Dickmann Petra, Bauer Michael
Department of Anaesthesiology and Intensive Care, University Hospital Jena.
Center for Sepsis Control and Care (CSCC), University Hospital Jena.
Z Orthop Unfall. 2020 Feb;158(1):81-89. doi: 10.1055/a-0853-2054. Epub 2019 Sep 9.
In spring 2016, an updated sepsis definition (Sepsis-3) introduced a new explanation for the clinical picture of sepsis. Until then, sepsis had been understood as a "systemic inflammatory response syndrome (SIRS)" resulting from infection. An improved understanding of the molecular mechanisms and broad epidemiological studies of the clinical appearance shifted the focus from the inflammatory response to the multicausal tissue damage resulting in organ dysfunction. This paradigm shift highlights organ failure as a result of a dysregulated response of an organism to infection. Central to the new definition is the understanding that sepsis patients form a heterogeneous group and that the clinical picture requires alternative explanation patterns: e.g. sepsis is insufficiently explained by an overwhelming inflammatory response, it also comprises "immune paralysis" as another important pattern. Furthermore, severity of sepsis reflects the capacity of an organism to adapt and to mitigate the tissue damage through metabolic changes and repair mechanisms. Consistent with the paradigm of the new sepsis definition, adaptation in the presence of infections is crucial for the organism. Seriously injured or multiple trauma patients represent a patient group at particular risk, as sepsis often complicates the courses of these patients due to nosocomial infections. Along with comorbidities, past infections and age, leakage of skin and intestinal barriers as well as impaired defence and repair mechanism predispose trauma patients for a septic course. New pathophysiological insights suggest that the control of extracellular haem is of paramount significance. Haemolysis, transfusion and the consecutive expression of haem binding (such as haemopexin) or haem catabolic pathways (such as haem oxygenase) impair the ability of an organism to adapt, correlate with the prognosis and/or are strongly influenced by the surgical treatment concepts. Established treatment concepts of early causal and supportive therapy (damage control, antibiotic and fluid therapy) contribute to the reduction of mortality, depending on stringent implementation as part of Standard Operating Procedures (SOPs) and quality management. The paradigm shift in sepsis research offers an improved understanding of the underlying pathogenic factors within complex and heterogeneous patient groups, such as nosocomial sepsis following trauma. These novel approaches will allow developing new treatment strategies potentially contributing to a significant reduction in morbidity and mortality of trauma patients.Key messages1) According to the new paradigm, the ability to adapt to the pathogenic load associated with trauma and infection is crucial for an organism.2) Seriously injured or multiple trauma patients are predisposed for septic courses due to impaired adaptation mechanisms.3) Established treatment concepts of early causal and supportive therapy (damage control, antibiotic treatment, restrictive transfusion, and volume resuscitation) reduce mortality, in particular as part of SOPs and quality management strategies.4) Newly emerging treatment concepts that focus on the control of extracellular haem are promising, but require more evidence for translation into clinical practice.
2016年春季,更新后的脓毒症定义(Sepsis-3)对脓毒症的临床表现给出了新的解释。在此之前,脓毒症一直被理解为由感染引起的“全身炎症反应综合征(SIRS)”。对分子机制的深入理解以及对临床表现的广泛流行病学研究,将焦点从炎症反应转移到了导致器官功能障碍的多因素组织损伤上。这种范式转变突出了机体对感染反应失调导致的器官衰竭。新定义的核心是认识到脓毒症患者构成一个异质性群体,其临床表现需要不同的解释模式:例如,脓毒症不能仅用压倒性的炎症反应来充分解释,它还包括“免疫麻痹”这一重要模式。此外,脓毒症的严重程度反映了机体通过代谢变化和修复机制进行适应并减轻组织损伤的能力。与新的脓毒症定义范式一致,感染时的适应能力对机体至关重要。严重受伤或多发伤患者是特别危险的患者群体,因为脓毒症常因医院感染而使这些患者的病程复杂化。除了合并症、既往感染和年龄外,皮肤和肠道屏障的渗漏以及防御和修复机制受损使创伤患者易发生脓毒症病程。新的病理生理学见解表明,细胞外血红素的控制至关重要。溶血、输血以及血红素结合(如血红素结合蛋白)或血红素分解代谢途径(如血红素加氧酶)的连续表达会损害机体的适应能力,与预后相关和/或受到手术治疗理念强烈影响。既定早期病因和支持性治疗(损伤控制、抗生素和液体治疗)的治疗理念有助于降低死亡率,这取决于作为标准操作规程(SOP)和质量管理一部分的严格实施。脓毒症研究中的范式转变有助于更好地理解复杂异质性患者群体(如创伤后医院获得性脓毒症)中的潜在致病因素。这些新方法将有助于开发新的治疗策略,可能显著降低创伤患者的发病率和死亡率。
关键信息
1)根据新范式,机体适应与创伤和感染相关致病负荷 的能力至关重要。
2)严重受伤或多发伤患者因适应机制受损而易发生脓毒症病程。
3)既定早期病因和支持性治疗(损伤控制、抗生素治疗、限制性输血和容量复苏)的治疗理念可降低死亡率,特别是作为SOP和质量管理策略的一部分。
4)专注于细胞外血红素控制的新兴治疗理念很有前景,但需要更多证据才能转化为临床实践。