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Temperature Management in Neurological and Neurosurgical Intensive Care Unit

2020; Mary Ann Liebert, Inc.; Volume: 10; Issue: 2 Linguagem: Inglês

10.1089/ther.2020.29072.pjl

2153-7933

Patrick D. Lyden, Gregory Kapinos, Mypinder S. Sekhon, Allan D. Levi,

Thermal Regulation in Medicine

Therapeutic Hypothermia and Temperature ManagementVol. 10, No. 2 Expert Panel DiscussionFree AccessTemperature Management in Neurological and Neurosurgical Intensive Care UnitModerator: Patrick Lyden, Participants: Gregory Kapinos, Mypinder S. Sekhon, and Allan D. LeviModerator: Patrick LydenDepartment of Neurology, Cedars-Sinai Medical Center, Los Angeles, California, USA.Search for more papers by this author, Participants: Gregory KapinosDepartment of Neurology, SUNY Downstate College of Medicine, New York, New York, USA.Search for more papers by this author, Mypinder S. SekhonDivision of Critical Care Medicine, Vancouver General Hospital of British Columbia, Vancouver, Canada.Search for more papers by this author, and Allan D. LeviDepartment of Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA.Search for more papers by this authorPublished Online:3 Jun 2020https://doi.org/10.1089/ther.2020.29072.pjlAboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail During the 2019 Therapeutic Hypothermia and Temperature Management Symposium in Miami, state-of-the-art lectures on the current advances in the use of temperature management and neurological and neurosurgical intensive care units were discussed. The panel was moderated by Dr. Patrick Lyden, Department of Neurology, Cedars-Sinai Medical Center. Dr. Gregory Kapinos, Department of Neurology, SUNY Downstate College of Medicine, discussed temperature targeted management in the neuro ICU as well as fever and shivering control. In another lecture, Dr. Mypinder S. Sekhon, Division of Critical Care Medicine, Vancouver General Hospital of British Columbia, discussed the pathophysiology of hypoxic ischemic brain injury after cardiac arrest and therapeutic interventions targeting this condition. Finally, Dr. Allan Levi, Department of Neurological Surgery, University of Miami Miller School of Medicine, updated the audience on the use of hypothermia in spinal surgery and injury including current results regarding the multicenter hypothermia trial. All the presentations were outstanding and led to informative discussions among the attendees of the conference.Question: This question is for Dr. Kapinos. In my experience I find magnesium is helpful for a more proactive approach because of the vasodilatory effect especially with vasoconstriction that happens before the shivering threshold. I was just wondering what your thoughts are since you use it a little bit later in the game.Dr. Gregory Kapinos: I agree that the drawbacks are so little that you can use magnesium earlier than what I suggested in my protocol. However, one of the caveats is that it is a drip. That is why I put it later in the steps of the protocol, but you may bump it up to almost a prophylactic approach if you prefer. So do not wait for a Bedside Shivering Assessment Scale (BSAS) of 2 to implement some magnesium, I agree.Dr. Patrick Lyden: Magnesium has been used since the Columbia Neuro ICU protocol was published but there is actually no data to support the use of magnesium. I am just curious by a show of hands, how many of you are from centers where magnesium is already part of your shivering protocol? And centers where it is not part of your protocol? Looks like about 50–50.Dr. Gregory Kapinos: I also want to say that my slide might be confusing because I put the BSAS and tier in a conflated way and I wanted to create a mnemonic with the alphabet. So, unfortunately, magnesium starts with M and it comes late in the game, but you can create any pathway you want.Question: For Dr. Sekhon, for some of us who have been trying to get our local IRBs to be able to let us do some invasive studies in cardiac arrest patients, could you share how you went about being able to get this kind of protocol approved and any advice for the rest of us who would like to implement this protocol.Dr. Mypinder S. Sekhon: Not surprisingly, it took a long time. In fact, I went physically to the IRB three times to present the rationale for wanting to do this in humans as opposed in animal models. To be honest with you, we have a good relationship with our IRB, but they did have significant concerns and justifiably so. We established a data safety monitoring board that would prospectively review every patient as soon as we enrolled them every day. After we finished the first 10 patients, I went back and presented what we found and so far we have not had any adverse events. My colleagues who have managed a few of these patients and I would describe them as early adopters and they are requesting this on clinical grounds.Dr. Patrick Lyden: I would like to follow up because you stated that this technology or this technique would not be generalizable outside of your clinical trial but you have shown effectiveness as well as opposite directions. You showed the one case where the PrX went to the right direction but things went bad because of differences in pathophysiology. Doesn't that argue in favor of using this technology in these cases more broadly?Dr. Mypinder S. Sekhon: Absolutely. I feel now uncomfortable flying blind with patients. I think it is like one of the cases in understanding critical care of the brain is relatively poor compared with the rest of the major organ function. If you think about all of the monitoring we have, look at the heart, there are a multitude of measurements taken as well as for the kidneys, but if you look at the brain for our site, what we have traditionally done if a cardiac arrest comes in, it used to be 33°C and then targeted temperature management (TTM) came out and people were saying 36°C and we would check pupils once an hour and maybe do a computed tomography (CT) scan. So, I think it is a unique opportunity for this disease to particularly characterize the physiology but to monitor these patients. I think invasive monitoring makes a lot of sense but certainly not generalizable to all patient populations. So the primary acute coronary syndrome (ACS) patients, you cannot do it on them, I would not be putting catheters in on people on ticagrelor or aspirin. I had huge hopes for cerebral asymmetry or near-infrared spectroscopy (NIRS) to correlate it with some sort of invasive monitoring. It did not work out for us but I think an undersold monitoring technique is jugular venous oximetry. I really think the potential is enormous as it pertains to oxygen uptake delivery, but also with all the work that people are doing with biomarkers that maybe one day there will be a troponin of the brain that you extract from the jugular venous oximeter.Dr. Patrick Lyden: I had a question for Dr. Levi. You showed us persuasive data that there was no time effect on outcome but you also showed that it took on average about 3 hours to reach target temperature and so if cooling starts between 4 and 8 hours and then it takes an additional 3 hours to get to target, your onset to target temperature is quite long. I know that in studies of stroke and recanalization therapy we did not see a time effect until we started treating patients under 3 hours to recanalization. I am just curious if there is no time effect that you have just missed. In preclinical literature, wouldn't it be expected that maybe the first hour or 2 hours is where the sweet spot would be in spinal cord injury.Dr. Allan D. Levi: I think that cerebral stroke and spinal cord injury are two very different diseases. There is obviously a vascular part of spinal cord injury but that is not the main primary pathophysiology. I would begin by saying that the ability to systemically cool a patient to target within an hour is technically impossible. You are absolutely correct that there is a 3-hour cooling phase but that has improved some with the new cooling catheters. In the first 24 hours, when we looked at that specific aspect, I would suspect that the few patients we could get cooled in maybe 3 hours that is probably the earliest, we just did not see an effect.Dr. Patrick Lyden: So, if I told you that if we had a catheter that could get you to target in 20 minutes, would you feel differently?Dr. Allan D. Levi: I think that would be great. I would use it. It would reduce the overall time that these patients are cooled. I think those kinds of questions sometimes are best asked in laboratory where you can have control of different parameters. Certainly in a spinal cord injured population that also has very heterogeneous injuries and times of arrival to trauma center it would be very difficult to do. I would be all for faster cooling catheters and they actually exist now.Question: This question is for Dr. Sekhon. First of all, great work and getting this through your IRB and actually doing this in a population that requires justification due to the fact that they are comatose. As we have been taught by the Brain Trauma Foundation and others, if you have a patient who is in coma you need to do neuromonitoring. I am glad to see that is happening in an organized way. How are you making a decision of when to stop monitoring? It looked like it was somewhat heterogeneous and why not do it in a uniform way because you will get more uniform data. The second question has to do with another monitor. I am assuming you are using in your arrest patients continuous electroencephalogram (EEG) and how have you incorporated that data analysis into what you are doing with multimodality. Our own experience with doing this surface and depth EEG alongside, bundle of microdialysis tubes, jugular bulb, we found some very interesting relationships between jugular venous saturation, PbO2, and changes in surface and depth EEG that seemed to precede some of the other changes that you may see metabolically. I am curious whether you are starting to look at them as well.Dr. Mypinder S. Sekhon: In terms of the cessation of neuromonitoring, the way that we got this through the IRB is having the clinician at the bedside. My colleagues were not blinded to the technologies that they were allowed to use to best resuscitate the patient. Once they were off sedation, normothermic, normocapnic, and there PbO2 were sustained >20 and the intracranial pressure (ICP) was sustained <20 then at that point, and the patient was shifted to pressure support, my colleagues would notify me that they are not using monitoring anymore to change the patient's outcome and the catheter was removed. That is what we do for our traumatic brain injury population. In the first 10 patients, regrettably we did not incorporate EEG; in the subsequent 10 patients we have. We do not have depth electrodes. We had Jan Klaussen come and visit us a few months ago, we had a really hard sell for it but that is the greatest thing in the world because a fifth catheter or wire would be better than four, right? In the subsequent 10 patients, we have recorded it. I have no clue how to analyze anything like this but I would appreciate people like yourself and your expertise indicating what we should be looking for. This is potentially an opportunity for collaboration.Question: This question is for Dr. Sekhon. I was impressed by the results you had on the 21-year-old patient and appreciate that people could have called it quits at that time. Could you comment on that value of CT early and maybe later in terms of the white grade differentiation? I have seen people making early commitments based on that on the pupils and the sensitivity, specificity of the pupils on day 3 at this point, and whether or not you had gotten other things like an EEG or perfusion testing on this 21-year old, what would you have done at that point if you were not doing all of this?Dr. Mypinder S. Sekhon: With respect to CT, I do not pay a lot of attention to any variable in isolation. If there is concordance in imaging, examination, electrophysiology, and they are all pointing in the same direction that to me for prognostication is a more compelling case than opposed to one single outcome like CT, the radiologist is commenting on the CT that there is some gray/white differentiation loss, I do not do that. With respect to pupils, I am probably much like you and everybody else here, on day 1 once the patient has received a bunch of epinephrine, again I do not pay much attention to pupils in isolation. The reason in this particular case I thought it was real because concordance of a CT that showed progressive edema, obliteration of the cisterns and on day 3 pupillary dilation made sense to me. This is uncal herniation given that clinical sign. The kicker in her was that my colleague looked at the case and said this does not fit, there is something missing here and when we are talking about concordance, here is somebody, a young person, but there is discordance between what the gray/white differentiation looks like and what I am seeing on clinical examination. We are missing something here. Instead of just agreeing with the prognostication and refer for organ donation, we said we need to ask more questions. So, what we actually did at that point was that the patient received a lot of osmotherapy and we took her to nuclear medicine for a perfusion scan and we saw that there was perfusion, so we have to give this a go.Question: I know it is an expensive endeavor but are we missing anything by not using magnetic resonance imaging, for example, in this patient population early on to really define the pathology a little bit more adequately?Dr. Mypinder S. Sekhon: I think that is a great question. Magnetic resonance (MR) is a unique opportunity to provide some more detailed information with where the restricted diffusion is like basal ganglia, thalamus, and hippocampus. The only reason we did not do MR in this case was it is in an area of our hospital that I do not want to send patients to, especially this particular patient because her brain was very unstable and I did not want her lying flat for 30 minutes in the basement. It is a great point. At our hospital, we look at MR as a technique that is great but we have not traditionally associated cardiac arrest as an emergency. Typically, when I started 7 years ago, most of these patients would be in the emergency room (ER) and the attitude was that they are in the trauma bay and we will get them up to ICU when we can get them up there whenever a bed is available, then we will cool them to 33°C or maybe 36°C, and then at 24 hours, stop sedation and hope for the best. Our clinical group's approach has been a very rudimentary approach to a complicated disease.Dr. Patrick Lyden: I wanted to ask both Greg and Mypinder about following temperature versus treating temperature. So, this came up yesterday with some of the shock and trauma talks as well. Temperature changes that occur as a result of the disease may be something we do not want to treat versus a disease that has not affected the temperature yet, and we want to use therapeutic hypothermia. So, could you speculate a little bit in each of your cases and especially in the cardiac arrest patient that you showed as the temperature went up more bad things were happening and if that was not reflective underlying pathophysiology and it was not temperature but the underlying mechanism that was getting worse at that moment and whether temperature management was at that point going to be counterproductive as opposed to spinal cord injury or other things wherein getting ahead of the temperature is going to be therapeutic.Dr. Gregory Kapinos: I feel like when we are waiting for the temperature to be really high and then use an intervention, then sometimes there is more rebound than if we are more prophylactic. So, that is why I do not like to wait for the temperature to rise really high. But as you pointed out, using only symptomatic treatment to mask something, rather than focusing on what is the underlying cause for this rise in temperature, might not make sense. So of course, we need to make sure there is no infection. But at the same time, saying "it is just central fever" is not acceptable and it is complex than that. I think there is a way to look at the trends and tackle the issue early. Providing symptomatic treatment but still being aware that fever is also detrimental to brain-injured patients, inherently, is the way we can reconcile.Dr. Mypinder S. Sekhon: That is a great question. In cardiac arrest, I would be curious to see what other people think. So often these patients have aspiration or something else to create some sort of fever 2 days into this, could it be cerebral ischemia down in the deep parts of the brain like the thalamus or hypothalamus that are leading to central fever? Certainly, with respect to the changes that I showed with temperature next to PtO2, everything else that would effect PtO2 was stable, that is, blood pressure stable, no difference in hemoglobin as temperature changed, PaO2. It appears to be an independent effect but is that effect or relationship or demonstrating changes as temperature changes and PtO2 comes down, is that harmful for the brain or creating secondary injury? I am not sure because tissue PtO2 does not tell you what intracellular hypoxia is, it is just telling you extracellular levels of hypoxia so is that causing the problems in the neurons. I would probably be able to tell you more once we analyze our microdialysis data.Dr. Gregory Kapinos: When I am hearing this discussion, it reminds me of the same debate we had about these EEG patterns that we frequently see in brain injury and whether or not they represent seizures. University of California at Los Angeles (UCLA) and Columbia have both published that within those epochs of near seizures, lactate/pyruvate ratio goes up and PbtO2 goes down. They use this close temporal correlation to infer causation with detrimental impact of these EEG patterns onto brain physiology. So, in TTM actually, rather than looking at the trend of PbtO2 and sudden changes in it in relation to those epochs of fever, it might be smarter to do a bootstrap analysis of all of those epochs of rise in temperature and see whether it is always associated with a drop of PbO2 and then do the same with microdialysis. So, that would be the best way to truly answer the question, "are all those febrile epochs deleterious, yes or no?"Question: I was just wondering whether you are able to cool before spine stabilization or do you stabilize before cooling?Dr. Allan D. Levi: So, you could take that question even to the next level. What about cooling in the ambulance? We have had a lot of discussions about that with fire rescue but unfortunately in Miami those conversations were not fruitful. For somebody with a spinal cord injury, the diagnosis is usually pretty obvious. We are basically limited to starting the process of cooling in the emergency department. We basically put the catheter in the emergency department and/or in the operating room as we are bringing the patient up for surgery. Another part of it is that this general recognition is that it is good to do surgery on these patients very early, even in the middle of the night if necessary. That is what we do and I think that is what is being done nationally. A question that often comes up, is it the rapid decompression or is it the cooling. We have actually looked at that to dissect out what variables such as if the patient had late surgery but early cooling, did they still do ok but in every patient who gets entered into the study, the mantra is the same, no steroids and get the patient to the operating room as soon as possible for decompression so hopefully every patient is standardized.Question: As I understand it, in the multicenter trial, the control group is undergoing rapid decompression with normothermic treatment, thereby inhibiting periods of hyperthermia. You have already done two things that we think improve outcome in that patient population. Again, it is going to be really interesting to see whether you can see a difference between those two groups if hypothermia compared with normothermia makes a difference. Getting to my favorite topic of hyperthermia or fever. When I was in the department of neurology many years ago, my chairman always accused me of trying to make things worse but not trying to make things better by reducing secondary insults. Just for the audience, in preclinical models, if you take a rat and produce a stroke, spinal cord injury, or brain trauma and you wait 24 hours and then just artificially elevate brain temperature to 39°C for 3 hours and then bring it back down, that one period of transient hyperthermia actually changes the outcome in that animal in terms of behavior and pathology. So, the important thing we heard today is that just one period of hyperthermia could be detrimental to long-term outcome, at least in an animal model. So getting back to spinal cord injury, how frequently do you have hyperthermia?Dr. Allan D. Levi: I think that hyperthermia is not that uncommon in hospitalized patients. These patients are prone to infectious complications such as pneumonia and urinary tract infection (UTI) and it becomes a question of what is the best way to manage it quickly. Like you said, time is important. You know we take out the catheter usually on about day 4 and so that may not be the mechanism where we keep the patients normothermic, it may be other mechanisms, Tylenol, cooling blankets, etc. That is an important part of this study and it is certainly an important part of taking care of the patient in the ICU.Question: Do we still talk about a dissociation between brain and core temperature after brain injury, for example?Dr. Gregory Kapinos: Ideally, we can measure the brain temperature with an invasive technique, but I go by the core temperature, unless they are comatose and we can get the brain temperature.Dr. Patrick Lyden: Apparently not, because they are not putting the probes in the way we do in animals.Question: I have a simple question but when we are looking at a low blood flow state due to edema or an alteration in the blood flow, how tightly are you controlling the patients' glucose levels to avoid an alternative form of metabolism because they are not able to restore that glucose and how are you managing that?Dr. Mypinder S. Sekhon: If they have microdialysis in place and I titrate it to the cerebral glucose and without that then euglycemia is 7–10 mmol/L.Dr. Gregory Kapinos: Great question about hypoglycorrachia or low glucose level in the brain in traumatic brain injury (TBI). I am curious to know what the audience feels. Would you be bold enough to push D50 or D5W in this setting, despite all the data that dextrose and hypotonic solutions are detrimental in TBI? So, if you have a low level of glucose in the brain, who in this audience would feel comfortable correcting the low glucose level? I am personally feeling ambivalent about it.Dr. Patrick Lyden: Does anybody routinely push glucose based on intracerebral microdialysis? Anybody not doing it? Looks like a lot of people are not.Question: I have been very suspicious of NIRS for a while but the slide that showed low signal on a mannequin and the one you have published on, there is actual raw signal of the NIRS with the blood pressure when you have been in your pressure passes state. Have they actually been tightly controlled or not related at all because I do not see that with the ultrasound NIRS.Dr. Mypinder S. Sekhon: The raw signal?Question: The correlation between the mean arterial pressure (MAPS) and the actual raw signal before you do any processing of the correlation between them?Dr. Mypinder S. Sekhon: There is no correlation.Question: Are you using transcranial direct-current stimulation (TCDs) in any of these patients and what are some of the initial observations that you have seen with TCDs and the correlation with the invasive devices?Dr. Mypinder S. Sekhon: Great question. In the second cohort of 10 patients, I have 6 patients who got simultaneous TCD with a helmet that we record but I cannot tell you in detail because I still need to analyze the data.Key References from Panel ParticipantsBasto FM, Lyden P. Hypothermia in acute ischemic stroke therapy. Handb Clin Neurol 2018;157:823–837. Crossref, Medline, Google ScholarCardim D, Griesdale DE, Ainslie PN, et al. A comparison of non-invasive versus invasive measures of intracranial pressure in hypoxic ischaemic brain injury after cardiac arrest. Resuscitation 2019;137:221–228. Crossref, Medline, Google ScholarDididze M, Green BA, Dietrich WD, et al. Systemic hypothermia in acute cervical spinal cord injury: a case-controlled study. Spinal Cord 2013;51:395–400. Crossref, Medline, Google ScholarGersey ZC, Burks SS, Anderson KD, et al. First human experience with autologous Schwann cells to supplement sciatic nerve repair: report of 2 cases with long-term follow-up. Neurosurg Focus 2017;42:E2. Crossref, Medline, Google ScholarJohnson JN, Cummock MD, Levi AD, et al. Moderate hypothermia for intradural spinal tumor resection: a cohort comparison and feasibility study. Ther Hypothermia Temp Manag 2014;4:137–144. Link, Google ScholarKapinos G, Becker LB. The American Academy of Neurology affirms the revival of cooling for the revived. Neurology 2017;88:2076–2077. Crossref, Medline, Google ScholarLevi AD, Anderson KD, Okonkwo DO, et al. Clinical outcomes from a multi-center study of human neural stem cell transplantation in chronic cervical spinal cord injury. J Neurotrauma 2019;36:891–902. Link, Google ScholarLyden PD. Thrombolytic therapy for acute ischemic stroke. Stroke 2019;50:2597–2603. Crossref, Medline, Google ScholarLyden PD, Lamb J, Kothari S, et al. Differential effects of hypothermia on neurovascular unit determine protective or toxic results: toward optimized therapeutic hypothermia. J Cereb Blood Flow Metab 2019;39:1693–1709. Crossref, Medline, Google ScholarLyden P, Paul J, Yokobori S, et al. Unique uses of cooling strategies. Ther Hypothermia Temp Manag 2018;8:126–130. Link, Google ScholarMaas MB, Kapinos G. Recanalization for large vessel stroke: necessary but not sufficient for reperfusion. Neurology 2019;92:1127–1128. Crossref, Medline, Google ScholarNichol G, Polderman KH, Friberg H, et al. Perspectives on temperature management. Ther Hypothermia Temp Manag 2018. [Epub ahead of print]. Link, Google ScholarSekhon MS, Ainslie PN, Griesdale DE. Clinical pathophysiology of hypoxic ischemic brain injury after cardiac arrest: a "two-hit" model. Crit Care 2017;21:90. Crossref, Medline, Google ScholarSekhon MS, Gooderham P, Menon DK, et al. The burden of brain hypoxia and optimal mean arterial pressure in patients with hypoxic ischemic brain injury after cardiac arrest. Crit Care Med 2019;47:960–969. Crossref, Medline, Google ScholarFiguresReferencesRelatedDetails Volume 10Issue 2Jun 2020 InformationCopyright 2020, Mary Ann Liebert, Inc., publishersTo cite this article:Moderator: Patrick Lyden, Participants: Gregory Kapinos, Mypinder S. Sekhon, and Allan D. Levi.Therapeutic Hypothermia and Temperature Management.Jun 2020.86-90.http://doi.org/10.1089/ther.2020.29072.pjlPublished in Volume: 10 Issue 2: June 3, 2020Online Ahead of Print:April 23, 2020PDF download