Center for Quality of Aging, Vanderbilt University School of Medicine; Center for Health Services Research, Vanderbilt University School of Medicine; Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine.
Department of Anesthesiology, Division of Critical Care Medicine, Vanderbilt University School of Medicine.
Chest. 2011 Sep;140(3):580-585. doi: 10.1378/chest.10-3065.
Delirium is a frequent form of acute brain dysfunction in patients who are critically ill and is associated with poor clinical outcomes, including a critical illness brain injury that may last for months to years. Despite widespread recognition of significant adverse outcomes, pharmacologic approaches to prevent or treat delirium during critical illness remain unproven. We hypothesize that commonly prescribed statin medications may prevent and treat delirium by targeting molecular pathways of inflammation (peripheral and central) and microglial activation that are central to the pathogenesis of delirium. Systemic inflammation, a principal mechanism of injury, for example, in sepsis, acute respiratory distress syndrome, and other critical illnesses, can cause neuronal apoptosis, blood-brain barrier injury, brain ischemia, and microglial activation. We hypothesize that the known pleiotropic effects of statins, which attenuate such neuroinflammation, may redirect microglial activation and promote an antiinflammatory phenotype, thereby offering the potential to reduce the public health burden of delirium and its associated long-term cognitive injury.
谵妄是危重病患者中常见的急性脑功能障碍形式，与不良的临床结局相关，包括可能持续数月至数年的危重病性脑损伤。尽管人们普遍认识到严重的不良后果，但在危重病期间预防或治疗谵妄的药物治疗方法仍未得到证实。我们假设，常用的他汀类药物可能通过靶向炎症（外周和中枢）和小胶质细胞激活的分子途径来预防和治疗谵妄，这些途径是谵妄发病机制的核心。全身炎症是损伤的主要机制，例如在脓毒症、急性呼吸窘迫综合征和其他危重病中，会导致神经元凋亡、血脑屏障损伤、脑缺血和小胶质细胞激活。我们假设，他汀类药物的已知多效作用可以减轻这种神经炎症，可能会重新定向小胶质细胞激活并促进抗炎表型，从而有可能减轻谵妄及其相关的长期认知损伤的公共卫生负担。
