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Medizinische Klinik, Intensivmedizin... Dec 2023Sepsis and septic shock, which are often caused by pneumonia, impact millions of people every year. Despite adequate antibiotic therapy, mortality remains high, up to... (Review)
Review
Sepsis and septic shock, which are often caused by pneumonia, impact millions of people every year. Despite adequate antibiotic therapy, mortality remains high, up to 45% in septic shock, which is characterized by an inappropriate, excessive immune response of the host. Moreover, critical illness-related corticosteroid insufficiency often coexists. Against this background, several trials and meta-analyses evaluated corticosteroid therapy as adjuvant therapy with heterogeneous results. Indeed, before 2000, high-dosage, short courses of corticosteroid treatment resulted in no benefit on mortality and a higher rate of adverse events. After 2000, thanks to a deeper understanding of the pathophysiology, low-dosage with longer courses of treatment were tested. With this regimen, a faster decrease in inflammation and faster resolution of shock, with a low rate of mild adverse events, was demonstrated although no clear effect on mortality was shown. To date, guidelines on sepsis and septic shock and guidelines on severe community-acquired pneumonia suggest corticosteroid use in selected patients. Furthermore, by utilizing latent class analysis, phenotypes of sepsis patients who benefit the most from corticosteroid treatment were recently identified. Future research should be guided by a precision medicine approach to identify adequate dosage and duration of corticosteroid treatment for appropriate patients. This article is freely available.
Topics: Humans; Shock, Septic; Adrenal Cortex Hormones; Sepsis; Community-Acquired Infections; Pneumonia
PubMed: 38051381
DOI: 10.1007/s00063-023-01093-w -
Burns : Journal of the International... Nov 2023The Surviving Sepsis Campaign was developed to improve outcomes for all patients with sepsis. Despite sepsis being the primary cause of death after thermal injury, burns...
INTRODUCTION
The Surviving Sepsis Campaign was developed to improve outcomes for all patients with sepsis. Despite sepsis being the primary cause of death after thermal injury, burns have always been excluded from the Surviving Sepsis efforts. To improve sepsis outcomes in burn patients, an international group of burn experts developed the Surviving Sepsis After Burn Campaign (SSABC) as a testable guideline to improve burn sepsis outcomes.
METHODS
The International Society for Burn Injuries (ISBI) reached out to regional or national burn organizations to recommend members to participate in the program. Two members of the ISBI developed specific "patient/population, intervention, comparison and outcome" (PICO) questions that paralleled the 2021 Surviving Sepsis Campaign [1]. SSABC participants were asked to search the current literature and rate its quality for each topic. At the Congress of the ISBI, in Guadalajara, Mexico, August 28, 2022, a majority of the participants met to create "statements" based on the literature. The "summary statements" were then sent to all members for comment with the hope of developing an 80% consensus. After four reviews, a consensus statement for each topic was created or "no consensus" was reported.
RESULTS
The committee developed sixty statements within fourteen topics that provide guidance for the early treatment of sepsis in burn patients. These statements should be used to improve the care of sepsis in burn patients. The statements should not be considered as "static" comments but should rather be used as guidelines for future testing of the best treatments for sepsis in burn patients. They should be updated on a regular basis.
CONCLUSION
Members of the burn community from the around the world have developed the Surviving Sepsis After Burn Campaign guidelines with the goal of improving the outcome of sepsis in burn patients.
Topics: Humans; Shock, Septic; Burns; Sepsis; Critical Care; Fluid Therapy
PubMed: 37839919
DOI: 10.1016/j.burns.2023.05.003 -
Intensive Care Medicine Mar 2024
Topics: Humans; Vasoconstriction; Shock, Septic
PubMed: 38358543
DOI: 10.1007/s00134-024-07332-8 -
Anesthesia and Analgesia Oct 2023Previous studies on the association between the timing of corticosteroid administration and mortality in septic shock focused only on short-term mortality and produced...
BACKGROUND
Previous studies on the association between the timing of corticosteroid administration and mortality in septic shock focused only on short-term mortality and produced conflicting results. We performed a retrospective review of a large administrative database of intensive care unit (ICU) patients to evaluate the association between the timing of hydrocortisone initiation and short- and long-term mortality in septic shock. We hypothesized that a longer duration between the first vasopressor use for sepsis and steroid initiation was associated with increased mortality.
METHODS
Data were extracted from the Medical Information Mart in the Intensive Care-IV database. We included adults who met Sepsis-3 definition for septic shock and received hydrocortisone. The exposure of interest was the time in hours from vasopressor use to hydrocortisone initiation (>12 as late and ≤12 as early). The primary outcome was 1-year mortality. Secondary outcomes included 28-day mortality, 90-day mortality, in-hospital mortality, and length of hospital stay. Cox proportional hazard models were used to estimate the association between exposure and mortality. Competing risk regression models were used to evaluate the association between exposure and length of hospital stay.
RESULTS
A total of 844 patients were included in this cohort: 553 in the early group and 291 in the late group. The median time to hydrocortisone initiation was 7 hours (interquartile range, 2.0-19.0 hours). After multivariable Cox proportional hazard analysis, we found that hydrocortisone initiation >12 hours after vasopressor use was associated with increased 1-year mortality when compared with initiation <12 hours (adjusted hazard ratio, 1.39; 95% confidence interval, 1.13-1.71; P = .002, E-value = 2.13). Hydrocortisone initiation >12 hours was also associated with increased 28-day, 90-day, and in-hospital mortality and prolonged length of hospital stay.
CONCLUSIONS
In patients with septic shock, initiating hydrocortisone >12 hours after vasopressor use was associated with an increased risk of both short-term and long-term mortality, and a prolonged length of hospital stay.
Topics: Adult; Humans; Shock, Septic; Hydrocortisone; Sepsis; Retrospective Studies; Hospital Mortality; Vasoconstrictor Agents; Intensive Care Units
PubMed: 37171987
DOI: 10.1213/ANE.0000000000006516 -
Critical Care (London, England) Jul 2023Albumin infusion is the primary therapeutic strategy for septic patients with liver cirrhosis. Although recent studies have investigated the efficacy of albumin in the...
BACKGROUND
Albumin infusion is the primary therapeutic strategy for septic patients with liver cirrhosis. Although recent studies have investigated the efficacy of albumin in the resuscitation stage of septic patients with liver cirrhosis, it remains unclear whether daily albumin administration can improve outcomes. Furthermore, the indications for initiating albumin therapy are not well defined.
METHODS
Septic patients with liver cirrhosis were obtained from the Medical Information Mart for Intensive Care (MIMIC-IV 2.0) database. Marginal structural Cox models were employed to investigate the association between daily albumin infusion and 28-day mortality. We also aimed to explore under what circumstances enrolled patients could benefit most from albumin administration, based on the clinical parameters collected on the day of albumin infusion, including serum albumin concentration, serum lactate concentration, mean arterial pressure (MAP), and vasopressor dosage.
RESULTS
A total of 2265 patients were included in the final analysis, of whom 1093 (48.3%) had received albumin treatment at least once. The overall 28-day mortality was 29.6%. After marginal structural modeling, daily albumin infusion was associated with a reduced risk of 28-day death (hazard ratio, 0.76; 95% CI 0.61-0.94). We found that patients benefit most from albumin infusion when initiated on the day of serum albumin concentration between 2.5 and 3.0 g/dL, serum lactate concentration greater than or equal to 2 mmol/L, MAP less than 60 mmHg, or vasopressor dosage between 0.2 and 0.3 mcg/kg/min (norepinephrine equivalent, NEE).
CONCLUSIONS
Albumin infusion is associated with a reduction in mortality in septic patients with liver cirrhosis under specific circumstances. Serum albumin concentration, serum lactate, MAP, and vasopressor dosage were found to be modifiers of treatment effectiveness and should be considered when deciding to initial albumin infusion.
Topics: Humans; Shock, Septic; Vasoconstrictor Agents; Lactic Acid; Liver Cirrhosis; Serum Albumin
PubMed: 37507790
DOI: 10.1186/s13054-023-04587-3 -
Shock (Augusta, Ga.) Nov 2023Background: Vasopressor plays a crucial role in septic shock. However, the time for vasopressor initiation remains controversial. We conducted a systematic review and... (Meta-Analysis)
Meta-Analysis
Background: Vasopressor plays a crucial role in septic shock. However, the time for vasopressor initiation remains controversial. We conducted a systematic review and meta-analysis to explore its initiation timing for septic shock patients. Methods: PubMed, Cochrane Library, Embase, and Web of Sciences were searched from inception to July 12, 2023, for relevant studies. Primary outcome was short-term mortality. Meta-analysis was performed using Stata 15.0. Results: Twenty-three studies were assessed, including 2 randomized controlled trials and 21 cohort studies. The early group resulted in lower short-term mortality than the late group (OR [95% CI] = 0.775 [0.673 to 0.893], P = 0.000, I2 = 67.8%). The significance existed in the norepinephrine and vasopressin in subgroup analysis. No significant difference was considered in the association between each hour's vasopressor delay and mortality (OR [95% CI] = 1.02 [0.99 to 1.051], P = 0.195, I2 = 57.5%). The early group had an earlier achievement of target MAP ( P < 0.001), shorter vasopressor use duration ( P < 0.001), lower serum lactate level at 24 h ( P = 0.003), lower incidence of kidney injury ( P = 0.001), renal replacement therapy use ( P = 0.022), and longer ventilation-free days to 28 days ( P < 0.001). Conclusions: Early initiation of vasopressor (1-6 h within septic shock onset) would be more beneficial to septic shock patients. The conclusion needs to be further validated by more well-designed randomized controlled trials.
Topics: Humans; Shock, Septic; Vasoconstrictor Agents; Norepinephrine; Cohort Studies; Renal Replacement Therapy
PubMed: 37695641
DOI: 10.1097/SHK.0000000000002214 -
Medicine Jul 2023Septic shock is a serious systemic disease with circulatory failure and abnormal cell metabolism caused by sepsis. However, the relationship between CD3D and CD247 and...
Septic shock is a serious systemic disease with circulatory failure and abnormal cell metabolism caused by sepsis. However, the relationship between CD3D and CD247 and septic shock remains unclear. The septic shock datasets GSE33118 and GSE142255 profiles were generated from the gene expression omnibus databases GPl570, GPl17586. Differentially expressed genes (DEGs) were screened and weighted gene co-expression network analysis was performed. The construction and analysis of protein-protein interaction (PPI) network, functional enrichment analysis, gene set enrichment analysis (GSEA) were performed. Gene expression heat map was drawn. Immune infiltration analysis was performed. Comparative toxicogenomics database (CTD) analysis were performed to find the disease most related to the core gene. Targets can was used to screen miRNAs regulating the hub DEGs. 467 DEGs were identified. According to the gene ontology analysis, they were mainly enriched in the regulation of immune response, cell activation, signaling receptor activity, enzyme binding. Kyoto encyclopedia of genes and genomes analysis showed that they were mainly enriched in the TCR signaling pathway, Fc epsilon RI signaling pathway. GSEA showed that the DEGs were mainly enriched in immune response regulation, cell activation, TCR signaling pathway, Fc epsilon RI signaling pathway. Positive regulation of Fc receptor signaling pathway, PID IL12 2 pathway, immune response was observed in go enrichment items in the enrichment items of metascape. PPI networks got 5 core genes. Gene expression heat map showed that 5 core genes (CD247, Lck, cd3e, cd3d, ITK) were lowly expressed in the sepsis shock samples and highly expressed in the normal samples. CTD analysis showed that 5 core genes (CD247, Lck, cd3e, cd3d, ITK) were found to be associated with hemorrhage and necrosis. Low expression of cd3d, CD247 was observed in septic shock, and the lower the level of cd3d, CD247, the worse the prognosis.
Topics: Humans; Shock, Septic; Gene Regulatory Networks; Protein Interaction Mapping; Receptors, IgE; Gene Expression Profiling; Sepsis; Receptors, Antigen, T-Cell; Computational Biology
PubMed: 37478215
DOI: 10.1097/MD.0000000000034295 -
Injury Aug 2023There is a paucity of research in the rates for sepsis and septic shock in the hip fracture population specifically, despite marked clinical and prognostic differences...
INTRODUCTION
There is a paucity of research in the rates for sepsis and septic shock in the hip fracture population specifically, despite marked clinical and prognostic differences between these conditions. The purpose of this study was to determine the incidence, risk factors, and mortality rates for sepsis and septic shock as well as evaluate potential infectious causes in the surgical hip fracture population.
METHODS
The ACS-NSQIP (2015-2019) was queried for patients who underwent hip fracture surgery. A backward elimination multivariate regression model was used to identify risk factors for sepsis and septic shock. Multivariate regression that controlled for preoperative variables and comorbidities was used to calculate the odds of 30-day mortality.
RESULTS
Of 86,438 patients included, 871 (1.0%) developed sepsis and 490 (0.6%) developed septic shock. Risk factors for both postoperative sepsis and septic shock were male gender, DM, COPD, dependent functional status, ASA class ≥3, anemia, and hypoalbuminemia. Unique risk factors for septic shock were CHF and ventilator dependence. The 30-day mortality rate was 4.8% in aseptic patients, 16.2% in patients with sepsis, and 40.8% in patients who developed septic shock (p < 0.001). Patients with sepsis (OR 2.87 [95% CI 2.37-3.48], p < 0.001) and septic shock (OR 11.27 [95% CI 9.26-13.72], p < 0.001) had increased odds of 30-day mortality compared to patients without postoperative septicemia. Infections that preceded a diagnosis of sepsis or septic shock included urinary tract infections (24.7%, 16.5%), pneumonia (17.6%, 30.8%), and surgical site infections (8.5%, 4.1%).
CONCLUSIONS
The incidence of sepsis and septic shock after hip fracture surgery was 1.0% and 0.6%, respectively. The 30-day mortality rate was 16.2% in patients with sepsis and 40.8% in patients with septic shock. Potentially modifiable risk factors for both sepsis and septic shock were anemia and hypoalbuminemia. Urinary tract infections, pneumonia, and surgical site infections preceded the majority of cases of sepsis and septic shock. Prevention, early identification, and successful treatment of sepsis and septic shock are paramount to lowering mortality after hip fracture surgery.
Topics: Humans; Male; Female; Shock, Septic; Surgical Wound Infection; Hypoalbuminemia; Sepsis; Hip Fractures; Risk Factors; Anemia; Pneumonia; Urinary Tract Infections; Retrospective Studies
PubMed: 37365091
DOI: 10.1016/j.injury.2023.05.064 -
International Journal of Molecular... Aug 2023Severe hemostatic disturbances and impaired fibrinolysis occur in sepsis. In the most serious cases, the dysregulation of fibrinolysis contributes to septic shock,... (Review)
Review
Severe hemostatic disturbances and impaired fibrinolysis occur in sepsis. In the most serious cases, the dysregulation of fibrinolysis contributes to septic shock, disseminated intravascular coagulation (DIC), and death. Therefore, an analysis of circulating concentrations of pro- and anti-fibrinolytic mediators could be a winning strategy in both the diagnosis and the treatment of sepsis. However, the optimal cutoff value, the timing of the measurements, and their combination with coagulation indicators should be further investigated. The purpose of this review is to summarize all relevant publications regarding the role of the main components of the plasminogen activation system (PAS) in the pathophysiology of sepsis. In addition, the clinical value of PAS-associated biomarkers in the diagnosis and the outcomes of patients with septic syndrome will be explored. In particular, experimental and clinical trials performed in emergency departments highlight the validity of soluble urokinase plasminogen activator receptor (suPAR) as a predictive and prognostic biomarker in patients with sepsis. The measurements of PAI-I may also be useful, as its increase is an early manifestation of sepsis and may precede the development of thrombocytopenia. The upcoming years will undoubtedly see progress in the use of PAS-associated laboratory parameters.
Topics: Humans; Plasminogen; Sepsis; Shock, Septic; Fibrinolysis; Serine Proteases; Biomarkers
PubMed: 37569751
DOI: 10.3390/ijms241512376 -
Medicine Oct 2023Vitamin C has been used as an adjuvant in the treatment of sepsis and septic shock; however, its role remains controversial. This study aimed to assess the effectiveness... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Vitamin C has been used as an adjuvant in the treatment of sepsis and septic shock; however, its role remains controversial. This study aimed to assess the effectiveness of intravenous high-dose vitamin C in sepsis and septic shock patients by meta-analysis.
METHODS
The PubMed, Embase, and Cochrane Library electronic databases were searched to identify relevant studies. The primary outcome was defined as the short-term all-cause mortality rate. Secondary outcomes included duration of vasoactive drug use, intensive care unit length of stay, sequential organ failure assessment scores up to 96 hours after treatment and 90-day mortality. Review Manager version 5.4 was used to perform the meta-analysis. Relative risk and mean differences (MD) with 95% confidence intervals were determined using fixed- or random-effects models.
RESULTS
Eight randomized controlled trials (RCTs) comprising 1394 patients were eligible for assessment. Overall, the pooled results showed that high-dose vitamin C decreased short-term all-cause mortality in patients with sepsis, but no significant differences were observed in patients with septic shock. Additionally, high-dose vitamin C was associated with decreased duration of vasoactive drug use in patients with sepsis, but not in patients with septic shock. However, it did not significantly affect the duration of intensive care unit stay in RCTs of patients with sepsis and septic shock. Additionally, it did not significantly affect sequential organ failure assessment scores 96 hours post-treatment or 90-day mortality.
CONCLUSION
These results suggest that intravenous high-dose vitamin C may improve outcomes in patients with sepsis, but do not benefit patients with septic shock. Further RCTs and other studies should be conducted to determine whether vitamin C should be recommended as an adjunctive sepsis treatment.
Topics: Humans; Shock, Septic; Randomized Controlled Trials as Topic; Sepsis; Intensive Care Units; Ascorbic Acid; Antineoplastic Agents
PubMed: 37861551
DOI: 10.1097/MD.0000000000035648