible. So whenever a surgical indication is clear, there is no evidence-based medicine. You cannot have it, simply. So what Dan Merriam said as a comment is still valid today and probably tomorrow. Ranking surgical evacuation of a large post-traumatic hematoma as an option is consistent with the methodology, is not consistent with the best medical practice. We have to produce guidelines for our medical practice, not for the methodology. This is the key point. Already in 2008, David Merriam said, the process of guidelines is neutral. This is a key point. If we look at the same papers, myself, David, you, Peter, or anyone, we arrive to the same conclusion. We thought, yes, no, it's wrong. This is steroids for spinal cord injury. This is published February 2013. It's the Cochrane Collaboration Study. They say there is an urgent study. We need more trials, but for the moment, there is a class one indication to use steroids. February 2013. They have reviewed, at the end, after selection, 43 papers. These guys have reviewed 47 papers. Among them, 40 papers were the same, and they have done this job, look here, in March 2013, one month later. Same papers. Conclusion, class one, you don't have to use steroids. In one month, with the same paper, we reach opposite conclusion. The result is a mess. These poor people are in South America. They have done a survey, and they say, what do we do? Sometimes we use steroids. Sometimes we don't use steroids, but we have evidence for both, for using and for not using. If we update guidelines, are we sure that we do better than before? That's the question. The more I travel, the more I think it's not sure. These are the last guidelines just published, the fourth edition. Tremendous work, with one part which is very important. They have added in the addendum the motivation. If they have changed the guidelines, they added motivation. Why we did so? This is very important and very thoughtful, which is here. I don't go. I don't have time, but if we go with the methodology, which is now almost a mistake, in my opinion, we have to change the system. If we go with the methodology, sometimes we don't do a good job. Look, the indication for ICP before abnormal CT scan in a comatose patient, very clear. We all know who are these patients. Management of severe TBI using information from ICP is recommended to reduce in hospital into weak mortality, which is good for methodology, but between these two, which is best? This, or the other one, we move from 20 to 22, the cutoff, 22. I come from a country with a lot of fantasy, but listen, guys, 20 to 22, which is different. Obviously, it's methodologically perfect, because there is one paper who says that the cutoff is at 22. Good paper, but before writing 22, you have to think, what am I writing? Is it correct? Do we need the key point, which I just go to finish? The other mistake we did, all of us, we took only ICP monitoring rate as a benchmark of the use of the guidelines. The guidelines were very complex, with 18 items. ICP was only one of these. ICP is important. We need ICP to cure our patients. For many of us, including me and our group, is a standard of care. We need ICP. We're not against ICP, but this study, which already has been shown, done in South America, showed by Randy Chestnut, we don't have time to discuss this side, but they show that if you control ICP, not monitoring ICP, but by repeating CT scan and checking CT scan, the results are similar in the treatment of patients. One problem is the ICP is one part of our study. This is a European study that we published a few years ago, and you see that when we decide to operate, we use ICP, clinical deterioration, and radiological deterioration together. We don't separate ICP from the other. This is a typical patient. You put an ICP monitor, the contusion blows. The patient is worse. The ICP increase, and we operate. But we took all three parameters together. We don't separate the number. We put the number in a context, which that's why we were never able to show that ICP monitoring improves outcome. We have opposite paper from the same country. This is a U.S. paper. This paper is saying we have demonstrated that ICP improve outcome, and this paper says we have demonstrated that ICP does not improve outcome. And it's why ICP is part of a management, is part of a monitoring, should be in the context of this monitoring. And then I just give you a brief overview, a view of all over the world. Where are we? Can we apply the same guidelines? This is my country, nice ICU, one nurse, one patient, monitoring, perfect. This is our management guidelines, good. And this is another part of the world. You see how many patients here, how many patients there without ventilator, because there are not enough ventilator, 10 operation per day, a different situation. What's a problem? Eighty-nine percent of the paper come from U.S., Canada, Australia, Japan, Europe. But there, there is only 18 percent of injuries. All the other injuries are everywhere else. These are the 15 most publishing countries in the world in neurosurgery. Almost half of what is published, 46.8 percent of what is published in the world comes from United States. Then we have China. Data are from 2016. China, Japan, Germany, United Kingdom, Italy. Only India is a country with limited resources. So we don't, basically we don't know what is about some huge part of the trauma that we have. So to finish, which are the message? I don't want to be negative. Guidelines are important. We need to know what comes from evidence-based. We don't need to say we don't use them anymore. They are important. There is no alternative to the guidelines. But we have to say that there is, as we have seen from Peter and from Andras before me, the patient is a complex patient. We don't have to take only one parameter as the key point to cure our patient. It's one part of the, of what we are doing. So what we have written to the guidelines publication is this. We need to take care that methodology alone probably is not enough. We need to combine methodology and patient's cure as we have done. And this is the reply of the authors which say we share your problems. And we agree with you that we don't run after formally correct guidelines. We run after guidelines which can be used in most part of the world, I would say. So we need to integrate the guidelines into locally available protocols. And probably we need to do a process of certification. What does it mean? Priorities. Which is, which part of the guideline should be applied first and which one comes later? Sorry. Thank you very much. Franko, thanks for those remarks. And those, again, of us that are old enough to remember the rollout of the first guidelines, remember that this really was a striking moment in not only neurotrauma, but neurosurgery. Because the document that was produced was not only scientifically rigorous, but it was practical. I mean, it was, you could actually follow actually follow it. You could actually develop a protocol based on the guidelines. And I think what many people saw with the rollout of those first guidelines was the ultimate limitation of the guidelines process. And that as the guidelines process became more and more scientifically rigorous, the end product became difficult to apply in local situations. So I think some of us are trying to get together and develop useful protocols based on the scientifically pure latest set of guidelines that we have. But thank you very much. Questions or comments from the audience, please. Who views the fourth most recent edition of the guidelines to be better than the first edition? My question to you stems from an observation, which is that the first set of guidelines, the first author was a subject matter expert, Ross Bullock, someone who has spent his whole life taking care of this patient population. And the most recent set of guidelines, the first author is a statistician. Correct. How do we take this back to the past? Because we have the same problem in our clinical trials where the statisticians force us to analyze the data with intention to treat instead of as treated. The statisticians force us to do these guidelines according to these very strict and formal methodologies and in the end we lose the whole point. How do we take it back? Andreas, do you want to use the microphone? It's easier for us because these guidelines are coming from the U.S. So it's really hard to work on it. But for us, we interpreted it and made the Hungarian guidelines. We took the liberty to put together a people of experts, a panel of experts and basically tried to adopt the guidelines to the actual situation with a clinical merit in it and a clinical flavor in it. I don't know whether they can be still scientifically assessed as having high scientific value, but practically it would not be useful for the Hungarian relations and for the practical utilization of these guidelines. That's what matters, right? I totally agree with him and we can't take them back. One day we will find out that the head injury is a continuum and it's not so simple that we divide them in different groups, as I will give in my talk as well. But we don't have an inquisition that makes the rules. We have a group of experts and the rules change according to time. We have better treatment methods maybe. We have maybe stem cells coming, something like that. So let us wait and see. Tony, did you want to add something? A lawyer will be next. Correct. Thank you so much.

Franco Servadai

President

World Federation of Neurological Surgeons

guidelines

traumatic brain injury

TBI