THERAPEUTIC HYPOTHERMIA AND TEMPERATURE MANAGEMENT Volume 7, Number 3, 2017 ª Mary Ann Liebert, Inc. DOI: 10.1089/ther.2017.29032.ply
Expert Panel Discussion
Downloaded by University of Rochester package NERL from online.liebertpub.com at 09/02/17. For personal use only.
Unique Uses of Cooling Strategies Moderator: Fred Rincon, MD, MSC, FACP1 Participants: Morten Bestle, MD, PhD,2 Gregor Brossner, MD, PhD,3 and Jitka Vanderpol, MD4
effects of the migraine benefit be related to the vasoconstrictive properties of oxygen? Is that possible?
During the 2017 Chilling at the Beach Annual Meeting in Miami, an expert panel discussion was conducted on the uses of therapeutic hypothermia (TH) and several clinical conditions. Dr. Fred Rincon, Department of Neurology, Thomas Jefferson University, moderated the session. Dr. Morten Bestle, University of Copenhagen, spoke on targeted temperature management (TTM) approaches to preventing and treating sepsis. Sepsis is a serious clinical condition and how best to treat this condition with temperature regulation is an active area of research. Dr. Grego Brossner, Department of Neurology, University Hospital, Innsbruck, discussed the uses of hypothermia in various clinical conditions and strategies to reduce fever and postrewarming problems. Dr. Jitka Vanderpol, Penrith Hospital, Cumbria, United Kingdom, reviewed the latest clinical data on the use of intranasal cooling in patients with migraine. Each of these presentations provided new information to the attendees and resulted in a rich question and answer period.
Dr. Jitka Vanderpol: There are a few trials and so far, the benefit was only reported when the oxygen was delivered in a hyperbaric setting, not normobaric oxygen. The evidence is controversial. There is not sufficient evidence from the migraine trials that treatment of migraine with oxygen would be helpful. It is not the same for cluster headaches. For the cluster headache, oxygen is one of the treatments. Question: Was there any perceived loss of equipoise as you enrolled patients to the point where it was felt by clinical divisions where one arm was performing better than the other? Let’s say the trial was stopped for futility; is there a plan in place for or expectation where you might consider doing further studies perhaps as an adaptive design around different target temperatures where you might perhaps zero in on a temperature that has greater advantages than disadvantages?
Question: Dr. Vanderpol, remind us what your target temperature is utilizing the intranasal cooling strategy?
Dr. Morten Bestle: At the moment, we have no plans to follow up on our study, but we need to look into the data more. Can you repeat the first question?
Dr. Jitka Vanderpol: We are targeting 20–22C for the nasal passages temperature. There is no change in body temperature. We measured the tympanic membrane temperature in the pilot trial and there was no significant change. We do not aim to change the temperature of the body; this is only for local treatment.
Question: I have been involved in large multicenter studies where we were enrolling a large number of patients and toward the end, we reached a point where every time we randomized a patient, the clinician would say I hope they end up in arm x, y, or z when objectively you should not be discussing this; you should be maintaining equipoise. I think this can have an impact on how the patient is treated depending on which arm he or she is in.
Question: So, have you had the opportunity to measure the pial vasculature on the cerebral cortex; do you think that temperature is going to be reduced? Dr. Jitka Vanderpol: There might be a reduction of maybe 1–2C, but unfortunately, because we have healthy individuals, this is not possible.
Dr. Morten Bestle: My personal feeling is that at my own center, we did not have these problems, but of course it is difficult to say. I feel that the centers followed the protocol and there was no selection bias, but it can happen.
Dr. Fred Rincon: Oxygen is one of the most potent vasoconstrictors. If you are inhaling cooled oxygen, would not the 1
Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania. Nordsjaellands Hospital, University of Copenhagen, Copenhagen, Denmark. Neurointensive Care Unit, Department of Neurology, University Hospital, Innsbruck, Austria. 4 Penrith Hospital, Cumbria Partnership NHS Foundation Trust, Cumbria, United Kingdom. 2 3
1
2
Downloaded by University of Rochester package NERL from online.liebertpub.com at 09/02/17. For personal use only.
Question: I was curious how you go about doing a placebo control for your migraine study? Dr. Jitka Vanderpol: For the placebo control, we have a bottle of water instead of the coolant. The perception of the patient when they feel the stream of blowing air on the hand is cold, but it is not actually cold, just our perception. We have to be careful when training our placebo group so they do not know they are getting a placebo. If you have never experienced this device before, the air running out of the nasal catheter feels cold even though the coolant is not being used. Question: Your subjects who are going to be enrolled in the larger study, are these individuals who have had chronic migraine for a very long time? These are not perimenopausal women who are having migraines once a month due to hormone changes? Dr. Jitka Vanderpol: We actually have recruited episodic migraine sufferers for the trial with
Expert Panel Discussion
Downloaded by University of Rochester package NERL from online.liebertpub.com at 09/02/17. For personal use only.
Unique Uses of Cooling Strategies Moderator: Fred Rincon, MD, MSC, FACP1 Participants: Morten Bestle, MD, PhD,2 Gregor Brossner, MD, PhD,3 and Jitka Vanderpol, MD4
effects of the migraine benefit be related to the vasoconstrictive properties of oxygen? Is that possible?
During the 2017 Chilling at the Beach Annual Meeting in Miami, an expert panel discussion was conducted on the uses of therapeutic hypothermia (TH) and several clinical conditions. Dr. Fred Rincon, Department of Neurology, Thomas Jefferson University, moderated the session. Dr. Morten Bestle, University of Copenhagen, spoke on targeted temperature management (TTM) approaches to preventing and treating sepsis. Sepsis is a serious clinical condition and how best to treat this condition with temperature regulation is an active area of research. Dr. Grego Brossner, Department of Neurology, University Hospital, Innsbruck, discussed the uses of hypothermia in various clinical conditions and strategies to reduce fever and postrewarming problems. Dr. Jitka Vanderpol, Penrith Hospital, Cumbria, United Kingdom, reviewed the latest clinical data on the use of intranasal cooling in patients with migraine. Each of these presentations provided new information to the attendees and resulted in a rich question and answer period.
Dr. Jitka Vanderpol: There are a few trials and so far, the benefit was only reported when the oxygen was delivered in a hyperbaric setting, not normobaric oxygen. The evidence is controversial. There is not sufficient evidence from the migraine trials that treatment of migraine with oxygen would be helpful. It is not the same for cluster headaches. For the cluster headache, oxygen is one of the treatments. Question: Was there any perceived loss of equipoise as you enrolled patients to the point where it was felt by clinical divisions where one arm was performing better than the other? Let’s say the trial was stopped for futility; is there a plan in place for or expectation where you might consider doing further studies perhaps as an adaptive design around different target temperatures where you might perhaps zero in on a temperature that has greater advantages than disadvantages?
Question: Dr. Vanderpol, remind us what your target temperature is utilizing the intranasal cooling strategy?
Dr. Morten Bestle: At the moment, we have no plans to follow up on our study, but we need to look into the data more. Can you repeat the first question?
Dr. Jitka Vanderpol: We are targeting 20–22C for the nasal passages temperature. There is no change in body temperature. We measured the tympanic membrane temperature in the pilot trial and there was no significant change. We do not aim to change the temperature of the body; this is only for local treatment.
Question: I have been involved in large multicenter studies where we were enrolling a large number of patients and toward the end, we reached a point where every time we randomized a patient, the clinician would say I hope they end up in arm x, y, or z when objectively you should not be discussing this; you should be maintaining equipoise. I think this can have an impact on how the patient is treated depending on which arm he or she is in.
Question: So, have you had the opportunity to measure the pial vasculature on the cerebral cortex; do you think that temperature is going to be reduced? Dr. Jitka Vanderpol: There might be a reduction of maybe 1–2C, but unfortunately, because we have healthy individuals, this is not possible.
Dr. Morten Bestle: My personal feeling is that at my own center, we did not have these problems, but of course it is difficult to say. I feel that the centers followed the protocol and there was no selection bias, but it can happen.
Dr. Fred Rincon: Oxygen is one of the most potent vasoconstrictors. If you are inhaling cooled oxygen, would not the 1
Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania. Nordsjaellands Hospital, University of Copenhagen, Copenhagen, Denmark. Neurointensive Care Unit, Department of Neurology, University Hospital, Innsbruck, Austria. 4 Penrith Hospital, Cumbria Partnership NHS Foundation Trust, Cumbria, United Kingdom. 2 3
1
2
Downloaded by University of Rochester package NERL from online.liebertpub.com at 09/02/17. For personal use only.
Question: I was curious how you go about doing a placebo control for your migraine study? Dr. Jitka Vanderpol: For the placebo control, we have a bottle of water instead of the coolant. The perception of the patient when they feel the stream of blowing air on the hand is cold, but it is not actually cold, just our perception. We have to be careful when training our placebo group so they do not know they are getting a placebo. If you have never experienced this device before, the air running out of the nasal catheter feels cold even though the coolant is not being used. Question: Your subjects who are going to be enrolled in the larger study, are these individuals who have had chronic migraine for a very long time? These are not perimenopausal women who are having migraines once a month due to hormone changes? Dr. Jitka Vanderpol: We actually have recruited episodic migraine sufferers for the trial with
