Future Sepsis Research Articles

Sepsis Biomarkers: Advancements and Clinical Applications-A Narrative Review.

Sepsis is now defined as a life-threatening syndrome of organ dysfunction triggered by a dysregulated host response to infection, posing significant challenges in critical care. The main objective of this review is to evaluate the potential of emerging biomarkers for early diagnosis and accurate prognosis in sepsis management, which are pivotal for enhancing patient outcomes. Despite advances in supportive care, traditional biomarkers like C-reactive protein and procalcitonin have limitations, and recent studies have identified novel biomarkers with increased sensitivity and specificity, including circular RNAs, HOXA distal transcript antisense RNA, microRNA-486-5p, protein C, triiodothyronine, and prokineticin 2. These emerging biomarkers hold promising potential for the early detection and prognostication of sepsis. They play a crucial role not only in diagnosis but also in guiding antibiotic therapy and evaluating treatment effectiveness. The introduction of point-of-care testing technologies has brought about a paradigm shift in biomarker application, enabling swift and real-time patient evaluation. Despite these advancements, challenges persist, notably concerning biomarker variability and the lack of standardized thresholds. This review summarizes the latest advancements in sepsis biomarker research, spotlighting the progress and clinical implications. It emphasizes the significance of multi-biomarker strategies and the feasibility of personalized medicine in sepsis management. Further verification of biomarkers on a large scale and their integration into clinical practice are advocated to maximize their efficacy in future sepsis treatment.

Combining ulinastatin with TIENAM improves the outcome of sepsis induced by cecal ligation and puncture in mice by reducing inflammation and regulating immune responses

Despite the high mortality associated with sepsis, effective and targeted treatments remain scarce. The use of conventional antibiotics such as TIENAM (imipenem and cilastatin sodium for injection, TIE) is challenging because of the increasing bacterial resistance, which diminishes their efficacy and leads to adverse effects. Our previous studies demonstrated that ulinastatin (UTI) exerts a therapeutic impact on sepsis by reducing systemic inflammation and modulating immune responses. In this study, we examined the possibility of administering UTI and TIE after inducing sepsis in a mouse model using cecal ligation and puncture (CLP). We assessed the rates of survival, levels of inflammatory cytokines, the extent of tissue damage, populations of immune cells, microbiota in ascites, and important signaling pathways. The combination of UTI and TIE significantly improved survival rates and reduced inflammation and bacterial load in septic mice, indicating potent antimicrobial properties. Notably, the survival rates of UTI+TIE-treated mice increased from 10 % to 75 % within 168 h compared to those of mice that were subjected to CLP. The dual treatment successfully regulated the levels of inflammatory indicators (interleukin [IL]-6, IL-1β, and tumor necrosis factor [TNF]-α) and immune cell numbers by reducing B cells, natural killer cells, and TNFR2+ Treg cells and increasing CD8+ T cells. Additionally, the combination of UTI and TIE alleviated tissue damage, reduced bacterial load in the peritoneal cavity, and suppressed the NF-κB signaling pathway. Our findings indicate that UTI and TIE combination therapy can significantly enhance sepsis outcomes by reducing inflammation and boosting the immune system. The results offer a promising therapeutic approach for future sepsis treatment.

Informative Subtyping of Patients with Sepsis.

Sepsis pathobiology is complex. Heterogeneity refers to the clinical and biological variation within sepsis cohorts. Sepsis subtypes refer to subpopulations within sepsis cohorts derived based on these observable variations and latent features. The overarching goal of such endeavors is to enable precision immunomodulation. However, we are yet to identify immune endotypes of sepsis to achieve this goal. The sepsis subtyping field is just starting to take shape. The current subtypes in the literature do not have a core set of shared features between studies. Thus, in this narrative review, we reason that there is a need to a priori state the purpose of sepsis subtyping and minimum set of features that would be required to achieve the goal of precision immunomodulation for future sepsis.

Dysregulation of Host-Pathogen Interactions in Sepsis: Host-Related Factors.

Sepsis stands as a prominent contributor to sickness and death on a global scale. The most current consensus definition characterizes sepsis as a life-threatening organ dysfunction stemming from an imbalanced host response to infection. This definition does not capture the intricate array of immune processes at play in sepsis, marked by simultaneous states of heightened inflammation and immune suppression. This overview delves into the immune-related processes of sepsis, elaborating about mechanisms involved in hyperinflammation and immune suppression. Moreover, we discuss stratification of patients with sepsis based on their immune profiles and how this could impact future sepsis management.

Analysis of the factors that contributed to the passage of Rory's regulations using the 3I + E framework: Implications for future sepsis policy

Analysis of the factors that contributed to the passage of Rory's regulations using the 3I + E framework: Implications for future sepsis policy

Improvement in ICU Mortality From Sepsis Associated With Recuperation From Septic Multiple-Organ Failure: A Retrospective, Single-Center, Cohort Study.

Although mortality due to sepsis has decreased in recent decades, there are few studies on the timing of death during ICU stay. Characteristics of patients related to changes over the years of ICU death and changes in the timing of ICU death will provide new insights for future sepsis management. This was a single-center, retrospective study. Patients admitted to the ICU for sepsis between 2005 and 2019 were included in the study. The study period was divided into three five-year intervals, and the timing of death in the ICU was divided into early-stage (1-3 ICU days), mid-stage (4-14 ICU days), and late-stage (15 or more ICU days). Patient characteristics related to ICU death at three five-year intervals and the timing of death were evaluated. ICU mortality for sepsis has decreased over time (2005-2009, 30.2%; 2010-2014, 21.0%; 2015-2019, 12.1%; p<0.01). In the timing of death, only mid-stage mortality decreased. Multiple-organ failure (OR, 4.53; 95% CI, 2.79-7.48) and hematological malignancies (OR, 2.48; 95% CI, 1.19-5.07) were associated with ICU mortality over entire study periods. Only multiple-organ failure was associated with ICU mortality at the five-year intervals (OR, 5.94; 95% CI, 2.73-13.7 for 2005-2009; OR, 4.01; 95% CI, 1.82-9.31 for 2010-2014; OR, 2.58; 95% CI, 1.05-6.59 for 2015-2019). Mid-stage mortality of multiple-organ failure decreased (2005-2009, 12.8%; 2010-2014, 7.6%; 2015-2019, 1.6%; p=0.02). However, early- and late-stage mortality of multiple-organ failure did not change. Improvement in mid-stage mortality in septic patients with multiple-organ failure can contribute to the improvement of overall ICU mortality in patients with sepsis.

Sepsis policy, guidelines and standards in Canada: a jurisdictional scoping review protocol

IntroductionTo our knowledge, this study is the first to identify and describe current sepsis policies, clinical practice guidelines, and health professional training standards in Canada to inform evidence-based policy recommendations.Methods...

Development of macrophage-associated genes prognostic signature predicts clinical outcome and immune infiltration for sepsis

Sepsis is a major global health problem, causing a significant burden of disease and death worldwide. Risk stratification of sepsis patients, identification of severe patients and timely initiation of treatment can effectively improve the prognosis of sepsis patients. We procured gene expression datasets for sepsis (GSE54514, GSE65682, GSE95233) from the Gene Expression Omnibus and performed normalization to mitigate batch effects. Subsequently, we applied weighted gene co-expression network analysis to categorize genes into modules that exhibit correlation with macrophage activity. To pinpoint macrophage-associated genes (MAAGs), we executed differential expression analysis and single sample gene set enrichment analysis. We then established a prognostic model derived from four MAAGs that were significantly differentially expressed. Functional enrichment analysis and immune infiltration assessments were instrumental in deciphering the biological mechanisms involved. Furthermore, we employed principal component analysis and conducted survival outcome analyses to delineate molecular subgroups within sepsis. Four novel MAAGs—CD160, CX3CR1, DENND2D, and FAM43A—were validated and used to create a prognostic model. Subgroup classification revealed distinct molecular profiles and a correlation with 28-day survival outcomes. The MAAGs risk score was developed through univariate Cox, LASSO, and multivariate Cox analyses to predict patient prognosis. Validation of the risk score upheld its prognostic significance. Functional enrichment implicated ribonucleoprotein complex biogenesis, mitochondrial matrix, and transcription coregulator activity in sepsis, with an immune infiltration analysis indicating an association between MAAGs risk score and immune cell populations. The four MAAGs exhibited strong diagnostic capabilities for sepsis. The research successfully developed a MAAG-based prognostic model for sepsis, demonstrating that such genes can significantly stratify risk and reflect immune status. Although in-depth mechanistic studies are needed, these findings propose novel targets for therapy and provide a foundation for future precise clinical sepsis management.

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.

Pathophysiology of sepsis

Up to now, sepsis is one of the most threatening diseases and its therapy remains challenging. Sepsis is currently defined as a severely dysregulated immune response to an infection resulting in organ dysfunction. The pathophysiology is mainly driven by exogenous PAMPs ("pathogen-associated molecular patterns") and endogenous DAMPs ("damage-associated molecular patterns"), which can activate PRRs ("pattern recognition receptors") on different cell types (mainly immune cells), leading to the initiation of manifold downstream pathways and a perpetuation of patients' immune response. Sepsis is neither an exclusive pro- nor an anti-inflammatory disease: both processes take place in parallel, resulting in an individual immunologic disease state depending on the severity of each component at different time points. Septic shock is a complex disorder of the macro- and microcirculation, provoking a severe lack of oxygenation further aggravating sepsis defining organ dysfunctions. An in-depth knowledge of the heterogeneity and the time-dependency of the septic immunopathology will be essential for the design of future sepsis trials and therapy planning in patients with sepsis. The big aim is to achieve a more individualized treatment strategy in patients suffering from sepsis or septic shock.

A machine learning approach using endpoint adjudication committee labels for the identification of sepsis predictors at the emergency department

Accurate sepsis diagnosis is paramount for treatment decisions, especially at the emergency department (ED). To improve diagnosis, clinical decision support (CDS) tools are being developed with machine learning (ML) algorithms, using a wide range of variable groups. ML models can find patterns in Electronic Health Record (EHR) data that are unseen by the human eye. A prerequisite for a good model is the use of high-quality labels. Sepsis gold-standard labels are hard to define due to a lack of reliable diagnostic tools for sepsis at the ED. Therefore, standard clinical tools, such as clinical prediction scores (e.g. modified early warning score and quick sequential organ failure assessment), and claims-based methods (e.g. ICD-10) are used to generate suboptimal labels. As a consequence, models trained with these “silver” labels result in ill-trained models. In this study, we trained ML models for sepsis diagnosis at the ED with labels of 375 ED visits assigned by an endpoint adjudication committee (EAC) that consisted of 18 independent experts. Our objective was to evaluate which routinely measured variables show diagnostic value for sepsis. We performed univariate testing and trained multiple ML models with 95 routinely measured variables of three variable groups; demographic and vital, laboratory and advanced haematological variables. Apart from known diagnostic variables, we identified added diagnostic value for less conventional variables such as eosinophil count and platelet distribution width. In this explorative study, we show that the use of an EAC together with ML can identify new targets for future sepsis diagnosis research.

Presentation of the septic patient to the emergency department with respect to age and sex – a retrospective cross-sectional study

ObjectiveIt is challenging to identify sepsis in the emergency department, in part due to the non-specific presentation of septic patients. Current clinical sepsis screening tools rely on vital signs but many patients present with near normal vital signs and are therefore not identified as septic. This suggests that variables, e.g. signs and symptoms, need to be included to improve sepsis detection in the emergency department. Our hypothesis was that the presentation of sepsis differs based age and sex. The potential differences in presentation could be used to apply to future sepsis screening tools. The aim was to analyze the prevalence of keywords reflecting the presentation of septic patients in the emergency department in relation to age and sex.MethodRetrospective cross-sectional study. Keywords reflecting sepsis presentation to the emergency department were quantified and compared between age categories and the sex. 479 patients admitted to the emergency department of Södersjukhuset, Stockholm during 2013 and discharged with an ICD-10 code consistent with sepsis were included. We adjusted for multiple comparisons by applying Bonferroni-adjusted significance levels for all comparisons.Result“Pain” and “risk factors for sepsis” were significantly more common among patients younger than 65 years as compared with those 75 years and older: (n = 87/137; 63.5% vs n = 99/240; 41.3%, P-value < 0.000) and (n = 74/137; 54.0% vs 55/240; 22.9%, P-value < 0.000) respectively. “Risk factors for sepsis” was also significantly more common among patients between 65 and 74 years as compared with those 75 years and older: (n = 43/102; 42.2% vs 55/240; 22.9%, P-value < 0.000). “Pain” and “gastrointestinal symptoms” were significantly more common among women as compared with men: (n = 128/224; 57.1% vs n = 102/255; 40.0%, P-value < 0.000) and (n = 82/244; 36.6% vs n = 55/255; 21.6%, P-value < 0.000) respectively.ConclusionThe keywords “pain” and “risk factors for sepsis” were more common among younger patients and “pain” and “gastrointestinal symptoms” were more common among women. However, most keywords had a similar prevalence irrespective of age and sex. The results could potentially be used to augment sepsis screening tools or clinical decision tools.

Association between age and the host response in critically ill patients with sepsis

BackgroundThe association of ageing with increased sepsis mortality is well established. Nonetheless, current investigations on the influence of age on host response aberrations are largely limited to plasma cytokine levels while neglecting other pathophysiological sepsis domains like endothelial cell activation and function, and coagulation activation. The primary objective of this study was to gain insight into the association of ageing with aberrations in key host response pathways and blood transcriptomes in sepsis.MethodsWe analysed the clinical outcome (n = 1952), 16 plasma biomarkers providing insight in deregulation of specific pathophysiological domains (n = 899), and blood leukocyte transcriptomes (n = 488) of sepsis patients stratified according to age decades. Blood transcriptome results were validated in an independent sepsis cohort and compared with healthy individuals.ResultsOlder age was associated with increased mortality independent of comorbidities and disease severity. Ageing was associated with lower endothelial cell activation and dysfunction, and similar inflammation and coagulation activation, despite higher disease severity scores. Blood leukocytes of patients ≥ 70 years, compared to patients < 50 years, showed decreased expression of genes involved in cytokine signaling, and innate and adaptive immunity, and increased expression of genes involved in hemostasis and endothelial cell activation. The diminished expression of gene pathways related to innate immunity and cytokine signaling in subjects ≥ 70 years was sepsis-induced, as healthy subjects ≥ 70 years showed enhanced expression of these pathways compared to healthy individuals < 50 years.ConclusionsThis study provides novel evidence that older age is associated with relatively mitigated sepsis-induced endothelial cell activation and dysfunction, and a blood leukocyte transcriptome signature indicating impaired innate immune and cytokine signaling. These data suggest that age should be considered in patient selection in future sepsis trials targeting the immune system and/or the endothelial cell response.Graphical abstract

A Quantitative Study of Decision Thresholds for Initiation of Antibiotics in Suspected Sepsis.

Clinicians' decision thresholds for initiating antibiotics in patients with suspected sepsis have not been quantified. We aimed to define an average threshold of infection likelihood at which clinicians initiate antibiotics when treating a patient with suspected infection and to evaluate the influence of severity of illness and clinician-related factors on the threshold. This was a prospective survey of 153 clinicians responding to 8 clinical vignettes constructed from real-world data from 3 health care systems in the United States. We treated each hour in the vignette as a decision to treat or not treat with antibiotics and assigned an infection probability to each hour using a previously developed infection prediction model. We then estimated decision thresholds using regression models based on the timing of antibiotic initiation. We compared thresholds across categories of severity of illness and clinician-related factors. Overall, the treatment threshold occurred at a 69% probability of infection, but the threshold varied significantly across severity of illness categories-when patients had high severity of illness, the treatment threshold occurred at a 55% probability of infection; when patients had intermediate severity, the threshold for antibiotic initiation occurred at an infection probability of 69%, and the threshold was 84% when patients had low severity of illness (P < 0.001 for group differences). Thresholds differed significantly across specialty, highest among infectious disease and lowest among emergency medicine clinicians and across years of experience, decreasing with increasing years of experience. The threshold infection probability above which physicians choose to initiate antibiotics in suspected sepsis depends on illness severity as well as clinician factors. Incorporating these context-dependent thresholds into discriminating and well-calibrated models will inform the development of future sepsis clinical decision support systems. Clinician-related differences in treatment thresholds suggests potential unwarranted variation and opportunities for performance improvement. Decision making about antibiotic initiation in suspected sepsis occurs under uncertainty, and little is known about clinicians' thresholds for treatment.In this prospective study, 153 clinicians from 3 health care systems reviewed 8 real-world clinical vignettes representing patients with sepsis and indicated the time that they would initiate antibiotics.Using a model-based approach, we estimated decision thresholds and found that thresholds differed significantly across illness severity categories and by clinician specialty and years of experience.

EVALUATING SEPSIS CRITERIA IN DETECTING ALTERATIONS IN CLINICAL, METABOLIC, AND INFLAMMATORY PARAMETERS IN BURN PATIENTS.

Sepsis has become the leading cause of death in burn patients. Furthermore, sepsis and septic complications result in significant morbidities and longer hospitalization, which has profound impacts on the healthcare system. Despite this, sepsis in burn patients is surprisingly poorly understood and characterized. This retrospective, single-institution cohort study aimed to increase our understanding of the septic response after burns. We hypothesized that different sepsis definitions will results in distinctive septic trajectories and biochemical patterns after injury. Sepsis was defined by our burn center-specific prospective definition, the American Burn Association criteria, Sepsis-3 criteria, and the Mann-Salinas criteria. Applying these definitions, we compared clinical, metabolic, and inflammatory markers in septic and nonseptic burn patients. We found that the Sepsis-3 criteria are the most reliable screening tool used before clinical diagnoses for detecting sepsis trajectories and biochemical patterns. Moreover, we characterized distinct temporal alterations in biomarkers during the pre- and post-septic periods in burn patients, which may be incorporated into future sepsis definitions to improve the accuracy of a sepsis diagnosis in burn patients.

Patient, Public, and Healthcare Professionals' Sepsis Awareness, Knowledge, and Information Seeking Behaviors: A Scoping Review.

OBJECTIVES:Sepsis awareness and understanding are important aspects of prevention, recognition, and clinical management of sepsis. We conducted a scoping review to identify and map the literature related to sepsis awareness, general knowledge, and information-seeking behaviors with a goal to inform future sepsis research and knowledge translation campaigns.DESIGN:Scoping review.SETTING:Using Arksey and O’Malley’s methodological framework, we conducted a systematic search on May 3, 2021, across four databases (MEDLINE, EMBASE, CINAHL, and Education Research Complete). Title/abstract and full-text screening was done in duplicate. One researcher extracted the data for each included article, and a second researcher checked data accuracy. The protocol was registered on Open Science Framework (https://doi.org/10.17605/OSF.IO/YX7AU).SUBJECTS:Articles related to sepsis awareness, knowledge, and information seeking behaviors among patients, public, and healthcare professionals.INTERVENTIONS:None.MEASUREMENTS AND MAIN RESULTS:Of 5,927 unique studies, 80 reported on patient (n = 13/80;16.3%), public (n = 15/80;18.8%), or healthcare professional (nurses, physicians, emergency medical technicians) (n = 48/80; 60%) awareness and knowledge of sepsis. Healthcare professional awareness and knowledge of sepsis is high compared with patients/public. The proportion of patients/public who had heard of the term sepsis ranged from 2% (Japan) to 88.6% (Germany). The proportions of patients/public who correctly identified the definition of sepsis ranged from 4.2% (Singapore) to 92% (Sweden). The results from the included studies appear to suggest that patient/public awareness of sepsis gradually improved over time. We found that the definition of sepsis was inconsistent in the literature and that few studies reported on patient, public, or healthcare professional knowledge of sepsis risk factors. Most patient/public get their sepsis information from the internet, whereas healthcare professionals get it from their role in healthcare through job training or educational training.CONCLUSIONS:Patient, public, and healthcare professional awareness and knowledge of sepsis vary globally. Future research may benefit from a consistent definition as well as country-specific data to support targeted public awareness campaigns.

Evaluation of the effect of adding a high-fidelity simulation to an existing didactic lecture to teach pharmacy undergraduates the management of sepsis in secondary care

Abstract Introduction Sepsis is potentially life-threatening, requiring rapid identification and treatment. ‘Sepsis Six’ (1) has become the recognised treatment pathway and has traditionally been taught to our undergraduate pharmacy students in didactic fashion. Interactive teaching methods, such as simulation, are the most effective forms of education to improve patient safety (2). Such approaches might be beneficial in the teaching of sepsis management. Aim To evaluate the effect of adding simulation-based teaching to an existing didactic lecture on the management of sepsis. Methods Year 4 students at the University of Bath (n=92) attended a sepsis lecture given by a teacher practitioner with experience in managing sepsis in March 2020. Students completed an online survey that used Likert scales to evaluate understanding of sepsis and confidence in managing it (see table). One week later, small groups of students completed a 30-minute simulation using a SimMan ALS ‘patient’ programmed to show physiological signs of sepsis. Simulations were facilitated by a teacher practitioner with experience of operating SimMan ALS. Each group had a brief outlining the required tasks: reviewing the patient; assessing sepsis risk; summarising a treatment plan and priority actions. After the simulation, students underwent de-brief and completed the same online survey a second time. Changes in students’ responses between surveys were analysed using Wilcoxon signed-rank tests in SPSS, therefore data from students who completed only one survey were not included. Results 26 students completed both surveys (response rate: 28%). Likert scores for questions 1, 2, 4 and 5 were significantly higher following the simulation, indicating improved confidence and knowledge (see table). Conclusion Adding a high-fidelity simulation to an existing didactic lecture increased student confidence in identifying and managing sepsis. Self-reported knowledge of sepsis red flags also increased (indicated by the responses to Statement 1). This study should encourage future sepsis teaching to include a blend of didactic and simulated learning. Limitations include the low response rate, evaluation at only one university and reliance on student self-assessment of knowledge. References (1) Daniels, R, Nutbeam, T. et al (2019) The Sepsis Manual 5th Edition. UK Sepsis Trust. www.sepsistrust.org (2) Yu A, Fontana G, Darzi A (2016). Evaluation of Education and Training Interventions for Patient Safety. A report by the Centre for Health Policy at Imperial College London, an academic partner to Health Education England and the Commission on Education and Training for Patient Safety. London.

Exploring nursing and medical perceptions of sepsis management in a New Zealand emergency department: A qualitative study.

Early sepsis recognition and treatment are essential in order to reduce the burden of disease. Initial assessment of patients with infection is often undertaken by ED nurses and resident doctors. This descriptive qualitative study aimed to explore their perceptions and perspectives regarding the factors that impede the identification and management of patients with sepsis. This was a qualitative study conducted between 30 January 2020 and 27 February 2020. Semi-structured focus group interviews were performed to collect data. All participants provided written informed consent and completed a basic demographic and work experience form. Two study investigators facilitated the interviews. Interviews were audio-recorded and later transcribed. Thematic analysis was performed with the aid of NVivo 12 software. Six focus group interviews were conducted involving 40 ED nurses and doctors. Interview length ranged from 27 to 38 min (mean 33.5min). Three major themes were identified: (i) clinical management; (ii) challenges and delays; and (iii) communication. Each of these themes was broken down into subthemes, which are presented in more detail. ED nurses and doctors have identified important factors that limit and enhance their capacity to recognise and respond to patients with sepsis. Complex interactions exist between clinical and organisational structures that can affect the care of patients and the ability of clinicians to provide optimal care. The three major themes and specific subthemes provide a useful framework and stimulus for service improvements and research that could help foster future sepsis management improvement strategies.

Keywords reflecting sepsis presentation based on mode of emergency department arrival: a retrospective cross-sectional study

BackgroundCurrent sepsis screening tools are predominantly based on vital signs. However, patients with serious infections frequently present with normal vital signs and there has been an increased interest to include other variables such as symptoms in screening tools to detect sepsis. The majority of patients with sepsis arrive to the emergency department by emergency medical services. Our hypothesis was that the presentation of sepsis, including symptoms, may differ between patients arriving to the emergency department by emergency medical services and patients arriving by other means. This information is of interest to adapt future sepsis screening tools to the population in which they will be implemented. The aim of the current study was to compare the prevalence of keywords reflecting the clinical presentation of sepsis based on mode of arrival among septic patients presenting to the emergency department.MethodsRetrospective cross-sectional study of 479 adult septic patients. Keywords reflecting sepsis presentation upon emergency department arrival were quantified and analyzed based on mode of arrival, i.e., by emergency medical services or by other means. We adjusted for multiple comparisons by applying Bonferroni-adjusted significance levels for all comparisons. Adjustments for age, gender, and sepsis severity were performed by stratification. All patients were admitted to the emergency department of Södersjukhuset, Stockholm, and discharged with an ICD-10 code compatible with sepsis between January 1, and December 31, 2013.Results“Abnormal breathing” (51.8% vs 20.5%, p value < 0.001), “abnormal circulation” (38.4% vs 21.3%, p value < 0.001), “acute altered mental status” (31.1% vs 13.1%, p value < 0.001), and “decreased mobility” (26.1% vs 10.7%, p value < 0.001) were more common among patients arriving by emergency medical services, while “pain” (71.3% vs 40.1%, p value < 0.001) and “risk factors for sepsis” (50.8% vs 30.8%, p value < 0.001) were more common among patients arriving by other means.ConclusionsThe distribution of most keywords related to sepsis presentation was similar irrespective of mode of arrival; however, some differences were present. This information may be useful in clinical decision tools or sepsis screening tools.

Single-Site Sampling versus Multisite Sampling for Blood Cultures: a Retrospective Clinical Study.

The performance of blood cultures (BCs) relies on optimal sampling. Sepsis guidelines do not specify which sampling protocol to use but recommend two sets of BC bottles, each set containing one aerobic and one anaerobic bottle. For the single-site sampling (SSS) protocol, only one venipuncture is performed for all four bottles. The predominating multisite sampling (MSS) protocol implies that BC bottles are collected from two separate venipuncture sites. The aim of this study was to compare SSS and MSS. Primary outcomes were number of BC sets collected, sample volume, and diagnostic performance. This was a retrospective clinical study comparing BC results in an emergency department before and after changing the sampling protocol to SSS from MSS. All BC samples were incubated in the BacT/Alert BC system. The analysis included 5,248 patients before and 5,364 patients after the implementation of SSS. There was a significantly higher proportion of positive BCs sampled with SSS compared with MSS, 1,049/5,364 (19.56%) and 932/5,248 (17.76%), respectively (P = 0.018). This difference was due to a higher proportion of solitary BC sets (two BC bottles) in MSS. Analyzing only patients with the recommended four BC bottles, there was no difference in positivity. SSS had a higher proportion of BC bottles with the recommended sample volumes of 8-12 ml than MSS (P < 0.001). Changing the sampling protocol to SSS from MSS resulted in higher positivity rates, higher sample volume and fewer solitary BC sets. These advantages of SSS should be considered in future sepsis guidelines.