Temporal limits of therapeutic hypothermia onset in clinical trials for acute ischemic stroke: How early is early enough?

Stroke is one of the leading causes of mortality and morbidity worldwide, and yet, current treatment is limited to thrombolysis through either t-PA or mechanical thrombectomy. While therapeutic hypothermia has been adopted in clinical contexts such as neuroprotection after cardiac resuscitation and...

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Main Authors: Hangil Lee, Yuchuan Ding
Format: Article
Language:English
Published: Wolters Kluwer Medknow Publications 2020-01-01
Series:Brain Circulation
Subjects:
Online Access:http://www.braincirculation.org/article.asp?issn=2394-8108;year=2020;volume=6;issue=3;spage=139;epage=144;aulast=Lee
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author Hangil Lee
Yuchuan Ding
author_facet Hangil Lee
Yuchuan Ding
author_sort Hangil Lee
collection DOAJ
description Stroke is one of the leading causes of mortality and morbidity worldwide, and yet, current treatment is limited to thrombolysis through either t-PA or mechanical thrombectomy. While therapeutic hypothermia has been adopted in clinical contexts such as neuroprotection after cardiac resuscitation and neonatal hypoxic-ischemic encephalitis, it is yet to be used in the context of ischemic stroke. The lack of ameliorative effect in ischemic stroke patients may be tied to the delayed cooling induction onset. In the trials where the cooling was initiated with significant delay (mostly systemic cooling methods), minimal benefit was observed; on the other hand, when cooling was initiated very early (mostly selective cooling methods), there was significant efficacy. Another timing factor that may play a role in amelioration may be the onset of cooling relative to thrombolysis therapy. Current understanding of the pathophysiology of acute ischemic injury and ischemia-reperfusion injury suggests that hypothermia before thrombolysis may be the most beneficial compared to cooling initiation during or after reperfusion. As many of the systemic cooling methods tend to require longer induction periods and extensive, separate procedures from thrombolysis therapy, they are generally delayed to hours after recanalization. On the other hand, selective cooling was generally performed simultaneously to thrombolysis therapy. As we conduct and design therapeutic hypothermia trials for stroke patients, the key to their efficacy may lie in quick and early cooling induction, both respective to the symptom onset and thrombolysis therapy.
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spelling doaj.art-6dc51ad67323414184eb18002c88b7c52022-12-21T23:42:05ZengWolters Kluwer Medknow PublicationsBrain Circulation2455-46262020-01-016313914410.4103/bc.bc_31_20Temporal limits of therapeutic hypothermia onset in clinical trials for acute ischemic stroke: How early is early enough?Hangil LeeYuchuan DingStroke is one of the leading causes of mortality and morbidity worldwide, and yet, current treatment is limited to thrombolysis through either t-PA or mechanical thrombectomy. While therapeutic hypothermia has been adopted in clinical contexts such as neuroprotection after cardiac resuscitation and neonatal hypoxic-ischemic encephalitis, it is yet to be used in the context of ischemic stroke. The lack of ameliorative effect in ischemic stroke patients may be tied to the delayed cooling induction onset. In the trials where the cooling was initiated with significant delay (mostly systemic cooling methods), minimal benefit was observed; on the other hand, when cooling was initiated very early (mostly selective cooling methods), there was significant efficacy. Another timing factor that may play a role in amelioration may be the onset of cooling relative to thrombolysis therapy. Current understanding of the pathophysiology of acute ischemic injury and ischemia-reperfusion injury suggests that hypothermia before thrombolysis may be the most beneficial compared to cooling initiation during or after reperfusion. As many of the systemic cooling methods tend to require longer induction periods and extensive, separate procedures from thrombolysis therapy, they are generally delayed to hours after recanalization. On the other hand, selective cooling was generally performed simultaneously to thrombolysis therapy. As we conduct and design therapeutic hypothermia trials for stroke patients, the key to their efficacy may lie in quick and early cooling induction, both respective to the symptom onset and thrombolysis therapy.http://www.braincirculation.org/article.asp?issn=2394-8108;year=2020;volume=6;issue=3;spage=139;epage=144;aulast=Leeacute ischemic strokeinter-ischemia hypothermiainter-reperfusion hypothermianeuroprotectionpostreperfusion hypothermiaprereperfusion hypothermiatherapeutic hypothermia
spellingShingle Hangil Lee
Yuchuan Ding
Temporal limits of therapeutic hypothermia onset in clinical trials for acute ischemic stroke: How early is early enough?
Brain Circulation
acute ischemic stroke
inter-ischemia hypothermia
inter-reperfusion hypothermia
neuroprotection
postreperfusion hypothermia
prereperfusion hypothermia
therapeutic hypothermia
title Temporal limits of therapeutic hypothermia onset in clinical trials for acute ischemic stroke: How early is early enough?
title_full Temporal limits of therapeutic hypothermia onset in clinical trials for acute ischemic stroke: How early is early enough?
title_fullStr Temporal limits of therapeutic hypothermia onset in clinical trials for acute ischemic stroke: How early is early enough?
title_full_unstemmed Temporal limits of therapeutic hypothermia onset in clinical trials for acute ischemic stroke: How early is early enough?
title_short Temporal limits of therapeutic hypothermia onset in clinical trials for acute ischemic stroke: How early is early enough?
title_sort temporal limits of therapeutic hypothermia onset in clinical trials for acute ischemic stroke how early is early enough
topic acute ischemic stroke
inter-ischemia hypothermia
inter-reperfusion hypothermia
neuroprotection
postreperfusion hypothermia
prereperfusion hypothermia
therapeutic hypothermia
url http://www.braincirculation.org/article.asp?issn=2394-8108;year=2020;volume=6;issue=3;spage=139;epage=144;aulast=Lee
work_keys_str_mv AT hangillee temporallimitsoftherapeutichypothermiaonsetinclinicaltrialsforacuteischemicstrokehowearlyisearlyenough
AT yuchuanding temporallimitsoftherapeutichypothermiaonsetinclinicaltrialsforacuteischemicstrokehowearlyisearlyenough