THERAPEUTIC HYPOTHERMIA AND TEMPERATURE MANAGEMENT Volume 4, Number 4, 2014 ª Mary Ann Liebert, Inc. DOI: 10.1089/ther.2014.1514
Expert Panel Discussions
Perspectives on Temperature Management Moderator: David Gaieski, MD1 Participants: Tetsuya Sakamoto, MD,2 David Greer, MD,3 and David Gaieski, MD1
A series of state-of-the-art lectures presented at the 2014 Therapeutic Hypothermia and Temperature Management meeting in Miami brought together experts in the field of critical care medicine and strategies to reduce the consequences of post–cardiac arrest syndrome. Dr. Sakamoto from Teikyo University spoke on therapeutic hypothermia for post–cardiac arrest syndrome with percutaneous cardiopulmonary support. He reviewed reports from the Japanese Society for Postcardiac Arrest as well as the results of the Save-J and J-Pulse with extracorporeal cardiopulmonary resuscitation (ECPR) introduced in the 1960s. Surgical procedures that are used to set up this support system were reviewed and results summarized. Dr. David Greer, Department of Neurology, Yale University, discussed neuroprognostication in the area of hypothermia. Dr. Greer emphasized strategies to predict poor or good outcome in this patient population and various guidelines for clinical examinations. The use of electrophysiological evoked potentials as well as EEG monitoring and the identification and testing of biomarkers was emphasized. New imaging strategies were also emphasized that can provide some clue to how the brain is doing in these patients. Finally, Dr. David Gaieski from the Department of Emergency Medicine, University of Pennsylvania, Philadelphia, discussed postarrest hemodynamic management. Strategies for optimizing hemodynamic parameters were emphasized, and opportunities for providing cooling, vasoactive agents, and fluid balance strategies were summarized. Combination approaches, including hypothermia, fluid balance, hemodynamic optimization, lactate, and neuroprognostication, were emphasized. Question: Dr. Greer, do you see evidence of convulsive or subclinical seizures in your patients? In the experimental traumatic brain injury (TBI) field, we are conducting EEG recordings in the posttraumatic phase, and it appears that there is a lot of evidence for abnormal neuronal hyperactivity that we are classifying as subclinical seizures. It appears that these periods of abnormal neuronal excitation may actually damage the posttraumatic brain. So, I wondered if anyone is looking at that in this particular patient population.
1 2 3
Dr. David Greer: You won’t see it if you don’t look for it, is point 1. We are doing a lot more monitoring of these patients and if you see seizures, again, you should treat them. The problem is, what people call a seizure is often variable. Sometimes people will be on this ictal/interictal continuum as they are calling it, and this is a nebulous term. Do you treat this or not? When you see rhythmic delta activity, is that an angry rhythm that is going to degenerate just like aflutter would go into afib? It is unclear what you do with cases like that. I think if you see clear electrographic status or nonconvulsive status, you treat that. You can argue how aggressively you would treat that. Some would argue that electrographic status is a natural and temporary phenomenon after cardiac arrest, and that they will ‘‘outgrow’’ it or it will simply go away on its own. I’m not in that camp. I think like any other acute brain injury, if you see electrographic status, that can be damaging to the brain on top of what else has been going on, and you treat it. I cannot sit by and watch that, although there are different camps on that. Question: Question to Professor Sakamoto. We did a couple of patients with extracorporeal membrane oxygenation (ECMO) and when you have to do it fast, then you also have complications. You didn’t show your complication rate in your trial. Did you have complications such as bleeding? Did the bleeding and hypotension influence your outcome? Dr. Tetsuya Sakamoto: Yes, we experienced some complications related to the extracorporeal saturation. The major problem is bleeding from the cannulation site. Another problem is ischemia because of the cannulation to the femoral artery. Question: Do you place an external femoral artery catheter? Dr. Tetsuya Sakamoto: We need another cannulation to the distal femoral artery. In some cases, we discontinue during the first several days. Question: So your complication rate influences your outcome?
Department of Emergency Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. Department of Emergency Medicine, Teikyo University, Tokyo, Japan. Department of Neurology, Yale University, New Haven, Connecticut.
150
EXPERT PANEL DISCUSSION
Dr. Tetsuya Sakamoto: Of course, the outcome that I presented today includes patients who have stopped CPR according to the complication, because this is the intention of this study. Dr. David Gaieski: One of the areas that still needs a lot of work is good neurologic outcomes in patients placed on bypasss. Dr. Sakamoto showed concerns about the survival rate of patients who just get regular hypothermia and postarrest care because they’ve had return of spontaneous circulation. In the Save-J trial, survival was significantly higher in the ECPR group; however, the percentage of neurologically intact survivors in most of the case series of bypass patients is down in the 50–60% range, and so there are more survivors who are injured when they go on to bypass. The question is how can we cut down on that percentage and get the numbers of patients up who survive neurologically intact to a similar percentage as in regular post-cardiac arrest hypothermia patients (those who achieve return of spontaneous circulation [ROSC] return of spontaneous circulation without ECPR)? Question: Coming from a community hospital, we do bypass, but we have limited resources and time for bypass. For Dr. Sakamoto and Dr. Gaieski, what we do have is many automated CPR devices in our community. So the consideration is a patient who is in persistent v-fib, maybe has been worked 15–20 minutes at the scene, and an endtidal CO2 that is good. What is your thought about the efficacy of these patients now being brought to the cath lab with an automated CPR device running as a subclass of patients, mainly as a substitute for going on to coronary bypass? Dr. David Gaieski: I think that is a great theory, and there are case reports that were presented during the case conference at AHA last year. In the New England Journal case presentation from September, there was a patient that they did exactly that for refractory ventricular fibrillation (VF), with ongoing CPR, and rapid transport to the cardiac catheterization laboratory. It’s a little unclear from the case report whether that was with a mechanical device, but most of the case reports have been with mechanical devices. Go to the cath lab and see if by opening the vessel you can interrupt the refractory VF. In the New England Journal case report, they ended up not being able to get the heart started—achieve ROSC—simply with opening the culprit vessel, so they put the patient on bypass in the cath lab. I think a lot of people would think you reverse that approach: put the patient on ECMO, then go to the cath lab. Certainly, the approach that Drs. Sakamoto and Nagao are using is early cannulation followed by catheterization, and their data would support that approach. Like from the Nagao article I showed you, it’s an interesting strategy. The only way we will know more about it is if more people start doing it either in case series or ideally in a more controlled, trial-based format. Question: We took 60 patients to the cath lab on the mechanical device, and few had a good outcome, about 3%.
151
physiological wakening during the CPR. Three died because we do not transport patients generally who don’t have ROSC or some physiologic parameter. One patient never had to be cooled because she woke up so fast, and the other one was cooled. Both had good neurologic outcome. Maybe the specificity of whom we choose, or the selectivity of who we choose to do this with is important. The second related issue is ECMO. ECMO is ‘‘damned if you do and damned if you don’t.’’ We just acquired ECMO at our facility for other purposes, and now this hard question is being asked, whether and who we would consider for ECMO. So in terms of moving from the university setting to the community hospital setting, please comment on who you would chose if you were going to do ECMO. Dr. David Gaieski: Dr. Sakamoto, do you want to address what you think is sort of the optimal candidate to put on ECMO? Dr. Tetsuya Sakamoto: So in this study, the candidate is not so old, and from the call to the hospital arrival should be a maximum of 45 minutes. But in the subgroup analysis what I generally see is that if the patient comes to hospital within 30 minutes, the outcome becomes much more vital. So the duration of the CPR is very important. But it depends upon the quality of the CPR I think. Another thing is cause of the cardiac arrest. Ninety percent of the patients sent to the extracorporeal resuscitation are cooled as soon as possible, usually within 1 hour. Dr. David Gaieski: So I think the starting point would be witnessed VF patients who remain in VF on arrival to the emergency department. We all don’t have that many of those patients. It’s interesting that you bring up physiologic parameters because the article that was done by Jerry Buckberg’s group at UCLA, where they took 34 people in refractory arrest and cannulated them for ECMO, they only put them on pump if they had certain physiologic parameters. They used that as a surrogate for quality of CPR and coronary perfusion pressure. So that’s another way to think about these patients, I think. Comment: Well we’ve been trying to look at endtidal CO2 also as a simple predictor because they have to get the A line in and, coming in from the field, make some decisions. Quick question on seizures. What are you treating them with if you see them? You’ve been aggressive in thinking if they’re there we’ve got to do something. What do you do? Dr. David Greer: I treat them like we treat any other status. So you go down the algorithm with Keppra versus Dilantin. They are both very good agents. They both work very well. But if they’re not responding to that, then you have to accelerate it or use valproate. Sometimes they’ll go on a barbiturate drip or medazolam. How long do you treat them? Again, we’re going to publish a case report on a patient who we treated for a very long period of time and actually ended up using ketamine, finally breaking her out of status. So, it’s your typical status algorithm. It’s not different from any other status epilepticus patient, unless they have a reason not to use one of the agents due to liver or renal failure.
Dr. David Gaieski: Yes, so that is not promising. Comment: We actually have taken five patients to the cath lab with ongoing mechanical CPR. All of those patients had
Question: So if your patient is already being sedated, let’s say you’re using benzodiazepine, you add more benzo? Or would you go to another agent like Keppra or Dilantin?
152
Dr. David Greer: So most people during their therapeutic hypothermia protocol would be using either midazolam or propofol to keep them sedated. If they are still seizing when they are sedated, you do not normally see external seizures because they are paralyzed. We have seen nonconvulsive status. I would add traditional agents first. Keppra is my preference. With Dilantin, cardiac toxicity, drug–drug interactions are much worse. So, start going down the line: if you need to bump up the dose of a general anesthetic such as propofol, then you can do that or start adding other agents. Comment: It’s actually more of a comment rather than a question, but I think it’s been a great discussion about extracorporeal support and ECMO. I think patient selection is obviously critically important. But I note that some physician-staffed EMS agencies in Europe are actually deploying ECMO in the field, particularly in Paris. I note that a community hospital in San Diego has a fairly successful emergency physician-based program initiating ECMO on these patients. There’s another similar program in Melbourne. So it probably requires patient selection and interest and expertise. I think there is a set of issues around who you start with; a mechanical CPR device in the field in transition to ECMO or not. But I think before we write off these approaches, I think we need to look at the experience that others are having and better understand how it fits. Dr. David Gaieski: Right. I completely agree with what Dr. Nichols is saying and you know, the goal of the Save-J trial was to try to elucidate how close to 100% mortality you have in patients who have had conventional CPR for an extended length of time and then whether you can salvage them or not. They showed some very intriguing data that you can salvage a percentage of them with rapid deployment of ECMO and that the survival is very low in the ongoing conventional CPR group. But once you get to that point, the conclusions are limited because of the study design, which, obviously, was not a randomized trial. Question: Okay, back to the seizure activity. In terms of antiepileptics, would you prefer to use an HDAC inhibitor? Valproate acid has been shown to reduce reperfusion injury. Can you comment on that for me please? Dr. David Greer: I’m not adverse to it. The problem with valproate is that if you’ve taken a hit to your liver during the arrest, which often these patients do, they have shock liver. So their metabolism is going to be off. The second is when you start using Valproate in the acute setting, a certain proportion of patients will get severe hyperammonemia, especially with the IV formulation as you’re treating status. So you have to keep that in mind. Doesn’t mean that you shouldn’t use it, and it doesn’t mean that there isn’t a theoretical benefit to using it. It’s not really the drug of choice right off the shelf to go for in status, but for some people it is. I think you could make a case for it. But again, it needs to be studied in comparison to other agents. Question: The bright abnormal hippocampal signals that you mentioned were associated with poor outcome, is that cell death or edema? Are those transient signals that can be therapeutically manipulated?
EXPERT PANEL DISCUSSION
Dr. David Greer: I was hoping not to be asked that question because it is not a validated finding. What is it and what does it mean? We know that the hippocampus is very metabolically active, and we know that it is very sensitive to ischemia and hypoxia. So is it just showing its vulnerability in that respect? But it’s interesting that clinically there is a correlation. Also because these patients, if they have anything neurocognitively afterward after survival, have short-term memory problems that persist. So we know it’s a vulnerable area. We don’t know that if it correlates beyond neuropsychological outcomes to more functional outcomes beyond that. It’s provocative. But it needs to be studied a lot more. Question: Dr. Gaieski, you said fast awakening, and if I understood you well, that fast awakening was in patients with good prehospital preservation? Dr. David Gaieski: The question is about the early arousal in these people. There was a trend toward early awakening being in VF patients with bystander CPR, but it wasn’t statistically significant. So, we saw early awakening in several nonshockable rhythm patients as well. You can’t generalize to one group. But there were factors that were associated with earlier arousal. Question: The awakening time, is that in the targeted temperature management (TTM) trial also? Did you look at the awakening time? Response: Those data will come forth sooner or later. Key References from Panel Participants
Abe T, Tokuda Y, Ishimatsu S; SOS-KANTO Study Group. Predictors for good cerebral performance among adult survivors of out-of-hospital cardiac arrest. Resuscitation 2009; 80:431–436. Arch AE, Chiappa K, Greer DM. False positive absent somatosensory evoked potentials in cardiac arrest with therapeutic hypothermia. Resuscitation 2014;85:e97–e98. Arch AE, Chiappa K, Greer DM. Reply to letter: false positive absent somatosensory evoked potentials in cardiac arrest with therapeutic hypothermia. Resuscitation 2014;85:e139. Blondin NA, Greer DM. Neurologic prognosis in cardiac arrest patients treated with therapeutic hypothermia. Neurologist 2011;17:241–248. Gaieski DF, Beylin ME, Abella BS, Grossestreuer AV, Perman SM. What is the optimal post-arrest hemodynamic strategy? Towards personalized resuscitation strategies. Intensive Care Med 2014;40:466. Greer DM, Rosenthal ES, Wu O. Neuroprognostication of hypoxic-ischaemic coma in the therapeutic hypothermia era. Nat Rev Neurol 2014;10:190–203. Greer DM. Unexpected good recovery in a comatose post-cardiac arrest patient with poor prognostic features. Resuscitation 2013;84:e81–e82. Greer DM, Rosenthal ES, Wu O. Neuroprognostication of hypoxic-ischaemic coma in the therapeutic hypothermia era. Nat Rev Neurol 2014;10:190–203. Greer DM, Yang J, Scripko PD, Sims JR, Cash S, Wu O, Hafler JP, Schoenfeld DA, Furie KL. Clinical examination for prognostication in comatose cardiac arrest patients. Resuscitation 2013;84:1546–1551.
EXPERT PANEL DISCUSSION
Grossestreuer AV, Abella BS, Leary M, Perman SM, Fuchs BD, Kolansky DM, Beylin ME, Gaieski DF. Time to awakening and neurologic outcome in therapeutic hypothermia-treated cardiac arrest patients. Resuscitation 2013;84:1741–1746. Gugelmann HM, Gaieski DF. Beau’s lines after cardiac arrest. Ther Hypothermia Temp Manag 2013;3:199–202. Hsu CH, Li J, Cinousis MJ, Sheak KR, Gaieski DF, Abella BS, Leary M. Cerebral performance category at hospital discharge predicts long-term survival of cardiac arrest survivors receiving targeted temperature management. Crit Care Med 2014;42:2575–2581. Leary M, Cinousis MJ, Mikkelsen ME, Gaieski DF, Abella BS, Fuchs BD. The association of body mass index with time to target temperature and outcomes following post-arrest targeted temperature management. Resuscitation 2014;85: 244–247. Mazer-Amirshahi M, Perman SM, Grossestreuer AV, Neumar RW, Gaieski DF. Magnesium depletion in patients treated with therapeutic hypothermia after cardiac arrest. Ther Hypothermia Temp Manag 2014. [Epub ahead of print] Mikkelsen ME, Christie JD, Abella BS, Kerlin MP, Fuchs BD, Schweickert WD, Berg RA, Mosesso VN, Shofer FS, Gaieski DF; American Heart Association’s Get With the GuidelinesResuscitation Investigators. Use of therapeutic hypothermia after in-hospital cardiac arrest. Crit Care Med 2013;41:1385– 1395. Morim ura N, Sakamoto T, Nagao K, Asai Y, Yokota H, Tahara Y, Atsumi T, Nara S, Hase M. Extracorporeal cardiopulmonary resuscitation for out-of-hospital cardiac ar-
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rest: a review of the Japanese literature. Resuscitation 2011; 82:10–14. Nakahara S, Tomio J, Takahashi H, Ichikawa M, Nishida M, Morimura N, Sakamoto T. Evaluation of pre-hospital administration of adrenaline (epinephrine) by emergency medical services for patients with out of hospital cardiac arrest in Japan: controlled propensity matched retrospective cohort study. BMJ 2013;347:f6829. Perman SM, Goyal M, Neumar RW, Topjian AA, Gaieski DF. Clinical applications of targeted temperature management. Chest 2014;145:386–393. Sakamoto T, Morimura N, Nagao K, Asai Y, Yokota H, Nara S, Hase M, Tahara Y, Atsumi T; SAVE-J Study Group. Extracorporeal cardiopulmonary resuscitation versus conventional cardiopulmonary resuscitation in adults with out-of-hospital cardiac arrest: a prospective observational study. Resuscitation 2014;85:762–768. SOS-KANTO Study Group. Relationship between the hemoglobin level at hospital arrival and post-cardiac arrest neurologic outcome. Am J Emerg Med 2012;30:770–774. Takeda Y, Kawashima T, Kiyota K, Oda S, Morimoto N, Kobata H, Isobe H, Honda M, Fujimi S, Onda J, I S, Sakamoto T, Ishikawa M, Nakano H, Sadamitsu D, Kishikawa M, Kinoshita K, Yokoyama T, Harada M, Kitaura M, Ichihara K, Beng HH, Beng HT, Yorifuji T, Nagano O, Katayama H, Ujike Y, Morita K. Feasibility study of immediate pharyngeal cooling initiation in cardiac arrest patients after arrival at the emergency room. Resuscitation 2014. [Epub ahead of print]; DOI: 10.1016/j.resuscitation.2014.09.014.
Expert Panel Discussions
Perspectives on Temperature Management Moderator: David Gaieski, MD1 Participants: Tetsuya Sakamoto, MD,2 David Greer, MD,3 and David Gaieski, MD1
A series of state-of-the-art lectures presented at the 2014 Therapeutic Hypothermia and Temperature Management meeting in Miami brought together experts in the field of critical care medicine and strategies to reduce the consequences of post–cardiac arrest syndrome. Dr. Sakamoto from Teikyo University spoke on therapeutic hypothermia for post–cardiac arrest syndrome with percutaneous cardiopulmonary support. He reviewed reports from the Japanese Society for Postcardiac Arrest as well as the results of the Save-J and J-Pulse with extracorporeal cardiopulmonary resuscitation (ECPR) introduced in the 1960s. Surgical procedures that are used to set up this support system were reviewed and results summarized. Dr. David Greer, Department of Neurology, Yale University, discussed neuroprognostication in the area of hypothermia. Dr. Greer emphasized strategies to predict poor or good outcome in this patient population and various guidelines for clinical examinations. The use of electrophysiological evoked potentials as well as EEG monitoring and the identification and testing of biomarkers was emphasized. New imaging strategies were also emphasized that can provide some clue to how the brain is doing in these patients. Finally, Dr. David Gaieski from the Department of Emergency Medicine, University of Pennsylvania, Philadelphia, discussed postarrest hemodynamic management. Strategies for optimizing hemodynamic parameters were emphasized, and opportunities for providing cooling, vasoactive agents, and fluid balance strategies were summarized. Combination approaches, including hypothermia, fluid balance, hemodynamic optimization, lactate, and neuroprognostication, were emphasized. Question: Dr. Greer, do you see evidence of convulsive or subclinical seizures in your patients? In the experimental traumatic brain injury (TBI) field, we are conducting EEG recordings in the posttraumatic phase, and it appears that there is a lot of evidence for abnormal neuronal hyperactivity that we are classifying as subclinical seizures. It appears that these periods of abnormal neuronal excitation may actually damage the posttraumatic brain. So, I wondered if anyone is looking at that in this particular patient population.
1 2 3
Dr. David Greer: You won’t see it if you don’t look for it, is point 1. We are doing a lot more monitoring of these patients and if you see seizures, again, you should treat them. The problem is, what people call a seizure is often variable. Sometimes people will be on this ictal/interictal continuum as they are calling it, and this is a nebulous term. Do you treat this or not? When you see rhythmic delta activity, is that an angry rhythm that is going to degenerate just like aflutter would go into afib? It is unclear what you do with cases like that. I think if you see clear electrographic status or nonconvulsive status, you treat that. You can argue how aggressively you would treat that. Some would argue that electrographic status is a natural and temporary phenomenon after cardiac arrest, and that they will ‘‘outgrow’’ it or it will simply go away on its own. I’m not in that camp. I think like any other acute brain injury, if you see electrographic status, that can be damaging to the brain on top of what else has been going on, and you treat it. I cannot sit by and watch that, although there are different camps on that. Question: Question to Professor Sakamoto. We did a couple of patients with extracorporeal membrane oxygenation (ECMO) and when you have to do it fast, then you also have complications. You didn’t show your complication rate in your trial. Did you have complications such as bleeding? Did the bleeding and hypotension influence your outcome? Dr. Tetsuya Sakamoto: Yes, we experienced some complications related to the extracorporeal saturation. The major problem is bleeding from the cannulation site. Another problem is ischemia because of the cannulation to the femoral artery. Question: Do you place an external femoral artery catheter? Dr. Tetsuya Sakamoto: We need another cannulation to the distal femoral artery. In some cases, we discontinue during the first several days. Question: So your complication rate influences your outcome?
Department of Emergency Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. Department of Emergency Medicine, Teikyo University, Tokyo, Japan. Department of Neurology, Yale University, New Haven, Connecticut.
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EXPERT PANEL DISCUSSION
Dr. Tetsuya Sakamoto: Of course, the outcome that I presented today includes patients who have stopped CPR according to the complication, because this is the intention of this study. Dr. David Gaieski: One of the areas that still needs a lot of work is good neurologic outcomes in patients placed on bypasss. Dr. Sakamoto showed concerns about the survival rate of patients who just get regular hypothermia and postarrest care because they’ve had return of spontaneous circulation. In the Save-J trial, survival was significantly higher in the ECPR group; however, the percentage of neurologically intact survivors in most of the case series of bypass patients is down in the 50–60% range, and so there are more survivors who are injured when they go on to bypass. The question is how can we cut down on that percentage and get the numbers of patients up who survive neurologically intact to a similar percentage as in regular post-cardiac arrest hypothermia patients (those who achieve return of spontaneous circulation [ROSC] return of spontaneous circulation without ECPR)? Question: Coming from a community hospital, we do bypass, but we have limited resources and time for bypass. For Dr. Sakamoto and Dr. Gaieski, what we do have is many automated CPR devices in our community. So the consideration is a patient who is in persistent v-fib, maybe has been worked 15–20 minutes at the scene, and an endtidal CO2 that is good. What is your thought about the efficacy of these patients now being brought to the cath lab with an automated CPR device running as a subclass of patients, mainly as a substitute for going on to coronary bypass? Dr. David Gaieski: I think that is a great theory, and there are case reports that were presented during the case conference at AHA last year. In the New England Journal case presentation from September, there was a patient that they did exactly that for refractory ventricular fibrillation (VF), with ongoing CPR, and rapid transport to the cardiac catheterization laboratory. It’s a little unclear from the case report whether that was with a mechanical device, but most of the case reports have been with mechanical devices. Go to the cath lab and see if by opening the vessel you can interrupt the refractory VF. In the New England Journal case report, they ended up not being able to get the heart started—achieve ROSC—simply with opening the culprit vessel, so they put the patient on bypass in the cath lab. I think a lot of people would think you reverse that approach: put the patient on ECMO, then go to the cath lab. Certainly, the approach that Drs. Sakamoto and Nagao are using is early cannulation followed by catheterization, and their data would support that approach. Like from the Nagao article I showed you, it’s an interesting strategy. The only way we will know more about it is if more people start doing it either in case series or ideally in a more controlled, trial-based format. Question: We took 60 patients to the cath lab on the mechanical device, and few had a good outcome, about 3%.
151
physiological wakening during the CPR. Three died because we do not transport patients generally who don’t have ROSC or some physiologic parameter. One patient never had to be cooled because she woke up so fast, and the other one was cooled. Both had good neurologic outcome. Maybe the specificity of whom we choose, or the selectivity of who we choose to do this with is important. The second related issue is ECMO. ECMO is ‘‘damned if you do and damned if you don’t.’’ We just acquired ECMO at our facility for other purposes, and now this hard question is being asked, whether and who we would consider for ECMO. So in terms of moving from the university setting to the community hospital setting, please comment on who you would chose if you were going to do ECMO. Dr. David Gaieski: Dr. Sakamoto, do you want to address what you think is sort of the optimal candidate to put on ECMO? Dr. Tetsuya Sakamoto: So in this study, the candidate is not so old, and from the call to the hospital arrival should be a maximum of 45 minutes. But in the subgroup analysis what I generally see is that if the patient comes to hospital within 30 minutes, the outcome becomes much more vital. So the duration of the CPR is very important. But it depends upon the quality of the CPR I think. Another thing is cause of the cardiac arrest. Ninety percent of the patients sent to the extracorporeal resuscitation are cooled as soon as possible, usually within 1 hour. Dr. David Gaieski: So I think the starting point would be witnessed VF patients who remain in VF on arrival to the emergency department. We all don’t have that many of those patients. It’s interesting that you bring up physiologic parameters because the article that was done by Jerry Buckberg’s group at UCLA, where they took 34 people in refractory arrest and cannulated them for ECMO, they only put them on pump if they had certain physiologic parameters. They used that as a surrogate for quality of CPR and coronary perfusion pressure. So that’s another way to think about these patients, I think. Comment: Well we’ve been trying to look at endtidal CO2 also as a simple predictor because they have to get the A line in and, coming in from the field, make some decisions. Quick question on seizures. What are you treating them with if you see them? You’ve been aggressive in thinking if they’re there we’ve got to do something. What do you do? Dr. David Greer: I treat them like we treat any other status. So you go down the algorithm with Keppra versus Dilantin. They are both very good agents. They both work very well. But if they’re not responding to that, then you have to accelerate it or use valproate. Sometimes they’ll go on a barbiturate drip or medazolam. How long do you treat them? Again, we’re going to publish a case report on a patient who we treated for a very long period of time and actually ended up using ketamine, finally breaking her out of status. So, it’s your typical status algorithm. It’s not different from any other status epilepticus patient, unless they have a reason not to use one of the agents due to liver or renal failure.
Dr. David Gaieski: Yes, so that is not promising. Comment: We actually have taken five patients to the cath lab with ongoing mechanical CPR. All of those patients had
Question: So if your patient is already being sedated, let’s say you’re using benzodiazepine, you add more benzo? Or would you go to another agent like Keppra or Dilantin?
152
Dr. David Greer: So most people during their therapeutic hypothermia protocol would be using either midazolam or propofol to keep them sedated. If they are still seizing when they are sedated, you do not normally see external seizures because they are paralyzed. We have seen nonconvulsive status. I would add traditional agents first. Keppra is my preference. With Dilantin, cardiac toxicity, drug–drug interactions are much worse. So, start going down the line: if you need to bump up the dose of a general anesthetic such as propofol, then you can do that or start adding other agents. Comment: It’s actually more of a comment rather than a question, but I think it’s been a great discussion about extracorporeal support and ECMO. I think patient selection is obviously critically important. But I note that some physician-staffed EMS agencies in Europe are actually deploying ECMO in the field, particularly in Paris. I note that a community hospital in San Diego has a fairly successful emergency physician-based program initiating ECMO on these patients. There’s another similar program in Melbourne. So it probably requires patient selection and interest and expertise. I think there is a set of issues around who you start with; a mechanical CPR device in the field in transition to ECMO or not. But I think before we write off these approaches, I think we need to look at the experience that others are having and better understand how it fits. Dr. David Gaieski: Right. I completely agree with what Dr. Nichols is saying and you know, the goal of the Save-J trial was to try to elucidate how close to 100% mortality you have in patients who have had conventional CPR for an extended length of time and then whether you can salvage them or not. They showed some very intriguing data that you can salvage a percentage of them with rapid deployment of ECMO and that the survival is very low in the ongoing conventional CPR group. But once you get to that point, the conclusions are limited because of the study design, which, obviously, was not a randomized trial. Question: Okay, back to the seizure activity. In terms of antiepileptics, would you prefer to use an HDAC inhibitor? Valproate acid has been shown to reduce reperfusion injury. Can you comment on that for me please? Dr. David Greer: I’m not adverse to it. The problem with valproate is that if you’ve taken a hit to your liver during the arrest, which often these patients do, they have shock liver. So their metabolism is going to be off. The second is when you start using Valproate in the acute setting, a certain proportion of patients will get severe hyperammonemia, especially with the IV formulation as you’re treating status. So you have to keep that in mind. Doesn’t mean that you shouldn’t use it, and it doesn’t mean that there isn’t a theoretical benefit to using it. It’s not really the drug of choice right off the shelf to go for in status, but for some people it is. I think you could make a case for it. But again, it needs to be studied in comparison to other agents. Question: The bright abnormal hippocampal signals that you mentioned were associated with poor outcome, is that cell death or edema? Are those transient signals that can be therapeutically manipulated?
EXPERT PANEL DISCUSSION
Dr. David Greer: I was hoping not to be asked that question because it is not a validated finding. What is it and what does it mean? We know that the hippocampus is very metabolically active, and we know that it is very sensitive to ischemia and hypoxia. So is it just showing its vulnerability in that respect? But it’s interesting that clinically there is a correlation. Also because these patients, if they have anything neurocognitively afterward after survival, have short-term memory problems that persist. So we know it’s a vulnerable area. We don’t know that if it correlates beyond neuropsychological outcomes to more functional outcomes beyond that. It’s provocative. But it needs to be studied a lot more. Question: Dr. Gaieski, you said fast awakening, and if I understood you well, that fast awakening was in patients with good prehospital preservation? Dr. David Gaieski: The question is about the early arousal in these people. There was a trend toward early awakening being in VF patients with bystander CPR, but it wasn’t statistically significant. So, we saw early awakening in several nonshockable rhythm patients as well. You can’t generalize to one group. But there were factors that were associated with earlier arousal. Question: The awakening time, is that in the targeted temperature management (TTM) trial also? Did you look at the awakening time? Response: Those data will come forth sooner or later. Key References from Panel Participants
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