从脓毒症诊治观念变迁看肾上腺皮质激素的应用

脓毒症是病原微生物感染引发的危及生命的器官功能障碍。由于病理生理机制的复杂性,自1991年对其概念的界定以来,已历经3次重要修订,但仍难以形成广泛共识。特别是在拯救脓毒症运动背景下,脓毒症发病率和死亡率居高不下、特效药物匮乏以及诸多经验性救治措施难以奏效的严峻现实表明,脓毒症非病原依赖性瀑布样介质反应尚有广阔的探索空间。肾上腺作为神经-内分泌-免疫调控网络的重要效应器官,通过接驳中枢应激信号和局部微环境反应,以效应激素形式参与对脓毒症机体反应的非线性、复杂性调控。其功能障碍的早期识别、替代治疗以及在脓毒症机体紊乱内环境中的再认识,无疑是脓毒症诊治的核心环节之一。近30年来,针对肾上腺皮质激素的多项临床研究以及争议性推荐意见进一步凸显其重要价值。为此,笔者基于预测性、预防性、个体化、参与性的"4P"医学模式,立足转化医学视角,从脓毒症定义及其内涵的变化,分析肾上腺皮质激素的诊治价值,并从内源性和外源性肾上腺皮质激素角度,阐述脓毒症治疗中基于神经-内分泌-免疫网络的微环境调控理论,尝试从肾上腺皮质激素(种类、用量、单独和联合治疗、时间窗)分析脓毒症理论研究瓶颈与临床实践困惑,旨在为脓毒症的肾上腺皮质激素应用提供有益的借鉴和启示。

Adrenocortical hormone application in view of the changes in the concept of diagnosis and treatment of sepsis

Sepsis is a life-threatening organ dysfunction caused by a pathogenic microbial infection. Due to the complexity of the pathophysiological mechanism, the definition of its concept had undergone three major revisions since 1991. But it remains difficult to reach a broad consensus. Especially in the context of " Surviving Sepsis Campaign" , the high incidence and mortality, the lack of specific drugs, and many disappointing empirical treatment measures indicate that there is a long way to explore the pathogen-independent mediator responses in sepsis. As an important effector of the neuro-endocrine-immune regulatory network, the adrenal gland participates in the nonlinear and complex regulation of sepsis via responsive hormones by linking central stress signals and local microenvironmental responses. The early identification and replacement therapy of adrenal dysfunction and the re-recognition in the environment of sepsis disorder are undoubtedly the key aspects in the diagnosis and treatment of sepsis. Growing evidences of international clinical studies on adrenocortical hormones and pending recommendations in the past 30 years have further shown their therapeutic capacity. To this end, based on the 4P (preventive, predictive, personalized, participatory) medical model in translational medicine, this paper analyzes the diagnosis and treatment of adrenalcortical hormones from the definition and connotation of sepsis, and elaborates the theory of microenvironmental regulation of neuro-endocrine-immune network from the endogenous and exogenous adrenalcortical hormones. We try to further analyze the bottlenecks and confusion from the diagnosis and treatment of sepsis via adrenocortical hormones (type, dosage, single and combined treatment, time window), aiming to provide useful reference and enlightenment for the application of adrenocortical hormones in sepsis.