The Brain and Hypothermia-From Aristotle to Targeted Temperature Management.
The Brain and Hypothermia-From Aristotle to Targeted Temperature Management.
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大脑和低温——从亚里士多德到有针对性的温度管理。
DOI：
10.1097/ccm.0000000000002182
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发表时间：
2017-02
影响因子：
8.8
通讯作者：
Jackson TC
中科院分区：
文献类型：
--
作者：
Kochanek PM;Jackson TC
Kochanek和Jackson 306 www.CcmJournal。Org 2017年2月·卷45·数字2如上所述，其更积极的使用，对温和的TH和温度调节及其对急性脑损伤的影响的欣赏重新出现在临床前文献中。Busto等人常常认为，温度上的“微小差异”在影响急性脑损伤预后中的重要性，以及认识到大脑和核心温度往往略有不同(7)。在这项研究中，全球缺血期间2摄氏度的温差-从36摄氏度到34摄氏度-显著减少了大鼠大脑中神经元的死亡，而将温度提高到39摄氏度则增加了神经元死亡。这篇文章影响了实验性脑损伤领域(8)，直到今天，急性脑损伤实验模型的临床前研究需要温度监测/控制，通常包括脑温度监测或替代物，如颞肌或鼓膜温度。该报告还挑战了这样一种观点，即TH的益处仅通过在缺血期间将能量需求减少到临界阈值以下来实现--暗示了其他未确定的机制。紧随其后的是成年动物心脏骤停(CA)模型和发育中动物窒息模型的研究，这些研究为临床试验奠定了基础，表明这两种环境都有好处(9-14)。轻度TH在治疗足月新生儿出生窒息方面的效果最好，在死亡、重大残疾、长期结局和神经成像结构保留方面受益于标准护理(15)。具有讽刺意味的是，鉴于新生儿科长期以来对冷应激的高度有害后果的担忧，TH在急性脑损伤中的最大益处出现在婴儿身上。已经提出了窒息后TH在对发育中的大脑特别重要的机制上的益处，例如细胞凋亡(17，18)。此外，非颤抖产热是婴儿与成人产热的主要机制，这可能需要一系列不同的发育调节生化反应或新生儿冷应激诱导的基因调节事件。与温和TH在CA中的应用相比，尽管早期的研究表明TH有能力降低颅内压，但在TBI中的多中心研究未能显示出对长期结果的益处。这包括成人和儿童在各种策略中的使用(19-23)。与使用TH治疗脑损伤相关的相对独特的并发症包括担心复温时血流动力学不稳定，如果颅内压升高，这可能是有害的；考虑到TH抑制细胞色素P-450介导的药物代谢，担心用于治疗脑损伤的许多药物及其毒性(24-26)。一些人建议有必要使用隔离脑降温来在脑外伤中实现无副作用的益处(27)。或者，脑外伤继发性损伤的潜在机制可能只是受到TH的影响不如CA，并被更大的副作用所抵消。
Kochanek and Jackson306 www. ccmjournal. org February 2017• Volume 45• Number 2 its more aggressive use, discussed above, resurgence in the appreciation of mild TH and temperature regulation and its impact on acute brain injury emerged from the preclinical literature. The importance of “small differences” in temperature in impacting outcome in acute brain injury and the recognition that brain and core temperature were often somewhat different is often attributed to Busto et al (7). In that study, a 2 C temperature difference during global ischemia—from 36 C to 34 C—markedly reduced neuronal death in rat brain, whereas increasing temperature to 39 C increased neuronal death. That article impacted the field of experimental brain injury (8), and to this day, preclinical studies in experimental models of acute brain injury require temperature monitoring/control and often include brain temperature monitoring or surrogates such as temporalis muscle or tympanic membrane temperature. That report also challenged the notion that the benefits of TH were mediated solely by a reduction in energy demands below a critical threshold during ischemia—suggesting other undefined mechanisms. It was followed by studies in models of cardiac arrest (CA) in adult animals and of asphyxia in developing animals that set the stage for clinical trials showing benefit in both settings (9–14). The greatest efficacy of mild TH is seen in the treatment of birth asphyxia in term newborns with benefit versus standard of care on death, major disability, long-term outcome, and structural preservation on neuroimaging (15). It is also ironic that the greatest benefit of TH in acute brain injury is seen in infants, given the longstanding concerns in neonatology about the highly deleterious consequences of cold stress (16). Benefit of TH after asphyxia on mechanisms of special importance to the developing brain, such as apoptosis, has been suggested (17, 18). Also, nonshivering thermogenesis is the primary mechanism of heat production in infants versus adults, which may necessitate a distinct series of developmentally regulated biochemical responses or gene-regulatory events induced by cold stress in newborn patients. Contrasting the success seen with the use of mild TH in CA, despite early work showing the ability of TH to lower ICP, multicenter studies in TBI have failed to show benefit on long-term outcome. This included use in both adults and children in a variety of strategies (19–23). Relatively unique complications associated with the use of TH in TBI have included concerns with hemodynamic instability during rewarming, which may be deleterious if ICP is elevated and concerns with the many drugs used to treat TBI and toxicities from them given the inhibition of cytochrome P-450-mediated drug metabolism by TH (24–26). Some have suggested the need to use isolated brain cooling to achieve benefit without side effects in TBI (27). Alternatively, the mechanisms underlying secondary injury in TBI may simply be less favorably influenced by TH than those in CA and counterbalanced by greater side effects.