THERAPEUTIC HYPOTHERMIA AND TEMPERATURE MANAGEMENT Volume 2, Number 3, 2012 ª Mary Ann Liebert, Inc. DOI: 10.1089/ther.2012.1513

Therapeutic Hypothermia in Post-Cardiac Arrest Moderator: Joseph P. Ornato, M.D.1 Participants: Carmelo Graffagnino, M.D.,2 Hans Friberg, M.D., Ph.D.,3 Michael R. Mooney, M.D.,4 and Eyal Herzog, M.D.5

Cardiovascular disease accounts for about 40% of all deaths in the West. Post-resuscitation care has changed in the last decade, and outcomes have been improved thanks to several combined measures including induced therapeutic hypothermia. Based on two landmark studies published in 2002 showing that the use of therapeutic hypothermia in cardiac arrest decreased mortality and improved neurological outcome, the International Liaison Committee on Resuscitation and the American Heart Association recommend the use of therapeutic hypothermia for cardiac arrest. Nevertheless, many hurdles remain for institutions and hospitals to initiate therapeutic hypothermia in this patient population. The development of interdisciplinary treatment teams including different specialties are needed to provide the best care throughout the treatment protocol. A series of state-of-the-art lectures presented at the 2nd Annual Therapeutic Hypothermia and Temperature Management Meeting in Miami brought together experts in the field of therapeutic hypothermia and cardiac arrest. Dr. Camillo Graffaginino, Department of Medicine and Neurology and Director of the Duke Neuroscience Critical Care Unit at Duke University, discussed dosing hypothermia and the use of physiological markers to guide therapy. The identification of various surrogate markers to help guide this therapy would be very useful to the field. Dr. Hans Friberg, Department of Emergency Medicine at Skane University Hospital, Lund University, discussed the long-term benefits of early cooling in a post-cardiac arrest patient. Therapeutic hypothermia can have long-term benefits, but it would be important to be able to determine early whether this treatment is having a beneficial effect. Dr. Michael Mooney, Minneapolis Heart Institute, discussed outof-hospital cardiac arrest hypothermia protocols and a need for resuscitation centers of excellence. It is becoming clear that several different disciplines with experienced treatment providers need to be included in therapeutic hypothermia treatment teams to evaluate and treat these patients. Finally, Dr. Eyal Herzog, Director of Cardiac Care Unit, St. Luke’s Roosevelt Hospital Center at College of Physicians and Surgeons at Columbia University, discussed systems of care in cardiac arrest. He emphasized the advanced cardiac admission program that consists of a series of projects that have been developed to bridge the gap between published guidelines and implementation of real world patient care. Dr. Joseph Ornato, Department of Emergency Medicine and Internal Medicine at Virginia Commonwealth Uni-

versity, moderated the program. Together this panel provided updated information regarding strategies for successful temperature management in the post-cardiac arrest patient. Dr. Carmelo Graffagnino: As one is building a team of champions to take care of these very sick patients, you really need to find the neurologist that understands this disease and actually gets involved from day 1. I think the worst thing you could do as a physician is to ask someone to come in on day 6 to evaluate somebody they have never seen. They have no idea what the trajectory of disease has been the entire time and have no idea what has been done for the patient except what they read in the chart. Then to have them make some kind of decision that is communicated to family members that they have never met and then prognosticate. In my experiences, taking my intensivist’s hat off when I’m asked to see these people, almost universally, the family does not want to hear from the cardiologist if they are going to survive and have normal neurologic function. At least in our institution, they want to hear from the neurologist, but you don’t have a relationship with these people. So if you get to a point for whatever reason that you are recommending that the prognosis is not favorable, it is very difficult, as opposed to if you have been involved from the beginning as a member of this cohort team following the patient. The other part of my comment is that if you monitor them from the beginning, between 25% and 40% of these patients will actually have seizures during the course of their illness. So involving the neurologist after 5 days of seizures is probably not appropriate either. If we think the spreading depression causes secondary damage, ongoing epileptogenesis definitely causes ongoing damage. So, I think for those two reasons—one as part of the cohesive team and then the other is managing the neurologic complications and consequences of seizures to all the cognitive parts—it makes it intuitive to get somebody involved very early. Dr. Michael Mooney: Just to respond to that, I think every medical community is balanced in a regional way. The problem with neurology, and this sort of resonates across the country, is that they really have not kept up on the new ele-


Department of Emergency Medicine and Internal Medicine, Virginia Commonwealth University, Richmond, Virginia. Department of Medicine and Neurology, Duke University Medical Center, Durham, North Carolina. 3 Department of Emergency Medicine, Skane Hospital, Lund University, Lund, Sweden. 4 Minneapolis Heart Institute, Minneapolis, Minnesota. 5 St. Luke’s Roosevelt Hospital Center, College of Physicians and Surgeons, Columbia University, New York, New York. 2


110 ments of neurocritical care specific to neuroprognositication and therapeutic hypothermia. So what happens is that they apply old standards to a new paradigm, and they suggest to the family that survivability would be unlikely, and in a fragile family they instantly go to comfort care when you know that there is really a good chance of survivability. It is not a theoretical thing; it is reacting to actual circumstances of what our consultants say to do. Dr. Eyal Herzog: I just want to comment. We have the neurologist activated from minute 0 because our paging system includes a neurologist. So if you are referring to the fact that you have to involve a neurologist first, yes, I agree with 100% of this. But what I want to learn from you, if you can teach me about the appropriate conditions for withdrawal of care, what tools should the cardiologist use? Dr. Hans Friberg: I can just comment, and we should not forget the intensivist with different background specialties. I represent them, and we actually talk to both cardiologists and neurologists. Dr. Joseph Ornato: All of you, in my humble estimation, are correct in part because it really is a partnership. I would like to add one little element that I think you have hinted at, but I’d like to put an underline on it. Post-resuscitation care is a disease process that lends itself best to regionalization of care. Clearly, as you’ll hear in the next session, every hospital has to be a player; every hospital in the community has to be able to get things started and in some cases provide advanced management of patients. It is best for the patients who have the greatest opportunity for survival to go to centers that treat 50 or 100 cases a year. In those centers, partnerships have been developed, because you are right, it is a learning curve for all of us but particularly for neurology. One of the important things that we all have to learn is when to ‘‘keep your hands in your pocket.’’ It is important for at least several days for all of us to be very humble and make it clear that time is one of the best elements that help us to prognosticate. Question: Did you get buy-in from all the cardiologists— particularly the interventionist for taking not only the STEMIs as well as the non-STEMIs arrest? Dr. Eyal Herzog: Outstanding question. When you put a team or a system to work, you first have to buy in to your interventional cardiologist, because in the first few years when we started it, we actually forced them, and then they believed in us. I’m not an interventional cardiologist, but I oversee them. We force them to do it, and then they say thank you that you included us in this because in the west side of Manhattan, all the V-fib arrests will go to the cath lab. Dr. Patrick Lyden: In Los Angeles, we have executive television producers who know CPR. But our problem at Cedar Sinai is sort of the reverse. It is a very, very busy STEMI center, and it is all about door-to-balloon time. Absolutely nothing gets in the way of getting to the cath lab, including hypothermia. So in our hospital, to get a patient cooled, you call neurology, and we come and take care of the hypothermia because cardiology won’t touch anything that gets in the way of their door-to-balloon time. So I think the real story is that

EXPERT PANEL DISCUSSION there are people who understand hypothermia and believe in it, and there are people who don’t. They might be cardiologists or they might be neurologists, but I think the knowledge about the value of therapeutic hypothermia is yet to be disseminated across a number of specialties. So one of the things I think we all need to do is to stop looking at where we come from and look where we want to go, which is to show our colleagues, whatever their specialty, that this is what we should be doing. With respect to prognostication, as Carmello said, the best time to involve the neurologist is early rather than late; it sort of goes without saying. But the other thing is that too many of us don’t know that you can’t prognosticate after hypothermia, that all rules are off. That is the second message that needs to get out in our specialty—that there really isn’t a good way now, today, of prognosticating in these patients and that is an area of future research. Dr. Eyal Herzog: This is in response to the other person’s question of how do you buy into the cardiologist to involve the neurologist. We got the interventionist to be actually willing to call the neurologist and to get this engagement into core body temperature cooling because we actually give the interventionist the tool; they put in the catheters. So they are the team leaders and they have the control. They do it very fast, very efficiently, and it works fantastically well. We also focus on data of balloon time, but we have the same balloon time because the patient goes to the cath lab when they get the cooling. Dr. Michael Mooney: Could I ask a question to someone who is involved with the American Heart Association because we were talking about this earlier. Two things that have really made a difference, I think, in expanding the practice of acute myocardial infarction and in particular what to do in acute stroke. One, is the establishment of guideline pathways that exist for hospitals to get credentialed and two, to be recognized for this. In stroke, we have a major focus on door-to-needle time for thrombolysis and a number of other metrics. Given that it is now at Level 1A recommendation by the AHA for hypothermia, would it not make sense to develop a set of steps with the guidelines for the institution of hypothermia so your hospital now has a set of metrics that they follow and report on, as for quality assurance? Everything from door-to-target temperature to all the multi-team monitoring would be important endpoints that may be one way to become more national. Dr. Joseph Ornato: An interesting philosophic tension enters into play here. I’m one of the science advisors establishing guidelines for inhospital resuscitation. We are beginning to have some dialogue about whether it makes sense to have more of an integrative approach as you’ve discussed. One question is whether every hospital should be treating these patients like many PCI centers treat STEMIs. The problem is that there are very few of these patients in a typical community who are going to qualify for this therapy relative to STEMIs. If we had a certification procedure, I think it would clearly help. Everybody likes the merit badge approach. I personally think the solution is to follow AHA regional guidelines, which say that you have to create Level 1 and Level 2 centers, and you certify at both levels.

EXPERT PANEL DISCUSSION Dr. Michael Mooney: You know that would be great. Unfortunately, it is at the early stage now, and Mission Lifeline, which is also AHA, is going in another direction. They are taking more of the University of Pennsylvania model where everybody does it and takes care of the patient. I think those of us who have been involved in the care are very impressed that it is resource intensive. I would say, more than just enthusiasm, you have to have a real commitment to developing a program that will successfully manage all the hurdles these patients encounter. So I think you are on the right track. Unfortunately, there are all these political diversions where, for a variety of reasons, that approach may or may not be supported fully. Dr. Robert Levene: I ran a neurological ICU and I wanted to echo what Joseph said because I’ve been pushing for regionalization of care. In Houston, we had a competition to see who could get most of these patients. No one wanted them at first. But then once they realized they could kind of get newspaper press, Herman Hospital wanted them and the Methodist then wanted them. But what we found was that they were being admitted to anyone who was on call that day. What I would tell you that you have done better than everyone else is that you have formed protocols. It is not whether a cardiologist is part of the protocol or neurologist because not every neurologist, as we know, is an intensivist. But there are some fabulous people doing neurocritical care, and not every cardiologist really takes care of cardiac arrest patients. But there are some fabulous cardiologist. So really, it’s who’s the champion, what is the level of commitment at the institution—I would agree, I think everyone needs to be on board from time zero. But you also need to have people who are trained and dedicated to the field, and for that alone, I think what Dr. Ornato said is exactly right. You need regionalization even in a city of four million people like Houston. Probably it should be one center that is doing this. It takes a tremendous amount of resources and 24-hour care on the entire team’s part to get this done right. So I think that that’s the way we need to do it, and I would say cardiac arrest in general and now neuroresuscitation needs to be done that way. Key References from Panel Participants Aziz EF, Javed F, Pratap B, Herzog E. Strategies for the prevention and treatment of sudden cardiac death. Open Access Emerg Med 2010;99–114. Friberg H, Rundgren M, Westhall E, Nielsen N, Cronberg T. Continuous evaluation of neurological prognosis after cardiac arrest. Acta Anaesthesiol Scand 2012 [Epub ahead of print; DOI: 10.1111/j.1399-6576.2012.02736.x. Herzog E, Aziz EF, Kukin M, Steinberg JS, Mittal S. Novel pathway for sudden cardiac death prevention. Crit Pathw Cardiol 2009;8:1–6.

111 Herzog E, Aziz EF, Shapiro JM. Integrating voices of survivors into the system of care post-cardiac arrest. Crit Pathw Cardiol 2011;10:113–114. Herzog E, Shapiro J, Aziz EF, Chong J, Hong MK, Wiener D, Lee R, Janis G, Azrieli Y, Velazquez B, Lacdao L, Mittal S. Pathway for the management of survivors of out-of-hospital cardiac arrest. Crit Pathw Cardiol 2010;9:49–54. Maron BJ, Maron MS, Maron BA, Haas TS, Altman RK, Smalley SJ, Doerer JJ, Link MS, Mooney MR. Successful therapeutic hypothermia in patients with hypertrophic cardiomyopathy. J Am Coll Cardiol 2011;57:2454–2456. Mooney MR, Unger BT, Boland LL, Burke MN, Kebed KY, Graham KJ, Henry TD, Katsiyiannis WT, Satterlee PA, Sendelbach S, Hodges JS, Parham WM. Therapeutic hypothermia after out-of-hospital cardiac arrest: evaluation of a regional system to increase access to cooling. Circulation 2011;124:206–214. Nielsen N, Friberg H. (2011) Insights from the evidence evaluation process—do we have the answers for therapeutic hypothermia? Resuscitation 2011;82:501–502. Nielsen N, Friberg H, Gluud C, Herlitz J, Wetterslev J. Hypothermia after cardiac arrest should be further evaluated—a systematic review of randomised trials with meta-analysis and trial sequential analysis. Int J Cardiol 2011;151:333–341. Nielsen N, Sunde K, Hovdenes J, Riker RR, Rubertsson S, Stammet P, Nilsson F, Friberg H; Hypothermia Network. Adverse events and their relation to mortality in out-ofhospital cardiac arrest patients treated with therapeutic hypothermia. Crit Care Med 2011;39:57–64. Nielsen N, Wetterslev J, al-Subaie N, Andersson B, Bro-Jeppesen J, Bishop G, Brunetti I, Cranshaw J, Cronberg T, Edqvist K, Erlinge D, Gasche Y, Glover G, Hassager C, Horn J, Hovdenes J, Johnsson J, Kjaergaard J, Kuiper M, Langørgen J, Macken L, Martinell L, Martner P, Pellis T, Pelosi P, Petersen P, Persson S, Rundgren M, Saxena M, Svensson R, Stammet P, Thore´n A, Unde´n J, Walden A, Wallskog J, Wanscher M, Wise MP, Wyon N, Aneman A, Friberg H. Target temperature management after out-of-hospital cardiac arrest—a randomized, parallel-group, assessor-blinded clinical trial—rationale and design. Am Heart J. 2012;163:541–548. Nolan JP, Ornato JP, Parr MJ, Perkins GD, Soar J. Celebrating 40 years of resuscitation. Resuscitation 2012 [Epub ahead of print]. Ornato JP, Peberdy MA, Reid RD, Feeser VR, Dhindsa HS; NRCPR Investigators. Impact of resuscitation system errors on survival from in-hospital cardiac arrest. Resuscitation. 2012;83:63–69. Ripley E, Ramsey C, Prorock-Ernest A, Foco R, Luckett S Jr, Ornato JP. EMS Providers and exception from informed consent research: benefits, ethics, and community consultation. Prehosp Emerg Care 2012 [Epub ahead of print]. Sendelbach S, Hearst MO, Johnson PJ, Unger BT, Mooney MR. Effects of variation in temperature management on cerebral performance category scores in patients who received therapeutic hypothermia post cardiac arrest. Resuscitation 2012;83: 829–834.

Therapeutic hypothermia in post-cardiac arrest.

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