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The Western Journal of Emergency... Feb 2021Most experts recommend norepinephrine as the first-line agent in septic shock. Our objective was to determine the effectiveness and safety of norepinephrine in patients... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Most experts recommend norepinephrine as the first-line agent in septic shock. Our objective was to determine the effectiveness and safety of norepinephrine in patients with septic shock.
METHODS
We searched the Cochrane Central Register of Controlled Trials and Epistemonikos, as well as MEDLINE from 1966 till August 2019. Screening of full texts, evaluation for eligibility, and data extraction were done by four independent reviewers. We estimated risk ratios (RR) and mean differences (MD) using a random-effects model with 95% confidence intervals (CI). The primary outcomes included the number of participants who achieved the target mean arterial pressure (MAP), time to achieve the target MAP, and number of participants with all-cause 28-day mortality. The secondary outcomes included the length of stay in the intensive care unit, length of hospital stay, incidence of arrhythmia and myocardial infarction, vasopressor-free days, and number of participants with all-cause 90-day mortality.
RESULTS
We identified 11 randomized controlled trials with a total of 4,803 participants. There was no difference in the number of participants who achieved the target MAP between those patients receiving norepinephrine and other vasopressors (RR 1.44; 95% CI, 0.32 to 6.54; P = 0.640; I = 94%; two trials, 116 participants). There was no significant difference in time to achieve the target MAP (MD -0.05; 95%, CI, -0.32 to 0.21; P = 0.690; I = 26%; two trials, 1763 participants) and all-cause 28-day mortality (RR 0.95; 95% CI, 0.89 to 1.02; P = 0.160; I = 0%; seven trials, 4,139 participants). Regarding the secondary outcome, norepinephrine may significantly reduce the incidence of arrhythmia as compared to other vasopressors (RR 0.64; 95% CI, 0.42 to 0.97; P = 0.030; I = 64%; six trials, 3974 participants). There was no difference in the incidence of myocardial infarction (RR 1.28; 95% CI, 0.79 to 2.09), vasopressor-free day (RR 0.46; 95% CI, -1.82 to 2.74) and all-cause 90-day mortality (RR 1.08; 95% CI, 0.96 to 1.21) between norepinephrine and vasopressors.
CONCLUSION
In minimizing the occurrence of an arrhythmia, norepinephrine is superior to other vasopressors, making it safe to be used in septic shock. However, there was insufficient evidence concerning mortality and achievement of the target MAP outcomes.
Topics: Humans; Intensive Care Units; Length of Stay; Norepinephrine; Shock, Septic; Vasoconstrictor Agents
PubMed: 33856300
DOI: 10.5811/westjem.2020.10.47825 -
Frontiers in Immunology 2022Early diagnosis of septic shock in children is critical for prognosis. This study committed to investigate the signature genes and their connection with immune cells in...
BACKGROUND
Early diagnosis of septic shock in children is critical for prognosis. This study committed to investigate the signature genes and their connection with immune cells in pediatric septic shock.
METHODS
We screened a dataset of children with septic shock from the GEO database and analyzed differentially expressed genes (DEGs). Functional enrichment analysis was performed for these DEGs. Weighted gene co-expression network analysis (WCGNA) was used to screen the key modules. Least absolute shrinkage and selection operator (LASSO) and random forest analysis were finally applied to identify the signature genes. Then gene set enrichment analysis (GSEA) was exerted to explore the signaling pathways related to the hub genes. And the immune cells infiltration was subsequently classified using CIBERSORT.
RESULTS
A total of 534 DEGs were screened from GSE26440. The data then was clustered into 17 modules WGCNA, which MEgrey module was significantly related to pediatric septic shock (cor=-0.62, <0.0001). LASSO and random forest algorithms were applied to select the signature genes, containing UPP1, S100A9, KIF1B, S100A12, SLC26A8. The receiver operating characteristic curve (ROC) of these signature genes was 0.965, 0.977, 0.984, 0.991 and 0.989, respectively, which were verified in the external dataset from GSE13904. GSEA analysis showed these signature genes involve in positively correlated fructose and mannose metabolism and starch and sucrose metabolism signaling pathway. CIBERSORT suggested these signature genes may participate in immune cells infiltration.
CONCLUSION
UPP1, S100A9, KIF1B, S100A12, SLC26A8 emerge remarkable diagnostic performance in pediatric septic shock and involved in immune cells infiltration.
Topics: Humans; Child; Shock, Septic; Gene Expression Profiling; S100A12 Protein; Prognosis; ROC Curve
PubMed: 36439140
DOI: 10.3389/fimmu.2022.1056750 -
International Journal of Molecular... Sep 2021Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to an infection; it carries a risk for mortality, considerably exceeding... (Review)
Review
Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to an infection; it carries a risk for mortality, considerably exceeding that of a mere infection. Sepsis is the leading cause for acute kidney injury (AKI) and the requirement for renal replacement therapy (RRT) in intensive care unit (ICU) patients. Almost every second critically ill patient with sepsis will develop AKI. In septic shock, the dysregulated host response to infectious pathogens leads to a cytokine storm with uncontrolled production and release of humoral proinflammatory mediators that evoke cellular toxicity and promote the development of organ dysfunction and increased mortality. In addition to treating AKI, RRT techniques can be employed for extracorporeal adsorption of inflammatory mediators using specifically developed adsorption membranes, hemoperfusion sorbent cartridges or columns; these techniques are intended to decrease the level and early deleterious effects of circulating proinflammatory cytokines and endotoxins during the first hours and days of septic shock treatment, in order to improve patient outcomes. Several methods and devices, such as high cut-off membranes, the Oxiris-AN69 membrane, CytoSorb and HA380 cytokine hemoadsorption, polymyxin B endotoxin adsorption, and plasmapheresis have been examined in small study series or are under evaluation as ways of improving patient outcomes in septic shock. However, to date, the data on actual outcome benefits have remained controversial, as discussed in this review.
Topics: Acute Kidney Injury; Animals; Cytokines; Humans; Inflammation Mediators; Kidney; Renal Replacement Therapy; Sepsis; Shock, Septic
PubMed: 34638575
DOI: 10.3390/ijms221910238 -
Ugeskrift For Laeger May 2020Toxic shock syndrome is a rare, life-threatening disease caused by Staphylococcus aureus or Streptococcus pyogenes. These bacteria are able to produce superantigens,... (Review)
Review
Toxic shock syndrome is a rare, life-threatening disease caused by Staphylococcus aureus or Streptococcus pyogenes. These bacteria are able to produce superantigens, which bypass normal antigen presentation and cause a clonal T-cell expansion and uncontrolled release of pro-inflammatory mediators, which results in severe multiple organ failure. Despite high morbidity and mortality, the disease is underdiagnosed. In order to reduce morbidity and mortality early diagnosis and treatment with a combination of beta-lactam antibiotics, clindamycin and intravenous immunoglobulin is essential, which is underlined in this review.
Topics: Humans; Shock, Septic; Staphylococcal Infections; Staphylococcus aureus; Streptococcal Infections; Streptococcus pyogenes; Superantigens
PubMed: 32400378
DOI: No ID Found -
Acta Bio-medica : Atenei Parmensis Jul 2022Septic shock is a main cause of morbidity and mortality in neonates. Septic shock evolves from compensated to uncompensated through 3 distinct phases. Prompt diagnosis... (Review)
Review
Septic shock is a main cause of morbidity and mortality in neonates. Septic shock evolves from compensated to uncompensated through 3 distinct phases. Prompt diagnosis is challenging, since neonatal septic shock may overlap with the physiological changes occurring at birth. The outcome of septic shock depends on a prompt recognition of symptoms and a strict adherence to cardiopulmonary resuscitation guidelines. Fluid administration plays a major role in the initial management of septic shock. If there is no response to volume filling, inotropes must be infused within one hour of onset (dopamine, dobutamine, adrenaline). Life-threatening infections require immediate and aggressive empiric use of antimicrobials. In the pediatric age, delay in antibiotic initiation for treating septic shock is associated with poor outcome and increased risk of mortality. There is a gap regarding first line interventions in neonatal septic shock. This review addresses initial interventions in the treatment of neonatal septic shock and discusses currently available evidences., These interventions may allow to improve the outcome if they are promptly carried out.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Child; Humans; Infant, Newborn; Resuscitation; Shock, Septic
PubMed: 35775767
DOI: 10.23750/abm.v93i3.12577 -
BMC Infectious Diseases Jun 2022Sepsis, a life-threatening organ dysfunction induced by infection, is a major public health problem. This study aimed to evaluate the frequency and mortality of sepsis,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Sepsis, a life-threatening organ dysfunction induced by infection, is a major public health problem. This study aimed to evaluate the frequency and mortality of sepsis, severe sepsis, and septic shock in China.
METHODS
We Searched MEDLINE, Embase, PubMed, and Cochrane Library from 1 January 1992 to 1 June 2020 for studies that reported on the frequency and mortality of sepsis, severe sepsis, and septic shock conducted in China. Random effects models were performed to estimate the pooled frequency and mortality of sepsis, severe sepsis, and septic shock.
RESULTS
Our search yielded 846 results, of which 29 studies were included in this review. The pooled frequency of sepsis was estimated at 33.6% (95% CI 25.9% to 41.3%, I = 99.2%; p < 0.001), and the pooled mortality of sepsis, severe sepsis and septic shock were 29.0% (95% CI 25.3%-32.8%, I = 92.1%; p = 0), 31.1% (95% CI 25.3% to 36.9%, I = 85.8%; p < 0.001) and 37.3% (95% CI 28.6%-46.0%, I = 93.5%; p < 0.001). There was significant heterogeneity between studies. With a small number of included studies and the changing definition of sepsis, trends in sepsis frequency and mortality were not sufficient for analysis. Epidemiological data on sepsis in the emergency department (ED) are severely lacking, and more research is urgently needed in this area is urgently needed.
CONCLUSIONS
Our findings indicated that the frequency and mortality of sepsis and septic shock in China were much higher than North America and Europe countries. Based on our results, an extremely high incidence and mortality of sepsis and septic shock in China's mainland requires more healthcare budget support. Epidemiological data on sepsis and septic shock in ED are severely lacking, and more research is urgently needed in this area. Trial registration This systematic review was conducted according to the statement of the preferred reporting items for systematic review (PROSPERO CRD42021243325) and the meta-analysis protocols (PRISMA-P).
Topics: Humans; China; Sepsis; Shock, Septic
PubMed: 35729526
DOI: 10.1186/s12879-022-07543-8 -
Chest Oct 2020Fluid and vasopressor management in septic shock remains controversial. In this randomized controlled trial, we evaluated the efficacy of dynamic measures (stroke volume... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Fluid and vasopressor management in septic shock remains controversial. In this randomized controlled trial, we evaluated the efficacy of dynamic measures (stroke volume change during passive leg raise) to guide resuscitation and improve patient outcome.
RESEARCH QUESTION
Will resuscitation that is guided by dynamic assessments of fluid responsiveness in patients with septic shock improve patient outcomes?
STUDY DESIGN AND METHODS
We conducted a prospective, multicenter, randomized clinical trial at 13 hospitals in the United States and United Kingdom. Patients presented to EDs with sepsis that was associated hypotension and anticipated ICU admission. Intervention arm patients were assessed for fluid responsiveness before clinically driven fluid bolus or increase in vasopressors occurred. The protocol included reassessment and therapy as indicated by the passive leg raise result. The control arm received usual care. The primary clinical outcome was positive fluid balance at 72 hours or ICU discharge, whichever occurred first.
RESULTS
In modified intent-to-treat analysis that included 83 intervention and 41 usual care eligible patients, fluid balance at 72 hours or ICU discharge was significantly lower (-1.37 L favoring the intervention arm; 0.65 ± 2.85 L intervention arm vs 2.02 ± 3.44 L usual care arm; P = .021. Fewer patients required renal replacement therapy (5.1% vs 17.5%; P = .04) or mechanical ventilation (17.7% vs 34.1%; P = .04) in the intervention arm compared with usual care. In the all-randomized intent-to-treat population (102 intervention, 48 usual care), there were no significant differences in safety signals.
INTERPRETATION
Physiologically informed fluid and vasopressor resuscitation with the use of the passive leg raise-induced stroke volume change to guide management of septic shock is safe and demonstrated lower net fluid balance and reductions in the risk of renal and respiratory failure. Dynamic assessments to guide fluid administration may improve outcomes for patients with septic shock compared with usual care.
CLINICAL TRIAL REGISTRATION
NCT02837731.
Topics: Aged; Combined Modality Therapy; Female; Fluid Therapy; Humans; Hypotension; Male; Middle Aged; Prospective Studies; Resuscitation; Sepsis; Shock, Septic; Treatment Outcome; Vasoconstrictor Agents
PubMed: 32353418
DOI: 10.1016/j.chest.2020.04.025 -
Molekuliarnaia Biologiia 2019An extensive network of regulation of systemic inflammation makes development of a reproducible experimental model of sepsis a complex task. There is no single mouse... (Review)
Review
An extensive network of regulation of systemic inflammation makes development of a reproducible experimental model of sepsis a complex task. There is no single mouse model that can capture all clinical aspects of this complicated pathology. However, a combination of existing approaches can go a long way towards analysis of specific mechanisms of sepsis development and to the design of novel therapeutic approaches. This review describes the popular mouse models of sepsis and septic shock, as well as their limitations and development strategies.
Topics: Animals; Disease Models, Animal; Inflammation; Mice; Sepsis; Shock, Septic
PubMed: 31661479
DOI: 10.1134/S0026898419050100 -
Gaceta Medica de Mexico 2020Sepsis is one of the main reasons for consultation at emergency departments.
INTRODUCTION
Sepsis is one of the main reasons for consultation at emergency departments.
OBJECTIVE
To identify the prevalence of sepsis in emergency departments of Mexico.
METHOD
Cross-sectional study with a 30-day follow-up of patients diagnosed with sepsis or septic shock; demographic variables, management and outcomes were analyzed.
RESULTS
In 68 emergency departments analyzed, 2379 patients were attended to, out of whom 307 had sepsis. The prevalence of sepsis was 12.9 %, and overall mortality was 16.93 %, which in the cases of sepsis was 9.39 %, and in those of septic shock, 65.85 %; no significant differences were identified in demographic variables or type of hospital. A significantly higher fluid balance was observed within the first three hours in those patients who died, as well as a lack of adherence to international resuscitation recommendations.
CONCLUSIONS
A high prevalence of sepsis was found in Mexican emergency departments. Mortality of patients with septic shock was similar and even higher than that internationally reported.
INTRODUCCIÓN
La sepsis es una de las principales causas de consulta en los servicios de urgencias médicas.
OBJETIVO
Identificar la prevalencia de la sepsis en servicios de urgencias médicas de México.
MÉTODO
Estudio transversal con seguimiento a 30 días de los pacientes con diagnóstico de sepsis o choque séptico; se analizaron las variables demográficas, el manejo y los desenlaces.
RESULTADOS
En 68 servicios de urgencias médicas analizados se atendió a 2379 pacientes, de los cuales 307 presentaron sepsis. La prevalencia de la sepsis fue de 12.9 %, con mortalidad global de 16.93 %, que en los casos de sepsis fue de 9.39 % y en los de choque séptico, de 65.85 %; no se identificaron diferencias significativas en las variables demográficas o tipo de hospital. Se observó balance hídrico alto en las primeras tres horas y falta de apego a las recomendaciones internacionales de reanimación superior en los pacientes que fallecieron.
CONCLUSIONES
Se encontró alta prevalencia de la sepsis en los servicios de urgencias médicas mexicanos. La mortalidad de los pacientes con choque séptico fue similar e, incluso, mayor a la reportada internacionalmente.
Topics: Cross-Sectional Studies; Emergency Service, Hospital; Female; Follow-Up Studies; Guideline Adherence; Humans; Male; Mexico; Middle Aged; Prevalence; Resuscitation; Sepsis; Severity of Illness Index; Shock, Septic
PubMed: 33877101
DOI: 10.24875/GMM.M21000492 -
Critical Care (London, England) May 2020Sepsis and septic shock remain drivers for mortality in critically ill patients. The heterogeneity of the syndrome hinders the generation of reproducible numbers on... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Sepsis and septic shock remain drivers for mortality in critically ill patients. The heterogeneity of the syndrome hinders the generation of reproducible numbers on mortality risks. Consequently, mortality rates range from 15 to 56%. We aimed to update and extend the existing knowledge from meta-analyses and estimate 30- and 90-day mortality rates for sepsis and septic shock separately, stratify rates by region and study type and assess mortality rates across different sequential organ failure assessment (SOFA) scores.
METHODS
We performed a systematic review of articles published in PubMed or in the Cochrane Database, between 2009 and 2019 in English language including interventional and observational studies. A meta-analysis of pooled 28/30- and 90-day mortality rated separately for sepsis and septic shock was done using a random-effects model. Time trends were assessed via Joinpoint methodology and for the assessment of mortality rate over different SOFA scores, and linear regression was applied.
RESULTS
Four thousand five hundred records were identified. After title/abstract screening, 783 articles were assessed in full text for eligibility. Of those, 170 studies were included. Average 30-day septic shock mortality was 34.7% (95% CI 32.6-36.9%), and 90-day septic shock mortality was 38.5% (95% CI 35.4-41.5%). Average 30-day sepsis mortality was 24.4% (95% CI 21.5-27.2%), and 90-day sepsis mortality was 32.2% (95% CI 27.0-37.5%). Estimated mortality rates from RCTs were below prospective and retrospective cohort studies. Rates varied between regions, with 30-day septic shock mortality being 33.7% (95% CI 31.5-35.9) in North America, 32.5% (95% CI 31.7-33.3) in Europe and 26.4% (95% CI 18.1-34.6) in Australia. A statistically significant decrease of 30-day septic shock mortality rate was found between 2009 and 2011, but not after 2011. Per 1-point increase of the average SOFA score, average mortality increased by 1.8-3.3%.
CONCLUSION
Trends of lower sepsis and continuous septic shock mortality rates over time and regional disparities indicate a remaining unmet need for improving sepsis management. Further research is needed to investigate how trends in the burden of disease influence mortality rates in sepsis and septic shock at 30- and 90-day mortality over time.
Topics: Australia; Europe; Humans; Mortality; North America; Sepsis; Shock, Septic
PubMed: 32430052
DOI: 10.1186/s13054-020-02950-2