Sepsis: From Pathophysiology to Individualized Patient Care

Ildikó László, Domonkos Trásy, Zsolt Molnár, János Fazakas, Ildikó László, Domonkos Trásy, Zsolt Molnár, János Fazakas

Abstract

Sepsis has become a major health economic issue, with more patients dying in hospitals due to sepsis related complications compared to breast and colorectal cancer together. Despite extensive research in order to improve outcome in sepsis over the last few decades, results of large multicenter studies were by-and-large very disappointing. This fiasco can be explained by several factors, but one of the most important reasons is the uncertain definition of sepsis resulting in very heterogeneous patient populations, and the lack of understanding of pathophysiology, which is mainly based on the imbalance in the host-immune response. However, this heroic research work has not been in vain. Putting the results of positive and negative studies into context, we can now approach sepsis in a different concept, which may lead us to new perspectives in diagnostics and treatment. While decision making based on conventional sepsis definitions can inevitably lead to false judgment due to the heterogeneity of patients, new concepts based on currently gained knowledge in immunology may help to tailor assessment and treatment of these patients to their actual needs. Summarizing where we stand at present and what the future may hold are the purpose of this review.

Figures

Figure 1
Figure 1
The “sepsis-triangles”: pathomechanism and treatment. SIRS: systemic inflammatory response syndrome, I-R: ischemia-reperfusion, DO2: oxygen delivery, VO2: oxygen consumption, PAMP: pathogen-associated molecular patterns, DAMP: damage-associated molecular patterns, EC: extra corporeal, and IPPV: intermittent positive pressure ventilation.
Figure 2
Figure 2
The main pillars of systemic inflammatory response. PAMPs: pathogen-associated molecular pattern, DAMPs: damage-associated molecular pattern molecules, MBL: mannose-binding lectin, NOD protein: nucleotide-binding oligomerization domain protein, and NALP: a type a NOD like receptors. For explanation, see text.
Figure 3
Figure 3
Procalcitonin response to consequent infectious insults. During regulated inflammatory response the two phenotypes of macrophages, (M) the proinflammatory (M1) and anti-inflammatory (M2), are balanced. As time goes by due to a dysregulated response patients become immunoparalyzed; in other words, M2 overwhelms M1; hence, forces are shifted towards “new balance.” This is reflected by lower PCT peak levels after each new infectious insult, which can be of the same gravity clinically. For further explanation see text.

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Source: PubMed

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