Preclinical Critical Care Unit, Florey Institute of Neuroscience and Mental Health, Melbourne, Victoria, Australia.
Centre for Integrated Critical Care, School of Medicine, University of Melbourne, Melbourne, Victoria, Australia.
Br J Pharmacol. 2021 Mar;178(6):1407-1425. doi: 10.1111/bph.15363. Epub 2021 Feb 15.
Agonists of α -adrenoceptors are increasingly being used for the provision of comfort, sedation and the management of delirium in critically ill patients, with and without sepsis. In this context, increased sympathetic and inflammatory activity are common pathophysiological features linked to multi-organ dysfunction, particularly in patients with sepsis or those undergoing cardiac surgery requiring cardiopulmonary bypass. Experimental and clinical studies support the notion that the α -adrenoceptor agonists, dexmedetomidine and clonidine, mitigate sympathetic and inflammatory overactivity in sepsis and cardiac surgery requiring cardiopulmonary bypass. These effects can protect vital organs, including the cardiovascular system, kidneys, heart and brain. We review the pharmacodynamic mechanisms by which α -adrenoceptor agonists might mitigate multi-organ dysfunction arising from pathophysiological conditions associated with excessive inflammatory and adrenergic stress in experimental studies. We also outline recent clinical trials that have examined the use of dexmedetomidine in critically ill patients with and without sepsis and in patients undergoing cardiac surgery.
α-肾上腺素受体激动剂越来越多地被用于为危重病患者（无论是否伴有败血症）提供舒适、镇静和治疗意识障碍。在这种情况下，交感神经和炎症活动增加是与多器官功能障碍相关的常见病理生理特征，特别是在败血症患者或需要体外循环的心脏手术患者中。实验和临床研究支持这样一种观点，即 α-肾上腺素受体激动剂右美托咪定和可乐定可减轻败血症和需要体外循环的心脏手术中的交感神经和炎症过度活跃。这些作用可以保护重要器官，包括心血管系统、肾脏、心脏和大脑。我们回顾了 α-肾上腺素受体激动剂通过何种药效学机制减轻与过度炎症和肾上腺素应激相关的病理生理条件引起的多器官功能障碍的实验研究。我们还概述了最近的临床试验，这些试验检查了在伴有或不伴有败血症的危重病患者以及心脏手术患者中使用右美托咪定的情况。
