Criteria For Sepsis Research Articles

Diagnostic and prognostic value of neutrophil CD64, IL-6, and PCT in ICU patients with sepsis

To explore the significance of neutrophil CD64 (nCD64), interleukin-6 (IL-6), and procalcitonin (PCT) alone and in combination in the diagnosis and prognosis evaluation of patients with sepsis. A prospective study was conducted. Adult patients admitted to the Western Intensive Care Unit (ICU) of Yantai Yuhuangding Hospital Affiliated to Medical College of Qingdao University from September 2020 to October 2021 were selected as subjects. The venous blood of the selected patients was collected within 6 hours of entering the ICU to measure the levels of nCD64, IL-6 and PCT. The levels of nCD64, IL-6 and PCT of septic patients were measured again on the 3rd and 7th days after admission to ICU. According to the diagnostic criteria of Sepsis-3, the patients were divided into sepsis group and non-sepsis group to evaluate the diagnostic value of nCD64, IL-6 and PCT in sepsis. The patients with sepsis were divided into sepsis group and septic shock group according to their condition on admission to ICU, and the evaluation value of three biomarkers for sepsis was evaluated. Sepsis patients were divided into the survival group and the death group according to survival after 28 days, and the relationship between the three biomarkers and the prognosis of sepsis was evaluated. Finally, 47 patients with sepsis, 43 patients with septic shock, and 41 patients without sepsis were enrolled. Seventy-six patients with sepsis survived and 14 died after 28 days. (1) The levels of nCD64, IL-6 and PCT on the first day of ICU admission in the sepsis group were significantly higher than those in the non-sepsis group [nCD64: 26.95 (14.05, 86.18) vs. 3.10 (2.55, 5.10), IL-6 (ng/L): 93.45 (52.73, 246.30) vs. 34.00 (9.76, 62.75), PCT (μg/L): 6.63 (0.57, 68.50) vs. 0.16 (0.08, 0.35), all P < 0.01]. The receiver operator characteristic curve (ROC curve) showed that the area under curve (AUC) of nCD64, IL-6 and PCT in the diagnosis of sepsis were 0.945, 0.792 and 0.888, respectively. The diagnostic value of nCD64 was the highest. When the cut-off value of nCD64 was 7.45, the sensitivity and specificity were 92.2% and 95.1% respectively. When nCD64, IL-6 and PCT were diagnosed in pairs or in combination, the combination of the three had the highest diagnostic performance, with AUC of 0.973, sensitivity of 92.2% and specificity of 97.6%. (2) The levels of nCD64, IL-6 and PCT in septic shock group were higher than those in sepsis group on the 1st, 3rd and 7th day after admission to ICU. ROC curve analysis showed that nCD64, IL-6 and PCT had some accuracy in evaluating the severity of sepsis on the 1st, 3rd and 7th day after entering ICU, with AUC ranging from 0.682 to 0.777. (3) The levels of nCD64, IL-6 and PCT in the death group were significantly higher than those in the survival group. Except for the nCD64 and PCT values on the first day after admission to the ICU, there were significant differences between the two groups in all indicators at other time points. ROC curve analysis showed that the AUC of nCD64, IL-6 and PCT predicting the prognosis of sepsis at each time point ranged from 0.600 to 0.981. The clearance rates of nCD64, IL-6 and PCT at 3 and 7 days after ICU admission were calculated by dividing the difference between the 1st and 3rd or 7th days after entering the ICU by the value at the 1st day. Logistic regression was used to analyze their predictive value for the prognosis of sepsis. The results showed that the clearance rates of nCD64, IL-6 and PCT on the 3rd and 7th day of ICU were protective factors for 28-day mortality in patients with sepsis, except the clearance rate of IL-6 on the 7th day. nCD64, IL-6 and PCT have good value as biomarkers for the diagnosis of sepsis. The diagnostic value of nCD64 is higher than that of PCT and IL-6. When they are used together, the diagnostic value is the highest. nCD64, IL-6 and PCT have certain value in evaluating the severity and predicting the prognosis of patients with sepsis. The higher the clearance rate of nCD64, IL-6 and PCT, the lower the 28-day mortality risk of patients with sepsis.

Operationalizing Appropriate Sepsis Definitions in Children Worldwide: Considerations for the Pediatric Sepsis Definition Taskforce.

Sepsis is a leading cause of global mortality in children, yet definitions for pediatric sepsis are outdated and lack global applicability and validity. In adults, the Sepsis-3 Definition Taskforce queried databases from high-income countries to develop and validate the criteria. The merit of this definition has been widely acknowledged; however, important considerations about less-resourced and more diverse settings pose challenges to its use globally. To improve applicability and relevance globally, the Pediatric Sepsis Definition Taskforce sought to develop a conceptual framework and rationale of the critical aspects and context-specific factors that must be considered for the optimal operationalization of future pediatric sepsis definitions. It is important to address challenges in developing a set of pediatric sepsis criteria which capture manifestations of illnesses with vastly different etiologies and underlying mechanisms. Ideal criteria need to be unambiguous, and capable of adapting to the different contexts in which children with suspected infections are present around the globe. Additionally, criteria need to facilitate early recognition and timely escalation of treatment to prevent progression and limit life-threatening organ dysfunction. To address these challenges, locally adaptable solutions are required, which permit individualized care based on available resources and the pretest probability of sepsis. This should facilitate affordable diagnostics which support risk stratification and prediction of likely treatment responses, and solutions for locally relevant outcome measures. For this purpose, global collaborative databases need to be established, using minimum variable datasets from routinely collected data. In summary, a "Think globally, act locally" approach is required.

Biomarker-Based Risk Stratification in Pediatric Sepsis From a Low-Middle Income Country.

Most biomarker studies of sepsis originate from high-income countries, whereas mortality risk is higher in low- and middle-income countries. The second version of the Pediatric Sepsis Biomarker Risk Model (PERSEVERE-II) has been validated in multiple North American PICUs for prognosis. Given differences in epidemiology, we assessed the performance of PERSEVERE-II in septic children from Pakistan, a low-middle income country. Due to uncertainty regarding how well PERSEVERE-II would perform, we also assessed the utility of other select biomarkers reflecting endotheliopathy, coagulopathy, and lung injury. Prospective cohort study. PICU in Aga Khan University Hospital in Karachi, Pakistan. Children (< 18 yr old) meeting pediatric modifications of adult Sepsis-3 criteria between November 2020 and February 2022 were eligible. None. Plasma was collected within 24 hours of admission and biomarkers quantified. The area under the receiver operating characteristic curve for PERSEVERE-II to discriminate 28-day mortality was determined. Additional biomarkers were compared between survivors and nonsurvivors and between subjects with and without acute respiratory distress syndrome. In 86 subjects (20 nonsurvivors, 23%), PERSEVERE-II discriminated mortality (area under the receiver operating characteristic curve, 0.83; 95% CI, 0.72-0.94) and stratified the cohort into low-, medium-, and high-risk of mortality. Biomarkers reflecting endotheliopathy (angiopoietin 2, intracellular adhesion molecule 1) increased across worsening risk strata. Angiopoietin 2, soluble thrombomodulin, and plasminogen activator inhibitor 1 were higher in nonsurvivors, and soluble receptor for advanced glycation end-products and surfactant protein D were higher in children meeting acute respiratory distress syndrome criteria. PERSEVERE-II performs well in septic children from Aga Khan University Hospital, representing the first validation of PERSEVERE-II in a low-middle income country. Patients possessed a biomarker profile comparable to that of sepsis from high-income countries, suggesting that biomarker-based enrichment strategies may be effective in this setting.

Unsupervised clustering identifies sub-phenotypes and reveals novel outcome predictors in patients with dialysis-requiring sepsis-associated acute kidney injury

Introduction Heterogeneity exists in sepsis-associated acute kidney injury (SA-AKI). This study aimed to perform unsupervised consensus clustering in critically ill patients with dialysis-requiring SA-AKI. Patients and Methods This prospective observational cohort study included all septic patients, defined by the Sepsis-3 criteria, with dialysis-requiring SA-AKI in surgical intensive care units in Taiwan between 2009 and 2018. We employed unsupervised consensus clustering based on 23 clinical variables upon initializing renal replacement therapy. Multivariate-adjusted Cox regression models and Fine–Gray sub-distribution hazard models were built to test associations between cluster memberships with mortality and being free of dialysis at 90 days after hospital discharge, respectively. Results Consensus clustering among 999 enrolled patients identified three sub-phenotypes characterized with distinct clinical manifestations upon renal replacement therapy initiation (n = 352, 396 and 251 in cluster 1, 2 and 3, respectively). They were followed for a median of 48 (interquartile range 9.5–128.5) days. Phenotypic cluster 1, featured by younger age, lower Charlson Comorbidity Index, higher baseline estimated glomerular filtration rate but with higher severity of acute illness was associated with an increased risk of death (adjusted hazard ratio of 3.05 [95% CI, 2.35–3.97]) and less probability to become free of dialysis (adjusted sub-distribution hazard ratio of 0.55 [95% CI, 0.38–0.8]) than cluster 3. By examining distinct features of the sub-phenotypes, we discovered that pre-dialysis hyperlactatemia ≥3.3 mmol/L was an independent outcome predictor. A clinical model developed to determine high-risk sub-phenotype 1 in this cohort (C-static 0.99) can identify a sub-phenotype with high in-hospital mortality risk (adjusted hazard ratio of 1.48 [95% CI, 1.25–1.74]) in another independent multi-centre SA-AKI cohort. Conclusions Our data-driven approach suggests sub-phenotypes with clinical relevance in dialysis-requiring SA-AKI and serves an outcome predictor. This strategy represents further development toward precision medicine in the definition of high-risk sub-phenotype in patients with SA-AKI.

End-to-End Sepsis Solution Incorporating Expert Telemedicine Consultation.

Introduction: Early detection and optimal resuscitation of critically ill sepsis patients may improve sepsis care delivery. The objective was to assess the feasibility of developing and implementing an end-to-end sepsis solution including early detection, monitoring, and teleconsultation. Methods: Prospective implementation of an end-to-end sepsis solution for potential sepsis patients presenting to a community hospital emergency department (ED) between 11 AM and 5 PM, Monday to Friday, during a 40-day period in 2019. Qualifying patients were compared with patients presenting at other times during the pilot screening period and to historic controls. Results: During the initial period, 203 patients met the screening criteria for potential sepsis; 77 patients (37.9%) had a primary diagnosis of sepsis, present on admission. Mean age was 60 ± 20 years; 50.7% were female; and 24 patients (11.8%) were primary sepsis, SEP-1 bundle eligible. Eighty of 203 (39.4%) had an initial lactate performed, mean, 2.7 ± 1.7 mmol/L. For the 24 primary sepsis, SEP-1 bundle eligible patients, 100% received antibiotics and intravenous fluid. Thirteen consults were performed on 12 patients; mean time from consult decision to beam in to the telemedicine robot was 7.3 ± 5.5 min; mean time from beam in to robot connection with the expert was 23.6 ± 13.2 s; mean consultation call time was 6.3 ± 4.3 min. Conclusions: In a convenience sample of patients with potential sepsis presenting to a community hospital ED, an end-to-end sepsis solution using early detection, tracking, and consultation was feasible and has the potential to improve sepsis detection and treatment.

SuPAR links a dysregulated immune response to tissue inflammation and sepsis-induced acute kidney injury.

Acute kidney injury (AKI) secondary to sepsis results in poor outcomes and conventional kidney function indicators lack diagnostic value. Soluble urokinase plasminogen activator receptor (suPAR) is an innate immune-derived molecule implicated in inflammatory organ damage. We characterized the diagnostic ability of longitudinal serum suPAR levels to discriminate severity and course of sepsis-induced AKI (SI-AKI) in 200 critically ill patients meeting Sepsis-3 criteria. The pathophysiologic relevance of varying suPAR levels in SI-AKI was explored in a polymicrobial sepsis model in WT, (s)uPAR-knockout, and transgenic suPAR-overexpressing mice. At all time points studied, suPAR provided a robust classification of SI-AKI disease severity, with improved prediction of renal replacement therapy (RRT) and mortality compared with established kidney biomarkers. Patients with suPAR levels of greater than 12.7 ng/mL were at highest risk for RRT or death, with an adjusted odds ratio of 7.48 (95% CI, 3.00-18.63). suPAR deficiency protected mice against SI-AKI. suPAR-overexpressing mice exhibited greater kidney damage and poorer survival through inflamed kidneys, accompanied by local upregulation of potent chemoattractants and pronounced kidney T cell infiltration. Hence, suPAR allows for an innate immune-derived and kidney function-independent staging of SI-AKI and offers improved longitudinal risk stratification. suPAR promotes T cell-based kidney inflammation, while suPAR deficiency improves SI-AKI.

Timing of vasopressin initiation and mortality in patients with septic shock: analysis of the MIMIC-III and MIMIC-IV databases

Backgroundvasopressin is commonly used as a second-line vasopressor for patients with septic shock, but the optimal timing of initiation is uncertain. This study was designed to investigate when vasopressin initiation may be beneficial for 28-day mortality in septic shock patients.MethodsThis was a retrospective observational cohort study from the MIMIC-III v1.4 and MIMIC-IV v2.0 databases. All adults diagnosed with septic shock according to Sepsis-3 criteria were included. Patients were stratified into two groups based on norepinephrine (NE) dose at the time of vasopressin initiation, defined as the low doses of NE group (NE<0.25 µg/kg/min) and the high doses of NE group (NE ≥ 0.25 µg/kg/min). The primary end‐point was 28‐day mortality after diagnosis of septic shock. The analysis involved propensity score matching (PSM), multivariable logistic regression, doubly robust estimation, the gradient boosted model, and an inverse probability‐weighting model.ResultsA total of 1817 eligible patients were included in our original cohort (613 in the low doses of NE group and 1204 in the high doses of NE group). After 1:1 PSM, 535 patients from each group with no difference in disease severity were included in the analysis. The results showed that vasopressin initiation at low doses of NE was associated with reduced 28-day mortality (odds ratio [OR] 0.660, 95% confidence interval [CI] 0.518–0.840, p < 0.001). Compared with patients in the high doses of NE group, patients in the low doses of NE group received significantly shorter duration of NE, with less intravenous fluid volume on the first day after initiation of vasopressin, more urine on the second day, and longer mechanical ventilation-free days and CRRT-free days. Nevertheless, there were no significant differences in hemodynamic response to vasopressin, duration of vasopressin, and ICU or hospital length of stay.ConclusionsAmong adults with septic shock, vasopressin initiation when low-dose NE was used was associated with an improvement in 28-day mortality.

Biology and Belonging.

Biology and Belonging.

Association between minimal decrease in platelet counts and outcomes in septic patients: a retrospective observational study

ObjectivesAlthough platelets have been linked to inflammatory development in sepsis, knowledge on their role as an indicator in sepsis treatment is scarce. Here, we investigated the association between time-dependent changes...

Editor’s Choice Articles for April

Editor’s Choice Articles for April

Influence of time from admission to norepinephrine administration and volume of fluids received on outcomes of patients meeting sepsis-3 criteria: a retrospective study using the MIMIC-IV database

ObjectivesVasopressors are a cornerstone in the management of sepsis, marked by distributive shock often unresponsive to fluid resuscitation. Prior research and clinician surveys have suggested that earlier usage of vasopressors...

Calprotectin as a Serodiagnostic Marker for Bacterial Sepsis

Introduction: Since sepsis is a major global health problem, a rapid and correct diagnosis and the initiation of therapy are essential to improve the patient consequences. This study aimed to assess the serum levels of calprotectin and a more widely used sepsis biomarker in the patients with bacterial sepsis (BS). Method: Subjects were classified into BS group with the patients who met the sepsis criteria at the beginning of the study and the control group. We investigated the concentrations of biomarkers in 300 blood samples collected at admission from all patients hospitalized in the Fatemeh Al-Zahra Hospital, Najafabad, Isfahan in April 2019 and April 2020. Results: The microbial etiology in the BS group was confirmed in 35 patients (100%). The most frequently cultivated pathogens were Escherichia coli (n=11). The serum concentrations of calprotectin and CRP were significantly higher in the patients with BS (n= 35) than in the healthy controls (n= 20). Conclusion: Our results suggest that the serum level of calprotectin could have the substantial added value to manage BS which is a reliable biomarker of BS.

The Diagnostic Value of Cerebrospinal Fluid Lactate for Detection of Sepsis in Community-Acquired Bacterial Meningitis.

Community-acquired bacterial meningitis conveys significant morbidity and mortality due to intracranial and systemic complications, and sepsis is a major contributor to the latter. While cerebrospinal fluid (CSF) analysis is essential in the diagnosis of bacterial meningitis, its predictive utility for detection of sepsis is unknown. We investigated the diagnostic performance of CSF parameters for sepsis defined by the Sepsis-3 criteria in a retrospective cohort of patients with community-acquired bacterial meningitis. Among 103 patients, 69.5% developed sepsis. CSF lactate was associated with sepsis with an odds ratio of 1.11 (p = 0.022), while CSF cell counts, glucose and protein levels were not (all p > 0.4). Employing the optimal cutoff of 8.2 mmol/L, elevated CSF lactate resulted in a sensitivity of 81.5% and specificity of 61.5% for sepsis. In exploratory analyses, CSF lactate was also associated with in-hospital mortality with an odds ratio of 1.21 (p = 0.011). Elevated CSF lactate might contribute to early diagnosis of sepsis as well as prognostication in patients with community-acquired bacterial meningitis.

Norepinephrine dose, lactate or heart rate: what impacts prognosis in sepsis and septic shock? Results from a prospective, monocentric registry

Objective The study comprehensively investigates the prognostic value of norepinephrine (NE) dose, lactate and heart rate in patients with sepsis and septic shock. Limited data regarding the prognostic value of NE dose, lactate and heart rate in patients meeting the sepsis-3 criteria is available. Methods Consecutive patients with sepsis and septic shock from 2019 to 2021 were included. The prognostic value of NE dose, lactate and heart rate was tested for 30-day all-cause mortality. Statistical analyses included univariable t-tests, Spearman’s correlations, C-statistics, Kaplan–Meier analyses, as well as one-factorial repeated measures analysis of variance (ANOVA) and Cox proportional regression analyses. Results 339 patients with sepsis or septic shock were included. With an area under the curve (AUC) of up to 0.638 and 0.685, NE dose and lactate revealed moderate prognostic accuracy for 30-day all-cause mortality, whereas heart rate was not associated with prognosis. Very high NE doses (i.e. > 1.0 mcg/kg/min) (HR = 2.938; 95% CI 1.933 − 4.464; p = .001) and lactate levels (i.e. ≥ 4 mmol/l) (HR = 2.963; 95% CI 2.095 − 4.191; p = .001) on admission were associated with highest risk of death. Finally, increasing NE doses and lactate levels from day 1 to 3 indicated increased risk of death, which was consistent after multivariable adjustment. Conclusion Both very high NE doses and lactate levels – but not heart rate – were associated with increased risk of 30-d all-cause mortality in patients with sepsis and septic shock.

Metagenomics by next-generation sequencing (mNGS) in the etiological characterization of neonatal and pediatric sepsis: A systematic review.

Pediatric and neonatal sepsis is one of the main causes of mortality and morbidity in these age groups. Accurate and early etiological identification is essential for guiding antibiotic treatment, improving survival, and reducing complications and sequelae. Currently, the identification is based on culture-dependent methods, which has many limitations for its use in clinical practice, and obtaining its results is delayed. Next-generation sequencing enables rapid, accurate, and unbiased identification of multiple microorganisms in biological samples at the same time. The objective of this study was to characterize the etiology of neonatal and pediatric sepsis by metagenomic techniques. A systematic review of the literature was carried out using the PRISMA-2020 guide. Observational, descriptive, and case report studies on pediatric patients were included, with a diagnostic evaluation by clinical criteria of sepsis based on the systemic inflammatory response, in sterile and non-sterile biofluid samples. The risk of bias assessment of the observational studies was carried out with the STROBE-metagenomics instrument and the CARE checklist for case reports. Five studies with a total of 462 patients were included. Due to the data obtained from the studies, it was not possible to perform a quantitative synthesis (meta-analysis). Based on the data from the included studies, the result identified that mNGS improves the etiological identification in neonatal and pediatric sepsis, especially in the context of negative cultures and in the identification of unusual microorganisms (bacteria that are difficult to grow in culture, viruses, fungi, and parasites). The number of investigations is currently limited, and the studies are at high risk of bias. Further research using this technology would have the potential to improve the rational use of antibiotics.

Predictors of outcomes in emergency department patients with suspected infections and without fulfillment of the sepsis criteria

BackgroundData on patient characteristics and determinants of serious outcomes for acutely admitted patients with infections who do not fulfill the sepsis criteria are sparse. The study aimed to characterize acutely admitted emergency department (ED) patients with infections and a composite outcome of in-hospital mortality or transfer to the intensive care unit without fulfilling the criteria for sepsis and to examine predictors of the composite outcome. MethodsThis was a secondary analysis of data from a prospective observational study of patients with suspected bacterial infection admitted to the ED between October 1, 2017 and March 31, 2018. A National Early Warning Score 2 (NEWS2) ≥ 5 within the first 4 h in the ED was assumed to represent a sepsis-like condition with a high risk for the composite endpoint. Patients who achieved the composite outcome were grouped according to fulfillment of the NEWS2 ≥ 5 criteria. We used logistic regression analysis to estimate the unadjusted and adjusted odds ratio (OR) for the composite endpoint among patients with either NEWS2 < 5 (NEWS2-) or NEWS2 ≥ 5 (NEWS2+). ResultsA total of 2055 patients with a median age of 73 years were included. Of these, 198 (9.6%) achieved the composite endpoint, including 59 (29.8%) NEWS2- and 139 (70.2%) NEWS2+ patients, respectively. Diabetes (OR 2.23;1.23–4.0), a Sequential Organ Failure Assessment (SOFA) score ≥ 2 (OR 2.57;1.37–4.79), and a Do-not-attempt-cardiopulmonary-resuscitation order (DNACPR) on admission (OR 3.70;1.75–7.79) were independent predictive variables for the composite endpoint in NEWS2- patients (goodness-of-fit test P = 0.291; area under the receiver operating characteristic curve for the model (AUROC) = 0.72). The regression model for NEWS2+ patients revealed that a SOFA score ≥ 2 (OR 2.79; 1.59–4.91), hypothermia (OR 2.48;1.30–4.75), and DNACPR order on admission were predictive variables for the composite endpoint (goodness-of-fit test P = 0.62; AUROC for the model = 0.70). ConclusionApproximately one-third of the patients with infections and serious outcomes during hospitalization did not meet the NEWS2 threshold for likely sepsis. Our study identified factors with independent predictive values for the development of serious outcomes that should be tested in future prediction models.

Prognostic performance of the REDS score, SOFA score, NEWS2 score, and the red-flag, NICE high-risk, and SIRS criteria to predict survival at 180 days, in emergency department patients admitted with suspected sepsis - An observational cohort study.

Patients admitted to hospital with sepsis are at persistent risk of poor outcome after discharge. Many tools are available to risk-stratify sepsis patients for in-hospital mortality. This study aimed to identify the best risk-stratification tool to prognosticate outcome 180 days after admission via the emergency department (ED) with suspected sepsis. A retrospective observational cohort study was performed of adult ED patients who were admitted after receiving intravenous antibiotics for the treatment of a suspected sepsis, between 1st March and 31st August 2019. The Risk-stratification of ED suspected Sepsis (REDS) score, SOFA score, Red-flag sepsis criteria met, NICE high-risk criteria met, the NEWS2 score and the SIRS criteria, were calculated for each patient. Death and survival at 180 days were noted. Patients were stratified in to high and low-risk groups as per accepted criteria for each risk-stratification tool. Kaplan-Meier curves were plotted for each tool and the log-rank test performed. The tools were compared using Cox-proportional hazard regression (CPHR). The tools were studied further in those without the following specified co-morbidities: Dementia, malignancy, Rockwood Frailty score of 6 or more, long-term oxygen therapy and previous do-not-resuscitate orders. Of the 1,057 patients studied 146 (13.8%) died at hospital discharge and 284 were known to have died within 180 days. Overall survival proportion was 74.4% at 180 days and 8.6% of the population was censored before 180 days. Only the REDS and SOFA scores identified less than 50% of the population as high-risk. All tools except the SIRS criteria, prognosticated for outcome at 180 days; Log-rank tests between high and low-risk groups were: REDS score p < 0.0001, SOFA score p < 0.0001, Red-flag criteria p = 0.001, NICE high-risk criteria p = 0.0001, NEWS2 score p = 0.003 and SIRS criteria p = 0.98. On CPHR, the REDS [Hazard ratio (HR) 2.54 (1.92-3.35)] and SOFA [HR 1.58 (1.24-2.03)] scores out-performed the other risk-stratification tools. In patients without the specified co-morbidities, only the REDS score and the SOFA score risk-stratified for outcome at 180 days. In this study, all the risk-stratification tools studied were found to prognosticate for outcome at 180 days, except the SIRS criteria. The REDS and SOFA scores outperformed the other tools.

Early adjunctive methylene blue in patients with septic shock: a randomized controlled trial

PurposeMethylene blue (MB) has been tested as a rescue therapy for patients with refractory septic shock. However, there is a lack of evidence on MB as an adjuvant therapy, its’ optimal timing, dosing and safety profile. We aimed to assess whether early adjunctive MB can reduce time to vasopressor discontinuation in patients with septic shock.MethodsIn this single-center randomized controlled trial, we assigned patients with septic shock according to Sepsis-3 criteria to MB or placebo. Primary outcome was time to vasopressor discontinuation at 28 days. Secondary outcomes included vasopressor-free days at 28 days, days on mechanical ventilator, length of stay in ICU and hospital, and mortality at 28 days.ResultsAmong 91 randomized patients, forty-five were assigned to MB and 46 to placebo. The MB group had a shorter time to vasopressor discontinuation (69 h [IQR 59–83] vs 94 h [IQR 74–141]; p < 0.001), one more day of vasopressor-free days at day 28 (p = 0.008), a shorter ICU length of stay by 1.5 days (p = 0.039) and shorter hospital length of stay by 2.7 days (p = 0.027) compared to patients in the control group. Days on mechanical ventilator and mortality were similar. There were no serious adverse effects related to MB administration.ConclusionIn patients with septic shock, MB initiated within 24 h reduced time to vasopressor discontinuation and increased vasopressor-free days at 28 days. It also reduced length of stay in ICU and hospital without adverse effects. Our study supports further research regarding MB in larger randomized clinical trials.Trial registration ClinicalTrials.gov registration number NCT04446871, June 25, 2020, retrospectively registered.

Patient characteristics in sepsis-related deaths: prevalence of advanced frailty, comorbidity, and age in a Norwegian hospital trust

ObjectiveTo examine the prevalence of advanced frailty, comorbidity, and age among sepsis-related deaths in an adult hospital population.MethodsRetrospective chart reviews of deceased adults within a Norwegian hospital trust, with a diagnosis of infection, over 2 years (2018–2019). The likelihood of sepsis-related death was evaluated by clinicians as sepsis-related, possibly sepsis-related, or not sepsis-related.ResultsOf 633 hospital deaths, 179 (28%) were sepsis-related, and 136 (21%) were possibly sepsis-related. Among these 315 patients whose deaths were sepsis-related or possibly sepsis-related, close to three in four patients (73%) were either 85 years or older, living with severe frailty (Clinical Frailty Scale, CFS, score of 7 or more), or an end-stage condition prior to the admission. Among the remaining 27%, 15% were either 80–84 years old, living with frailty corresponding to a CFS score of 6, or severe comorbidity, defined as 5 points or more on the Charlson Comorbidity Index (CCI). The last 12% constituted the presumably healthiest cluster, but in this group as well, the majority died with limitations of care due to their premorbid functional status and/ or comorbidity. Findings remained stable if the population was limited to sepsis-related deaths on clinicians’ reviews or those fulfilling the Sepsis-3 criteria.ConclusionsAdvanced frailty, comorbidity, and age were predominant in hospital fatalities where infection contributed to death, with or without sepsis. This is of importance when considering sepsis-related mortality in similar populations, the applicability of study results to everyday clinical work, and future study designs.

Validity of Eosinopenia in Bacterial Sepsis Patients Based on Sepsis-3 Consensus Criteria

Sepsis remains a major global healthcare problem, indicate as most frequently cause of morbidity and mortality worldwide. The last consensus of sepsis in 2016 defined sepsis as life threatening organ dysfunction caused by a dysregulated host response to infection. Dysfunction of organs can be represented by Sequential [Sepsis-Related] Organ Failure Assessment (SOFA) score. Score2 points or more consequent to the infection. Nowadays, there is ideal biomarkers of sepsis such as procalcitonin (PCT). However, the use of that markers in developing countries are hardly accessible. Eosinopenia is an prepossess biomarker because eosinophil count is always measured in daily practice and considered as a forgotten marker. The study purpose is to determine the validity of absolute eosinopenia in bacterial sepsis patients. This study is a descriptive observational study, collecting 118 patient’s medical record data from the past, diagnosed as sepsis using consensus criteria of Sepsis-3 between January 1st 2018–December 31st 2019. Eosinopenia validity test in sepsis patients showed 92.7% specificity and 71.4% sensitivity. This study also showed significant differences of absolute eosinophil count between positive sepsis patients and negative group with p value &lt;0.001. Eosinopenia had high specificity so it could be used as a marker of diagnostic in septic patients.