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Sepsis: The evolution in definition, pathophysiology, and management.

ABSTRACT: There has been a significant evolution in the definition and management of sepsis over the last three decades. This is driven in part due to the advances made in our understanding of its pathophysiology. There is evidence to show that the manifestations of sepsis can no longer be attributed only to the infectious agent and the immune response it engenders, but also to significant alterations in coagulation, immunosuppression, and organ dysfunction. A revolutionary change in the way we manage sepsis has been the adoption of early goal-directed therapy. This involves the early identification of at-risk patients and prompt treatment with antibiotics, hemodynamic optimization, and appropriate supportive care. This has contributed significantly to the overall improved outcomes with sepsis. Investigation into clinically relevant biomarkers of sepsis are ongoing and have yet to yield effective results. Scoring systems such as the sequential organ failure assessment and Acute Physiology and Chronic Health Evaluation help risk-stratify patients with sepsis. Advances in precision medicine techniques and the development of targeted therapy directed at limiting the excesses of the inflammatory and coagulatory cascades offer potentially viable avenues for future research. This review summarizes the progress made in the diagnosis and management of sepsis over the past two decades and examines promising avenues for future research.

SUBMITTER: Gyawali B

PROVIDER: S-EPMC6429642 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Sepsis: The evolution in definition, pathophysiology, and management.

Gyawali Bishal B Ramakrishna Karan K Dhamoon Amit S AS

SAGE open medicine 20190321

There has been a significant evolution in the definition and management of sepsis over the last three decades. This is driven in part due to the advances made in our understanding of its pathophysiology. There is evidence to show that the manifestations of sepsis can no longer be attributed only to the infectious agent and the immune response it engenders, but also to significant alterations in coagulation, immunosuppression, and organ dysfunction. A revolutionary change in the way we manage sep ...[more]

PMID: 30915218

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Project description:BackgroundThe disruption of immune homeostasis after trauma is a major cause of post-traumatic organ dysfunction and/or sepsis. Recently, a variety of neutrophil phenotypes with distinct functions have been identified and suggested as involved in various clinical conditions. The association between neutrophil phenotypes and post-traumatic immunodeficiency has also been reported, yet the specific neutrophil phenotypes and their functional significance in post-traumatic sepsis have not been fully clarified. Therefore, we sought to investigate neutrophil phenotypic changes in a murine model, as these may hold prognostic value in post-traumatic sepsis.Materials and methodsThird-degree burns affecting 25% of the body surface area were used to establish trauma model, and sepsis was induced 24 h later through cecal ligation and puncture (CLP). The Burn/CLP post-traumatic sepsis model and the Sham/CLP control model were established to assess the immunological status after trauma. Histopathological evaluation was performed on the spleen, liver, kidneys, and lung tissues. Immunological evaluation included the assessment of neutrophil markers using mass cytometry as well as cytokine measurements in serum and ascitic fluid through multiplex analysis using LUMINEX®.ResultsThe Burn/CLP group had a lower survival rate than the Sham/CLP group. Histopathological examination revealed an impaired immune response and more advanced organ damage in the Burn/CLP group. Furthermore, the Burn/CLP group exhibited higher levels of transforming growth factor-beta 1 in the blood and generally lower levels of cytokines than the Sham/CLP group. CD11b, which is involved in neutrophil adhesion and migration, was highly expressed on neutrophils in the Burn/CLP group. The expression of CD172a, which is related to the inhibition of phagocytosis, was also upregulated on neutrophils in the Burn/CLP group. The expression of sialic acid-binding lg-like lectin F and CD68 also differed between the two groups.ConclusionDifferent neutrophil phenotypes were observed between Burn/CLP and Sham/CLP groups, suggesting that neutrophils are implicated in the immune imbalance following trauma. However, further studies are needed to prove the causal relationships between neutrophil phenotypes and outcomes, including survival rate and organ dysfunction.

Project description:ObjectiveTo determine the associations of demographic, clinical, laboratory, organ dysfunction, and illness severity variable values with: 1) sepsis, severe sepsis, or septic shock in children with infection and 2) multiple organ dysfunction or death in children with sepsis, severe sepsis, or septic shock.Data sourcesMEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched from January 1, 2004, and November 16, 2020.Study selectionCase-control studies, cohort studies, and randomized controlled trials in children greater than or equal to 37-week-old postconception to 18 years with suspected or confirmed infection, which included the terms "sepsis," "septicemia," or "septic shock" in the title or abstract.Data extractionStudy characteristics, patient demographics, clinical signs or interventions, laboratory values, organ dysfunction measures, and illness severity scores were extracted from eligible articles. Random-effects meta-analysis was performed.Data synthesisOne hundred and six studies met eligibility criteria of which 81 were included in the meta-analysis. Sixteen studies (9,629 patients) provided data for the sepsis, severe sepsis, or septic shock outcome and 71 studies (154,674 patients) for the mortality outcome. In children with infection, decreased level of consciousness and higher Pediatric Risk of Mortality scores were associated with sepsis/severe sepsis. In children with sepsis/severe sepsis/septic shock, chronic conditions, oncologic diagnosis, use of vasoactive/inotropic agents, mechanical ventilation, serum lactate, platelet count, fibrinogen, procalcitonin, multi-organ dysfunction syndrome, Pediatric Logistic Organ Dysfunction score, Pediatric Index of Mortality-3, and Pediatric Risk of Mortality score each demonstrated significant and consistent associations with mortality. Pooled mortality rates varied among high-, upper middle-, and lower middle-income countries for patients with sepsis, severe sepsis, and septic shock (p < 0.0001).ConclusionsStrong associations of several markers of organ dysfunction with the outcomes of interest among infected and septic children support their inclusion in the data validation phase of the Pediatric Sepsis Definition Taskforce.

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Sepsis: The evolution in definition, pathophysiology, and management.

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Sepsis: The evolution in definition, pathophysiology, and management.

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