THERAPEUTIC HYPOTHERMIA AND TEMPERATURE MANAGEMENT Volume 3, Number 4, 2013 ª Mary Ann Liebert, Inc. DOI: 10.1089/ther.2013.1515
Expert Panel Discussions
Therapeutic Hypothermia in Post Cardiac Arrest Moderator: W. Dalton Dietrich, PhD1 Participants: Michel Le May, MD,2 Justin B. Lundbye, MD, FACC,3 and Mark Preston Adams, RN, BSN 4
Out-of-hospital cardiac arrest is one of the major clinical settings in which therapeutic hypothermia has been used to promote better survival and recovery in patients. Although several multicenter trials have been completed that show the efficacy of therapeutic hypothermia, there are still many hurdles that need to be cleared to make this treatment protocol successful in the hospital setting. A series of state-of-the-art lectures presented at the 3rd Annual Therapeutic Hypothermia and Temperature Management meeting in Miami, Florida, brought together several experts in the field of therapeutic hypothermia to provide their opinions regarding this treatment strategy as well as answer questions from the audience. Dr. Michel Le May, University of Ottawa Heart Institute, Division of Cardiology, Canada, discussed strategies to reduce the length of stay following cardiac arrest. Dr. Le May described his temperature management strategies and the benefits of both heating and cooling certain patients in terms of enhancing outcome. Again, the multidisciplinary aspect of cooling protocols was emphasized with big challenges, including identifying a champion to help move these therapies forward. Dr. Justin Lundbye, chief of cardiology at the Hospital of Central Connecticut, spoke about going beyond the standing practice of using hypothermia in post–cardiac arrest and how we can improve upon what we are currently accomplishing. Specifically, he discussed how to best determine who should be cooled as well as what indicators of the need for prolonged cooling are currently available to the treating physician. Other questions regarding whether 32 or 33 degrees results in better cooling and the implications in terms of protecting heart versus brain tissues was also emphasized. Mr. Mark Adams from the University of Virginia Health System emphasized the role of nursing management in post– cardiac arrest hypothermia protocols. Mr. Adams emphasized the need to educate the clinical fellows and other healthcare providers in terms of the rationale for cooling subjects as well as emphasizing the various phases that are involved in the cooling process. One solution to this complex problem included the development of flow sheets and Electronic Medical Record (EMR) order sets that integrate physician procedures, nursing management, and pharmacological interventions. Additionally, shivering management protocols were presented that helped the treating physicians and staff to control temperatures with less effort. Also, the establishment of temperature work groups was thought to promote discussion and clarification of different protocols. This panel discussion resulted in an informative discussion between the participants and the attendees of the meeting.
Question: We appreciate that it can be very difficult to bring everybody together and convince people to buy into the administration of hypothermia therapy. So congratulations to everyone on what you have accomplished. What do you think are the biggest challenges when you start trying to convince people and get things moving forward? Anyone can answer that. Dr. Justin Lundbye: I’d say one of the biggest challenges is having the literature base. There are those clinicians who demand three or four studies before they’ll latch onto any new therapy. And sometimes, as we’ve noted over the last two days, that just doesn’t happen. At least not quickly. Dr. Michel Le May: One of the challenges, as I alluded to in the presentation, was the concern that patients who survive after treatment with therapeutic hypothermia will be transferred to the wards and then have a very lengthy hospital stay. Many of the stakeholders are truly concerned about this happening. They feel that implementation of a cardiac arrest program will be associated with many logistical problems, which may seriously impact the care of other patients since healthcare resources are limited. There is concern that therapeutic hypothermia will be applied unselectively to all patients without using the criteria developed in trials and that this process will consume a lot of resources. There is concern that the process could create serious issues regarding the availability of beds in cardiac centers like our own. A new pool of patients who occupy beds in a cardiac center may hamper the transfer of patients from other institutions or community hospitals who, for example, need cardiac catheterization. We currently have a very, very busy relationship with our peripheral hospitals, and we need to service them. When we rolled out our regional ST-elevation myocardial infarction (STEMI) program, everybody was keen to participate. But I sensed some resistance in developing a regional cardiac arrest program, because we are going to have people survive, but possibly with acute brain injury and not quite ready for discharge. So that’s been one of the big obstacles of implementing this kind of program. Dr. Justin Lundbye: Yes, I think early on it was the negative sort of physician or another clinician that would say this
Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida. Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada. 3 Department of Cardiology, The Hospital of Central Connecticut, New Britain, Connecticut. 4 Coronary Care Unit, University of Virginia Health System, Charlottesville, Virginia. 2
162 doesn’t work, that this is almost hocus-pocus. Now it has become standard of care, and everybody is recognizing the potential benefits. We are getting the skeptics involved. They would come up to us now and say, ‘‘Wow! I just had another great save on my patient!’’ The other challenge that we faced, probably somewhat related to what Mark Adams and his team has worked on, is the concept of having continuous new staff and residents coming through the system, trying to keep them ahead of the curve; to make sure they’re aware of exactly what is going on and know what to do at 2:00 in the morning when you don’t have the same attending support as you do during the day. I think bringing in APRN’s that become the champions for that, and also having nurse champions that are available to become the expert for hypothermia, has been a very successful tool. Question: I’ve got a question for Dr. Lundbye. You said that when patients shiver, they have a better outcome. Dr. Justin Lundbye: Yes, I did. Question: Let me restate my question. We also have patients who come in very cold. Then we have to rewarm them to get to 34 degrees Celsius. All those patients die when we have to rewarm them. Is that also your experience? Dr. Justin Lundbye: We don’t have a large population of accidental hypothermia. I think there is actually going to be a talk on this next. Response: They are not accidental. They are patients who come in after cardiac arrest and who came in already cold. They have cardiac output, and they are not dead. In our experience, this group of patients who come in cold all die. Dr. Justin Lundbye: We have had rescues from this. It’s anecdotal. I don’t have any data on it. But we’ve had good outcomes from patients who are cold. I can’t speculate the etiology, if it’s just because they were cardiac arrest and they were down so long. It’s a tough one. Dr. Michel Le May: We believe that cooling rapidly is the best approach, but in some cases it seems like the patient has already done this for us. There is something that bothers me about a patient who arrives in the cath lab and was sent expeditiously from the emergency department, and the temperature is already down to 32–33C. We are in the process of handing over the endovascular cooling device to the circulating nurse and somebody tells us, ‘‘You know he’s already at 32.’’ I think these patients have kind of declared themselves. You need to go back and look at the EMS records, determine if the arrest was witnessed, who was doing CPR, and how long CPR was performed before return of spontaneous circulation. What was the downtime of these patients? What was the initial rhythm at presentation? Where was the patient found? Those are the kind of details that you need to review. I think that if we are going to look at the speed of cooling and impact on clinical outcomes we will need to take these variables into consideration. Comment: I know with our exclusion criteria actually, we don’t put them on the hypothermia program if they are less
EXPERT PANEL DISCUSSION than 30 degrees Celsius. We then basically wait to see if they actually warm up on their own and get back to a relatively usable body temperature. Or if they are going to, as you said, declare themselves, then basically they are on their way to dying. So we put that cut-off point in our protocol. Still, we have only seen a handful out of 700 patients for whom we even had to make that decision. Question: I have another question about the coronary arteriogram that you mentioned. Is there time for doing a study to divide them in doing primary cardio arteriograms? When we do a cardiogram on all of the patients you’ve got a lot of groups who are going to die. Forty percent of your patients are going to die. Even more patients have a cerebral performance category (CPC) score of about 3 or 4. So would it be cost effective to conduct a coronary arteriogram in every patient in reference to health economics? Dr. Michel Le May: I think that the pendulum is swinging toward doing more angiography. Patients with STEMIs are relatively straightforward. There are other situations. A patient, for example, who has chest discomfort calls 911, and then the medics arrive and the patient’s electrocardiogram (EKG) doesn’t show a STEMI. This is suggestive of an ischemic picture. What we are finding is the example that I showed you of an acute coronary occlusion without the findings of STEMI on the EKG. The case highlights very well that there are patients for which the EKG doesn’t quite tell you that there is actually an ongoing ischemic process. There are also cases that have coronary disease but no obvious culprit lesion, and then you have to decide what to do. What is the goal here? There is some data to support an invasive approach. The Parisian Region Out of Hospital Cardiac Arrest (PROCAT) trial concluded that there is clinical benefit in intervening on an occluded coronary artery. There is also benefit in diagnosing and knowing more information about the patient. Whether or not you are dealing with coronary disease, you are getting a better picture of what is going on with the patient. Can there be a downside to taking the patient to the cath lab? Perhaps. We are pumping contrast into the patient with the added risk of acute kidney injury and inserting catheters into the patient with the use of anticoagulants that may cause bleeding. But at the end of the day, the cath lab experience makes you focus on the patient. It’s a team approach, and I think that we now have interventionalists with expertise at inserting lines. Consultation with other specialists as well can be obtained in the cath lab, for example, anesthetists or cardiac cath techs (RTs). You’ve got this patient in your lab, and you’re focused on managing the patient; the whole team is focused. This includes managing shock if it is present or develops. What happens many times in the cardiac care unit (CCU), and the emergency room, is that key members of the team are called away, come and go, and are not quite as focused as the team members in the cath lab at a time that is so critical for the patient who had a cardiac arrest not so long ago. I think that there is an advantage to being in the cath lab for this purpose. Question: This is to Mr. Adams. So during your development—and you guys have been cooling for a long time—have you found that your relationship with EMS is satisfactory, as far as the drugs they’re administering in the field? Because
EXPERT PANEL DISCUSSION EMS might be cooling in the field, when they arrive at the emergency room, they have already paralyzed their patients, inhibiting the way we assess their neurological status in the ER. As a community, with EMS and ED working closely together, is there a good way to disseminate that information? Obviously, there are no studies out there as far as prehospital paralytic administration. It’s a hurdle that we are facing. Mr. Mark Adams: The prehospital administration of neuromuscular blockers can certainly confound your assessment. My background was as a paramedic for 15 years. I was also a regional EMS council director for 6 years. So I am well acquainted with the various prehospital treatments. We run a mixture of urban paid services and rural volunteer services. Most just have morphine, Demerol, Versed, and we actually lean more toward that. Because I’ve never understood as an old paramedic why, if someone’s dead, you need to give them a neuromuscular blocker. If you have a regional emergency medical services council that has standardized protocols, that is where I would start. That may be difficult if you have multiple municipal agencies. I understand the need for rapid sequence intubation (RSI), but in these cases, that is usually not the case. It can confound your exam, and the big thing you want to stress is it’s going to delay the initiation of cooling efforts. Comment: Right, because it is the critical access hospitals that are going to be transporting patients to a more definitive care center. I can see the use of paralyzing agents if their transport time is long. Or they initiate some sort of cooling method in order to transport them to a bigger facility where they can get more definitive care. But, okay. I just needed your feedback on that. Question: So I have a couple of questions. The first question is whether you do a CT scan before you transfer a patient to the cath lab. Because as far as I know, 15% have arachnoid hemorrhage and therefore, I want to cool the fibrillation. Second is the prognostication. Does it really depend on your first neurological exam? I’m not aware if there are studies for that. And the third question is when do you really decide to stop your therapy and based on what parameters? Dr. Justin Lundbye: So the first question regarding the CT scan. We only do CT scans if we have a high index of suspicion that there is something that happened acutely in the head to cause the cardiac arrest. I’m hearing you on the 15%. In the beginning, when we first started this back in 2006, everybody got a CT scan. In the Emergency Department, depending on the flow and how busy, a CT scan can sometimes take hours to obtain, which would delay the care of this patient by not expediting hypothermia and door-to-balloon time. So we decided to eliminate CT scans on everybody and just order it if we felt that there was a need. The second question I think you answered, so I don’t need to answer that. Regarding the third question, I’m embarrassed to say that we don’t have a very robust biomarker program at my institution. Usually, it takes a long time to get the biomarker back, and by the time we get it back, we commonly have the information needed to make an accurate assessment for prognosis. Early prognostication, I think, is not very useful. And I think you alluded to that in most cases anyway. We allow for complete cooling and re-
163 warming and don’t do very much until then before we start prognosticating. And it includes imaging, magnetic resonance imaging, electroencephalography, and a physical examination. Comment: Maybe I can add my comments on that regarding what we do in Rotterdam for patients not to have cardiac arrest by STEMI on the EKG. We all do CT scans on those patients, and your experience of 15% is about 8 to 10% in our experience, so it is much lower. But maybe we missed some because when they have a real STEMI, we don’t do a CT scan. So only if we have no diagnosis and the EKG is normal do we then perform a CT scan on every patient. Comments and Question: I just wanted to make a couple comments and ask about the use of echocardiography. When we first got started with therapeutic hypothermia as an applied clinical mode in 2002, we also started another program called No Heart Attack Left Behind. The No Heart Attack Left Behind was basically two troponins 90 minutes apart, a brain natriuretic peptide (BNP) and two EKGs 90 minutes apart, and a front-loaded echocardiogram. That’s been particularly useful for looking for wall motion abnormalities, looking for the STEMIs that are disguised by an EKG, when you can’t read the STEMI because it’s a resuscitated patient. And we haven’t gotten a very good EKG yet. We see the aortic stenosis, the occasional interesting wall motion abnormalities, and so forth. Have you been using a front-loaded echo on those patients when they appear in the ER? Has that been helpful to you? Dr. Michel Le May: For STEMI patients, the metric is always minutes. You need to get these patients over to the cath lab as quickly as possible. We always talk in terms of door-to-balloon time. STEMI patients who have arrested and have altered mental status and ROSC take longer to assess and transfer. The metric remains the same for these patients—it’s minutes. For those who are not STEMI patients, we managed them as a CODE ROSC. For these patients, it appears that we have a bit more time on our hands. We’re not thinking in terms of minutes, but we’re thinking of getting the patient to the cath lab as soon as possible. In these patients, it is interesting that you bring up the use of echocardiography. We’ve started doing a lot of echocardiograms with a pocket echo device. Our residents now carry this small device in their pocket. If the images suggest ischemia, then we have a good reason to go to the cath lab. Dr. Justin Lundbye: We also get an early echo, but it is not commonly done in the ER. It is usually in the CCU once we’ve stabilized the patient. If there is a big wall motion abnormality, we’ll bring it into the cath lab. Question: Dr. Lundbye, I have one question. Do you have the data on the effect of hypothermia on non-shockable rhythms—PEA or asystole? If the downtime is over 30 minutes, you do not apply hypothermia. I want to know the reason or upper limitation on the non-shockable rhythm. Dr. Justin Lundbye: We used to have very rigid criteria of 30 minutes based on some of the studies we had come across and applied to the non-shockable population. We have moved
164 away from that, and the thinking is that if we are planning on bringing the patient to the ICU and doing everything, we might as well cool them too. In our data, we’ve seen that after 17 minutes downtime in non-shockable rhythm cardiac arrest patients, the prognosis is very poor. So for most patients with pulseless electrical activity or asystole and a downtime greater than 17 minutes, there is no recovery. Dr. Michel Le May: You need to have a protocol driven by evidence-based medicine. We use a downtime of less than 30 minutes as part of our protocol. So when this is the case, the team will be called in. With longer downtime, there has to be a consultation. So you have to take into consideration the clinical picture and the likelihood of good results: Is the patient a 30-year-old or an 80-year-old? What was the background? What is the history? Where is the patient coming from? The gym or a nursing home? There are times when things are done automatically according to protocol, and there are times when you need to have a discussion about what you are doing. Comment: Two of you mentioned when you were discussing the Bernard and Hypothermia After Cardiac Arrest (HACA) studies that the number needed to treat was 4 for beneficial outcome, good survival. Each of you commented that it was a small number without saying what small or big meant. I just wanted to put that number needed to treat into a little bit of context for people who don’t think about the number needed to treat all the time. If we do percutaneous coronary intervention (PCI) to prevent death, we actually have to do 29 cases to prevent 1 death. This one works with my colleagues who don’t like giving tissue plasminogen activator (tPA) for stroke, where the number needed to treat is 7. Do you give coumadin for afib? Well, of course I give coumadin for afib. The number needed to treat to prevent one stroke is 25—coumadin for afib, aspirin for myocardial infarction (MI). The number needed to prevent one MI is 40. You know, if you give your patients Lipitor or statin, the number needed to treat is 400, but if the patient doesn’t have known coronary artery disease, the number needed to save one death from MI or major event is 5,000. Then, if you wear your seatbelt, the number needed to treat is 25,000. Question: This is a question for Dr. Le May. You obviously have a very diverse population, and we know younger patients do better. But is there any kind of age cut-off that you’ve noticed, at which it’s almost universally going to be a futile effort? Of course, it has to do with patients’ neuroscore coming in and how sick they are and their physiology. We have young patients in our hospital who are very sick and are not going to do well no matter what and, similarly, elderly patients that do very well because they are physiologically young. But I was just wondering if there is a signal in your data that after age 80 or 85, none of them do well? Dr. Michel Le May: So when you look at the data, younger people have a better chance at survival than older people. Age is an independent factor in predicting outcome. Contrary to the trials, in applying this to a regional system just like with primary PCI, we don’t have a cut-off for age. Early trials comparing fibrinolytic therapy versus primary PCI had an age cut-off. We don’t have an age cut-off for our STEMI program. Similarly, we don’t have an age cut-off for our
EXPERT PANEL DISCUSSION cardiac arrest program. I have shown examples of young people who experienced a cardiac arrest while exercising to highlight the impact of treatment on youth. Everybody reacts to that. But we’ve also had some elderly people that have done well. We are currently treating every patient with therapeutic hypothermia unless there are reasons not to. In a situation where a patient comes from a nursing home and has advanced directives, then we would proceed with therapeutic hypothermia. Question: Do individuals with a previous MI respond well to therapeutic hypothermia? Is there any situation in which this preconditioning would be a very negative factor in terms of outcome? Dr. Justin Lundbye: We certainly have had patients with previous MI’s, and they have done fine. We haven’t looked specifically at this question. So I’m speaking by anecdote that most patients have done very well, even with previous acute coronary syndrome (ACS), STEMIs, etc. I think for cardiomyopathy, if a patient comes with a very low EF because of a massive STEMI in the past, they will usually fare worse just because they have a poor EF to start with, just like any other literature. Question: It was earlier stated that there is a 20% increase in risk of death for every hour initiation of cooling is delayed. What do you think about that? Dr. Michel Le May: This data comes from an article by Mike Mooney, reporting on registry data from their program, and is very provocative. It suggests that it is better to cool fast. But like the gentleman alluded to before, sometimes some patients have already declared themselves by presenting ‘‘already cooled.’’ There is a need for a randomized trial. I don’t think that we’ve yet answered how fast we need to cool. I think that everybody has bought into the concept of cooling fast. Some are applying ice in the ambulance, and ice in the ED; some are using blankets or endovascular cooling in the ED. The concept comes across that we need to cool fast. It seems to make sense. If you are going to wait until you’ve done the angioplasty to start cooling, then you may lose some of the benefits. Comment: I just have a quick comment. In a similar mode, you also need to look at what the percentage of pulseless electrical activity (PEA) asystole arrests are versus the ventricular tachycardia/ventricular fibrillation (VT/Vfib). Because from looking at the Minnesota data compared to ours, they have a much higher STEMI population within their cardiac arrest database than, say, I do, because 65% of my cardiac arrests are in PEA or asystole. So, even when we are comparing notes, we really need to look at ‘‘apples to apples.’’ Dr. Michel Le May: You are absolutely correct, because if we look at 2008, we had 400 patients that arrested in our city. About 50% of the time, the dispatch called off CPR before the patient reached the hospital. So by the time we see these patients and they make their way into our database, they’ve been screened. This explains why we have a large percentage of patients in our database who present with VT or Vfib. It’s because protocols based on the current available literature are being used to triage these patients.
EXPERT PANEL DISCUSSION Key References from Panel Participants Ganga HV, Kallur K, Patel NB, Sawyer KN, Gowd PB, Nair SU, Puppala VK, Manandhi R, Gupta AV, Lundbye JB. (2013). The impact of severe acidemia on neurologic outcome of cardiac arrest survivors undergoing therapeutic hypothermia. Resuscitation 2013 [Epub ahead of print]; DOI: 10.1016/j.re suscitation.2013.07.006. Hibbert B, MacDougall A, Labinaz M, O’Brien ER, So DY, Dick A, Glover C, Froeschl M, Marquis JF, Wells GA, Blondeau M, Le May MR. Bivalirudin for primary percutaneous coronary interventions: outcome assessment in the Ottawa STEMI registry. Circ Cardiovasc Interv 2012;5:805–812. Le May MR, Dionne R, Maloney J, Poirier P. The role of paramedics in a primary PCI program for ST-elevation myocardial infarction. Prog Cardiovasc Dis 2010;53:183–187. Le May MR, Wells GA, So DY, Glover CA, Froeschl M, Maloney J, Dionne R, Marquis JF, O’Brien ER, Dick A, Sherrard HL, Trickett J, Poirier P, Blondeau M, Bernick J, Labinaz
165 M. Reduction in mortality as a result of direct transport from the field to a receiving center for primary percutaneous coronary intervention. J Am Coll Cardiol 2012;60:1223– 1230. Lundbye JB, Rai M, Ramu B, Hosseini-Khalili A, Li D, Slim HB, Bhavnani SP, Nair SU, Kluger J. Therapeutic hypothermia is associated with improved neurologic outcome and survival in cardiac arrest survivors of non-shockable rhythms. Resuscitation 2012;83:202–207. Maze R, Le May MR, Hibbert B, So DY, Froeschl M, Glover CA, Dick A, Marquis JF, Blondeau M, Labinaz M. The impact of therapeutic hypothermia as adjunctive therapy in a regional primary PCI program. Resuscitation 2013;84:460–464. Nair SU, Lundbye JB. The occurrence of shivering in cardiac arrest survivors undergoing therapeutic hypothermia is associated with a good neurologic outcome. Resuscitation 2013;84:626–629. Rai M, Lundbye JB. Successful use of therapeutic mild hypothermia after cardiac arrest. J Cardiovasc Med (Hagerstown) 2012;13:462–464.