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British Journal of Anaesthesia Dec 2016Sepsis is as a dysregulated systemic response to infection. Morbidity and mortality of the syndrome are very high worldwide. Recent definitions have redefined criteria... (Review)
Review
Sepsis is as a dysregulated systemic response to infection. Morbidity and mortality of the syndrome are very high worldwide. Recent definitions have redefined criteria for sepsis. The new definition (Sepsis-3) classifies sepsis as infection with organ dysfunction (the old 'severe sepsis'). Septic patients are at risk for secondary injuries, thus aggressive source control, resuscitation, and antibiotic therapy are the mainstays of management. Central to sepsis physiology is vasodilated shock. Many patients respond to i.v. fluid therapy. Pathophysiology also includes energy failure, or a cellular inability to oxidize fuel, and immune incompetence, often manifest by susceptibility to superinfections. Sepsis treatment is optimized by timely resuscitation and control of infection. Early recognition and resuscitation are associated with improved outcomes, although no single resuscitation end point is as good as overall patient assessment. Dynamic resuscitation metrics might be useful to avoid overinfusion of fluid therapies. Antibiotics should treat likely pathogens, with broader coverage for sicker patients (e.g. those with septic shock). Avoidance of iatrogenic injury, such as ventilator-induced lung injury from large tidal volumes, helps to prevent subsequent tissue damage and worsened systemic response. Single-agent therapies to block the systemic response have not fulfilled promise in sepsis, probably because part of the complex syndrome is adaptive. However, early aggressive care based on bundles is associated with improved outcomes. Research opportunities include understanding the role of neurological, endocrine, immune, and metabolic pathophysiology in the syndrome.
Topics: Anesthesia; Anesthesiologists; Cardiopulmonary Resuscitation; Critical Care; Humans; Sepsis; Shock, Septic
PubMed: 27940455
DOI: 10.1093/bja/aew333 -
Transactions of the Royal Society of... Nov 2017Recommendations for haemodynamic assessment and support in sepsis and septic shock in resource-limited settings are largely lacking. (Review)
Review
BACKGROUND
Recommendations for haemodynamic assessment and support in sepsis and septic shock in resource-limited settings are largely lacking.
METHODS
A task force of six international experts in critical care medicine, all of them members of the Global Intensive Care Working Group of the European Society of Intensive Care Medicine and with extensive bedside experience in resource-limited intensive care units, reviewed the literature and provided recommendations regarding haemodynamic assessment and support, keeping aspects of efficacy and effectiveness, availability and feasibility and affordability and safety in mind.
RESULTS
We suggest using capillary refill time, skin mottling scores and skin temperature gradients; suggest a passive leg raise test to guide fluid resuscitation; recommend crystalloid solutions as the initial fluid of choice; recommend initial fluid resuscitation with 30 ml/kg in the first 3 h, but with extreme caution in settings where there is a lack of mechanical ventilation; recommend against an early start of vasopressors; suggest starting a vasopressor in patients with persistent hypotension after initial fluid resuscitation with at least 30 ml/kg, but earlier when there is lack of vasopressors and mechanical ventilation; recommend using norepinephrine (noradrenaline) as a first-line vasopressor; suggest starting an inotrope with persistence of plasma lactate >2 mmol/L or persistence of skin mottling or prolonged capillary refill time when plasma lactate cannot be measured, and only after initial fluid resuscitation; suggest the use of dobutamine as a first-line inotrope; recommend administering vasopressors through a central venous line and suggest administering vasopressors and inotropes via a central venous line using a syringe or infusion pump when available.
CONCLUSION
Recommendations for haemodynamic assessment and support in sepsis and septic shock in resource-limited settings have been developed by a task force of six international experts in critical care medicine with extensive practical experience in resource-limited settings.
Topics: Critical Care; Developing Countries; Early Diagnosis; Evidence-Based Medicine; Fluid Therapy; Guidelines as Topic; Hemodynamics; Humans; International Cooperation; Sepsis; Shock, Septic
PubMed: 29438568
DOI: 10.1093/trstmh/try007 -
Minerva Pediatrica Apr 2015The pediatric sepsis syndrome remains a common cause of morbidity, mortality, and health care utilization costs worldwide. The initial resuscitation and management of... (Review)
Review
The pediatric sepsis syndrome remains a common cause of morbidity, mortality, and health care utilization costs worldwide. The initial resuscitation and management of pediatric sepsis is focused on 1) rapid recognition of abnormal tissue perfusion and restoration of adequate cardiovascular function; 2) eradication of the inciting invasive infection, including prompt administration of empiric broad-spectrum antimicrobial medications; and 3) supportive care of organ system dysfunction. Efforts to improve early and aggressive initial resuscitation and ongoing management strategies have improved outcomes in pediatric severe sepsis and septic shock, though many questions still remain as to the optimal therapeutic strategies for many patients. In this article, we will briefly review the definitions, epidemiology, clinical manifestations, and pathophysiology of sepsis and provide an extensive overview of both current and novel therapeutic strategies used to resuscitate and manage pediatric patients with severe sepsis and septic shock.
Topics: Age Factors; Child; Humans; Multiple Organ Failure; Resuscitation; Severity of Illness Index; Shock, Septic
PubMed: 25604591
DOI: No ID Found -
Six potential biomarkers in septic shock: a deep bioinformatics and prospective observational study.Frontiers in Immunology 2023Septic shock occurs when sepsis is related to severe hypotension and leads to a remarkable high number of deaths. The early diagnosis of septic shock is essential to... (Observational Study)
Observational Study
BACKGROUND
Septic shock occurs when sepsis is related to severe hypotension and leads to a remarkable high number of deaths. The early diagnosis of septic shock is essential to reduce mortality. High-quality biomarkers can be objectively measured and evaluated as indicators to accurately predict disease diagnosis. However, single-gene prediction efficiency is inadequate; therefore, we identified a risk-score model based on gene signature to elevate predictive efficiency.
METHODS
The gene expression profiles of GSE33118 and GSE26440 were downloaded from the Gene Expression Omnibus (GEO) database. These two datasets were merged, and the differentially expressed genes (DEGs) were identified using the limma package in R software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments of DEGs were performed. Subsequently, Lasso regression and Boruta feature selection algorithm were combined to identify the hub genes of septic shock. GSE9692 was then subjected to weighted gene co-expression network analysis (WGCNA) to identify the septic shock-related gene modules. Subsequently, the genes within such modules that matched with septic shock-related DEGs were identified as the hub genes of septic shock. To further understand the function and signaling pathways of hub genes, we performed gene set variation analysis (GSVA) and then used the CIBERSORT tool to analyze the immune cell infiltration pattern of diseases. The diagnostic value of hub genes in septic shock was determined using receiver operating characteristic (ROC) analysis and verified using quantitative PCR (qPCR) and Western blotting in our hospital patients with septic shock.
RESULTS
A total of 975 DEGs in the GSE33118 and GSE26440 databases were obtained, of which 30 DEGs were remarkably upregulated. With the use of Lasso regression and Boruta feature selection algorithm, six hub genes (, , , , , and ) with expression differences in septic shock were screened as potential diagnostic markers for septic shock among the significant DEGs and were further validated in the GSE9692 dataset. WGCNA was used to identify the co-expression modules and module-trait correlation. Enrichment analysis showed significant enrichment in the reactive oxygen species pathway, hypoxia, phosphatidylinositol 3-kinases (PI3K)/Protein Kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling, nuclear factor-κβ/tumor necrosis factor alpha (NF-κβ/TNF-α), and interleukin-6 (IL-6)/Janus Kinase (JAK)/Signal Transducers and Activators of Transcription 3 (STAT3) signaling pathways. The receiver operating characteristic curve (ROC) of these signature genes was 0.938, 0.914, 0.939, 0.956, 0.932, and 0.914, respectively. In the immune cell infiltration analysis, the infiltration of M0 macrophages, activated mast cells, neutrophils, CD8 T cells, and naive B cells was more significant in the septic shock group. In addition, higher expression levels of , and messenger RNA (mRNA) were observed in peripheral blood mononuclear cells (PBMCs) isolated from septic shock patients than from healthy donors. Higher expression levels of CD177 and MMP8 proteins were also observed in the PBMCs isolated from septic shock patients than from control participants.
CONCLUSIONS
, , , , , and were identified as hub genes, which were of considerable value in the early diagnosis of septic shock patients. These preliminary findings are of great significance for studying immune cell infiltration in the pathogenesis of septic shock, which should be further validated in clinical studies and basic studies.
Topics: Humans; Shock, Septic; Matrix Metalloproteinase 8; Leukocytes, Mononuclear; Phosphatidylinositol 3-Kinases; Biomarkers; Tumor Necrosis Factor-alpha; Computational Biology; Receptors, Cell Surface; Lectins, C-Type
PubMed: 37359526
DOI: 10.3389/fimmu.2023.1184700 -
Minerva Anestesiologica Nov 2015We present a review of the hemodynamic management of septic shock. Although substantial amount of evidence is present in this area, most key decisions on the management... (Review)
Review
We present a review of the hemodynamic management of septic shock. Although substantial amount of evidence is present in this area, most key decisions on the management of these patients remain dependent on physiological reasoning and on pathophysiological principles rather than randomized controlled trials. During primary (early) resuscitation, restoration of adequate arterial pressure and cardiac output using fluids and vasopressor and/or inotropic drugs is guided by basic hemodynamic monitoring and physical examination in the emergency department. When more advanced level of monitoring is present in these patients, i.e. during secondary resuscitation (later phase in the emergency department and in the ICU), hemodynamic management can be guided by more advanced measurements of the macrocirculation. Our understanding of the microcirculation in septic shock is limited and reliable therapeutic modalities to optimize it do not yet exist. No specific hemodynamic treatment strategy, be it medications including fluids, monitoring devices or treatment algorithms has yet been proved to improve outcome. Moreover, there is virtually no data on the optimal management of the resolution phase of septic shock. Despite these gaps in knowledge, the data from observational studies and trials suggests that mortality in septic shock has been generally decreasing during the last decade.
Topics: Fluid Therapy; Hemodynamics; Humans; Shock, Septic; Vasoconstrictor Agents
PubMed: 25369134
DOI: No ID Found -
Platelets Dec 2023Studies investigating the prognostic role of platelets commonly include critically ill patients, whereas data regarding the prognostic impact of platelet count in...
Studies investigating the prognostic role of platelets commonly include critically ill patients, whereas data regarding the prognostic impact of platelet count in patients admitted with sepsis and septic shock is limited. Therefore, the study investigates the prognostic role of platelet count in patients with sepsis and septic shock. Consecutive patients with sepsis and septic shock from 2019 to 2021 were included monocentrically. Blood samples were retrieved from the day of disease onset (day 1), days 2, 3, 5, 7 and 10. Firstly, the diagnostic value of platelet count was tested for septic shock compared to sepsis. Secondly, the prognostic value of platelet count was tested for 30-day all-cause mortality. Statistical analyses included univariable -test, Spearman's correlation, C-statistics, Kaplan-Meier analyses, as well as multivariable mixed analysis of variance (ANOVA), Cox proportional regression analyses and propensity score matching. A total of 358 patients with sepsis and septic shock were included with a median platelet count of 176 × 10/ml. The presence of thrombocytopenia (i.e. <150 × 10/ml) was associated with increased risk of 30-day mortality (HR = 1.409; 95% CI 1.057-1.878; = .019), which was still demonstrated after propensity score matching. During the course of sepsis, a nadir was observed on sepsis day 5 with a decrease in the mean platelet count by 21.5%. Especially serum lactate, mean arterial pressure and the presence of malignancies were found to predict platelet decline during the course of sepsis/septic shock. The presence of platelet decline >25% was associated with an increased risk of 30-day all-cause mortality (HR = 1.484; 95% CI 1.045-2.109; = .028). Following platelet decline, recovery was observed from day 5 to day 10 (mean increase 7.5%). However, platelet recovery was not found to be associated with 30-day all-cause mortality (HR = 1.072; 95% CI 0.567-2.026; = .832). In conclusion, both thrombocytopenia and platelet decline during the course of sepsis were associated with an increased risk of 30-day all-mortality in patients admitted with sepsis or septic shock.
Topics: Humans; Shock, Septic; Prognosis
PubMed: 36484263
DOI: 10.1080/09537104.2022.2131753 -
Virulence Jan 2014Morbidity and mortality from sepsis remains unacceptably high. Large variability in clinical practice, plus the increasing awareness that certain processes of care... (Review)
Review
Morbidity and mortality from sepsis remains unacceptably high. Large variability in clinical practice, plus the increasing awareness that certain processes of care associated with improved critical care outcomes, has led to the development of clinical practice guidelines in a variety of areas related to infection and sepsis. The Surviving Sepsis Guidelines for Management of Severe Sepsis and Septic Shock were first published in 2004, revised in 2008, and recently revised again and published in 2013. The first part of this manuscript is a summary of the 2013 guidelines with some editorial comment. The second part of the manuscript characterizes hospital based sepsis performance improvement programs and highlights the sepsis bundles from the Surviving Sepsis Campaign as a key component of such a program.
Topics: Anti-Bacterial Agents; Bacterial Infections; Biomarkers; Critical Care; Humans; Shock, Septic; Steroids; Treatment Outcome
PubMed: 24335487
DOI: 10.4161/viru.27409 -
Brazilian Journal of Anesthesiology... 2015Severe sepsis and septic shock represent a major healthcare challenge. Much of the improvement in mortality associated with septic shock is related to early recognition... (Review)
Review
Severe sepsis and septic shock represent a major healthcare challenge. Much of the improvement in mortality associated with septic shock is related to early recognition combined with timely fluid resuscitation and adequate antibiotics administration. The main goals of septic shock resuscitation include intravascular replenishment, maintenance of adequate perfusion pressure and oxygen delivery to tissues. To achieve those goals, fluid responsiveness evaluation and complementary interventions - i.e. vasopressors, inotropes and blood transfusion - may be necessary. This article is a literature review of the available evidence on the initial hemodynamic support of the septic shock patients presenting to the emergency room or to the intensive care unit and the main interventions available to reach those targets, focusing on fluid and vasopressor therapy, blood transfusion and inotrope administration.
Topics: Arterial Pressure; Blood Transfusion; Central Venous Pressure; Fluid Therapy; Hemodynamics; Humans; Lactic Acid; Oxygen; Resuscitation; Shock, Septic
PubMed: 26323739
DOI: 10.1016/j.bjane.2014.11.006 -
European Journal of Clinical... Apr 2016During the past decade, global human movement created a virtually "borderless world". Consequently, the developed world is facing "forgotten" and now imported infectious... (Review)
Review
During the past decade, global human movement created a virtually "borderless world". Consequently, the developed world is facing "forgotten" and now imported infectious diseases. Many infections are observed upon travel and migration, and the clinical spectrum is diverse, ranging from asymptomatic infection to severe septic shock. The severity of infection depends on the etiology and timeliness of diagnosis. While assessing the etiology of severe infection in travelers and migrants, it is important to acquire a detailed clinical history; geography, dates of travel, places visited, type of transportation, lay-overs and intermediate stops, potential exposure to exotic diseases, and activities that were undertaken during travelling and prophylaxis and vaccines either taken or not before travel are all important parameters. Tuberculosis, malaria, pneumonia, visceral leishmaniasis, enteric fever and hemorrhagic fever are the most common etiologies in severely infected travelers and migrants. The management of severe sepsis and septic shock in migrants and returning travelers requires a systematic approach in the evaluation of these patients based on travel history. Early and broad-spectrum therapy is recommended for the management of septic shock comprising broad spectrum antibiotics, source control, fluid therapy and hemodynamic support, corticosteroids, tight glycemic control, and organ support and monitoring. We here review the diagnostic and therapeutic routing of severely ill travelers and migrants, stratified by the nature of the infectious agents most often encountered among them.
Topics: Case Management; Critical Care; Humans; Shock, Septic; Transients and Migrants; Travel
PubMed: 26825315
DOI: 10.1007/s10096-016-2575-2 -
Critical Care (London, England) Feb 2024Septic shock typically requires the administration of vasopressors. Adrenergic agents remain the first choice, namely norepinephrine. However, their use to counteract... (Review)
Review
Septic shock typically requires the administration of vasopressors. Adrenergic agents remain the first choice, namely norepinephrine. However, their use to counteract life-threatening hypotension comes with potential adverse effects, so that non-adrenergic vasopressors may also be considered. The use of agents that act through different mechanisms may also provide an advantage. Nitric oxide (NO) is the main driver of the vasodilation that leads to hypotension in septic shock, so several agents have been tested to counteract its effects. The use of non-selective NO synthase inhibitors has been of questionable benefit. Methylene blue, an inhibitor of soluble guanylate cyclase, an important enzyme involved in the NO signaling pathway in the vascular smooth muscle cell, has also been proposed. However, more than 25 years since the first clinical evaluation of MB administration in septic shock, the safety and benefits of its use are still not fully established, and it should not be used routinely in clinical practice until further evidence of its efficacy is available.
Topics: Humans; Methylene Blue; Shock, Septic; Hypotension; Soluble Guanylyl Cyclase; Norepinephrine; Vasoconstrictor Agents
PubMed: 38365828
DOI: 10.1186/s13054-024-04839-w