Beyond the Horizon: A Comprehensive Review of Contemporary Strategies in Sepsis Management Encompassing Predictors, Diagnostic Tools, and Therapeutic Advances.

This comprehensive review offers a detailed exposition of contemporary strategies in sepsis management, encompassing predictors, diagnostic tools, and therapeutic advances. The analysis elucidates the dynamic nature of sepsis, emphasizing the crucial role of early detection and intervention. The multifaceted strategies advocate for a holistic and personalized approach to sepsis care from traditional clinical methodologies to cutting-edge technologies. The implications for clinical practice underscore clinicians' need to adapt to evolving definitions, integrate advanced diagnostic tools, and embrace precision medicine. Integrating artificial intelligence and telemedicine necessitates a commitment to training and optimization. Judicious antibiotic use and recognition of global health disparities emphasize the importance of a collaborative, global effort in sepsis care. Looking ahead, recommendations for future research underscore priorities such as longitudinal studies on biomarkers, precision medicine trials, implementation science in technology, global health interventions, and innovative antibiotic stewardship strategies. These research priorities aim to contribute to transformative advancements in sepsis management, ultimately enhancing patient outcomes and reducing the global impact of this critical syndrome.

Evaluation of Vitek-2 and MicroScan ASTs directly from positive blood culture: A cost-effective 24-h reduction for Enterobacterales and staphylococci.

The reduction of antimicrobial susceptibility testing (AST) time-to-result is a central need, especially in sepsis treatment. The current automated rapid ASTs are still too expensive for many laboratories. We aimed to evaluate three pre-treatment methods for a same-day inoculation on both automated AST platforms available in our laboratory. We tested 100 Enterobacterales or staphylococci positive bottles. We obtained good results with the different methods and instruments. In particular, Vitek-2 showed good performances with Enterobacterales AST when inoculated with bacterial pellet (96.6% categorical agreement - CA-, 93.3% essential agreement - EA). Also short-term incubation colonies for staphylococci AST had acceptable CA (94.2%), even if with 77.5% EA. MicroScan system for staphylococci AST with both short-term incubation and direct blood inoculation reached >95% CA, but 92.5% and 83.6% EA, respectively. On the other hand, Enterobacterales AST showed optimal performances only with bacterial pellet inoculation (97.6% CA). In fact, direct blood inoculation showed not acceptable parameters for several molecules. Both systems allow a 24-h reduction in time-to-result, by using the same instruments of routine activity after rapid and cheap pre-treatments.

Applications of peptides in nanosystems for diagnosing and managing bacterial sepsis.

Sepsis represents a critical medical condition stemming from an imbalanced host immune response to infections, which is linked to a significant burden of disease. Despite substantial efforts in laboratory and clinical research, sepsis remains a prominent contributor to mortality worldwide. Nanotechnology presents innovative opportunities for the advancement of sepsis diagnosis and treatment. Due to their unique properties, including diversity, ease of synthesis, biocompatibility, high specificity, and excellent pharmacological efficacy, peptides hold great potential as part of nanotechnology approaches against sepsis. Herein, we present a comprehensive and up-to-date review of the applications of peptides in nanosystems for combating sepsis, with the potential to expedite diagnosis and enhance management outcomes. Firstly, sepsis pathophysiology, antisepsis drug targets, current modalities in management and diagnosis with their limitations, and the potential of peptides to advance the diagnosis and management of sepsis have been adequately addressed. The applications have been organized into diagnostic or managing applications, with the last one being further sub-organized into nano-delivered bioactive peptides with antimicrobial or anti-inflammatory activity, peptides as targeting moieties on the surface of nanosystems against sepsis, and peptides as nanocarriers for antisepsis agents. The studies have been grouped thematically and discussed, emphasizing the constructed nanosystem, physicochemical properties, and peptide-imparted enhancement in diagnostic and therapeutic efficacy. The strengths, limitations, and research gaps in each section have been elaborated. Finally, current challenges and potential future paths to enhance the use of peptides in nanosystems for combating sepsis have been deliberately spotlighted. This review reaffirms peptides' potential as promising biomaterials within nanotechnology strategies aimed at improving sepsis diagnosis and management.

Navigating the Complexity of Scoring Systems in Sepsis Management: A Comprehensive Review.

This comprehensive review navigates the intricate landscape of sepsis scoring systems, aiming to provide healthcare professionals and researchers with a nuanced understanding of their role in contemporary sepsis management. Beginning with a succinct overview of sepsis, the review emphasizes the significance of scoring systems in standardizing assessments and guiding clinical decision-making. Through a detailed analysis of prominent systems such as SOFA, APACHE, and qSOFA, the review delineates their unique attributes, strengths, and limitations. The implications for sepsis management and patient outcomes are discussed, highlighting the potential for these tools to enhance early detection and intervention. The review concludes with a compelling call to action, urging healthcare professionals to integrate scoring systems into routine practice and researchers to explore novel approaches. By synthesizing current knowledge and addressing future directions, this review serves as a valuable resource for those seeking clarity and guidance in the dynamic landscape of sepsis management.

Compliance with maternal sepsis guidelines in a tertiary hospital in the Netherlands.

OBJECTIVES: Sepsis is a common cause of maternal mortality and morbidity. Early detection and rapid management are essential. In this study, we evaluate the compliance with the implemented maternity-specific Early Warning Score (EWS), Rapid Response Team (RRT) protocol and the Surviving Sepsis Campaign (SSC) Hour-1 Bundle in a tertiary hospital in the Netherlands. METHODS: We performed a retrospective patient chart review from July 2019 to June 2020 at the Leiden University Medical Centre. We included women who received therapeutic antibiotics and were admitted for at least 24 hours. RESULTS: We included 240 women: ten were admitted twice and one woman three times, comprising 252 admissions. A clinical diagnosis of sepsis was made in 22 women. The EWS was used in 29% (n = 73/252) of admissions. Recommendations on the follow-up of the EWS were carried out in 53% (n = 46/87). Compliance with the RRT protocol was highest for assessment by a medical doctor within 30 minutes (n = 98/117, 84%) and lowest for RRT involvement (n = 7/23, 30%). In women with sepsis, compliance with the SSC Bundle was highest for acquiring blood cultures (n = 19/22, 85%), while only 64% (n = 14/22) received antibiotics within 60 minutes of the sepsis diagnosis. CONCLUSION: The adherence to the maternity-specific EWS and the SSC Hour-1 bundle was insufficient, even within this tertiary setting in a high-income country.

Nanomaterial-based methods for sepsis management.

Sepsis is a serious disease caused by an impaired host immune response to infection, resulting in organ dysfunction, tissue damage and is responsible for high in-hospital mortality (approximately 20%). Recently, WHO documented sepsis as a global health priority. Nevertheless, there is still no effective and specific therapy for clinically detecting sepsis. Nanomaterial-based approaches have appeared as promising tools for identifying bacterial infections. In this review, recent biosensors are introduced and summarized as nanomaterial-based platforms for sepsis management and severe complications. Biosensors can be used as tools for the diagnosis and treatment of sepsis and as nanocarriers for drug delivery. In general, diagnostic methods for sepsis-associated bacteria, biosensors developed for this purpose are presented in detail, and their strengths and weaknesses are discussed. In other words, readers of this article will gain a comprehensive understanding of biosensors and their applications in sepsis management.

New potential for an old kid on the block: Impact of premorbid metformin use on lactate kinetics, kidney injury and mortality in sepsis and septic shock, an observational study.

INTRODUCTION: Sepsis and septic shock cause significant mortality worldwide, with no targeted molecular therapies available. Metformin has pleomorphic effects that may be beneficial in sepsis, but at present, the impact of metformin exposure on sepsis remains controversial. Metformin might alter lactate metabolism, but little is known about its influence on lactate kinetics. We therefore investigated the impact of preadmission metformin use on lactate kinetics, acute kidney injury (AKI) and mortality in sepsis. MATERIALS AND METHODS: We retrospectively analysed all ICU admissions with sepsis and septic shock between January 2013 and September 2020, identifying 77 users and 390 nonusers (subdivided in diabetics, n = 48 and nondiabetics, n = 342). RESULTS: (Sub)groups did not differ in illness severity or sepsis aetiology. Admission lactate levels were similar, but evolution in lactate over the first 24 h showed a larger decrease in users vs nonusers (median - 53% vs. -36%, p = .010). No difference in AKI or renal replacement therapy was found. Mortality was lower in users vs nonusers in case of septic shock (21.9% (n = 7) vs. 42.7% (n = 61) for 90d mortality, p = .029, OR 0.38 [95% CI: 0.15-0.93]), but showed no significant differences in the combined sepsis and septic shock population. CONCLUSIONS: In our data, preadmission metformin use is associated with a significantly larger decrease in lactate after admission with sepsis or septic shock and with reduced mortality in septic shock. This underscores the need for further studies investigating the interplay between metformin, lactate and sepsis, thereby exploring the potential use of metformin or its pathways in sepsis.

Time to decision in sepsis.

OBJECTIVE: This study aimed to identify the common barriers leading to delayed initial management, microbiological diagnosis, and appropriate empirical antimicrobial treatment in sepsis. METHODS: A cross-sectional study was performed by the application of a population-based survey. Four different surveys were designed, targeting the healthcare personnel located in main hospital areas [emergency department (SEMES); infectious diseases and clinical microbiology-microbiological diagnosis (SEIMC-M); intensive care and infectious diseases, (SEMICYUC-GTEIS); and infectious diseases and clinical microbiology-clinical diagnosis, (SEIMC-C)]. RESULTS: A total of 700 valid surveys were collected from June to November 2019: 380 (54.3%) of SEMES, 127 (18.1%) of SEIMC-M, 97 (13.9%) de SEMICYUC-GTEIS and 96 (13.7%) of SEIMC-C, in 270 hospitals of all levels of care. The qSOFA score was used as a screening tool. The most used biomarker was procalcitonin (n=92, 39.8%). The sepsis code was implemented in 157 of 235 participating centers (66.2%), particularly in tertiary level hospitals. The mean frequency of contaminated blood cultures was 8.9% (8.7). In 85 (78.7%) centers, positive results of blood cultures were available within the first 72 hours and were communicated to the treating physician effectively by phone or e-mail in 76 (81.7%) cases. The main reason for escalating treatment was clinical deterioration, and the reason for de-escalating antimicrobials was significantly different between the specialties. Quality indicators were not frequently monitored among the different participating centers. CONCLUSIONS: There are significant barriers that hinder adequate management processes in sepsis in Spanish hospitals.

Precise engineering of neutrophil membrane coated with polymeric nanoparticles concurrently absorbing of proinflammatory cytokines and endotoxins for management of sepsis.

Sepsis, ensuing from unrestrained inflammatory replies to bacterial infections, endures with high injury and mortality worldwide. Presently, active sepsis management is missing in the hospitals during the surgery, and maintenance remnants mainly helpful. Now, we have constructed the macrophage bio-mimic nanoparticles for the treatment of sepsis and its management. Biomimetic macrophage nanoparticles containing a recyclable polymeric nanoparticle covered with cellular membrane resulting from macrophages (represented PEG-Mac@NPs) have an antigenic external similar to the cells. The PEG-Mac@NPs, Isorhamnetin (Iso) on the free LPS encouraged endotoxin in BALB/c mice through evaluating the nitric acid, TNF-α, and IL-6. Further, the COX-2 and iNOS expression ratio was examined to recognize the connection of several trails to find the exact mode of action PEG-Mac@NPs and Iso. The outcome reveals that the PEG-Mac@NPs inhibited and LPS triggered the NO production though the macrophages peritoneal. Furthermore, the anti-inflammatory possessions were additionally categorized through the reduction of COX-2 and iNOS protein expressions. Engaging PEG-Mac@NPs as a biomimetic decontamination approach displays potential for refining sepsis patient consequences, possibly in the use of sepsis management.

Sepsis Management in the Emergency Department.

Sepsis is a deadly and costly condition, but effectively managing sepsis in the emergency department (ED) can help to improve patient outcomes. A key part of sepsis management is improving compliance with sepsis bundles, which can be challenging in the ED setting. Bedside nurses in the ED have a unique opportunity to facilitate early identification and treatment of patients with sepsis, which increases sepsis bundle compliance and improves patient outcomes. Interventions reviewed in this article can help to improve early identification and treatment, along with ways to standardize care, provide education, and implement feedback.

A Whole-Body Mathematical Model of Sepsis Progression and Treatment Designed in the BioGears Physiology Engine.

Sepsis is a debilitating condition associated with a high mortality rate that greatly strains hospital resources. Though advances have been made in improving sepsis diagnosis and treatment, our understanding of the disease is far from complete. Mathematical modeling of sepsis has the potential to explore underlying biological mechanisms and patient phenotypes that contribute to variability in septic patient outcomes. We developed a comprehensive, whole-body mathematical model of sepsis pathophysiology using the BioGears Engine, a robust open-source virtual human modeling project. We describe the development of a sepsis model and the physiologic response within the BioGears framework. We then define and simulate scenarios that compare sepsis treatment regimens. As such, we demonstrate the utility of this model as a tool to augment sepsis research and as a training platform to educate medical staff.

Current Issues and Perspectives in Patients with Possible Sepsis at Emergency Departments.

In the area of Emergency Room (ER), many patients present criteria compatible with a SIRS, but only some of them have an associated infection. The new definition of sepsis by the European Society of Intensive Care Medicine and the Society of Critical Care Medicine (2016), revolutionizes precedent criteria, overcoming the concept of SIRS and clearly distinguishing the infection with the patient's physiological response from the symptoms of sepsis. Another fundamental change concerns the recognition method: The use of SOFA (Sequential-Sepsis Related-Organ Failure Assessment Score) as reference score for organ damage assessment. Also, the use of the qSOFA is based on the use of three objective parameters: Altered level of consciousness (GCS <15 or AVPU), systolic blood pressure ≤ 100 mmHg, and respiratory rate ≥ 22/min. If patients have at least two of these altered parameters in association with an infection, then there is the suspicion of sepsis. In these patients the risk of death is higher, and it is necessary to implement the appropriate management protocols, indeed the hospital mortality rate of these patients exceeds 40%. Patients with septic shock can be identified by the association of the clinical symptoms of sepsis with persistent hypotension, which requires vasopressors to maintain a MAP of 65 mmHg, and serum lactate levels >18 mg/dL in despite of an adequate volume resuscitation. Then, patient first management is mainly based on: (1) Recognition of the potentially septic patient (sepsis protocol-qSOFA); (2) Laboratory investigations; (3) Empirical antibiotic therapy in patients with sepsis and septic shock. With this in mind, the authors discuss the most important aspects of the sepsis in both adults and infants, and also consider the possible treatment according current guidelines. In addition, the possible role of some nutraceuticals as supportive therapy in septic patient is also discussed.

Does Gender Matter in Septic Patient Outcomes?

PURPOSE: The purpose of this study was to examine potential gender disparities in relation to factors associated with sepsis management among a cohort of patients admitted through an emergency department with a discharge diagnosis of severe sepsis or septic shock. Sepsis is one of the leading causes of death globally, with significant associated costs. Predictors of survival for those with sepsis-related diagnoses are complex. DESIGN AND METHODS: The study had a retrospective, descriptive cross-sectional design. The sample (N = 482) included patients 18 years of age or older who presented to the emergency department of a nonprofit, Magnet-recognized, acute care hospital located in southern California. Subjects included those who subsequently met the criteria for a discharge diagnosis of severe sepsis or septic shock as defined by the Surviving Sepsis Campaign. Patient characteristics, clinical variables, care management processes, and outcomes were extracted from the electronic health record. A multivariate model was analyzed. FINDINGS: The sample included 234 women (48.5%) and 248 men (51.5%). Logistic regression with eight independent variables (discharge diagnosis, age, comorbidities, length of hospital stay, source of infection, first serum lactate level measured, recommended fluids administered, and gender) reliably predicted odds for patient survival, Ï°2 (12) = 118.38, p < .001, and correctly classified 77.3% of cases. All eight independent variables significantly contributed to the model. Men had a higher likelihood of hospital survival than women (odds ratio 1.68; 95% confidence interval 1.01-2.79; p = .045). CONCLUSIONS: The Surviving Sepsis Campaign has provided a clear pathway for care of patients with sepsis-related diagnoses. Therapeutic strategies should be developed to address differences in outcome by gender. The adoption of more aggressive applications of evidence-based interventions for these patients may result in better patient outcomes. CLINICAL RELEVANCE: Providers should understand the importance of adhering to sepsis protocols, minimizing treatment disparities, and recognizing gender differences.

Can pre-hospital administration reduce time to initial antibiotic therapy in septic patients?

OBJECTIVE: To quantify the potential time saved with pre-hospital antibiotic therapy in sepsis. METHODS: Study data for adult patients transported by Ambulance Victoria (AV), and enrolled into the Australasian Resuscitation In Sepsis Evaluation (ARISE), were linked with pre-hospital electronic records. RESULTS: An AV record was identified for 240 of 341 ARISE patients. The pre-hospital case notes referred to potential infection in 165 patients. The median time to first antibiotic administration from loading the patient into the ambulance was 107 (74-160) min. CONCLUSIONS: ARISE patients in Victoria were frequently identified pre-hospital. An opportunity exists to study the feasibility of pre-hospital antibiotic therapy.

Predictive value of the kinetics of procalcitonin and C-reactive protein for early clinical stability in patients with bloodstream infections due to Gram-negative bacteria.

OBJECTIVE: To investigate whether the magnitude of the change in procalcitonin (PCT) and C-reactive protein (CRP) levels between day 1 and day 2 after the blood culture date is associated with early clinical stability (ECS) on day 3 in patients with bacteremia due to Gram-negative bacteria (GNB). MATERIALS/METHODS: A prospective cohort study carried out in a 950-bed tertiary hospital in Spain between March 2013 and May 2014. Patients with GNB bacteremia were included. Changes in PCT and CRP kinetics from day 1 to day 2 (∆%PCT, ∆%CRP) were expressed as percentage of decline in blood levels. Logistic regression was used to identify predictors of ECS. Classification and regression tree analysis was performed to identify breakpoints. The discriminatory power of ∆%CRP and ∆%PCT as predictors of ECS was assessed by the area under the ROC (AUROC). RESULTS: 71 patients were included, and 53 (74.56%) reached ECS. Multivariate analyses showed that SOFA score on day 1, ∆%PCT, and ∆%CRP were associated with ECS after controlling for confounders. ∆%PCT ≥ 30% (decline) and ∆%CRP ≥ 10% (decline) predicted ECS only among patients with SOFA≤3 on day 1 (n = 54; 43 reached ECS). In these patients, the AUROCs for the prediction of ECS were 0.96 (95% CI: 0.90-1) for ∆%CRP and 0.96 (95% CI: 0.90-1) for ∆%PCT, respectively. CONCLUSIONS: In the subgroup of patients with a SOFA score on day 1 ≤3, a ≥30% decline in PCT or a ≥10% decline in CRP between day 1 and day 2 was a very good predictor of ECS (which in turn was associated with a lower 30-day mortality and a greater clinical cure on day 14). Patients who do not achieve this decrease may need more intensive workup. In this subgroup (with a SOFA on day 1 ≤3), CRP may be preferred due to its lower cost.

Evidence is stronger than you think: a meta-analysis of vitamin C use in patients with sepsis.

Two recent publications by Sheikh and Horner and Teng et al. reviewed studies on incorporating vitamin C to treat septic patients; however, a meta-analysis was not offered in either report. This commentary extends both reviews by integrating a meta-analysis and sharing aggregated results. Pooled analyses demonstrated a marked reduction in mortality and duration of vasopressor administration in the group with the use of vitamin C.

Recent advances in understanding and managing sepsis.

The last two to three years provided several "big steps" regarding our understanding and management of sepsis. The increasing insight into pathomechanisms of post-infectious defense led to some new models of host response. Besides hyper-, hypo-, and anti-inflammation as the traditional approaches to sepsis pathophysiology, tolerance and resilience were described as natural ways that organisms react to microbes. In parallel, huge data analyses confirmed these research insights with a new way to define sepsis and septic shock (called "Sepsis-3"), which led to discussions within the scientific community. In addition to these advances in understanding and defining the disease, follow-up protocols of the initial "sepsis bundles" from the Surviving Sepsis Campaign were created; some of them were part of quality management studies by clinicians, and some were in the form of mandatory procedures. As a result, new "bundles" were initiated with the goal of enabling standardized management of sepsis and septic shock, especially in the very early phase. This short commentary provides a brief overview of these two major fields as recent hallmarks of sepsis research.

Recognition and Management of Sepsis in the Obstetric Patient.

Sepsis is one of the principal causes of maternal mortality in obstetrics. Physiologic changes that occur during pregnancy create a vulnerable environment, predisposing pregnant patients to the development of sepsis. Furthermore, these changes can mask sepsis indicators normally seen in the nonobstetric population, making it difficult to recognize and treat sepsis in a timely manner. The use of maternal-specific early warning tools for sepsis identification and knowledge of appropriate interventions and their effects on the mother and fetus can help clinicians obtain the best patient outcomes in acute care settings. This article outlines the signs and symptoms of sepsis in obstetric patients and discusses treatment options used in critical care settings.

Computerised sepsis protocol management. Description of an early warning system. / Protocolo informático de manejo integral de la sepsis. Descripción de un sistema de identificación precoz.

INTRODUCTION: New strategies need to be developed for the early recognition and rapid response for the management of sepsis. To achieve this purpose, the Multidisciplinary Sepsis Team (MST) developed the Computerised Sepsis Protocol Management (PIMIS). The aim of this study was to evaluate the convenience of using PIMIS, as well as the activity of the MST. METHODS: An analysis was performed on the data collected from solicited MST consultations (direct activation of PIMIS by attending physician or telephone request) and unsolicited ones (by referral from the microbiology laboratory or an automatic referral via the hospital vital signs recording software [SIDCV]), as well as the hospital department, source of infection, treatment recommendation, and acceptance of this. RESULTS: Of the 1,581 first consultations, 65.1% were solicited consultations (84.1% activation of PIMIS and 15.9% by telephone). The majority of unsolicited consultations were generated by the microbiology laboratory (95.2%), and 4.8% from the SIDCV. Referral from solicited consultations were generated sooner (5.63days vs 8.47days; P<.001) and came from clinical specialties rather than from the surgical ward (73.0% vs 39.1%; P<.001). A recommendation was made for antimicrobial prescription change in 32% of first consultations. The treating physician accepted 78.1% of recommendations. CONCLUSIONS: The high rate of solicited consultations and acceptance of recommended prescription changes suggest that a MST is seen as a helpful resource, and that PIMIS software is perceived to be useful and convenient to use, as it is the main source of referral.

Feasibility of automated titration of vasopressor infusions using a novel closed-loop controller.

Blood pressure management is a central concern in critical care patients. For a variety of reasons, titration of vasopressor infusions may be an ideal use-case for computer assistance. Using our previous experience gained in the bench-to-bedside development of a computer-assisted fluid management system, we have developed a novel controller for this purpose. The aim of this preliminary study was to assess the feasibility of using this controller in simulated patients to maintain a target blood pressure in both stable and variable blood-pressure scenarios. We tested the controller in two sets of simulation scenarios: one with stable underlying blood pressure and a second with variable underlying blood pressure. In addition, in the variable phase of the study, we tested infusion-line delays of 8-60 s. The primary outcome for both testing conditions (stable and variable) was % case time in target range. We determined a priori that acceptable performance on the first phase of the protocol would require greater than 95% case-time in-target given the simple nature of the protocol, and for the second phase of the study 80% or greater given the erratic nature of the blood pressure changes taking place. 250 distinct cases for each simulation condition, both managed and unmanaged, were run over 4 days. In the stable hemodynamic conditions, the unmanaged group had an MAP of 57.5 ± 4.6 mmHg and spent only 5.6% of case time in-target. The managed group had an MAP of 70.3 ± 2.6 and spent a total of 99.5% of case time in-target (p < 0.00001 for both comparisons between groups). In the variable hemodynamic conditions, the unmanaged group had an MAP of 53.1 ± 5.0 mmHg and spent 0% of case time in-target. The managed group had an MAP of 70.5 ± 3.2 mmHg (p < 0.00001 compared to unmanaged group) and spent 88.6% of case time in-target (p < 0.00001 compared to unmanaged group), with 6.4% of case time over and 5.1% of case time under target. Increasing infusion lag increased coefficient of variation by about 10% per 15 s of lag (p = 0.001). This study demonstrated that this novel controller for vasopressor administration is able to main a target mean arterial pressure in a simulated physiologic model in the face of random disturbances and infusion-line lag.