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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 -
Nanotheranostics 2024Though there have been developments in clinical care and management, early and accurate diagnosis and risk stratification are still bottlenecks in septic shock patients.... (Review)
Review
Though there have been developments in clinical care and management, early and accurate diagnosis and risk stratification are still bottlenecks in septic shock patients. Since septic shock is multifactorial with patient-specific underlying co-morbid conditions, early assessment of sepsis becomes challenging due to variable symptoms and clinical manifestations. Moreover, the treatment strategies are traditionally based on their progression and corresponding clinical symptoms, not personalized. The complex pathophysiology assures that a single biomarker cannot identify, stratify, and describe patients affected by septic shock. Traditional biomarkers like CRP, PCT, and cytokines are not sensitive and specific enough to be used entirely for a patient's diagnosis and prognosis. Thus, the need of the hour is a sensitive and specific biomarker after comprehensive analysis that may facilitate an early diagnosis, prognosis, and drug development. Integration of clinical data with metabolomics would provide means to understand the patient's condition, stratify patients better, and predict the clinical outcome.
Topics: Humans; Shock, Septic; Sepsis; Biomarkers; Prognosis; Cytokines
PubMed: 38577320
DOI: 10.7150/ntno.94071 -
The Canadian Veterinary Journal = La... Sep 2023The term "sepsis-induced cardiomyopathy" (SIC) is used to describe transient cardiac dysfunction in septic patients. However, there is no universally accepted definition... (Review)
Review
The term "sepsis-induced cardiomyopathy" (SIC) is used to describe transient cardiac dysfunction in septic patients. However, there is no universally accepted definition of SIC; a reduction in left ventricular ejection fraction (LVEF) is often used. In addition to systolic dysfunction, diastolic dysfunction is now recognized as an essential component of SIC. It can be emphasized that previous animal experiments played an essential role in revealing SIC and hemodynamic instability in sepsis and septic shock. The diagnostic and prognostic capabilities of echocardiography for the assessment of SIC have been extensively studied since its introduction into intensive care clinical practice. Recent studies in dogs, calves, and horses have shown that left and right ventricular systolic dysfunction, left ventricular diastolic dysfunction, and circulatory dysfunction can occur in sepsis, severe sepsis, and septic shock in animals. Echocardiographic variables have also shown that indices of left and right ventricular dysfunction and circulatory failure are valuable indicators of mortality in septic animals.
Topics: Animals; Cattle; Dogs; Horses; Shock, Septic; Stroke Volume; Ventricular Function, Left; Sepsis; Cardiomyopathies; Echocardiography; Cattle Diseases; Dog Diseases; Horse Diseases
PubMed: 37663026
DOI: No ID Found -
Clinical Chemistry and Laboratory... Apr 2024Sepsis is a life-threatening condition implicating an inadequate activation of the immune system. Platelets act as modulators and contributors to immune processes.... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Sepsis is a life-threatening condition implicating an inadequate activation of the immune system. Platelets act as modulators and contributors to immune processes. Indeed, altered platelet turnover, thrombotic events, and changes in thrombopoietin levels in systemic inflammation have been reported, but thrombopoietin-levels in sepsis and septic-shock have not yet been systematically evaluated. We therefore performed a meta-analysis of thrombopoietin (TPO)-levels in patients with sepsis.
METHODS
Two independent reviewers screened records and full-text articles for inclusion. Scientific databases were searched for studies examining thrombopoietin levels in adult sepsis and septic-shock patients until August 1st 2022.
RESULTS
Of 95 items screened, six studies met the inclusion criteria, including 598 subjects. Both sepsis and severe sepsis were associated with increased levels of thrombopoietin (sepsis vs. control: standardized mean difference 3.06, 95 % CI 1.35-4.77; Z=3.50, p=0.0005) (sepsis vs. severe sepsis: standardized mean difference -1.67, 95 % CI -2.46 to -0.88; Z=4.14, p<0.0001). TPO-levels did not show significant differences between severe sepsis and septic shock patients but differed between sepsis and inflammation-associated non-septic controls. Overall, high heterogeneity and low sample size could be noted.
CONCLUSIONS
Concluding, increased levels of thrombopoietin appear to be present both in sepsis and severe sepsis with high heterogeneity but thrombopoietin does not allow to differentiate between severe sepsis and septic-shock. TPO may potentially serve to differentiate sepsis from non-septic trauma and/or tissue damage related (systemic) inflammation. Usage of different assays and high heterogeneity demand standardization of methods and further large multicenter trials.
Topics: Adult; Humans; Shock, Septic; Thrombopoietin; Sepsis
PubMed: 38037809
DOI: 10.1515/cclm-2023-0792 -
Critical Care (London, England) Oct 2023Mega-dose sodium ascorbate (NaAscorbate) appears beneficial in experimental sepsis. However, its physiological effects in patients with septic shock are unknown. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Mega-dose sodium ascorbate (NaAscorbate) appears beneficial in experimental sepsis. However, its physiological effects in patients with septic shock are unknown.
METHODS
We conducted a pilot, single-dose, double-blind, randomized controlled trial. We enrolled patients with septic shock within 24 h of diagnosis. We randomly assigned them to receive a single mega-dose of NaAscorbate (30 g over 1 h followed by 30 g over 5 h) or placebo (vehicle). The primary outcome was the total 24 h urine output (UO) from the beginning of the study treatment. Secondary outcomes included the time course of the progressive cumulative UO, vasopressor dose, and sequential organ failure assessment (SOFA) score.
RESULTS
We enrolled 30 patients (15 patients in each arm). The mean (95% confidence interval) total 24-h UO was 2056 (1520-2593) ml with placebo and 2948 (2181-3715) ml with NaAscorbate (mean difference 891.5, 95% confidence interval [- 2.1 to 1785.2], P = 0.051). Moreover, the progressive cumulative UO was greater over time on linear mixed modelling with NaAscorbate (P < 0.001). Vasopressor dose and SOFA score changes over time showed faster reductions with NaAscorbate (P < 0.001 and P = 0.042). The sodium level, however, increased more over time with NaAscorbate (P < 0.001). There was no statistical difference in other clinical outcomes.
CONCLUSION
In patients with septic shock, mega-dose NaAscorbate did not significantly increase cumulative 24-h UO. However, it induced a significantly greater increase in UO and a greater reduction in vasopressor dose and SOFA score over time. One episode of hypernatremia and one of hemolysis were observed in the NaAscorbate group. These findings support further cautious investigation of this novel intervention. Trial registration Australian New Zealand Clinical Trial Registry (ACTRN12620000651987), Date registered June/5/2020.
Topics: Humans; Shock, Septic; Ascorbic Acid; Australia; Sepsis; Double-Blind Method; Vasoconstrictor Agents
PubMed: 37828547
DOI: 10.1186/s13054-023-04644-x -
Neurochemistry International Oct 2023Pyroptosis is a unique pro-inflammatory form of programmed cell death which plays a critical role in promoting the pathogenesis of multiple inflammatory and autoimmune...
AIMS
Pyroptosis is a unique pro-inflammatory form of programmed cell death which plays a critical role in promoting the pathogenesis of multiple inflammatory and autoimmune diseases. However, the current drug that is capable of inhibition pyroptosis has not been translated successfully in the clinic, suggesting a requirement for drug screening in depth.
METHODS
We screened more than 20,000 small molecules and found D359-0396 demonstrates a potent anti-pyroptosis and anti-inflammation effect in both mouse and human macrophage. In vivo, EAE (a mouse model of MS) and septic shock mouse model was used to investigate the protective effect of D359-0396. In vitro experiments we used LPS plus ATP/nigericin/MSU to induce pyroptosis in both mouse and human macrophage, and finally the anti-pyroptosis function of D359-0396 was assessed.
RESULTS
Our findings show that D359-0396 is well-tolerated without remarkable disruption of homeostasis. Mechanistically, while D359-0396 is capable of inhibiting pyroptosis and IL-1β release in macrophages, this process depends on the NLRP3-Casp1-GSDMD pathway rather than NF-κB, AIM2 or NLRC4 inflammasome signaling. Consistently, D359-0396 significantly suppresses the oligomerization of NLRP3, ASC, and the cleavage of GSDMD. In vivo, D359-0396 not only ameliorates the severity of EAE (a mouse model of MS), but also exhibits a better therapeutic effect than teriflunomide, the first-line drug of MS. Similarly, D359-0396 treatment also significantly protects mice from septic shock.
CONCLUSION
Our study identified D359-0396 as a novel small-molecule with potential application in NLRP3-associated diseases.
Topics: Humans; Mice; Animals; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Shock, Septic; NF-kappa B; Signal Transduction; Disease Models, Animal
PubMed: 37385448
DOI: 10.1016/j.neuint.2023.105565 -
Revista Espanola de Anestesiologia Y... Feb 2024Septic shock is a highly lethal and prevalent disease. Progressive circulatory dysfunction leads to tissue hypoperfusion and hypoxia, eventually evolving to multiorgan... (Review)
Review
Septic shock is a highly lethal and prevalent disease. Progressive circulatory dysfunction leads to tissue hypoperfusion and hypoxia, eventually evolving to multiorgan dysfunction and death. Prompt resuscitation may revert these pathogenic mechanisms, restoring oxygen delivery and organ function. High heterogeneity exists among the determinants of circulatory dysfunction in septic shock, and current algorithms provide a stepwise and standardized approach to conduct resuscitation. This review provides the pathophysiological and clinical rationale behind ANDROMEDA-SHOCK-2, an ongoing multicenter randomized controlled trial that aims to compare a personalized resuscitation strategy based on clinical phenotyping and peripheral perfusion assessment, versus standard of care, in early septic shock resuscitation.
Topics: Humans; Shock, Septic; Fluid Therapy; Resuscitation; Algorithms; Multicenter Studies as Topic
PubMed: 38244774
DOI: 10.1016/j.redare.2024.01.003 -
The American Journal of Emergency... Jun 2024Most children receive emergency care by general emergency physicians and not in designated children's hospitals. There are unique considerations in the care of children... (Review)
Review
Most children receive emergency care by general emergency physicians and not in designated children's hospitals. There are unique considerations in the care of children that differ from the care of adults. Many management principles can be extrapolated from adult studies, but the unique pathophysiology of pediatric disease requires specialized attention and management updates. This article highlights ten impactful articles from the year 2023 whose findings can improve the care of children in the Emergency Department (ED). These studies address pediatric resuscitation, traumatic arrest, septic shock, airway management, nailbed injuries, bronchiolitis, infant fever, cervical spine injuries, and cancer risk from radiation (Table 1). The findings in these articles have the potential to impact the evaluation and management of children (Table 2).
Topics: Humans; Pediatric Emergency Medicine; Emergency Service, Hospital; Child; Airway Management; Resuscitation; Shock, Septic; Bronchiolitis
PubMed: 38518545
DOI: 10.1016/j.ajem.2024.03.010 -
Journal of Intensive Care Medicine Oct 2023Bioimpedance may be a useful tool to guide fluid treatment and avoid organ dysfunction related to fluid overload. We examined the correlation between bioimpedance and... (Observational Study)
Observational Study
Bioimpedance may be a useful tool to guide fluid treatment and avoid organ dysfunction related to fluid overload. We examined the correlation between bioimpedance and organ dysfunction in patients with septic shock. Prospective observational study of adult intensive care unit patients fulfilling the sepsis-3 criteria. Bioimpedance was measured using a body composition monitor (BCM) and BioScan Touch i8 (MBS). We measured impedance at inclusion and after 24 h and reported the impedance, change in impedance, bioimpedance-derived fluid balance, and changes in bioimpedance-derived fluid balance. Organ markers on respiratory, circulatory, and kidney function and overall disease severity were ascertained on days 1-7. The effect of bioimpedance on the change in organ function was assessed by mixed effects linear models. We considered < .01 as significant. Forty-nine patients were included. None of the single baseline measurements or derived fluid balances were associated with the course of organ dysfunction. Changes in impedance were associated with the course of overall disease severity ( < .001; with MBS), and with changes in noradrenaline dose ( < .001; with MBS) and fluid balance ( < .001; with BCM). The changes in bioimpedance-derived fluid balance were associated with changes in noradrenaline dose ( < .001; with BCM), cumulative fluid balances ( < .001; with MBS), and lactate concentrations ( < .001; with BCM). Changes in bioimpedance were correlated with the duration of overall organ failure, circulatory failure, and fluid status. Single measurements of bioimpedance were not associated with any changes in organ dysfunction.
Topics: Adult; Humans; Shock, Septic; Multiple Organ Failure; Body Composition; Water-Electrolyte Imbalance; Norepinephrine
PubMed: 37186782
DOI: 10.1177/08850666231175819 -
Journal of Intensive Care Medicine Sep 2023The prevalence and its impact on mortality of sepsis-induced cardiomyopathy (SICM) remain controversial. In this systematic review and meta-analysis, we investigated... (Meta-Analysis)
Meta-Analysis Review
The prevalence and its impact on mortality of sepsis-induced cardiomyopathy (SICM) remain controversial. In this systematic review and meta-analysis, we investigated the prevalence and prognosis of SICM. We searched MEDLINE, Cochrane Central Register of Controlled Trials, and Embase. Titles and abstracts were evaluated based on the following criteria: (1) published in English, (2) randomized controlled trials, cohort studies, or cross-sectional studies, (3) ≥ 18 years with sepsis, (4) reporting the prevalence and/or comparison of short-term mortality between those with and without SICM, defined as the new-onset reduction in left ventricular ejection fraction (LVEF) within 72 h on admission or from the diagnosis of sepsis. The random-effect model was used for all analyses. This meta-analysis was registered at PROSPERO (CDR42022332896). Sixteen studies reported the prevalence of SICM and the pooled prevalence of SICM was 20% (95% confidence interval [CI], 16-25%; = 89.9%, P < 0.01). Eleven studies reported short-term mortality and SICM was associated with significantly higher short-term mortality (The pooled odds ratio: 2.30, 95% CI, 1.43-3.69; = 0%, P = 0.001). The prevalence of SICM was 20% in patients with sepsis, and the occurrence of SICM was associated with significantly higher short-term mortality.
Topics: Humans; Stroke Volume; Ventricular Function, Left; Prevalence; Cross-Sectional Studies; Sepsis; Cardiomyopathies; Prognosis; Shock, Septic
PubMed: 37272081
DOI: 10.1177/08850666231180526