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Acta Clinica Croatica Jun 2022Sepsis is a life-threatening organ dysfunction caused by an unregulated response of a host. Septic shock is its most severe form. It is manifested by a drop in blood... (Review)
Review
Sepsis is a life-threatening organ dysfunction caused by an unregulated response of a host. Septic shock is its most severe form. It is manifested by a drop in blood pressure, which decreases tissue perfusion pressure, causing hypoxia that is characteristic of shock. Sepsis is still one of the leading causes of mortality worldwide. Its incidence has increased since the first consensus definitions were established in 1991. Raising sepsis awareness, its significance and the need for better treatment, has led to an improvement in in defining sepsis and the development of guidelines for its treatment. The first guidelines were published in 2004, the second 2008, the third 2013, the fourth 2016, and the last revised guidelines appeared in 2021. This paper will describe the previous and new definitions of sepsis and septic shock, the previous guidelines for the recognition and treatment, and the latest recommendations for treatment. Timely diagnosis is crucial for the outcomes for patients with sepsis and septic shock. The fact is that the sepsis care bundles have been modified to increasingly shorter time determinants, which emphasizes the importance of emergency physicians, who frequently first recognize and begin emergency treatment of septic patients.
Topics: Humans; Shock, Septic; Sepsis; Critical Care; Blood Pressure; Time Factors
PubMed: 36304809
DOI: 10.20471/acc.2022.61.s1.11 -
Military Medical Research Oct 2022Sepsis is a common complication of combat injuries and trauma, and is defined as a life-threatening organ dysfunction caused by a dysregulated host response to... (Review)
Review
Sepsis is a common complication of combat injuries and trauma, and is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. It is also one of the significant causes of death and increased health care costs in modern intensive care units. The use of antibiotics, fluid resuscitation, and organ support therapy have limited prognostic impact in patients with sepsis. Although its pathophysiology remains elusive, immunosuppression is now recognized as one of the major causes of septic death. Sepsis-induced immunosuppression is resulted from disruption of immune homeostasis. It is characterized by the release of anti-inflammatory cytokines, abnormal death of immune effector cells, hyperproliferation of immune suppressor cells, and expression of immune checkpoints. By targeting immunosuppression, especially with immune checkpoint inhibitors, preclinical studies have demonstrated the reversal of immunocyte dysfunctions and established host resistance. Here, we comprehensively discuss recent findings on the mechanisms, regulation and biomarkers of sepsis-induced immunosuppression and highlight their implications for developing effective strategies to treat patients with septic shock.
Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents; Biomarkers; Cytokines; Humans; Immune Checkpoint Inhibitors; Immunosuppression Therapy; Sepsis
PubMed: 36209190
DOI: 10.1186/s40779-022-00422-y -
EBioMedicine Dec 2022Management of the patient with sepsis comprises three key branches: control of the underlying infection, haemodynamic stabilization, and modulation of the host response.... (Review)
Review
Management of the patient with sepsis comprises three key branches: control of the underlying infection, haemodynamic stabilization, and modulation of the host response. Each aspect should be considered in all patients and, when relevant, managed at the same time. Infection control is applicable to all patients with sepsis and will include antibiotic therapy and often surgical intervention to remove an infectious source. Haemodynamic support involves fluid administration in all patients and vasoactive agents in patients with associated circulatory shock. Noradrenaline is the first choice vasopressor agent; inotropic agents, usually dobutamine, may be added in case of myocardial depression. No interventions directed at individual components of the host response to sepsis have yet been shown to improve outcomes, but glucocorticoids and vasopressin have a global impact on the response and can thus be considered in this category. A move toward more personalized treatment is needed across all three arms of sepsis management.
Topics: Humans; Shock, Septic; Sepsis; Vasoconstrictor Agents; Hemodynamics; Anti-Bacterial Agents
PubMed: 36470828
DOI: 10.1016/j.ebiom.2022.104318 -
Current Cardiology Reports May 2020To briefly review epidemiology and pathophysiology of SICM and provide a more extensive review of the data on diagnostic and management strategies. (Review)
Review
PURPOSE OF REVIEW
To briefly review epidemiology and pathophysiology of SICM and provide a more extensive review of the data on diagnostic and management strategies.
RECENT FINDINGS
SICM is likely underdiagnosed and that has mortality implications. Current evidence supports speckle tracking echocardiography to identify decreased contractility irrespective of left ventricular ejection fraction for the diagnosis of SICM. There continues to be a dearth of large clinical trials evaluating the treatment of SICM and current consensus focuses on supportive measures such as vasopressors and inotropes. Sepsis is a significant cause of mortality, and sepsis-induced cardiomyopathy has both prognostic and management implications for these patients. Individualized work-up and management of these patients is crucial to improving outcomes.
Topics: Cardiomyopathies; Echocardiography; Heart; Humans; Sepsis; Stroke Volume; Ventricular Dysfunction, Left; Ventricular Function, Left
PubMed: 32377972
DOI: 10.1007/s11886-020-01277-2 -
International Journal of Molecular... Oct 2019Sepsis is defined as "a life-threatening organ dysfunction caused by a host's dysfunctional response to infection". Although the treatment of sepsis has developed... (Review)
Review
Sepsis is defined as "a life-threatening organ dysfunction caused by a host's dysfunctional response to infection". Although the treatment of sepsis has developed rapidly in the past few years, sepsis incidence and mortality in clinical treatment is still climbing. Moreover, because of the diverse manifestations of sepsis, clinicians continue to face severe challenges in the diagnosis, treatment, and management of patients with sepsis. Here, we review the recent development in our understanding regarding the cellular pathogenesis and the target of clinical diagnosis of sepsis, with the goal of enhancing the current understanding of sepsis. The present state of research on targeted therapeutic drugs is also elaborated upon to provide information for the treatment of sepsis.
Topics: Autophagy; Biomarkers; Blood Coagulation Disorders; Endoplasmic Reticulum Stress; Humans; Incidence; Inflammation; Mitochondrial Diseases; Neuroendocrine Cells; Sepsis; Virulence
PubMed: 31671729
DOI: 10.3390/ijms20215376 -
Romanian Journal of Internal Medicine =... Sep 2020Sepsis is an overwhelming reaction to infection that comes with high morbidity and mortality, which requires urgent interventions in order to improve outcomes. Surviving... (Review)
Review
Sepsis is an overwhelming reaction to infection that comes with high morbidity and mortality, which requires urgent interventions in order to improve outcomes. Surviving Sepsis is an international campaign that aims to improve sepsis outcomes. The 2016 guideline modifies the previous definition of sepsis and proposes some specific diagnostic and therapeutic measures, such as the protocolized use of fluid resuscitation and antibiotics. We aim to summarize the main recommendations of the 2016 guideline that are relevant to the internist and evidence-base update them to the year 2020. In the current context, this review doesn't address patients affected by SARS-COV2 induced disease.
Topics: Anti-Bacterial Agents; Biomarkers; Fluid Therapy; Humans; Practice Guidelines as Topic; Sepsis; Vasoconstrictor Agents
PubMed: 32396142
DOI: 10.2478/rjim-2020-0012 -
Polish Archives of Internal Medicine Aug 2022The 2021 Surviving Sepsis Campaign Guidelines provided evidence-based recommendations for adult patients with sepsis and septic shock. This iteration of the guidelines... (Review)
Review
The 2021 Surviving Sepsis Campaign Guidelines provided evidence-based recommendations for adult patients with sepsis and septic shock. This iteration of the guidelines placed increased emphasis on a diverse, global perspective, as well as on the long-term sequelae of sepsis experienced by patients and their families. The guidelines encompassed the following sections: 1) screening and early treatment; 2) infection; 3) hemodynamic management; 4) ventilation; 5) additional therapies; and 6) goals of care and long-term outcomes. In this review, we provide a summary of key recommendations of interest to the practicing clinician, which are either novel or require a change in practice, as well as those for which the evidence has substantially evolved in the 5 years since the 2016 iteration of the Guidelines. Rather than reviewing the underlying evidence, we emphasize the practical aspects of interpretation, dissemination, and implementation of these recommendations in the clinical setting.
Topics: Adult; Humans; Sepsis; Shock, Septic
PubMed: 35791800
DOI: 10.20452/pamw.16290 -
Critical Care (London, England) Jan 2022A biomarker describes a measurable indicator of a patient's clinical condition that can be measured accurately and reproducibly. Biomarkers offer utility for diagnosis,... (Review)
Review
A biomarker describes a measurable indicator of a patient's clinical condition that can be measured accurately and reproducibly. Biomarkers offer utility for diagnosis, prognosis, early disease recognition, risk stratification, appropriate treatment (theranostics), and trial enrichment for patients with sepsis or suspected sepsis. In this narrative review, we aim to answer the question, "Do biomarkers in patients with sepsis or septic shock predict mortality, multiple organ dysfunction syndrome (MODS), or organ dysfunction?" We also discuss the role of pro- and anti-inflammatory biomarkers and biomarkers associated with intestinal permeability, endothelial injury, organ dysfunction, blood-brain barrier (BBB) breakdown, brain injury, and short and long-term mortality. For sepsis, a range of biomarkers is identified, including fluid phase pattern recognition molecules (PRMs), complement system, cytokines, chemokines, damage-associated molecular patterns (DAMPs), non-coding RNAs, miRNAs, cell membrane receptors, cell proteins, metabolites, and soluble receptors. We also provide an overview of immune response biomarkers that can help identify or differentiate between systemic inflammatory response syndrome (SIRS), sepsis, septic shock, and sepsis-associated encephalopathy. However, significant work is needed to identify the optimal combinations of biomarkers that can augment diagnosis, treatment, and good patient outcomes.
Topics: Biomarkers; Humans; Leukocytosis; Sepsis; Shock, Septic; Systemic Inflammatory Response Syndrome
PubMed: 34991675
DOI: 10.1186/s13054-021-03862-5 -
Critical Care (London, England) Jun 2020Sepsis biomarkers can have important diagnostic, therapeutic, and prognostic functions. In a previous review, we identified 3370 references reporting on 178 different... (Review)
Review
INTRODUCTION
Sepsis biomarkers can have important diagnostic, therapeutic, and prognostic functions. In a previous review, we identified 3370 references reporting on 178 different biomarkers related to sepsis. In the present review, we evaluate the progress in the research of sepsis biomarkers.
METHODS
Using the same methodology as in our previous review, we searched the PubMed database from 2009 until September 2019 using the terms "Biomarker" AND "Sepsis." There were no restrictions by age or language, and all studies, clinical and experimental, were included.
RESULTS
We retrieved a total of 5367 new references since our previous review. We identified 258 biomarkers, 80 of which were new compared to our previous list. The majority of biomarkers have been evaluated in fewer than 5 studies, with 81 (31%) being assessed in just a single study. Apart from studies of C-reactive protein (CRP) or procalcitonin (PCT), only 26 biomarkers have been assessed in clinical studies with more than 300 participants. Forty biomarkers have been compared to PCT and/or CRP for their diagnostic value; 9 were shown to have a better diagnostic value for sepsis than either or both of these biomarkers. Forty-four biomarkers have been evaluated for a role in answering a specific clinical question rather than for their general diagnostic or prognostic properties in sepsis.
CONCLUSIONS
The number of biomarkers being identified is still increasing although at a slower rate than in the past. Most of the biomarkers have not been well-studied; in particular, the clinical role of these biomarkers needs to be better evaluated.
Topics: Biomarkers; Humans; Sepsis; Standard of Care
PubMed: 32503670
DOI: 10.1186/s13054-020-02993-5 -
Signal Transduction and Targeted Therapy Nov 2021Sepsis is defined as life-threatening organ dysfunction caused by dysregulated host systemic inflammatory and immune response to infection. Over decades, advanced... (Review)
Review
Sepsis is defined as life-threatening organ dysfunction caused by dysregulated host systemic inflammatory and immune response to infection. Over decades, advanced understanding of host-microorganism interaction has gradually unmasked the genuine nature of sepsis, guiding toward new definition and novel therapeutic approaches. Diverse clinical manifestations and outcomes among infectious patients have suggested the heterogeneity of immunopathology, while systemic inflammatory responses and deteriorating organ function observed in critically ill patients imply the extensively hyperactivated cascades by the host defense system. From focusing on microorganism pathogenicity, research interests have turned toward the molecular basis of host responses. Though progress has been made regarding recognition and management of clinical sepsis, incidence and mortality rate remain high. Furthermore, clinical trials of therapeutics have failed to obtain promising results. As far as we know, there was no systematic review addressing sepsis-related molecular signaling pathways and intervention therapy in literature. Increasing studies have succeeded to confirm novel functions of involved signaling pathways and comment on efficacy of intervention therapies amid sepsis. However, few of these studies attempt to elucidate the underlining mechanism in progression of sepsis, while other failed to integrate preliminary findings and describe in a broader view. This review focuses on the important signaling pathways, potential molecular mechanism, and pathway-associated therapy in sepsis. Host-derived molecules interacting with activated cells possess pivotal role for sepsis pathogenesis by dynamic regulation of signaling pathways. Cross-talk and functions of these molecules are also discussed in detail. Lastly, potential novel therapeutic strategies precisely targeting on signaling pathways and molecules are mentioned.
Topics: Critical Illness; Humans; Sepsis; Signal Transduction
PubMed: 34824200
DOI: 10.1038/s41392-021-00816-9