Baker Turner S, Kellner Christopher P, Colbourne Frederick, Rincon Fred, Kollmar Rainer, Badjatia Neeraj, Dangayach Neha, Mocco J, Selim Magdy H, Lyden Patrick, Polderman Kees, Mayer Stephan
Icahn School of Medicine at Mount Sinai, Sinai BioDesign, New York, NY, United States.
Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
Front Neurol. 2022 Aug 17;13:859894. doi: 10.3389/fneur.2022.859894. eCollection 2022.
Therapeutic hypothermia (TH), or targeted temperature management (TTM), is a classic treatment option for reducing inflammation and potentially other destructive processes across a wide range of pathologies, and has been successfully used in numerous disease states. The ability for TH to improve neurological outcomes seems promising for inflammatory injuries but has yet to demonstrate clinical benefit in the intracerebral hemorrhage (ICH) patient population. Minimally invasive ICH evacuation also presents a promising option for ICH treatment with strong preclinical data but has yet to demonstrate functional improvement in large randomized trials. The biochemical mechanisms of action of ICH evacuation and TH appear to be synergistic, and thus combining hematoma evacuation with cooling therapy could provide synergistic benefits. The purpose of this working group was to develop consensus recommendations on optimal clinical trial design and outcomes for the use of therapeutic hypothermia in ICH in conjunction with minimally invasive ICH evacuation.
An international panel of experts on the intersection of critical-care TH and ICH was convened to analyze available evidence and form a consensus on critical elements of a focal cooling protocol and clinical trial design. Three focused sessions and three full-group meetings were held virtually from December 2020 to February 2021. Each meeting focused on a specific subtopic, allowing for guided, open discussion.
These recommendations detail key elements of a clinical cooling protocol and an outline for the roll-out of clinical trials to test and validate the use of TH in conjunction with hematoma evacuation as well as late-stage protocols to improve the cooling approach. The combined use of systemic normothermia and localized moderate (33.5°C) hypothermia was identified as the most promising treatment strategy.
These recommendations provide a general outline for the use of TH after minimally invasive ICH evacuation. More research is needed to further refine the use and combination of these promising treatment paradigms for this patient population.
治疗性低温（TH），即目标温度管理（TTM），是一种经典的治疗方法，可减轻多种病理状态下的炎症以及潜在的其他破坏过程，并已成功应用于多种疾病状态。TH改善神经功能结局的能力对于炎症性损伤似乎很有前景，但尚未在脑出血（ICH）患者群体中证明其临床益处。微创脑出血清除术对于ICH治疗也是一个有前景的选择，有强有力的临床前数据支持，但在大型随机试验中尚未证明其能改善功能。脑出血清除术和TH的生化作用机制似乎具有协同性，因此将血肿清除与降温治疗相结合可能会带来协同效益。该工作组的目的是就治疗性低温联合微创脑出血清除术在ICH中的最佳临床试验设计和结局制定共识性建议。
召集了一个由重症监护TH与ICH交叉领域的国际专家小组，以分析现有证据，并就局部降温方案和临床试验设计的关键要素达成共识。2020年12月至2021年2月以线上方式举行了三次专题会议和三次全体会议。每次会议聚焦一个特定子主题，进行有引导的开放式讨论。
这些建议详细阐述了临床降温方案的关键要素，以及用于测试和验证TH联合血肿清除术的临床试验开展大纲，还有用于改进降温方法的后期方案。全身正常体温与局部中度（33.5°C）低温联合使用被确定为最有前景的治疗策略。
这些建议为微创脑出血清除术后使用TH提供了总体框架。对于该患者群体，需要更多研究来进一步优化这些有前景的治疗模式的使用和组合。
