The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)

PubMed Central

Singer, Mervyn; Deutschman, Clifford S.; Seymour, Christopher Warren; Shankar-Hari, Manu; Annane, Djillali; Bauer, Michael; Bellomo, Rinaldo; Bernard, Gordon R.; Chiche, Jean-Daniel; Coopersmith, Craig M.; Hotchkiss, Richard S.; Levy, Mitchell M.; Marshall, John C.; Martin, Greg S.; Opal, Steven M.; Rubenfeld, Gordon D.; van der Poll, Tom; Vincent, Jean-Louis; Angus, Derek C.

2016-01-01

IMPORTANCE Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination. OBJECTIVE To evaluate and, as needed, update definitions for sepsis and septic shock. PROCESS A task force (n = 19) with expertise in sepsis pathobiology, clinical trials, and epidemiology was convened by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. Definitions and clinical criteria were generated through meetings, Delphi processes, analysis of electronic health record databases, and voting, followed by circulation to international professional societies, requesting peer review and endorsement (by 31 societies listed in the Acknowledgment). KEY FINDINGS FROMEVIDENCE SYNTHESIS Limitations of previous definitions included an excessive focus on inflammation, the misleading model that sepsis follows a continuum through severe sepsis to shock, and inadequate specificity and sensitivity of the systemic inflammatory response syndrome (SIRS) criteria. Multiple definitions and terminologies are currently in use for sepsis, septic shock, and organ dysfunction, leading to discrepancies in reported incidence and observed mortality. The task force concluded the term severe sepsis was redundant. RECOMMENDATIONS Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. For clinical operationalization, organ dysfunction can be represented by an increase in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more, which is associated with an in-hospital mortality greater than 10%. Septic shock should be defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a

The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).

PubMed

Singer, Mervyn; Deutschman, Clifford S; Seymour, Christopher Warren; Shankar-Hari, Manu; Annane, Djillali; Bauer, Michael; Bellomo, Rinaldo; Bernard, Gordon R; Chiche, Jean-Daniel; Coopersmith, Craig M; Hotchkiss, Richard S; Levy, Mitchell M; Marshall, John C; Martin, Greg S; Opal, Steven M; Rubenfeld, Gordon D; van der Poll, Tom; Vincent, Jean-Louis; Angus, Derek C

2016-02-23

Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination. To evaluate and, as needed, update definitions for sepsis and septic shock. A task force (n = 19) with expertise in sepsis pathobiology, clinical trials, and epidemiology was convened by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. Definitions and clinical criteria were generated through meetings, Delphi processes, analysis of electronic health record databases, and voting, followed by circulation to international professional societies, requesting peer review and endorsement (by 31 societies listed in the Acknowledgment). Limitations of previous definitions included an excessive focus on inflammation, the misleading model that sepsis follows a continuum through severe sepsis to shock, and inadequate specificity and sensitivity of the systemic inflammatory response syndrome (SIRS) criteria. Multiple definitions and terminologies are currently in use for sepsis, septic shock, and organ dysfunction, leading to discrepancies in reported incidence and observed mortality. The task force concluded the term severe sepsis was redundant. Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. For clinical operationalization, organ dysfunction can be represented by an increase in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more, which is associated with an in-hospital mortality greater than 10%. Septic shock should be defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone. Patients with septic shock

Biomarkers of sepsis

PubMed Central

2013-01-01

Sepsis is an unusual systemic reaction to what is sometimes an otherwise ordinary infection, and it probably represents a pattern of response by the immune system to injury. A hyper-inflammatory response is followed by an immunosuppressive phase during which multiple organ dysfunction is present and the patient is susceptible to nosocomial infection. Biomarkers to diagnose sepsis may allow early intervention which, although primarily supportive, can reduce the risk of death. Although lactate is currently the most commonly used biomarker to identify sepsis, other biomarkers may help to enhance lactate’s effectiveness; these include markers of the hyper-inflammatory phase of sepsis, such as pro-inflammatory cytokines and chemokines; proteins such as C-reactive protein and procalcitonin which are synthesized in response to infection and inflammation; and markers of neutrophil and monocyte activation. Recently, markers of the immunosuppressive phase of sepsis, such as anti-inflammatory cytokines, and alterations of the cell surface markers of monocytes and lymphocytes have been examined. Combinations of pro- and anti-inflammatory biomarkers in a multi-marker panel may help identify patients who are developing severe sepsis before organ dysfunction has advanced too far. Combined with innovative approaches to treatment that target the immunosuppressive phase, these biomarkers may help to reduce the mortality rate associated with severe sepsis which, despite advances in supportive measures, remains high. PMID:23480440

Sepsis 2018: Definitions and Guideline Changes.

PubMed

Napolitano, Lena M

Sepsis is a global healthcare issue and continues to be the leading cause of death from infection. Early recognition and diagnosis of sepsis is required to prevent the transition into septic shock, which is associated with a mortality rate of 40% or more. New definitions for sepsis and septic shock (Third International Consensus Definitions for Sepsis and Septic Shock [Sepsis-3]) have been developed. A new screening tool for sepsis (quick Sequential Organ Failure Assessment [qSOFA]) has been proposed to predict the likelihood of poor outcome in out-of-intensive care unit (ICU) patients with clinical suspicion of sepsis. The Surviving Sepsis Campaign Guidelines were recently updated and include greater evidence-based recommendations for treatment of sepsis in attempts to reduce sepsis-associated mortality. This review discusses the new Sepsis-3 definitions and guidelines.

A Sepsis-related Diagnosis Impacts Interventions and Predicts Outcomes for Emergency Patients with Severe Sepsis.

PubMed

Kim, Mitchell; Watase, Taketo; Jablonowski, Karl D; Gatewood, Medley O; Henning, Daniel J

2017-10-01

Many patients meeting criteria for severe sepsis are not given a sepsis-related diagnosis by emergency physicians (EP). This study 1) compares emergency department (ED) interventions and in-hospital outcomes among patients with severe sepsis, based on the presence or absence of sepsis-related diagnosis, and 2) assesses how adverse outcomes relate to three-hour sepsis bundle completion among patients fulfilling severe sepsis criteria but not given a sepsis-related diagnosis. We performed a retrospective cohort study using patients meeting criteria for severe sepsis at two urban, academic tertiary care centers from March 2015 through May 2015. We included all ED patients with the following: 1) the 1992 Consensus definition of severe sepsis, including two or more systemic inflammatory response syndrome criteria and evidence of organ dysfunction; or 2) physician diagnosis of severe sepsis or septic shock. We excluded patients transferred to or from another hospital and those <18 years old. Patients with an EP-assigned sepsis diagnosis created the "Physician Diagnosis" group; the remaining patients composed the "Consensus Criteria" group. The primary outcome was in-hospital mortality. Secondary outcomes included completed elements of the current three-hour sepsis bundle; non-elective intubation; vasopressor administration; intensive care unit (ICU) admission from the ED; and transfer to the ICU in < 24 hours. We compared proportions of each outcome between groups using the chi-square test, and we also performed a stratified analysis using chi square to assess the association between failure to complete the three-hour bundle and adverse outcomes in each group. Of 418 patients identified with severe sepsis we excluded 54, leaving 364 patients for analysis: 121 "Physician Diagnosis" and 243 "Consensus Criteria." The "Physician Diagnosis" group had a higher in-hospital mortality (12.4% vs 3.3%, P < 0.01) and compliance with the three-hour sepsis bundle (52.1% vs 20.2%, P

Quality improvement in pediatric sepsis.

PubMed

Melendez, Elliot; Bachur, Richard

2015-06-01

Although there is abundant literature detailing the impact of quality improvement in adult sepsis, the pediatric literature is lacking. Despite consensus definitions for sepsis, which patients along the sepsis spectrum should receive aggressive management and the exact onset of sepsis ('time zero') are not clearly established. In the adult emergency department (ED), sepsis onset is defined as the time of entry into the ED; however, this definition cannot be applied to hospitalized patients or patients who evolve during their ED course. Since the time of sepsis onset will dictate the timeliness of subsequent process measures, the variable definitions in the literature make it difficult to generalize findings among prior studies. Despite the variation in defining time zero, aggressive fluid administration, timely antibiotics, and compliance with sepsis bundles have been shown to improve mortality and to reduce hospital and intensive care length of stay. In addition, early identification tools show promise in beginning to define sepsis onset and retrospective search tools may allow improved case finding of those children of concern for sepsis. Quality improvement in pediatric sepsis is evolving. As we continue to define quality measures, we must standardize the definition of sepsis onset. This definition should be applicable to any treatment venue to ensure measures can be evaluated across all settings. In addition, we must delineate which patients along the sepsis spectrum should be candidates for timely interventions and standardize other outcome measures beyond mortality.

Systemic inflammatory response syndrome-based severe sepsis screening algorithms in emergency department patients with suspected sepsis.

PubMed

Shetty, Amith L; Brown, Tristam; Booth, Tarra; Van, Kim Linh; Dor-Shiffer, Daphna E; Vaghasiya, Milan R; Eccleston, Cassanne E; Iredell, Jonathan

2016-06-01

Systemic inflammatory response syndrome (SIRS)-based severe sepsis screening algorithms have been utilised in stratification and initiation of early broad spectrum antibiotics for patients presenting to EDs with suspected sepsis. We aimed to investigate the performance of some of these algorithms on a cohort of suspected sepsis patients. We conducted a retrospective analysis on an ED-based prospective sepsis registry at a tertiary Sydney hospital, Australia. Definitions for sepsis were based on the 2012 Surviving Sepsis Campaign guidelines. Numerical values for SIRS criteria and ED investigation results were recorded at the trigger of sepsis pathway on the registry. Performance of specific SIRS-based screening algorithms at sites from USA, Canada, UK, Australia and Ireland health institutions were investigated. Severe sepsis screening algorithms' performance was measured on 747 patients presenting with suspected sepsis (401 with severe sepsis, prevalence 53.7%). Sensitivity and specificity of algorithms to flag severe sepsis ranged from 20.2% (95% CI 16.4-24.5%) to 82.3% (95% CI 78.2-85.9%) and 57.8% (95% CI 52.4-63.1%) to 94.8% (95% CI 91.9-96.9%), respectively. Variations in SIRS values between uncomplicated and severe sepsis cohorts were only minor, except a higher mean lactate (>1.6 mmol/L, P < 0.01). We found the Ireland and JFK Medical Center sepsis algorithms performed modestly in stratifying suspected sepsis patients into high-risk groups. Algorithms with lactate levels thresholds of >2 mmol/L rather than >4 mmol/L performed better. ED sepsis registry-based characterisation of patients may help further refine sepsis definitions of the future. © 2016 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

Pediatric sepsis

PubMed Central

Randolph, Adrienne G; McCulloh, Russell J

2014-01-01

Sepsis is the leading cause of death in children worldwide. Although the diagnosis and management of sepsis in infants and children is largely influenced by studies done in adults, there are important considerations relevant for pediatrics. This article highlights pediatric-specific issues related to the definition of sepsis and its epidemiology and management. We review how the capacity of the immune system to respond to infection develops over early life. We also bring attention to primary immune deficiencies that should be considered in children recurrently infected with specific types of organisms. The management of pediatric sepsis must be tailored to the child’s age and immune capacity, and to the site, severity, and source of the infection. It is important for clinicians to be aware of infection-related syndromes that primarily affect children. Although children in developed countries are more likely to survive severe infections than adults, many survivors have chronic health impairments. PMID:24225404

Sepsis in Pediatric Cardiac Intensive Care.

PubMed

Wheeler, Derek S; Wong, Hector R

2016-08-01

In this review, we will discuss risk factors for developing sepsis; the role of biomarkers in establishing an early diagnosis, in monitoring therapeutic efficacy, in stratification, and for the identification of sepsis endotypes; and the pathophysiology and management of severe sepsis and septic shock, with an emphasis on the impact of sepsis on cardiovascular function. MEDLINE and PubMed. There is a lot of excitement in the field of sepsis research today. Scientific advances in the diagnosis and clinical staging of sepsis, as well as a personalized approach to the treatment of sepsis, offer tremendous promise for the future. However, at the same time, it is also evident that sepsis mortality has not improved enough, even with progress in our understanding of the molecular pathophysiology of sepsis.

Sepsis and septic shock

PubMed Central

Hotchkiss, Richard S.; Moldawer, Lyle L.; Opal, Steven M.; Reinhart, Konrad; Turnbull, Isaiah R.; Vincent, Jean-Louis

2017-01-01

For more than two decades, sepsis was defined as a microbial infection that produces fever (or hypothermia), tachycardia, tachypnoea and blood leukocyte changes. Sepsis is now increasingly being considered a dysregulated systemic inflammatory and immune response to microbial invasion that produces organ injury for which mortality rates are declining to 15–25%. Septic shock remains defined as sepsis with hyperlactataemia and concurrent hypotension requiring vasopressor therapy, with in-hospital mortality rates approaching 30–50%. With earlier recognition and more compliance to best practices, sepsis has become less of an immediate life-threatening disorder and more of a long-term chronic critical illness, often associated with prolonged inflammation, immune suppression, organ injury and lean tissue wasting. Furthermore, patients who survive sepsis have continuing risk of mortality after discharge, as well as long-term cognitive and functional deficits. Earlier recognition and improved implementation of best practices have reduced in-hospital mortality, but results from the use of immunomodulatory agents to date have been disappointing. Similarly, no biomarker can definitely diagnose sepsis or predict its clinical outcome. Because of its complexity, improvements in sepsis outcomes are likely to continue to be slow and incremental. PMID:28117397

Diagnosis and management of sepsis

NASA Astrophysics Data System (ADS)

Arifin

2018-03-01

Sepsis is the life-threatening condition with organ dysfunction caused by dysregulated host response to the infection. Septic shock is part of sepsis where circulatory abnormalities and cellular metabolism occur. Sepsis and septic shock are still a problem in the world, where one in four people with sepsis will die. As well as any trauma case, acute myocardial infarction, or stroke, early identification and appropriate treatment of sepsis immediately after sepsis will improve the prognosis of the patient. Comprehensive management of septic patients is required, ranging from infection controls that include antibiotic administration and infection source control as well as hemodynamic stabilization that included fluid resuscitation and vasoactive drug delivery.

Sepsis in Pediatric Cardiac Intensive Care

PubMed Central

Wheeler, Derek S.; Wong, Hector R.

2016-01-01

Objectives In this review we will discuss risk factors for developing sepsis; the role of biomarkers in establishing an early diagnosis, monitoring therapeutic efficacy, stratification, and for the identification of sepsis endotypes; and the pathophysiology and management of severe sepsis and septic shock, with an emphasis on the impact of sepsis on cardiovascular function. Data Source MEDLINE, PubMed Conclusion There is a lot of excitement in the field of sepsis research today. Scientific advances in the diagnosis and clinical staging of sepsis, as well as a personalized approach to the treatment of sepsis, offer tremendous promise for the future. However, at the same time, it is also evident that sepsis mortality has not improved enough, even with progress in our understanding of the molecular pathophysiology of sepsis. PMID:27490609

The new sepsis definition: limitations and contribution to research and diagnosis of sepsis.

PubMed

Verdonk, Franck; Blet, Alice; Mebazaa, Alexandre

2017-04-01

Based on recent clinical, epidemiological, and pathophysiological data, a third international consensus conference was carried out to define new criteria of sepsis in February 2016. This review presents the different items of this new definition, their limitations and their contribution to research and diagnosis of sepsis, in comparison with the previous definitions. Incidence, management, and pathophysiological knowledge of sepsis have improved over the past 20 years. However, sepsis still evolves to a mortal outcome, in one case out of five, with no new recent or specific therapy showing its efficacy on the patient's prognosis. These findings have led to the development of new definition. The new definition of sepsis incorporates relevant clinical and biological criteria such as SOFA score or serum lactate levels. It no longer takes into account the items of the systemic inflammatory response syndrome, which present a lack of specificity. It also simplifies the different stages of severity by deleting the term of 'severe sepsis' and by defining septic shock as a subset of sepsis. This definition, endorsed by only two international societies of intensive care, has some limitations and so merits prospective validation at different levels.

Surgical trauma induces overgrowth in lower limb gigantism: regulation with use of rapamycin is promising.

PubMed

Pinto, Rohan Sebastian; Harrison, William David; Graham, Kenneth; Nayagam, Durai

2018-01-04

We describe an unclassified overgrowth syndrome characterised by unregulated growth of dermal fibroblasts in the lower limbs of a 35-year-old woman. A PIK3CA gene mutation resulted in lower limb gigantism. Below the waist, she weighed 117 kg with each leg measuring over 100 cm in circumference. Her total adiposity was 50% accounted for by her legs mainly. Liposuction and surgical debulking were performed to reduce the size of the limbs but had exacerbated the overgrowth in her lower limbs. Systemic sepsis from an infected foot ulcer necessitated treatment by an above-knee amputation. Postoperatively, the stump increased in size by 19 kg. A trial of rapamycin to reverse the growth of the stump has shown promise. We discuss the clinical and genetic features of this previously unclassified disorder and the orthopaedic considerations involved. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Neutrophil apoptosis: a marker of disease severity in sepsis and sepsis-induced acute respiratory distress syndrome

PubMed Central

Fialkow, Léa; Fochesatto Filho, Luciano; Bozzetti, Mary C; Milani, Adriana R; Rodrigues Filho, Edison M; Ladniuk, Roberta M; Pierozan, Paula; de Moura, Rafaela M; Prolla, João C; Vachon, Eric; Downey, Gregory P

2006-01-01

Introduction Apoptosis of neutrophils (polymorphonuclear neutrophils [PMNs]) may limit inflammatory injury in sepsis and acute respiratory distress syndrome (ARDS), but the relationship between the severity of sepsis and extent of PMN apoptosis and the effect of superimposed ARDS is unknown. The objective of this study was to correlate neutrophil apoptosis with the severity of sepsis and sepsis-induced ARDS. Methods A prospective cohort study was conducted in intensive care units of three tertiary hospitals in Porto Alegre, southern Brazil. Fifty-seven patients with sepsis (uncomplicated sepsis, septic shock, and sepsis-induced ARDS) and 64 controls were enrolled. Venous peripheral blood was collected from patients with sepsis within 24 hours of diagnosis. All surgical groups, including controls, had their blood drawn 24 hours after surgery. Control patients on mechanical ventilation had blood collected within 24 hours of initiation of mechanical ventilation. Healthy controls were blood donors. Neutrophils were isolated, and incubated ex vivo, and apoptosis was determined by light microscopy on cytospun preparations. The differences among groups were assessed by analysis of variance with Tukeys. Results In medical patients, the mean percentage of neutrophil apoptosis (± standard error of the mean [SEM]) was lower in sepsis-induced ARDS (28% ± 3.3%; n = 9) when compared with uncomplicated sepsis (57% ± 3.2%; n = 8; p < 0.001), mechanical ventilation without infection, sepsis, or ARDS (53% ± 3.0%; n = 11; p < 0.001) and healthy controls (69% ± 1.1%; n = 33; p < 0.001) but did not differ from septic shock (38% ± 3.7%; n = 12; p = 0.13). In surgical patients with sepsis, the percentage of neutrophil apoptosis was lower for all groups when compared with surgical controls (52% ± 3.6%; n = 11; p < 0.001). Conclusion In medical patients with sepsis, neutrophil apoptosis is inversely proportional to the severity of sepsis and thus may be a marker of the severity of

Sepsis in Older Adults.

PubMed

Rowe, Theresa A; McKoy, June M

2017-12-01

Sepsis disproportionally affects older adults with more than 60% of sepsis diagnoses attributed to adults aged 65 years and older. Identifying, diagnosing, and treating sepsis in older individuals remain a challenge for clinicians, and few studies focus specifically on older adults with multiple medical comorbidities. Principles guiding management of sepsis for older adults are generally the same as in younger adults; however, unique considerations particularly pertinent to the care older adults include antimicrobial selection and dosing, delirium management, and goals of care discussions. Other factors, such as medical comorbidities, cognitive impairment, and functional status, impact outcomes more than age alone. Copyright © 2017 Elsevier Inc. All rights reserved.

Sepsis and Septic Shock Strategies.

PubMed

Armstrong, Bracken A; Betzold, Richard D; May, Addison K

2017-12-01

Three therapeutic principles most substantially improve organ dysfunction and survival in sepsis: early, appropriate antimicrobial therapy; restoration of adequate cellular perfusion; timely source control. The new definitions of sepsis and septic shock reflect the inadequate sensitivity, specify, and lack of prognostication of systemic inflammatory response syndrome criteria. Sequential (sepsis-related) organ failure assessment more effectively prognosticates in sepsis and critical illness. Inadequate cellular perfusion accelerates injury and reestablishing perfusion limits injury. Multiple organ systems are affected by sepsis and septic shock and an evidence-based multipronged approach to systems-based therapy in critical illness results in improve outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

Bilateral lower limb amputations in a nigerian child following high-voltage electrical burns injury: a case report.

PubMed

Dim, Em; Amanari, Oc; Nottidge, Te; Inyang, Uc; Nwashindi, A

2013-07-01

The human body conducts electricity very well. Direct contact with electric current can be lethal. The passage of electric current through the body is capable of producing a wide spectrum of injuries, including serious damage to the heart, brain, skin and muscles. Naked high-voltage electric cables negligently abandoned in residential, commercial and industrial areas are a recipe for disaster. This is a case report of a 5-year girl child who had bilateral lower limb gangrene following electrical burns injury. She presented with a fourday history of electrical burns injuries of both lower limbs including both gluteal regions, associated with a three-day history of fever, with full thickness burns and sepsis, ultimately leading to bilateral above knee guillotine amputations. High-voltage electric current, bilateral lower limb gangrene, bilateral above knee amputation.

A Multicenter Survey of House Staff Knowledge About Sepsis and the "Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock".

PubMed

Watkins, Richard R; Haller, Nairmeen; Wayde, Melinda; Armitage, Keith B

2017-01-01

We aimed to assess the knowledge, attitudes, and perceptions of resident physicians regarding sepsis in general and the Surviving Sepsis Campaign Guidelines in particular. After institutional review board approval, we surveyed internal medicine (IM) and emergency medicine (EM) house staff from 3 separate institutions. House staff were notified of the survey via e-mail from their residency director or chief resident. The survey was Internet-based (using http://www.surveymonkey.com ), voluntary, and anonymous. The Surviving Sepsis Campaign Guidelines were used to develop the survey. The survey was open between December 2015 and April 2016. No incentives for participation were given. Reminder e-mails were sent approximately every 3 to 4 weeks to all eligible participants. Comparisons of responses were evaluated using the N-1 2-proportion test. A total of 133 responses were received. These included 84 from IM house staff, 27 from EM house staff, and 22 who selected "other." Eighty (101/126) percent reported managing at least 1 patient with sepsis in the preceding 30 days, 85% (97/114) rated their knowledge of the Surviving Sepsis Guidelines as "very familiar" or at least "somewhat familiar," and 84% (91/108) believed their training in the diagnosis and management of sepsis was "excellent" or at least "good." However, 43% (47/108) reported not receiving any feedback on their treatment of patients with sepsis in the last 30 days, while 24% (26/108) received feedback once. Both IM and EM house staff received comparable rates of feedback (62% vs 48%, respectively; P = .21). For the 3 questions that directly tested knowledge of the guidelines, the scores of the IM and EM house staff were similar. Notably, <20% of both groups correctly identified diagnostic criteria for sepsis. Additional education of IM and EM house staff on the Surviving Sepsis Campaign Guidelines is warranted, along with more consistent feedback regarding their diagnosis and management of sepsis.

Global epidemiology of pediatric severe sepsis: the sepsis prevalence, outcomes, and therapies study.

PubMed

Weiss, Scott L; Fitzgerald, Julie C; Pappachan, John; Wheeler, Derek; Jaramillo-Bustamante, Juan C; Salloo, Asma; Singhi, Sunit C; Erickson, Simon; Roy, Jason A; Bush, Jenny L; Nadkarni, Vinay M; Thomas, Neal J

2015-05-15

Limited data exist about the international burden of severe sepsis in critically ill children. To characterize the global prevalence, therapies, and outcomes of severe sepsis in pediatric intensive care units to better inform interventional trials. A point prevalence study was conducted on 5 days throughout 2013-2014 at 128 sites in 26 countries. Patients younger than 18 years of age with severe sepsis as defined by consensus criteria were included. Outcomes were severe sepsis point prevalence, therapies used, new or progressive multiorgan dysfunction, ventilator- and vasoactive-free days at Day 28, functional status, and mortality. Of 6,925 patients screened, 569 had severe sepsis (prevalence, 8.2%; 95% confidence interval, 7.6-8.9%). The patients' median age was 3.0 (interquartile range [IQR], 0.7-11.0) years. The most frequent sites of infection were respiratory (40%) and bloodstream (19%). Common therapies included mechanical ventilation (74% of patients), vasoactive infusions (55%), and corticosteroids (45%). Hospital mortality was 25% and did not differ by age or between developed and resource-limited countries. Median ventilator-free days were 16 (IQR, 0-25), and vasoactive-free days were 23 (IQR, 12-28). Sixty-seven percent of patients had multiorgan dysfunction at sepsis recognition, with 30% subsequently developing new or progressive multiorgan dysfunction. Among survivors, 17% developed at least moderate disability. Sample sizes needed to detect a 5-10% absolute risk reduction in outcomes within interventional trials are estimated between 165 and 1,471 [corrected] patients per group. Pediatric severe sepsis remains a burdensome public health problem, with prevalence, morbidity, and mortality rates similar to those reported in critically ill adult populations. International clinical trials targeting children with severe sepsis are warranted.

Update on pediatric sepsis: a review.

PubMed

Kawasaki, Tatsuya

2017-01-01

Sepsis is one of the leading causes of mortality among children worldwide. Unfortunately, however, reliable evidence was insufficient in pediatric sepsis and many aspects in clinical practice actually depend on expert consensus and some evidence in adult sepsis. More recent findings have given us deep insights into pediatric sepsis since the publication of the Surviving Sepsis Campaign guidelines 2012. New knowledge was added regarding the hemodynamic management and the timely use of antimicrobials. Quality improvement initiatives of pediatric "sepsis bundles" were reported to be successful in clinical outcomes by several centers. Moreover, a recently published global epidemiologic study (the SPROUT study) did not only reveal the demographics, therapeutic interventions, and prognostic outcomes but also elucidated the inappropriateness of the current definition of pediatric sepsis. With these updated knowledge, the management of pediatric sepsis would be expected to make further progress. In addition, it is meaningful that the fundamental data on which future research should be based were established through the SPROUT study.

Temporal trends in the systemic inflammatory response syndrome, sepsis, and medical coding of sepsis.

PubMed

Thomas, Benjamin S; Jafarzadeh, S Reza; Warren, David K; McCormick, Sandra; Fraser, Victoria J; Marschall, Jonas

2015-11-24

Recent reports using administrative claims data suggest the incidence of community- and hospital-onset sepsis is increasing. Whether this reflects changing epidemiology, more effective diagnostic methods, or changes in physician documentation and medical coding practices is unclear. We performed a temporal-trend study from 2008 to 2012 using administrative claims data and patient-level clinical data of adult patients admitted to Barnes-Jewish Hospital in St. Louis, Missouri. Temporal-trend and annual percent change were estimated using regression models with autoregressive integrated moving average errors. We analyzed 62,261 inpatient admissions during the 5-year study period. 'Any SIRS' (i.e., SIRS on a single calendar day during the hospitalization) and 'multi-day SIRS' (i.e., SIRS on 3 or more calendar days), which both use patient-level data, and medical coding for sepsis (i.e., ICD-9-CM discharge diagnosis codes 995.91, 995.92, or 785.52) were present in 35.3 %, 17.3 %, and 3.3 % of admissions, respectively. The incidence of admissions coded for sepsis increased 9.7 % (95 % CI: 6.1, 13.4) per year, while the patient data-defined events of 'any SIRS' decreased by 1.8 % (95 % CI: -3.2, -0.5) and 'multi-day SIRS' did not change significantly over the study period. Clinically-defined sepsis (defined as SIRS plus bacteremia) and severe sepsis (defined as SIRS plus hypotension and bacteremia) decreased at statistically significant rates of 5.7 % (95 % CI: -9.0, -2.4) and 8.6 % (95 % CI: -4.4, -12.6) annually. All-cause mortality, SIRS mortality, and SIRS and clinically-defined sepsis case fatality did not change significantly during the study period. Sepsis mortality, based on ICD-9-CM codes, however, increased by 8.8 % (95 % CI: 1.9, 16.2) annually. The incidence of sepsis, defined by ICD-9-CM codes, and sepsis mortality increased steadily without a concomitant increase in SIRS or clinically-defined sepsis. Our results highlight the need to develop

Comparison of the Performance Between Sepsis-1 and Sepsis-3 in ICUs in China: A Retrospective Multicenter Study.

PubMed

Cheng, Baoli; Li, Zhongwang; Wang, Jingya; Xie, Guohao; Liu, Xu; Xu, Zhipeng; Chu, Lihua; Zhao, Jialian; Yao, Yongming; Fang, Xiangming

2017-09-01

The definition of sepsis was updated to sepsis-3 in February 2016. However, the performance of the previous and new definition of sepsis remains unclear in China. This was a retrospective multicenter study in six intensive care unit (ICUs) from five university-affiliated hospitals to compare the performance between sepsis-1 and sepsis-3 in China. From May 1, 2016 to June 1, 2016, 496 patients were enrolled consecutively. Data were extracted from the electronic clinical records. We evaluated the performance of sepsis-1 and sepsis-3 by measuring the area under the receiver operating characteristic curves (AUROC) to predict 28-day mortality rates. Of 496 enrolled patients, 186 (37.5%) were diagnosed with sepsis according to sepsis-1, while 175 (35.3%) fulfilled the criteria of sepsis-3. The AUROC of systemic inflammatory response syndrome (SIRS) is significantly smaller than that of sequential organ failure assessment (SOFA) (0.55 [95% confidence interval, 0.46-0.64] vs. 0.69 (95% confidence interval, 0.61-0.77], P = 0.008) to predict 28-day mortality rates of infected patients. Moreover, 5.9% infected patients (11 patients) were diagnosed as sepsis according to sepsis-1 but not to sepsis-3. The APACHE II, SOFA scores, and mortality rate of the 11 patients were significantly lower than of patients whose sepsis was defined by both the previous and new criteria (8.6±3.5 vs. 16.3±6.2, P =  < 0.001; 1 (0-1) vs. 6 (4-8), P = <0.001; 0.0 vs. 33.1%, P = 0.019). In addition, the APACHE II, length of stay in ICU, and 28-day mortality rate of septic patients rose gradually corresponding with the raise in SOFA score (but not the SIRS score). Sepsis-3 performed better than sepsis-1 in the study samples in ICUs in China.

Animal models of sepsis.

PubMed

Fink, Mitchell P

2014-01-01

Sepsis remains a common, serious, and heterogeneous clinical entity that is difficult to define adequately. Despite its importance as a public health problem, efforts to develop and gain regulatory approval for a specific therapeutic agent for the adjuvant treatment of sepsis have been remarkably unsuccessful. One step in the critical pathway for the development of a new agent for adjuvant treatment of sepsis is evaluation in an appropriate animal model of the human condition. Unfortunately, the animal models that have been used for this purpose have often yielded misleading findings. It is likely that there are multiple reasons for the discrepancies between the results obtained in tests of pharmacological agents in animal models of sepsis and the outcomes of human clinical trials. One of important reason may be that the changes in gene expression, which are triggered by trauma or infection, are different in mice, a commonly used species for preclinical testing, and humans. Additionally, many species, including mice and baboons, are remarkably resistant to the toxic effects of bacterial lipopolysaccharide, whereas humans are exquisitely sensitive. New approaches toward the use of animals for sepsis research are being investigated. But, at present, results from preclinical studies of new therapeutic agents for sepsis must be viewed with a degree of skepticism.

Global Epidemiology of Pediatric Severe Sepsis: The Sepsis Prevalence, Outcomes, and Therapies Study

PubMed Central

Weiss, Scott L.; Pappachan, John; Wheeler, Derek; Jaramillo-Bustamante, Juan C.; Salloo, Asma; Singhi, Sunit C.; Erickson, Simon; Roy, Jason A.; Bush, Jenny L.; Nadkarni, Vinay M.; Thomas, Neal J.

2015-01-01

Rationale: Limited data exist about the international burden of severe sepsis in critically ill children. Objectives: To characterize the global prevalence, therapies, and outcomes of severe sepsis in pediatric intensive care units to better inform interventional trials. Methods: A point prevalence study was conducted on 5 days throughout 2013–2014 at 128 sites in 26 countries. Patients younger than 18 years of age with severe sepsis as defined by consensus criteria were included. Outcomes were severe sepsis point prevalence, therapies used, new or progressive multiorgan dysfunction, ventilator- and vasoactive-free days at Day 28, functional status, and mortality. Measurements and Main Results: Of 6,925 patients screened, 569 had severe sepsis (prevalence, 8.2%; 95% confidence interval, 7.6–8.9%). The patients’ median age was 3.0 (interquartile range [IQR], 0.7–11.0) years. The most frequent sites of infection were respiratory (40%) and bloodstream (19%). Common therapies included mechanical ventilation (74% of patients), vasoactive infusions (55%), and corticosteroids (45%). Hospital mortality was 25% and did not differ by age or between developed and resource-limited countries. Median ventilator-free days were 16 (IQR, 0–25), and vasoactive-free days were 23 (IQR, 12–28). Sixty-seven percent of patients had multiorgan dysfunction at sepsis recognition, with 30% subsequently developing new or progressive multiorgan dysfunction. Among survivors, 17% developed at least moderate disability. Sample sizes needed to detect a 5–10% absolute risk reduction in outcomes within interventional trials are estimated between 165 and 1,437 patients per group. Conclusions: Pediatric severe sepsis remains a burdensome public health problem, with prevalence, morbidity, and mortality rates similar to those reported in critically ill adult populations. International clinical trials targeting children with severe sepsis are warranted. PMID:25734408

Pharmacological management of sepsis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fletcher, J.R.

Systemic sepsis continues to be the most-difficult management problem in caring for the combat casualty. The complications of sepsis pervade all areas of injury to soldiers in the field, whether it is mechanical (missiles), thermal (burns), chemical, biological, or radiation injury. With the advent of tactical nuclear weapons, the problem of sepsis will be much higher in future wars than has previously been experienced through the world. The purpose of this chapter is a) to review the data suggesting pharmacological agents that may benefit the septic patient, and b) to emphasize the adjunctive therapies that should be explored in clinicalmore » trials. The pharmacological management of sepsis remains controversial. Most of the drugs utilized clinically treat the symptoms of the disease and are not necessarily directed at fundamental mechanisms that are known to be present in sepsis. A broad data base is emerging, indicating that NSAID should be used in human clinical trials. Prostaglandins are sensitive indicators of cellular injury and may be mediators for a number of vasoactive chemicals. Opiate antagonists and calcium channel blockers require more in-depth data; however, recent studies generate excitement for their potential use in the critically ill patient. Pharmacological effects of antibiotics, in concert with other drugs, suggest an entirely new approach to pharmacological treatment in sepsis. There is no doubt that new treatment modalities or adjunctive therapies must be utilized to alter the poor prognosis of severe sepsis that we have observed in the past 4 decades.« less

[Diagnostic value of a combination of biomarkers in patients with sepsis and severe sepsis in emergency department].

PubMed

Zhao, Yongzhen; Li, Chunsheng

2014-03-01

To determine a combination of biomarkers that assure the diagnosis of sepsis and severe sepsis in patients in emergency department (ED). A total of 652 patients with systemic inflammatory response syndrome (SIRS) were enrolled for this prospective study in the ED of Beijing Chaoyang Hospital of the Capital Medical University between March 2010 and March 2013. Eight biomarkers were determined, including levels of procalcitonin (PCT), interleukin-6 (IL-6), D-dimer, C-reactive protein (CRP), brain natriuretic peptide (BNP), white blood cell count (WBC), percentage of immature neutrophil, and platelet count (PLT). Patients were divided into the sepsis group (452 cases) and non-sepsis group (200 cases) according to the diagnostic criteria of sepsis. Then all these patients were stratified into severe sepsis group (190 cases, including septic shock) and non-severe sepsis group (462 cases) according to the diagnosis of severe sepsis. Logistic regression was performed to identify the independent factors for the diagnosis of sepsis and severe sepsis, and the optimal combination of biomarkers was established. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic ability of the combination and the biomarkers.A total of 652 patients with systemic inflammatory response syndrome (SIRS) were enrolled for this prospective study in the ED of Beijing Chaoyang Hospital of the Capital Medical University between March 2010 and March 2013. Eight biomarkers were determined, including levels of procalcitonin (PCT), interleukin-6 (IL-6), D-dimer, C-reactive protein (CRP), brain natriuretic peptide (BNP), white blood cell count (WBC), percentage of immature neutrophil, and platelet count (PLT). Patients were divided into the sepsis group (452 cases) and non-sepsis group (200 cases) according to the diagnostic criteria of sepsis. Then all these patients were stratified into severe sepsis group (190 cases, including septic shock) and non-severe sepsis group (462

Differential expression of plasma miR-146a in sepsis patients compared with non-sepsis-SIRS patients.

PubMed

Wang, Lina; Wang, Hua-Cheng; Chen, Cha; Zeng, Jianming; Wang, Qian; Zheng, Lei; Yu, Huan-DU

2013-04-01

Sepsis is a subtype of systemic inflammatory response syndrome (SIRS), which is characterized by infection. Circulating microRNAs (miRNAs), including miR-150, miR-146a and miR-223, are potential biomarkers of sepsis. In this study, we demonstrated that measuring the relative expression of miR-146a/U6 in plasma, using the 2 -ΔΔCt method, provides a method for differentiating between sepsis and non-sepsis-SIRS. We observed a significant increase in miR-146a expression in the initial cohort of 6 non-sepsis-SIRS patients compared to the 4 sepsis patients (P=0.01) and in the second cohort of 8 non-sepsis-SIRS patients compared to the 10 sepsis patients (P=0.027). Additionally, we identified that sodium citrate and ethylenediaminetetraacetic acid (EDTA) K 2 may be used as anticoagulant reagents. Generation of a standard curve is not necessary in these diagnostic tests, unless the standard of normalization is carefully selected. Thus we provide more detailed guidance for the clinical use of circulating miRNA biomarkers.

Triage sepsis alert and sepsis protocol lower times to fluids and antibiotics in the ED.

PubMed

Hayden, Geoffrey E; Tuuri, Rachel E; Scott, Rachel; Losek, Joseph D; Blackshaw, Aaron M; Schoenling, Andrew J; Nietert, Paul J; Hall, Greg A

2016-01-01

Early identification of sepsis in the emergency department (ED), followed by adequate fluid hydration and appropriate antibiotics, improves patient outcomes. We sought to measure the impact of a sepsis workup and treatment protocol (SWAT) that included an electronic health record (EHR)-based triage sepsis alert, direct communication, mobilization of resources, and standardized order sets. We conducted a retrospective, quasiexperimental study of adult ED patients admitted with suspected sepsis, severe sepsis, or septic shock. We defined a preimplementation (pre-SWAT) group and a postimplementation (post-SWAT) group and further broke these down into SWAT A (septic shock) and SWAT B (sepsis with normal systolic blood pressure). We performed extensive data comparisons in the pre-SWAT and post-SWAT groups, including demographics, systemic inflammatory response syndrome criteria, time to intravenous fluids bolus, time to antibiotics, length-of-stay times, and mortality rates. There were 108 patients in the pre-SWAT group and 130 patients in the post-SWAT group. The mean time to bolus was 31 minutes less in the postimplementation group, 51 vs 82 minutes (95% confidence interval, 15-46; P value < .01). The mean time to antibiotics was 59 minutes less in the postimplementation group, 81 vs 139 minutes (95% confidence interval, 44-74; P value < .01). Segmented regression modeling did not identify secular trends in these outcomes. There was no significant difference in mortality rates. An EHR-based triage sepsis alert and SWAT protocol led to a significant reduction in the time to intravenous fluids and time to antibiotics in ED patients admitted with suspected sepsis, severe sepsis, and septic shock. Copyright © 2015 Elsevier Inc. All rights reserved.

The evolutionary logic of sepsis.

PubMed

Rózsa, Lajos; Apari, Péter; Sulyok, Mihály; Tappe, Dennis; Bodó, Imre; Hardi, Richárd; Müller, Viktor

2017-11-01

The recently proposed Microbiome Mutiny Hypothesis posits that members of the human microbiome obtain information about the host individuals' health status and, when host survival is compromised, switch to an intensive exploitation strategy to maximize residual transmission. In animals and humans, sepsis is an acute systemic reaction to microbes invading the normally sterile body compartments. When induced by formerly mutualistic or neutral microbes, possibly in response to declining host health, sepsis appears to fit the 'microbiome mutiny' scenario except for its apparent failure to enhance transmission of the causative organisms. We propose that the ability of certain species of the microbiome to induce sepsis is not a fortuitous side effect of within-host replication, but rather it might, in some cases, be the result of their adaptive evolution. Whenever host health declines, inducing sepsis can be adaptive for those members of the healthy human microbiome that are capable of colonizing the future cadaver and spread by cadaver-borne transmission. We hypothesize that such microbes might exhibit switches along the 'mutualist - lethal pathogen - decomposer - mutualist again' scenario, implicating a previously unsuspected, surprising level of phenotypic plasticity. This hypothesis predicts that those species of the healthy microbiome that are recurring causative agents of sepsis can participate in the decomposition of cadavers, and can be transmitted as soil-borne or water-borne infections. Furthermore, in individual sepsis cases, the same microbial clones that dominate the systemic infection that precipitates sepsis, should also be present in high concentration during decomposition following death: this prediction is testable by molecular fingerprinting in experimentally induced animal models. Sepsis is a leading cause of human death worldwide. If further research confirms that some cases of sepsis indeed involve the 'mutiny' (facultative phenotypic switching) of

Sepsis in general surgery: a deadly complication.

PubMed

Moore, Laura J; Moore, Frederick A; Jones, Stephen L; Xu, Jiaqiong; Bass, Barbara L

2009-12-01

Sepsis is a deadly and potentially preventable complication. A better understanding of sepsis in general surgery patients is needed to help direct resources to those patients at highest risk for death from sepsis. We identified risk factors for sepsis in general surgery patients by using the National Surgical Quality Improvement Project database. Analysis of the database identified 3 major risk factors for both the development of sepsis and death from sepsis in general surgery patients. These risk factors are age older than 60 years, need for emergency surgery, and the presence of comorbid conditions. Risk factors for death from sepsis or septic shock in general surgery patients include age older than 60 years, need for emergency surgery, and the presence of preexisting comorbidities. These findings emphasize the need for early recognition through aggressive sepsis screening and rapid implementation of evidence-based interventions for sepsis and septic shock in general surgery patients with these risk factors.

Sepsis in Children: Global Implications of the World Health Assembly Resolution on Sepsis.

PubMed

Kissoon, Niranjan; Reinhart, Konrad; Daniels, Ron; Machado, Machado Flavia R; Schachter, Raymond D; Finfer, Simon

2017-12-01

Sepsis, worldwide the leading cause of death in children, has now been recognized as the global health emergency it is. On May 26, 2017, the World Health Assembly, the decision-making body of the World Health Organization, adopted a resolution proposed by the Global Sepsis Alliance to improve the prevention, diagnosis, and management of sepsis. To discuss the implications of this resolution for children worldwide. The resolution highlights sepsis as a global threat and urges the 194 United Nations member states to take specific actions and implement appropriate measures to reduce its human and health economic burden. The resolution is a major step toward achieving the targets outlined by the Sustainable Developmental Goals for decreasing mortality in infants and children, but implementing it will require a concerted global effort.

Premise for Standardized Sepsis Models.

PubMed

Remick, Daniel G; Ayala, Alfred; Chaudry, Irshad; Coopersmith, Craig M; Deutschman, Clifford; Hellman, Judith; Moldawer, Lyle; Osuchowski, Marcin

2018-06-05

Sepsis morbidity and mortality exacts a toll on patients and contributes significantly to healthcare costs. Preclinical models of sepsis have been used to study disease pathogenesis and test new therapies, but divergent outcomes have been observed with the same treatment even when using the same sepsis model. Other disorders such as diabetes, cancer, malaria, obesity and cardiovascular diseases have used standardized, preclinical models that allow laboratories to compare results. Standardized models accelerate the pace of research and such models have been used to test new therapies or changes in treatment guidelines. The National Institutes of Health (NIH) mandated that investigators increase data reproducibility and the rigor of scientific experiments and has also issued research funding announcements about the development and refinement of standardized models. Our premise is that refinement and standardization of preclinical sepsis models may accelerate the development and testing of potential therapeutics for human sepsis, as has been the case with preclinical models for other disorders. As a first step towards creating standardized models, we suggest 1) standardizing the technical standards of the widely used cecal ligation and puncture model and 2) creating a list of appropriate organ injury and immune dysfunction parameters. Standardized sepsis models could enhance reproducibility and allow comparison of results between laboratories and may accelerate our understanding of the pathogenesis of sepsis.

Defining sepsis on the wards: results of a multi-centre point-prevalence study comparing two sepsis definitions.

PubMed

Szakmany, T; Pugh, R; Kopczynska, M; Lundin, R M; Sharif, B; Morgan, P; Ellis, G; Abreu, J; Kulikouskaya, S; Bashir, K; Galloway, L; Al-Hassan, H; Grother, T; McNulty, P; Seal, S T; Cains, A; Vreugdenhil, M; Abdimalik, M; Dennehey, N; Evans, G; Whitaker, J; Beasant, E; Hall, C; Lazarou, M; Vanderpump, C V; Harding, K; Duffy, L; Guerrier Sadler, A; Keeling, R; Banks, C; Ng, S W Y; Heng, S Y; Thomas, D; Puw, E W; Otahal, I; Battle, C; Minik, O; Lyons, R A; Hall, J E

2018-02-01

Our aim was to prospectively determine the predictive capabilities of SEPSIS-1 and SEPSIS-3 definitions in the emergency departments and general wards. Patients with National Early Warning Score (NEWS) of 3 or above and suspected or proven infection were enrolled over a 24-h period in 13 Welsh hospitals. The primary outcome measure was mortality within 30 days. Out of the 5422 patients screened, 431 fulfilled inclusion criteria and 380 (88%) were recruited. Using the SEPSIS-1 definition, 212 patients had sepsis. When using the SEPSIS-3 definitions with Sequential Organ Failure Assessment (SOFA) score ≥ 2, there were 272 septic patients, whereas with quickSOFA score ≥ 2, 50 patients were identified. For the prediction of primary outcome, SEPSIS-1 criteria had a sensitivity (95%CI) of 65% (54-75%) and specificity of 47% (41-53%); SEPSIS-3 criteria had a sensitivity of 86% (76-92%) and specificity of 32% (27-38%). SEPSIS-3 and SEPSIS-1 definitions were associated with a hazard ratio (95%CI) 2.7 (1.5-5.6) and 1.6 (1.3-2.5), respectively. Scoring system discrimination evaluated by receiver operating characteristic curves was highest for Sequential Organ Failure Assessment score (0.69 (95%CI 0.63-0.76)), followed by NEWS (0.58 (0.51-0.66)) (p < 0.001). Systemic inflammatory response syndrome criteria (0.55 (0.49-0.61)) and quickSOFA score (0.56 (0.49-0.64)) could not predict outcome. The SEPSIS-3 definition identified patients with the highest risk. Sequential Organ Failure Assessment score and NEWS were better predictors of poor outcome. The Sequential Organ Failure Assessment score appeared to be the best tool for identifying patients with high risk of death and sepsis-induced organ dysfunction. © 2017 The Association of Anaesthetists of Great Britain and Ireland.

Pediatric sepsis in the developing world: challenges in defining sepsis and issues in post-discharge mortality.

PubMed

Wiens, Matthew O; Kumbakumba, Elias; Kissoon, Niranjan; Ansermino, J Mark; Ndamira, Andrew; Larson, Charles P

2012-01-01

Sepsis represents the progressive underlying inflammatory pathway secondary to any infectious illness, and ultimately is responsible for most infectious disease-related deaths. Addressing issues related to sepsis has been recognized as an important step towards reducing morbidity and mortality in developing countries, where the majority of the 7.5 million annual deaths in children under 5 years of age are considered to be secondary to sepsis. However, despite its prevalence, sepsis is largely neglected. Application of sepsis definitions created for use in resource-rich countries are neither practical nor feasible in most developing country settings, and alternative definitions designed for use in these settings need to be established. It has also been recognized that the inflammatory state created by sepsis increases the risk of post-discharge morbidity and mortality in developed countries, but exploration of this issue in developing countries is lacking. Research is urgently required to characterize better this potentially important issue.

Costs of postoperative sepsis: the business case for quality improvement to reduce postoperative sepsis in veterans affairs hospitals.

PubMed

Vaughan-Sarrazin, Mary S; Bayman, Levent; Cullen, Joseph J

2011-08-01

To estimate the incremental costs associated with sepsis as a complication of general surgery, controlling for patient risk factors that may affect costs (eg, surgical complexity and comorbidity) and hospital-level variation in costs. Database analysis. One hundred eighteen Veterans Health Affairs hospitals. A total of 13 878 patients undergoing general surgery during fiscal year 2006 (October 1, 2005, through September 30, 2006). Incremental costs associated with sepsis as a complication of general surgery (controlling for patient risk factors and hospital-level variation of costs), as well as the increase in costs associated with complications that co-occur with sepsis. Costs were estimated using the Veterans Health Affairs Decision Support System, and patient risk factors and postoperative complications were identified in the Veterans Affairs Surgical Quality Improvement Program database. Overall, 564 of 13 878 patients undergoing general surgery developed postoperative sepsis, for a rate of 4.1%. The average unadjusted cost for patients with no sepsis was $24 923, whereas the average cost for patients with sepsis was 3.6 times higher at $88 747. In risk-adjusted analyses, the relative costs were 2.28 times greater for patients with sepsis relative to patients without sepsis (95% confidence interval, 2.19-2.38), with the difference in risk-adjusted costs estimated at $26 972 (ie, $21 045 vs $48 017). Sepsis often co-occurred with other types of complications, most frequently with failure to wean the patient from mechanical ventilation after 48 hours (36%), postoperative pneumonia (31%), and reintubation for respiratory or cardiac failure (29%). Costs were highest when sepsis occurred with pneumonia or failure to wean the patient from mechanical ventilation after 48 hours. Given the high cost of treating sepsis, a business case can be made for quality improvement initiatives that reduce the likelihood of postoperative sepsis.

Endoplasmic Reticulum Stress in Sepsis

PubMed Central

Khan, Mohammad Moshahid; Yang, Weng-Lang; Wang, Ping

2015-01-01

Sepsis is an enormous public health issue and the leading cause of death in critically ill patients in intensive care units (ICU). Overwhelming inflammation, characterized by cytokine storm, oxidative threats, and neutrophil sequestration is an underlying component of sepsis-associated organ failure. Despite recent advances in sepsis research, there is still no effective treatment available beyond the standard of care and supportive therapy. To reduce sepsis-related mortality, a better understanding of the biological mechanism associated with the sepsis is essential. Endoplasmic reticulum (ER), a subcellular organelle is responsible for the facilitation of protein folding and assembly and involved in several other physiological activities. Under the stress and inflammation condition, ER loses the homeostasis in its function, which is termed as ER stress. During ER stress, unfolded protein response (UPR) is activated to restore ER function to its normal balance. However, once the stress is beyond the compensatory capacity of UPR or protracted, the apoptosis would be initiated by triggering cell injuries, even to cell death. As such, ER stress and UPR are reported to be implicated in several pathological and inflammatory conditions. Although the detrimental role of ER stress during infections has been demonstrated, there is growing evidences that ER stress participate in the pathogenesis of sepsis. In this review, we summarize the current research in the context of ER stress and UPR signaling associated with sepsis and its related clinical conditions, such as trauma- hemorrhage, and ischemia/reperfusion (I/R) injury. We also discuss the potential implication of ER stress as a novel therapeutic target and prognostic marker in patients with sepsis. PMID:26125088

Pediatric sepsis: actions to decrease sepsis in children.

PubMed

Marraro, Giuseppe A

2009-10-01

The European Society of Pediatric and Neonatal Intensive Care is the physicians' and nurses' annual meeting that was held in Verona, Italy from 14 to 17 June 2009, and approximately 1000 participants from around the world (84 countries) attended. The Congress gave an opportunity to experts to discuss ongoing research and exchange opinions on the future development of studies to identify optimal supportive, preventive and therapeutic strategies for sepsis. A wide range of topics were discussed and several lectures, oral presentations and posters were dedicated to sepsis and its treatment. High scientific-level topics were presented, and stimulated much interest and discussion.

C-Reactive Protein and Hemogram Parameters for the Non-Sepsis Systemic Inflammatory Response Syndrome and Sepsis: What Do They Mean?

PubMed

Gucyetmez, Bulent; Atalan, Hakan K

2016-01-01

Sepsis is one of the most common reasons of increased mortality and morbidity in the intensive care unit. The changes in CRP levels and hemogram parameters and their combinations may help to distinguish sepsis from non-sepsis SIRS. The aim of this study is to investigate the CRP and hemogram parameters as an indicator of sepsis. A total of 2777 patients admitted to the ICU of two centers between 2006-2013 were evaluated retrospectively. The patients were diagnosed as SIRS (-), non-sepsis SIRS and sepsis. The patients who were under 18 years old, re-admitted, diagnosed with hematological disease, on corticosteroid and immunosuppressive therapy, SIRS (-), culture negative, undocumented laboratory values and outcomes were excluded. 1257 patients were divided into 2 groups as non-sepsis SIRS and sepsis. The patients' demographic data, CRP levels, hemogram parameters, length of ICU stay and mortality were recorded. 1257 patients were categorized as non-sepsis SIRS (816, 64.9%) and sepsis (441, 35.1%). In the multivariate analysis, the likelihood of sepsis was increased 3.2 (2.2-4.6), 1.7 (1.2-2.4), 1.6 (1.2-2.1), 2.3 (1.4-3.8), 1.5 (1.1-2.1) times by the APACHE II≥13, SOFA score≥4, CRP≥4.0, LymC<0.45 and PLTC<150 respectively (p<0.001 p = 0.007 p = 0.004 p<0.001 p = 0.027). The likelihood of sepsis was increased 18.1 (8.4-38.7) times by the combination of CRP≥4.0, lymC<0.45 and PLTC<150 (P<0.001). While WBCC, NeuC, Neu%, NLCR and EoC are far from being the indicators to distinguish sepsis from non-sepsis SIRS, the combinations of CRP, LymC and PLTC can be used to determine the likelihood of sepsis.

Methionine Metabolites in Patients With Sepsis.

PubMed

Wexler, Orren; Gough, Michael S; Morgan, Mary Anne M; Mack, Cynthia M; Apostolakos, Michael J; Doolin, Kathleen P; Mooney, Robert A; Arning, Erland; Bottiglieri, Teodoro; Pietropaoli, Anthony P

2018-01-01

Sepsis is characterized by microvascular dysfunction and thrombophilia. Several methionine metabolites may be relevant to this sepsis pathophysiology. S-adenosylmethionine (SAM) serves as the methyl donor for trans-methylation reactions. S-adenosylhomocysteine (SAH) is the by-product of these reactions and serves as the precursor to homocysteine. Relationships between plasma total homocysteine concentrations (tHcy) and vascular disease and thrombosis are firmly established. We hypothesized that SAM, SAH, and tHcy levels are elevated in patients with sepsis and associated with mortality. This was a combined case-control and prospective cohort study consisting of 109 patients with sepsis and 50 control participants without acute illness. The study was conducted in the medical and surgical intensive care units of the University of Rochester Medical Center. Methionine, SAM, SAH, and tHcy concentrations were compared in patients with sepsis versus control participants and in sepsis survivors versus nonsurvivors. Patients with sepsis had significantly higher plasma SAM and SAH concentrations than control participants (SAM: 164 [107-227] vs73 [59-87 nM], P < .001; SAH: 99 [60-165] vs 35 [28-45] nM, P < .001). In contrast, plasma tHcy concentrations were lower in sepsis patients compared to healthy control participants (4 [2-6]) vs 7 [5-9] μM; P = .04). In multivariable analysis, quartiles of SAM, SAH, and tHcy were independently associated with sepsis ( P = .006, P = .05, and P < .001, respectively). Sepsis nonsurvivors had significantly higher plasma SAM and SAH concentrations than survivors (SAM: 223 [125-260] vs 136 [96-187] nM; P = .01; SAH: 139 [81-197] vs 86 [55-130] nM, P = .006). Plasma tHcy levels were similar in survivors vs nonsurvivors. The associations between SAM or SAH and hospital mortality were no longer significant after adjusting for renal dysfunction. Methionine metabolite concentrations are abnormal in sepsis and linked with clinical outcomes

Lower Leg Anterior and Lateral Intracompartmental Pressure Changes Before and After Classic Versus Skate Nordic Rollerskiing.

PubMed

Woods, Katherine M; Petron, David J; Shultz, Barry B; Hicks-Little, Charlie A

2015-08-01

Chronic exertional compartment syndrome (CECS) is a debilitating condition resulting in loss of function and a decrease in athletic performance. Cases of CECS are increasing among Nordic skiers; therefore, analysis of intracompartmental pressures (ICPs) before and after Nordic skiing is warranted. To determine if lower leg anterior and lateral ICPs and subjective lower leg pain levels increased after a 20-minute Nordic rollerskiing time trial and to examine if differences existed between postexercise ICPs for the 2 Nordic rollerskiing techniques, classic and skate. Crossover study. Outdoor paved loop. Seven healthy Division I Nordic skiers (3 men, 4 women; age = 22.71 ± 1.38 y, height = 175.36 ± 6.33 cm, mass = 70.71 ± 6.58 kg). Participants completed two 20-minute rollerskiing time trials using the classic and skate technique in random order. The time trials were completed 7 days apart. Anterior and lateral ICPs and lower leg pain scores were obtained at baseline and at minutes 1 and 5 after rollerskiing. Anterior and lateral ICPs (mm Hg) were measured using a Stryker Quic STIC handheld monitor. Subjective measures of lower leg pain were recorded using the 11-point Numeric Rating Scale. Increases in both anterior (P = .000) and lateral compartment (P = .002) ICPs were observed, regardless of rollerskiing technique used. Subjective lower leg pain increased after the classic technique for the men from baseline to 1 minute postexercise and after the skate technique for the women. Significant 3-way interactions (technique × time × sex) were observed for the anterior (P = .002) and lateral (P = .009) compartment ICPs and lower leg pain (P = .005). Postexercise anterior and lateral ICPs increased compared with preexercise ICPs after both classic and skate rollerskiing techniques. Lower leg pain is a primary symptom of CECS. The subjective lower leg pain 11-point Numeric Rating Scale results indicate that increases in lower leg ICPs sustained during Nordic

Sepsis

MedlinePlus

... pressure drops and the heart weakens, leading to septic shock. Anyone can get sepsis, but the risk is higher in People with weakened immune systems Infants and children The elderly People with chronic ...

Pre-Sepsis Depressive Symptoms Are Associated with Incident Cognitive Impairment in Survivors of Severe Sepsis: A Prospective Cohort Study of Older Americans

PubMed Central

Davydow, Dimitry S.; Hough, Catherine L.; Langa, Kenneth M.; Iwashyna, Theodore J.

2012-01-01

Objectives To test the hypothesis that pre-sepsis depressive symptoms are associated with an increased risk of new cognitive impairment in severe sepsis survivors. Design Prospective longitudinal cohort study. Setting Population-based cohort of older U.S. adults interviewed as part of the Health and Retirement Study (1998–2006). Participants 447 patients with normal pre-sepsis cognition who survived 540 hospitalizations for severe sepsis and completed at least one follow-up interview. Measurements Severe sepsis was identified using a validated algorithm in Medicare claims. Depressive symptoms were assessed prospectively with a modified version of the Center for Epidemiologic Studies Depression Scale. Cognitive function was assessed using versions of the Telephone Interview for Cognitive Status (TICS). We used logistic regression with robust standard errors to examine associations between substantial depressive symptoms at any interview before sepsis and incident cognitive impairment (either mild or moderate-to-severe cognitive impairment) at any interview after sepsis. Results The prevalence of substantial depressive symptoms in those with normal cognition before sepsis was 38% (95%Confidence Interval [CI]: 34%, 42%). After severe sepsis, 18% (95%CI: 15%, 20%) of survivors had incident cognitive impairment. In unadjusted analyses, pre-sepsis substantial depressive symptoms were associated with post-sepsis incident cognitive impairment (Odds Ratio [OR] 2.56, 95%CI: 1.53, 4.27). After adjustment for demographics, health-risk behaviors, clinical characteristics of the sepsis episode, and pre-sepsis TICS scores, pre-sepsis substantial depressive symptoms remained the strongest factor associated with post-sepsis incident cognitive impairment (OR 2.58, 95%CI: 1.45, 4.59). Conclusion Pre-sepsis substantial depressive symptoms are independently associated with incident post-sepsis cognitive impairment. Depressed older adults may be particularly at risk for developing

Autophagy in sepsis: Degradation into exhaustion?

PubMed

Ho, Jeffery; Yu, Jun; Wong, Sunny H; Zhang, Lin; Liu, Xiaodong; Wong, Wai T; Leung, Czarina C H; Choi, Gordon; Wang, Maggie H T; Gin, Tony; Chan, Matthew T V; Wu, William K K

2016-07-02

Autophagy is one of the innate immune defense mechanisms against microbial challenges. Previous in vitro and in vivo models of sepsis demonstrated that autophagy was activated initially in sepsis, followed by a subsequent phase of impairment. Autophagy modulation appears to be protective against multiple organ injuries in these murine sepsis models. This is achieved in part by preventing apoptosis, maintaining a balance between the productions of pro- and anti-inflammatory cytokines, and preserving mitochondrial functions. This article aims to discuss the role of autophagy in sepsis and the therapeutic potential of autophagy enhancers.

Readmissions for Recurrent Sepsis: New or Relapsed Infection?

PubMed

DeMerle, Kimberley Marie; Royer, Stephanie C; Mikkelsen, Mark E; Prescott, Hallie C

2017-10-01

Sepsis hospitalizations are frequently followed by hospital readmissions, often for recurrent sepsis. However, it is unclear how often sepsis readmissions are for relapsed/recrudescent versus new infections. The aim of this study was to assess the extent to which 90-day readmissions for recurrent sepsis are due to infection of the same site and same pathogen as the initial episode. Retrospective cohort study. University of Michigan Health System. All hospitalizations (May 15, 2013 to May 14, 2015) with a principal International Classification of Diseases, Ninth revision, Clinical Modification diagnosis of septicemia (038.x), severe sepsis (995.92), or septic shock (785.52), as well as all subsequent hospitalizations and sepsis readmissions within 90 days. We determined organism and site of sepsis through manual chart abstraction. None. We identified 472 readmissions within 90 days of sepsis, of which 137 (29.1%) were for sepsis. In sepsis readmissions, the site and organisms were most commonly urinary (29.2%), gastrointestinal (20.4%), Gram negative (29.9%), Gram positive (16.8%), and culture negative (30.7%). Ninety-four readmissions (68.6%) were for infection at the same site as initial sepsis hospitalization. Nineteen percent of readmissions were confirmed to be same site and same organism. However, accounting for the uncertainty from culture-negative sepsis, as many as 53.2% of readmissions could plausibly due to infections with both the same organism and same site. Of the patients readmitted with sepsis within 90 days, two thirds had infection at the same site as their initial admission. Just 19% had infection confirmed to be from the same site and organism as the initial sepsis hospitalization. Half of readmissions were definitively for new infections, whereas an additional 34% were unclear since cultures were negative in one of the hospitalizations.

Implementation of an Inpatient Pediatric Sepsis Identification Pathway.

PubMed

Bradshaw, Chanda; Goodman, Ilyssa; Rosenberg, Rebecca; Bandera, Christopher; Fierman, Arthur; Rudy, Bret

2016-03-01

Early identification and treatment of severe sepsis and septic shock improves outcomes. We sought to identify and evaluate children with possible sepsis on a pediatric medical/surgical unit through successful implementation of a sepsis identification pathway. The sepsis identification pathway, a vital sign screen and subsequent physician evaluation, was implemented in October 2013. Quality improvement interventions were used to improve physician and nursing adherence with the pathway. We reviewed charts of patients with positive screens on a monthly basis to assess for nursing recognition/physician notification, physician evaluation for sepsis, and subsequent physician diagnosis of sepsis and severe sepsis/septic shock. Adherence data were analyzed on a run chart and statistical process control p-chart. Nursing and physician pathway adherence of >80% was achieved over a 6-month period and sustained for the following 6 months. The direction of improvements met standard criteria for special causes. Over a 1-year period, there were 963 admissions to the unit. Positive screens occurred in 161 (16.7%) of these admissions and 38 (23.5%) of these had a physician diagnosis of sepsis, severe sepsis, or septic shock. One patient with neutropenia and septic shock had a negative sepsis screen due to lack of initial fever. Using quality improvement methodology, we successfully implemented a sepsis identification pathway on our pediatric unit. The pathway provided a standardized process to identify and evaluate children with possible sepsis requiring timely evaluation and treatment. Copyright © 2016 by the American Academy of Pediatrics.

HMGB1 redox during sepsis.

PubMed

Abdulmahdi, Wasan; Patel, Devika; Rabadi, May M; Azar, Tala; Jules, Edson; Lipphardt, Mark; Hashemiyoon, Rameen; Ratliff, Brian B

2017-10-01

During sepsis, the alarmin HMGB1 is released from tissues and promotes systemic inflammation that results in multi-organ damage, with the kidney particularly susceptible to injury. The severity of inflammation and pro-damage signaling mediated by HMGB1 appears to be dependent on the alarmin's redox state. Therefore, we examined HMGB1 redox in kidney cells during sepsis. Using intravital microscopy, CellROX labeling of kidneys in live mice indicated increased ROS generation in the kidney perivascular endothelium and tubules during lipopolysaccharide (LPS)-induced sepsis. Subsequent CellROX and MitoSOX labeling of LPS-stressed endothelial and kidney proximal tubule cells demonstrated increased ROS generation in these cells as sepsis worsens. Consequently, HMGB1 oxidation increased in the cytoplasm of kidney cells during its translocation from the nucleus to the circulation, with the degree of oxidation dependent on the severity of sepsis, as measured in in vivo mouse samples using a thiol assay and mass spectrometry (LC-MS/MS). The greater the oxidation of HMGB1, the greater the ability of the alarmin to stimulate pro-inflammatory cyto-/chemokine release (measured by Luminex Multiplex) and alter mitochondrial ATP generation (Luminescent ATP Detection Assay). Administration of glutathione and thioredoxin inhibitors to cell cultures enhanced HMGB1 oxidation during sepsis in endothelial and proximal tubule cells, respectively. In conclusion, as sepsis worsens, ROS generation and HMGB1 oxidation increases in kidney cells, which enhances HMGB1's pro-inflammatory signaling. Conversely, the glutathione and thioredoxin systems work to maintain the protein in its reduced state. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Surviving Sepsis: Taming a Deadly Immune Response

MedlinePlus

... Issues Subscribe August 2014 Print this issue Surviving Sepsis Taming a Deadly Immune Response En español Send ... Mouth? Looking at Lupus Wise Choices Signs of Sepsis Sepsis can be hard to spot, because its ...

Fever in sepsis.

PubMed

Schortgen, F

2012-11-01

Fever is a common symptom of sepsis usually believed to predict better survival. Experimental data suggest that body temperature elevation may slow micro-organism growth and enhance host immune responses. In patients with sepsis, however, the high energy cost of fever may exacerbate the life-threatening situation. Fever control is widely used in the ICU, mainly in patients with infections. The efficacy of antipyretic drugs in lowering body temperature remains uncertain, however, and all antipyretics have well known adverse effects. Surface cooling methods are efficient but require sedation to avoid the harmful effects of shivering. A recent controlled trial in patients with septic shock suggests that external cooling for fever control may diminish vasopressor requirements and improve early survival. In this review, we examine the benefits and risks of fever and of controlled normothermia. The fever control modalities that provide the best risk/benefit ratio in sepsis are discussed.

Post–Acute Care Use and Hospital Readmission after Sepsis

PubMed Central

Jones, Tiffanie K.; Fuchs, Barry D.; Small, Dylan S.; Halpern, Scott D.; Hanish, Asaf; Umscheid, Craig A.; Baillie, Charles A.; Kerlin, Meeta Prasad; Gaieski, David F.

2015-01-01

Rationale: The epidemiology of post–acute care use and hospital readmission after sepsis remains largely unknown. Objectives: To examine the rate of post–acute care use and hospital readmission after sepsis and to examine risk factors and outcomes for hospital readmissions after sepsis. Methods: In an observational cohort study conducted in an academic health care system (2010–2012), we compared post–acute care use at discharge and hospital readmission after 3,620 sepsis hospitalizations with 108,958 nonsepsis hospitalizations. We used three validated, claims-based approaches to identify sepsis and severe sepsis. Measurements and Main Results: Post–acute care use at discharge was more likely after sepsis, driven by skilled care facility placement (35.4% after sepsis vs. 15.8%; P < 0.001), with the highest rate observed after severe sepsis. Readmission rates at 7, 30, and 90 days were higher postsepsis (P < 0.001). Compared with nonsepsis hospitalizations (15.6% readmitted within 30 d), the increased readmission risk was present regardless of sepsis severity (27.3% after sepsis and 26.0–26.2% after severe sepsis). After controlling for presepsis characteristics, the readmission risk was found to be 1.51 times greater (95% CI, 1.38–1.66) than nonsepsis hospitalizations. Readmissions after sepsis were more likely to result in death or transition to hospice care (6.1% vs. 13.3% after sepsis; P < 0.001). Independent risk factors associated with 30-day readmissions after sepsis hospitalizations included age, malignancy diagnosis, hospitalizations in the year prior to the index hospitalization, nonelective index admission type, one or more procedures during the index hospitalization, and low hemoglobin and high red cell distribution width at discharge. Conclusions: Post–acute care use and hospital readmissions were common after sepsis. The increased readmission risk after sepsis was observed regardless of sepsis severity and was associated with

Sirtuin-2 Regulates Sepsis Inflammation in ob/ob Mice

PubMed Central

Wang, Xianfeng; Buechler, Nancy L.; Martin, Ayana; Wells, Jonathan; Yoza, Barbara; McCall, Charles E.; Vachharajani, Vidula

2016-01-01

Objective Obesity increases morbidity and resource utilization in sepsis patients. Sepsis transitions from early/hyper-inflammatory to late/hypo-inflammatory phase. Majority of sepsis-mortality occurs during the late sepsis; no therapies exist to treat late sepsis. In lean mice, we have shown that sirtuins (SIRTs) modulate this transition. Here, we investigated the role of sirtuins, especially the adipose-tissue abundant SIRT-2 on transition from early to late sepsis in obese with sepsis. Methods Sepsis was induced using cecal ligation and puncture (CLP) in ob/ob mice. We measured microvascular inflammation in response to lipopolysaccharide/normal saline re-stimulation as a “second-hit” (marker of immune function) at different time points to track phases of sepsis in ob/ob mice. We determined SIRT-2 expression during different phases of sepsis. We studied the effect of SIRT-2 inhibition during the hypo-inflammatory phase on immune function and 7-day survival. We used a RAW264.7 (RAW) cell model of sepsis for mechanistic studies. We confirmed key findings in diet induced obese (DIO) mice with sepsis. Results We observed that the ob/ob-septic mice showed an enhanced early inflammation and a persistent and prolonged hypo-inflammatory phase when compared to WT mice. Unlike WT mice that showed increased SIRT1 expression, we found that SIRT2 levels were increased in ob/ob mice during hypo-inflammation. SIRT-2 inhibition in ob/ob mice during the hypo-inflammatory phase of sepsis reversed the repressed microvascular inflammation in vivo via activation of endothelial cells and circulating leukocytes and significantly improved survival. We confirmed the key finding of the role of SIRT2 during hypo-inflammatory phase of sepsis in this project in DIO-sepsis mice. Mechanistically, in the sepsis cell model, SIRT-2 expression modulated inflammatory response by deacetylation of NFκBp65. Conclusion SIRT-2 regulates microvascular inflammation in obese mice with sepsis and may

The Effect of Sepsis on the Erythrocyte

PubMed Central

Bateman, Ryon M.; Sharpe, Michael D.; Singer, Mervyn; Ellis, Christopher G.

2017-01-01

Sepsis induces a wide range of effects on the red blood cell (RBC). Some of the effects including altered metabolism and decreased 2,3-bisphosphoglycerate are preventable with appropriate treatment, whereas others, including decreased erythrocyte deformability and redistribution of membrane phospholipids, appear to be permanent, and factors in RBC clearance. Here, we review the effects of sepsis on the erythrocyte, including changes in RBC volume, metabolism and hemoglobin’s affinity for oxygen, morphology, RBC deformability (an early indicator of sepsis), antioxidant status, intracellular Ca2+ homeostasis, membrane proteins, membrane phospholipid redistribution, clearance and RBC O2-dependent adenosine triphosphate efflux (an RBC hypoxia signaling mechanism involved in microvascular autoregulation). We also consider the causes of these effects by host mediated oxidant stress and bacterial virulence factors. Additionally, we consider the altered erythrocyte microenvironment due to sepsis induced microvascular dysregulation and speculate on the possible effects of RBC autoxidation. In future, a better understanding of the mechanisms involved in sepsis induced erythrocyte pathophysiology and clearance may guide improved sepsis treatments. Evidence that small molecule antioxidants protect the erythrocyte from loss of deformability, and more importantly improve septic patient outcome suggest further research in this area is warranted. While not generally considered a critical factor in sepsis, erythrocytes (and especially a smaller subpopulation) appear to be highly susceptible to sepsis induced injury, provide an early warning signal of sepsis and are a factor in the microvascular dysfunction that has been associated with organ dysfunction. PMID:28885563

The Effect of Sepsis on the Erythrocyte.

PubMed

Bateman, Ryon M; Sharpe, Michael D; Singer, Mervyn; Ellis, Christopher G

2017-09-08

Sepsis induces a wide range of effects on the red blood cell (RBC). Some of the effects including altered metabolism and decreased 2,3-bisphosphoglycerate are preventable with appropriate treatment, whereas others, including decreased erythrocyte deformability and redistribution of membrane phospholipids, appear to be permanent, and factors in RBC clearance. Here, we review the effects of sepsis on the erythrocyte, including changes in RBC volume, metabolism and hemoglobin's affinity for oxygen, morphology, RBC deformability (an early indicator of sepsis), antioxidant status, intracellular Ca 2+ homeostasis, membrane proteins, membrane phospholipid redistribution, clearance and RBC O₂-dependent adenosine triphosphate efflux (an RBC hypoxia signaling mechanism involved in microvascular autoregulation). We also consider the causes of these effects by host mediated oxidant stress and bacterial virulence factors. Additionally, we consider the altered erythrocyte microenvironment due to sepsis induced microvascular dysregulation and speculate on the possible effects of RBC autoxidation. In future, a better understanding of the mechanisms involved in sepsis induced erythrocyte pathophysiology and clearance may guide improved sepsis treatments. Evidence that small molecule antioxidants protect the erythrocyte from loss of deformability, and more importantly improve septic patient outcome suggest further research in this area is warranted. While not generally considered a critical factor in sepsis, erythrocytes (and especially a smaller subpopulation) appear to be highly susceptible to sepsis induced injury, provide an early warning signal of sepsis and are a factor in the microvascular dysfunction that has been associated with organ dysfunction.

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.

PubMed

Rhodes, Andrew; Evans, Laura E; Alhazzani, Waleed; Levy, Mitchell M; Antonelli, Massimo; Ferrer, Ricard; Kumar, Anand; Sevransky, Jonathan E; Sprung, Charles L; Nunnally, Mark E; Rochwerg, Bram; Rubenfeld, Gordon D; Angus, Derek C; Annane, Djillali; Beale, Richard J; Bellinghan, Geoffrey J; Bernard, Gordon R; Chiche, Jean-Daniel; Coopersmith, Craig; De Backer, Daniel P; French, Craig J; Fujishima, Seitaro; Gerlach, Herwig; Hidalgo, Jorge Luis; Hollenberg, Steven M; Jones, Alan E; Karnad, Dilip R; Kleinpell, Ruth M; Koh, Younsuk; Lisboa, Thiago Costa; Machado, Flavia R; Marini, John J; Marshall, John C; Mazuski, John E; McIntyre, Lauralyn A; McLean, Anthony S; Mehta, Sangeeta; Moreno, Rui P; Myburgh, John; Navalesi, Paolo; Nishida, Osamu; Osborn, Tiffany M; Perner, Anders; Plunkett, Colleen M; Ranieri, Marco; Schorr, Christa A; Seckel, Maureen A; Seymour, Christopher W; Shieh, Lisa; Shukri, Khalid A; Simpson, Steven Q; Singer, Mervyn; Thompson, B Taylor; Townsend, Sean R; Van der Poll, Thomas; Vincent, Jean-Louis; Wiersinga, W Joost; Zimmerman, Janice L; Dellinger, R Phillip

2017-03-01

To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012". A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.

PubMed

Rhodes, Andrew; Evans, Laura E; Alhazzani, Waleed; Levy, Mitchell M; Antonelli, Massimo; Ferrer, Ricard; Kumar, Anand; Sevransky, Jonathan E; Sprung, Charles L; Nunnally, Mark E; Rochwerg, Bram; Rubenfeld, Gordon D; Angus, Derek C; Annane, Djillali; Beale, Richard J; Bellinghan, Geoffrey J; Bernard, Gordon R; Chiche, Jean-Daniel; Coopersmith, Craig; De Backer, Daniel P; French, Craig J; Fujishima, Seitaro; Gerlach, Herwig; Hidalgo, Jorge Luis; Hollenberg, Steven M; Jones, Alan E; Karnad, Dilip R; Kleinpell, Ruth M; Koh, Younsuck; Lisboa, Thiago Costa; Machado, Flavia R; Marini, John J; Marshall, John C; Mazuski, John E; McIntyre, Lauralyn A; McLean, Anthony S; Mehta, Sangeeta; Moreno, Rui P; Myburgh, John; Navalesi, Paolo; Nishida, Osamu; Osborn, Tiffany M; Perner, Anders; Plunkett, Colleen M; Ranieri, Marco; Schorr, Christa A; Seckel, Maureen A; Seymour, Christopher W; Shieh, Lisa; Shukri, Khalid A; Simpson, Steven Q; Singer, Mervyn; Thompson, B Taylor; Townsend, Sean R; Van der Poll, Thomas; Vincent, Jean-Louis; Wiersinga, W Joost; Zimmerman, Janice L; Dellinger, R Phillip

2017-03-01

To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012." A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.

Biology of sepsis: its relevance to pediatric nephrology.

PubMed

Blatt, Neal B; Srinivasan, Sushant; Mottes, Theresa; Shanley, Maureen M; Shanley, Thomas P

2014-12-01

Because of its multi-organ involvement, the syndrome of sepsis provides clinical challenges to a wide variety of health care providers. While multi-organ dysfunction triggered by sepsis requires general supportive critical care provided by intensivists, the impact of sepsis on renal function and the ability of renal replacement therapies to modulate its biologic consequences provide a significant opportunity for pediatric nephrologists and related care providers to impact outcomes. In this review, we aim to highlight newer areas of understanding of the pathobiology of sepsis with special emphasis on those aspects of particular interest to pediatric nephrology. As such, we aim to: (1) review the definition of sepsis and discuss advances in our mechanistic understanding of sepsis; (2) review current hypotheses regarding sepsis-induced acute kidney injury (AKI) and describe its epidemiology based on evolving definitions of AKI; (3) review the impact of renal failure on the immune system, highlighting the sepsis risk in this cohort and strategies that might minimize this risk; (4) review how renal replacement therapeutic strategies may impact sepsis-induced AKI outcomes. By focusing the review on these specific areas, we have omitted other important areas of the biology of sepsis and additional interactions with renal function from this discussion; however, we have aimed to provide a comprehensive list of references that provide contemporary reviews of these additional areas.

Pharmacological management of pediatric patients with sepsis.

PubMed

Simmons, Marroyln L; Durham, Spencer H; Carter, Chenita W

2012-01-01

With an overall mortality rate of 4.2%, sepsis is one of the most common causes of death in children worldwide. The Surviving Sepsis Campaign outlines rapid initiation of volume resuscitation with crystalloids and timely administration of broad-spectrum antibiotics as the backbone of sepsis treatment. Initial antibiotics should be broad enough to cover the most likely pathogens, but antibiotic therapy should be de-escalated when culture results become available. Therapy with a vasopressor and/or an inotrope is often necessary in patients with sepsis to improve blood pressure and cardiac output. Adjunctive therapy with hydrocortisone is sometimes beneficial in the setting of catecholamine resistance and/or adrenal insufficiency. Insulin may also be needed in some patients for the treatment of hyperglycemia. Current guidelines have improved the treatment of sepsis, but more research is needed. This article reviews sepsis pathophysiology, treatment, and supportive care specifically as they relate to pediatric patients.

The effect of bacterial sepsis severity on triglyceride value

NASA Astrophysics Data System (ADS)

Fahila, R.; Kembaren, T.; Rahimi, A.

2018-03-01

Sepsis can increase the amount of triglyceride as well as change the functional and structural components of lipoproteins. The triglyceride level is directly proportional to the severity of sepsis and associated with a systemic inflammatory response. The study aims to determine the correlation between the severity of bacterial sepsis with triglyceride value. An observational study with case control design from January2017 to March 2017 in 30 sepsis and 30 non-sepsis patients at H. Adam Malik General Hospital Medan. We examined Procalcitonin (PCT) and triglyceride level on the 1st, 3rd and 5th day and then analyzed using MannWhitney to assess their correlation.The triglyceride value in the sepsis group was 120 ± 5.1 mg/dl on day 1, non-sepsis 117.53 ± 36.37mg/dl. However, on the fifth day, the sepsis group of triglyceride values was 124.2±50.29mg/dl and the non-sepsis group triglyceride values 134.03±68.12mg/dl. There was no specific connection between the severity of sepsis and triglyceride value in a patient with sepsis.

A blueprint for a sepsis protocol.

PubMed

Shapiro, Nathan I; Howell, Michael; Talmor, Daniel

2005-04-01

Despite numerous advances in medicine, sepsis remains an unconquered challenge. Although outcomes have improved slightly over decades, the unacceptably high mortality rate of 30%-50% for severe sepsis and septic shock continues. However, after years of unsuccessful clinical trials, several investigations over the last few years have reported survival benefit in the treatment of sepsis. Physicians now have several proven therapies to treat sepsis, but have yet to implement them on a widespread, systematic basis. This led 11 international professional societies spanning multiple specialties and continents to come together to create the Surviving Sepsis Campaign. The product of their work is an international effort organized to improve care of patients with sepsis and includes consensus, evidence-based guidelines for care that improves survival in septic patients, and an action plan for change. Given the clear role of early identification and treatment in stopping the sepsis cascade, therapy must start early in the emergency department (ED) and continue throughout the hospital course. The first of the recommendations by the Surviving Sepsis Campaign is the aggressive resuscitation strategy of early goal-directed therapy (EGDT). EGDT is reported to reduce absolute mortality by a staggering 16%. The use of recombinant activated protein C was demonstrated to confer a 6% absolute survival benefit. Steroid supplementation in adrenal insufficiency produced a 10% benefit. Additionally, early and appropriate use of antibiotics remains a cornerstone of therapy. Although no randomized trial will be performed, the effects are undisputed. Finally, although predominantly intensive care unit therapies, tight glucose control and low-tidal-volume ventilation strategies have also led to improved survival. Armed with these new therapies, the medical community must rise to this call to action. Clinicians must change the approach to this disease, as well as the way the septic patient is

Role of kidney injury in sepsis.

PubMed

Doi, Kent

2016-01-01

Kidney injury, including acute kidney injury (AKI) and chronic kidney disease (CKD), has become very common in critically ill patients treated in ICUs. Many epidemiological studies have revealed significant associations of AKI and CKD with poor outcomes of high mortality and medical costs. Although many basic studies have clarified the possible mechanisms of sepsis and septic AKI, translation of the obtained findings to clinical settings has not been successful to date. No specific drug against human sepsis or AKI is currently available. Remarkable progress of dialysis techniques such as continuous renal replacement therapy (CRRT) has enabled control of "uremia" in hemodynamically unstable patients; however, dialysis-requiring septic AKI patients are still showing unacceptably high mortality of 60-80 %. Therefore, further investigations must be conducted to improve the outcome of sepsis and septic AKI. A possible target will be remote organ injury caused by AKI. Recent basic studies have identified interleukin-6 and high mobility group box 1 (HMGB1) as important mediators for acute lung injury induced by AKI. Another target is the disease pathway that is amplified by pre-existing CKD. Vascular endothelial growth factor and HMGB1 elevations in sepsis were demonstrated to be amplified by CKD in CKD-sepsis animal models. Understanding the role of kidney injury as an amplifier in sepsis and multiple organ failure might support the identification of new drug targets for sepsis and septic AKI.

The impact of a multifaceted intervention including sepsis electronic alert system and sepsis response team on the outcomes of patients with sepsis and septic shock.

PubMed

Arabi, Yaseen M; Al-Dorzi, Hasan M; Alamry, Ahmed; Hijazi, Ra'ed; Alsolamy, Sami; Al Salamah, Majid; Tamim, Hani M; Al-Qahtani, Saad; Al-Dawood, Abdulaziz; Marini, Abdellatif M; Al Ehnidi, Fatimah H; Mundekkadan, Shihab; Matroud, Amal; Mohamed, Mohamed S; Taher, Saadi

2017-12-01

Compliance with the clinical practice guidelines of sepsis management has been low. The objective of our study was to describe the results of implementing a multifaceted intervention including an electronic alert (e-alert) with a sepsis response team (SRT) on the outcome of patients with sepsis and septic shock presenting to the emergency department. This was a pre-post two-phased implementation study that consisted of a pre-intervention phase (January 01, 2011-September 24, 2012), intervention phase I (multifaceted intervention including e-alert, from September 25, 2012-March 03, 2013) and intervention phase II when SRT was added (March 04, 2013-October 30, 2013) in a 900-bed tertiary-care academic hospital. We recorded baseline characteristics and processes of care in adult patients presenting with sepsis or septic shock. The primary outcome measures were hospital mortality. Secondary outcomes were the need for mechanical ventilation and length of stay in the intensive unit and in the hospital. After implementing the multifaceted intervention including e-alert and SRT, cases were identified with less severe clinical and laboratory abnormalities and the processes of care improved. When adjusted to propensity score, the interventions were associated with reduction in hospital mortality [for intervention phase II compared to pre-intervention: adjusted odds ratio (aOR) 0.71, 95% CI 0.58-0.85, p = 0.003], reduction in the need for mechanical ventilation (aOR 0.45, 95% CI 0.37-0.55, p < 0.0001) and reduction in ICU LOS and hospital LOS for all patients as well as ICU LOS for survivors. Implementing a multifaceted intervention including sepsis e-alert with SRT was associated with earlier identification of sepsis, increase in compliance with sepsis resuscitation bundle and reduction in the need for mechanical ventilation and reduction in hospital mortality and LOS.

Liver - guardian, modifier and target of sepsis.

PubMed

Strnad, Pavel; Tacke, Frank; Koch, Alexander; Trautwein, Christian

2017-01-01

Sepsis and septic shock are characterized by life-threatening organ dysfunction caused by a dysregulated host response to infection. The liver has a central role during sepsis, and is essential to the regulation of immune defence during systemic infections by mechanisms such as bacterial clearance, acute-phase protein or cytokine production and metabolic adaptation to inflammation. However, the liver is also a target for sepsis-related injury, including hypoxic hepatitis due to ischaemia and shock, cholestasis due to altered bile metabolism, hepatocellular injury due to drug toxicity or overwhelming inflammation, as well as distinct pathologies such as secondary sclerosing cholangitis in critically ill patients. Hence, hepatic dysfunction substantially impairs the prognosis of sepsis and serves as a powerful independent predictor of mortality in the intensive care unit. Sepsis is particularly problematic in patients with liver cirrhosis (who experience increased bacterial translocation from the gut and impaired microbial defence) as it can trigger acute-on-chronic liver failure - a syndrome with high short-term mortality. Here, we review the importance of the liver as a guardian, modifier and target of sepsis, the factors that contribute to sepsis in patients with liver cirrhosis and new therapeutic strategies.

[Value of sepsis single-disease manage system in predicting mortality in patients with sepsis].

PubMed

Chen, J; Wang, L H; Ouyang, B; Chen, M Y; Wu, J F; Liu, Y J; Liu, Z M; Guan, X D

2018-04-03

Objective: To observe the effect of sepsis single-disease manage system on the improvement of sepsis treatment and the value in predicting mortality in patients with sepsis. Methods: A retrospective study was conducted. Patients with sepsis admitted to the Department of Surgical Intensive Care Unit of Sun Yat-Sen University First Affiliated Hospital from September 22, 2013 to May 5, 2015 were enrolled in this study. Sepsis single-disease manage system (Rui Xin clinical data manage system, China data, China) was used to monitor 25 clinical quality parameters, consisting of timeliness, normalization and outcome parameters. Based on whether these quality parameters could be completed or not, the clinical practice was evaluated by the system. The unachieved quality parameter was defined as suspicious parameters, and these suspicious parameters were used to predict mortality of patients with receiver operating characteristic curve (ROC). Results: A total of 1 220 patients with sepsis were enrolled, included 805 males and 415 females. The mean age was (59±17) years, and acute physiology and chronic health evaluation (APACHE Ⅱ) scores was 19±8. The area under ROC curve of total suspicious numbers for predicting 28-day mortality was 0.70; when the suspicious parameters number was more than 6, the sensitivity was 68.0% and the specificity was 61.0% for predicting 28-day mortality. In addition, the area under ROC curve of outcome suspicious number for predicting 28-day mortality was 0.89; when the suspicious outcome parameters numbers was more than 1, the sensitivity was 88.0% and the specificity was 78.0% for predicting 28-day mortality. Moreover, the area under ROC curve of total suspicious number for predicting 90-day mortality was 0.73; when the total suspicious parameters number was more than 7, the sensitivity was 60.0% and the specificity was 74.0% for predicting 90-day mortality. Finally, the area under ROC curve of outcome suspicious numbers for predicting 90

Emerging drugs in sepsis.

PubMed

Leone, Marc; Textoris, Julien; Michel, Fabrice; Wiramus, Sandrine; Martin, Claude

2010-03-01

Sepsis remains a major cause of death in intensive care units. Despite an intense research, a new drug that is effective in reducing mortality in sepsis is still awaited. The literature was analyzed with Pubmed() during the 2008 - 2009 period. If required, seminal articles published before 2008 were cited. Clinical trials focusing on 'sepsis' were first assessed. Next, relevant experimental data in this field were reported. The goal of the review is to determine the role for new licensed antibiotics, to give an insight into the conflict on adjuvant therapies and to disclose new experimental concepts. New licensed antibiotics will offer the opportunity to refine the treatment choices. Direct hemoperfusion using polymyxin B-immobilized fiber column may be an option in sepsis due to Gram-negative bacilli. Among non-antibiotic drugs, new ongoing studies will clarify the role of drotrecogin alfa (activated) and low dose hydrocortisone. The modulation of monocytic human leukocyte antigen-DR seems the most prominent treatment. The use of cardiovascular drugs requires well-conducted clinical trials. The regulation of high mobility group box 1, adenosine blockade or correction of the impaired energy production is still at the experimental level.

The pediatric sepsis biomarker risk model: potential implications for sepsis therapy and biology.

PubMed

Alder, Matthew N; Lindsell, Christopher J; Wong, Hector R

2014-07-01

Sepsis remains a major cause of morbidity and mortality in adult and pediatric intensive care units. Heterogeneity of demographics, comorbidities, biological mechanisms, and severity of illness leads to difficulty in determining which patients are at highest risk of mortality. Determining mortality risk is important for weighing the potential benefits of more aggressive interventions and for deciding whom to enroll in clinical trials. Biomarkers can be used to parse patients into different risk categories and can outperform current methods of patient risk stratification based on physiologic parameters. Here we review the Pediatric Sepsis Biomarker Risk Model that has also been modified and applied to estimate mortality risk in adult patients. We compare the two models and speculate on the biological implications of the biomarkers in patients with sepsis.

Lower Leg Anterior and Lateral Intracompartmental Pressure Changes Before and After Classic Versus Skate Nordic Rollerskiing

PubMed Central

Woods, Katherine M.; Petron, David J.; Shultz, Barry B.; Hicks-Little, Charlie A.

2015-01-01

Context Chronic exertional compartment syndrome (CECS) is a debilitating condition resulting in loss of function and a decrease in athletic performance. Cases of CECS are increasing among Nordic skiers; therefore, analysis of intracompartmental pressures (ICPs) before and after Nordic skiing is warranted. Objective To determine if lower leg anterior and lateral ICPs and subjective lower leg pain levels increased after a 20-minute Nordic rollerskiing time trial and to examine if differences existed between postexercise ICPs for the 2 Nordic rollerskiing techniques, classic and skate. Design Crossover study. Setting Outdoor paved loop. Patients or Other Participants Seven healthy Division I Nordic skiers (3 men, 4 women; age = 22.71 ± 1.38 y, height = 175.36 ± 6.33 cm, mass = 70.71 ± 6.58 kg). Intervention(s) Participants completed two 20-minute rollerskiing time trials using the classic and skate technique in random order. The time trials were completed 7 days apart. Anterior and lateral ICPs and lower leg pain scores were obtained at baseline and at minutes 1 and 5 after rollerskiing. Main Outcome Measure(s) Anterior and lateral ICPs (mm Hg) were measured using a Stryker Quic STIC handheld monitor. Subjective measures of lower leg pain were recorded using the 11-point Numeric Rating Scale. Results Increases in both anterior (P = .000) and lateral compartment (P = .002) ICPs were observed, regardless of rollerskiing technique used. Subjective lower leg pain increased after the classic technique for the men from baseline to 1 minute postexercise and after the skate technique for the women. Significant 3-way interactions (technique × time × sex) were observed for the anterior (P = .002) and lateral (P = .009) compartment ICPs and lower leg pain (P = .005). Conclusions Postexercise anterior and lateral ICPs increased compared with preexercise ICPs after both classic and skate rollerskiing techniques. Lower leg pain is a primary symptom of CECS. The subjective

Pediatric severe sepsis in U.S. children's hospitals.

PubMed

Balamuth, Fran; Weiss, Scott L; Neuman, Mark I; Scott, Halden; Brady, Patrick W; Paul, Raina; Farris, Reid W D; McClead, Richard; Hayes, Katie; Gaieski, David; Hall, Matt; Shah, Samir S; Alpern, Elizabeth R

2014-11-01

To compare the prevalence, resource utilization, and mortality for pediatric severe sepsis identified using two established identification strategies. Observational cohort study from 2004 to 2012. Forty-four pediatric hospitals contributing data to the Pediatric Health Information Systems database. Children 18 years old or younger. We identified patients with severe sepsis or septic shock by using two International Classification of Diseases, 9th edition, Clinical Modification-based coding strategies: 1) combinations of International Classification of Diseases, 9th edition, Clinical Modification codes for infection plus organ dysfunction (combination code cohort); 2) International Classification of Diseases, 9th edition, Clinical Modification codes for severe sepsis and septic shock (sepsis code cohort). Outcomes included prevalence of severe sepsis, as well as hospital and ICU length of stay, and mortality. Outcomes were compared between the two cohorts examining aggregate differences over the study period and trends over time. The combination code cohort identified 176,124 hospitalizations (3.1% of all hospitalizations), whereas the sepsis code cohort identified 25,236 hospitalizations (0.45%), a seven-fold difference. Between 2004 and 2012, the prevalence of sepsis increased from 3.7% to 4.4% using the combination code cohort and from 0.4% to 0.7% using the sepsis code cohort (p < 0.001 for trend in each cohort). Length of stay (hospital and ICU) and costs decreased in both cohorts over the study period (p < 0.001). Overall, hospital mortality was higher in the sepsis code cohort than the combination code cohort (21.2% [95% CI, 20.7-21.8] vs 8.2% [95% CI, 8.0-8.3]). Over the 9-year study period, there was an absolute reduction in mortality of 10.9% (p < 0.001) in the sepsis code cohort and 3.8% (p < 0.001) in the combination code cohort. Prevalence of pediatric severe sepsis increased in the studied U.S. children's hospitals over the past 9 years, whereas

Biomarkers for diagnosis of neonatal sepsis: a literature review.

PubMed

Sharma, Deepak; Farahbakhsh, Nazanin; Shastri, Sweta; Sharma, Pradeep

2018-06-01

Sepsis is an important cause of mortality and morbidity in neonatal populations. There has been constant search of an ideal sepsis biomarker that have high sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV), so that both the diagnosis and exclusion of neonatal sepsis can be made at the earliest possible and appropriate antibiotics can be started to neonate. Ideal sepsis biomarker will help in guiding us when not to start antibiotics in case of suspect sepsis and total duration of antibiotics course in case of proven sepsis. There are numerous sepsis biomarkers that have been evaluated for early detection of neonatal sepsis but till date there is no single ideal biomarker that fulfills all essential criteria's for being an ideal biomarker. The most commonly used biomarkers are C-reactive protein (CRP) and procalcitonin (PCT), but both have shown varied sensitivity, specificity, PPV and NPV in different studies. We conducted literature search for various neonatal sepsis biomarkers and this review article will cover briefly all the markers with current available evidence.

Diagnostic value of Pentraxin-3 in patients with sepsis and septic shock in accordance with latest sepsis-3 definitions.

PubMed

Hamed, Sonja; Behnes, Michael; Pauly, Dominic; Lepiorz, Dominic; Barre, Max; Becher, Tobias; Lang, Siegfried; Akin, Ibrahim; Borggrefe, Martin; Bertsch, Thomas; Hoffmann, Ursula

2017-08-09

Pentraxin-3 (PTX-3) is an acute-phase protein involved in inflammatory and infectious processes. This study assesses its diagnostic and prognostic value in patients with sepsis or septic shock in a medical intensive care unit (ICU). The study includes 213 ICU patients with clinical criteria of sepsis and septic shock. 77 donors served as controls. Plasma levels of PTX-3, procalcitonin (PCT) and interleukin-6 were measured on day 1, 3 and 8. PTX-3 correlated with higher lactate levels as well as with APACHE II and SOFA scores (p = 0.0001). PTX-3 levels of patients with sepsis or septic shock were consistently significantly higher than in the control group (p ≤ 0.001). Plasma levels were able to discriminate sepsis and septic shock significantly on day 1, 3 and 8 (range of AUC 0.73-0.92, p = 0.0001). Uniform cut-off levels were defined at ≥5 ng/ml for at least sepsis, ≥9 ng/ml for septic shock (p = 0.0001). PTX-3 reveals diagnostic value for sepsis and septic shock during the first week of intensive care treatment, comparable to interleukin-6 according to latest Sepsis-3 definitions. NCT01535534 . Registered 14.02.2012.

Improving Outcomes in Patients With Sepsis.

PubMed

Armen, Scott B; Freer, Carol V; Showalter, John W; Crook, Tonya; Whitener, Cynthia J; West, Cheri; Terndrup, Thomas E; Grifasi, Marissa; DeFlitch, Christopher J; Hollenbeak, Christopher S

2016-01-01

Sepsis mortality may be improved by early recognition and appropriate treatment based on evidence-based guidelines. An intervention was developed that focused on earlier identification of sepsis, early antimicrobial administration, and an educational program that was disseminated throughout all hospital units and services. There were 1331 patients with sepsis during the intervention period and 1401 patients with sepsis during the control period. After controlling for expected mortality, patients in the intervention period had 30% lower odds of dying (odds ratio = 0.70, 95% confidence interval [CI] = 0.57 to 0.84). They also had 1.07 fewer days on average in the intensive care unit (95% CI = -1.98 to -0.16), 2.15 fewer hospital days (95% CI = -3.45 to -0.86), and incurred on average $1949 less in hospital costs, although the effect on costs was not statistically significant. Continued incremental improvement and sustainment is anticipated through organizational oversight, continued education, and initiation of an automated electronic sepsis alert function. © The Author(s) 2014.

Improving Outcomes in Patients With Sepsis

PubMed Central

Armen, Scott B.; Freer, Carol V.; Showalter, John W.; Crook, Tonya; Whitener, Cynthia J.; West, Cheri; Terndrup, Thomas E.; Grifasi, Marissa; DeFlitch, Christopher J.; Hollenbeak, Christopher S.

2017-01-01

Sepsis mortality may be improved by early recognition and appropriate treatment based on evidence-based guidelines. An intervention was developed that focused on earlier identification of sepsis, early antimicrobial administration, and an educational program that was disseminated throughout all hospital units and services. There were 1331 patients with sepsis during the intervention period and 1401 patients with sepsis during the control period. After controlling for expected mortality, patients in the intervention period had 30% lower odds of dying (odds ratio = 0.70, 95% confidence interval [CI] = 0.57 to 0.84). They also had 1.07 fewer days on average in the intensive care unit (95% CI = −1.98 to −0.16), 2.15 fewer hospital days (95% CI = −3.45 to −0.86), and incurred on average $1949 less in hospital costs, although the effect on costs was not statistically significant. Continued incremental improvement and sustainment is anticipated through organizational oversight, continued education, and initiation of an automated electronic sepsis alert function. PMID:25216849

Regulators of Intestinal Epithelial Migration in Sepsis.

PubMed

Meng, Mei; Klingensmith, Nathan J; Liang, Zhe; Lyons, John D; Fay, Katherine T; Chen, Ching-Wen; Ford, Mandy L; Coopersmith, Craig M

2018-02-08

The gut is a continuously renewing organ, with cell proliferation, migration and death occurring rapidly under basal conditions. Since the impact of critical illness on cell movement from crypt base to villus tip is poorly understood, the purpose of this study was to determine how sepsis alters enterocyte migration. Wild type, transgenic and knockout mice were injected with 5-bromo-2'deoxyuridine (BrdU) to label cells in S phase before and after the onset of cecal ligation and puncture and were sacrificed at pre-determined endpoints to determine distance proliferating cells migrated up the crypt-villus unit. Enterocyte migration rate was decreased from 24-96 hours following sepsis. BrdU was not detectable on villi 6 days after sham laparotomy, meaning all cells had migrated the length of the gut and been exfoliated into its lumen. However, BrdU positive cells were detectable on villi 10 days after sepsis. Multiple components of gut integrity altered enterocyte migration. Sepsis decreased crypt proliferation, which further slowed enterocyte transit as mice injected with BrdU after the onset of sepsis (decreased proliferation) had slower migration than mice injected with BrdU prior to the onset of sepsis (normal proliferation). Decreasing intestinal apoptosis via gut-specific overexpression of Bcl-2 prevented sepsis-induced slowing of enterocyte migration. In contrast, worsened intestinal hyperpermeability by genetic deletion of JAM-A increased enterocyte migration. Sepsis therefore significantly slows enterocyte migration, and intestinal proliferation, apoptosis and permeability all affect migration time, which can potentially be targeted both genetically and pharmacologically.

Development and Implementation of Sepsis Alert Systems.

PubMed

Harrison, Andrew M; Gajic, Ognjen; Pickering, Brian W; Herasevich, Vitaly

2016-06-01

Development and implementation of sepsis alert systems is challenging, particularly outside the monitored intensive care unit (ICU) setting. Barriers to wider use of sepsis alerts include evolving clinical definitions of sepsis, information overload, and alert fatigue, due to suboptimal alert performance. Outside the ICU, barriers include differences in health care delivery models, charting behaviors, and availability of electronic data. Current evidence does not support routine use of sepsis alert systems in clinical practice. Continuous improvement in the afferent and efferent aspects will help translate theoretic advantages into measurable patient benefit. Copyright © 2016 Elsevier Inc. All rights reserved.

A patient cohort on long-term sequelae of sepsis survivors: study protocol of the Mid-German Sepsis Cohort.

PubMed

Scherag, André; Hartog, Christiane S; Fleischmann, Carolin; Ouart, Dominique; Hoffmann, Franziska; König, Christian; Kesselmeier, Miriam; Fiedler, Sandra; Philipp, Monique; Braune, Anke; Eichhorn, Cornelia; Gampe, Christin; Romeike, Heike; Reinhart, Konrad

2017-08-23

An increasing number of patients survive sepsis; however, we lack valid data on the long-term impact on morbidity from prospective observational studies. Therefore, we designed an observational cohort to quantify mid-term and long-term functional disabilities after intensive care unit (ICU)-treated sepsis. Ultimately, findings for the Mid-German Sepsis Cohort (MSC) will serve as basis for the implementation of follow-up structures for patients with sepsis and help to increase quality of care for sepsis survivors. All patients surviving ICU-treated sepsis are eligible and are recruited from five study centres in Germany (acute care hospital setting in Jena, Halle/Saale, Leipzig, Bad Berka, Erfurt; large long-term acute care hospital and rehabilitation setting in Klinik Bavaria Kreischa). Screening is performed by trained study nurses. Data are collected on ICU management of sepsis. On written informed consent provided by patients or proxies, follow-up is carried out by trained research staff at 3, 6 and 12 months and yearly thereafter. The primary outcome is functional disability as assessed by (instrumental) activities of daily living. Other outcomes cover domains like mortality, cognitive, emotional and physical impairment, and resource use. The estimated sample size of 3000 ICU survivors is calculated to allow detection of relevant changes in the primary outcome in sepsis survivors longitudinally. The study is conducted according to the current version of the Declaration of Helsinki and has been approved by four local/federal responsible institutional ethics committees and by the respective federal data protection commissioners. Results of MSC will be fed back to the patients and published in peer-reviewed journals. German Clinical Trials Registry DRKS00010050. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The Epidemiology of Hospital Death Following Pediatric Severe Sepsis: When, Why, and How Children With Sepsis Die.

PubMed

Weiss, Scott L; Balamuth, Fran; Hensley, Josey; Fitzgerald, Julie C; Bush, Jenny; Nadkarni, Vinay M; Thomas, Neal J; Hall, Mark; Muszynski, Jennifer

2017-09-01

The epidemiology of in-hospital death after pediatric sepsis has not been well characterized. We investigated the timing, cause, mode, and attribution of death in children with severe sepsis, hypothesizing that refractory shock leading to early death is rare in the current era. Retrospective observational study. Emergency departments and ICUs at two academic children's hospitals. Seventy-nine patients less than 18 years old treated for severe sepsis/septic shock in 2012-2013 who died prior to hospital discharge. None. Time to death from sepsis recognition, cause and mode of death, and attribution of death to sepsis were determined from medical records. Organ dysfunction was assessed via daily Pediatric Logistic Organ Dysfunction-2 scores for 7 days preceding death with an increase greater than or equal to 5 defined as worsening organ dysfunction. The median time to death was 8 days (interquartile range, 1-12 d) with 25%, 35%, and 49% of cumulative deaths within 1, 3, and 7 days of sepsis recognition, respectively. The most common cause of death was refractory shock (34%), then multiple organ dysfunction syndrome after shock recovery (27%), neurologic injury (19%), single-organ respiratory failure (9%), and nonseptic comorbidity (6%). Early deaths (≤ 3 d) were mostly due to refractory shock in young, previously healthy patients while multiple organ dysfunction syndrome predominated after 3 days. Mode of death was withdrawal in 72%, unsuccessful cardiopulmonary resuscitation in 22%, and irreversible loss of neurologic function in 6%. Ninety percent of deaths were attributable to acute or chronic manifestations of sepsis. Only 23% had a rise in Pediatric Logistic Organ Dysfunction-2 that indicated worsening organ dysfunction. Refractory shock remains a common cause of death in pediatric sepsis, especially for early deaths. Later deaths were mostly attributable to multiple organ dysfunction syndrome, neurologic, and respiratory failure after life-sustaining therapies

Sepsis and Shock Response Team: Impact of a Multidisciplinary Approach to Implementing Surviving Sepsis Campaign Guidelines and Surviving the Process.

PubMed

Grek, Ami; Booth, Sandra; Festic, Emir; Maniaci, Michael; Shirazi, Ehsan; Thompson, Kristine; Starbuck, Angela; Mcree, Chad; Naessens, James M; Moreno Franco, Pablo

The Surviving Sepsis Campaign guidelines are designed to decrease mortality through consistent application of a 7-element bundle. This study evaluated the impact of improvement in bundle adherence using a time-series analysis of compliance with the bundle elements before and after interventions intended to improve the process, while also looking at hospital mortality. This article describes interventions used to improve bundle compliance and hospital mortality in patients admitted through the emergency department with sepsis, severe sepsis, or septic shock. Quality improvement methodology was used to develop high-impact interventions that led to dramatically improved adherence to the Surviving Sepsis Campaign guidelines bundle. Improved performance was associated with a significant decrease in the in-hospital mortality of severe sepsis patients presenting to the emergency department.

Pediatric Severe Sepsis in US Children’s Hospitals

PubMed Central

Balamuth, Fran; Weiss, Scott L.; Neuman, Mark I.; Scott, Halden; Brady, Patrick W.; Paul, Raina; Farris, Reid W.D.; McClead, Richard; Hayes, Katie; Gaieski, David; Hall, Matt; Shah, Samir S.; Alpern, Elizabeth R.

2014-01-01

Objective To compare the prevalence, resource utilization, and mortality for pediatric severe sepsis identified using two established identification strategies. Design Observational cohort study from 2004–2012. Setting Forty-four pediatric hospitals contributing data to the Pediatric Health Information Systems database. Patients Children ≤18 years of age. Measurements and Main Results We identified patients with severe sepsis or septic shock by using two International Classification of Diseases, 9th edition-Clinical Modification (ICD9-CM) based coding strategies: 1) combinations of ICD9-CM codes for infection plus organ dysfunction (combination code cohort); 2) ICD9-CM codes for severe sepsis and septic shock (sepsis code cohort). Outcomes included prevalence of severe sepsis, as well as hospital and intensive care unit (ICU) length of stay (LOS), and mortality. Outcomes were compared between the two cohorts examining aggregate differences over the study period and trends over time. The combination code cohort identified, 176,124 hospitalizations (3.1% of all hospitalizations), while the sepsis code cohort identified 25,236 hospitalizations (0.45%), a 7-fold difference. Between 2004 and 2012, the prevalence of sepsis increased from 3.7% to 4.4% using the combination code cohort and from 0.4% to 0.7% using the sepsis code cohort (p<0.001 for trend in each cohort). LOS (hospital and ICU) and costs decreased in both cohorts over the study period (p<0.001). Overall hospital mortality was higher in the sepsis code cohort than the combination code cohort (21.2%, (95% CI: 20.7–21.8 vs. 8.2%,(95% CI: 8.0–8.3). Over the 9 year study period, there was an absolute reduction in mortality of 10.9% (p<0.001) in the sepsis code cohort and 3.8% (p<0.001) in the combination code cohort. Conclusions Prevalence of pediatric severe sepsis increased in the studied US children’s hospitals over the past 9 years, though resource utilization and mortality decreased. Epidemiologic

Using Heuristic Evaluation to Improve Sepsis Alert Usability.

PubMed

Pertiwi, Ariani Arista Putri; Fraczkowski, Dan; Stogis, Sheryl L; Lopez, Karen Dunn

2018-06-01

Sepsis, life-threatening organ dysfunction in response to infection, is an alarmingly common and aggressive illness in US hospitals, especially for intensive care patients. Preventing sepsis deaths rests on the clinicians' ability to promptly recognize and treat sepsis. To aid early recognition, many organizations have employed clinician-facing electronic sepsis alert systems. However, the effectiveness of the alert relies on heavily on the visual interface, textual information, and overall usability. This article reports a usability inspection of a sepsis alert system. The authors found violations in 12 of the 14 usability principles and promote use of this method in practice to systematically identify usability problems. Copyright © 2018 Elsevier Inc. All rights reserved.

Sepsis is a preventable public health problem.

PubMed

Kempker, Jordan A; Wang, Henry E; Martin, Greg S

2018-05-06

There is a paradigm shift happening for sepsis. Sepsis is no longer solely conceptualized as problem of individual patients treated in emergency departments and intensive care units but also as one that is addressed as public health issue with population- and systems-based solutions. We offer a conceptual framework for sepsis as a public health problem by adapting the traditional model of primary, secondary, and tertiary prevention.

Mechanisms of intestinal barrier dysfunction in sepsis

PubMed Central

Yoseph, Benyam P.; Klingensmith, Nathan J.; Liang, Zhe; Breed, Elise R.; Burd, Eileen M.; Mittal, Rohit; Dominguez, Jessica A.; Petrie, Benjamin; Ford, Mandy L.; Coopersmith, Craig M.

2016-01-01

Intestinal barrier dysfunction is thought to contribute to the development of multiple organ dysfunction syndrome in sepsis. Although there are similarities in clinical course following sepsis, there are significant differences in the host response depending on the initiating organism and time course of the disease, and pathways of gut injury vary widely in different preclinical models of sepsis. The purpose of this study was to determine whether the timecourse and mechanisms of intestinal barrier dysfunction are similar in disparate mouse models of sepsis with similar mortalities. FVB/N mice were randomized to receive cecal ligation and puncture (CLP) or sham laparotomy, and permeability was measured to fluoresceinisothiocyanate conjugated-dextran (FD-4) six to 48 hours later. Intestinal permeability was elevated following CLP at all timepoints measured, peaking at six to 12 hours. Tight junction proteins claudin 1, 2, 3, 4, 5, 7, 8, 13 and 15, JAM-A, occludin, and ZO-1 were than assayed by Western blot, real-time polymerase chain reaction, and immunohistochemistry 12 hours after CLP to determine potential mechanisms underlying increases in intestinal permeability. Claudin 2 and JAM-A were increased by sepsis whereas claudin-5 and occludin were decreased by sepsis. All other tight junction proteins were unchanged. A further timecourse experiment demonstrated that alterations in claudin-2 and occludin were detectable as early as 1 hour after the onset of sepsis. Similar experiments were then performed in a different group of mice subjected to Pseudomonas aeruginosa pneumonia. Mice with pneumonia had an increase in intestinal permeability similar in timecourse and magnitude to that seen in CLP. Similar changes in tight junction proteins were seen in both models of sepsis although mice subjected to pneumonia also had a marked decrease in ZO-1 not seen in CLP. These results indicate that two disparate, clinically relevant models of sepsis induce a significant increase

Mechanisms of Intestinal Barrier Dysfunction in Sepsis.

PubMed

Yoseph, Benyam P; Klingensmith, Nathan J; Liang, Zhe; Breed, Elise R; Burd, Eileen M; Mittal, Rohit; Dominguez, Jessica A; Petrie, Benjamin; Ford, Mandy L; Coopersmith, Craig M

2016-07-01

Intestinal barrier dysfunction is thought to contribute to the development of multiple organ dysfunction syndrome in sepsis. Although there are similarities in clinical course following sepsis, there are significant differences in the host response depending on the initiating organism and time course of the disease, and pathways of gut injury vary widely in different preclinical models of sepsis. The purpose of this study was to determine whether the timecourse and mechanisms of intestinal barrier dysfunction are similar in disparate mouse models of sepsis with similar mortalities. FVB/N mice were randomized to receive cecal ligation and puncture (CLP) or sham laparotomy, and permeability was measured to fluoresceinisothiocyanate conjugated-dextran (FD-4) six to 48 h later. Intestinal permeability was elevated following CLP at all timepoints measured, peaking at 6 to 12 h. Tight junction proteins claudin 1, 2, 3, 4, 5, 7, 8, 13, and 15, Junctional Adhesion Molecule-A (JAM-A), occludin, and ZO-1 were than assayed by Western blot, real-time polymerase chain reaction, and immunohistochemistry 12 h after CLP to determine potential mechanisms underlying increases in intestinal permeability. Claudin 2 and JAM-A were increased by sepsis, whereas claudin-5 and occludin were decreased by sepsis. All other tight junction proteins were unchanged. A further timecourse experiment demonstrated that alterations in claudin-2 and occludin were detectable as early as 1 h after the onset of sepsis. Similar experiments were then performed in a different group of mice subjected to Pseudomonas aeruginosa pneumonia. Mice with pneumonia had an increase in intestinal permeability similar in timecourse and magnitude to that seen in CLP. Similar changes in tight junction proteins were seen in both models of sepsis although mice subjected to pneumonia also had a marked decrease in ZO-1 not seen in CLP. These results indicate that two disparate, clinically relevant models of sepsis

The New York Sepsis Severity Score: Development of a Risk-Adjusted Severity Model for Sepsis.

PubMed

Phillips, Gary S; Osborn, Tiffany M; Terry, Kathleen M; Gesten, Foster; Levy, Mitchell M; Lemeshow, Stanley

2018-05-01

In accordance with Rory's Regulations, hospitals across New York State developed and implemented protocols for sepsis recognition and treatment to reduce variations in evidence informed care and preventable mortality. The New York Department of Health sought to develop a risk assessment model for accurate and standardized hospital mortality comparisons of adult septic patients across institutions using case-mix adjustment. Retrospective evaluation of prospectively collected data. Data from 43,204 severe sepsis and septic shock patients from 179 hospitals across New York State were evaluated. Prospective data were submitted to a database from January 1, 2015, to December 31, 2015. None. Maximum likelihood logistic regression was used to estimate model coefficients used in the New York State risk model. The mortality probability was estimated using a logistic regression model. Variables to be included in the model were determined as part of the model-building process. Interactions between variables were included if they made clinical sense and if their p values were less than 0.05. Model development used a random sample of 90% of available patients and was validated using the remaining 10%. Hosmer-Lemeshow goodness of fit p values were considerably greater than 0.05, suggesting good calibration. Areas under the receiver operator curve in the developmental and validation subsets were 0.770 (95% CI, 0.765-0.775) and 0.773 (95% CI, 0.758-0.787), respectively, indicating good discrimination. Development and validation datasets had similar distributions of estimated mortality probabilities. Mortality increased with rising age, comorbidities, and lactate. The New York Sepsis Severity Score accurately estimated the probability of hospital mortality in severe sepsis and septic shock patients. It performed well with respect to calibration and discrimination. This sepsis-specific model provides an accurate, comprehensive method for standardized mortality comparison of adult

Inadequate exercise as a risk factor for sepsis mortality.

PubMed

Williams, Paul T

2013-01-01

Test whether inadequate exercise is related to sepsis mortality. Mortality surveillance of an epidemiological cohort of 155,484 National Walkers' and Runners' Health Study participants residing in the United States. Deaths were monitored for an average of 11.6-years using the National Death index through December 31, 2008. Cox proportional hazard analyses were used to compare sepsis mortality (ICD-10 A40-41) to inadequate exercise (<1.07 METh/d run or walked) as measured on their baseline questionnaires. Deaths occurring within one year of the baseline survey were excluded. Sepsis was the underlying cause in 54 deaths (sepsis(underlying)) and a contributing cause in 184 deaths (sepsis(contributing)), or 238 total sepsis-related deaths (sepsis(total)). Inadequate exercise was associated with 2.24-fold increased risk for sepsis(underlying) (95%CI: 1.21 to 4.07-fold, P = 0.01), 2.11-fold increased risk for sepsis(contributing) (95%CI: 1.51- to 2.92-fold, P<10(-4)), and 2.13-fold increased risk for sepsis(total) (95%CI: 1.59- to 2.84-fold, P<10(-6)) when adjusted for age, sex, race, and cohort. The risk increase did not differ significantly between runners and walkers, by sex, or by age. Sepsis(total) risk was greater in diabetics (P = 10(-5)), cancer survivors (P = 0.0001), and heart attack survivors (P = 0.003) and increased with waist circumference (P = 0.0004). The sepsis(total) risk associated with inadequate exercise persisted when further adjusted for diabetes, prior cancer, prior heart attack and waist circumference, and when excluding deaths with cancer, or cardiovascular, respiratory, or genitourinary disease as the underlying cause. Inadequate exercise also increased sepsis(total) risk in 2163 baseline diabetics (4.78-fold, 95%CI: 2.1- to 13.8-fold, P = 0.0001) when adjusted, which was significantly greater (P = 0.03) than the adjusted risk increase in non-diabetics (1.80-fold, 95%CI: 1.30- to 2.46-fold, P = 0

Management of sepsis: a 47-year-old woman with an indwelling intravenous catheter and sepsis.

PubMed

Angus, Derek C

2011-04-13

Severe sepsis is the term used to describe the host response to infection when complicated by acute organ dysfunction. Severe sepsis occurs in more than 750,000 individuals in the United States each year, with a hospital mortality of about 30%. Although the classic presentation is of florid shock with frank hypotension, fever, and elevated white blood cell count, many patients can present with cryptogenic shock (shock without hypotension) with more subtle signs of vital organ compromise. Using the case of Ms C, a 47-year-old woman with short gut syndrome and an indwelling intravenous catheter who developed an episode of severe sepsis secondary to a central line infection, treatment of sepsis is discussed. Management consists of prompt intervention with broad-spectrum antibiotics and fluid resuscitation, even in the absence of hypotension, and institution of a variety of strategies in the emergency setting to prevent development or worsening of vital organ dysfunction. Although advances in understanding the host immune response have fueled considerable interest in immunomodulatory therapy, the role of such agents in clinical practice remains limited and controversial.

Preventing intensive care admissions for sepsis in tropical Africa (PICASTA): an extension of the international pediatric global sepsis initiative: an African perspective.

PubMed

Pollach, Gregor; Namboya, Felix

2013-07-01

The Global Sepsis Initiative recommends prevention of sepsis through immunizations, vitamins, breast feeding, and other important interventions. In our study, we consider a second set of proposals for preventing intensive care admissions for sepsis in tropical Africa, which have been specifically designed to further prevent ICU admissions for sepsis in the group A nation hospital setting. To reduce admissions with severe sepsis in an ICU of a group A nation through the identification of challenges leading to preventable, foreseeable, or nosocomial sepsis specific to our setting. Malawi is one of the poorest countries in the world. Lacking the ability to comply with standard sepsis treatment, we conducted over 4 years several studies, audits, and surveys to identify challenges leading to preventable pediatric sepsis in our setting. We developed a method to identify malnourished children through a "gatekeeper" in the theaters without any equipment, tried to implement the World Health Organization's Safe Surgery Campaign checklist, evaluated our educational courses for the districts to improve the quality of referrals, looked into the extreme fasting times discovered in our hospital, trained different cadres in the districts to deal with peripartal and posttraumatic sepsis, and identified the needs in human resources to deal with pediatric sepsis in our setting. Six foci were identified as promising to work on in future. Focus 1: Preventing elective operations and procedures in malnourished children in the hospital and in the district: 134 of 145 nurses (92.4%) and even 25 of 31 African laymen (80.6%) were able to identify malnourished children with their own fingers. Focus 2: Preventing sepsis-related problems in emergencies through the implementation of the Safe Surgery Campaign checklist: only 100 of 689 forms (14.5%) were filled in due to challenges in ownership, communication responsibility, and time constraints. Focus 3: Preventing sepsis through the reduction

Neutrophil dysregulation during sepsis: an overview and update.

PubMed

Shen, Xiao-Fei; Cao, Ke; Jiang, Jin-Peng; Guan, Wen-Xian; Du, Jun-Feng

2017-09-01

Sepsis remains a leading cause of death worldwide, despite advances in critical care, and understanding of the pathophysiology and treatment strategies. No specific therapy or drugs are available for sepsis. Neutrophils play a critical role in controlling infection under normal conditions, and it is suggested that their migration and antimicrobial activity are impaired during sepsis which contribute to the dysregulation of immune responses. Recent studies further demonstrated that interruption or reversal of the impaired migration and antimicrobial function of neutrophils improves the outcome of sepsis in animal models. In this review, we provide an overview of the associated mediators and signal pathways involved which govern the survival, migration and antimicrobial function of neutrophils in sepsis, and discuss the potential of neutrophils as a target to specifically diagnose and/or predict the outcome of sepsis. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

The Prehospital Sepsis Project: out-of-hospital physiologic predictors of sepsis outcomes.

PubMed

Baez, Amado Alejandro; Hanudel, Priscilla; Wilcox, Susan Renee

2013-12-01

Severe sepsis and septic shock are common, expensive and often fatal medical problems. The care of the critically sick and injured often begins in the prehospital setting; there is limited data available related to predictors and interventions specific to sepsis in the prehospital arena. The objective of this study was to assess the predictive effect of physiologic elements commonly reported in the out-of-hospital setting in the outcomes of patients transported with sepsis. This was a cross-sectional descriptive study. Data from the years 2004-2006 were collected. Adult cases (≥18 years of age) transported by Emergency Medical Services to a major academic center with the diagnosis of sepsis as defined by ICD-9-CM diagnostic codes were included. Descriptive statistics and standard deviations were used to present group characteristics. Chi-square was used for statistical significance and odds ratio (OR) to assess strength of association. Statistical significance was set at the .05 level. Physiologic variables studied included mean arterial pressure (MAP), heart rate (HR), respiratory rate (RR) and shock index (SI). Sixty-three (63) patients were included. Outcome variables included a mean hospital length of stay (HLOS) of 13.75 days (SD = 9.97), mean ventilator days of 4.93 (SD = 7.87), in-hospital mortality of 22 out of 63 (34.9%), and mean intensive care unit length-of-stay (ICU-LOS) of 7.02 days (SD = 7.98). Although SI and RR were found to predict intensive care unit (ICU) admissions, [OR 5.96 (CI, 1.49-25.78; P = .003) and OR 4.81 (CI, 1.16-21.01; P = .0116), respectively] none of the studied variables were found to predict mortality (MAP <65 mmHg: P = .39; HR >90: P = .60; RR >20 P = .11; SI >0.7 P = .35). This study demonstrated that the out-of-hospital shock index and respiratory rate have high predictability for ICU admission. Further studies should include the development of an out-of-hospital sepsis score.

Prognostic markers of pediatric meningococcal sepsis.

PubMed

Briassoulis, George; Galani, Angeliki

2014-09-01

Having available tools to determine the prognosis of pediatric meningococcal sepsis at admission to the Intensive Care Unit or during the course of the disease constitutes a clinical necessity. Recently, new readily measurable circulating biomarkers have been described as an additional tool for severity classification and prediction of mortality in meningococcal disease. These biomarkers have been associated with increased risk of mortality scores and a number of organ failures in heterogeneous samples of critically ill children. In future, genetic markers may be used for identification of high-risk patients by creating prediction rules for clinical course and sequelae, and potentially provide more insight in the complex immune response in meningococcal sepsis. We briefly summarize the data pointing at the emerging genome-wide expression profiling studies and review the prognostic value of the main markers investigated in pediatric meningococcal sepsis putting them in the current frame of sepsis in general.

Autophagy Primes Neutrophils for Neutrophil Extracellular Trap Formation during Sepsis.

PubMed

Park, So Young; Shrestha, Sanjeeb; Youn, Young-Jin; Kim, Jun-Kyu; Kim, Shin-Yeong; Kim, Hyun Jung; Park, So-Hee; Ahn, Won-Gyun; Kim, Shin; Lee, Myung Goo; Jung, Ki-Suck; Park, Yong Bum; Mo, Eun-Kyung; Ko, Yousang; Lee, Suh-Young; Koh, Younsuck; Park, Myung Jae; Song, Dong-Keun; Hong, Chang-Won

2017-09-01

Neutrophils are key effectors in the host's immune response to sepsis. Excessive stimulation or dysregulated neutrophil functions are believed to be responsible for sepsis pathogenesis. However, the mechanisms regulating functional plasticity of neutrophils during sepsis have not been fully determined. We investigated the role of autophagy in neutrophil functions during sepsis in patients with community-acquired pneumonia. Neutrophils were isolated from patients with sepsis and stimulated with phorbol 12-myristate 13-acetate (PMA). The levels of reactive oxygen species generation, neutrophil extracellular trap (NET) formation, and granule release, and the autophagic status were evaluated. The effect of neutrophil autophagy augmentation was further evaluated in a mouse model of sepsis. Neutrophils isolated from patients who survived sepsis showed an increase in autophagy induction, and were primed for NET formation in response to subsequent PMA stimulation. In contrast, neutrophils isolated from patients who did not survive sepsis showed dysregulated autophagy and a decreased response to PMA stimulation. The induction of autophagy primed healthy neutrophils for NET formation and vice versa. In a mouse model of sepsis, the augmentation of autophagy improved survival via a NET-dependent mechanism. These results indicate that neutrophil autophagy primes neutrophils for increased NET formation, which is important for proper neutrophil effector functions during sepsis. Our study provides important insights into the role of autophagy in neutrophils during sepsis.

Novel biomarkers for sepsis: A narrative review.

PubMed

Larsen, Frederik Fruergaard; Petersen, J Asger

2017-11-01

Sepsis is a prevalent condition among hospitalized patients that carries a high risk of morbidity and mortality. Rapid recognition of sepsis as the cause of deterioration is desirable, so effective treatment can be initiated rapidly. Traditionally, diagnosis was based on presence of two or more positive SIRS criteria due to infection. However, recently published sepsis-3 criteria put more emphasis on organ dysfunction caused by infection in the definition of sepsis. Regardless of this, no gold standard for diagnosis exist, and clinicians still rely on a number of traditional and novel biomarkers to discriminate between patients with and without infection, as the cause of deterioration. Narrative review of current literature. A number of the most promising biomarkers for diagnoses and prognostication of sepsis are presented. Procalcitonin, presepsin, CD64, suPAR, and sTREM-1 are the best evaluated biomarkers for diagnosis and prognostication of sepsis to date. All have limitations in differentiation between infected and non-infected patients with SIRS, and their future role in diagnosis needs to be evaluated. It is important to test utility, performance, and validity of future biomarkers before implementing them in routine clinical care. Copyright © 2017 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Mitochondrial Function in Sepsis

PubMed Central

Arulkumaran, Nishkantha; Deutschman, Clifford S.; Pinsky, Michael R.; Zuckerbraun, Brian; Schumacker, Paul T.; Gomez, Hernando; Gomez, Alonso; Murray, Patrick; Kellum, John A.

2015-01-01

Mitochondria are an essential part of the cellular infrastructure, being the primary site for high energy adenosine triphosphate (ATP) production through oxidative phosphorylation. Clearly, in severe systemic inflammatory states, like sepsis, cellular metabolism is usually altered and end organ dysfunction not only common but predictive of long term morbidity and mortality. Clearly, interest is mitochondrial function both as a target for intracellular injury and response to extrinsic stress have been a major focus of basic science and clinical research into the pathophysiology of acute illness. However, mitochondria have multiple metabolic and signaling functions that may be central in both the expression of sepsis and its ultimate outcome. In this review, the authors address five primary questions centered on the role of mitochondria in sepsis. This review should be used as both a summary source in placing mitochondrial physiology within the context of acute illness and as a focal point for addressing new research into diagnostic and treatment opportunities these insights provide. PMID:26871665

MITOCHONDRIAL FUNCTION IN SEPSIS.

PubMed

Arulkumaran, Nishkantha; Deutschman, Clifford S; Pinsky, Michael R; Zuckerbraun, Brian; Schumacker, Paul T; Gomez, Hernando; Gomez, Alonso; Murray, Patrick; Kellum, John A

2016-03-01

Mitochondria are an essential part of the cellular infrastructure, being the primary site for high-energy adenosine triphosphate production through oxidative phosphorylation. Clearly, in severe systemic inflammatory states, like sepsis, cellular metabolism is usually altered, and end organ dysfunction is not only common, but also predictive of long-term morbidity and mortality. Clearly, interest is mitochondrial function both as a target for intracellular injury and response to extrinsic stress have been a major focus of basic science and clinical research into the pathophysiology of acute illness. However, mitochondria have multiple metabolic and signaling functions that may be central in both the expression of sepsis and its ultimate outcome. In this review, the authors address five primary questions centered on the role of mitochondria in sepsis. This review should be used both as a summary source in placing mitochondrial physiology within the context of acute illness and as a focal point for addressing new research into diagnostic and treatment opportunities these insights provide.

Trends in the epidemiology of pediatric severe sepsis*.

PubMed

Hartman, Mary E; Linde-Zwirble, Walter T; Angus, Derek C; Watson, R Scott

2013-09-01

In the past decade, guidelines have been developed for the early detection and management of severe sepsis in children and neonates. However, severe sepsis continues to be a significant U.S. healthcare problem, accounting for over 720,000 annual hospitalizations. Large-scale epidemiologic studies of severe sepsis continue to be limited, particularly in children. We present data from 1995, 2000, and 2005 in seven U.S. states, examining how case mix, outcome, and resource use for pediatric severe sepsis have changed over time. We constructed a database including all acute-care hospitalizations for children in the seven states. For each case, we extracted data on demographic characteristics; the principal diagnosis, up to six secondary diagnoses, and six procedures as classified by the International Classification of Diseases, 9th Revision, Clinical Modification codes; and in-hospital fatality. We identified patients with severe sepsis using International Classification of Diseases, 9th Revision, Clinical Modification codes for both infection and acute organ failure. Retrospective observational cohort dataset from seven U.S. states from 1995, 2000, and 2005. Children in the U.S. 0-19 years old. None. In 2005, 17,542 children were hospitalized with severe sepsis in the seven states; there was an 81% increase in pediatric severe sepsis cases since 1995 and a 45% increase since 2000. This corresponded to an increase in prevalence from 0.56 to 0.89 cases per 1,000 pediatric population. Between 1995 and 2005, the prevalence of severe sepsis in newborns more than doubled, from 4.5 to 9.7 cases per 1,000 births. The most common infecting organisms in all 3 years were Staphylococcus species. From 1995 to 2005, the case-fatality rate decreased from 10.3% to 8.9%. Case fatality associated with Staphylococcus aureus increased, whereas fatality associated with Streptococcus pneumoniae decreased by 75%. Nationally, there were 75,255 pediatric hospitalizations in 2005 involving

Targeting macrophage immunometabolism: Dawn in the darkness of sepsis.

PubMed

Kumar, V

2018-05-01

Sepsis is known since the time (470 BC) of great Greek physician, Hippocrates. Advancement in modern medicine and establishment of separate branches of medical science dealing with sepsis research have improved its outcome. However, mortality associated with sepsis still remains higher (25-30%) that further increases to 40-50% in the presence of septic shock. For example, sepsis-associated deaths account more in comparison to deaths-associated with myocardial-infarction and certain cancers (i.e. breast and colorectal cancer). However, it is now well established that profound activation of innate immune cells including macrophages play a very important role in the immunopathogenesis of sepsis. Macrophages are sentinel cells of the innate immune system with their location varying from peripheral blood to various target organs including lungs, liver, brain, kidneys, skin, testes, vascular endothelium etc. Thus, profound and dysregulated activation of these cells during sepsis can directly impact the outcome of sepsis. However, the emergence of the concept of immunometabolism as a major controller of immune response has raised a new hope for identifying new targets for immunomodulatory therapeutic approaches. Thus this present review starts with an introduction of sepsis as a major medical problem worldwide and signifies the role of dysregulated innate immune response including macrophages in its immunopathogenesis. Thereafter, subsequent sections describe changes in immunometabolic stage of macrophages (both M1 and M2) during sepsis. The article ends with the discussion of novel macrophage-specific therapeutic targets targeting their immunometabolism during sepsis and epigenetic regulation of macrophage immunometabolism and vice versa. Copyright © 2018 Elsevier B.V. All rights reserved.

In-Hospital Quality-of-Care Measures for Pediatric Sepsis Syndrome.

PubMed

Odetola, Folafoluwa O; Freed, Gary; Shevrin, Caroline; Madden, Brian; McCormick, Julie; Dombkowski, Kevin

2017-07-24

Sepsis syndrome, comprising sepsis, severe sepsis, and septic shock, is a leading cause of child mortality and morbidity, for which the delivery of time-sensitive care leads to improved survival. We aimed to describe the development and testing of quality measures for in-hospital care of pediatric sepsis syndrome. Seven measures of quality of care for children hospitalized with sepsis syndrome were developed by using an iterative process including literature review, development of concepts and candidate measures, and selection of measures for feasibility and importance by 2 panels of experts. The measures were tested for reliability and validity among children 0 to 18 years of age hospitalized with sepsis syndrome from January 1, 2012, to June 30, 2013. Of 27 hospitals, 59% had no protocol for the identification and treatment of pediatric sepsis syndrome. Blood culture was performed in only 70% of patients with pediatric sepsis syndrome. Antibiotics were administered within 1 hour of diagnosis in 70% of patients with pediatric severe sepsis or septic shock, and timely fluid resuscitation was performed in 50% of patients with severe sepsis or septic shock. Documentation of heart rate during fluid resuscitation of children with severe sepsis or septic shock was observed in 18% of cases. Two measures could not be rigorously tested for validity and reliability given the rarity of septic shock and were deemed infeasible. This multisite study to develop and validate measures of the quality of hospital care of children with sepsis syndrome highlights the existence of important gaps in delivery of care. Copyright © 2017 by the American Academy of Pediatrics.

Immune cell phenotype and function in sepsis

PubMed Central

Rimmelé, Thomas; Payen, Didier; Cantaluppi, Vincenzo; Marshall, John; Gomez, Hernando; Gomez, Alonso; Murray, Patrick; Kellum, John A.

2015-01-01

Cells of the innate and adaptive immune systems play a critical role in the host response to sepsis. Moreover, their accessibility for sampling and their capacity to respond dynamically to an acute threat increases the possibility that leukocytes might serve as a measure of a systemic state of altered responsiveness in sepsis. The working group of the 14th Acute Dialysis Quality Initiative (ADQI) conference sought to obtain consensus on the characteristic functional and phenotypic changes in cells of the innate and adaptive immune system in the setting of sepsis. Techniques for the study of circulating leukocytes were also reviewed and the impact on cellular phenotypes and leukocyte function of non extracorporeal treatments and extracorporeal blood purification therapies proposed for sepsis was analyzed. A large number of alterations in the expression of distinct neutrophil and monocyte surface markers have been reported in septic patients. The most consistent alteration seen in septic neutrophils is their activation of a survival program that resists apoptotic death. Reduced expression of HLA-DR is a characteristic finding on septic monocytes but monocyte antimicrobial function does not appear to be significantly altered in sepsis. Regarding adaptive immunity, sepsis-induced apoptosis leads to lymphopenia in patients with septic shock and it involves all types of T cells (CD4, CD8 and Natural Killer) except T regulatory cells, thus favoring immunosuppression. Finally, numerous promising therapies targeting the host immune response to sepsis are under investigation. These potential treatments can have an effect on the number of immune cells, the proportion of cell subtypes and the cell function. PMID:26529661

IMMUNE CELL PHENOTYPE AND FUNCTION IN SEPSIS.

PubMed

Rimmelé, Thomas; Payen, Didier; Cantaluppi, Vincenzo; Marshall, John; Gomez, Hernando; Gomez, Alonso; Murray, Patrick; Kellum, John A

2016-03-01

Cells of the innate and adaptive immune systems play a critical role in the host response to sepsis. Moreover, their accessibility for sampling and their capacity to respond dynamically to an acute threat increases the possibility that leukocytes might serve as a measure of a systemic state of altered responsiveness in sepsis.The working group of the 14th Acute Dialysis Quality Initiative (ADQI) conference sought to obtain consensus on the characteristic functional and phenotypic changes in cells of the innate and adaptive immune system in the setting of sepsis. Techniques for the study of circulating leukocytes were also reviewed and the impact on cellular phenotypes and leukocyte function of nonextracorporeal treatments and extracorporeal blood purification therapies proposed for sepsis was analyzed.A large number of alterations in the expression of distinct neutrophil and monocyte surface markers have been reported in septic patients. The most consistent alteration seen in septic neutrophils is their activation of a survival program that resists apoptotic death. Reduced expression of HLA-DR is a characteristic finding on septic monocytes, but monocyte antimicrobial function does not appear to be significantly altered in sepsis. Regarding adaptive immunity, sepsis-induced apoptosis leads to lymphopenia in patients with septic shock and it involves all types of T cells (CD4, CD8, and Natural Killer) except T regulatory cells, thus favoring immunosuppression. Finally, numerous promising therapies targeting the host immune response to sepsis are under investigation. These potential treatments can have an effect on the number of immune cells, the proportion of cell subtypes, and the cell function.

Hospital Variation in Risk-Adjusted Pediatric Sepsis Mortality.

PubMed

Ames, Stefanie G; Davis, Billie S; Angus, Derek C; Carcillo, Joseph A; Kahn, Jeremy M

2018-05-01

With continued attention to pediatric sepsis at both the clinical and policy levels, it is important to understand the quality of hospitals in terms of their pediatric sepsis mortality. We sought to develop a method to evaluate hospital pediatric sepsis performance using 30-day risk-adjusted mortality and to assess hospital variation in risk-adjusted sepsis mortality in a large state-wide sample. Retrospective cohort study using administrative claims data. Acute care hospitals in the state of Pennsylvania from 2011 to 2013. Patients between the ages of 0-19 years admitted to a hospital with sepsis defined using validated International Classification of Diseases, Ninth revision, Clinical Modification, diagnosis and procedure codes. None. During the study period, there were 9,013 pediatric sepsis encounters in 153 hospitals. After excluding repeat visits and hospitals with annual patient volumes too small to reliably assess hospital performance, there were 6,468 unique encounters in 24 hospitals. The overall unadjusted mortality rate was 6.5% (range across all hospitals: 1.5-11.9%). The median number of pediatric sepsis cases per hospital was 67 (range across all hospitals: 30-1,858). A hierarchical logistic regression model for 30-day risk-adjusted mortality controlling for patient age, gender, emergency department admission, infection source, presence of organ dysfunction at admission, and presence of chronic complex conditions showed good discrimination (C-statistic = 0.80) and calibration (slope and intercept of calibration plot: 0.95 and -0.01, respectively). The hospital-specific risk-adjusted mortality rates calculated from this model varied minimally, ranging from 6.0% to 7.4%. Although a risk-adjustment model for 30-day pediatric sepsis mortality had good performance characteristics, the use of risk-adjusted mortality rates as a hospital quality measure in pediatric sepsis is not useful due to the low volume of cases at most hospitals. Novel metrics to

Hypothermia in the sepsis syndrome and clinical outcome. The Methylprednisolone Severe Sepsis Study Group.

PubMed

Clemmer, T P; Fisher, C J; Bone, R C; Slotman, G J; Metz, C A; Thomas, F O

1992-10-01

To evaluate the consequences of clinical hypothermia associated with sepsis syndrome and septic shock. Analysis of data from a multi-institutional, randomized, placebo-controlled, prospective study with predetermined end-point analysis of development of shock, recovery from shock, hospital length of stay, and death. Multi-institutional medical and surgical ICUs. Patients meeting predetermined criteria for severe sepsis syndrome. Appropriate sepsis and shock care with 50% of patients receiving methylprednisolone and 50% receiving placebo. The occurrence rate of hypothermia (< 35.5 degrees C) is 9% in this population. When compared with febrile patients, hypothermic patients had a higher frequency of central nervous system dysfunction (88% vs. 60%), increased serum bilirubin concentration (35% vs. 15%), prolonged prothrombin times (50% vs. 23%), shock (94% vs. 61%), failure to recover from shock (66% vs. 26%), and death (62% vs. 26%). The hypothermic patients were also more likely to be classified as having a rapidly or ultimately fatal disease upon study admission. This prospective study confirms that hypothermia associated with sepsis syndrome has a significant relationship to outcome manifest by increased frequency of shock and death from shock. This finding is in sharp contrast to the protective effects of induced hypothermia in septic animals and perhaps man.

An Evidence Based Approach to Sepsis: Educational Program

ERIC Educational Resources Information Center

Perez, Dolores

2015-01-01

Evidence-based guidelines for recognizing and treating sepsis have been available for decades, yet healthcare providers do not adhere to the recommendations. Sepsis can progress rapidly if not recognized early. Literature reports reveal that sepsis is the leading cause of death in non-cardiac intensive care units (ICUs), and it is one of the most…

Differences in reported sepsis incidence according to study design: a literature review.

PubMed

Mariansdatter, Saga Elise; Eiset, Andreas Halgreen; Søgaard, Kirstine Kobberøe; Christiansen, Christian Fynbo

2016-10-12

Sepsis and severe sepsis are common conditions in hospital settings, and are associated with high rates of morbidity and mortality, but reported incidences vary considerably. In this literature review, we describe the variation in reported population-based incidences of sepsis and severe sepsis. We also examine methodological and demographic differences between studies that may explain this variation. We carried out a literature review searching three major databases and reference lists of relevant articles, to identify all original studies reporting the incidence of sepsis or severe sepsis in the general population. Two authors independently assessed all articles, and the final decision to exclude an article was reached by consensus. We extracted data according to predetermined variables, including study country, sepsis definition, and data source. We then calculated descriptive statistics for the reported incidences of sepsis and severe sepsis. The studies were classified according to the method used to identify cases of sepsis or severe sepsis: chart-based (i.e. review of patient charts) or code-based (i.e. predetermined International Classification of Diseases [ICD] codes). Among 482 articles initially screened, we identified 23 primary publications reporting incidence of sepsis and/or severe sepsis in the general population. The reported incidences ranged from 74 to 1180 per 100,000 person-years and 3 to 1074 per 100,000 person-years for sepsis and severe sepsis, respectively. Most chart-based studies used the Bone criteria (or a modification hereof) and Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study criteria to identify cases of sepsis and severe sepsis. Most code-based studies used ICD-9 codes, but the number of codes used ranged from 1 to more than 1200. We found that the incidence varied according to how sepsis was identified (chart-based vs. code-based), calendar year, data source, and world region. The reported incidences of sepsis and

Septic arthritis associated with systemic sepsis.

PubMed

Jung, Sung-Weon; Kim, Dong-Hee; Shin, Sung-Jin; Kang, Byoung-Youl; Eho, Yil-Ju; Yang, Seong-Wook

2018-01-01

Septic arthritis presents with good joint function, but sometimes leads to poor outcomes. Concurrent systemic sepsis has been regarded as the poor outcome, and the exact cause remains unclear. This paper was performed to identify factors associated with concurrent systemic sepsis and to research results to predict poor outcomes in patients with septic arthritis. Laboratory and medical data were reviewed for 137 adults with acute septic arthritis who underwent open or arthroscopic surgical debridement at our institution between January 2005 and December 2014. The patients were divided according to whether they had septic arthritis alone (Group A) or in combination with systemic sepsis (Group B). Systemic sepsis was defined as two more systemic inflammatory signs in response to an infectious process. Patient characteristics, laboratory findings, synovial fluid findings and cultures, and surgical results were compared between two groups. Of the 137 patients, 41 (29.9%) had initial systemic sepsis at the diagnosis of septic arthritis. Independent t test revealed that duration of prodromal symptom (p = 0.012), serum neutrophil percent (p = 0.008), C-reactive protein (p = 0.001), Charlson comorbidity index (p = 0.001), positive culture in synovial fluid (p = 0.001), and methicillin-sensitive Staphylococcus aureus (MSSA) isolate in synovial fluid (p = 0.001) had significant correlations with the group B. Repeated debridement was performed for those who had recurrence of infection, and this procedure was more often in group B (23 versus 21 joints, 23.9 versus 51.2%, p = 0.012). Progression of arthritis occurred more often in group B (16 versus 17 joints, 16.7 versus 41.5%, p = 0.001). Septic arthritis combined with systemic sepsis was related to duration of prodromal symptom, serum neutrophil percent, C-reactive protein, Charlson comorbidity index, positive culture in synovial fluid, and a MSSA isolate in synovial fluid. Concurrent systemic sepsis led to

Depressive Symptoms in Spouses of Older Patients with Severe Sepsis

PubMed Central

Davydow, Dimitry S; Hough, Catherine L; Langa, Kenneth M; Iwashyna, Theodore J

2013-01-01

Objective To examine whether spouses of patients with severe sepsis are at increased risk for depression independent of the spouse’s pre-sepsis history, whether this risk differs by sex, and is associated with a sepsis patient’s disability after hospitalization. Design Prospective longitudinal cohort study. Setting Population-based cohort of U.S. adults over 50 years old interviewed as part of the Health and Retirement Study (1993–2008). Patients 929 patient-spouse dyads comprising 1,212 hospitalizations for severe sepsis. Measurements and Main Results Severe sepsis was identified using a validated algorithm in Medicare claims. Depression was assessed with a modified version of the Center for Epidemiologic Studies Depression Scale. All analyses were stratified by gender. The prevalence of substantial depressive symptoms in wives of patients with severe sepsis increased by 14 percentage points at the time of severe sepsis (from 20% at a median of 1.1 years pre-sepsis to 34% at a median of 1 year post-sepsis), an odds ratio (OR) of 3.74 (95% Confidence Interval [CI]: 2.20, 6.37), in multivariable regression. Husbands had an 8 percentage point increase in the prevalence of substantial depressive symptoms, which was not significant in multivariable regression (OR 1.90, 95%CI: 0.75, 4.71). The increase in depression was not explained by bereavement; women had greater odds of substantial depressive symptoms even when their spouse survived a severe sepsis hospitalization (OR 2.86, 95%CI 1.06, 7.73). Wives of sepsis survivors who were disabled were more likely to be depressed (OR 1.35 per ADL limitation of sepsis survivor, 95%CI: 1.12, 1.64); however, controlling for patient disability only slightly attenuated the association between sepsis and wives’ depression (OR 2.61, 95%CI: 0.93, 7.38). Conclusions Older women may be at greater risk for depression if their spouse is hospitalized for severe sepsis. Spouses of patients with severe sepsis may benefit from greater

Hospital-related cost of sepsis: A systematic review.

PubMed

Arefian, Habibollah; Heublein, Steffen; Scherag, André; Brunkhorst, Frank Martin; Younis, Mustafa Z; Moerer, Onnen; Fischer, Dagmar; Hartmann, Michael

2017-02-01

This article systematically reviews research on the costs of sepsis and, as a secondary aim, evaluates the quality of economic evaluations reported in peer-reviewed journals. We systematically searched the MEDLINE, National Health Service (Abstracts of Reviews of Effects, Economic Evaluation and Health Technology Assessment), Cost-effectiveness Analysis Registry and Web of Knowledge databases for studies published between January 2005 and June 2015. We selected original articles that provided cost and cost-effectiveness analyses, defined sepsis and described their cost calculation method. Only studies that considered index admissions and re-admissions in the first 30 days were published in peer-reviewed journals and used standard treatments were considered. All costs were adjusted to 2014 US dollars. Medians and interquartile ranges (IQRs) for various costs of sepsis were calculated. The quality of economic studies was assessed using the Drummond 10-item checklist. Overall, 37 studies met our eligibility criteria. The median of the mean hospital-wide cost of sepsis per patient was $32,421 (IQR $20,745-$40,835), and the median of the mean ICU cost of sepsis per patient was $27,461 (IQR $16,007-$31,251). Overall, the quality of economic studies was low. Estimates of the hospital-related costs of sepsis varied considerably across the included studies depending on the method used for cost calculation, the type of sepsis and the population that was examined. A standard model for conducting cost improve the quality of studies on the costs of sepsis. Copyright © 2016 The British Infection Association. All rights reserved.

Polarization of microglia and its role in bacterial sepsis.

PubMed

Michels, Monique; Sonai, Beatriz; Dal-Pizzol, Felipe

2017-02-15

Microglial polarization in response to brain inflammatory conditions is a crescent field in neuroscience. However, the effect of systemic inflammation, and specifically sepsis, is a relatively unexplored field that has great interest and relevance. Sepsis has been associated with both early and late harmful events of the central nervous system, suggesting that there is a close link between sepsis and neuroinflammation. During sepsis evolution it is supposed that microglial could exert both neurotoxic and repairing effects depending on the specific microglial phenotype assumed. In this context, here it was reviewed the role of microglial polarization during sepsis-associated brain dysfunction. Copyright © 2017 Elsevier B.V. All rights reserved.

ACUTE DIALYSIS QUALITY INITIATIVE (ADQI) XIV SEPSIS PHENOTYPES AND TARGETS FOR BLOOD PURIFICATION IN SEPSIS: THE BOGOTÁ CONSENSUS.

PubMed

Kellum, John A; Gómez, Hernando; Gómez, Alonso; Murray, Patrick; Ronco, Claudio

2016-03-01

Despite widespread use, there is currently no consensus on how extracorporeal blood purification therapies should be applied or studied in patients with sepsis. One major obstacle has been the lack of clear descriptions of specific sepsis phenotypes tied to mechanisms that would permit the identification of molecular targets. Current evidence suggests that sepsis-related morbidity and mortality involve widely different clinical phenotypes that variably include mitochondrial dysfunction, abnormalities of vascular biology including endothelial dysfunction and coagulopathy, epithelial dysfunction, and immune suppression and dysregulation. While most cases of sepsis involve some element of all of these pathobiologic processes, the magnitude of each varies greatly from patient to patient in part as a result of the pathogen and in part related to host-specific factors. Thus, the purpose of the fourteenth international consensus conference of acute dialysis quality initiative was to develop consensus for a conceptual model of sepsis-induced organ failure that can be treated by extracorporeal blood purification and possibly also with drugs or other therapies. We assembled a group of experts from around the world and used a modified Delphi method to reach consensus. Specific findings and recommendations for future research are provided in the four accompanying papers.

Quantifying the improvement in sepsis diagnosis, documentation, and coding: the marginal causal effect of year of hospitalization on sepsis diagnosis.

PubMed

Jafarzadeh, S Reza; Thomas, Benjamin S; Marschall, Jonas; Fraser, Victoria J; Gill, Jeff; Warren, David K

2016-01-01

To quantify the coinciding improvement in the clinical diagnosis of sepsis, its documentation in the electronic health records, and subsequent medical coding of sepsis for billing purposes in recent years. We examined 98,267 hospitalizations in 66,208 patients who met systemic inflammatory response syndrome criteria at a tertiary care center from 2008 to 2012. We used g-computation to estimate the causal effect of the year of hospitalization on receiving an International Classification of Diseases, Ninth Revision, Clinical Modification discharge diagnosis code for sepsis by estimating changes in the probability of getting diagnosed and coded for sepsis during the study period. When adjusted for demographics, Charlson-Deyo comorbidity index, blood culture frequency per hospitalization, and intensive care unit admission, the causal risk difference for receiving a discharge code for sepsis per 100 hospitalizations with systemic inflammatory response syndrome, had the hospitalization occurred in 2012, was estimated to be 3.9% (95% confidence interval [CI], 3.8%-4.0%), 3.4% (95% CI, 3.3%-3.5%), 2.2% (95% CI, 2.1%-2.3%), and 0.9% (95% CI, 0.8%-1.1%) from 2008 to 2011, respectively. Patients with similar characteristics and risk factors had a higher of probability of getting diagnosed, documented, and coded for sepsis in 2012 than in previous years, which contributed to an apparent increase in sepsis incidence. Copyright © 2016 Elsevier Inc. All rights reserved.

Feasibility of modified surviving sepsis campaign guidelines in a resource-restricted setting based on a cohort study of severe S. aureus sepsis [corrected].

PubMed

Mahavanakul, Weera; Nickerson, Emma K; Srisomang, Pramot; Teparrukkul, Prapit; Lorvinitnun, Pichet; Wongyingsinn, Mingkwan; Chierakul, Wirongrong; Hongsuwan, Maliwan; West, T Eoin; Day, Nicholas P; Limmathurotsakul, Direk; Peacock, Sharon J

2012-01-01

The Surviving Sepsis Campaign (SSC) guidelines describe best practice for the management of severe sepsis and septic shock in developed countries, but most deaths from sepsis occur where healthcare is not sufficiently resourced to implement them. Our objective was to define the feasibility and basis for modified guidelines in a resource-restricted setting. We undertook a detailed assessment of sepsis management in a prospective cohort of patients with severe sepsis caused by a single pathogen in a 1,100-bed hospital in lower-middle income Thailand. We compared their management with the SSC guidelines to identify care bundles based on existing capabilities or additional activities that could be undertaken at zero or low cost. We identified 72 patients with severe sepsis or septic shock associated with S. aureus bacteraemia, 38 (53%) of who died within 28 days. One third of patients were treated in intensive care units (ICUs). Numerous interventions described by the SSC guidelines fell within existing capabilities, but their implementation was highly variable. Care available to patients on general wards covered the fundamental principles of sepsis management, including non-invasive patient monitoring, antimicrobial administration and intravenous fluid resuscitation. We described two additive care bundles, one for general wards and the second for ICUs, that if consistently performed would be predicted to improve outcome from severe sepsis. It is feasible to implement modified sepsis guidelines that are scaled to resource availability, and that could save lives prior to the publication of international guidelines for developing countries.

Rethinking the concept of sepsis and septic shock.

PubMed

A Cabrita, Joana; Pinheiro, Isabel; Menezes Falcão, L

2018-06-16

Sepsis is a major global health problem and represents a challenge for physicians all over the world. The knowledge of sepsis and septic shock is a topic of interest among the scientific community and society in general. New guidelines for management of sepsis and septic shock were developed in 2016, providing an update on this area. In Sepsis-3 new definitions for sepsis and septic shock were published. The purpose of this narrative review is to discuss and compare the new criteria of 2016 with the old criteria, purposing at the same time an alternative approach for this topic. SOFA criteria (Sequential Organ Failure Assessment Score) are more complete, but too extensive and usually difficult to apply outside the intensive care units, therefore inducing potentially delay in the proper treatment. We purpose combined criteria for the selection of sepsis patients. Initially, we could apply qSOFA (quick Sepsis Related Organ Failure Assessment) criteria, due to its easy application, associated with the SIRS (systemic inflammatory response syndrome) criteria, allowing to select the patients who are infected and need faster treatment. In that way we would use the best of old and newest criteria, allowing the early selection of patients who are infected and require faster treatment, while the search for a better and faster tool continues. Copyright © 2018 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Sepsis in Obstetrics: Clinical Features and Early Warning Tools.

PubMed

Parfitt, Sheryl E; Bogat, Mary L; Hering, Sandra L; Ottley, Charlotte; Roth, Cheryl

Morbidity and mortality associated with sepsis has gained widespread attention on a local, state, and national level, yet, it remains a complicated disorder that can be difficult to identify in a timely manner. Sepsis in obstetric patients further complicates the diagnosis as alterations in physiology related to pregnancy can mask sepsis indicators normally seen in the general population. If early signs of sepsis go unrecognized, septic shock can develop, leading to organ dysfunction and potential death. Maternal early warning tools have been designed to assist clinicians in recognizing early indications of illness. Through use of clinical pathway-specific tools, disease processes may be detected early, subsequently benefitting patients with aggressive treatment management and intervention.This article is the second in a series of three that discuss the importance of sepsis and septic shock in pregnancy. Risk factors, causes of sepsis, signs and symptoms, and maternal early warning tools are discussed.

Maternal sepsis: a Scottish population-based case-control study.

PubMed

Acosta, C D; Bhattacharya, S; Tuffnell, D; Kurinczuk, J J; Knight, M

2012-03-01

To describe the risk of maternal sepsis associated with obesity and other understudied risk factors such as operative vaginal delivery. Population-based, case-control study. North NHS region of Scotland. All cases of pregnant, intrapartum and postpartum women with International Classification of Disease-9 codes for sepsis or severe sepsis recorded in the Aberdeen Maternal and Neonatal Databank (AMND) from 1986 to 2009. Four controls per case selected from the AMND were frequency matched on year-of-delivery. Cases and controls were compared; significant variables from univariable regression were adjusted in a multivariable logistic regression model. Dependent variables were uncomplicated sepsis or severe ('near-miss') sepsis. Independent variables were demographic, medical and clinical delivery characteristics. Unadjusted and adjusted odds ratios (OR) with 95% confidence intervals (95% CI) are reported. Controlling for mode of delivery and demographic and clinical factors, obese women had twice the odds of uncomplicated sepsis (OR 2.12; 95% CI 1.14-3.89) compared with women of normal weight. Age <25 years (OR 5.15; 95% CI 2.43-10.90) and operative vaginal delivery (OR 2.20; 95% CI 1.02-4.87) were also significant predictors of sepsis. Known risk factors for maternal sepsis were also significant in this study (OR for uncomplicated and severe sepsis respectively): multiparity (OR 6.29, 12.04), anaemia (OR 3.43, 18.49), labour induction (OR 3.92 severe only), caesarean section (OR 3.23, 13.35), and preterm birth (OR 2.46 uncomplicated only). Obesity, operative vaginal delivery and age <25 years are significant risk factors for sepsis and should be considered in clinical obstetric care. © 2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2012 RCOG.

Plasma procalcitonin concentrations are increased in dogs with sepsis

PubMed Central

Goggs, Robert; Milloway, Matthew; Troia, Roberta; Giunti, Massimo

2018-01-01

Sepsis, the life-threatening organ dysfunction caused by a dysregulated host response to infection, is difficult to identify and to prognosticate for. In people with sepsis, procalcitonin (PCT) measurement aids diagnosis, enables therapeutic monitoring and improves prognostic accuracy. This study used a commercial canine PCT assay to measure plasma PCT concentrations in dogs with gastric dilatation volvulus (GDV) syndrome and in dogs with sepsis. It was hypothesised that dogs with GDV syndrome and with sepsis have greater plasma PCT concentrations than healthy dogs and that dogs with sepsis have greater PCT concentrations than dogs with GDV syndrome. Before analysing canine plasma samples, the ability of the assay to identify canine PCT, in addition to assay imprecision and the lower limit of detection were established. The assay had low imprecision with coefficients of variation ≤4.5 per cent. The lower limit of detection was 3.4 pg/ml. Plasma PCT concentrations were measured in 20 dogs with sepsis, in 32 dogs with GDV syndrome and in 52 healthy dogs. Median (IQR) PCT concentration in dogs with sepsis 78.7 pg/ml (39.1–164.7) was significantly greater than in healthy dogs 49.8 pg/ml (36.2–63.7) (P=0.019), but there were no significant differences between PCT concentrations in dogs with GDV syndrome and controls (P=0.072) or between dogs with sepsis and GDV syndrome (P=1.000). Dogs with sepsis have significantly increased plasma PCT concentrations compared with healthy dogs, although considerable overlap between these populations was identified. Future investigations should confirm this finding in other populations and evaluate the diagnostic and prognostic value of PCT in dogs with sepsis. PMID:29682292

Identifying Pediatric Severe Sepsis and Septic Shock: Accuracy of Diagnosis Codes.

PubMed

Balamuth, Fran; Weiss, Scott L; Hall, Matt; Neuman, Mark I; Scott, Halden; Brady, Patrick W; Paul, Raina; Farris, Reid W D; McClead, Richard; Centkowski, Sierra; Baumer-Mouradian, Shannon; Weiser, Jason; Hayes, Katie; Shah, Samir S; Alpern, Elizabeth R

2015-12-01

To evaluate accuracy of 2 established administrative methods of identifying children with sepsis using a medical record review reference standard. Multicenter retrospective study at 6 US children's hospitals. Subjects were children >60 days to <19 years of age and identified in 4 groups based on International Classification of Diseases, Ninth Revision, Clinical Modification codes: (1) severe sepsis/septic shock (sepsis codes); (2) infection plus organ dysfunction (combination codes); (3) subjects without codes for infection, organ dysfunction, or severe sepsis; and (4) infection but not severe sepsis or organ dysfunction. Combination codes were allowed, but not required within the sepsis codes group. We determined the presence of reference standard severe sepsis according to consensus criteria. Logistic regression was performed to determine whether addition of codes for sepsis therapies improved case identification. A total of 130 out of 432 subjects met reference SD of severe sepsis. Sepsis codes had sensitivity 73% (95% CI 70-86), specificity 92% (95% CI 87-95), and positive predictive value 79% (95% CI 70-86). Combination codes had sensitivity 15% (95% CI 9-22), specificity 71% (95% CI 65-76), and positive predictive value 18% (95% CI 11-27). Slight improvements in model characteristics were observed when codes for vasoactive medications and endotracheal intubation were added to sepsis codes (c-statistic 0.83 vs 0.87, P = .008). Sepsis specific International Classification of Diseases, Ninth Revision, Clinical Modification codes identify pediatric patients with severe sepsis in administrative data more accurately than a combination of codes for infection plus organ dysfunction. Copyright © 2015 Elsevier Inc. All rights reserved.

New or Progressive Multiple Organ Dysfunction Syndrome in Pediatric Severe Sepsis: A Sepsis Phenotype With Higher Morbidity and Mortality.

PubMed

Lin, John C; Spinella, Philip C; Fitzgerald, Julie C; Tucci, Marisa; Bush, Jenny L; Nadkarni, Vinay M; Thomas, Neal J; Weiss, Scott L

2017-01-01

To describe the epidemiology, morbidity, and mortality of new or progressive multiple organ dysfunction syndrome in children with severe sepsis. Secondary analysis of a prospective, cross-sectional, point prevalence study. International, multicenter PICUs. Pediatric patients with severe sepsis identified on five separate days over a 1-year period. None. Of 567 patients from 128 PICUs in 26 countries enrolled, 384 (68%) developed multiple organ dysfunction syndrome within 7 days of severe sepsis recognition. Three hundred twenty-seven had multiple organ dysfunction syndrome on the day of sepsis recognition. Ninety-one of these patients developed progressive multiple organ dysfunction syndrome, whereas an additional 57 patients subsequently developed new multiple organ dysfunction syndrome, yielding a total proportion with severe sepsis-associated new or progressive multiple organ dysfunction syndrome of 26%. Hospital mortality in patients with progressive multiple organ dysfunction syndrome was 51% compared with patients with new multiple organ dysfunction syndrome (28%) and those with single-organ dysfunction without multiple organ dysfunction syndrome (10%) (p < 0.001). Survivors of new or progressive multiple organ dysfunction syndrome also had a higher frequency of moderate to severe disability defined as a Pediatric Overall Performance Category score of greater than or equal to 3 and an increase of greater than or equal to 1 from baseline: 22% versus 29% versus 11% for progressive, new, and no multiple organ dysfunction syndrome, respectively (p < 0.001). Development of new or progressive multiple organ dysfunction syndrome is common (26%) in severe sepsis and is associated with a higher risk of morbidity and mortality than severe sepsis without new or progressive multiple organ dysfunction syndrome. Our data support the use of new or progressive multiple organ dysfunction syndrome as an important outcome in trials of pediatric severe sepsis although efforts

A Review of GM-CSF Therapy in Sepsis

PubMed Central

Mathias, Brittany; Szpila, Benjamin E.; Moore, Frederick A.; Efron, Philip A.; Moldawer, Lyle L.

2015-01-01

Abstract Determine what clinical role, if any, GM-CSF may have in the clinical treatment of sepsis in the adult patient. Advancements in the management of sepsis have led to significant decreases in early mortality; however, sepsis remains a significant source of long-term mortality and disability which places strain on healthcare resources with a substantial growing economic impact. Historically, early multiple organ failure (MOF) and death in patients with severe sepsis was thought to result from an exaggerated proinflammatory response called the systemic inflammatory response syndrome (SIRS). Numerous prospective randomized controlled trials (PRCTs) tested therapies aimed at decreasing the organ injury associated with an exaggerated inflammatory response. With few exceptions, the results from these PRCTs have been disappointing, and currently no specific therapeutic agent is approved to counteract the early SIRS response in patients with severe sepsis. It has long been recognized that there is a delayed immunosuppressive state that contributes to long-term morbidity. However, recent findings now support a concurrent proinflammatory and anti-inflammatory response present throughout sepsis. Multiple immunomodulating agents have been studied to combat the immunosuppressive phase of sepsis with the goal of decreasing secondary infection, reducing organ dysfunction, decreasing ICU stays, and improving survival. Granulocyte-macrophage colony stimulating factor (GM-CSF), a myelopoietic growth factor currently used in patients with neutropenia secondary to chemotherapy-induced myelosuppression, has been studied as a potential immune-activating agent. The applicability of GM-CSF as a standard therapy for generalized sepsis is still largely understudied; however, small-scale studies available have demonstrated some improved recovery from infection, decreased hospital length of stay, decreased days requiring mechanical ventilation, and decreased medical costs. PMID

Bacterial Sepsis in Patients with Visceral Leishmaniasis in Northwest Ethiopia

PubMed Central

Takele, Yegnasew; Woldeyohannes, Desalegn; Tiruneh, Moges; Mohammed, Rezika; Lynen, Lutgarde; van Griensven, Johan

2014-01-01

Background and Objectives. Visceral leishmaniasis (VL) is one of the neglected diseases affecting the poorest segment of world populations. Sepsis is one of the predictors for death of patients with VL. This study aimed to assess the prevalence and factors associated with bacterial sepsis, causative agents, and their antimicrobial susceptibility patterns among patients with VL. Methods. A cross-sectional study was conducted among parasitologically confirmed VL patients suspected of sepsis admitted to the University of Gondar Hospital, Northwest Ethiopia, from February 2012 to May 2012. Blood cultures and other clinical samples were collected and cultured following the standard procedures. Results. Among 83 sepsis suspected VL patients 16 (19.3%) had culture confirmed bacterial sepsis. The most frequently isolated organism was Staphylococcus aureus (68.8%; 11/16), including two methicillin-resistant isolates (MRSA). Patients with focal bacterial infection were more likely to have bacterial sepsis (P < 0.001). Conclusions. The prevalence of culture confirmed bacterial sepsis was high, predominantly due to S. aureus. Concurrent focal bacterial infection was associated with bacterial sepsis, suggesting that focal infections could serve as sources for bacterial sepsis among VL patients. Careful clinical evaluation for focal infections and prompt initiation of empiric antibiotic treatment appears warranted in VL patients. PMID:24895569

Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy

PubMed Central

Hotchkiss, Richard S.; Monneret, Guillaume; Payen, Didier

2014-01-01

Sepsis — severe life-threatening infection with organ dysfunction — initiates a complex interplay of host pro- and anti-inflammatory processes. In a real sense, sepsis can be considered a race to the death between the pathogens and the host immune system. It is the proper balance between the often competing pro- and anti-inflammatory pathways that determines the fate of the individual. Although the field of sepsis research has witnessed the failure of many highly-touted clinical trials, a better understanding of the pathophysiological basis of the disorder and the mechanisms responsible for the associated pro- and anti-inflammatory responses is leading to a novel approach to treat this highly lethal condition. Biomarker-guided immunotherapy administered to patients at the proper immune phase of sepsis represents a potential major advance in the treatment of sepsis and more broadly in the field of infectious disease. PMID:24232462

Predictive Validity of Sepsis-3 Definitions and Sepsis Outcomes in Critically Ill Patients: A Cohort Study in 49 ICUs in Argentina.

PubMed

Estenssoro, Elisa; Kanoore Edul, Vanina S; Loudet, Cecilia I; Osatnik, Javier; Ríos, Fernando G; Vázquez, Daniela N; Pozo, Mario O; Lattanzio, Bernardo; Pálizas, Fernando; Klein, Francisco; Piezny, Damián; Rubatto Birri, Paolo N; Tuhay, Graciela; Díaz, Anatilde; Santamaría, Analía; Zakalik, Graciela; Dubin, Arnaldo

2018-05-08

The new Sepsis-3 definitions have been scarcely assessed in low- and middle-income countries; besides, regional information of sepsis outcomes is sparse. Our objective was to evaluate Sepsis-3 definition performance in Argentina. Cohort study of 3-month duration beginning on July 1, 2016. Forty-nine ICUs. Consecutive patients admitted to the ICU with suspected infection that triggered blood cultures and antibiotic administration. None. Patients were classified as having infection, sepsis (infection + change in Sequential Organ Failure Assessment ≥ 2 points), and septic shock (vasopressors + lactate > 2 mmol/L). Patients on vasopressors and lactate less than or equal to 2 mmol/L (cardiovascular dysfunction) were analyzed separately, as those on vasopressors without serum lactate measurement. Systemic inflammatory response syndrome was also recorded. Main outcome was hospital mortality. Of 809 patients, 6% had infection, 29% sepsis, 20% cardiovascular dysfunction, 40% septic shock, and 3% received vasopressors with lactate unmeasured. Hospital mortality was 13%, 20%, 39%, 51%, and 41%, respectively (p = 0.000). Independent predictors of outcome were lactate, Sequential Organ Failure Assessment score, comorbidities, prior duration of symptoms (hr), mechanical ventilation requirement, and infection by highly resistant microorganisms. Area under the receiver operating characteristic curves for mortality for systemic inflammatory response syndrome and Sequential Organ Failure Assessment were 0.53 (0.48-0.55) and 0.74 (0.69-0.77), respectively (p = 0.000). Increasing severity of Sepsis-3 categories adequately tracks mortality; cardiovascular dysfunction subgroup, not included in Sepsis-3, has distinct characteristics. Sequential Organ Failure Assessment score shows adequate prognosis accuracy-contrary to systemic inflammatory response syndrome. This study supports the predictive validity of Sepsis-3 definitions.

Hepatic metabolic response to injury and sepsis.

PubMed

Dahn, M S; Mitchell, R A; Lange, M P; Smith, S; Jacobs, L A

1995-05-01

Experimental reports have indicated that hepatic oxidative and synthetic metabolism may become depressed in sepsis. Because the mechanism of infection-related liver dysfunction has not been established, further study of these functional alterations could contribute to the therapeutic management of septic organ failure syndromes. However, recently controversy has arisen over the existence of these derangements that must be reconciled before further progress in this field can be made. Splanchnic balance studies for the measurement of glucose output and oxygen consumption were used to assess hepatic function in fasted normal volunteers (n = 18), injured patients (n = 10), and patients with sepsis (n = 18). The liver's contribution to splanchnic metabolism was estimated from a comparison of splanchnic oxygen utilization in response to increases in the liver-specific process of glucogenesis. In addition, in vivo liver albumin production was determined by using the [14C] carbonate technique. Glucose output after injury and sepsis was increased by 12.8% and 76.6%, respectively, compared with controls. On the basis of substrate balance studies, gluconeogenesis was estimated to account for 46%, 87%, and 93%, respectively, of splanchnic glucose output in each of the three groups. In patients with sepsis glucose output was also noted to be linearly related to regional oxygen consumption, indicating that these processes were coupled and increases in the respiratory activity of the splanchnic cellular mass could be accounted for by increases in new glucose output and gluconeogenic substrate clearance. The mean albumin synthetic rate increased during injury and sepsis by 22% and 29%, respectively, compared with normal volunteers. These studies cast doubt on the commonly held notion that tissue respiratory dysfunction may occur during sepsis. On the contrary, hepatic function is accelerated during hyperdynamic sepsis, and evidence indicating oxidative or synthetic functional

Anaesthetic management of patients with severe sepsis.

PubMed

Eissa, D; Carton, E G; Buggy, D J

2010-12-01

Severe sepsis, a syndrome characterized by systemic inflammation and acute organ dysfunction in response to infection, is a major healthcare problem affecting all age groups throughout the world. Anaesthetists play a central role in the multidisciplinary management of patients with severe sepsis from their initial deterioration at ward level, transfer to the diagnostic imaging suite, and intraoperative management for emergency surgery. The timely administration of appropriate i.v. antimicrobial therapy is a crucial step in the care of patients with severe sepsis who may require surgery to control the source of sepsis. Preoperative resuscitation, aimed at optimizing major organ perfusion, is based on judicious use of fluids, vasopressors, and inotropes. Intraoperative anaesthesia management requires careful induction and maintenance of anaesthesia, optimizing intravascular volume status, avoidance of lung injury during mechanical ventilation, and ongoing monitoring of arterial blood gases, lactate concentration, haematological and renal indices, and electrolyte levels. Postoperative care overlaps with ongoing management of the severe sepsis syndrome patient in the intensive care unit. These patients are by definition, high risk, already requiring multiple supports, and require experienced and skilful decision-making to optimize their chances of a favourable outcome. Similar to acute myocardial infarction, stroke, or acute trauma, the initial hours (golden hours) of clinical management of severe sepsis represent an important opportunity to reduce morbidity and mortality. Rapid clinical assessment, resuscitation and surgical management by a focused multidisciplinary team, and early effective antimicrobial therapy are the key components to improved patient outcome.

[Pharmaconutrition with parenteral selenium in sepsis].

PubMed

Langlois, P L; de Oliveira Figliolino, L F; Hardy, G; Manzanares, W

2014-04-01

Critical illness is characterized by oxidative stress which leads to multiple organ failure, and sepsis-related organ dysfunction remains the most common cause of death in the intensive care unit. Over the last 2 decades, different antioxidant therapies have been developed to improve outcomes in septic patients. According to recent evidence, selenium therapy should be considered the cornerstone of the antioxidant strategies. Selenium given as selenious acid or sodium selenite should be considered as a drug or pharmaconutrient with prooxidant and cytotoxic effects when a loading dose in intravenous bolus form is administered, particularly in the early stage of severe sepsis/septic shock. To date, several phase ii trials have demonstrated that selenium therapy may be able to decrease mortality, improve organ dysfunction and reduce infections in critically ill septic patients. The effect of selenium therapy in sepsis syndrome must be confirmed by large, well designed phase iii clinical trials. The purpose of this review is to discuss current evidence on selenium pharmaconutrition in sepsis syndrome. Copyright © 2013 Elsevier España, S.L. and SEMICYUC. All rights reserved.

The epidemiology of sepsis in Brazilian intensive care units (the Sepsis PREvalence Assessment Database, SPREAD): an observational study.

PubMed

Machado, Flavia R; Cavalcanti, Alexandre Biasi; Bozza, Fernando Augusto; Ferreira, Elaine M; Angotti Carrara, Fernanda Sousa; Sousa, Juliana Lubarino; Caixeta, Noemi; Salomao, Reinaldo; Angus, Derek C; Pontes Azevedo, Luciano Cesar

2017-11-01

The sepsis burden on acute care services in middle-income countries is a cause for concern. We estimated incidence, prevalence, and mortality of sepsis in adult Brazilian intensive care units (ICUs) and association of ICU organisational factors with outcome. We did a 1-day point prevalence study with follow-up of patients in ICU with sepsis in a nationally representative pseudo-random sample. We produced a sampling frame initially stratified by geographical region. Each stratum was then stratified by hospitals' main source of income (serving general public vs privately insured individuals) and ICU size (ten or fewer beds vs more than ten beds), finally generating 40 strata. In each stratum we selected a random sample of ICUs so as to enrol the total required beds in 1690 Brazilian adult ICUs. We followed up patients until hospital discharge censored at 60 days, estimated incidence from prevalence and length of stay, and generated national estimates. We assessed mortality prognostic factors using random-effects logistic regression models. On Feb 27, 2014, 227 (72%) of 317 ICUs that were randomly selected provided data on 2632 patients, of whom 794 had sepsis (30·2 septic patients per 100 ICU beds, 95% CI 28·4-31·9). The ICU sepsis incidence was 36·3 per 1000 patient-days (95% CI 29·8-44·0) and mortality was observed in 439 (55·7%) of 788 patients (95% CI 52·2-59·2). Low availability of resources (odds ratio [OR] 1·67, 95% CI 1·02-2·75, p=0·045) and adequacy of treatment (OR 0·56, 0·37-0·84, p=0·006) were independently associated with mortality. The projected incidence rate is 290 per 100 000 population (95% CI 237·9-351·2) of adult cases of ICU-treated sepsis per year, which yields about 420 000 cases annually, of whom 230 000 die in hospital. The incidence, prevalence, and mortality of ICU-treated sepsis is high in Brazil. Outcome varies considerably, and is associated with access to adequate resources and treatment. Our results show the

Sepsis Within 30 Days of Geriatric Hip Fracture Surgery.

PubMed

Bohl, Daniel D; Iantorno, Stephanie E; Saltzman, Bryan M; Tetreault, Matthew W; Darrith, Brian; Della Valle, Craig J

2017-10-01

Sepsis after hip fracture typically develops from one of the 3 potential infectious sources: urinary tract infection (UTI), pneumonia, and surgical site infection (SSI). The purpose of this investigation is to determine (1) the proportion of cases of sepsis that arises from each of these potential infectious sources; (2) baseline risk factors for developing each of the potential infectious sources; and (3) baseline risk factors for developing sepsis. The National Surgical Quality Improvement Program database was searched for geriatric patients (aged >65 years) who underwent surgery for hip fracture during 2005-2013. Patients subsequently diagnosed with sepsis were categorized according to concomitant diagnosis with UTI, SSI, and/or pneumonia. Multivariate regression was used to test for associations while adjusting for baseline characteristics. Among the 466 patients who developed sepsis (2.4% of all patients), 157 (33.7%) also had a UTI, 135 (29.0%) also had pneumonia, and 36 (7.7%) also had SSI. The rate of sepsis was elevated in patients who developed UTI (13.0% vs 1.7%; P < .001), pneumonia (18.2% vs 1.8%; P < .001), or SSI (14.8% vs 2.3%; P < .001). The mortality rate was elevated among those who developed sepsis (21.0% vs 3.8%; P < .001). Sepsis occurs in about 1 in 40 patients after geriatric hip fracture surgery. Of these septic cases, 1 in 3 is associated with UTI, 1 in 3 with pneumonia, and 1 in 15 with SSI. The cause of sepsis is often unknown on clinical diagnosis, and this distribution of potential infectious sources allows clinicians for direct identification and treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

Gut microbial colonisation in premature neonates predicts neonatal sepsis

PubMed Central

Madan, Juliette C; Salari, Richard Cowper; Saxena, Deepti; Davidson, Lisa; O’Toole, George A; Moore, Jason H; Sogin, Mitchell L; Foster, James A; Edwards, William H; Palumbo, Paul; Hibberd, Patricia L

2013-01-01

Background Neonatal sepsis due to intestinal bacterial translocation is a major cause of morbidity and mortality. Understanding microbial colonisation of the gut in prematurity may predict risk of sepsis to guide future strategies to manipulate the microbiome. Methods Prospective longitudinal study of premature infants. Stool samples were obtained weekly. DNA was extracted and the V6 hypervariable region of 16S rRNA was amplified followed by high throughput pyrosequencing, comparing subjects with and without sepsis. Results Six neonates were 24–27 weeks gestation at birth and had 18 samples analysed. Two subjects had no sepsis during the study period, two developed late-onset culture-positive sepsis and two had culture-negative systemic inflammation. 324 350 sequences were obtained. The meconium was not sterile and had predominance of Lactobacillus, Staphylococcus and Enterobacteriales. Overall, infants who developed sepsis began life with low microbial diversity, and acquired a predominance of Staphylococcus, while healthy infants had more diversity and predominance of Clostridium, Klebsiella and Veillonella. Conclusions In very low birth weight infants, the authors found that meconium is not sterile and is less diverse from birth in infants who will develop late-onset sepsis. Empiric, prolonged antibiotics profoundly decrease microbial diversity and promote a microbiota that is associated not only with neonatal sepsis, but the predominant pathogen previously identified in the microbiome. Our data suggest that there may be a ‘healthy microbiome’ present in extremely premature neonates that may ameliorate risk of sepsis. More research is needed to determine whether altered antibiotics, probiotics or other novel therapies can re-establish a healthy microbiome in neonates. PMID:22562869

Serum levels of osteopontin are increased in SIRS and sepsis.

PubMed

Vaschetto, Rosanna; Nicola, Stefania; Olivieri, Carlo; Boggio, Elena; Piccolella, Fabio; Mesturini, Riccardo; Damnotti, Federica; Colombo, Davide; Navalesi, Paolo; Della Corte, Francesco; Dianzani, Umberto; Chiocchetti, Annalisa

2008-12-01

In sepsis, dysregulation of the immune response leads to rapid multiorgan failure and death. Accurate and timely diagnosis is lifesaving and should discriminate sepsis from the systemic inflammatory response syndrome (SIRS) caused by non-infectious agents. Osteopontin acts as an extracellular matrix component or a soluble cytokine in inflamed tissues. Its exact role in immune response and sepsis remains to be elucidated. Therefore, we investigated the role of osteopontin in SIRS and sepsis. Prospective, observational study. Intensive care unit of a university hospital. Fifty-six patients with SIRS or sepsis and 56 healthy subjects were enrolled. We analyzed the serum levels of osteopontin and TH1-TH2 cytokines and investigated the role of osteopontin on interleukin 6 secretion by monocytes. Serum osteopontin levels were strikingly higher in patients than in controls and in sepsis than in SIRS, and decreased during the resolution of both the disorders. Receiver operating characteristic curves showed that osteopontin levels have discriminative power between SIRS and sepsis with an area under the curve of 0.796. Osteopontin levels directly correlated with those of interleukin 6 and in vitro, recombinant osteopontin increased interleukin 6 secretion by monocytes in both the absence and presence of high doses of lipopolysaccharide. These data suggest that osteopontin might be a mediator involved in the pathogenesis of SIRS and sepsis, possibly by supporting interleukin 6 secretion. 45. SIRS/Sepsis: clinical studies.

Using the integrated nurse leadership program to reduce sepsis mortality.

PubMed

Kliger, Julie; Singer, Sara J; Hoffman, Frank H

2015-06-01

The Integrated Nurse Leadership Program (INLP) is a collaborative improvement model focused on developing practical leadership skills of nurses and other frontline clinicians to lead quality improvement efforts. Sepsis is a major challenge to treat because it arises unpredictably and can progress rapidly. Nine San Francisco Bay Area hospitals participated in a 22-month INLP Sepsis Mortality Reduction Project to improve sepsis detection and management. The INLP focused on developing leadership and process improvement skills of nurses and other frontline clinicians. Teams of trained clinicians then implemented three strategies to improve early identification and timely treatment of sepsis: (1) sepsis screening of all patients, with diagnostic testing according to protocol; (2) timely treatment on the basis of key elements of Early Goal-Directed Therapy (EGDT); and (3) ongoing data review. Each hospital agreed to pursue the goal of reducing sepsis mortality by 15% by the end of the project. In the data collection period (baseline, July-December 2008 and project completion, January-June 2011), team members showed strong improvement in perceived leadership skills, team effectiveness, and ability to improve care quality. During this period, sepsis mortality for eight of the participating hospitals (Hospital 9 joined the project six months after it began) decreased by 43.7%-from 28% in the baseline period to 16% at project completion. Sepsis mortality rates trended downward for all hospitals, significantly decreasing (p<.05 at one hospital, p<.01 for four hospitals). In addition to improvement in safety culture and management of septic patients, hospitals participating in the INLP Sepsis Mortality Reduction Project achieved reductions in sepsis mortality during the study period and sustained reductions for more than one year later. The INLP model can be readily applied beyond sepsis management and mortality to other quality problems.

Fine Particulate Matter Pollution and Risk of Community-Acquired Sepsis

PubMed Central

McClure, Leslie A.; Griffin, Russell; Al-Hamdan, Mohammad Z.; Wang, Henry E.

2018-01-01

While air pollution has been associated with health complications, its effect on sepsis risk is unknown. We examined the association between fine particulate matter (PM2.5) air pollution and risk of sepsis hospitalization. We analyzed data from the 30,239 community-dwelling adults in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort linked with satellite-derived measures of PM2.5 data. We defined sepsis as a hospital admission for a serious infection with ≥2 systemic inflammatory response (SIRS) criteria. We performed incidence density sampling to match sepsis cases with 4 controls by age (±5 years), sex, and race. For each matched group we calculated mean daily PM2.5 exposures for short-term (30-day) and long-term (one-year) periods preceding the sepsis event. We used conditional logistic regression to evaluate the association between PM2.5 exposure and sepsis, adjusting for education, income, region, temperature, urbanicity, tobacco and alcohol use, and medical conditions. We matched 1386 sepsis cases with 5544 non-sepsis controls. Mean 30-day PM2.5 exposure levels (Cases 12.44 vs. Controls 12.34 µg/m3; p = 0.28) and mean one-year PM2.5 exposure levels (Cases 12.53 vs. Controls 12.50 µg/m3; p = 0.66) were similar between cases and controls. In adjusted models, there were no associations between 30-day PM2.5 exposure levels and sepsis (4th vs. 1st quartiles OR: 1.06, 95% CI: 0.85–1.32). Similarly, there were no associations between one-year PM2.5 exposure levels and sepsis risk (4th vs. 1st quartiles OR: 0.96, 95% CI: 0.78–1.18). In the REGARDS cohort, PM2.5 air pollution exposure was not associated with risk of sepsis. PMID:29690517

Fine Particulate Matter Pollution and Risk of Community-Acquired Sepsis.

PubMed

Sarmiento, Elisa J; Moore, Justin Xavier; McClure, Leslie A; Griffin, Russell; Al-Hamdan, Mohammad Z; Wang, Henry E

2018-04-21

While air pollution has been associated with health complications, its effect on sepsis risk is unknown. We examined the association between fine particulate matter (PM 2.5 ) air pollution and risk of sepsis hospitalization. We analyzed data from the 30,239 community-dwelling adults in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort linked with satellite-derived measures of PM 2.5 data. We defined sepsis as a hospital admission for a serious infection with ≥2 systemic inflammatory response (SIRS) criteria. We performed incidence density sampling to match sepsis cases with 4 controls by age (±5 years), sex, and race. For each matched group we calculated mean daily PM 2.5 exposures for short-term (30-day) and long-term (one-year) periods preceding the sepsis event. We used conditional logistic regression to evaluate the association between PM 2.5 exposure and sepsis, adjusting for education, income, region, temperature, urbanicity, tobacco and alcohol use, and medical conditions. We matched 1386 sepsis cases with 5544 non-sepsis controls. Mean 30-day PM 2.5 exposure levels (Cases 12.44 vs. Controls 12.34 µg/m³; p = 0.28) and mean one-year PM 2.5 exposure levels (Cases 12.53 vs. Controls 12.50 µg/m³; p = 0.66) were similar between cases and controls. In adjusted models, there were no associations between 30-day PM 2.5 exposure levels and sepsis (4th vs. 1st quartiles OR: 1.06, 95% CI: 0.85⁻1.32). Similarly, there were no associations between one-year PM 2.5 exposure levels and sepsis risk (4th vs. 1st quartiles OR: 0.96, 95% CI: 0.78⁻1.18). In the REGARDS cohort, PM 2.5 air pollution exposure was not associated with risk of sepsis.

Use of biomarkers in pediatric sepsis: literature review.

PubMed

Lanziotti, Vanessa Soares; Póvoa, Pedro; Soares, Márcio; Silva, José Roberto Lapa E; Barbosa, Arnaldo Prata; Salluh, Jorge Ibrain Figueira

2016-01-01

Despite advances in recent years, sepsis is still a leading cause of hospitalization and mortality in infants and children. The presence of biomarkers during the response to an infectious insult makes it possible to use such biomarkers in screening, diagnosis, prognosis (risk stratification), monitoring of therapeutic response, and rational use of antibiotics (for example, the determination of adequate treatment length). Studies of biomarkers in sepsis in children are still relatively scarce. This review addresses the use of biomarkers in sepsis in pediatric patients with emphasis on C-reactive protein, procalcitonin, interleukins 6, 8, and 18, human neutrophil gelatinase, and proadrenomedullin. Assessment of these biomarkers may be useful in the management of pediatric sepsis.

Use of biomarkers in pediatric sepsis: literature review

PubMed Central

Lanziotti, Vanessa Soares; Póvoa, Pedro; Soares, Márcio; Silva, José Roberto Lapa e; Barbosa, Arnaldo Prata; Salluh, Jorge Ibrain Figueira

2016-01-01

Despite advances in recent years, sepsis is still a leading cause of hospitalization and mortality in infants and children. The presence of biomarkers during the response to an infectious insult makes it possible to use such biomarkers in screening, diagnosis, prognosis (risk stratification), monitoring of therapeutic response, and rational use of antibiotics (for example, the determination of adequate treatment length). Studies of biomarkers in sepsis in children are still relatively scarce. This review addresses the use of biomarkers in sepsis in pediatric patients with emphasis on C-reactive protein, procalcitonin, interleukins 6, 8, and 18, human neutrophil gelatinase, and proadrenomedullin. Assessment of these biomarkers may be useful in the management of pediatric sepsis. PMID:28099644

Pulmonary vs Nonpulmonary Sepsis and Mortality in Acute Lung Injury

PubMed Central

Sevransky, Jonathan E.; Martin, Greg S.; Mendez-Tellez, Pedro; Shanholtz, Carl; Brower, Roy; Pronovost, Peter J.; Needham, Dale M.

2010-01-01

Background Acute lung injury (ALI) is a frequent complication of sepsis. It is unclear if a pulmonary vs nonpulmonary source of sepsis affects mortality in patients with sepsis-induced ALI. Methods Two hundred eighty-eight consecutive patients with sepsis-induced ALI from 14 ICUs at four hospitals in Baltimore,MDwere prospectively classified as having a pulmonary vs nonpulmonary source of sepsis. Multiple logistic regression was conducted to evaluate the independent association of a pulmonary vs nonpulmonary source of sepsis with inpatient mortality. Results In an unadjusted analysis, in-hospital mortality was lower for pulmonary vs nonpulmonary source of sepsis (42% vs 66%, p < 0.0001). Patients with pulmonary sepsis had lower acute physiology and chronic health evaluation (APACHE) II and sequential organ failure assessment (SOFA) scores, shorter ICU stays prior to the development of ALI, and higher lung injury scores. In the adjusted analysis, several factors were predictive of mortality: age (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.01 to 1.06), Charlson comorbidity index (OR, 1.15; 95% CI, 1.02 to 1.30), ICU length of stay prior to ALI diagnosis (OR, 1.19; 95% CI, 1.01 to 1.39), APACHE II score (OR, 1.07; 95% CI, 1.03 to 1.12), lung injury score (OR, 1.64; 95% CI, 1.11 to 2.43), SOFA score (OR, 1.15; 95% CI, 1.06 to 1.26), and cumulative fluid balance in the first 7 days after ALI diagnosis (OR, 1.06; 95% CI, 1.03 to 1.10). A pulmonary vs nonpulmonary source of sepsis was not independently associated with mortality (OR, 0.72; 95% CI, 0.38 to 1.35). Conclusions Although lower mortality was observed for ALI patients with a pulmonary vs nonpulmonary source of sepsis, this finding is likely due to a lower severity of illness in those with pulmonary sepsis. Pulmonary vs nonpulmonary source of sepsis was not independently predictive of mortality for patients with ALI. PMID:18641112

A prospective, observational registry of patients with severe sepsis: the Canadian Sepsis Treatment and Response Registry.

PubMed

Martin, Claudio M; Priestap, Fran; Fisher, Harold; Fowler, Robert A; Heyland, Daren K; Keenan, Sean P; Longo, Christopher J; Morrison, Teresa; Bentley, Diane; Antman, Neil

2009-01-01

To determine the location of acquisition, timing, and outcomes associated with severe sepsis in community and teaching hospital critical care units. Prospective, observational study. Twelve Canadian community and teaching hospital critical care units. All patients admitted between March 17, 2003, and November 30, 2004 to the study critical care units with at least a 24-hr length of stay or severe sepsis identified during the first 24 hrs. Daily monitoring for severe sepsis. We recorded data describing characteristics of patients, infections, systemic responses, and organ dysfunction. Severe sepsis occurred in 1238 patients (overall rate, 19.0%; range, 8.2%-35.3%). Hospital mortality was 38.1% (95% confidence interval [CI]: 35.4-40.8). Median intensive care unit length of stay was 10.3 days (interquartile range: 5.5, 17.9). Variables associated with mortality in multivariable analysis included age (odds ratio [OR] by decade 1.50; 95% CI: 1.36-1.65), acquisition location of severe sepsis (with community as the reference-hospital [OR: 1.69; CI: 1.16-2.46], early intensive care unit [OR: 2.15; CI: 1.42-3.25], late intensive care unit [OR: 2.65; CI: 1.82-3.87]), late intensive care unit (OR: 2.65; CI: 1.82-3.87), any comorbidity (OR: 1.42; CI: 1.04-1.93), chronic renal failure (OR: 2.03; CI: 1.10-3.76), oliguria (OR: 1.34; CI: 1.02-1.76), thrombocytopenia (OR: 2.12; CI: 1.43-3.13), metabolic acidosis (OR: 1.54; CI: 1.13-2.10), Multiple Organ Dysfunction Score (OR: 1.15; CI: 1.09-1.21) and Acute Physiology and Chronic Health Evaluation II predicted risk (OR: 3.75; CI: 2.08-6.76). These data confirm that sepsis is common and has high mortality in general intensive care unit populations. Our results can inform healthcare system planning and clinical study designs. Modifiable variables associated with worse outcomes, such as nosocomial infection (hospital acquisition), and metabolic acidosis indicate potential targets for quality improvement initiatives that could decrease

Implications of the new international sepsis guidelines for nursing care.

PubMed

Kleinpell, Ruth; Aitken, Leanne; Schorr, Christa A

2013-05-01

Sepsis is a serious worldwide health care condition that is associated with high mortality rates, despite improvements in the ability to manage infection. New guidelines for the management of sepsis were recently released that advocate for implementation of care based on evidence-based practice for both adult and pediatric patients. Critical care nurses are directly involved in the assessment of patients at risk for developing sepsis and in the treatment of patients with sepsis and can, therefore, affect outcomes for critically ill patients. Nurses' knowledge of the recommendations in the new guidelines can help to ensure that patients with sepsis receive therapies that are based on the latest scientific evidence. This article presents an overview of new evidence-based recommendations for the treatment of adult patients with sepsis, highlighting the role of critical care nurses.

New Approaches to Sepsis: Molecular Diagnostics and Biomarkers

PubMed Central

Bauer, Michael; Riedemann, Niels C.; Hartog, Christiane S.

2012-01-01

Summary: Sepsis is among the most common causes of death in hospitals. It arises from the host response to infection. Currently, diagnosis relies on nonspecific physiological criteria and culture-based pathogen detection. This results in diagnostic uncertainty, therapeutic delays, the mis- and overuse of antibiotics, and the failure to identify patients who might benefit from immunomodulatory therapies. There is a need for new sepsis biomarkers that can aid in therapeutic decision making and add information about screening, diagnosis, risk stratification, and monitoring of the response to therapy. The host response involves hundreds of mediators and single molecules, many of which have been proposed as biomarkers. It is, however, unlikely that one single biomarker is able to satisfy all the needs and expectations for sepsis research and management. Among biomarkers that are measurable by assays approved for clinical use, procalcitonin (PCT) has shown some usefulness as an infection marker and for antibiotic stewardship. Other possible new approaches consist of molecular strategies to improve pathogen detection and molecular diagnostics and prognostics based on transcriptomic, proteomic, or metabolic profiling. Novel approaches to sepsis promise to transform sepsis from a physiologic syndrome into a group of distinct biochemical disorders and help in the development of better diagnostic tools and effective adjunctive sepsis therapies. PMID:23034322

Serum amyloid A in the diagnosis of feline sepsis.

PubMed

Troìa, Roberta; Gruarin, Marta; Foglia, Armando; Agnoli, Chiara; Dondi, Francesco; Giunti, Massimo

2017-11-01

Systemic inflammatory response syndrome (SIRS) and sepsis can be challenging to diagnose in cats. Retrospectively, we investigated the diagnostic and prognostic potential of serum amyloid A (SAA), a major feline acute-phase protein (APP), in a population of critically ill cats with SIRS related to trauma or sepsis. A total of 56 SIRS cats (trauma n = 27; sepsis n = 29) were included and compared with healthy controls ( n = 18). SAA concentration was significantly increased in SIRS cats compared to controls, confirming its potential for the detection of systemic inflammation in this species. Significantly higher values of SAA were detected in cats belonging to the sepsis group; however, according to the results of the receiver operating characteristic curve analysis, the value of using SAA (>81 mg/L) to discriminate septic cats was only moderate (AUC = 0.76). Additionally, cats with sepsis had significantly higher serum bilirubin concentrations and toxic neutrophil changes compared to the trauma group. Overall, 38 of 56 cats were survivors; 18 of 56 were non-survivors, with 83% of the non-survivors (15 of 18) belonging to the sepsis group. Serum bilirubin concentration, but not SAA, was able to predict outcome. Prospective studies are needed to assess the potential of SAA in the diagnosis of feline sepsis and outcome prediction.

Coding pulmonary sepsis and mortality statistics in Rio de Janeiro, RJ.

PubMed

Cardoso, Bruno Baptista; Kale, Pauline Lorena

2016-01-01

This study aimed to describe "pulmonary sepsis" reported as a cause of death, measure its association to pneumonia, and the significance of the coding rules in mortality statistics, including the diagnosis of pneumonia on death certificates (DC) with the mention of pulmonary sepsis in Rio de Janeiro, Brazil, in 2011. DC with mention of pulmonary sepsis was identified, regardless of the underlying cause of death. Medical records related to the certificates with reference to "pulmonary sepsis" were reviewed and physicians were interviewed to measure the association between pulmonary sepsis and pneumonia. A simulation was performed in the mortality data by inserting the International Classification of Diseases (ICD-10) code for pneumonia in the certificates with pulmonary sepsis. "Pulmonary sepsis" constituted 30.9% of reported sepsis and pneumonia was not reported in 51.3% of these DC. Pneumonia was registered in 82.8% of the sample of the medical records. Among physicians interviewed, 93.3% declared pneumonia as the most common cause of "pulmonary sepsis." The simulation of the coding process resulted in a different underlying cause of death for 7.8% of the deaths with sepsis reported and 2.4% of all deaths, regardless the original cause. The conclusion is that "pulmonary sepsis" is frequently associated to pneumonia and that the addition of the ICD-10 code for pneumonia in DC could affect the mortality statistics, highlighting the need to improve mortality coding rules.

Evaluation of Vitamin C for Adjuvant Sepsis Therapy

PubMed Central

2013-01-01

Abstract Significance: Evidence is emerging that parenteral administration of high-dose vitamin C may warrant development as an adjuvant therapy for patients with sepsis. Recent Advances: Sepsis increases risk of death and disability, but its treatment consists only of supportive therapies because no specific therapy is available. The characteristics of severe sepsis include ascorbate (reduced vitamin C) depletion, excessive protein nitration in microvascular endothelial cells, and microvascular dysfunction composed of refractive vasodilation, endothelial barrier dysfunction, and disseminated intravascular coagulation. Parenteral administration of ascorbate prevents or even reverses these pathological changes and thereby decreases hypotension, edema, multiorgan failure, and death in animal models of sepsis. Critical Issues: Dehydroascorbic acid appears to be as effective as ascorbate for protection against microvascular dysfunction, organ failure, and death when injected in sepsis models, but information about pharmacodynamics and safety in human subjects is only available for ascorbate. Although the plasma ascorbate concentration in critically ill and septic patients is normalized by repletion protocols that use high doses of parenteral ascorbate, and such doses are tolerated well by most healthy subjects, whether such large amounts of the vitamin trigger adverse effects in patients is uncertain. Future Directions: Further study of sepsis models may determine if high concentrations of ascorbate in interstitial fluid have pro-oxidant and bacteriostatic actions that also modify disease progression. However, the ascorbate depletion observed in septic patients receiving standard care and the therapeutic mechanisms established in models are sufficient evidence to support clinical trials of parenteral ascorbate as an adjuvant therapy for sepsis. Antioxid. Redox Signal. 19, 2129–2140. PMID:23682970

Gas gangrene in the diabetic foot: lessons learned from a salvaged limb.

PubMed

Aerden, D; Lipsky, B A; Denecker, N; Nieboer, K; Keymeulen, B

2014-01-01

A 55 year old man was seen in the emergency department with an infected right foot and sepsis. Examination of the right foot revealed subcutaneous crepitus from the metatarsal head up to the tarsus; interstitial and intramedullary gas was confirmed on x-rays and computed tomographic scans. During 44 days of hospitalization, the patient was treated with multiple courses of antibiotic therapy, various wound care modalities (including negative wound pressure therapy) and several surgical interventions (debridements, amputations, revascularizations and reconstructive plastic surgery). Although limb salvage was ultimately accomplished, in retrospect many management decisions were suboptimal. A critical reassessment of our approach to this patient allowed us to identify several areas for improvement and this audit provided us an opportunity to learn from managing this difficult case.

Haplotypes composed of minor frequency single nucleotide polymorphisms of the TNF gene protect from progression into sepsis: A study using the new sepsis classification.

PubMed

Retsas, Theodoros; Huse, Klaus; Lazaridis, Lazaros-Dimitrios; Karampela, Niki; Bauer, Michael; Platzer, Matthias; Kolonia, Virginia; Papageorgiou, Eirini; Giamarellos-Bourboulis, Evangelos J; Dimopoulos, George

2018-02-01

Several articles have provided conflicting results regarding the role of single nucleotide polymorphisms (SNPs) in the promoter region of the TNF gene in susceptibility to sepsis. Former articles have been based on previous definitions of sepsis. This study investigated the influence of TNF haplotypes on the development of sepsis using the new Sepsis-3 definitions. DNA was isolated from patients suffering from infection and systemic inflammatory response syndrome. Haplotyping was performed for six SNPs of TNF. The serum levels of tumour necrosis factor alpha (TNF-α) of these patients were measured using an enzyme immunosorbent assay. Patients were classified into infection and sepsis categories using the Sepsis-3 definitions. Associations between the TNF haplotypes and the clinical characteristics and serum TNF-α levels of the patients were examined. The most common TNF haplotype h1 was composed of major alleles of the studied SNPs. Carriage of haplotypes composed of minor frequency alleles was associated with a lower risk of developing sepsis (odds ratio 0.41, 95% confidence interval 0.19-0.88, p=0.022), but this did not affect the 28-day outcome. Serum TNF-α levels were significantly higher among patients homozygous for h1 haplotypes who developed sepsis compared to infection (p=0.032); a similar result was not observed for patients carrying other haplotypes. Haplotypes containing minor frequency SNP alleles of TNF protect against the development of sepsis without affecting the outcome. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Cyclooxygenase Inhibition in Sepsis: Is There Life after Death?

PubMed Central

Aronoff, David M.

2012-01-01

Prostaglandins are important mediators and modulators of the inflammatory response to infection. The prostaglandins participate in the pathogenesis of hemodynamic collapse, organ failure, and overwhelming inflammation that characterize severe sepsis and shock. In light of this, cyclooxygenase (COX) inhibiting pharmacological agents have been extensively studied for their capacity to ameliorate the aberrant physiological and immune responses during severe sepsis. Animal models of sepsis, using the systemic administration of pathogen-associated molecular patterns (PAMPs) or live pathogens, have been used to examine the effectiveness of COX inhibition as a treatment for severe sepsis. These studies have largely shown beneficial effects on mortality. However, human studies have failed to show clinical utility of COX inhibitor treatment in severely septic patients. Why this approach “worked” in animals but not in humans might reflect differences in the controlled nature of animal investigations compared to human studies. This paper contrasts the impact of COX inhibitors on mortality in animal models of sepsis and human studies of sepsis and examines potential reasons for differences between these two settings. PMID:22665954

High Levels of Morbidity and Mortality Among Pediatric Hematopoietic Cell Transplant Recipients With Severe Sepsis: Insights From the Sepsis PRevalence, OUtcomes, and Therapies International Point Prevalence Study.

PubMed

Lindell, Robert B; Gertz, Shira J; Rowan, Courtney M; McArthur, Jennifer; Beske, Florian; Plunkett, Adrian; Weiss, Scott L; Thomas, Neal J; Nadkarni, Vinay M; Fitzgerald, Julie C

2017-12-01

Pediatric severe sepsis is a major cause of morbidity and mortality worldwide, and hematopoietic cell transplant patients represent a high-risk population. We assessed the epidemiology of severe sepsis in hematopoietic cell transplant patients, describing patient outcomes compared with children with no history of hematopoietic cell transplant. Secondary analysis of the Sepsis PRevalence, OUtcomes, and Therapies point prevalence study, comparing demographics, sepsis etiology, illness severity, organ dysfunction, and sepsis-related treatments in patients with and without hematopoietic cell transplant. The primary outcome was hospital mortality. Multivariable logistic regression models were used to determine adjusted differences in mortality. International; 128 PICUs in 26 countries. Pediatric patients with severe sepsis prospectively identified over a 1-year period. None. In patients with severe sepsis, 37/567 (6.5%) had a history of hematopoietic cell transplant. Compared with patients without hematopoietic cell transplant, hematopoietic cell transplant patients had significantly higher hospital mortality (68% vs 23%; p < 0.001). Hematopoietic cell transplant patients were more likely to have hospital acquired sepsis and had more preexisting renal and hepatic dysfunction than non-hematopoietic cell transplant patients with severe sepsis. History of hematopoietic cell transplant, renal replacement therapy, admission from inpatient floor, and number of organ dysfunctions at severe sepsis recognition were independently associated with hospital mortality in multivariable analysis; hematopoietic cell transplant conferred the highest odds of mortality (odds ratio, 4.00; 95% CI, 1.78-8.98). In secondary analysis of hematopoietic cell transplant patients compared with other immunocompromised patients with severe sepsis, history of hematopoietic cell transplant remained independently associated with hospital mortality (odds ratio, 3.03; 95% CI, 1.11-8.27). In an

Genome Wide Association Study of Sepsis in Extremely Premature Infants

PubMed Central

Srinivasan, Lakshmi; Page, Grier; Kirpalani, Haresh; Murray, Jeffrey C.; Das, Abhik; Higgins, Rosemary D.; Carlo, Waldemar A.; Bell, Edward F.; Goldberg, Ronald N.; Schibler, Kurt; Sood, Beena G.; Stevenson, David K.; Stoll, Barbara J.; Van Meurs, Krisa P.; Johnson, Karen J.; Levy, Joshua; McDonald, Scott A.; Zaterka-Baxter, Kristin M.; Kennedy, Kathleen A.; Sánchez, Pablo J.; Duara, Shahnaz; Walsh, Michele C.; Shankaran, Seetha; Wynn, James L.; Cotten, C. Michael

2017-01-01

Objective To identify genetic variants associated with sepsis (early and late-onset) using a genome wide association (GWA) analysis in a cohort of extremely premature infants. Study Design Previously generated GWA data from the Neonatal Research Network’s anonymized genomic database biorepository of extremely premature infants were used for this study. Sepsis was defined as culture-positive early-onset or late-onset sepsis or culture-proven meningitis. Genomic and whole genome amplified DNA was genotyped for 1.2 million single nucleotide polymorphisms (SNPs); 91% of SNPs were successfully genotyped. We imputed 7.2 million additional SNPs. P values and false discovery rates were calculated from multivariate logistic regression analysis adjusting for gender, gestational age and ancestry. Target statistical value was p<10−5. Secondary analyses assessed associations of SNPs with pathogen type. Pathway analyses were also run on primary and secondary end points. Results Data from 757 extremely premature infants were included: 351 infants with sepsis and 406 infants without sepsis. No SNPs reached genome-wide significance levels (5×10−8); two SNPs in proximity to FOXC2 and FOXL1 genes achieved target levels of significance. In secondary analyses, SNPs for ELMO1, IRAK2 (Gram positive sepsis), RALA, IMMP2L (Gram negative sepsis) and PIEZO2 (fungal sepsis) met target significance levels. Pathways associated with sepsis and Gram negative sepsis included gap junctions, fibroblast growth factor receptors, regulators of cell division and Interleukin-1 associated receptor kinase 2 (p values<0.001 and FDR<20%). Conclusions No SNPs met genome-wide significance in this cohort of ELBW infants; however, areas of potential association and pathways meriting further study were identified. PMID:28283553

New perspectives on immunomodulatory therapy for bacteraemia and sepsis.

PubMed

Opal, Steven M

2010-12-01

Systemic immune dysregulation is generally acknowledged to be the fundamental molecular mechanism that underlies the pathophysiology of severe sepsis and septic shock. In the presence of a systemic infection, microbial pathogens and their soluble mediators induce generalised immune activation and coagulation activation, leading to severe sepsis and septic shock. For decades, immune-based therapies have been devised with the specific intent of inhibiting the pro-inflammatory events that are thought to precipitate the septic process. Despite a clear therapeutic rationale based upon the available experimental evidence, anti-inflammatory therapies targeting the innate or acquired immune response have largely been unsuccessful in clinical trials of sepsis. Compelling evidence now exists that a prolonged state of sepsis-induced immune suppression follows the initial period of stabilisation and resuscitation in many critically ill patients. Sepsis-related immune suppression is evidenced by histological findings of markedly enhanced lymphocytic and monocytic apoptosis, poor response to neoantigens and recall antigens, and increased incidence of infections by opportunistic pathogens. Candidiasis, cytomegalovirus activation and secondary infections by relatively avirulent bacterial pathogens such as Stenotrophomonas and Acinetobacter spp. are commonplace in septic patients during prolonged Intensive Care Unit stays. Immunological tools to detect sepsis-induced immunosuppression are now available, and novel immunoadjuvants are in development to re-establish immune competence in sepsis patients. The intelligent use of immunomodulatory agents in sepsis will necessitate a personalised medicine approach to treat each patient at the appropriate time and with the optimal therapy. Copyright © 2010 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Monitoring sepsis using electrical cell profiling.

PubMed

Prieto, Javier L; Su, Hao-Wei; Hou, Han Wei; Vera, Miguel Pinilla; Levy, Bruce D; Baron, Rebecca M; Han, Jongyoon; Voldman, Joel

2016-11-01

Sepsis is a potentially lethal condition that may be ameliorated through early monitoring of circulating activated leukocytes for faster stratification of severity of illness and improved administration of targeted treatment. Characterization of the intrinsic electrical properties of leukocytes is label-free and can provide a quick way to quantify the number of activated cells as sepsis progresses. Iso-dielectric separation (IDS) uses dielectrophoresis (DEP) to characterize the electrical signatures of cells. Here, we use IDS to show that activated and non-activated leukocytes have different electrical properties. We then present a double-sided version of the IDS platform to increase throughput to characterize thousands of cells. This new platform is less prone to cell fouling and allows faster characterization. Using peripheral blood samples from a cecal ligation and puncture (CLP) model of polymicrobial sepsis in mice, we estimate the number of activated leukocytes by looking into differences in the electrical properties of cells. We show for the first time using animal models that electrical cell profiling correlates with flow cytometry (FC) results and that IDS is therefore a good candidate for providing rapid monitoring of sepsis by quantifying the number of circulating activated leukocytes.

Pharmacist involvement in a multidisciplinary initiative to reduce sepsis-related mortality.

PubMed

Beardsley, James R; Jones, Catherine M; Williamson, John; Chou, Jason; Currie-Coyoy, Margaret; Jackson, Teresa

2016-02-01

Pharmacy department contributions to a medical center's broad initiative to improve sepsis care outcomes are described. Timely and appropriate antimicrobial therapy is a key factor in optimizing treatment outcomes in patients with severe sepsis or septic shock. The inpatient pharmacy at Wake Forest Baptist Health implemented standardized processes to reduce order turnaround time and facilitate prompt antibiotic administration as part of the hospital's multidisciplinary "Code Sepsis" initiative. The program includes (1) nurse-conducted screening for sepsis using a standard assessment instrument, (2) pager alerts notifying rapid-response, pharmacy, and other personnel of cases of suspected sepsis, (3) activation of an electronic order set including guideline-based antibiotic therapy recommendations based on local pathogen patterns, and (4) a protocol allowing pharmacists to select an antibiotic regimen if providers are busy with other patient care duties. Assessments conducted during and after implementation of the Code Sepsis initiative showed improvements in key program metrics. The mean ± S.D. time from receipt of a Code Sepsis page to antibiotic delivery was reduced to 14.1 ± 13.7 minutes, the mean time from identification of suspected sepsis to antibiotic administration was reduced to 31 minutes in the hospital's intensive care units and to 51 minutes in non-critical care units, and the institution's performance on a widely used measure of sepsis-related mortality improved dramatically. Implementation of the Code Sepsis initiative was associated with reductions in order turnaround time, time to antibiotic administration, and sepsis-related mortality. Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Gram-negative sepsis: a dilemma of modern medicine.

PubMed Central

Bone, R C

1993-01-01

Gram-negative sepsis is an increasingly common problem, with up to 300,000 cases occurring each year in the United States alone. Despite the ongoing development of new antibiotics, mortality from gram-negative sepsis remains unacceptably high. To stimulate earlier therapeutic intervention by physicians, a new set of broad definitions has been proposed to define the systemic inflammatory response characteristic of sepsis. In this review, the signs and symptoms of this progressive, injurious process are reviewed and its management is discussed, as are the mechanisms by which bacterial endotoxin triggers the biochemical events that lead to such serious complications as shock, adult respiratory distress syndrome, and disseminated intravascular coagulation. These events often occur even when appropriate antimicrobial therapy has been instituted. An increased understanding of the structure of endotoxin and its role in the development of sepsis, together with advances in hybridoma technology, has led to the development of monoclonal antibodies that bind to endotoxin and significantly attenuate its adverse effects. These agents promise to substantially reduce the morbidity and mortality associated with gram-negative sepsis. PMID:8457980

Ghrelin-mediated sympathoinhibition and suppression of inflammation in sepsis

PubMed Central

Cheyuo, Cletus; Jacob, Asha

2012-01-01

Sepsis, a systemic inflammatory response to infection, continues to carry a high mortality despite advances in critical care medicine. Elevated sympathetic nerve activity in sepsis has been shown to contribute to early hepatocellular dysfunction and subsequently multiple organ failure, resulting in a poor prognosis, especially in the elderly. Thus, suppression of sympathetic nerve activity represents a novel therapeutic option for sepsis. Ghrelin is a 28-amino acid peptide shown to inhibit sympathetic nerve activity and inflammation in animal models of tissue injury. Age-related ghrelin hyporesponsiveness has also been shown to exacerbate sepsis. However, the mechanistic relationship between ghrelin-mediated sympathoinhibition and suppression of inflammation remains poorly understood. This review assesses the therapeutic potential of ghrelin in sepsis in the context of the neuroanatomical and molecular basis of ghrelin-mediated suppression of inflammation through inhibition of central sympathetic outflow. PMID:22068604

Early detection strategy and mortality reduction in severe sepsis.

PubMed

Westphal, Glauco Adrieno; Feijó, Janaína; Andrade, Patrícia Silva de; Trindade, Louise; Suchard, Cezar; Monteiro, Márcio Andrei Gil; Martins, Sheila Fonseca; Nunes, Fernanda; Caldeira Filho, Milton

2009-06-01

To evaluate the impact of implementing an institutional policy for detection of severe sepsis and septic shock. Study before (stage I), after (stage II) with prospective data collection in a 195 bed public hospital.. Stage I: Patients with severe sepsis or septic shock were included consecutively over 15 months and treated according to the Surviving Sepsis Campaign guidelines. Stage II: In the 10 subsequent months, patients with severe sepsis or septic shock were enrolled based on an active search for signs suggesting infection (SSI) in hospitalized patients. The two stages were compared for demographic variables, time needed for recognition of at least two signs suggesting infection (SSI-Δt), compliance to the bundles of 6 and 24 hours and mortality. We identified 124 patients with severe sepsis or septic shock, 68 in stage I and 56 in stage II. The demographic variables were similar in both stages. The Δt-SSI was 34 ± 54 hours in stage I and 7 ± 8.4 hours in stage II (p <0.001). There was no difference in compliance to the bundles. In parallel there was significant reduction of mortality rates at 28 days (54.4% versus 30%, p <0.02) and hospital (67.6% versus 41%, p <0.003). The strategy used helped to identify early risk of sepsis and resulted in decreased mortality associated with severe sepsis and septic shock.

Importance of measuring lactate levels in children with sepsis.

PubMed

Anil, Nisha

2017-10-10

Sepsis is a major public health problem as well as one of the leading causes of preventable death in children because of failure to recognise the early signs and symptoms and to resuscitate rapidly. Blood lactate levels are used to assess the severity of sepsis and the effectiveness of resuscitation. Lactate levels are easily obtainable and should be checked in all patients admitted with suspected sepsis within six hours of presentation. The test should be repeated four and eight-hours post-diagnosis of sepsis. For the diagnosis of sepsis, patients' clinical symptoms, along with the combined analysis of partial pressure of oxygen, carbon dioxide and lactate levels, should be used. A multitude of factors can cause elevated lactate levels and so clinicians should use elevated levels cautiously by considering all other aetiologies. This article, which focuses on practice in Australia but makes reference to the UK, discusses the importance of measuring lactate levels in sepsis, the pathophysiology of lactate production, causes of elevated lactate levels, lactate measurement, nursing management of patients with elevated lactate levels, limitations of using lactate as a biomarker for diagnosing sepsis and implications for practice. ©2012 RCN Publishing Company Ltd. All rights reserved. Not to be copied, transmitted or recorded in any way, in whole or part, without prior permission of the publishers.

Construction and management of ARDS/sepsis registry with REDCap.

PubMed

Pang, Xiaoqing; Kozlowski, Natascha; Wu, Sulong; Jiang, Mei; Huang, Yongbo; Mao, Pu; Liu, Xiaoqing; He, Weiqun; Huang, Chaoyi; Li, Yimin; Zhang, Haibo

2014-09-01

The study aimed to construct and manage an acute respiratory distress syndrome (ARDS)/sepsis registry that can be used for data warehousing and clinical research. The workflow methodology and software solution of research electronic data capture (REDCap) was used to construct the ARDS/sepsis registry. Clinical data from ARDS and sepsis patients registered to the intensive care unit (ICU) of our hospital formed the registry. These data were converted to the electronic case report form (eCRF) format used in REDCap by trained medical staff. Data validation, quality control, and database management were conducted to ensure data integrity. The clinical data of 67 patients registered to the ICU between June 2013 and December 2013 were analyzed. Of the 67 patients, 45 (67.2%) were classified as sepsis, 14 (20.9%) as ARDS, and eight (11.9%) as sepsis-associated ARDS. The patients' information, comprising demographic characteristics, medical history, clinical interventions, daily assessment, clinical outcome, and follow-up data, was properly managed and safely stored in the ARDS/sepsis registry. Data efficiency was guaranteed by performing data collection and data entry twice weekly and every two weeks, respectively. The ARDS/sepsis database that we constructed and manage with REDCap in the ICU can provide a solid foundation for translational research on the clinical data of interest, and a model for development of other medical registries in the future.

Implications of the new sepsis definition on research and practice.

PubMed

Peach, Brian C

2017-04-01

The Society of Critical-Care Medicine and the European Society of Intensive Care Medicine recently announced a marked change in the sepsis definition. A task force of 19 sepsis clinicians and researchers made the change based on advances in the pathobiological understanding of the septic process. The task force determined that there were numerous justifications for a revision of the sepsis definition, which are outlined in this article. The systemic inflammatory response criteria have been replaced by the Sequential Organ Failure Assessment (SOFA) score in the newly operationalized definition (Singer et al., 2016). In addition to the definition change, the task force recommended using the new quick SOFA (qSOFA) score in non-ICU settings, as a risk stratification tool to identify patients who may be septic or be at risk of developing sepsis. The change in definition will likely have a negative impact on sepsis research in the short-term as hospitals adjust their coding for the new definition, but may result in less misclassification bias and improved research data in the long-term. While the intent of the SCCM/ESICM task force was to better define sepsis for coding and epidemiological research purposes, there is the potential for improved patient outcomes if clinicians are better able to differentiate between sepsis and inflammatory events. The qSOFA tool may also aid clinicians in recognizing sepsis in a quicker manner, leading to more timely treatment, and potentially better outcomes. While the new operationalized Sepsis-3 definition appears on the surface to be an improvement over the previous iterations, it remains to be seen if research data will be more robust using the new criteria. There is the potential for better patient outcomes if clinicians are better able to differentiate sepsis from inflammatory events with the new definition, and if sepsis cases are recognized sooner with qSOFA. Future research on the impact of this definition change on research and

Bowel sonography in sepsis with pathological correlation: an experimental study.

PubMed

Kim, Hwa-Young; Kim, In-One; Kim, Woo Sun; Kang, Gyeong Hoon

2011-02-01

Sepsis predisposes full-term infants to necrotizing enterocolitis (NEC). As such, experimental induction of NEC was applied to a sepsis model to evaluate the potential role of US in the early diagnosis of NEC in full-term infants. To evaluate the resistive index (RI) of the superior mesenteric artery (SMA) on Doppler sonography in experimentally induced sepsis and correlate it with the pathological findings. Fifteen 1-week-old New Zealand white rabbits (control group n = 3, sepsis group n = 12) were used in this study. We injected 1 mg/kg of E. coli O55-B5 lipopolysaccharide (LPS) into 12 rabbits to induce sepsis. Then we conducted grayscale evaluation of the caliber of the abdominal aorta as well as bowel wall thickness and echogenicity. In addition, we measured peak systolic and end-diastolic velocities and SMA RI on Doppler sonography. Pathological findings were analyzed and correlated with RI readings. Peak systolic and end-diastolic velocities and SMA RI values were analyzed statistically at each hour using the Wilcoxon rank sum test; the control and sepsis groups were compared using the Mann-Whitney test. The bowel wall thickness in the sepsis group was significantly increased after LPS injection. The caliber of the abdominal aorta in the sepsis group was significantly decreased after LPS injection. There were echogenic foci (<10 in axial plane) in the bowel wall after LPS injection. Peak systolic velocity in the sepsis group was not significantly changed, but end-diastolic velocity was decreased. SMA RIs in the sepsis group were significantly increased post-LPS injection from baseline. In the control group there were no significant changes in bowel wall thickness, abdominal aorta caliber, bowel wall echogenicity or peak systolic and end-diastolic velocities and RIs. Pathologically, eight of the 12 rabbits in the sepsis group showed grade 1 intestinal injury, three showed grade 2 injury and one showed grade 3 injury. SMA RIs were higher in grades 2

The Temporal Kinetics of Circulating Angiopoietin Levels in Children with Sepsis

PubMed Central

Giuliano, John S.; Tran, Kevin; Li, Fang-yong; Northrup, Veronika; Tala, Joana A.; Bhandari, Vineet

2013-01-01

Objective Capillary integrity continues to challenge critical care physicians worldwide when treating children with sepsis. Vascular growth factors, specifically angiopoietin (angpt)-1 and angpt-2, play opposing roles in capillary stabilization in septic patients, respectively. We aim to determine whether pediatric patients with severe sepsis/shock have persistently high angpt-2/1 ratios when compared to non-septic pediatric intensive care unit (PICU) patients over a 7-day period. Design Prospective, observational study. Patients were classified within 24h of admission into: non-systemic inflammatory response syndrome (non-SIRS), SIRS/sepsis, or severe sepsis/shock. Plasma levels of angpt-1 and angpt-2 were measured via ELISA. The angpt-2/1 ratio was graphically plotted and determined whether patients fell into ‘constant’ or ‘variable’ patterns. Setting Tertiary care center PICU. Patients Critically ill pediatric patients with varying sepsis severity. Interventions None Measurements and Main Results Forty five patients were enrolled (n=9 non-SIRS, n=19 SIRS/sepsis, and n=17 severe sepsis/shock). Gender, age, weight, comorbidities and PICU length of stay were not significantly different between the groups. Admission pediatric risk stratification scores and net fluid ins/outs were significantly elevated in the severe sepsis/shock group when compared (all p<0.05). Admission angpt-2 levels and angpt-2/1 ratios were significantly different in the severe sepsis/shock group when all groups were compared (both p<0.05). Additionally, the latter were significantly elevated in the severe sepsis/shock group at multiple time points (all p≤0.05) with the peak occurring on day 2 of illness. In a separate analysis, 32% of SIRS/sepsis and 82% of severe sepsis/shock had ‘variable’ angpt-2/1 ratio patterns compared to none in the control group (p<0.001). Conclusions Pediatric patients with severe sepsis and septic shock possess significantly elevated angpt-2/1 ratios

Higher platelet reactivity and platelet-monocyte complex formation in Gram-positive sepsis compared to Gram-negative sepsis.

PubMed

Tunjungputri, Rahajeng N; van de Heijden, Wouter; Urbanus, Rolf T; de Groot, Philip G; van der Ven, Andre; de Mast, Quirijn

2017-09-01

Platelets may play a role in the high risk for vascular complications in Gram-positive sepsis. We compared the platelet reactivity of 15 patients with Gram-positive sepsis, 17 with Gram-negative sepsis and 20 healthy controls using a whole blood flow cytometry-based assay. Patients with Gram-positive sepsis had the highest median fluorescence intensity (MFI) of the platelet membrane expression of P-selectin upon stimulation with high dose adenosine diphosphate (ADP; P = 0.002 vs. Gram-negative and P = 0.005 vs. control groups) and cross-linked collagen-related peptide (CRP-XL; P = 0.02 vs. Gram-negative and P = 0.0001 vs. control groups). The Gram-positive group also demonstrated significantly higher ADP-induced fibrinogen binding (P = 0.001), as wll as platelet-monocyte complex formation (P = 0.02), compared to the Gram-negative group and had the highest plasma levels of platelet factor 4, β-thromboglobulin and soluble P-selectin. In contrast, thrombin-antithrombin complex and C-reactive protein levels were comparable in both patient groups. In conclusion, common Gram-positive pathogens induce platelet hyperreactivity, which may contribute to a higher risk for vascular complications.

Oxidative stress biomarkers in pediatric sepsis: a prospective observational pilot study.

PubMed

Molina, Víctor; von Dessauer, Bettina; Rodrigo, Ramón; Carvajal, Cristian

2017-11-01

Oxidative stress is known to participate in the progression of sepsis. Definite data regarding the behavior of oxidative stress biomarkers in pediatric sepsis is still lacking. This study hypothesized that oxidative stress occurs in pediatric sepsis and that the magnitude of the redox derangement is associated with worse clinical progression. Forty-two previously healthy pediatric patients with sepsis and a group of control subjects were included. Oxidative stress and inflammatory activity biomarkers were determined in blood samples. Patients were prospectively followed until their discharge or death. Patients with non-severe and severe sepsis showed higher levels of plasmatic antioxidant capacity, lower erythrocyte thiol index, lower superoxide dismutase and catalase activities, higher glutathione peroxidase activity, and higher plasmatic F 2 -isoprostanes concentration than controls. Patients with severe sepsis had higher NF-kappaB activation than those with non-severe sepsis. Although we observed changes in some biomarkers in patients with worse clinical evolution, the explored biomarkers did not correlate with clinical estimators of outcome. Oxidative stress occurs in pediatric sepsis, resulting in oxidative damage. The explored biomarkers are not useful as outcome predictors in the studied population. The behavior of these biomarkers still needs to be addressed in broader groups of pediatric patients with sepsis.

Knowledge and recognition of SIRS and sepsis among pediatric nurses.

PubMed

Jeffery, Alvin D; Mutsch, Karen Steffen; Knapp, Lisa

2014-01-01

A large amount of research demonstrates the importance of key interventions in reducing mortality rates of pediatric patients with sepsis (Dellinger et al., 2008). Assessment and recognition of declining status must occur for interventions to be initiated. Of health care practitioners, nurses typically spend the most time with patients, and they must be knowledgeable in recognizing the systemic inflammatory response syndrome and sepsis while also being aware of the importance of prompt intervention. The literature does not discuss pediatric nurses' knowledge of systemic inflammatory response syndrome (SIRS)/sepsis recognition. The purpose of this study was to assess the knowledge of acute and critical care pediatric nurses of SIRS diagnostic criteria, sepsis guidelines, and the importance of SIRS recognition. This cross-sectional, quantitative, correlational descriptive study included 242 acute and critical care pediatric nurses at a 490-bed urban pediatric hospital. Participants completed an original questionnaire with face and content validity regarding SIRS criteria, sepsis guidelines, priority interventions, and attitude toward the importance of SIRS recognition. Findings demonstrated a significant knowledge deficit among participants in several key areas of SIRS/sepsis recognition. The mean score was 60.8% ± 7.4%. Item analyses demonstrated nurses easily recognize septic shock but have difficulty recognizing patients in earlier stages of the sepsis continuum. Significant confusion was evident regarding the role of blood pressure and serum lactic acid levels in diagnosing sepsis. It is recommended that an educational intervention be created for acute and critical care pediatric nurses to aid them in recognizing sepsis in its earlier stages.

Potentially modifiable factors contributing to sepsis-associated encephalopathy.

PubMed

Sonneville, Romain; de Montmollin, Etienne; Poujade, Julien; Garrouste-Orgeas, Maïté; Souweine, Bertrand; Darmon, Michael; Mariotte, Eric; Argaud, Laurent; Barbier, François; Goldgran-Toledano, Dany; Marcotte, Guillaume; Dumenil, Anne-Sylvie; Jamali, Samir; Lacave, Guillaume; Ruckly, Stéphane; Mourvillier, Bruno; Timsit, Jean-François

2017-08-01

Identifying modifiable factors for sepsis-associated encephalopathy may help improve patient care and outcomes. We conducted a retrospective analysis of a prospective multicenter database. Sepsis-associated encephalopathy (SAE) was defined by a score on the Glasgow coma scale (GCS) <15 or when features of delirium were noted. Potentially modifiable risk factors for SAE at ICU admission and its impact on mortality were investigated using multivariate logistic regression analysis and Cox proportional hazard modeling, respectively. We included 2513 patients with sepsis at ICU admission, of whom 1341 (53%) had sepsis-associated encephalopathy. After adjusting for baseline characteristics, site of infection, and type of admission, the following factors remained independently associated with sepsis-associated encephalopathy: acute renal failure [adjusted odds ratio (aOR) = 1.41, 95% confidence interval (CI) 1.19-1.67], hypoglycemia <3 mmol/l (aOR = 2.66, 95% CI 1.27-5.59), hyperglycemia >10 mmol/l (aOR = 1.37, 95% CI 1.09-1.72), hypercapnia >45 mmHg (aOR = 1.91, 95% CI 1.53-2.38), hypernatremia >145 mmol/l (aOR = 2.30, 95% CI 1.48-3.57), and S. aureus (aOR = 1.54, 95% CI 1.05-2.25). Sepsis-associated encephalopathy was associated with higher mortality, higher use of ICU resources, and longer hospital stay. After adjusting for age, comorbidities, year of admission, and non-neurological SOFA score, even mild alteration of mental status (i.e., a score on the GCS of 13-14) remained independently associated with mortality (adjusted hazard ratio = 1.38, 95% CI 1.09-1.76). Acute renal failure and common metabolic disturbances represent potentially modifiable factors contributing to sepsis-associated encephalopathy. However, a true causal relationship has yet to be demonstrated. Our study confirms the prognostic significance of mild alteration of mental status in patients with sepsis.

New criteria for sepsis-induced coagulopathy (SIC) following the revised sepsis definition: a retrospective analysis of a nationwide survey.

PubMed

Iba, Toshiaki; Nisio, Marcello Di; Levy, Jerrold H; Kitamura, Naoya; Thachil, Jecko

2017-09-27

Recent clinical studies have shown that anticoagulant therapy might be effective only in specific at-risk subgroups of patients with sepsis and coagulation dysfunction. The definition of sepsis was recently modified, and as such, old scoring systems may no longer be appropriate for the diagnosis of sepsis-associated coagulopathy. The aim of this study was to evaluate prognostic factors in patients diagnosed with sepsis and coagulopathy according to the new sepsis definition and assess their accuracy in comparison with existing models. Retrospective analysis of the nationwide survey for recombinant human soluble thrombomodulin. General emergency and critical care centres in secondary and tertiary care hospitals. We evaluated the prognostic value of the newly proposed diagnostic criteria for sepsis-induced coagulopathy (SIC). A total of 1498 Japanese patients with sepsis and coagulopathy complications who were treated with recombinant thrombomodulin were analysed in this study. The platelet count, prothrombin time (PT) ratio, fibrinogen/fibrin degradation products, systemic inflammatory response syndrome score and Sequential Organ Failure Assessment (SOFA) score obtained just before the start of treatment were examined in relation to the 28-day mortality rate. The platelet count, PT ratio and total SOFA were independent predictors of a fatal outcome in a logistic regression model. A SIC score was defined using the three above-mentioned variables with a positivity threshold of 4 points or more. The SIC score predicted higher 28-day mortality rate compared with the current Japanese Association for Acute Medicine-disseminated intravascular coagulation score (38.4%vs34.7%). The SIC score is based on readily available parameters, is easy to calculate and has a high predictive value for 28-day mortality. Future studies are warranted to evaluate whether the SIC score may guide the decision to initiate anticoagulant therapy. © Article author(s) (or their employer(s) unless

A Computable Definition of Sepsis Facilitates Screening and Performance Improvement Tracking.

PubMed

Alessi, Lauren J; Warmus, Holly R; Schaffner, Erin K; Kantawala, Sajel; Carcillo, Joseph; Rosen, Johanna; Horvat, Christopher M

2018-03-01

Sepsis kills almost 5,000 children annually, accounting for 16% of pediatric health care spending in the United States. We sought to identify sepsis within the Electronic Health Record (EHR) of a quaternary children's hospital to characterize disease incidence, improve recognition and response, and track performance metrics. Methods are organized in a plan-do-study-act cycle. During the "plan" phase, electronic definitions of sepsis (blood culture and antibiotic within 24 hours) and septic shock (sepsis plus vasoactive medication) were created to establish benchmark data and track progress with statistical process control. The performance of a screening tool was evaluated in the emergency department. During the "do" phase, a novel inpatient workflow is being piloted, which involves regular sepsis screening by nurses using the tool, and a regimented response to high risk patients. Screening tool use in the emergency department reduced time to antibiotics (Fig. 1). Of the 6,159 admissions, EHR definitions identified 1,433 (23.3%) between July and December 2016 with sepsis, of which 159 (11.1%) had septic shock. Hospital mortality for all sepsis patients was 2.2% and 15.7% for septic shock (Table 1). These findings approximate epidemiologic studies of sepsis and severe sepsis, which report a prevalence range of 0.45-8.2% and mortality range of 8.2-25% (Table 2). 1-5 . Implementation of a sepsis screening tool is associated with improved performance. The prevalence of sepsis conditions identified with electronic definitions approximates the epidemiologic landscape characterized by other point-prevalence and administrative studies, providing face validity to this approach, and proving useful for tracking performance improvement.

High serum 25-hydroxyvitamin D levels are associated with pediatric sepsis.

PubMed

Aydemir, Gokhan; Cekmez, Ferhat; Kalkan, Gokhan; Fidanci, M Kursat; Kaya, Guven; Karaoglu, Abdulbaki; Meral, Cihan; Arzıman, İbrahim; Karademir, Ferhan; Ayar, Ganime; Gunduz, Ramiz Coskun; Suleymanoglu, Selami

2014-12-01

Despite major advances in intensive care, sepsis continues to be a major cause of morbidity and mortality. Vitamin D is involved in various physiologic functions, including cellular responses during infection and inflammation. The aim of this study was to evaluate diagnostic value of 25-hydroxyvitamin D in childhood sepsis because it can be fatal if diagnosis delayed. The study included 40 children with sepsis and 20 children without sepsis (control group). We included only the patients with high probable sepsis, judged by clinical and laboratory findings, including positive blood culture. Blood samples were collected from patients with sepsis before treatment (pre-treatment group) and 48-72 hours later (post-treatment group). Treatment varied from ampicillin-sulbactam to cephalosporin. Blood samples were collected from control group once on admission. Serum 25-hydroxyvitamin D levels were significantly higher in sepsis (pre-treatment group) than control group (74 ± 8 ng/ml vs. 28 ± 12 ng/ml, p = 0.01) and the serum 25-hydroxyvitamin D levels were decreased to 44 ± 5 ng/ml (p = 0.01) after treatment. Moreover, we found significant positive correlation between 25-hydroxyvitamin D and each of well-know sepsis markers, C-reactive protein, tumor necrosis factor-α and interleukin-6. A cut-off point of 20 ng/mL for serum 25-hydroxyvitamin D showed 84% sensitivity and 76% specificity for sepsis diagnosis. This is the first study evaluating the diagnostic role of vitamin D in pediatric sepsis, thereby suggesting that serum 25-hydroxyvitamin D level can be used as a diagnostic marker for sepsis with high sensitivity and specificity.

Lymphocyte integrin expression differences between SIRS and sepsis patients.

PubMed

Heffernan, D S; Monaghan, S F; Ayala, Alfred

2017-11-01

Systemic Inflammatory Response Syndrome (SIRS) and sepsis remain leading causes of death. Despite many similarities, the two entities are very distinct clinically and immunologically. T-Lymphocytes play a key pivotal role in the pathogenesis and ultimately outcome following both SIRS and sepsis. Integrins are essential in the trafficking and migration of lymphocytes. They also serve vital roles in efficient wound healing and clearance of infections. Here, we investigate whether integrin expression, specifically β1 (CD29) and β2 (CD18), are disrupted in SIRS and sepsis, and assess differences in integrin expression between these two critically ill clinical categories. T-Lymphocytes were isolated from whole blood collected from ICU patients exhibiting SIRS or sepsis. Samples were analyzed for CD18 (β2) and CD29 (β1) on CD3 + T cells through flow cytometry. Septic patients were stratified into either exclusively abdominal or non-abdominal sources of sepsis. CD18 was almost ubiquitously expressed on CD3 + T cells irrespective of clinical condition. However, CD29 (β1 integrin) was lowest in SIRS patients (20.4% of CD3 + T cells) when compared with either septic patients (35.5%) or healthy volunteers (54.1%). Furthermore, there was evidence of compartmentalization in septic patients, where abdominal sources had a greater percentage of CD3 + CD29 + T cells (41.7%) when compared with those with non-abdominal sources (29.5%). Distinct differences in T-cell integrin expression exists between patients in SIRS versus sepsis, as well as relative to the source of sepsis. Further work is needed to understand cause and effect relative to the progression from SIRS into sepsis.

Personalized identification of differentially expressed pathways in pediatric sepsis.

PubMed

Li, Binjie; Zeng, Qiyi

2017-10-01

Sepsis is a leading killer of children worldwide with numerous differentially expressed genes reported to be associated with sepsis. Identifying core pathways in an individual is important for understanding septic mechanisms and for the future application of custom therapeutic decisions. Samples used in the study were from a control group (n=18) and pediatric sepsis group (n=52). Based on Kauffman's attractor theory, differentially expressed pathways associated with pediatric sepsis were detected as attractors. When the distribution results of attractors are consistent with the distribution of total data assessed using support vector machine, the individualized pathway aberrance score (iPAS) was calculated to distinguish differences. Through attractor and Kyoto Encyclopedia of Genes and Genomes functional analysis, 277 enriched pathways were identified as attractors. There were 81 pathways with P<0.05 and 59 pathways with P<0.01. Distribution outcomes of screened attractors were mostly consistent with the total data demonstrated by the six classifying parameters, which suggested the efficiency of attractors. Cluster analysis of pediatric sepsis using the iPAS method identified seven pathway clusters and four sample clusters. Thus, in the majority pediatric sepsis samples, core pathways can be detected as different from accumulated normal samples. In conclusion, a novel procedure that identified the dysregulated attractors in individuals with pediatric sepsis was constructed. Attractors can be markers to identify pathways involved in pediatric sepsis. iPAS may provide a correlation score for each of the signaling pathways present in an individual patient. This process may improve the personalized interpretation of disease mechanisms and may be useful in the forthcoming era of personalized medicine.

Circulating Endothelial Cells and Endothelial Progenitor Cells in Pediatric Sepsis.

PubMed

Zahran, Asmaa Mohamad; Elsayh, Khalid Ibrahim; Mohamad, Ismail Lotfy; Hassan, Gamal Mohamad; Abdou, Madleen Adel A

2016-03-01

The aim of the study was to measure the number of circulating endothelial cells (CECs) and circulating endothelial progenitor cells (CEPs) in pediatric patients with sepsis and correlating it with the severity of the disease and its outcome. The study included 19 children with sepsis, 26 with complicated sepsis, and 30 healthy controls. The patients were investigated within 48 hours of pediatric intensive care unit admission together with flow cytometric detection of CECs and CEPs. The levels of both CECs and CEPs were significantly higher in patient with sepsis and complicated sepsis than the controls. The levels of CECs were higher in patients with complicated sepsis, whereas the levels of CEPs were lower in patients with complicated sepsis. Comparing the survival and nonsurvival septic patients, the levels of CEPs were significantly higher in the survival than in nonsurvival patients, whereas the levels of CECs were significantly lower in the survival than in nonsurvival patients. Serum albumin was higher in survival than in nonsurvival patients. Estimation of CECs and CEPs and their correlation with other parameters such as serum albumen could add important information regarding prognosis in septic pediatric patients.

Understanding the Inflammatory Cytokine Response in Pneumonia and Sepsis

PubMed Central

Kellum, John A.; Kong, Lan; Fink, Mitchell P.; Weissfeld, Lisa A.; Yealy, Donald M.; Pinsky, Michael R.; Fine, Jonathan; Krichevsky, Alexander; Delude, Russell L.; Angus, Derek C.

2015-01-01

Background Severe sepsis is common and frequently fatal, and community-acquired pneumonia (CAP) is the leading cause. Although severe sepsis is often attributed to uncontrolled and unbalanced inflammation, evidence from humans with infection syndromes across the breadth of disease is lacking. In this study we describe the systemic cytokine response to pneumonia and determine if specific patterns, including the balance of pro-inflammatory and anti-inflammatory markers, are associated with severe sepsis and death. Methods This is a cohort study of 1886 subjects hospitalized with CAP through the emergency departments in 28 US academic and community hospitals. We defined severe sepsis as CAP complicated by new-onset organ dysfunction, following international consensus conference criteria. We measured plasma tumor necrosis factor, IL-6 (interleukin 6), and IL-10 levels daily for the first week and weekly thereafter. Our main outcome measures were severe sepsis and 90-day mortality. Results A total of 583 patients developed severe sepsis (31%), of whom 149 died (26%). Systemic cytokine level elevation occurred in 82% of all subjects with CAP. Mean cytokine concentrations were highest at presentation, declined rapidly over the first few days, but remained elevated throughout the first week, beyond resolution of clinical signs of infection. Cytokine levels were highest in fatal severe sepsis and lowest in CAP with no severe sepsis. Unbalanced (high/low) cytokine patterns were unusual (4.6%) and not associated with decreased survival. Highest risk of death was with combined high levels of the proinflammatory IL-6 and anti-inflammatory IL-10 cytokine activity (hazard ratio, 20.5; 95% confidence interval, 10.8–39.0) (P<.001). Conclusions The circulating cytokine response to pneumonia is heterogeneous and continues for more than a week after presentation, with considerable overlap between those who do and do not develop severe sepsis. Unbalanced activation is uncommon, and

Vasopressin, Sepsis, and Renal Perfusion - A VASST Deficit in Our Understanding

DTIC Science & Technology

2014-06-01

including the Pediatric Subgroup: Surviving sepsis campaign: International guidelines for management of severe sepsis and septic shock: 2012. Crit Care...JUN 2014 2. REPORT TYPE N/A 3. DATES COVERED - 4. TITLE AND SUBTITLE Vasopressin, Sepsis , and Renal PerfusionâA VASST Deficit in Our...AKI with vasopressin. The current Surviving Sepsis Campaign Guidelines (3), based largely on the results of the VASST trial (4), recommend vasopressin

Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008

PubMed Central

Levy, Mitchell M.; Carlet, Jean M.; Bion, Julian; Parker, Margaret M.; Jaeschke, Roman; Reinhart, Konrad; Angus, Derek C.; Brun-Buisson, Christian; Beale, Richard; Calandra, Thierry; Dhainaut, Jean-Francois; Gerlach, Herwig; Harvey, Maurene; Marini, John J.; Marshall, John; Ranieri, Marco; Ramsay, Graham; Sevransky, Jonathan; Thompson, B. Taylor; Townsend, Sean; Vender, Jeffrey S.; Zimmerman, Janice L.; Vincent, Jean-Louis

2007-01-01

Objective To provide an update to the original Surviving Sepsis Campaign clinical management guidelines, “Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock,” published in 2004. Design Modified Delphi method with a consensus conference of 55 international experts, several subsequent meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. This process was conducted independently of any industry funding. Methods We used the GRADE system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations. A strong recommendation [1] indicates that an intervention's desirable effects clearly outweigh its undesirable effects (risk, burden, cost), or clearly do not. Weak recommendations [2] indicate that the tradeoff between desirable and undesirable effects is less clear. The grade of strong or weak is considered of greater clinical importance than a difference in letter level of quality of evidence. In areas without complete agreement, a formal process of resolution was developed and applied. Recommendations are grouped into those directly targeting severe sepsis, recommendations targeting general care of the critically ill patient that are considered high priority in severe sepsis, and pediatric considerations. Results Key recommendations, listed by category, include: early goal-directed resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures prior to antibiotic therapy (1C); imaging studies performed promptly to confirm potential source of infection (1C); administration of broad-spectrum antibiotic therapy within 1 hr of diagnosis of septic shock (1B) and severe sepsis without septic shock (1D); reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate (1C); a usual 7–10 days of antibiotic

Ureteric stent dwelling time: a risk factor for post-ureteroscopy sepsis.

PubMed

Nevo, Amihay; Mano, Roy; Baniel, Jack; Lifshitz, David A

2017-07-01

To evaluate the association between stent dwelling time and sepsis after ureteroscopy, and identify risk factors for sepsis in this setting. The prospectively collected database of a single institution was queried for all patients who underwent ureteroscopy for stone extraction between 2010 and 2016. Demographic, clinical, preoperative and operative data were collected. The primary study endpoint was sepsis within 48 h of ureteroscopy. Logistic regressions were performed to identify predictors of post-ureteroscopy sepsis in the ureteroscopy cohort and specifically in patients with prior stent insertion. Between October 2010 and April 2016, 1 256 patients underwent ureteroscopy for stone extraction. Risk factors for sepsis included prior stent placement, female gender and Charlson comorbidity index. A total of 601 patients had a ureteric stent inserted before the operation and were included in the study cohort, in which the median age was 56 years, 90 patients were women (30%), and 97 patients were treated for positive preoperative urine cultures (16.1%). Postoperative sepsis, <48 h after surgery, occurred in eight (1.2%) non-stented patients and in 28 patients (4.7%) with prior stent insertion. Sepsis rates after stent dwelling times of 1, 2, 3 and >3 months were 1, 4.9, 5.5 and 9.2%, respectively. On multivariate analysis, stent dwelling time, stent insertion because of sepsis, and female gender were significantly associated with post-ureteroscopy sepsis in patients with prior stent placement. Patients who undergo ureteroscopy after ureteric stent insertion have a higher risk of postoperative sepsis. Prolonged stent dwelling time, sepsis as an indication for stent insertion, and female gender are independent risk factors. Stent placement should be considered cautiously, and if inserted, ureteroscopy should be performed within 1 month. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

A Computable Definition of Sepsis Facilitates Screening and Performance Improvement Tracking

PubMed Central

Warmus, Holly R.; Schaffner, Erin K.; Kantawala, Sajel; Carcillo, Joseph; Rosen, Johanna; Horvat, Christopher M.

2018-01-01

Background: Sepsis kills almost 5,000 children annually, accounting for 16% of pediatric health care spending in the United States. Objectives: We sought to identify sepsis within the Electronic Health Record (EHR) of a quaternary children’s hospital to characterize disease incidence, improve recognition and response, and track performance metrics. Methods: Methods are organized in a plan-do-study-act cycle. During the “plan” phase, electronic definitions of sepsis (blood culture and antibiotic within 24 hours) and septic shock (sepsis plus vasoactive medication) were created to establish benchmark data and track progress with statistical process control. The performance of a screening tool was evaluated in the emergency department. During the “do” phase, a novel inpatient workflow is being piloted, which involves regular sepsis screening by nurses using the tool, and a regimented response to high risk patients. Results: Screening tool use in the emergency department reduced time to antibiotics (Fig. 1). Of the 6,159 admissions, EHR definitions identified 1,433 (23.3%) between July and December 2016 with sepsis, of which 159 (11.1%) had septic shock. Hospital mortality for all sepsis patients was 2.2% and 15.7% for septic shock (Table 1). These findings approximate epidemiologic studies of sepsis and severe sepsis, which report a prevalence range of 0.45–8.2% and mortality range of 8.2–25% (Table 2).1–5 Conclusions/Implications: Implementation of a sepsis screening tool is associated with improved performance. The prevalence of sepsis conditions identified with electronic definitions approximates the epidemiologic landscape characterized by other point-prevalence and administrative studies, providing face validity to this approach, and proving useful for tracking performance improvement. PMID:29732457

Immature platelet fraction in bacterial sepsis severity assessment

NASA Astrophysics Data System (ADS)

Djuang, M. H.; Ginting, F.; Hariman, H.

2018-03-01

Sepsis is an infection-induced syndrome, mostly caused by bacteria, of organ dysfunctions that caused by host response dysregulations. One of the simplest sepsis-indicator is platelet and its indexes. A new platelet parameter called immature platelet count (IPF) became theinterest in this study. The study aims to see whether IPF could assess sepsis severity by procalcitonin (PCT).Sixty-four of seventy-one patients with increased PCT were included in this cross-sectional study and separated into three groups based on their PCT levels. IPF showed no significance among the three groups (p-value>0.05) while platelet count was significant (p-value<0.05). Mean Platelet Volume (MPV) and Platelet Distribution Width (PDW) showed a strongpositive correlation with IPF. Higher sepsis severity based on PCT showed larger platelet count, as the result of platelet destructions caused by pro-inflammatory cytokines and endotoxins.

Immunotherapy in the management of sepsis.

PubMed

Sikora, Janusz Piotr

2002-01-01

This work presents the role of Gram-negative bacteria endotoxins, pro- and anti-inflammatory cytokines and reactive oxygen species (ROS) in the complex and not fully explained pathogenesis of sepsis. The so-called "respiratory burst" of neutrophils and the antioxidant mechanisms of the host are also discussed. The work focuses on possible approaches to the management of sepsis connected with immunotherapy. Neutralization of endotoxin lipopolysaccharide (LPS), anti-tumor necrosis factor alpha (TNF-alpha) therapy with monoclonal antibodies or pentoxifylline (PTXF), as well as soluble recombinant cytokine agonists and antagonists used in clinical trials are taken into consideration. In addition, cytokine manipulation therapy, anti-adhesion techniques, glucocorticoides and antioxidant barrier interference are also described. So far there has been no immunotherapy of sepsis in children of proven clinical efficacy, which prompts an aggressive examination of the immune system aimed at affecting its function.

Biosensor of endotoxin and sepsis

NASA Astrophysics Data System (ADS)

Shao, Yang; Wang, Xiang; Wu, Xi; Gao, Wei; He, Qing-hua; Cai, Shaoxi

2001-09-01

To investigate the relation between biosensor of endotoxin and endotoxin of plasma in sepsis. Method: biosensor of endotoxin was designed with technology of quartz crystal microbalance bioaffinity sensor ligand of endotoxin were immobilized by protein A conjugate. When a sample soliton of plasma containing endotoxin 0.01, 0.03, 0.06, 0.1, 0.5, 1.0Eu, treated with perchloric acid and injected into slot of quartz crystal surface respectively, the ligand was released from the surface of quartz crystal to form a more stable complex with endotoxin in solution. The endotoxin concentration corresponded to the weight change on the crystal surface, and caused change of frequency that occurred when desorbed. The result was biosensor of endotoxin might detect endotoxin of plasma in sepsis, measurements range between 0.05Eu and 0.5Eu in the stop flow mode, measurement range between 0.1Eu and 1Eu in the flow mode. The sensor of endotoxin could detect the endotoxin of plasm rapidly, and use for detection sepsis in clinically.

Development of an e-learning package for sepsis care.

PubMed

Davis, Anna; Henderson, James; Langmack, Gill

Severe sepsis is a major cause of morbidity and mortality in the UK. This article describes the collaborative development and implementation of an interactive online learning package to understand the key role nurses have in recognising and then starting to apply the Sepsis Six care bundle in clinical practice. The e-learning package, developed in a UK teaching hospital, uses a case study approach to address the knowledge that is required to be able to recognise sepsis, to understand the processes that occur and the ongoing care and treatment required. The package is relevant to final-year student nurses, newly registered nurses in preceptorship and other health professionals involved in assessing and treating patients who may be developing sepsis.

Multicentre observational study of adherence to Sepsis Six guidelines in emergency general surgery.

PubMed

2017-01-01

Evidence-based interventions may reduce mortality in surgical patients. This study documented the prevalence of sepsis, adherence to guidelines in its management, and timing of source control in general surgical patients presenting as an emergency. Patients aged 16 years or more presenting with emergency general surgery problems were identified over a 7-day period and then screened for sepsis compliance (using the Sepsis Six standards, devised for severe sepsis) and the timing of source control (whether radiological or surgical). Exploratory analyses examined associations between the mode (emergency department or general practitioner) and time of admission, adherence to the sepsis guidelines, and outcomes (complications or death within 30 days). Of a total of 5067 patients from 97 hospitals across the UK, 911 (18·0 per cent) fulfilled the criteria for sepsis, 165 (3·3 per cent) for severe sepsis and 24 (0·5 per cent) for septic shock. Timely delivery of all Sepsis Six guidelines for patients with severe sepsis was achieved in four patients. For patients with severe sepsis, 17·6-94·5 per cent of individual guidelines within the Sepsis Six were delivered. Oxygen was the criterion most likely to be missed, followed by blood cultures in all sepsis severity categories. Surgery for source control occurred a median of 19·8 (i.q.r. 10·0-35·4) h after diagnosis. Omission of Sepsis Six parameters did not appear to be associated with an increase in morbidity or mortality. Although sepsis was common in general surgical patients presenting as an emergency, adherence to severe sepsis guidelines was incomplete in the majority. Despite this, no evidence of harm was apparent. © 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.

AspiriN To Inhibit SEPSIS (ANTISEPSIS) randomised controlled trial protocol.

PubMed

Eisen, Damon P; Moore, Elizabeth M; Leder, Karin; Lockery, Jessica; McBryde, Emma S; McNeil, John J; Pilcher, David; Wolfe, Rory; Woods, Robyn L

2017-01-20

Sepsis is a leading global cause of morbidity and mortality, and is more common at the extremes of age. Moreover, the cost of in-hospital care for elderly patients with sepsis is significant. There are indications from experimental and observational studies that aspirin may reduce inflammation associated with infection. This paper describes the rationale and design of the AspiriN To Inhibit SEPSIS (ANTISEPSIS) trial, a substudy of ASPirin in Reducing Events in the Elderly (ASPREE). ANTISEPSIS primarily aims to determine whether low-dose aspirin reduces sepsis-related deaths in older people. Additionally, it will assess whether low-dose aspirin reduces sepsis-related hospitalisations and sepsis-related Intensive Care Unit (ICU) admissions. ASPREE is a double-blinded, randomised, placebo-controlled primary prevention trial that will determine whether daily low-dose aspirin extends disability-free longevity in 19 000 healthy older people recruited in Australia and the USA. The ANTISEPSIS substudy involves additional ASPREE trial data collection to assess the impact of daily low-dose aspirin on sepsis-related events in the 16 703 ASPREE participants aged 70 years and over, recruited in Australia. The intervention is a daily 100 mg dose of enteric-coated aspirin versus matching placebo, with 1:1 randomisation. The primary outcome for the ANTISEPSIS substudy is the incidence of sepsis-related death in eligible patients. The incidence of sepsis-related hospital and ICU admissions are secondary outcomes. ANTISEPSIS is to be conducted between 2012 and 2018. This substudy will determine whether aspirin, an inexpensive and accessible therapy, safely reduces sepsis-related deaths and hospitalisations in older Australians. If shown to be the case, this would have profound effects on the health of older Australians. Pre-results, ACTRN12613000349741. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go

Calpastatin Controls Polymicrobial Sepsis by Limiting Procoagulant Microparticle Release

PubMed Central

Gerotziafas, Grigoris; Byrnes, Colleen; Hu, Xuzhen; Perez, Joelle; Lévi, Charlène; Placier, Sandrine; Letavernier, Emmanuel; Leelahavanichkul, Asada; Haymann, Jean-philippe; Elalamy, Ismail; Miller, Jeffrey L.; Star, Robert A.; Yuen, Peter S. T.; Baud, Laurent

2012-01-01

Rationale: Sepsis, a leading cause of death worldwide, involves widespread activation of inflammation, massive activation of coagulation, and lymphocyte apoptosis. Calpains, calcium-activated cysteine proteases, have been shown to increase inflammatory reactions and lymphocyte apoptosis. Moreover, calpain plays an essential role in microparticle release. Objectives: We investigated the contribution of calpain in eliciting tissue damage during sepsis. Methods: To test our hypothesis, we induced polymicrobial sepsis by cecal ligation and puncture in wild-type (WT) mice and transgenic mice expressing high levels of calpastatin, a calpain-specific inhibitor. Measurements and Main Results: In WT mice, calpain activity increased transiently peaking at 6 hours after cecal ligation and puncture surgery. Calpastatin overexpression improved survival, organ dysfunction (including lung, kidney, and liver damage), and lymphocyte apoptosis. It decreased the sepsis-induced systemic proinflammatory response and disseminated intravascular coagulation, by reducing the number of procoagulant circulating microparticles and therefore delaying thrombin generation. The deleterious effect of microparticles in this model was confirmed by transferring microparticles from septic WT to septic transgenic mice, worsening their survival and coagulopathy. Conclusions: These results demonstrate an important role of the calpain/calpastatin system in coagulation/inflammation pathways during sepsis, because calpain inhibition is associated with less severe disseminated intravascular coagulation and better overall outcomes in sepsis. PMID:22268136

Age, exercise, and the outcome of sepsis.

PubMed

Banerjee, Debasree; Opal, Steven M

2017-11-23

We report on the increasingly important need to diagnose and care for the elderly with sepsis as a distinct patient population. We share an overview of age-related changes in sepsis physiology and the potential role of exercise.See related research by Tyml et al., https://ccforum.biomedcentral.com/articles/10.1186/s13054-017-1783-1.

Trends and disparities in sepsis hospitalisations in Victoria, Australia.

PubMed

Ore, Timothy

2016-11-01

Objective The aim of the present study was to determine the clinical and epidemiological characteristics of patients with sepsis admitted to hospitals in Victoria, Australia, during the period 2004-14. The data include incidence, severity and mortality. Methods In all, 44222 sepsis hospitalisations were identified between 2004-05 and 2013-14 from the Victorian Admitted Episodes Dataset. The dataset contains clinical and demographic information on all admissions to acute public and private hospitals. Using the International Classification of Diseases (10th Revision) Australian Modification codes, incidence rates, severity of disease and mortality were calculated. Results Sepsis hospitalisation rates per 10000 population increased significantly (P<0.01) over the period, from 6.9 (95% confidence interval (CI) 5.6-7.8) to 10.0 (95% CI 9.1-11.1), an annual growth rate of 3.8%. The age-standardised in-hospital death rates per 100000 population grew significantly (P<0.01) from 9.2 (95% CI 7.8-10.4) in 2004-05 to 13.0 (95% CI 11.7-14.6) in 2013-14, an annual growth rate of 3.1%. Among people under 45 years of age, the 0-4 years age group had the highest hospitalisation rate (3.0 per 10000 population; 95% CI 2.7-3.4). Nearly half (46.2%) of all sepsis hospitalisations were among patients born overseas, with a rate of 14.5 per 10000 population (95% CI 12.4-16.2) in that group compared with a rate of 5.9 per 10000 population (95% CI 5.3-6.7) for patients born in Australia. The age-standardised sepsis hospitalisation rate was 2.6-fold greater in the lowest compared with highest socioeconomic areas (12.7 per 10000 population (95% CI 11.2-13.8) vs 4.8 per 10000 population (95% CI 4.1-5.7), respectively). Conclusion This paper shows a significant upward trend in both sepsis separation rates and in-hospital death rates over the period; unlike sepsis, in-hospital death rates from all diagnoses fell over the same period. The results can be used to stimulate review of clinical

Sepsis National Hospital Inpatient Quality Measure (SEP-1): Multistakeholder Work Group Recommendations for Appropriate Antibiotics for the Treatment of Sepsis.

PubMed

Septimus, Edward J; Coopersmith, Craig M; Whittle, Jessica; Hale, Caleb P; Fishman, Neil O; Kim, Thomas J

2017-10-16

The Center for Medicare and Medicaid Services adopted the Early Management Bundle, Severe Sepsis/Septic Shock (SEP-1) performance measure to the Hospital Inpatient Quality Reporting Program in July 2015 to help address the high mortality and high cost associated with sepsis. The SEP-1 performance measure requires, among other critical interventions, timely administration of antibiotics to patients with sepsis or septic shock. The multistakeholder workgroup recognizes the need for SEP-1 but strongly believes that multiple antibiotics listed in the antibiotic tables for SEP-1 are not appropriate and the use of these antibiotics, as called for in the SEP-1 measure, is not in alignment with prudent antimicrobial stewardship. To promote the appropriate use of antimicrobials and combat antimicrobial resistance, the workgroup provides recommendations for appropriate antibiotics for the treatment of sepsis. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

An Interpretable Machine Learning Model for Accurate Prediction of Sepsis in the ICU.

PubMed

Nemati, Shamim; Holder, Andre; Razmi, Fereshteh; Stanley, Matthew D; Clifford, Gari D; Buchman, Timothy G

2018-04-01

Sepsis is among the leading causes of morbidity, mortality, and cost overruns in critically ill patients. Early intervention with antibiotics improves survival in septic patients. However, no clinically validated system exists for real-time prediction of sepsis onset. We aimed to develop and validate an Artificial Intelligence Sepsis Expert algorithm for early prediction of sepsis. Observational cohort study. Academic medical center from January 2013 to December 2015. Over 31,000 admissions to the ICUs at two Emory University hospitals (development cohort), in addition to over 52,000 ICU patients from the publicly available Medical Information Mart for Intensive Care-III ICU database (validation cohort). Patients who met the Third International Consensus Definitions for Sepsis (Sepsis-3) prior to or within 4 hours of their ICU admission were excluded, resulting in roughly 27,000 and 42,000 patients within our development and validation cohorts, respectively. None. High-resolution vital signs time series and electronic medical record data were extracted. A set of 65 features (variables) were calculated on hourly basis and passed to the Artificial Intelligence Sepsis Expert algorithm to predict onset of sepsis in the proceeding T hours (where T = 12, 8, 6, or 4). Artificial Intelligence Sepsis Expert was used to predict onset of sepsis in the proceeding T hours and to produce a list of the most significant contributing factors. For the 12-, 8-, 6-, and 4-hour ahead prediction of sepsis, Artificial Intelligence Sepsis Expert achieved area under the receiver operating characteristic in the range of 0.83-0.85. Performance of the Artificial Intelligence Sepsis Expert on the development and validation cohorts was indistinguishable. Using data available in the ICU in real-time, Artificial Intelligence Sepsis Expert can accurately predict the onset of sepsis in an ICU patient 4-12 hours prior to clinical recognition. A prospective study is necessary to determine the

Sepsis and identification of reliable biomarkers for postoperative period prognosis.

PubMed

Siloşi, Cristian Adrian; Siloşi, Isabela; Pădureanu, Vlad; Bogdan, Maria; Mogoantă, Stelian Ştefăniţă; Ciurea, Marius Eugen; Cojocaru, Manole; Boldeanu, Lidia; Avrămescu, Carmen Silvia; Boldeanu, Mihail Virgil; Popa, Dragoş George

2018-01-01

Sepsis is currently defined as the presence of organ dysfunction occurring as the result of a disturbed host response to a serious infection. Sepsis is one of the most common diseases, which cause mortality and a considerable absorber of healthcare resources. Despite progress in technology and improving knowledge of pathophysiology, the disease mechanism is still poorly understood. At present, diagnosis is based on non-specific physiological criteria and on the late identification of the pathogen. For these reasons, the diagnosis may be uncertain, treatment delayed or an immunomodulatory therapy cannot be established. An early and reliable diagnosis is essential to achieve better outcomes on disease progression. The host response to infection involves hundreds of many mediators of which have been proposed as biomarkers. There is a need for new diagnostic approaches for sepsis, new sepsis biomarkers that can aid in diagnosis, therapeutic decision and monitoring of the response to therapy. The differentiation of sepsis from non-infectious systemic inflammatory response syndrome is difficult, and the search for a highly accurate biomarker of sepsis has become one important objective of the medicine. The goal of our review is to summarize the recent advances on the most commonly studied serum biomarkers, evaluated in clinical and experimental studies, for early diagnosis of sepsis and their informative value in diagnosis, prognosis, or response to therapy. In this context, we have tracked the clinical utility of measuring serum biomarkers, such as procalcitonin, pro- and anti-inflammatory cytokines, C-reactive protein, leptin and their combinations. Currently, has not been identified an ideal biomarker to aid in the diagnosis of sepsis. It is hoped that the discovery of new serum markers, as well as their combinations, will serve for the diagnosis and prognosis of sepsis.

Serum decoy receptor 3, a potential new biomarker for sepsis.

PubMed

Hou, Yan-Qiang; Xu, Ping; Zhang, Mei; Han, Deping; Peng, Liang; Liang, Dong-Yu; Yang, Shanmin; Zhang, Zhenhuan; Hong, Jinsheng; Lou, Xiao-Li; Zhang, Lurong; Kim, Sunghee

2012-04-11

Sepsis, a common deadly systemic infection caused by a variety of pathogens, has some clinical symptoms similar to the systemic inflammatory response syndrome (SIRS), a whole-body non-infectious inflammatory reaction to severe insults, such as burn, trauma, hypotensive shock and so on. Treatment of sepsis depends mainly on anti-microbial, while remedy for SIRS might require steroids that could possibly enhance the spread of microbes. Unfortunately, it is very difficult to distinguish these two completely different serious conditions without blood culture, which takes days to grow and identify causative pathogens. We examined a biomarker, serum decoy receptor 3 (DcR3), was evaluated for its utility in the differential diagnosis between sepsis and SIRS. Serum DcR3 level in 118 healthy controls, 24 sepsis patients and 43 SIRS patients, was quantitatively measured by enzyme-linked immunosorbent assay (ELISA). The serum DcR3 was significantly increased in sepsis patients compared with SIRS patients and healthy controls (6.11±2.58 ng/ml vs 2.62±1.46 ng/ml, and 0.91±0.56 ng/ml, respectively, p<0.001). The areas under the receiver operating characteristic curve of DcR3 for the normal vs. SIRS, normal vs. sepsis and SIRS vs. sepsis were 0.910 (0.870-0.950), 0.992 (0.984-1.000) and 0.896 (0.820-0.973), respectively. In addition, the DcR3 exhibited a positive correlation coefficient with APACHE II score, a most commonly used index for the severity of sepsis (r=0.556, p=0.005). The serum DcR3 has a potential to serve as a new biomarker for sepsis with its high specificity and sensitivity. Copyright © 2012 Elsevier B.V. All rights reserved.

Systemic bioinformatics analysis of skeletal muscle gene expression profiles of sepsis

PubMed Central

Yang, Fang; Wang, Yumei

2018-01-01

Sepsis is a type of systemic inflammatory response syndrome with high morbidity and mortality. Skeletal muscle dysfunction is one of the major complications of sepsis that may also influence the outcome of sepsis. The aim of the present study was to explore and identify potential mechanisms and therapeutic targets of sepsis. Systemic bioinformatics analysis of skeletal muscle gene expression profiles from the Gene Expression Omnibus was performed. Differentially expressed genes (DEGs) in samples from patients with sepsis and control samples were screened out using the limma package. Differential co-expression and coregulation (DCE and DCR, respectively) analysis was performed based on the Differential Co-expression Analysis package to identify differences in gene co-expression and coregulation patterns between the control and sepsis groups. Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways of DEGs were identified using the Database for Annotation, Visualization and Integrated Discovery, and inflammatory, cancer and skeletal muscle development-associated biological processes and pathways were identified. DCE and DCR analysis revealed several potential therapeutic targets for sepsis, including genes and transcription factors. The results of the present study may provide a basis for the development of novel therapeutic targets and treatment methods for sepsis. PMID:29805480

Basic and advanced echocardiographic evaluation of myocardial dysfunction in sepsis and septic shock.

PubMed

Vallabhajosyula, S; Pruthi, S; Shah, S; Wiley, B M; Mankad, S V; Jentzer, J C

2018-01-01

Sepsis continues to be a leading cause of mortality and morbidity in the intensive care unit. Cardiovascular dysfunction in sepsis is associated with worse short- and long-term outcomes. Sepsis-related myocardial dysfunction is noted in 20%-65% of these patients and manifests as isolated or combined left or right ventricular systolic or diastolic dysfunction. Echocardiography is the most commonly used modality for the diagnosis of sepsis-related myocardial dysfunction. With the increasing use of ultrasonography in the intensive care unit, there is a renewed interest in sepsis-related myocardial dysfunction. This review summarises the current scope of literature focused on sepsis-related myocardial dysfunction and highlights the use of basic and advanced echocardiographic techniques for the diagnosis of sepsis-related myocardial dysfunction and the management of sepsis and septic shock.

Reprioritization of hepatic plasma protein release in trauma and sepsis.

PubMed

Sganga, G; Siegel, J H; Brown, G; Coleman, B; Wiles, C E; Belzberg, H; Wedel, S; Placko, R

1985-02-01

We studied the temporal pattern of seven hepatic synthesized plasma proteins in 26 severely injured patients beginning in the immediate posttrauma period. Clinical sepsis developed in ten patients between three and eight days after injury, and 16 patients had nonseptic courses. In the initial five days after injury, except for albumin, all acute-phase protein levels rose. However, if sepsis developed, C-reactive protein, fibrinogen, ceruloplasmin, and alpha 1-antitrypsin levels continued to be elevated after the initial five posttrauma days, while transferrin, albumin, and alpha 2-macroglobulin levels fell. This differential response became more extreme as sepsis progressed. Covariance analysis of the regression of the five true acute-phase hepatic proteins on C-reactive protein showed that, when sepsis occurred after major traumatic injury, the C-reactive protein rise was associated with a significant reprioritization of hepatic acute-phase plasma protein release. This reprioritization response seems to be both a predictor of sepsis as well as a measure of the adequacy of the host response to trauma and sepsis.

Systematic review of use of β-blockers in sepsis.

PubMed

Chacko, Cyril Jacob; Gopal, Shameer

2015-01-01

We proposed a review of present literature and systematic analysis of present literature to summarize the evidence on the use of β-blockers on the outcome of a patient with severe sepsis and septic shock. Medline, EMBASE, Cochrane Library were searched from 1946 to December 2013. The bibliography of all relevant articles was hand searched. Full-text search of the grey literature was done through the medical institution database. The database search identified a total of 1241 possible studies. The citation list was hand searched by both the authors. A total of 9 studies were identified. Most studies found a benefit from β-blocker administration in sepsis. This included improved heart rate (HR) control, decreased mortality and improvement in acid-base parameters. Chronic β-blocker usage in sepsis was also associated with improved mortality. The administration of β-blockers during sepsis was associated with better control of HR. The methodological quality of all the included studies, however, was poor. There is insufficient evidence to justify the routine use of β-blockers in sepsis. A large adequately powered multi-centered randomized controlled clinical trial is required to address the question on the efficacy of β-blocker usage in sepsis. This trial should also consider a number of important questions including the choice of β-blocker used, optimal dosing, timing of intervention, duration of intervention and discontinuation of the drug. Until such time based on the available evidence, there is no place for the use of β-blockers in sepsis in current clinical practice.

Barriers to implementing the Sepsis Six guidelines in an acute hospital setting.

PubMed

Breen, Sarah-Jane; Rees, Sharon

2018-05-10

To identify the barriers to implementation of the Sepsis Six pathway. Research has suggested that compliance with the Sepsis Six pathway remains low. A convenience sample of doctors and nurses from one emergency department, two medical wards and two surgical wards were asked to complete a survey questionnaire. Data from 108 respondents were available for analysis. Doctors and nurses agreed that lack of sepsis recognition during observation rounds and failure to associate sepsis with deranged temperature and blood results acted as barriers to the identification of sepsis. Doctors and nurses agreed that nursing delays and knowledge deficits were the top barriers leading to delay in sepsis treatment. Knowledge deficits, lack of resources and practical issues were barriers identified in this survey. This will inform the educational and process needs of both doctors and nurses in order to improve sepsis care.

Sepsis biomarkers.

PubMed

Prucha, Miroslav; Bellingan, Geoff; Zazula, Roman

2015-02-02

Sepsis is the most frequent cause of death in non-coronary intensive care units (ICUs). In the past 10 years, progress has been made in the early identification of septic patients and in their treatment and these improvements in support and therapy mean that the mortality is gradually decreasing but it still remains unacceptably high. Leaving clinical diagnosis aside, the laboratory diagnostics represent a complex range of investigations that can place significant demands on the system given the speed of response required. There are hundreds of biomarkers which could be potentially used for diagnosis and prognosis in septic patients. The main attributes of successful markers would be high sensitivity, specificity, possibility of bed-side monitoring, and financial accessibility. Only a fraction is used in routine clinical practice because many lack sufficient sensitivity or specificity. The following review gives a short overview of the current epidemiology of sepsis, its pathogenesis and state-of-the-art knowledge on the use of specific biochemical, hematological and immunological parameters in its diagnostics. Prospective approaches towards discovery of new diagnostic biomarkers have been shortly mentioned. Copyright © 2014 Elsevier B.V. All rights reserved.

Modulation of myocardial mitochondrial mechanisms during severe polymicrobial sepsis in the rat.

PubMed

Chopra, Mani; Golden, Honey B; Mullapudi, Srinivas; Dowhan, William; Dostal, David E; Sharma, Avadhesh C

2011-01-01

We tested the hypothesis that 5-Hydroxydecanoic acid (5HD), a putative mitoK(ATP) channel blocker, will reverse sepsis-induced cardiodynamic and adult rat ventricular myocyte (ARVM) contractile dysfunction, restore mitochondrial membrane permeability alterations and improve survival. Male Sprague-Dawley rats (350-400 g) were made septic using 400 mg/kg cecal inoculum, ip. Sham animals received 5% dextrose water, ip. The Voltage Dependent Anion Channels (VDAC1), Bax and cytochrome C levels were determined in isolated single ARVMs obtained from sham and septic rat heart. Mitochondria and cytosolic fractions were isolated from ARVMs treated with norepinephrine (NE, 10 µmoles) in the presence/absence of 5HD (100 µmoles). A continuous infusion of 5HD using an Alzet pump reversed sepsis-induced mortality when administered at the time of induction of sepsis (-40%) and at 6 hr post-sepsis (-20%). Electrocardiography revealed that 5HD reversed sepsis-induced decrease in the average ejection fraction, Simpsons+m Mode (53.5±2.5 in sepsis and 69.2±1.2 at 24 hr in sepsis+5HD vs. 79.9±1.5 basal group) and cardiac output (63.3±1.2 mL/min sepsis and 79.3±3.9 mL/min at 24 hr in sepsis+5HD vs. 85.8±1.5 mL/min basal group). The treatment of ARVMs with 5HD also reversed sepsis-induced depressed contractility in both the vehicle and NE-treated groups. Sepsis produced a significant downregulation of VDAC1, and upregulation of Bax levels, along with mitochondrial membrane potential collapse in ARVMs. Pretreatment of septic ARVMs with 5HD blocked a NE-induced decrease in the VDAC1 and release of cytochrome C. The data suggest that Bax activation is an upstream event that may precede the opening of the mitoK(ATP) channels in sepsis. We concluded that mitoK(ATP) channel inhibition via decreased mitochondrial membrane potential and reduced release of cytochrome C provided protection against sepsis-induced ARVM and myocardial contractile dysfunction.

Progranulin Plays a Central Role in Host Defense during Sepsis by Promoting Macrophage Recruitment.

PubMed

Song, Zhixin; Zhang, Xuemei; Zhang, Liping; Xu, Fang; Tao, Xintong; Zhang, Hua; Lin, Xue; Kang, Lihua; Xiang, Yu; Lai, Xaiofei; Zhang, Qun; Huang, Kun; Dai, Yubing; Yin, Yibing; Cao, Ju

2016-11-15

Progranulin, a widely expressed protein, has multiple physiological functions. The functional role of progranulin in the host response to sepsis remains unknown. To assess the role of progranulin in the host response to sepsis. Effects of progranulin on host response to sepsis were determined. Progranulin concentrations were significantly elevated in adult (n = 74) and pediatric (n = 26) patients with sepsis relative to corresponding healthy adult (n = 36) and pediatric (n = 17) control subjects, respectively. By using a low-lethality model of nonsevere sepsis, we observed that progranulin deficiency not only increased mortality but also decreased bacterial clearance during sepsis. The decreased host defense to sepsis in progranulin-deficient mice was associated with reduced macrophage recruitment, with correspondingly impaired chemokine CC receptor ligand 2 (CCL2) production in peritoneal lavages during the early phase of sepsis. Progranulin derived from hematopoietic cells contributed to host defense in sepsis. Therapeutic administration of recombinant progranulin not only rescued impaired host defense in progranulin-deficient mice after nonsevere sepsis but also protected wild-type mice against a high-lethality model of severe sepsis. Progranulin-mediated protection against sepsis was closely linked to improved peritoneal macrophage recruitment. In addition, CCL2 treatment of progranulin-deficient mice improved survival and decreased peritoneal bacterial loads during sepsis, at least in part through promotion of peritoneal macrophage recruitment. This proof-of-concept study supports a central role of progranulin-dependent macrophage recruitment in host defense to sepsis, opening new opportunities to host-directed therapeutic strategy that manipulate host immune response in the treatment of sepsis.

Circulating Long Noncoding RNAs as Potential Biomarkers of Sepsis: A Preliminary Study.

PubMed

Dai, Yu; Liang, Zhixin; Li, Yulin; Li, Chunsun; Chen, Liangan

2017-11-01

Long noncoding RNAs (lncRNAs) are becoming promising biomarker candidates in various diseases as assessed via sequencing technologies. Sepsis is a life-threatening disease without ideal biomarkers. The aim of this study was to investigate the expression profile of lncRNAs in the peripheral blood of sepsis patients and to find potential biomarkers of sepsis. A lncRNA expression profile was performed using peripheral blood from three sepsis patients and three healthy volunteers using microarray screening. The differentially expressed lncRNAs were validated by real-time quantitative polymerase chain reaction (qRT-PCR) in a further set of 22 sepsis patients and 22 healthy volunteers. Among 1316 differentially expressed lncRNAs, 771 were downregulated and 545 were upregulated. Results of the qRT-PCR were consistent with the microarray data. lncRNA ENST00000452391.1, uc001vji.1, and uc021zxw.1 were significantly differentially expressed between sepsis patients and healthy volunteers. Moreover, lncRNA ENST00000504301.1 and ENST00000452391.1 were significantly differentially expressed between sepsis survivors and nonsurvivors. The lncRNA expression profile in the peripheral blood of sepsis patients significantly differed from that of healthy volunteers. Circulating lncRNAs may be good candidates for sepsis biomarkers.

Multi-analytical Approaches Informing the Risk of Sepsis

NASA Astrophysics Data System (ADS)

Gwadry-Sridhar, Femida; Lewden, Benoit; Mequanint, Selam; Bauer, Michael

Sepsis is a significant cause of mortality and morbidity and is often associated with increased hospital resource utilization, prolonged intensive care unit (ICU) and hospital stay. The economic burden associated with sepsis is huge. With advances in medicine, there are now aggressive goal oriented treatments that can be used to help these patients. If we were able to predict which patients may be at risk for sepsis we could start treatment early and potentially reduce the risk of mortality and morbidity. Analytic methods currently used in clinical research to determine the risk of a patient developing sepsis may be further enhanced by using multi-modal analytic methods that together could be used to provide greater precision. Researchers commonly use univariate and multivariate regressions to develop predictive models. We hypothesized that such models could be enhanced by using multiple analytic methods that together could be used to provide greater insight. In this paper, we analyze data about patients with and without sepsis using a decision tree approach and a cluster analysis approach. A comparison with a regression approach shows strong similarity among variables identified, though not an exact match. We compare the variables identified by the different approaches and draw conclusions about the respective predictive capabilities,while considering their clinical significance.

Sepsis: Multiple Abnormalities, Heterogeneous Responses, and Evolving Understanding

PubMed Central

Iskander, Kendra N.; Osuchowski, Marcin F.; Stearns-Kurosawa, Deborah J.; Kurosawa, Shinichiro; Stepien, David; Valentine, Catherine

2013-01-01

Sepsis represents the host's systemic inflammatory response to a severe infection. It causes substantial human morbidity resulting in hundreds of thousands of deaths each year. Despite decades of intense research, the basic mechanisms still remain elusive. In either experimental animal models of sepsis or human patients, there are substantial physiological changes, many of which may result in subsequent organ injury. Variations in age, gender, and medical comorbidities including diabetes and renal failure create additional complexity that influence the outcomes in septic patients. Specific system-based alterations, such as the coagulopathy observed in sepsis, offer both potential insight and possible therapeutic targets. Intracellular stress induces changes in the endoplasmic reticulum yielding misfolded proteins that contribute to the underlying pathophysiological changes. With these multiple changes it is difficult to precisely classify an individual's response in sepsis as proinflammatory or immunosuppressed. This heterogeneity also may explain why most therapeutic interventions have not improved survival. Given the complexity of sepsis, biomarkers and mathematical models offer potential guidance once they have been carefully validated. This review discusses each of these important factors to provide a framework for understanding the complex and current challenges of managing the septic patient. Clinical trial failures and the therapeutic interventions that have proven successful are also discussed. PMID:23899564

A rational approach to fluid therapy in sepsis.

PubMed

Marik, P; Bellomo, R

2016-03-01

Aggressive fluid resuscitation to achieve a central venous pressure (CVP) greater than 8 mm Hg has been promoted as the standard of care, in the management of patients with severe sepsis and septic shock. However recent clinical trials have demonstrated that this approach does not improve the outcome of patients with severe sepsis and septic shock. Pathophysiologically, sepsis is characterized by vasoplegia with loss of arterial tone, venodilation with sequestration of blood in the unstressed blood compartment and changes in ventricular function with reduced compliance and reduced preload responsiveness. These data suggest that sepsis is primarily not a volume-depleted state and recent evidence demonstrates that most septic patients are poorly responsive to fluids. Furthermore, almost all of the administered fluid is sequestered in the tissues, resulting in severe oedema in vital organs and, thereby, increasing the risk of organ dysfunction. These data suggest that a physiologic, haemodynamically guided conservative approach to fluid therapy in patients with sepsis would be prudent and would likely reduce the morbidity and improve the outcome of this disease. © The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Escherichia coli counting using lens-free imaging for sepsis diagnosis

NASA Astrophysics Data System (ADS)

Moon, Sangjun; Manzur, Fahim; Manzur, Tariq; Klapperich, Catherine; Demirci, Utkan

2009-09-01

Sepsis causes 9.3% of overall deaths in United States. To diagnose sepsis, cell/bacteria capture and culturing methods have been widely investigated in the medical field. Escherichia Coli (E. Coli) is used as a model organism for sepsis in blood stream since wide variety of antibodies are established and the genetic modification process is well documented for fluorescent tagging. In point-of-care testing applications, the sepsis diagnostics require fast monitoring, inexpensive testing, and reliable results at resource limited settings, i.e. battle field, home care for dialysis. However, the cell/E.coli are hard to directly capture and see at the POCT because of the small size, 2 μm long and 0.5 μm in diameter, and the bacteria are rare in the blood stream in sepsis. Here, we propose a novel POCT platform to image and enumerate cell/E.coli on a microfluidic surface to diagnose sepsis at resource limited conditions. We demonstrate that target cells are captured from 5 μl of whole blood using specific antibodies and E.coli are imaged using a lens-free imaging platform, 2.2 μm pixel CMOS based imaging sensor. This POCT cell/bacteria capture and enumeration approach can further be used for medical diagnostics of sepsis. We also show approaches to rapidly quantify white blood cell counts from blood which can be used to monitor immune response.

Procalcitonin - Assisted Antibiotic Strategy in Sepsis.

PubMed

Trásy, Domonkos; Molnár, Zsolt

2017-05-01

Sepsis is one of the biggest challenges in critical care nowadays. Defining sepsis is a difficult task on its own and its diagnosis and treatment requires well trained, devoted personnel with interdisciplinary collaboration in order to provide the patients the best chance for survival. Immediate resuscitation, early adequate antimicrobial therapy, source control and highly sophisticated organ support on the intensive care units are all inevitable necessities for successful recovery. To help fast and accurate diagnosis biomarkers have been measured for decades. Procalcitonin (PCT) is one of the most studied, but the results are conflicting. Sepsis means a very loose cohort of a large heterogeneous patient population, hence defining certain cut off values for PCT to differentiate between different severities of the disease is almost impossible. Clinicians first have to understand the pathophysiological background of sepsis to be able to interpret correctly the PCT results. Nevertheless, PCT has been shown to have the best sensitivity and specificity to indicate infection, antibiotic appropriateness and stopping therapy. In this article we will focus on some important aspects of pathophysiology and advice on how to implement that in the everyday clinical practice. We believe that this multimodal evaluation of the clinical picture together with PCT results can be a useful tool to make the most out of the PCT results, and do the best for patients on the ICU.

Comparison of oxidative stress & leukocyte activation in patients with severe sepsis & burn injury

PubMed Central

Mühl, Diana; Woth, Gábor; Drenkovics, Livia; Varga, Adrienn; Ghosh, Subhamay; Csontos, Csaba; Bogár, Lajos; Wéber, György; Lantos, János

2011-01-01

Background & objectives: We evaluated pro- and anti-oxidant disturbances in sepsis and non-sepsis burn patients with systemic inflammatory response syndrome (SIRS). Adhesion molecules and inflammation markers on leukocytes were also analyzed. We hypothesized that oxidative stress and leukocyte activation markers can lead to the severity of sepsis. Methods: In 28 severe sepsis and 27 acute burn injury patients blood samples were collected at admission and 4 days consecutively. Oxidative stress markers: production of reactive oxygen species (ROS), myeloperoxidase, malondialdehyde and endogenous antioxidants: plasma protein sulphydryl groups, reduced glutathione, superoxide dismutase and catalase were measured. Flow cytometry was used to determine CD11a, CD14, CD18, CD49d and CD97 adhesion molecules on leukocytes. Procalcitonin, C-reactive protein, fibrinogen, platelet count and lactate were also analyzed. Results: Pro-oxidant parameters were significantly elevated in sepsis patients at admission, ROS intensity increased in burn patients until the 5th day. Endogenous antioxidant levels except catalase showed increased levels after burn trauma compared to sepsis. Elevated granulocyte activation and suppressed lymphocyte function were found at admission and early activation of granulocytes caused by increasing activation/migration markers in sepsis. Leukocyte adhesion molecule expression confirmed the suppressed lymphocyte and monocyte function in sepsis. Interpretation & conclusions: Severe sepsis is accompanied by oxidative stress and pathological leukocyte endothelial cell interactions. The laboratory parameters used for the evaluation of sepsis and several markers of pro- and antioxidant status were different between sepsis and non-sepsis burn patients. The tendency of changes in these parameters may refer to major oxidative stress in sepsis and developing SIRS in burns. PMID:21808137

New Sepsis Definition (Sepsis-3) and Community-acquired Pneumonia Mortality. A Validation and Clinical Decision-Making Study.

PubMed

Ranzani, Otavio T; Prina, Elena; Menéndez, Rosario; Ceccato, Adrian; Cilloniz, Catia; Méndez, Raul; Gabarrus, Albert; Barbeta, Enric; Bassi, Gianluigi Li; Ferrer, Miquel; Torres, Antoni

2017-11-15

The Sepsis-3 Task Force updated the clinical criteria for sepsis, excluding the need for systemic inflammatory response syndrome (SIRS) criteria. The clinical implications of the proposed flowchart including the quick Sequential (Sepsis-related) Organ Failure Assessment (qSOFA) and SOFA scores are unknown. To perform a clinical decision-making analysis of Sepsis-3 in patients with community-acquired pneumonia. This was a cohort study including adult patients with community-acquired pneumonia from two Spanish university hospitals. SIRS, qSOFA, the Confusion, Respiratory Rate and Blood Pressure (CRB) score, modified SOFA (mSOFA), the Confusion, Urea, Respiratory Rate, Blood Pressure and Age (CURB-65) score, and Pneumonia Severity Index (PSI) were calculated with data from the emergency department. We used decision-curve analysis to evaluate the clinical usefulness of each score and the primary outcome was in-hospital mortality. Of 6,874 patients, 442 (6.4%) died in-hospital. SIRS presented the worst discrimination, followed by qSOFA, CRB, mSOFA, CURB-65, and PSI. Overall, overestimation of in-hospital mortality and miscalibration was more evident for qSOFA and mSOFA. SIRS had lower net benefit than qSOFA and CRB, significantly increasing the risk of over-treatment and being comparable with the "treat-all" strategy. PSI had higher net benefit than mSOFA and CURB-65 for mortality, whereas mSOFA seemed more applicable when considering mortality/intensive care unit admission. Sepsis-3 flowchart resulted in better identification of patients at high risk of mortality. qSOFA and CRB outperformed SIRS and presented better clinical usefulness as prompt tools for patients with community-acquired pneumonia in the emergency department. Among the tools for a comprehensive patient assessment, PSI had the best decision-aid tool profile.

The Impact of HIV Co-Infection on the Genomic Response to Sepsis

PubMed Central

Huson, Michaëla A. M.; Scicluna, Brendon P.; van Vught, Lonneke A.; Wiewel, Maryse A.; Hoogendijk, Arie J.; Cremer, Olaf L.; Bonten, Marc J. M.; Schultz, Marcus J.; Franitza, Marek; Toliat, Mohammad R.; Nürnberg, Peter; Grobusch, Martin P.; van der Poll, Tom

2016-01-01

HIV patients have an increased risk to develop sepsis and HIV infection affects several components of the immune system involved in sepsis pathogenesis. We hypothesized that HIV infection might aggrevate the aberrant immune response during sepsis, so we aimed to determine the impact of HIV infection on the genomic host response to sepsis. We compared whole blood leukocyte gene expression profiles among sepsis patients with or without HIV co-infection in the intensive care unit (ICU) and validated our findings in a cohort of patients admitted to the same ICUs in a different time frame. To examine the influence of HIV infection per se, we also determined the expression of genes of interest in a cohort of asymptomatic HIV patients. We identified a predominantly common host response in sepsis patients with or without HIV co-infection. HIV positive sepsis patients in both ICU cohorts showed overexpression of genes involved in granzyme signaling (GZMA, GZMB), cytotoxic T-cell signaling (CD8A, CD8B) and T-cell inhibitory signaling (LAG3), compared to HIV negative patients. Enhanced expression of CD8A, CD8B and LAG3 was also unmasked in asymptomatic HIV patients. Plasma levels of granzymes in sepsis patients were largely below detection limit, without differences according to HIV status. These results demonstrate that sepsis is characterized by a massive common response with few differences between HIV positive and HIV negative sepsis patients. Observed differences in granzyme signaling, cytotoxic T-cell signaling and T-cell inhibitory signaling appear to be changes commonly observed in asymptomatic HIV patients which persist during sepsis. PMID:26871709

Predicting Sepsis Risk Using the "Sniffer" Algorithm in the Electronic Medical Record.

PubMed

Olenick, Evelyn M; Zimbro, Kathie S; DʼLima, Gabrielle M; Ver Schneider, Patricia; Jones, Danielle

The Sepsis "Sniffer" Algorithm (SSA) has merit as a digital sepsis alert but should be considered an adjunct to versus an alternative for the Nurse Screening Tool (NST), given lower specificity and positive predictive value. The SSA reduced the risk of incorrectly categorizing patients at low risk for sepsis, detected sepsis high risk in half the time, and reduced redundant NST screens by 70% and manual screening hours by 64% to 72%. Preserving nurse hours expended on manual sepsis alerts may translate into time directed toward other patient priorities.

Early-Onset Neonatal Sepsis

PubMed Central

Simonsen, Kari A.; Anderson-Berry, Ann L.; Delair, Shirley F.

2014-01-01

SUMMARY Early-onset sepsis remains a common and serious problem for neonates, especially preterm infants. Group B streptococcus (GBS) is the most common etiologic agent, while Escherichia coli is the most common cause of mortality. Current efforts toward maternal intrapartum antimicrobial prophylaxis have significantly reduced the rates of GBS disease but have been associated with increased rates of Gram-negative infections, especially among very-low-birth-weight infants. The diagnosis of neonatal sepsis is based on a combination of clinical presentation; the use of nonspecific markers, including C-reactive protein and procalcitonin (where available); blood cultures; and the use of molecular methods, including PCR. Cytokines, including interleukin 6 (IL-6), interleukin 8 (IL-8), gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α), and cell surface antigens, including soluble intercellular adhesion molecule (sICAM) and CD64, are also being increasingly examined for use as nonspecific screening measures for neonatal sepsis. Viruses, in particular enteroviruses, parechoviruses, and herpes simplex virus (HSV), should be considered in the differential diagnosis. Empirical treatment should be based on local patterns of antimicrobial resistance but typically consists of the use of ampicillin and gentamicin, or ampicillin and cefotaxime if meningitis is suspected, until the etiologic agent has been identified. Current research is focused primarily on development of vaccines against GBS. PMID:24396135

Novel Predictors of Sepsis Outperform the American Burn Association Sepsis Criteria in the Burn Intensive Care Unit Patient

DTIC Science & Technology

2013-01-01

increase in insulin requirement over 24 hours; or enteral feeding intol- erance: abdominal distension pr gastric residuals more than two times feeding...performance. However, the inclusion criteria were based on bacteremia (positive blood cul- ture), not coupled with a clinical suspicion of sepsis; only...subtle clinical changes is present in the early stages of infection and sepsis,6 but compiling trends is difficult for busy clinical staff. The

Monocyte Profiles in Critically Ill Patients With Pseudomonas Aeruginosa Sepsis

ClinicalTrials.gov

2017-02-02

Pseudomonas Infections; Pseudomonas Septicemia; Pseudomonas; Pneumonia; Pseudomonal Bacteraemia; Pseudomonas Urinary Tract Infection; Pseudomonas Gastrointestinal Tract Infection; Sepsis; Sepsis, Severe; Critically Ill

HLA-DR expression, cytokines and bioactive lipids in sepsis

PubMed Central

2014-01-01

Sepsis accounts for more than 200,000 deaths annually in the USA alone. Both inflammatory and anti-inflammatory responses occur simultaneously in sepsis, the early phase dominated by the hyperinflammatory response and the late phase by immunosuppression. This late immunosuppression phase leads to loss of the delayed type hypersensitivity response, failure to clear the primary infection and development of secondary infections. Based on the available data, I hypothesize that failure to produce adequate amounts of inflammation resolving lipid mediators may be at the centre of both the hyperinflammatory response and late immunosuppression seen in sepsis. These proresolving lipids – lipoxins, resolvins and protectins – suppress exacerbated activation of leukocytes and macrophages, inhibit excess production of pro-inflammatory cytokines, initiate resolution of inappropriate inflammation, augment clearance of bacteria and other pathogens, and restore homeostasis. If true, this implies that administration of naturally occurring lipoxins, resolvins, protectins, maresins and nitrolipids by themselves or their more stable synthetic analogues such as 15-epi-16-(para-fluorophenoxy)-lipoxin A4-methyl ester, a synthetic analogue of 15-epi-lipoxin A4, and 15(R/S)-methyl-LXA4 may form a new approach in the prevention (in the high-risk subjects), management of sepsis and in resolving the imbalanced inflammatory process such that sepsis is ameliorated early. In addition, recent studies have suggested that nociceptin and cold inducible RNA binding protein (CIRBP) also have a role in the pathobiology of sepsis. It is suggested that both nociceptin and CIRBP inhibit the production of lipoxins, resolvins, protectins, maresins, and nitrolipids and thus play a role in sepsis and septic shock. PMID:24904669

The clinical utility of fibrin-related biomarkers in sepsis.

PubMed

Toh, Julien M H; Ken-Dror, Gie; Downey, Colin; Abrams, Simon T

2013-12-01

Sepsis is associated with systemic inflammatory responses and induction of intravascular fibrin formation. Our aim is to investigate whether three fibrin-related markers (FRM) reflect the extent of coagulation activation in vivo and evaluate their clinical usefulness in identifying as well as monitoring patients with sepsis. Fibrin-degradation products (FDP), D-dimer and soluble fibrin monomer assays were measured on plasma samples from patients in the ICU with sepsis (n = 37), systemic inflammatory response syndrome (SIRS) (n = 35) and healthy individuals (n = 15). The levels were correlated with each other and also with fibrinogen, prothrombin time, platelets and antithrombin III. Clinical correlation was also performed for the diagnosis of sepsis and longitudinal monitoring for survival or death.There was strong correlation between the three FRM (r = 0.38-0.93, P < 0.0001) with only fibrin monomer correlating significantly with prothrombin time, fibrinogen and platelet levels. Clinically, all three FRM could discriminate between patients with sepsis, SIRS and healthy individuals with FDP, and D-dimer showing statistical significance (P < 0.05). No FRM predicted outcome from a single measurement but FDP was significantly able to predict patient survival from serial samples [mean FDP (μg/ml) from 35.36 to 21.37 (first to third ICU-day), P < 0.05]. Fibrin monomer appears the most sensitive indicator of coagulation activation, whereas D-dimer and FDP levels can significantly differentiate ICU patients with sepsis from those without. In addition, FDP would be preferable for monitoring with its statistically significant time-dependent prediction of survival or death from sepsis.

Sepsis attenuates the anabolic response to skeletal muscle contraction

PubMed Central

Steiner, Jennifer L.; Lang, Charles H.

2014-01-01

Electrically stimulated muscle contraction is a potential clinical therapy to treat sepsis-induced myopathy; however, whether sepsis alters contraction-induced anabolic signaling is unknown. Polymicrobial peritonitis was produced by cecal ligation and puncture (CLP) in male C57BL/6 mice and time-matched, pair-fed controls (CON). At ~24 h post-CLP, the right hindlimb was electrically stimulated via the sciatic nerve to evoke maximal muscle contractions and the gastrocnemius was collected 2 h later. Protein synthesis was increased by muscle contraction in CON mice. Sepsis suppressed the rate of synthesis in both the non-stimulated (31%) and stimulated (57%) muscle versus CON. Contraction of muscle in CON mice increased the phosphorylation of mTORC1 substrates S6K1 Thr389 (8-fold), S6K1 Thr421/Ser424 (7-fold) and 4E-BP1 Ser65 (11-fold). Sepsis blunted the contraction-induced phosphorylation of S6K1 Thr389 (67%), S6K1 Thr421/Ser424 (46%) and 4E-BP1 Ser65 (85%). Conversely, sepsis did not appear to modulate protein elongation as eEF2 Thr56 phosphorylation was decreased similarly by muscle contraction in both groups. MAPK signaling was discordant following muscle contraction in septic muscle; phosphorylation of ERK Thr202/Tyr204 and p38 Thr180/Tyr182 was increased similarly in both CON and CLP mice while sepsis prevented the contraction-induced phosphorylation of JNK Thr183/Tyr185 and c-JUN Ser63. The expression of IL-6 and TNF-α mRNA in muscle was increased by sepsis, and contraction increased TNF-α to a greater extent in muscle from septic than CON mice. Injection of the mTOR inhibitor Torin2 in separate mice confirmed that contraction-induced increases in S6K1 and 4E-BP1 were mTOR-mediated. These findings demonstrate that resistance to contraction-induced anabolic signaling occurs during sepsis and is predominantly mTORC1-dependent. PMID:25423127

Sepsis attenuates the anabolic response to skeletal muscle contraction.

PubMed

Steiner, Jennifer L; Lang, Charles H

2015-04-01

Electrically stimulated muscle contraction is a potential clinical therapy to treat sepsis-induced myopathy; however, whether sepsis alters contraction-induced anabolic signaling is unknown. Polymicrobial peritonitis was produced by cecal ligation and puncture (CLP) in male C57BL/6 mice and time-matched, pair-fed controls (CON). At ∼24 h post-CLP, the right hindlimb was electrically stimulated via the sciatic nerve to evoke maximal muscle contractions, and the gastrocnemius was collected 2 h later. Protein synthesis was increased by muscle contraction in CON mice. Sepsis suppressed the rate of synthesis in both the nonstimulated (31%) and stimulated (57%) muscle versus CON. Contraction of muscle in CON mice increased the phosphorylation of mTORC1 (mammalian target of rapamycin [mTOR] complex 1) substrates S6K1 (70-kd ribosomal protein S6 kinase 1) Thr (8-fold), S6K1 ThrSer (7-fold) and 4E-BP1 Ser (11-fold). Sepsis blunted the contraction-induced phosphorylation of S6K1 Thr (67%), S6K1 ThrSer (46%), and 4E-BP1 Ser (85%). Conversely, sepsis did not appear to modulate protein elongation as eEF2 Thr phosphorylation was decreased similarly by muscle contraction in both groups. Mitogen-activated protein kinase signaling was discordant following contraction in septic muscle; phosphorylation of extracellular signal-regulated kinase ThrTyr and p38 ThrTyr was increased similarly in both CON and CLP mice, while sepsis prevented the contraction-induced phosphorylation of JNK ThrTyr and c-JUN Ser. The expression of interleukin 6 and tumor necrosis factor α (TNF-α) mRNA in muscle was increased by sepsis, and contraction increased TNF-α to a greater extent in muscle from septic than CON mice. Injection of the mTOR inhibitor Torin2 in separate mice confirmed that contraction-induced increases in S6K1 and 4E-BP1 were mTOR mediated. These findings demonstrate that resistance to contraction-induced anabolic signaling occurs during sepsis and is predominantly mTORC1-dependent.

Role of Cytokines as a Double-edged Sword in Sepsis

PubMed Central

CHAUDHRY, HINA; ZHOU, JUHUA; ZHONG, YIN; ALI, MIR MUSTAFA; MCGUIRE, FRANKLIN; NAGARKATTI, PRAKASH S.; NAGARKATTI, MITZI

2014-01-01

Background Sepsis is a deadly immunological disorder and its pathophysiology is still poorly understood. We aimed to determine if specific pro-inflammatory and anti-inflammatory cytokines can be used as diagnostic and therapeutic targets for sepsis. Materials and Methods Recent publications in the MEDLINE database were searched for articles regarding the clinical significance of inflammatory cytokines in sepsis. Results In response to pathogen infection, pro-inflammatory cytokines [interleukin-6 (IL-6), IL-8, IL-18 and tumor necrosis factor-α (TNF-α)] and anti-inflammatory cytokine (IL-10) increased in patients with sepsis. Importantly, a decrease in IL-6 was associated with a better prognosis and overproduction of IL-10 was found to be the main predictor of severity and fatal outcome. Conclusion Both pro-inflammatory and anti-inflammatory cytokines constitute a double-edged sword in sepsis; on one hand they are critical to eliminate the infection while on the other, excessive production can cause tissue and organ damage. Increase in cytokines such as IL-6, Il-8, IL-10, IL-18 and TNF-α may have implications in diagnosis and treatment of sepsis. PMID:24292568

Reduced Expression of SARM in Mouse Spleen during Polymicrobial Sepsis.

PubMed

Gong, Yu; Zou, Lin; Cen, Dongzhi; Chao, Wei; Chen, Dunjin

2016-12-01

Objective Immune dysfunction, including prominent apoptosis of immune cells and decreased functioning of the remaining immune cells, plays a central role in the pathogenesis of sepsis. Sterile α and HEAT/armadillo motif-containing protein (SARM) is implicated in the regulation of immune cell apoptosis. This study aimed to elucidate SARM contributes to sepsis-induced immune cell death and immunosuppression. Methods A mouse model of polymicrobial sepsis was generated by cecum ligation and puncture (CLP). SARM gene and protein expression, caspase 3 cleavage and intracellular ATP production were measured in the mouse spleens. Results CLP-induced polymicrobial sepsis specifically attenuated both the gene and protein expression of SARM in the spleens. Moreover, the attenuation of SARM expression synchronized with splenocyte apoptosis, as evidenced by increased caspase 3 cleavage and ATP depletion. Conclusions These findings suggest that SARM is a potential regulator of sepsis-induced splenocyte apoptosis.

Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012.

PubMed

Dellinger, R P; Levy, Mitchell M; Rhodes, Andrew; Annane, Djillali; Gerlach, Herwig; Opal, Steven M; Sevransky, Jonathan E; Sprung, Charles L; Douglas, Ivor S; Jaeschke, Roman; Osborn, Tiffany M; Nunnally, Mark E; Townsend, Sean R; Reinhart, Konrad; Kleinpell, Ruth M; Angus, Derek C; Deutschman, Clifford S; Machado, Flavia R; Rubenfeld, Gordon D; Webb, Steven; Beale, Richard J; Vincent, Jean-Louis; Moreno, Rui

2013-02-01

To provide an update to the "Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock," last published in 2008. A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict of interest policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independent of any industry funding. A stand-alone meeting was held for all subgroup heads, co- and vice-chairs, and selected individuals. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations as strong (1) or weak (2). The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. Recommendations were classified into three groups: (1) those directly targeting severe sepsis; (2) those targeting general care of the critically ill patient and considered high priority in severe sepsis; and (3) pediatric considerations. Key recommendations and suggestions, listed by category, include: early quantitative resuscitation of the septic patient during the first 6 h after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm a potential source of infection (UG); administration of broad-spectrum antimicrobials therapy within 1 h of the recognition of septic shock (1B) and severe sepsis without septic shock (1C) as the goal of therapy; reassessment of antimicrobial therapy daily for de-escalation, when appropriate (1B

Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012.

PubMed

Dellinger, R Phillip; Levy, Mitchell M; Rhodes, Andrew; Annane, Djillali; Gerlach, Herwig; Opal, Steven M; Sevransky, Jonathan E; Sprung, Charles L; Douglas, Ivor S; Jaeschke, Roman; Osborn, Tiffany M; Nunnally, Mark E; Townsend, Sean R; Reinhart, Konrad; Kleinpell, Ruth M; Angus, Derek C; Deutschman, Clifford S; Machado, Flavia R; Rubenfeld, Gordon D; Webb, Steven A; Beale, Richard J; Vincent, Jean-Louis; Moreno, Rui

2013-02-01

To provide an update to the "Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock," last published in 2008. A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict of interest policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independent of any industry funding. A stand-alone meeting was held for all subgroup heads, co- and vice-chairs, and selected individuals. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations as strong (1) or weak (2). The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. Some recommendations were ungraded (UG). Recommendations were classified into three groups: 1) those directly targeting severe sepsis; 2) those targeting general care of the critically ill patient and considered high priority in severe sepsis; and 3) pediatric considerations. Key recommendations and suggestions, listed by category, include: early quantitative resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm a potential source of infection (UG); administration of broad-spectrum antimicrobials therapy within 1 hr of recognition of septic shock (1B) and severe sepsis without septic shock (1C) as the goal of therapy; reassessment of antimicrobial therapy daily for de

[New Concept for Surviving Sepsis: from Phenomenon to Essence].

PubMed

Liao, Xue-Lian; Xie, Zhi-Chao; Kang, Yan

2016-07-01

Sepsis is a critical clinical syndrome which keep puzzling the medical profession for many years. Recently, the results from several large-scale trials challenged the necessity of early goal directed therapy (EGDT) in surviving sepsis bundle, These trials were not opposed to EGDT but bring new concept that it is essential to utilize therapy with multiple monitoring measures in order to minimize injury while guarantee the safety . Deeper understanding in the pathogenesis of sepsis gives rise to the update of its definition based on vital organ dysfunction. The importance of dynamic monitoring in defining sepsis also need to be emphasized. Developing more effective monitoring measures could provide better treatments, thus improve the prognosis of septic patients. Copyright© by Editorial Board of Journal of Sichuan University (Medical Science Edition).

Molecular Regulatory Pathways Link Sepsis With Metabolic Syndrome: Non-coding RNA Elements Underlying the Sepsis/Metabolic Cross-Talk.

PubMed

Meydan, Chanan; Bekenstein, Uriya; Soreq, Hermona

2018-01-01

Sepsis and metabolic syndrome (MetS) are both inflammation-related entities with high impact for human health and the consequences of concussions. Both represent imbalanced parasympathetic/cholinergic response to insulting triggers and variably uncontrolled inflammation that indicates shared upstream regulators, including short microRNAs (miRs) and long non-coding RNAs (lncRNAs). These may cross talk across multiple systems, leading to complex molecular and clinical outcomes. Notably, biomedical and RNA-sequencing based analyses both highlight new links between the acquired and inherited pathogenic, cardiac and inflammatory traits of sepsis/MetS. Those include the HOTAIR and MIAT lncRNAs and their targets, such as miR-122, -150, -155, -182, -197, -375, -608 and HLA-DRA. Implicating non-coding RNA regulators in sepsis and MetS may delineate novel high-value biomarkers and targets for intervention.

Role of presepsin for the evaluation of sepsis in the emergency department.

PubMed

Pizzolato, Elisa; Ulla, Marco; Galluzzo, Claudia; Lucchiari, Manuela; Manetta, Tilde; Lupia, Enrico; Mengozzi, Giulio; Battista, Stefania

2014-10-01

Sepsis, severe sepsis and septic shock are among the most common conditions handled in the emergency department (ED). According to new Sepsis Guidelines, early diagnosis and treatment are the keys to improve survival. Plasma C-reactive protein (CRP) and procalcitonin (PCT) levels, when associated with documented or suspected infection, are now part of the definitions of sepsis. Blood culture is the gold standard method for detecting microorganisms but it requires too much time for results to be known. Sensitive biomarkers are required for early diagnosis and as indexes of prognosis sepsis. CRP is one of the acute phase proteins synthesized by the liver: it has a great sensitivity but a very poor specificity for bacterial infections. Moreover, the evolution of sepsis does not correlate with CRP plasma changes. In recent years PCT has been widely used for sepsis differential diagnosis, because of its close correlation with infections, but it still retains some limitations and false positivity (such as in multiple trauma and burns). Soluble CD14 subtype (sCD14-ST), also known as presepsin, is a novel and promising biomarker that has been shown to increase significantly in patients with sepsis, in comparison to the healthy population. Studies pointed out the capability of this biomarker for diagnosing sepsis, assessing the severity of the disease and providing a prognostic evaluation of patient outcome. In this mini review we mainly focused on presepsin: we evaluate its diagnostic and prognostic roles in patients presenting to the ED with systemic inflammatory response syndrome (SIRS), suspected sepsis or septic shock.

Risk of acute stroke after hospitalization for sepsis: A case-crossover study

PubMed Central

Boehme, Amelia K.; Ranawat, Purnima; Luna, Jorge; Kamel, Hooman; Elkind, Mitchell S. V.

2017-01-01

Background and Purpose Infections have been found to increase the risk of stroke over the short-term. We hypothesized that stroke risk would be highest shortly after a sepsis hospitalization, but that the risk would decrease, yet remain up to 1-year after sepsis. Methods This case-crossover analysis utilized data obtained from the California State Inpatient Database of the Healthcare Cost and Utilization Project (HCUP). All stroke admissions were included. Exposure was defined as hospitalization for sepsis or septicemia 180, 90, 30 or 15 days before stroke (risk period) or similar time intervals exactly 1 or 2 years before stroke (control period). Conditional logistic regression was used to calculate the odds ratio and 95% confidence interval (OR, 95% CI) for the association between sepsis/septicemia and ischemic or hemorrhagic stroke. Results Ischemic (n=37,377) and hemorrhagic (n=12,817) strokes that occurred in 2009 were extracted where 3188 (8.5%) ischemic and 1101 (8.6%) hemorrhagic stroke patients had sepsis. Sepsis within 15 days prior to the stroke placed patients at the highest risk of ischemic (OR 28.36, 95% CI 20.02 –40.10) and hemorrhagic stroke (OR 12.10, 95% CI 7.54–19.42); however while the risk decreased, it remained elevated 181- 365 days after sepsis for ischemic (OR 2.59, 95%CI 2.20–3.06) and hemorrhagic (O 3.92, 95%CI 3.29–4.69) strokes. There was an interaction with age (p=0.0006); risk of developing an ischemic stroke within 180 days of hospitalization for sepsis increased 18% with each 10-year decrease in age. Conclusion Risk of stroke is high after sepsis, and this risk persists for up to a year. Younger sepsis patients have a particularly increased risk of stroke after sepsis. PMID:28196938

Clinical Epidemiology of SIRS and Sepsis in Newly Admitted Children.

PubMed

Ganjoo, Sheetal; Ahmad, Kaisar; Qureshi, Umar Amin; Mir, Zahed Hussain

2015-08-01

To assess the clinical and demographic profile of Systemic Inflammatory Response Syndrome (SIRS) and sepsis, among newly admitted children in different age groups in a hospital in North India. This prospective study was conducted at a referral care centre in Northern India. All children, age group 0 to <18 y, admitted on days selected for study were screened and those with abnormal temperature and abnormal leukocyte count were included for further assessment. A total of twenty "24 h" periods were randomly chosen during the study period. Patients were assessed according to age specific vital signs and laboratory values to diagnose Systemic Inflammatory Response Syndrome (SIRS) and sepsis and to gain clinical and demographic data. The criteria laid at International consensus conference, 2002, were used to define patients as SIRS, Sepsis, Severe sepsis and Septic shock. During the study period, a total of 865 patients were screened for SIRS. Prevalence of SIRS amongst hospitalised children was 23 % (n = 201). Seventy nine percent (n = 159) of patients had infection associated SIRS and 21 % (42) had non-infective SIRS. Sixty four percent (n = 129) SIRS patients had uncomplicated sepsis, 15 % (n = 30) patients fulfilled criteria for severe sepsis. Out of the latter 30, 19 had septic shock. Organ dysfunction in SIRS was noted in 25 % (n = 51). 37.25 % (n = 19) had multiple organ dysfunction syndrome (MODS). The most common organism isolated was Staphylococcus aureus (n = 9). Focus of infection in majority was pulmonary (44 %). Mean duration of antibiotic therapy and hospital stay in the SIRS group were 6.4 and 6.5 d respectively. In the group without SIRS, mean duration were 2.44 d and 3.07 d respectively The differences were statistically significant. In conclusion, the proportion of sepsis contributing to SIRS is high in a tertiary care hospital. Therefore rapid recognition of SIRS is essential. Goal directed treatment of sepsis is

A simple intervention to improve antibiotic treatment times for neutropenic sepsis.

PubMed

Botten, J; Beard, J; Zorzi, A; Thompson, A

2016-01-01

Patients with suspected Neutropenic sepsis require rapid antibiotic administration, but despite extensive education, only 67% of patients received antibiotics within 60 minutes . A Neutropenic Sepsis Alert Card was created, as a Patient Specific Directive - this allows nurses to administer antibiotics to specific patients without prior medical review. Since the intervention, 301 patients presented with suspected neutropenic sepsis. 277 patients (92%) received their first dose of intravenous antibiotics within 1 hour of arrival into hospital, compared to 95 out of 143 patients (67%) presenting between January and June of 2014 (p=0.036). The Neutropenic Sepsis Alert Card can significantly improve door to antibiotic needle time for chemotherapy patients with suspected neutropenic sepsis. This intervention is inexpensive and easily replicable in other health care organisations.

Expression and role of neuroglobin in rats with sepsis-associated encephalopathy.

PubMed

Zhang, Li-Na; Ai, Yu-Hang; Gong, Hua; Guo, Qu-Lian; Huang, Li; Liu, Zhi-Yong; Yao, Bo

2014-01-01

To determine the role of neuroglobin in the pathology of sepsis-associated encephalopathy and ascertain if neuroglobin has any protective effects against sepsis-associated encephalopathy. Randomized laboratory animal study. Research university animal laboratory. Two hundred and forty adult male Sprague-Dawley rats. Rats received cecal puncture and ligation (or sham) surgery to induce sepsis, then broken up into groups based on whether or not the rat developed sepsis-associated encephalopathy as determined by electroencephalograph and evoked potential recordings. The rats were then left untreated to examine the effect of sepsis-associated encephalopathy on neuroglobin, treated with a neuroglobin antisense nucleotide to block gene expression, or given hemin, a neuroglobin inducer. Following sepsis induction, diagnosis, and treatment, the brains were analyzed for both gross and ultrastructural morphology. Also, neuronal neuroglobin immunoreactivity and apoptosis (via terminal uridine nucleotide end-labeling) were examined. Blood serum levels were then analyzed for neuroglobin, superoxide dismutase, and malondialdehyde levels. We determined that sepsis-associated encephalopathy induces damage evident when examining both gross and ultrastructural morphology, as well as induces neuronal neuroglobin expression. Also, blockade of neuroglobin expression via antisense treatment will exacerbate these pathological effects, while increasing neuroglobin levels via hemin will ameliorate them. Blood analysis found that levels of superoxide dismutase and malondialdehyde mirrored the level of pathology found in the brain, while plasma neuroglobin levels reflected the amount of neuronal neuroglobin immunoreactivity. We conclude that neuroglobin is involved in the pathogenesis of sepsis-associated encephalopathy and has neuroprotective effects. We also determined that hemin has protective effects against sepsis-associated encephalopathy as well, most probably due to its effect on

CD39 improves survival in microbial sepsis by attenuating systemic inflammation

PubMed Central

Csóka, Balázs; Németh, Zoltán H.; Törő, Gábor; Koscsó, Balázs; Kókai, Endre; Robson, Simon C.; Enjyoji, Keiichi; Rolandelli, Rolando H.; Erdélyi, Katalin; Pacher, Pál; Haskó, György

2015-01-01

Sepsis remains the leading cause of morbidity and mortality in critically ill patients. Excessive inflammation is a major cause of organ failure and mortality in sepsis. Ectonucleoside triphosphate diphosphohydrolase 1, ENTPDase1 (CD39) is a cell surface nucleotide-metabolizing enzyme, which degrades the extracellular purines ATP and ADP, thereby regulating purinergic receptor signaling. Although the role of purinergic receptor signaling in regulating inflammation and sepsis has been addressed previously, the role of CD39 in regulating the host’s response to sepsis is unknown. We found that the CD39 mimic apyrase (250 U/kg) decreased and knockout or pharmacologic blockade with sodium polyoxotungstate (5 mg/kg; IC50 ≈ 10 μM) of CD39 increased mortality of mice with polymicrobial sepsis induced by cecal ligation and puncture. CD39 decreased inflammation, organ damage, immune cell apoptosis, and bacterial load. Use of bone marrow chimeric mice revealed that CD39 expression on myeloid cells decreases inflammation in septic mice. CD39 expression is upregulated during sepsis in mice, as well as in both murine and human macrophages stimulated with Escherichia coli. Moreover, E. coli increases CD39 promoter activity in macrophages. Altogether, these data indicate CD39 as an evolutionarily conserved inducible protective pathway during sepsis. We propose CD39 as a novel therapeutic target in the management of sepsis.—Csóka, B., Németh, Z. H., Törő, G., Koscsó, B., Kókai, E., Robson, S. C., Enjyoji, K., Rolandelli, R. H., Erdélyi, K., Pacher, P., Haskó, G. CD39 improves survival in microbial sepsis by attenuating systemic inflammation. PMID:25318479

Modulation of Myocardial Mitochondrial Mechanisms during Severe Polymicrobial Sepsis in the Rat

PubMed Central

Chopra, Mani; Golden, Honey B.; Mullapudi, Srinivas; Dowhan, William; Dostal, David E.; Sharma, Avadhesh C.

2011-01-01

Background We tested the hypothesis that 5-Hydroxydecanoic acid (5HD), a putative mitoKATP channel blocker, will reverse sepsis-induced cardiodynamic and adult rat ventricular myocyte (ARVM) contractile dysfunction, restore mitochondrial membrane permeability alterations and improve survival. Methodology/Principal Findings Male Sprague-Dawley rats (350–400 g) were made septic using 400 mg/kg cecal inoculum, ip. Sham animals received 5% dextrose water, ip. The Voltage Dependent Anion Channels (VDAC1), Bax and cytochrome C levels were determined in isolated single ARVMs obtained from sham and septic rat heart. Mitochondria and cytosolic fractions were isolated from ARVMs treated with norepinephrine (NE, 10 µmoles) in the presence/absence of 5HD (100 µmoles). A continuous infusion of 5HD using an Alzet pump reversed sepsis-induced mortality when administered at the time of induction of sepsis (−40%) and at 6 hr post-sepsis (−20%). Electrocardiography revealed that 5HD reversed sepsis-induced decrease in the average ejection fraction, Simpsons+m Mode (53.5±2.5 in sepsis and 69.2±1.2 at 24 hr in sepsis+5HD vs. 79.9±1.5 basal group) and cardiac output (63.3±1.2 mL/min sepsis and 79.3±3.9 mL/min at 24 hr in sepsis+5HD vs. 85.8±1.5 mL/min basal group). The treatment of ARVMs with 5HD also reversed sepsis-induced depressed contractility in both the vehicle and NE-treated groups. Sepsis produced a significant downregulation of VDAC1, and upregulation of Bax levels, along with mitochondrial membrane potential collapse in ARVMs. Pretreatment of septic ARVMs with 5HD blocked a NE-induced decrease in the VDAC1 and release of cytochrome C. Conclusion The data suggest that Bax activation is an upstream event that may precede the opening of the mitoKATP channels in sepsis. We concluded that mitoKATP channel inhibition via decreased mitochondrial membrane potential and reduced release of cytochrome C provided protection against sepsis-induced ARVM and myocardial

Heart-rate variability depression in porcine peritonitis-induced sepsis without organ failure.

PubMed

Jarkovska, Dagmar; Valesova, Lenka; Chvojka, Jiri; Benes, Jan; Danihel, Vojtech; Sviglerova, Jitka; Nalos, Lukas; Matejovic, Martin; Stengl, Milan

2017-05-01

Depression of heart-rate variability (HRV) in conditions of systemic inflammation has been shown in both patients and experimental animal models and HRV has been suggested as an early indicator of sepsis. The sensitivity of HRV-derived parameters to the severity of sepsis, however, remains unclear. In this study we modified the clinically relevant porcine model of peritonitis-induced sepsis in order to avoid the development of organ failure and to test the sensitivity of HRV to such non-severe conditions. In 11 anesthetized, mechanically ventilated and instrumented domestic pigs of both sexes, sepsis was induced by fecal peritonitis. The dose of feces was adjusted and antibiotic therapy was administered to avoid multiorgan failure. Experimental subjects were screened for 40 h from the induction of sepsis. In all septic animals, sepsis with hyperdynamic circulation and increased plasma levels of inflammatory mediators developed within 12 h from the induction of peritonitis. The sepsis did not progress to multiorgan failure and there was no spontaneous death during the experiment despite a modest requirement for vasopressor therapy in most animals (9/11). A pronounced reduction of HRV and elevation of heart rate developed quickly (within 5 h, time constant of 1.97 ± 0.80 h for HRV parameter TINN) upon the induction of sepsis and were maintained throughout the experiment. The frequency domain analysis revealed a decrease in the high-frequency component. The reduction of HRV parameters and elevation of heart rate preceded sepsis-associated hemodynamic changes by several hours (time constant of 11.28 ± 2.07 h for systemic vascular resistance decline). A pronounced and fast reduction of HRV occurred in the setting of a moderate experimental porcine sepsis without organ failure. Inhibition of parasympathetic cardiac signaling probably represents the main mechanism of HRV reduction in sepsis. The sensitivity of HRV to systemic inflammation may allow

Severe sepsis in pre-hospital emergency care: analysis of incidence, care, and outcome.

PubMed

Seymour, Christopher W; Rea, Thomas D; Kahn, Jeremy M; Walkey, Allan J; Yealy, Donald M; Angus, Derek C

2012-12-15

Severe sepsis is common and highly morbid, yet the epidemiology of severe sepsis at the frontier of the health care system-pre-hospital emergency care-is unknown. We examined the epidemiology of pre-hospital severe sepsis among emergency medical services (EMS) encounters, relative to acute myocardial infarction and stroke. Retrospective study using a community-based cohort of all nonarrest, nontrauma King County EMS encounters from 2000 to 2009 who were transported to a hospital. Overall incidence rate of hospitalization with severe sepsis among EMS encounters, as well as pre-hospital characteristics, admission diagnosis, and outcomes. Among 407,176 EMS encounters, we identified 13,249 hospitalizations for severe sepsis, of whom 2,596 died in the hospital (19.6%). The crude incidence rate of severe sepsis was 3.3 per 100 EMS encounters, greater than for acute myocardial infarction or stroke (2.3 per 100 and 2.2 per 100 EMS encounters, respectively). More than 40% of all severe sepsis hospitalizations arrived at the emergency department after EMS transport, and 80% of cases were diagnosed on admission. Pre-hospital care intervals, on average, exceeded 45 minutes for those hospitalized with severe sepsis. One-half or fewer of patients with severe sepsis were transported by paramedics (n = 7,114; 54%) or received pre-hospital intravenous access (n = 4,842; 37%). EMS personnel care for a substantial and increasing number of patients with severe sepsis, and spend considerable time on scene and during transport. Given the emphasis on rapid diagnosis and intervention for sepsis, the pre-hospital interval may represent an important opportunity for recognition and care of sepsis.

Choice of Fluid Therapy in the Initial Management of Sepsis, Severe Sepsis, and Septic Shock.

PubMed

Chang, Ronald; Holcomb, John B

2016-07-01

Sepsis results in disruption of the endothelial glycocalyx layer and damage to the microvasculature, resulting in interstitial accumulation of fluid and subsequently edema. Fluid resuscitation is a mainstay in the initial treatment of sepsis, but the choice of fluid is unclear. The ideal resuscitative fluid is one that restores intravascular volume while minimizing edema; unfortunately, edema and edema-related complications are common consequences of current resuscitation strategies. Crystalloids are recommended as first-line therapy, but the type of crystalloid is not specified. There is increasing evidence that normal saline is associated with increased mortality and kidney injury; balanced crystalloids may be a safer alternative. Albumin is similar to crystalloids in terms of outcomes in the septic population but is costlier. Hydroxyethyl starches appear to increase mortality and kidney injury in the critically ill and are no longer indicated in these patients. In the trauma population, the shift to plasma-based resuscitation with decreased use of crystalloid and colloid in the treatment of hemorrhagic shock has led to decreased inflammatory and edema-mediated complications. Studies are needed to determine if these benefits also occur with a similar resuscitation strategy in the setting of sepsis.

The characteristics and impact of source of infection on sepsis-related ICU outcomes.

PubMed

Jeganathan, Niranjan; Yau, Stephen; Ahuja, Neha; Otu, Dara; Stein, Brian; Fogg, Louis; Balk, Robert

2017-10-01

Source of infection is an independent predictor of sepsis-related mortality. To date, studies have failed to evaluate differences in septic patients based on the source of infection. Retrospective study of all patients with sepsis admitted to the ICU of a university hospital within a 12month time period. Sepsis due to intravascular device and multiple sources had the highest number of positive blood cultures and microbiology whereas lung and abdominal sepsis had the least. The observed hospital mortality was highest for sepsis due to multiple sources and unknown cause, and was lowest when due to abdominal, genitourinary (GU) or skin/soft tissue. Patients with sepsis due to lungs, unknown and multiple sources had the highest rates of multi-organ failure, whereas those with sepsis due to GU and skin/soft tissue had the lowest rates. Those with multisource sepsis had a significantly higher median ICU length of stay and hospital cost. There are significant differences in patient characteristics, microbiology positivity, organs affected, mortality, length of stay and cost based on the source of sepsis. These differences should be considered in future studies to be able to deliver personalized care. Copyright © 2017 Elsevier Inc. All rights reserved.

Emerging infection and sepsis biomarkers: will they change current therapies?

PubMed Central

Jacobs, Lauren

2016-01-01

Introduction Sepsis is a heterogeneous syndrome characterized by both immune hyperactivity and relative immune suppression. Biomarkers have the potential to improve recognition and management of sepsis through three main applications: diagnosis, monitoring response to treatment, and stratifying patients based on prognosis or underlying biological response. Areas Covered This review focuses on specific examples of well-studied, evidence-supported biomarkers, and discusses their role in clinical practice with special attention to antibiotic stewardship and cost-effectiveness. Biomarkers were selected based on availability of robust prospective trials and meta-analyses which supported their role as emerging tools to improve the clinical management of sepsis. Expert Commentary Great strides have been made in candidate sepsis biomarker discovery and testing, with the biomarkers in this review showing promise. Yet sepsis remains a dynamic illness with a great degree of biological heterogeneity – heterogeneity which may be further resolved by recently discovered gene expression-based endotypes in septic shock. PMID:27533847

Procalcitonin levels in patients with positive blood culture, positive body fluid culture, sepsis, and severe sepsis: a cross-sectional study.

PubMed

Yu, Ying; Li, Xia-Xi; Jiang, Ling-Xiao; Du, Meng; Liu, Zhan-Guo; Cen, Zhong-Ran; Wang, Hua; Guo, Zhen-Hui; Chang, Ping

2016-01-01

Numerous investigations on procalcitonin (PCT) have been carried out, although few with large sample size. To deal with the complexity of sepsis, an understanding of PCT in heterogeneous clinical conditions is required. Hospitalized patients aged 10-79 years were included in this retrospective and cross-sectional study. PCT tests were assayed within 2 days of blood culture. A total of 2952 cases (from 2538 patients) were enrolled in this study, including 440 cases in the 'positive BC' group, 123 cases in the 'positive body fluid culture' group, and 2389 cases in the 'negative all culture' group. Median PCT values were 4.53 ng/ml, 2.95 ng/ml, and 0.49 ng/ml, respectively. Median PCT values in the gram-negative BC group and gram-positive BC group, respectively, were 6.99 ng/ml and 2.96 ng/ml. Median PCT values in the 'positive hydrothorax culture' group, 'positive ascites culture' group, 'positive bile culture' group, and 'positive cerebrospinal fluid culture' group, respectively, were 1.39 ng/ml, 8.32 ng/ml, 5.98 ng/ml, and 0.46 ng/ml. In all, 357 cases were classified into the 'sepsis' group, 150 of them were classified into the 'severe sepsis' group. Median PCT values were 5.63 ng/ml and 11.06 ng/ml, respectively. PCT could be used in clinical algorithms to diagnose positive infections and sepsis. Different PCT levels could be related to different kinds of microbemia, different infection sites, and differing severity of sepsis.

Sleep apnoea patients have higher mortality when confronting sepsis.

PubMed

Huang, Chien-Yu; Chen, Yung-Tai; Wu, Li-An; Liu, Chia-Jen; Chang, Shi-Chuan; Perng, Diahn-Warng; Chen, Yuh-Min; Chen, Tzeng-Ji; Lee, Yu-Chin; Chou, Kun-Ta

2014-01-01

Sleep is essential for the maintenance of an intact immune function. Patients with sleep apnoea experience frequent sleep interruption due to apnoea-related arousals, possibly adversely impacting their immunity and affecting their outcomes when confronting sepsis. This case-control study aimed to compare the outcomes of sepsis patients with and without sleep apnoea. From 2000 to 2009, 168 sleep apnoea patients who were first admitted for sepsis were identified from the Taiwan National Health Insurance Research Database. Also, 672 sepsis patients without sleep apnoea, who were matched by age, gender and Charlson's comorbidity index scores, served as controls. Hospital outcomes of the two groups were compared. Binary logistic regression was employed for multivariate analysis. The mortality rates of sepsis patients with and without sleep apnoea were 60.1% and 47.9%, respectively (P = 0. 005). After multivariate adjustment, sleep apnoea (OR: 1.805, 95% CI: 1.227-2.656, P = 0.003), presence of shock (OR: 3.600, 95% CI: 2.144-6.046, P < 0.001) and number of organs with dysfunction (OR: 1.591, 95% CI: 1.087-2.329, P = 0.017) were found to be independently associated with mortality. Sleep apnoea patients who needed continuous positive airway pressure treatment had an even higher risk of mortality. Sepsis patients with sleep apnoea may have poorer hospital outcomes than those without sleep apnoea. © 2013 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.

[Value of interleukin-27 as a diagnostic biomarker of sepsis in critically ill adults].

PubMed

Fu, Junjing; Wang, Yongtao; Zeng, Ping; Niu, Shanshan

2015-06-01

To evaluate interleukin-27 (IL-27) as a sepsis diagnostic biomarker in critically ill adults with sepsis. A retrospetive study was conducted. A total of 176 systemic inflammatory response syndrome (SIRS) patients in Department of Critical Care Medicine of Xinxiang Medical College First Affiliated Hospital from March to November in 2014 were enrolled. The patients were divided into no sepsis group (n=66), pulmonary originated sepsis group (n=65), and non-pulmonary originated sepsis group (n=45). Plasma IL-27 and procalcitonin (PCT) were determined with enzyme linked immunosorbent assay (ELISA). Receiver operating characteristic curve (ROC) and classification and regression tree methodology was used to evaluate diagnostic biomarker performance. The proportion of patients in pulmonary original sepsis group whose body temperature in line with SIRS criteria was significantly higher than no sepsis group (66.2% vs. 44.5%, P<0.05), and they were easy to suffer from tumor (44.6% vs. 22.7%, P<0.05). The proportion of patients in non-pulmonary originated sepsis group whose white blood cell count in line with SIRS criteria was significantly higher than no sepsis group (68.9% vs. 42.7%, P<0.05). It indicated that patients in pulmonary originated sepsis group and non-pulmonary originated sepsis group were more in line with SIRS criteria compared with no sepsis group. It was shown by ROC curve that IL-27 and PCT was not effective in discriminating sepsis among unselected patients showing symptoms and signs of SIRS. The area under the curve (AUC) was 0.59 [95% confidence interval (95%CI)=0.49-0.65] and 0.61 (95%CI=0.55-0.71). According to the further analysis from different infection sources, the highest AUC was 0.71 (95%CI=0.59-0.79) for IL-27 in patients with a non-pulmonary originated sepsis. A decision tree incorporating IL-27, PCT, and age had an AUC of 0.78 (95%CI=0.71-0.87) in patients with a non-pulmonary originated sepsis, which was higher than IL-27 [0.71(95%CI=0

Maternal epidural use and neonatal sepsis evaluation in afebrile mothers.

PubMed

Goetzl, L; Cohen, A; Frigoletto, F; Ringer, S A; Lang, J M; Lieberman, E

2001-11-01

Epidural use has been associated with a higher rate of neonatal sepsis evaluation. Epidural-related fever explains some of the increase but not the excess of neonatal sepsis evaluations in afebrile women We studied 1109 women who had singleton term pregnancies and who presented in spontaneous labor and were afebrile during labor (<100.4 degrees F). Neonatal sepsis evaluation generally was performed on the basis of the presence of 1 major or 2 minor criteria. Major criteria included rupture of membranes for >24 hours or sustained fetal heart rate of >160 beats per minute. Minor criteria included a maternal temperature of 99.6 degrees F to 100.4 degrees F, rupture of membranes for 12 to 24 hours, maternal admission white blood cell count of >15 000 cells/mL(3), or an Apgar score of <7 at 5 minutes. Infants of afebrile women with epidural analgesia were more likely to be evaluated for sepsis than infants of women without epidural (20.4% vs 8.9%), although not more likely to have neonatal sepsis. An increased risk of sepsis evaluation persisted in regression analysis (odds ratio: 3.1; 95% confidence interval: 2.0, 4.7) after controlling for confounders and was not explained by longer labors with epidural. Women with epidural were significantly more likely to have major and minor criteria for sepsis evaluation, including fetal tachycardia (4.4% vs 0.4%), rupture of membranes for >24 hours (6.2% vs 3.4%), low-grade fever of 99.6 degrees F to 100.4 degrees F (24.3% vs 5.2%), and rupture of membranes for 12 to 24 hours (21.4% vs 5.2%) than women without epidural. Epidural analgesia is associated with increased rates of major and minor criteria for neonatal sepsis evaluations in afebrile women.

An unusual case of sepsis and petechial rash.

PubMed

Gardner, Christina

2017-05-01

This article describes a man who presented to the ED in acute distress with signs and symptoms of sepsis, pneumonia, and a new petechial rash on his chest. He was eventually diagnosed with Rocky Mountain spotted fever. Aggressive treatment of sepsis and timely administration of empiric antibiotics were lifesaving in this situation.

Pathway cross-talk network analysis identifies critical pathways in neonatal sepsis.

PubMed

Meng, Yu-Xiu; Liu, Quan-Hong; Chen, Deng-Hong; Meng, Ying

2017-06-01

Despite advances in neonatal care, sepsis remains a major cause of morbidity and mortality in neonates worldwide. Pathway cross-talk analysis might contribute to the inference of the driving forces in bacterial sepsis and facilitate a better understanding of underlying pathogenesis of neonatal sepsis. This study aimed to explore the critical pathways associated with the progression of neonatal sepsis by the pathway cross-talk analysis. By integrating neonatal transcriptome data with known pathway data and protein-protein interaction data, we systematically uncovered the disease pathway cross-talks and constructed a disease pathway cross-talk network for neonatal sepsis. Then, attract method was employed to explore the dysregulated pathways associated with neonatal sepsis. To determine the critical pathways in neonatal sepsis, rank product (RP) algorithm, centrality analysis and impact factor (IF) were introduced sequentially, which synthetically considered the differential expression of genes and pathways, pathways cross-talks and pathway parameters in the network. The dysregulated pathways with the highest IF values as well as RP<0.01 were defined as critical pathways in neonatal sepsis. By integrating three kinds of data, only 6919 common genes were included to perform the pathway cross-talk analysis. By statistic analysis, a total of 1249 significant pathway cross-talks were selected to construct the pathway cross-talk network. Moreover, 47 dys-regulated pathways were identified via attract method, 20 pathways were identified under RP<0.01, and the top 10 pathways with the highest IF were also screened from the pathway cross-talk network. Among them, we selected 8 common pathways, i.e. critical pathways. In this study, we systematically tracked 8 critical pathways involved in neonatal sepsis by integrating attract method and pathway cross-talk network. These pathways might be responsible for the host response in infection, and of great value for advancing

Development and Validation of a Disease Severity Scoring Model for Pediatric Sepsis.

PubMed

Hu, Li; Zhu, Yimin; Chen, Mengshi; Li, Xun; Lu, Xiulan; Liang, Ying; Tan, Hongzhuan

2016-07-01

Multiple severity scoring systems have been devised and evaluated in adult sepsis, but a simplified scoring model for pediatric sepsis has not yet been developed. This study aimed to develop and validate a new scoring model to stratify the severity of pediatric sepsis, thus assisting the treatment of sepsis in children. Data from 634 consecutive patients who presented with sepsis at Children's hospital of Hunan province in China in 2011-2013 were analyzed, with 476 patients placed in training group and 158 patients in validation group. Stepwise discriminant analysis was used to develop the accurate discriminate model. A simplified scoring model was generated using weightings defined by the discriminate coefficients. The discriminant ability of the model was tested by receiver operating characteristic curves (ROC). The discriminant analysis showed that prothrombin time, D-dimer, total bilirubin, serum total protein, uric acid, PaO2/FiO2 ratio, myoglobin were associated with severity of sepsis. These seven variables were assigned with values of 4, 3, 3, 4, 3, 3, 3 respectively based on the standardized discriminant coefficients. Patients with higher scores had higher risk of severe sepsis. The areas under ROC (AROC) were 0.836 for accurate discriminate model, and 0.825 for simplified scoring model in validation group. The proposed disease severity scoring model for pediatric sepsis showed adequate discriminatory capacity and sufficient accuracy, which has important clinical significance in evaluating the severity of pediatric sepsis and predicting its progress.

Automated Detection of Sepsis Using Electronic Medical Record Data: A Systematic Review.

PubMed

Despins, Laurel A

Severe sepsis and septic shock are global issues with high mortality rates. Early recognition and intervention are essential to optimize patient outcomes. Automated detection using electronic medical record (EMR) data can assist this process. This review describes automated sepsis detection using EMR data. PubMed retrieved publications between January 1, 2005 and January 31, 2015. Thirteen studies met study criteria: described an automated detection approach with the potential to detect sepsis or sepsis-related deterioration in real or near-real time; focused on emergency department and hospitalized neonatal, pediatric, or adult patients; and provided performance measures or results indicating the impact of automated sepsis detection. Detection algorithms incorporated systemic inflammatory response and organ dysfunction criteria. Systems in nine studies generated study or care team alerts. Care team alerts did not consistently lead to earlier interventions. Earlier interventions did not consistently translate to improved patient outcomes. Performance measures were inconsistent. Automated sepsis detection is potentially a means to enable early sepsis-related therapy but current performance variability highlights the need for further research.

[Potential lowering of sepsis-related mortality via screening and implementation of guidelines].

PubMed

van Zanten, Arthur R H; Arbous, M Sesmu; Brinkman, Sylvia

2014-01-01

The incidence of sepsis continues to increase. However, over the past decade marked reductions in sepsis-related in-hospital mortality have been reported. Large variations in the presentation and severity of illness may be encountered in ICU patients with severe sepsis, which might preclude the success of screening and guideline programmes. However, the authors of this article were able to prove that a national programme involving screening and a package of interventions did lower relative in-hospital mortality by 16.7% over 3.5 years in 52 participating hospitals in the Netherlands. In-hospital mortality did not change in 30 non-participating hospitals. Therefore, the authors recommend implementing updated guidelines, sepsis quality indicators and programmes with a package of interventions to further reduce sepsis mortality. Furthermore, additional research on long term consequences in sepsis survivors is warranted.

Objective Sepsis Surveillance Using Electronic Clinical Data

PubMed Central

Rhee, Chanu; Kadri, Sameer; Huang, Susan S.; Murphy, Michael V.; Li, Lingling; Platt, Richard; Klompas, Michael

2016-01-01

OBJECTIVE To compare the accuracy of surveillance of severe sepsis using electronic health record clinical data vs claims and to compare incidence and mortality trends using both methods. DESIGN We created an electronic health record–based surveillance definition for severe sepsis using clinical indicators of infection (blood culture and antibiotic orders) and concurrent organ dysfunction (vasopressors, mechanical ventilation, and/or abnormal laboratory values). We reviewed 1,000 randomly selected medical charts to characterize the definition’s accuracy and stability over time compared with a claims-based definition requiring infection and organ dysfunction codes. We compared incidence and mortality trends from 2003–2012 using both methods. SETTING Two US academic hospitals. PATIENTS Adult inpatients. RESULTS The electronic health record–based clinical surveillance definition had stable and high sensitivity over time (77% in 2003–2009 vs 80% in 2012, P=.58) whereas the sensitivity of claims increased (52% in 2003–2009 vs 67% in 2012, P=.02). Positive predictive values for claims and clinical surveillance definitions were comparable (55% vs 53%, P=.65) and stable over time. From 2003 to 2012, severe sepsis incidence imputed from claims rose by 72% (95% CI, 57%–88%) and absolute mortality declined by 5.4% (95% CI, 4.6%–6.7%). In contrast, incidence using the clinical surveillance definition increased by 7.7% (95% CI, −1.1% to 17%) and mortality declined by 1.7% (95% CI, 1.1%–2.3%). CONCLUSIONS Sepsis surveillance using clinical data is more sensitive and more stable over time compared with claims and can be done electronically. This may enable more reliable estimates of sepsis burden and trends. PMID:26526737

Sepsis and Critical Illness Research Center investigators: protocols and standard operating procedures for a prospective cohort study of sepsis in critically ill surgical patients

PubMed Central

Loftus, Tyler J; Mira, Juan C; Ozrazgat-Baslanti, Tezcan; Ghita, Gabriella L; Wang, Zhongkai; Stortz, Julie A; Brumback, Babette A; Bihorac, Azra; Segal, Mark S; Anton, Stephen D; Leeuwenburgh, Christiaan; Mohr, Alicia M; Efron, Philip A; Moldawer, Lyle L; Moore, Frederick A; Brakenridge, Scott C

2017-01-01

Introduction Sepsis is a common, costly and morbid cause of critical illness in trauma and surgical patients. Ongoing advances in sepsis resuscitation and critical care support strategies have led to improved in-hospital mortality. However, these patients now survive to enter state of chronic critical illness (CCI), persistent low-grade organ dysfunction and poor long-term outcomes driven by the persistent inflammation, immunosuppression and catabolism syndrome (PICS). The Sepsis and Critical Illness Research Center (SCIRC) was created to provide a platform by which the prevalence and pathogenesis of CCI and PICS may be understood at a mechanistic level across multiple medical disciplines, leading to the development of novel management strategies and targeted therapies. Methods Here, we describe the design, study cohort and standard operating procedures used in the prospective study of human sepsis at a level 1 trauma centre and tertiary care hospital providing care for over 2600 critically ill patients annually. These procedures include implementation of an automated sepsis surveillance initiative, augmentation of clinical decisions with a computerised sepsis protocol, strategies for direct exportation of quality-filtered data from the electronic medical record to a research database and robust long-term follow-up. Ethics and dissemination This study has been registered at ClinicalTrials.gov, approved by the University of Florida Institutional Review Board and is actively enrolling subjects. Dissemination of results is forthcoming. PMID:28765125

Autophagy and skeletal muscles in sepsis.

PubMed

Mofarrahi, Mahroo; Sigala, Ioanna; Guo, Yeting; Godin, Richard; Davis, Elaine C; Petrof, Basil; Sandri, Marco; Burelle, Yan; Hussain, Sabah N A

2012-01-01

Mitochondrial injury develops in skeletal muscles during the course of severe sepsis. Autophagy is a protein and organelle recycling pathway which functions to degrade or recycle unnecessary, redundant, or inefficient cellular components. No information is available regarding the degree of sepsis-induced mitochondrial injury and autophagy in the ventilatory and locomotor muscles. This study tests the hypotheses that the locomotor muscles are more prone to sepsis-induced mitochondrial injury, depressed biogenesis and autophagy induction compared with the ventilatory muscles. Adult male C57/Bl6 mice were injected with i.p. phosphate buffered saline (PBS) or E. coli lipopolysaccharide (LPS, 20 mg/kg) and sacrificed 24 h later. The tibialis anterior (TA), soleus (SOLD) and diaphragm (DIA) muscles were quickly excised and examined for mitochondrial morphological injury, Ca(++) retention capacity and biogenesis. Autophagy was detected with electron microscopy, lipidation of Lc3b proteins and by measuring gene expression of several autophagy-related genes. Electron microscopy revealed ultrastructural injuries in the mitochondria of each muscle, however, injuries were more severe in the TA and SOL muscles than they were in the DIA. Gene expressions of nuclear and mitochondrial DNA transcription factors and co-activators (indicators of biogenesis) were significantly depressed in all treated muscles, although to a greater extent in the TA and SOL muscles. Significant autophagosome formation, Lc3b protein lipidation and upregulation of autophagy-related proteins were detected to a greater extent in the TA and SOL muscles and less so in the DIA. Lipidation of Lc3b and the degree of induction of autophagy-related proteins were significantly blunted in mice expressing a muscle-specific IκBα superrepresor. We conclude that locomotor muscles are more prone to sepsis-induced mitochondrial injury, decreased biogenesis and increased autophagy compared with the ventilatory muscles

Autophagy and Skeletal Muscles in Sepsis

PubMed Central

Mofarrahi, Mahroo; Sigala, Ioanna; Guo, Yeting; Godin, Richard; Davis, Elaine C.; Petrof, Basil; Sandri, Marco

2012-01-01

Background Mitochondrial injury develops in skeletal muscles during the course of severe sepsis. Autophagy is a protein and organelle recycling pathway which functions to degrade or recycle unnecessary, redundant, or inefficient cellular components. No information is available regarding the degree of sepsis-induced mitochondrial injury and autophagy in the ventilatory and locomotor muscles. This study tests the hypotheses that the locomotor muscles are more prone to sepsis-induced mitochondrial injury, depressed biogenesis and autophagy induction compared with the ventilatory muscles. Methodology/Principal Findings Adult male C57/Bl6 mice were injected with i.p. phosphate buffered saline (PBS) or E. coli lipopolysaccharide (LPS, 20 mg/kg) and sacrificed 24 h later. The tibialis anterior (TA), soleus (SOLD) and diaphragm (DIA) muscles were quickly excised and examined for mitochondrial morphological injury, Ca++ retention capacity and biogenesis. Autophagy was detected with electron microscopy, lipidation of Lc3b proteins and by measuring gene expression of several autophagy-related genes. Electron microscopy revealed ultrastructural injuries in the mitochondria of each muscle, however, injuries were more severe in the TA and SOL muscles than they were in the DIA. Gene expressions of nuclear and mitochondrial DNA transcription factors and co-activators (indicators of biogenesis) were significantly depressed in all treated muscles, although to a greater extent in the TA and SOL muscles. Significant autophagosome formation, Lc3b protein lipidation and upregulation of autophagy-related proteins were detected to a greater extent in the TA and SOL muscles and less so in the DIA. Lipidation of Lc3b and the degree of induction of autophagy-related proteins were significantly blunted in mice expressing a muscle-specific IκBα superrepresor. Conclusion/Significance We conclude that locomotor muscles are more prone to sepsis-induced mitochondrial injury, decreased biogenesis

Prevalence and Characteristics of Phantom Limb Pain and Residual Limb Pain in the Long Term after Upper Limb Amputation

ERIC Educational Resources Information Center

Desmond, Deirdre M.; MacLachlan, Malcolm

2010-01-01

This study aims to describe the prevalence and characteristics of phantom limb pain and residual limb pain after upper limb amputation. One-hundred and forty-one participants (139 males; mean age 74.8 years; mean time since amputation 50.1 years) completed a self-report questionnaire assessing residual and phantom limb pain experience. Prevalence…

Assessment of Clinical Criteria for Sepsis

PubMed Central

Seymour, Christopher W.; Liu, Vincent X.; Iwashyna, Theodore J.; Brunkhorst, Frank M.; Rea, Thomas D.; Scherag, André; Rubenfeld, Gordon; Kahn, Jeremy M.; Shankar-Hari, Manu; Singer, Mervyn; Deutschman, Clifford S.; Escobar, Gabriel J.; Angus, Derek C.

2016-01-01

IMPORTANCE The Third International Consensus Definitions Task Force defined sepsis as “life-threatening organ dysfunction due to a dysregulated host response to infection.” The performance of clinical criteria for this sepsis definition is unknown. OBJECTIVE To evaluate the validity of clinical criteria to identify patients with suspected infection who are at risk of sepsis. DESIGN, SETTINGS, AND POPULATION Among 1.3 million electronic health record encounters from January 1, 2010, to December 31, 2012, at 12 hospitals in southwestern Pennsylvania, we identified those with suspected infection in whom to compare criteria. Confirmatory analyses were performed in 4 data sets of 706 399 out-of-hospital and hospital encounters at 165 US and non-US hospitals ranging from January 1, 2008, until December 31, 2013. EXPOSURES Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score, systemic inflammatory response syndrome (SIRS) criteria, Logistic Organ Dysfunction System (LODS) score, and a new model derived using multivariable logistic regression in a split sample, the quick Sequential [Sepsis-related] Organ Failure Assessment (qSOFA) score (range, 0–3 points, with 1 point each for systolic hypotension [≤100 mm Hg], tachypnea [≥22/min], or altered mentation). MAIN OUTCOMES AND MEASURES For construct validity, pairwise agreement was assessed. For predictive validity, the discrimination for outcomes (primary: in-hospital mortality; secondary: in-hospital mortality or intensive care unit [ICU] length of stay ≥3 days) more common in sepsis than uncomplicated infection was determined. Results were expressed as the fold change in outcome over deciles of baseline risk of death and area under the receiver operating characteristic curve (AUROC). RESULTS In the primary cohort, 148 907 encounters had suspected infection (n = 74 453 derivation; n = 74 454 validation), of whom 6347 (4%) died. Among ICU encounters in the validation cohort (n = 7932 with suspected

The Immune System’s Role in Sepsis Progression, Resolution and Long-Term Outcome

PubMed Central

Delano, Matthew J.; Ward, Peter A.

2016-01-01

SUMMARY Sepsis occurs when an infection exceeds local tissue containment and induces a series of dysregulated physiologic responses that result in organ dysfunction. A subset of patients with sepsis progress to septic shock, defined by profound circulatory, cellular, and metabolic abnormalities, and associated with a greater mortality. Historically, sepsis-induced organ dysfunction and lethality were attributed to the complex interplay between the initial inflammatory and later anti-inflammatory responses. With advances in intensive care medicine and goal-directed interventions, early 30-day sepsis mortality has diminished, only to steadily escalate long after “recovery” from acute events. Since so many sepsis survivors succumb later to persistent, recurrent, nosocomial and secondary infections, many investigators have turned their attention to the long-term sepsis-induced alterations in cellular immune function. Sepsis clearly alters the innate and adaptive immune responses for sustained periods of time after clinical recovery, with immune suppression, chronic inflammation, and persistence of bacterial representing such alterations. Understanding that sepsis-associated immune cell defects correlate with long-term mortality, more investigations have centered on the potential for immune modulatory therapy to improve long term patient outcomes. These efforts are focused on more clearly defining and effectively reversing the persistent immune cell dysfunction associated with long-term sepsis mortality. PMID:27782333

[Clinical study on sepsis in 2 pediatric intensive care units in Beijing].

PubMed

2012-03-01

To investigate the incidence, mortality, causes and risk factors of sepsis in children in pediatric intensive care units (PICU) in Beijing through large sample prospective clinical research. From 1st November 2008 to 31st December 2009, all patients aged from 29 days to 18 years admitted to PICU of the two children's hospitals in Beijing were surveyed. Patients who met the conditions of Chinese pediatric critical illness score (PCIS) < 90 or American guidelines for PICU admission were defined as critically ill cases. According to the definitions of sepsis of 2005 international pediatric sepsis consensus conference and 2006 Chinese Medical Association meeting, sepsis, sever sepsis, and septic shock cases were selected from these critically ill patients. The qualified subjects were surveyed by questionnaire until discharge or death the data were analyzed by SPSS. A total of 1531 of PICU admissions were enrolled within a 14-month period, of whom 1250 met the criteria of critically ill case; 486 developed sepsis, of whom 55 died. The morbidity of sepsis for all in critically ill patients in PICU was 38.9% (486/1250) and the mortality was 11.3% (55/486). The morbidity of sepsis, severe sepsis and septic shock in these PICU was 25.5% (319/1250), 10.3% (129/1250), 3.0% (38/1250) and the mortality was 2.2% (7/319), 23.3% (30/129), and 47.4% (18/38), respectively. The proportion of less than 3 years old was 75.5% (367/486). Respiratory system diseases (71.8%), such as pneumonia (63.6%), were the underlying primary infectious diseases of sepsis. Bacterial etiology accounted for 64.1% of the cases with sepsis with definite etiological test results. The proportion of gram-positive bacteria and gram-negative bacteria were 46.1% and 53.9%, respectively. PCIS and disease severity were negatively correlated (r = -0.583, P < 0.01). Multiple stepwise logistic regression analysis showed that depressed PCIS and use of mechanical ventilation were the risk factors for death. Average

Clinical, laboratory, and hemostatic findings in cats with naturally occurring sepsis.

PubMed

Klainbart, Sigal; Agi, Limor; Bdolah-Abram, Tali; Kelmer, Efrat; Aroch, Itamar

2017-11-01

OBJECTIVE To characterize clinical and laboratory findings in cats with naturally occurring sepsis, emphasizing hemostasis-related findings, and evaluate these variables for associations with patient outcomes. DESIGN Prospective, observational, clinical study. ANIMALS 31 cats with sepsis and 33 healthy control cats. PROCEDURES Data collected included history; clinical signs; results of hematologic, serum biochemical, and hemostatic tests; diagnosis; and outcome (survival vs death during hospitalization or ≤ 30 days after hospital discharge). Differences between cats with and without sepsis and associations between variables of interest and death were analyzed statistically. RESULTS The sepsis group included cats with pyothorax (n = 10), septic peritonitis (7), panleukopenia virus infection (5), bite wounds (5), abscesses and diffuse cellulitis (3), and pyometra (1). Common clinical abnormalities included dehydration (21 cats), lethargy (21), anorexia (18), pale mucous membranes (15), and dullness (15). Numerous clinicopathologic abnormalities were identified in cats with sepsis; novel findings included metarubricytosis, hypertriglyceridemia, and high circulating muscle enzyme activities. Median activated partial thromboplastin time and plasma D-dimer concentrations were significantly higher, and total protein C and antithrombin activities were significantly lower, in the sepsis group than in healthy control cats. Disseminated intravascular coagulopathy was uncommon (4/22 [18%] cats with sepsis). None of the clinicopathologic abnormalities were significantly associated with death on multivariate analysis. CONCLUSIONS AND CLINICAL RELEVANCE Cats with sepsis had multiple hematologic, biochemical, and hemostatic abnormalities on hospital admission, including several findings suggestive of hemostatic derangement. Additional research including larger numbers of cats is needed to further investigate these findings and explore associations with outcome.

Limb deficiency and prosthetic management. 2. Aging with limb loss.

PubMed

Flood, Katherine M; Huang, Mark E; Roberts, Toni L; Pasquina, Paul F; Nelson, Virginia S; Bryant, Phillip R

2006-03-01

This self-directed learning module highlights the issues faced by people aging with limb loss. It is part of the study guide on limb deficiency and vascular rehabilitation in the Self-Directed Physiatric Education Program for practitioners and trainees in physical medicine and rehabilitation. This article specifically focuses on the impact that limb loss has on health and physical function throughout the life span. Case examples are used to illustrate what effect limb loss in childhood or young adulthood has on the incidence and management of new impairments or disease processes commonly associated with aging. To discuss the impact of early-life limb loss on the incidence and management of physiologic and functional changes associated with aging.

Novel insights for systemic inflammation in sepsis and hemorrhage.

PubMed

Cai, Bolin; Deitch, Edwin A; Ulloa, Luis

2010-01-01

The inflammatory responses in sepsis and hemorrhage remain a major cause of death. Clinically, it is generally accepted that shock in sepsis or hemorrhage differs in its mechanisms. However, the recognition of inflammatory cytokines as a common lethal pathway has become consent. Proinflammatory cytokines such as tumor necrosis factor (TNF) or high-mobility group box1 (HMGB1) are fanatically released and cause lethal multiorgan dysfunction. Inhibition of these cytokines can prevent the inflammatory responses and organ damage. In seeking potential anti-inflammatory strategies, we reported that ethyl pyruvate and alpha7 nicotinic acetylcholine receptor (alpha7nAChR) agonists effectively restrained cytokine production to provide therapeutic benefits in both experimental sepsis and hemorrhage. Here, we review the inflammatory responses and the anti-inflammatory strategies in experimental models of sepsis and hemorrhage, as they may have a consistent inflammatory pathway in spite of their different pathophysiological processes.

Community-onset sepsis and its public health burden: a systematic review.

PubMed

Tsertsvadze, Alexander; Royle, Pam; Seedat, Farah; Cooper, Jennifer; Crosby, Rebecca; McCarthy, Noel

2016-05-18

Sepsis is a life-threatening condition and major contributor to public health and economic burden in the industrialised world. The difficulties in accurate diagnosis lead to great variability in estimates of sepsis incidence. There has been even greater uncertainty regarding the incidence of and risk factors for community-onset sepsis (COS). We systematically reviewed the recent evidence on the incidence and risk factors of COS in high income countries (North America, Australasia, and North/Western Europe). Cohort and case-control studies were eligible for inclusion. Medline and Embase databases were searched from 2002 onwards. References of relevant publications were hand-searched. Two reviewers screened titles/abstracts and full-texts independently. One reviewer extracted data and appraised studies which were cross-checked by independent reviewers. Disagreements were resolved via consensus. Odds ratios (ORs) and 95 percent confidence intervals (95 % CIs) were ascertained by type of sepsis (non-severe, severe, and septic shock). Ten cohort and 4 case-control studies were included. There was a wide variation in the incidence (# cases per 100,000 per year) of non-severe sepsis (range: 64-514), severe sepsis (range: 40-455), and septic shock (range: 9-31). Heterogeneity precluded statistical pooling. Two cohort and 4 case-control studies reported risk factors for sepsis. In one case-control and one cohort study, older age and diabetes were associated with increased risk of sepsis. The same case-control study showed an excess risk for sepsis in participants with clinical conditions (e.g., immunosuppression, lung disease, and peripheral artery disease). In one cohort study, higher risk of sepsis was associated with being a nursing home resident (OR = 2.60, 95 % CI: 1.20, 5.60) and in the other cohort study with being physically inactive (OR = 1.33, 95 % CI: 1.13, 1.56) and smoking tobacco (OR = 1.85, 95 % CI: 1.54, 2.22). The evidence on sex, ethnicity, statin use, and

In Search of a Cure for Sepsis: Taming the Monster in Critical Care Medicine.

PubMed

Okeke, Emeka B; Uzonna, Jude E

2016-01-01

In spite of over half a century of research, sepsis still constitutes a major problem in health care delivery. Although advances in research have significantly increased our knowledge of the pathogenesis of sepsis and resulted in better prognosis and improved survival outcome, sepsis still remains a major challenge in modern medicine with an increase in occurrence predicted and a huge socioeconomic burden. It is generally accepted that sepsis is due to an initial hyperinflammatory response. However, numerous efforts aimed at targeting the proinflammatory cytokine network have been largely unsuccessful and the search for novel potential therapeutic targets continues. Recent studies provide compelling evidence that dysregulated anti-inflammatory responses may also contribute to sepsis mortality. Our previous studies on the role of regulatory T cells and phosphoinositide 3-kinases in sepsis highlight immunological approaches that could be explored for sepsis therapy. In this article, we review the current and emerging concepts in sepsis, highlight novel potential therapeutic targets and immunological approaches for sepsis treatment and propose a biphasic treatment approach for management of the condition. © 2016 S. Karger AG, Basel.

Epidemiology and Changes in Mortality of Sepsis After the Implementation of Surviving Sepsis Campaign Guidelines.

PubMed

Herrán-Monge, Rubén; Muriel-Bombín, Arturo; García-García, Marta M; Merino-García, Pedro A; Martínez-Barrios, Miguel; Andaluz, David; Ballesteros, Juan Carlos; Domínguez-Berrot, Ana María; Moradillo-Gonzalez, Susana; Macías, Santiago; Álvarez-Martínez, Braulio; Fernández-Calavia, M José; Tarancón, Concepción; Villar, Jesús; Blanco, Jesús

2017-01-01

To determine the epidemiology and outcome of severe sepsis and septic shock after 9 years of the implementation of the Surviving Sepsis Campaign (SSC) and to build a mortality prediction model. This is a prospective, multicenter, observational study performed during a 5-month period in 2011 in a network of 11 intensive care units (ICUs). We compared our findings with those obtained in the same ICUs in a study conducted in 2002. The current cohort included 262 episodes of severe sepsis and/or septic shock, and the 2002 cohort included 324. The prevalence was 14% (95% confidence interval: 12.5-15.7) with no differences to 2002. The population-based incidence was 31 cases/100 000 inhabitants/year. Patients in 2011 had a significantly lower Acute Physiology and Chronic Health Evaluation II (APACHE II; 21.9 ± 6.6 vs 25.5 ± 7.07), Logistic Organ Dysfunction Score (5.6 ± 3.2 vs 6.3 ± 3.6), and Sequential Organ Failure Assessment (SOFA) scores on day 1 (8 ± 3.5 vs 9.6 ± 3.7; P < .01). The main source of infection was intraabdominal (32.5%) although microbiologic isolation was possible in 56.7% of cases. The 2011 cohort had a marked reduction in 48-hour (7% vs 14.8%), ICU (27.2% vs 48.2%), and in-hospital (36.7% vs 54.3%) mortalities. Most relevant factors associated with death were APACHE II score, age, previous immunosuppression and liver insufficiency, alcoholism, nosocomial infection, and Delta SOFA score. Although the incidence of sepsis/septic shock remained unchanged during a 10-year period, the implementation of the SSC guidelines resulted in a marked decrease in the overall mortality. The lower severity of patients on ICU admission and the reduced early mortality suggest an improvement in early diagnosis, better initial management, and earlier antibiotic treatment.

Novel hybrid technology for early diagnostics of sepsis

NASA Astrophysics Data System (ADS)

Saknite, Inga; Grabovskis, Andris; Kazune, Sigita; Rubins, Uldis; Marcinkevics, Zbignevs; Volceka, Karina; Kviesis-Kipge, Edgars; Spigulis, Janis

2017-02-01

Sepsis is a potentially fatal disease with mortality rate as high as 50% in patients with septic shock; mortality rate can increase by 7.6% per hour if appropriate treatment is not started. Internationally accepted guidelines for diagnosis of sepsis rely on vital sign monitoring and laboratory tests in order to recognize organ failure. This pilot study aims to explore the potential of hyperspectral and thermal imaging techniques to identify and quantify early alterations in skin oxygenation and perfusion induced by sepsis. The study comprises both physiological model experiments on healthy volunteers in a laboratory environment, as well as screening case series of patients with septic shock in the intensive care department. Hyperspectral imaging is used to determine one of the main characteristic visual signs of skin oxygenation abnormalities - skin mottling, whereas changes in peripheral perfusion have been visualized by thermal imaging as heterogeneous skin temperature areas. In order to mimic septic skin mottling in a reproducible way in laboratory environment, arterial occlusion provocation test was utilized on healthy volunteers. Visualization of oxygen saturation by hyperspectral imaging allows diagnosing microcirculatory alterations induced by sepsis earlier than visual assessment of mottling. Thermal images of sepsis patients in the clinic clearly reveal hotspots produced by perforating arteries, as well as cold regions of low blood supply. The results of this pilot study show that thermal imaging in combination with hyperspectral imaging allows the determination of oxygen supply and utilization in critically ill septic patients.

Culture-positive sepsis in neonatal camelids: 21 cases.

PubMed

Dolente, Brett A; Lindborg, Susan; Palmer, Jonathan E; Wilkins, Pamela A

2007-01-01

There is limited literature on neonatal bacterial sepsis in New World (NW) camelids. Bacterial culture-positive crias have clinical differences based on the specific bacterial genera isolated. Bacterial culture-positive NW camelid crias <21 days of age from 1990 to 2005 were included. Historic physical examination and cliniopathologic data were retrieved from medical records as were the identity and antibiograms of bacterial isolates. Cases were categorized by outcome (survival versus nonsurvival) and type of sepsis (gram-negative or gram-positive). Kruskal-Wallis and chi-square testing were used to evaluate differences between groups. Twenty-one crias met the inclusion criteria. Median age was 2 days. Failure of passive transfer was common. There were few differences identified on the basis of outcome or type of sepsis. Crias without gastrointestinal or central nervous system involvement survived in greater numbers. Forty-six percent of isolates were gram-positive. The most common isolates were the following: Escherichia coli, Enterococcus spp., Listeria monocytogenes, and Citrobacter spp. Overall survival was 67% (14/21). Crias with sepsis do not appear to present with major biochemical, hematologic, or blood gas abnormalities, potentially complicating diagnosis. Affected crias may not have localizing signs at presentation and are not usually febrile, although hypothermia, tachypnea, and tachycardia are relatively common. Total protein concentration was not a substitute for immunoglobulin G measurement in septic crias in this study. Familiarity with the clinical presentation and common pathogens isolated should improve early recognition and treatment and ultimately outcome of crias with sepsis.

A review of supernumerary and absent limbs and digits of the upper limb.

PubMed

Klaassen, Zachary; Choi, Monica; Musselman, Ruth; Eapen, Deborah; Tubbs, R Shane; Loukas, Marios

2012-03-01

For years people have been enamored by anomalies of the human limbs, particularly supernumerary and absent limbs and digits. Historically, there are a number of examples of such anomalies, including royal families of ancient Chaldea, tribes from Arabia, and examples from across nineteenth century Europe. The development of the upper limbs in a growing embryo is still being elucidated with the recent advent of homeobox genes, but researchers agree that upper limbs develop between stages 12-23 through a complex embryological process. Maternal thalidomide intake during limb development is known to cause limb reduction and subsequent amelia or phocomelia. Additionally, a number of clinical reports have illustrated different limb anomaly cases, with each situation unique in phenotype and developmental abnormality. Supernumerary and absent limbs and digits are not unique to humans, and a number of animal cases have also been reported. This review of the literature illustrates the historical, anatomical, and clinical aspects of supernumerary and absent limbs and digits for the upper limb.

Betacaryophyllene - A phytocannabinoid as potential therapeutic modality for human sepsis?

PubMed

Meza, Angel; Lehmann, Christian

2018-01-01

Sepsis is a clinical condition resulting from a dysregulated immune response to an infection that leads to organ dysfunction. Despite numerous efforts to optimize treatment, sepsis remains to be the main cause of death in most intensive care units. The endogenous cannabinoid system (ECS) plays an important role in inflammation. Cannabinoid receptor 2 (CB2R) activation is immunosuppressive, which might be beneficial during the hyper-inflammatory phase of sepsis. Beta-caryophyllene (BCP) is a non-psychoactive natural cannabinoid (phytocannabinoid) found in Cannabis sativa and in essential oils of spices and food plants, that acts as a selective agonist of CB2R. We propose BCP administration as novel treatment to reduce hyper-inflammation in human sepsis. Copyright © 2017 Elsevier Ltd. All rights reserved.

SOMANZ guidelines for the investigation and management sepsis in pregnancy.

PubMed

Bowyer, Lucy; Robinson, Helen L; Barrett, Helen; Crozier, Timothy M; Giles, Michelle; Idel, Irena; Lowe, Sandra; Lust, Karin; Marnoch, Catherine A; Morton, Mark R; Said, Joanne; Wong, Maggie; Makris, Angela

2017-10-01

SOMANZ (Society of Obstetric Medicine Australia and New Zealand) has written a guideline to provide evidence-based guidance for the investigation and care of women with sepsis in pregnancy or the postpartum period. The guideline is evidence-based and incorporates recent changes in the definition of sepsis. The etiology, investigation and treatment of bacterial, viral and non-infective causes of sepsis are discussed. Obstetric considerations relevant to anaesthetic and intensive care treatment in sepsis are also addressed. A multi-disciplinary group of clinicians with experience in all aspects of the care of pregnant women have contributed to the development of the guidelines. This is an executive summary of the guidelines. © 2017 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Prophylactic antibiotics reduce sepsis after biopsy of the prostate.

PubMed

Hayatzaki, Khalilullah; Menne, Sveinar; Nielsen, Karsten

2014-11-01

Prostate cancer is the most common form of cancer in Danish men, and the incidence is rising. The diag-nosis is made by transrectal prostate biopsy guided by ultrasound. This procedure has several complications, the most severe being sepsis. In our department, this is sought prevented by administering the prophylactic antibiotics metronidazol and ciprofloxacin. This study examined the rate of sepsis in patients who had the procedure performed at our department. The electronic patient records of all patients who had transrectal ultrasound of the prostate with biopsies performed at the Department of Urology at Naestved Hospital in the period from 1 May 2009 to 31 May 2011 were examined, and all admissions to our department (or any department in the same region) due to sepsis within two weeks of the procedure were registered. A total of 438 patients had the procedure performed, some multiple times, which resulted in a total of 511 procedures. In all, four patients were later admitted due to sepsis, corresponding to 0.91%. Three of the patients had positive blood and urine cultures in which Escherichia coli resistant to ciprofloxacin were found, the last had been prescribed antibiotics by a general practitioner the previous day, and no bacteria could be cultured. The frequency of sepsis after transrectal needle biopsies from the prostate at our department was found to be below 1% in this study, which is comparable to international findings. Most of the cases of sepsis were related to ciprofloxacin-resistant bacteria. Further randomised studies are needed to investigate the ideal prophylactic regime. not relevant. not relevant.

Degree of agreement among sepsis diagnosis criteria in adult emergency room patients with infection

NASA Astrophysics Data System (ADS)

Sinto, R.; Chandra, A. T.; Lie, K. C.; Suwarto, S.

2018-03-01

The study on the degree of agreement among three established sepsis diagnosis criteria become the necessity to investigate the best sepsis diagnosis criteria in Indonesia further. A cross-sectional study of adult Emergency Room patients hospitalized with a diagnosis of infection in CiptoMangunkusumo Hospital, Indonesia was conducted during March and April 2017. We recorded diagnosis, gender, age, comorbidities, infection source, and origin. Every subject was classified into sepsis and non-sepsis based on 1991, 2001 and sepsis-3 criteria. Raw % and Kappa agreement coefficients (κ) were calculated according to previously established formula to measure the degree of agreement among three diagnostic criteria. As many as 278 subjects were included in this study. The raw % agreement and κ between 1991 and 2001 criteria is 69.07% and 0.34 respectively. The raw % agreement and κ between 2001 and sepsis-3 criteria is 56.12% and 0.15 respectively. The raw % agreement and κ between 1991 and sepsis-3 criteria is 48.19% and -0.02. In conclusions, there is afair agreement between 1991 and 2001 criteria, poor agreement between 2001 and sepsis-3 criteria, and poor disagreement between 1991 and sepsis-3 criteria. This necessitates further Indonesian study of the best diagnosis criteria to diagnose an infected patient with sepsis.

Metabolomics with Nuclear Magnetic Resonance Spectroscopy in a Drosophila melanogaster Model of Surviving Sepsis

PubMed Central

Bakalov, Veli; Amathieu, Roland; Triba, Mohamed N.; Clément, Marie-Jeanne; Reyes Uribe, Laura; Le Moyec, Laurence; Kaynar, Ata Murat

2016-01-01

Patients surviving sepsis demonstrate sustained inflammation, which has been associated with long-term complications. One of the main mechanisms behind sustained inflammation is a metabolic switch in parenchymal and immune cells, thus understanding metabolic alterations after sepsis may provide important insights to the pathophysiology of sepsis recovery. In this study, we explored metabolomics in a novel Drosophila melanogaster model of surviving sepsis using Nuclear Magnetic Resonance (NMR), to determine metabolite profiles. We used a model of percutaneous infection in Drosophila melanogaster to mimic sepsis. We had three experimental groups: sepsis survivors (infected with Staphylococcus aureus and treated with oral linezolid), sham (pricked with an aseptic needle), and unmanipulated (positive control). We performed metabolic measurements seven days after sepsis. We then implemented metabolites detected in NMR spectra into the MetExplore web server in order to identify the metabolic pathway alterations in sepsis surviving Drosophila. Our NMR metabolomic approach in a Drosophila model of recovery from sepsis clearly distinguished between all three groups and showed two different metabolomic signatures of inflammation. Sham flies had decreased levels of maltose, alanine, and glutamine, while their level of choline was increased. Sepsis survivors had a metabolic signature characterized by decreased glucose, maltose, tyrosine, beta-alanine, acetate, glutamine, and succinate. PMID:28009836

Plasma lactoferrin levels in newborn preterm infants with sepsis.

PubMed

Decembrino, Lidia; DeAmici, Mara; De Silvestri, Annalisa; Manzoni, Paolo; Paolillo, Piermichele; Stronati, Mauro

2017-12-01

Lactoferrin (Lf) is one of the major proteins of all exocrine secretions with a role in the antinfective process. Our aim was to evaluate how plasma Fl levels may change in response to infection in newborn preterm infants. A total of 15 (8 females, 7 males) newborn preterm infants with a postnatal age >72 h of life, underwent to blood culture and others markers of infection, for suspected sepsis, were enrolled in the study. We found that Lf serum concentration was significantly lowest in four neonates (26.7%) with confirmed sepsis than in 11 (73.3%) with clinical sepsis. The AUC was 0.90 (95%CI: 0.63-0.99). The optimal cutoff for Lf was <1.2 μg/ml with a sensibility of 100% and a specificity of 81.8%. Lf serum concentration was positively correlated with WBC or neutrophil (Spearman rho = 0.69 and 0.49, respectively). Serum Lf could prove a promising, sensitive and specific marker in the diagnostic approach to infants with suspected sepsis, thanks to its role in defense mechanisms and physiological functions of the immune system. Low levels of Lf in sepsis may suggest an immature response due to suboptimal leukocites activity in newborn preterm infants.

Functional outcomes in pediatric severe sepsis: further analysis of the researching severe sepsis and organ dysfunction in children: a global perspective trial.

PubMed

Farris, Reid W D; Weiss, Noel S; Zimmerman, Jerry J

2013-11-01

To evaluate risk factors for poor functional outcome in 28-day survivors after an episode of severe sepsis. Retrospective cohort study examining data from the Researching Severe Sepsis and Organ Dysfunction in Children: A Global Perspective trial (NCT00049764). One hundred and four pediatric centers in 18 countries. Children with severe sepsis who required both vasoactive-inotropic infusions and mechanical ventilation and who survived to 28 days (n = 384). None. Poor functional outcome was defined as a Pediatric Overall Performance Category score greater than or equal to 3 and an increase from baseline when measured 28 days after trial enrollment. Median Pediatric Overall Performance Category at enrollment was 1 (interquartile range, 1-2). Median Pediatric Overall Performance Category at 28 days was 2 (interquartile range, 1-4). Thirty-four percent of survivors had decline in their functional status at 28 days, and 18% were determined to have a "poor" functional outcome. Hispanic ethnicity was associated with poor functional outcome compared to the white referent group (risk ratio = 1.9; 95% CI: 1.0-3.0). Clinical factors associated with increased risk of poor outcome included CNS and intra-abdominal infection sources compared to the lung infection referent category (risk ratio = 3.3; 95% CI: 1.4-5.6 and 2.4; 95% CI: 1.0-4.5, respectively); a history of recent trauma (risk ratio = 3.9; 95% CI: 1.4-5.4); receipt of cardiopulmonary resuscitation prior to enrollment (risk ratio = 5.1; 95% CI: 2.9-5.7); and baseline Pediatric Risk of Mortality III score of 20-29 (risk ratio = 2.8; 95% CI: 1.2-5.2) and Pediatric Risk of Mortality III greater than or equal to 30 (risk ratio = 4.5; 95% CI: 1.6-8.0) compared to the referent group with Pediatric Risk of Mortality III scores of 0-9. In this sample of 28-day survivors of pediatric severe sepsis diminished functional status was common. This analysis provides evidence that particular patient characteristics and aspects of an

Designing and testing computer based screening engine for severe sepsis/septic shock.

PubMed

Herasevich, V; Afessa, B; Chute, C G; Gajic, O

2008-11-06

This study addresses the role of a sepsis "sniffer", an automatic screening tool for the timely identification of patients with severe sepsis/septic shock, based electronic medical records. During the two months prospective implementation in a medical intensive care unit, 37 of 320 consecutive patients developed severe sepsis/septic shock. The sniffer demonstrated a sensitivity of 48% and specificity of 86%, and positive predictive value 32%. Further improvements are needed prior to the implementation of sepsis sniffer in clinical practice and research.

DcR3, a new biomarker for sepsis, correlates with infection severity and procalcitonin.

PubMed

Gao, Liqin; Yang, Bin; Zhang, Hairong; Ou, Qishui; Lin, Yulan; Zhang, Mei; Zhang, Zhenhuan; Kim, Sunghee; Wu, Bing; Wang, Zeng; Fu, Lengxi; Lin, Jingan; Chen, Ruiqing; Lan, Ruilong; Chen, Junying; Chen, Wei; Chen, Long; Zhang, Hengshan; Han, Deping; Chen, Jingrong; Okunieff, Paul; Lin, Jianhua; Zhang, Lurong

2018-02-16

Early diagnosis of sepsis is critical for successful treatment. The clinical value of DcR3 in early diagnosis of sepsis was determined in a dynamic follow-up study. Alterations in plasma levels of DcR3, PCT, CRP, and IL-6 were measured by ELISA and compared among patients with sepsis ( n = 134), SIRS ( n = 60) and normal adults ( n = 50). Correlations and dynamic patterns among the biomarkers, APACHE II scores, clinical outcomes, and pathogens were also examined. Plasma DcR3 was significantly increased in sepsis compared to SIRS and normal adults (median 3.87 vs. 1.28 and 0.17 ng/ml). The elevated DcR3 could be detected in 97.60% sepsis patients 1-2 days prior to the result of blood culture reported. For diagnosis of sepsis, the sensitivity was 97.69% and specificity 98.04%; and for differential diagnosis of sepsis from SIRS, the sensitivity was 90.77% and specificity 98.40%. DcR3 level was positively correlated with severity of sepsis ( r s = 0.82). In 41 patients who died of sepsis, DcR3 elevated as early as 1-2 days before blood culture and peaked on day 3 after blood culture performed. In 90% of sepsis patients, the dynamic alteration pattern of DcR3 was identical to that of PCT, while pattern of 10% patients differed in which clinical data was consistent with DcR3. In 13% sepsis patients, while PCT remained normal, DcR3 levels were at a high level. DcR3 levels had no difference among various pathogens infected. DcR3, a new biomarker, will aid in early diagnosis of sepsis and monitoring its outcome, especially when sepsis patients were PCT negative.

Heparanase level and procoagulant activity are reduced in severe sepsis.

PubMed

Matan, Moshe; King, Daniel; Peled, Eli; Ackerman, Shanny; Bar-Lavi, Yaron; Brenner, Benjamin; Nadir, Yona

2018-02-01

During severe sepsis, levels and activity of all coagulation proteins are reduced. Heparanase is implicated in angiogenesis and tumor progression. We previously demonstrated that heparanase also affected the hemostatic system. It forms a complex and increases the activity of the blood coagulation initiator tissue factor. To evaluate heparanase levels and procoagulant activity as predictors of sepsis severity. Twenty-one patients with non-trauma, non-surgical sepsis admitted to the intensive care unit and 35 controls were recruited. Plasma samples were drawn from the study participants on days 1 and 7 following admission. Heparanase levels and procoagulant activity on day 1 were significantly reduced in patients compared to controls (P < .0001, P < .0001, respectively). Day 1 heparanase procoagulant activity ≥350 ng/mL yielded a negative predictive value for severe sepsis of 89%. Additionally, heparanase procoagulant activity on day 7 correlated with the change in the APACHE score between days 1 and 7 (r = .66, P = .007). Heparanase procoagulant activity decreases during sepsis and returns to normal levels as soon as the patient recovers. Hence, it can be potentially used to predict the risk of severe sepsis. These findings need to be further explored in large-scale studies. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Improving Diagnosis of Sepsis After Burn Injury Using a Portable Sepsis Alert System

DTIC Science & Technology

vital signs of heart rate variability, regional tissue oxygenation, and noninvasive cardiac output can diagnose burn sepsis earlier, reducing...morbidity and mortality. Rationale: Heart Rate Variability (HRV), regional Tissue Oxygenation, and non-invasive Cardiac Output (CO), have shown promise in

The Rate of Sepsis in a National Pediatric Population, 2006 to 2012.

PubMed

Schuller, Kristin A; Hsu, Benson S; Thompson, Allyson B

2017-10-01

The rate of pediatric severe sepsis is reported to be on the rise in the United States, increasing by approximately 6000 cases annually. The goal of this study was to determine the rate of pediatric sepsis per 100 000 inpatient discharges over time. The 2006, 2009, and 2012 Agency for Healthcare Research and Quality Healthcare Cost Utilization Project Kid's Inpatient Databases were used to analyze the rate of sepsis in children over time. The rate of pediatric sepsis has increased over time from 92.8 per 100 000 in 2006 to 158.7 per 100 000 in 2012. Children less than a year old with Medicaid coverage and 3 or more procedures during hospitalization have significantly higher rates than their counterparts. This study helps clarify the population demographics that are at greater risk for sepsis infections. Understanding the at-risk population aids policymakers and care providers in targeting these populations and make drastic changes to sepsis policies.

Hyperglycemia and glycemic variability are associated with the severity of sepsis in nondiabetic subjects.

PubMed

Preechasuk, Lukana; Suwansaksri, Nattakarn; Ipichart, Nantawan; Vannasaeng, Sathit; Permpikul, Chairat; Sriwijitkamol, Apiradee

2017-04-01

The purpose was to compare glucose variability (GV) obtained via continuous glucose monitoring between nondiabetic sepsis patients and healthy subjects and to seek associations between GV and sepsis severity in nondiabetic sepsis patients. Nondiabetic sepsis inpatients and healthy controls received a 72-hour continuous glucose monitoring (iPro2, Medtronic) postadmission and post-oral glucose tolerance test, respectively. The mean glucose level (MGL) along with GV represented by standard deviation (SD) and the mean amplitude of glycemic excursion (MAGE) were calculated at 24 and 72 hours. Sepsis severity was evaluated with the Sepsis-related Organ Failure Assessment Score (SOFA). MGL and GV in patients with SOFA ≥9 and <9 were compared. Thirty nondiabetic sepsis and 10 healthy subjects were recruited. No differences were found between groups except for higher patient age in sepsis patients. The MGL and MAGE 72h of sepsis patients were significantly higher than those of healthy subjects. MGL and GV 24h were higher in patients with SOFA ≥9 than in patients with SOFA <9 (MGL 24h 195±17 vs 139±27, P<.001; SD 24h 32 [28, 36] vs 19 [5, 58], P=.02; and MAGE 24h 94 [58, 153] vs 54 [16, 179], P=.01). Nondiabetic sepsis patients had higher MGL and GV values than healthy subjects. MGL and GV 24h were associated with sepsis severity. Copyright © 2016 Elsevier Inc. All rights reserved.

Computer versus paper system for recognition and management of sepsis in surgical intensive care.

PubMed

Croft, Chasen A; Moore, Frederick A; Efron, Philip A; Marker, Peggy S; Gabrielli, Andrea; Westhoff, Lynn S; Lottenberg, Lawrence; Jordan, Janeen; Klink, Victoria; Sailors, R Matthew; McKinley, Bruce A

2014-02-01

A system to provide surveillance, diagnosis, and protocolized management of surgical intensive care unit (SICU) sepsis was undertaken as a performance improvement project. A system for sepsis management was implemented for SICU patients using paper followed by a computerized system. The hypothesis was that the computerized system would be associated with improved process and outcomes. A system was designed to provide early recognition and guide patient-specific management of sepsis including (1) modified early warning signs-sepsis recognition score (MEWS-SRS; summative point score of ranges of vital signs, mental status, white blood cell count; after every 4 hours) by bedside nurse; (2) suspected site assessment (vascular access, lung, abdomen, urinary tract, soft tissue, other) at bedside by physician or extender; (3) sepsis management protocol (replicable, point-of-care decisions) at bedside by nurse, physician, and extender. The system was implemented first using paper and then a computerized system. Sepsis severity was defined using standard criteria. In January to May 2012, a paper system was used to manage 77 consecutive sepsis encounters (3.9 ± 0.5 cases per week) in 65 patients (77% male; age, 53 ± 2 years). In June to December 2012, a computerized system was used to manage 132 consecutive sepsis encounters (4.4 ± 0.4 cases per week) in 119 patients (63% male; age, 58 ± 2 years). MEWS-SRS elicited 683 site assessments, and 201 had sepsis diagnosis and protocol management. The predominant site of infection was abdomen (paper, 58%; computer, 53%). Recognition of early sepsis tended to occur more using the computerized system (paper, 23%; computer, 35%). Hospital mortality rate for surgical ICU sepsis (paper, 20%; computer, 14%) was less with the computerized system. A computerized sepsis management system improves care process and outcome. Early sepsis is recognized and managed with greater frequency compared with severe sepsis or septic shock. The system

Clinical review: Extracorporeal blood purification in severe sepsis

PubMed Central

Venkataraman, Ramesh; Subramanian, Sanjay; Kellum, John A

2003-01-01

Sepsis and septic shock are the leading causes of acute renal failure, multiple organ system dysfunction, and death in the intensive care unit. The pathogenesis of sepsis is complex and comprises a mosaic of interconnected pathways. Several attempts to improve patient outcomes by targeting specific components of this network have been unsuccessful. For these reasons, the ideal immunomodulating strategy would be one that restores immunologic stability rather than blindly inhibiting or stimulating one or another component of this complex network. Hence, the recent focus of immunomodulatory therapy in sepsis has shifted to nonspecific methods of influencing the entire inflammatory response without suppressing it. Here, we discuss the various modalities of extracorporeal blood purification, the existing evidence, and future prospects. PMID:12720560

Septris: a novel, mobile, online, simulation game that improves sepsis recognition and management.

PubMed

Evans, Kambria H; Daines, William; Tsui, Jamie; Strehlow, Matthew; Maggio, Paul; Shieh, Lisa

2015-02-01

Annually affecting over 18 million people worldwide, sepsis is common, deadly, and costly. Despite significant effort by the Surviving Sepsis Campaign and other initiatives, sepsis remains underrecognized and undertreated. Research indicates that educating providers may improve sepsis diagnosis and treatment; thus, the Stanford School of Medicine has developed a mobile-accessible, case-based, online game entitled Septris (http://med.stanford.edu/septris/). Septris, launched online worldwide in December 2011, takes an innovative approach to teaching early sepsis identification and evidence-based management. The free gaming platform leverages the massive expansion over the past decade of smartphones and the popularity of noneducational gaming.The authors sought to assess the game's dissemination and its impact on learners' sepsis-related knowledge, skills, and attitudes. In 2012, the authors trained Stanford pregraduate (clerkship) and postgraduate (resident) medical learners (n = 156) in sepsis diagnosis and evidence-based practices via 20 minutes of self-directed game play with Septris. The authors administered pre- and posttests. By October 2014, Septris garnered over 61,000 visits worldwide. After playing Septris, both pre- and postgraduate groups improved their knowledge on written testing in recognizing and managing sepsis (P < .001). Retrospective self-reporting on their ability to identify and manage sepsis also improved (P < .001). Over 85% of learners reported that they would or would maybe recommend Septris. Future evaluation of Septris should assess its effectiveness among different providers, resource settings, and cultures; generate information about how different learners make clinical decisions; and evaluate the correlation of game scores with sepsis knowledge.

Gene Network for Identifying the Entropy Changes of Different Modules in Pediatric Sepsis.

PubMed

Yang, Jing; Zhang, Pingli; Wang, Lumin

2016-01-01

Pediatric sepsis is a disease that threatens life of children. The incidence of pediatric sepsis is higher in developing countries due to various reasons, such as insufficient immunization and nutrition, water and air pollution, etc. Exploring the potential genes via different methods is of significance for the prevention and treatment of pediatric sepsis. This study aimed to identify potential genes associated with pediatric sepsis utilizing analysis of gene network and entropy. The mRNA expression in the blood samples collected from 20 septic children and 30 healthy controls was quantified by using Affymetrix HG-U133A microarray. Two condition-specific protein-protein interaction networks (PINs), one for the healthy control and the other one for the children with sepsis, were deduced by combining the fundamental human PINs with gene expression profiles in the two phenotypes. Subsequently, distinct modules from the two conditional networks were extracted by adopting a maximal clique-merging approach. Delta entropy (ΔS) was calculated between sepsis and control modules. Then, key genes displaying changes in gene composition were identified by matching the control and sepsis modules. Two objective modules were obtained, in which ribosomal protein RPL4 and RPL9 as well as TOP2A were probably considered as the key genes differentiating sepsis from healthy controls. According to previous reports and this work, TOP2A is the potential gene therapy target for pediatric sepsis. The relationship between pediatric sepsis and RPL4 and RPL9 needs further investigation. © 2016 The Author(s) Published by S. Karger AG, Basel.

The Timing of Early Antibiotics and Hospital Mortality in Sepsis.

PubMed

Liu, Vincent X; Fielding-Singh, Vikram; Greene, John D; Baker, Jennifer M; Iwashyna, Theodore J; Bhattacharya, Jay; Escobar, Gabriel J

2017-10-01

Prior sepsis studies evaluating antibiotic timing have shown mixed results. To evaluate the association between antibiotic timing and mortality among patients with sepsis receiving antibiotics within 6 hours of emergency department registration. Retrospective study of 35,000 randomly selected inpatients with sepsis treated at 21 emergency departments between 2010 and 2013 in Northern California. The primary exposure was antibiotics given within 6 hours of emergency department registration. The primary outcome was adjusted in-hospital mortality. We used detailed physiologic data to quantify severity of illness within 1 hour of registration and logistic regression to estimate the odds of hospital mortality based on antibiotic timing and patient factors. The median time to antibiotic administration was 2.1 hours (interquartile range, 1.4-3.1 h). The adjusted odds ratio for hospital mortality based on each hour of delay in antibiotics after registration was 1.09 (95% confidence interval [CI], 1.05-1.13) for each elapsed hour between registration and antibiotic administration. The increase in absolute mortality associated with an hour's delay in antibiotic administration was 0.3% (95% CI, 0.01-0.6%; P = 0.04) for sepsis, 0.4% (95% CI, 0.1-0.8%; P = 0.02) for severe sepsis, and 1.8% (95% CI, 0.8-3.0%; P = 0.001) for shock. In a large, contemporary, and multicenter sample of patients with sepsis in the emergency department, hourly delays in antibiotic administration were associated with increased odds of hospital mortality even among patients who received antibiotics within 6 hours. The odds increased within each sepsis severity strata, and the increased odds of mortality were greatest in septic shock.

Identifying patients with severe sepsis using administrative claims: patient-level validation of the angus implementation of the international consensus conference definition of severe sepsis.

PubMed

Iwashyna, Theodore J; Odden, Andrew; Rohde, Jeffrey; Bonham, Catherine; Kuhn, Latoya; Malani, Preeti; Chen, Lena; Flanders, Scott

2014-06-01

Severe sepsis is a common and costly problem. Although consistently defined clinically by consensus conference since 1991, there have been several different implementations of the severe sepsis definition using ICD-9-CM codes for research. We conducted a single center, patient-level validation of 1 common implementation of the severe sepsis definition, the so-called "Angus" implementation. Administrative claims for all hospitalizations for patients initially admitted to general medical services from an academic medical center in 2009-2010 were reviewed. On the basis of ICD-9-CM codes, hospitalizations were sampled for review by 3 internal medicine-trained hospitalists. Chart reviews were conducted with a structured instrument, and the gold standard was the hospitalists' summary clinical judgment on whether the patient had severe sepsis. Three thousand one hundred forty-six (13.5%) hospitalizations met ICD-9-CM criteria for severe sepsis by the Angus implementation (Angus-positive) and 20,142 (86.5%) were Angus-negative. Chart reviews were performed for 92 randomly selected Angus-positive and 19 randomly-selected Angus-negative hospitalizations. Reviewers had a κ of 0.70. The Angus implementation's positive predictive value was 70.7% [95% confidence interval (CI): 51.2%, 90.5%]. The negative predictive value was 91.5% (95% CI: 79.0%, 100%). The sensitivity was 50.4% (95% CI: 14.8%, 85.7%). Specificity was 96.3% (95% CI: 92.4%, 100%). Two alternative ICD-9-CM implementations had high positive predictive values but sensitivities of <20%. The Angus implementation of the international consensus conference definition of severe sepsis offers a reasonable but imperfect approach to identifying patients with severe sepsis when compared with a gold standard of structured review of the medical chart by trained hospitalists.

Identifying Patients with Severe Sepsis Using Administrative Claims: Patient-Level Validation of the Angus Implementation of the International Consensus Conference Definition of Severe Sepsis

PubMed Central

Iwashyna, Theodore J.; Odden, Andrew; Rohde, Jeffrey; Bonham, Catherine; Kuhn, Latoya; Malani, Preeti; Chen, Lena; Flanders, Scott

2012-01-01

Background Severe sepsis is a common and costly problem. Although consistently defined clinically by consensus conference since 1991, there have been several different implementations of the severe sepsis definition using ICD-9-CM codes for research. We conducted a single center, patient-level validation of one common implementation of the severe sepsis definition, the so-called “Angus” implementation. Methods Administrative claims for all hospitalizations for patients initially admitted to general medical services from an academic medical center in 2009–2010 were reviewed. On the basis of ICD-9-CM codes, hospitalizations were sampled for review by three internal medicine-trained hospitalists. Chart reviews were conducted with a structured instrument, and the gold standard was the hospitalists’ summary clinical judgment on whether the patient had severe sepsis. Results 3,146 (13.5%) hospitalizations met ICD-9-CM criteria for severe sepsis by the Angus implementation (“Angus-positive”) and 20,142 (86.5%) were Angus-negative. Chart reviews were performed for 92 randomly-selected Angus-positive and 19 randomly-selected Angus-negative hospitalizations. Reviewers had a kappa of 0.70. The Angus implementation’s positive predictive value (PPV) was 70.7% (95%CI: 51.2%, 90.5%). The negative predictive value was 91.5% (95%CI: 79.0%, 100%). The sensitivity was 50.4% (95%CI: 14.8%, 85.7%). Specificity was 96.3% (95%CI: 92.4%, 100%). Two alternative ICD-9-CM implementations had high PPVs but sensitivities of less than 20%. Conclusions The Angus implementation of the international consensus conference definition of severe sepsis offers a reasonable but imperfect approach to identifying patients with severe sepsis when compared with a gold standard of structured review of the medical chart by trained hospitalists. PMID:23001437

Immunotherapy in the management of sepsis.

PubMed Central

Fagan, E. A.; Singer, M.

1995-01-01

The pathophysiological effects of severe sepsis, septic shock and related syndromes result from tissues damaged by the uncontrolled production of the mediators of inflammation. Early deaths are related primarily to the acute effects of the systemic inflammatory response. Later deaths are related more closely to the consequences of multiple organ dysfunction. Monoclonal antibodies and other immunotherapies have been developed against bacterial products, cytokines and other mediators involved in this systemic inflammatory response. Immunotherapies may improve outcome in the critically ill with sepsis if used early and as part of the therapeutic regimen of antimicrobial agents and intensive care support. PMID:7724438

Metabolomics in Sepsis and Its Impact on Public Health.

PubMed

Evangelatos, Nikolaos; Bauer, Pia; Reumann, Matthias; Satyamoorthy, Kapaettu; Lehrach, Hans; Brand, Angela

2017-01-01

Sepsis, with its often devastating consequences for patients and their families, remains a major public health concern that poses an increasing financial burden. Early resuscitation together with the elucidation of the biological pathways and pathophysiological mechanisms with the use of "-omics" technologies have started changing the clinical and research landscape in sepsis. Metabolomics (i.e., the study of the metabolome), an "-omics" technology further down in the "-omics" cascade between the genome and the phenome, could be particularly fruitful in sepsis research with the potential to alter the clinical practice. Apart from its benefit for the individual patient, metabolomics has an impact on public health that extends beyond its applications in medicine. In this review, we present recent developments in metabolomics research in sepsis, with a focus on pneumonia, and we discuss the impact of metabolomics on public health, with a focus on free/libre open source software. © 2018 S. Karger AG, Basel.

Therapeutic interventions in sepsis: current and anticipated pharmacological agents

PubMed Central

Shukla, Prashant; Rao, G Madhava; Pandey, Gitu; Sharma, Shweta; Mittapelly, Naresh; Shegokar, Ranjita; Mishra, Prabhat Ranjan

2014-01-01

Sepsis is a clinical syndrome characterized by a multisystem response to a pathogenic assault due to underlying infection that involves a combination of interconnected biochemical, cellular and organ–organ interactive networks. After the withdrawal of recombinant human-activated protein C (rAPC), researchers and physicians have continued to search for new therapeutic approaches and targets against sepsis, effective in both hypo- and hyperinflammatory states. Currently, statins are being evaluated as a viable option in clinical trials. Many agents that have shown favourable results in experimental sepsis are not clinically effective or have not been clinically evaluated. Apart from developing new therapeutic molecules, there is great scope for for developing a variety of drug delivery strategies, such as nanoparticulate carriers and phospholipid-based systems. These nanoparticulate carriers neutralize intracorporeal LPS as well as deliver therapeutic agents to targeted tissues and subcellular locations. Here, we review and critically discuss the present status and new experimental and clinical approaches for therapeutic intervention in sepsis. PMID:24977655

Application of sepsis definitions to pediatric patients admitted with suspected infections in Uganda

PubMed Central

Wiens, Matthew O.; Larson, Charles P.; Kumbakumba, Elias; Kissoon, Niranjan; Ansermino, J. Mark; Singer, Joel; Wong, Hubert; Ndamira, Andrew; Kabakyenga, Jerome; Moschovis, Peter; Kiwanuka, Julius

2017-01-01

Objectives Acute infectious diseases are the most common cause of under-5 mortality. However, the hospital burden of non-neonatal pediatric sepsis has not previously been described in the resource poor setting. The objective of this study was to determine the prevalence of sepsis among children 6 months to 5 years of age admitted with proven or suspected infection and to evaluate the presence of sepsis as a predictive tool for mortality during admission. Design In this Prospective cohort study we used the pediatric International Consensus Conference definition of sepsis to determine the prevalence of sepsis among children admitted to the pediatric ward with a proven or suspected infection. The diagnosis of sepsis, as well as each individual component of the sepsis definition, were evaluated for capturing in-hospital mortality. Setting The pediatric ward of two hospitals in Mbarara, Uganda Patients Admitted children between 6 months and 5 years with a confirmed or suspected infection. Interventions None Measurements and Main Results One thousand three hundred and seven (1307) subjects with a confirmed or suspected infection were enrolled and 65 children died (5.0%) during their admission. One thousand one hundred and twenty-one (85.9%) met the systemic inflammatory response syndrome criteria, and therefore were defined as having sepsis. The sepsis criteria captured 61 deaths, demonstrating a sensitivity and specificity of 95% (95% CI 90% – 100%) and 15% (95% CI 13% – 17%), respectively. The most discriminatory individual component of the SIRS criteria was the leukocyte count which alone had a sensitivity of 72% and a specificity of 56% for the identification of mortality in hospital. Conclusions This study is among the first to quantify the burden of non-neonatal pediatric sepsis in children with suspected infection, using the international consensus sepsis definition, in a typical resource constrained setting in Africa. This definition was found to be highly

Application of Sepsis Definitions to Pediatric Patients Admitted With Suspected Infections in Uganda.

PubMed

Wiens, Matthew O; Larson, Charles P; Kumbakumba, Elias; Kissoon, Niranjan; Ansermino, J Mark; Singer, Joel; Wong, Hubert; Ndamira, Andrew; Kabakyenga, Jerome; Moschovis, Peter; Kiwanuka, Julius

2016-05-01

Acute infectious diseases are the most common cause of under-5 mortality. However, the hospital burden of nonneonatal pediatric sepsis has not previously been described in the resource poor setting. The objective of this study was to determine the prevalence of sepsis among children 6 months to 5 years old admitted with proven or suspected infection and to evaluate the presence of sepsis as a predictive tool for mortality during admission. In this prospective cohort study, we used the pediatric International Consensus Conference definition of sepsis to determine the prevalence of sepsis among children admitted to the pediatric ward with a proven or suspected infection. The diagnosis of sepsis, as well as each individual component of the sepsis definition, was evaluated for capturing in-hospital mortality. The pediatric ward of two hospitals in Mbarara, Uganda. Admitted children between 6 months and 5 years with a confirmed or suspected infection. None. One thousand three hundred seven (1,307) subjects with a confirmed or suspected infection were enrolled, and 65 children died (5.0%) during their admission. One thousand one hundred twenty-one (85.9%) met the systemic inflammatory response syndrome criteria, and therefore, they were defined as having sepsis. The sepsis criteria captured 61 deaths, demonstrating a sensitivity and a specificity of 95% (95% CI, 90-100%) and 15% (95% CI, 13-17%), respectively. The most discriminatory individual component of the systemic inflammatory response syndrome criteria was the leukocyte count, which alone had a sensitivity of 72% and a specificity of 56% for the identification of mortality in hospital. This study is among the first to quantify the burden of nonneonatal pediatric sepsis in children with suspected infection, using the international consensus sepsis definition, in a typical resource-constrained setting in Africa. This definition was found to be highly sensitive in identifying those who died but had very low

Adrenomedullin and adrenomedullin binding protein-1 attenuate vascular endothelial cell apoptosis in sepsis.

PubMed

Zhou, Mian; Simms, H Hank; Wang, Ping

2004-08-01

To determine whether vascular endothelial cell apoptosis occurs in the late stage of sepsis and, if so, whether administration of a potent vasodilatory peptide adrenomedullin and its newly reported specific binding protein (AM/AMBP-1) prevents sepsis-induced endothelial cell apoptosis. Polymicrobial sepsis is characterized by an early, hyperdynamic phase followed by a late, hypodynamic phase. Our recent studies have shown that administration of AM/AMBP-1 delays or even prevents the transition from the hyperdynamic phase to the hypodynamic phase of sepsis, attenuates tissue injury, and decreases sepsis-induced mortality. However, the mechanisms responsible for the beneficial effects of AM/AMBP-1 in sepsis remain unknown. Polymicrobial sepsis was induced by cecal ligation and puncture in adult male rats. Human AMBP-1 (40 microg/kg body weight) was infused intravenously at the beginning of sepsis for 20 minutes and synthetic AM (12 microg/kg body weight) was continuously administered for the entire study period using an Alzert micro-osmotic pump, beginning 3 hours prior to the induction of sepsis. The thoracic aorta and pulmonary tissues were harvested at 20 hours after cecal ligation and puncture (ie, the late stage of sepsis). Apoptosis was determined using TUNEL assay, M30 Cytodeath immunostaining, and electromicroscopy. In addition, anti-apoptotic Bcl-2 and pro-apoptotic Bax gene expression and protein levels were assessed by RT-PCR and Western blot analysis, respectively. Vascular endothelial cells underwent apoptosis formation at 20 hours after cecal ligation and puncture as determined by three different methods. Moreover, partial detached endothelial cell in the aorta was observed. Bcl-2 mRNA and protein levels decreased significantly at 20 hours after the onset of sepsis while Bax was not altered. Administration of AM/AMBP-1 early after sepsis, however, significantly reduced the number of apoptotic endothelial cells. This was associated with significantly

Reporting of Sepsis Cases for Performance Measurement Versus for Reimbursement in New York State.

PubMed

Prescott, Hallie C; Cope, Tara M; Gesten, Foster C; Ledneva, Tatiana A; Friedrich, Marcus E; Iwashyna, Theodore J; Osborn, Tiffany M; Seymour, Christopher W; Levy, Mitchell M

2018-05-01

Under "Rory's Regulations," New York State Article 28 acute care hospitals were mandated to implement sepsis protocols and report patient-level data. This study sought to determine how well cases reported under state mandate align with discharge records in a statewide administrative database. Observational cohort study. First 27 months of mandated sepsis reporting (April 1, 2014, to June 30, 2016). Hospitalizations with sepsis at New York State Article 28 acute care hospitals. Sepsis regulations with mandated reporting. We compared cases reported to the New York State Department of Health Sepsis Clinical Database with discharge records in the Statewide Planning and Research Cooperative System database. We classified discharges as 1) "coded sepsis discharges"-a diagnosis code for severe sepsis or septic shock and 2) "possible sepsis discharges," using Dombrovskiy and Angus criteria. Of 111,816 sepsis cases reported to the New York State Department of Health Sepsis Clinical Database, 105,722 (94.5%) were matched to discharge records in Statewide Planning and Research Cooperative System. The percentage of coded sepsis discharges reported increased from 67.5% in the first quarter to 81.3% in the final quarter of the study period (mean, 77.7%). Accounting for unmatched cases, as many as 82.7% of coded sepsis discharges were potentially reported, whereas at least 17.3% were unreported. Compared with unreported discharges, reported discharges had higher rates of acute organ dysfunction (e.g., cardiovascular dysfunction 63.0% vs 51.8%; p < 0.001) and higher in-hospital mortality (30.2% vs 26.1%; p < 0.001). Hospital characteristics (e.g., number of beds, teaching status, volume of sepsis cases) were similar between hospitals with a higher versus lower percent of discharges reported, p values greater than 0.05 for all. Hospitals' percent of discharges reported was not correlated with risk-adjusted mortality of their submitted cases (Pearson correlation coefficient 0.11; p

Immunosuppression in patients who die of sepsis and multiple organ failure.

PubMed

Boomer, Jonathan S; To, Kathleen; Chang, Kathy C; Takasu, Osamu; Osborne, Dale F; Walton, Andrew H; Bricker, Traci L; Jarman, Stephen D; Kreisel, Daniel; Krupnick, Alexander S; Srivastava, Anil; Swanson, Paul E; Green, Jonathan M; Hotchkiss, Richard S

2011-12-21

Severe sepsis is typically characterized by initial cytokine-mediated hyperinflammation. Whether this hyperinflammatory phase is followed by immunosuppression is controversial. Animal studies suggest that multiple immune defects occur in sepsis, but data from humans remain conflicting. To determine the association of sepsis with changes in host innate and adaptive immunity and to examine potential mechanisms for putative immunosuppression. Rapid postmortem spleen and lung tissue harvest was performed at the bedsides of 40 patients who died in intensive care units (ICUs) of academic medical centers with active severe sepsis to characterize their immune status at the time of death (2009-2011). Control spleens (n = 29) were obtained from patients who were declared brain-dead or had emergent splenectomy due to trauma; control lungs (n = 20) were obtained from transplant donors or from lung cancer resections. Cytokine secretion assays and immunophenotyping of cell surface receptor-ligand expression profiles were performed to identify potential mechanisms of immune dysfunction. Immunohistochemical staining was performed to evaluate the loss of immune effector cells. The mean ages of patients with sepsis and controls were 71.7 (SD, 15.9) and 52.7 (SD, 15.0) years, respectively. The median number of ICU days for patients with sepsis was 8 (range, 1-195 days), while control patients were in ICUs for 4 or fewer days. The median duration of sepsis was 4 days (range, 1-40 days). Compared with controls, anti-CD3/anti-CD28-stimulated splenocytes from sepsis patients had significant reductions in cytokine secretion at 5 hours: tumor necrosis factor, 5361 (95% CI, 3327-7485) pg/mL vs 418 (95% CI, 98-738) pg/mL; interferon γ, 1374 (95% CI, 550-2197) pg/mL vs 37.5 (95% CI, -5 to 80) pg/mL; interleukin 6, 3691 (95% CI, 2313-5070) vs 365 (95% CI, 87-642) pg/mL; and interleukin 10, 633 (95% CI, -269 to 1534) vs 58 (95% CI, -39 to 156) pg/mL; (P < .001 for all). There were similar

The German Quality Network Sepsis: study protocol for the evaluation of a quality collaborative on decreasing sepsis-related mortality in a quasi-experimental difference-in-differences design.

PubMed

Schwarzkopf, Daniel; Rüddel, Hendrik; Gründling, Matthias; Putensen, Christian; Reinhart, Konrad

2018-01-18

While sepsis-related mortality decreased substantially in other developed countries, mortality of severe sepsis remained as high as 44% in Germany. A recent German cluster randomized trial was not able to improve guideline adherence and decrease sepsis-related mortality within the participating hospitals, partly based on lacking support by hospital management and lacking resources for documentation of prospective data. Thus, more pragmatic approaches are needed to improve quality of sepsis care in Germany. The primary objective of the study is to decrease sepsis-related hospital mortality within a quality collaborative relying on claims data. The German Quality Network Sepsis (GQNS) is a quality collaborative involving 75 hospitals. This study protocol describes the conduction and evaluation of the start-up period of the GQNS running from March 2016 to August 2018. Democratic structures assure participatory action, a study coordination bureau provides central support and resources, and local interdisciplinary quality improvement teams implement changes within the participating hospitals. Quarterly quality reports focusing on risk-adjusted hospital mortality in cases with sepsis based on claims data are provided. Hospitals committed to publish their individual risk-adjusted mortality compared to the German average. A complex risk-model is used to control for differences in patient-related risk factors. Hospitals are encouraged to implement a bundle of interventions, e.g., interdisciplinary case analyses, external peer-reviews, hospital-wide staff education, and implementation of rapid response teams. The effectiveness of the GQNS is evaluated in a quasi-experimental difference-in-differences design by comparing the change of hospital mortality of cases with sepsis with organ dysfunction from a retrospective baseline period (January 2014 to December 2015) and the intervention period (April 2016 to March 2018) between the participating hospitals and all other German

Estrogen protects the liver and intestines against sepsis-induced injury in rats.

PubMed

Sener, Göksel; Arbak, Serap; Kurtaran, Pelin; Gedik, Nursal; Yeğen, Berrak C

2005-09-01

Sepsis is commonly associated with enhanced generation of reactive oxygen metabolites, leading to multiple organ dysfunctions. The aim of this study was to examine the putative protective role of estradiol against sepsis-induced oxidative organ damage. Sepsis was induced by cecal ligation and puncture method in Wistar albino rats. Sham-operated (control) and sepsis groups received saline or estradiol propionate (10 mg/kg) intraperitoneally immediately after the operation and at 12 h. Twenty-four hours after the surgery, rats were decapitated and malondialdehyde, glutathione levels, and myeloperoxidase activity were determined in the liver and ileum, while oxidant-induced tissue fibrosis was determined by collagen contents. Tissues were also examined microscopically. Serum aspartate aminotransferase, alanine aminotransferase levels, and lactate dehydrogenase were measured for the evaluation of liver functions and tissue damage, respectively. Tumor necrosis factor-alpha was also assayed in serum samples. In the saline-treated sepsis group, glutathione levels were decreased significantly, while the malondialdehyde levels, myeloperoxidase activity, and collagen content were increased in the tissues (P < 0.01 to P < 0.001), suggesting oxidative organ damage, which was also verified histologically. In the estradiol-treated sepsis group, all of these oxidant responses were reversed significantly (P < 0.05 to P < 0.01). Liver function tests and tumor necrosis factor-alpha levels, which were increased significantly (P < 0.001) following sepsis, were decreased (P < 0.05 to P < 0.001) with estradiol treatment. The results demonstrate the role of oxidative mechanisms in sepsis-induced tissue damage, and estradiol, by its antioxidant properties, ameliorates oxidative organ injury, implicating that treatment with estrogens might be applicable in clinical situations to ameliorate multiple organ damage induced by sepsis.

The global maternal sepsis study and awareness campaign (GLOSS): study protocol.

PubMed

Bonet, Mercedes; Souza, Joao Paulo; Abalos, Edgardo; Fawole, Bukola; Knight, Marian; Kouanda, Seni; Lumbiganon, Pisake; Nabhan, Ashraf; Nadisauskiene, Ruta; Brizuela, Vanessa; Metin Gülmezoglu, A

2018-01-30

Maternal sepsis is the underlying cause of 11% of all maternal deaths and a significant contributor to many deaths attributed to other underlying conditions. The effective prevention, early identification and adequate management of maternal and neonatal infections and sepsis can contribute to reducing the burden of infection as an underlying and contributing cause of morbidity and mortality. The objectives of the Global Maternal Sepsis Study (GLOSS) include: the development and validation of identification criteria for possible severe maternal infection and maternal sepsis; assessment of the frequency of use of a core set of practices recommended for prevention, early identification and management of maternal sepsis; further understanding of mother-to-child transmission of bacterial infection; assessment of the level of awareness about maternal and neonatal sepsis among health care providers; and establishment of a network of health care facilities to implement quality improvement strategies for better identification and management of maternal and early neonatal sepsis. This is a facility-based, prospective, one-week inception cohort study. This study will be implemented in health care facilities located in pre-specified geographical areas of participating countries across the WHO regions of Africa, Americas, Eastern Mediterranean, Europe, South East Asia, and Western Pacific. During a seven-day period, all women admitted to or already hospitalised in participating facilities with suspected or confirmed infection during any stage of pregnancy through the 42nd day after abortion or childbirth will be included in the study. Included women will be followed during their stay in the facilities until hospital discharge, death or transfer to another health facility. The maximum intra-hospital follow-up period will be 42 days. GLOSS will provide a set of actionable criteria for identification of women with possible severe maternal infection and maternal sepsis. This study

Ghrelin clearance is reduced at the late stage of polymicrobial sepsis.

PubMed

Wu, Rongqian; Zhou, Mian; Cui, Xiaoxuan; Simms, H Hank; Wang, Ping

2003-11-01

The cardiovascular response to sepsis is characterized by an early, hyperdynamic phase followed by a late, hypodynamic phase. Ghrelin, a newly-identified endogenous ligand for growth hormone secretagogue receptor (i.e., ghrelin receptor), was recently demonstrated to be a potent vasoactive peptide in addition to its effects on growth hormone release and energy homeostasis. We have shown that ghrelin (via its receptor) may play an important role in regulating cardiovascular responses in the progression of polymicrobial sepsis. However, it remains unknown whether the clearance of this peptide is altered in sepsis. To determine this, male adult rats were injected with 125I-ghrelin through the jugular vein at 5 or 20 h after cecal ligation and puncture (CLP, i.e., sepsis model) or sham operation. The blood sample was collected every 2 min for 30 min for determining half-life (t1/2). Tissue samples (i.e., kidneys, liver, brain, heart, lungs, spleen, stomach, small intestine, large intestine, skin and muscle) were then harvested. The radioactivities of samples were counted. The results indicate that 125I-ghrelin's t1/2 and its distribution were not significantly altered in early sepsis (5 h after CLP). However, the t1/2 increased significantly in late sepsis (20 h after CLP). Tissue distribution of 125I-ghrelin was far greater in the kidneys than in any other tissues tested in both sham and septic animals. Moreover, the kidneys and liver had significantly less radioactive uptake at 20 h after CLP, but the radioactivity in blood was much higher at the same time point. There were no significant changes in 125I-ghrelin distribution in other organs at the late stage of sepsis. These results indicate that the kidneys are the primary site of ghrelin clearance, which is significantly diminished in late sepsis. In addition, the liver also plays a role in the clearance of ghrelin, which was also reduced in late sepsis. The decreased clearance of ghrelin by the kidneys and liver

Delay Within the 3-Hour Surviving Sepsis Campaign Guideline on Mortality for Patients With Severe Sepsis and Septic Shock.

PubMed

Pruinelli, Lisiane; Westra, Bonnie L; Yadav, Pranjul; Hoff, Alexander; Steinbach, Michael; Kumar, Vipin; Delaney, Connie W; Simon, Gyorgy

2018-04-01

To specify when delays of specific 3-hour bundle Surviving Sepsis Campaign guideline recommendations applied to severe sepsis or septic shock become harmful and impact mortality. Retrospective cohort study. One health system composed of six hospitals and 45 clinics in a Midwest state from January 01, 2011, to July 31, 2015. All adult patients hospitalized with billing diagnosis of severe sepsis or septic shock. Four 3-hour Surviving Sepsis Campaign guideline recommendations: 1) obtain blood culture before antibiotics, 2) obtain lactate level, 3) administer broad-spectrum antibiotics, and 4) administer 30 mL/kg of crystalloid fluid for hypotension (defined as "mean arterial pressure" < 65) or lactate (> 4). To determine the effect of t minutes of delay in carrying out each intervention, propensity score matching of "baseline" characteristics compensated for differences in health status. The average treatment effect in the treated computed as the average difference in outcomes between those treated after shorter versus longer delay. To estimate the uncertainty associated with the average treatment effect in the treated metric and to construct 95% CIs, bootstrap estimation with 1,000 replications was performed. From 5,072 patients with severe sepsis or septic shock, 1,412 (27.8%) had in-hospital mortality. The majority of patients had the four 3-hour bundle recommendations initiated within 3 hours. The statistically significant time in minutes after which a delay increased the risk of death for each recommendation was as follows: lactate, 20.0 minutes; blood culture, 50.0 minutes; crystalloids, 100.0 minutes; and antibiotic therapy, 125.0 minutes. The guideline recommendations showed that shorter delays indicates better outcomes. There was no evidence that 3 hours is safe; even very short delays adversely impact outcomes. Findings demonstrated a new approach to incorporate time t when analyzing the impact on outcomes and provide new evidence for clinical practice

Vitamin C: The next step in sepsis management?

PubMed

Teng, J; Pourmand, A; Mazer-Amirshahi, M

2018-02-01

Sepsis is a life-threatening medical condition, affecting approximately 26 million people worldwide every year. The disease is a continuum, marked by dysregulated inflammation and hemodynamic instability leading to shock, multi-system organ dysfunction, and death. Over the past decades, there has been a focus on the early identification and treatment of sepsis primarily with bundled and goal directed therapy. Despite these advances, morbidity and mortality has remained high, prompting investigation into novel therapies. Vitamin C is a water-soluble vitamin that plays a role in mediating inflammation through antioxidant activities and is also important in the synthesis of cortisol, catecholamines, and vasopressin, which are key mediators in the disease process. Emerging evidence provides cursory data in support of the administration of vitamin C in addition to standard therapy to ameliorate the effects of inflammation and improve hemodynamic stability in patients with sepsis and septic shock; however, further evidence is needed to support this practice. This review discusses the physiologic role of vitamin C as well as the recent literature and evidence for the use of vitamin C in patients presenting with sepsis. Copyright © 2017 Elsevier Inc. All rights reserved.

Bacterial lung sepsis in patients with febrile neutropenia.

PubMed

Lanoix, Jean-Philippe; Schmit, Jean-Luc; Douadi, Youcef

2012-05-01

This review provides an update on microbiological and therapeutic data in febrile neutropenic patients in general and those with bacterial lung sepsis in particular. Although the Infectious Diseases Society of America updated its guidelines on febrile neutropenia in 2010, changing epidemiological factors and the spread of new drug resistance constitutes challenges for initial treatment of this condition. Lung sepsis stands out because of the frequent absence of microbiological identification. We review the use of newly available, novel, broad-spectrum antibiotics (linezolid, tigecycline, daptomycin, etc.) in this indication. Although the incidence of Gram-negative infections in neutropenic fever is leveling off, there is a worrying increase in resistance. New drugs are available but not well studied in febrile neutropenia; daptomycin and tigecycline should not be used in suspected lung sepsis in these patients. New diagnostic tools (such as the procalcitonin assay and the LightCycler SeptiFast assay, Roche Molecular Systems) appear to be unhelpful in febrile neutropenia, although more data on fungal sepsis are required. There are no specific features of the treatment of pneumonia or septic shock in neutropenic fever, but both conditions increase the mortality rate.

Chronic Alcohol Ingestion Delays T Cell Activation and Effector Function in Sepsis.

PubMed

Margoles, Lindsay M; Mittal, Rohit; Klingensmith, Nathan J; Lyons, John D; Liang, Zhe; Serbanescu, Mara A; Wagener, Maylene E; Coopersmith, Craig M; Ford, Mandy L

2016-01-01

Sepsis is the leading cause of death in intensive care units in the US, and it is known that chronic alcohol use is associated with higher incidence of sepsis, longer ICU stays, and higher mortality from sepsis. Both sepsis and chronic alcohol use are associated with immune deficits such as decreased lymphocyte numbers, impaired innate immunity, delayed-type hypersensitivity reactions, and susceptibility to infections; however, understanding of specific pathways of interaction or synergy between these two states of immune dysregulation is lacking. This study therefore sought to elucidate mechanisms underlying the immune dysregulation observed during sepsis in the setting of chronic alcohol exposure. Using a murine model of chronic ethanol ingestion followed by sepsis induction via cecal ligation and puncture, we determined that while CD4+ and CD8+ T cells isolated from alcohol fed mice eventually expressed the same cellular activation markers (CD44, CD69, and CD43) and effector molecules (IFN-γ, TNF) as their water fed counterparts, there was an overall delay in the acquisition of these phenotypes. This early lag in T cell activation was associated with significantly reduced IL-2 production at a later timepoint in both the CD4+ and CD8+ T cell compartments in alcohol sepsis, as well as with a reduced accumulation of CD8dim activated effectors. Taken together, these data suggest that delayed T cell activation may result in qualitative differences in the immune response to sepsis in the setting of chronic alcohol ingestion.

Immunomodulatory intervention with Gamma interferon in mice with sepsis.

PubMed

Wang, Yu; Kong, Bing-Bing; Yang, Wen-Ping; Zhao, Xin; Zhang, Rong

2017-09-15

Sepsis-triggered immune paralysis including T-cell dysfunction increase susceptibility to infection. Gamma interferon (IFNg) exert beneficial effects in patients with sepsis. Herein, we speculated that IFNg may attenuate T-cell dysfunction induced by sepsis, although the mechanisms remain elusive. To test this hypothesis, we used a model based on cecal ligation and puncture (CLP) to induce sepsis in mice. Male C57BL/6 mice were pretreated with recombinant human IFNg (0.01μg/g of body weight) before CLP. The immunophenotyping of cell surface receptor expression, and regulatory T cells (CD4+CD25+Foxp3+) were quantified by flow cytometry. Immunohistochemical staining was performed to evaluate the loss of immune effector cells. Formation of IFNg and interleukin 4 (IL-4) in the spleen and plasma levels of TNF-α, IL-6, high-mobility group box 1 (HMGB1) were determined using enzyme-linked immunosorbent assay. IFNg markedly inhibited the reduction in cytokine secretion from lipopolysaccharide (LPS)-stimulated splenocytes. IFNg-treated mices had significantly decreased percentages of programmed cell death 1 (PD-1) receptors, increased the percentages of positive costimulatory receptor CD28 on CD4 T cells expressing. IFNg markedly reduced T-cell apoptosis through upregulating the expression of Bcl-2. CLP-induced formation of regulatory T cells in the spleen was abolished in IFNg -treated mices. Moreover, IFNg treatment reduced plasma levels of TNF-α, IL-6, HMGB1. IFNg can be a powerful regulator of immune function under sepsis conditions. Therefore, targeted immune-enhancement with IFNg may be a valid therapeutic approach in sepsis. Copyright © 2017 Elsevier Inc. All rights reserved.

Diagnostic and prognostic biomarkers of sepsis in critical care.

PubMed

Kibe, Savitri; Adams, Kate; Barlow, Gavin

2011-04-01

Sepsis is a leading cause of mortality in critically ill patients. Delay in diagnosis and initiation of antibiotics have been shown to increase mortality in this cohort. However, differentiating sepsis from non-infectious triggers of the systemic inflammatory response syndrome (SIRS) is difficult, especially in critically ill patients who may have SIRS for other reasons. It is this conundrum that predominantly drives broad-spectrum antimicrobial use and the associated evolution of antibiotic resistance in critical care environments. It is perhaps unsurprising, therefore, that the search for a highly accurate biomarker of sepsis has become one of the holy grails of medicine. Procalcitonin (PCT) has emerged as the most studied and promising sepsis biomarker. For diagnostic and prognostic purposes in critical care, PCT is an advance on C-reactive protein and other traditional markers of sepsis, but is not accurate enough for clinicians to dispense with clinical judgement. There is stronger evidence, however, that measurement of PCT has a role in reducing the antibiotic exposure of critical care patients. For units intending to incorporate PCT assays into routine clinical practice, the cost-effectiveness of this is likely to depend on the pre-implementation length of an average antibiotic course and the subsequent impact of implementation on emerging antibiotic resistance. In most of the trials to date, the average baseline duration of the antibiotic course was longer than is currently standard practice in many UK critical care units. Many other biomarkers are currently being investigated. To be highly useful in clinical practice, it may be necessary to combine these with other novel biomarkers and/or traditional markers of sepsis.

Forebrain Cholinergic Dysfunction and Systemic and Brain Inflammation in Murine Sepsis Survivors

PubMed Central

Zaghloul, Nahla; Addorisio, Meghan E.; Silverman, Harold A.; Patel, Hardik L.; Valdés-Ferrer, Sergio I.; Ayasolla, Kamesh R.; Lehner, Kurt R.; Olofsson, Peder S.; Nasim, Mansoor; Metz, Christine N.; Wang, Ping; Ahmed, Mohamed; Chavan, Sangeeta S.; Diamond, Betty; Tracey, Kevin J.; Pavlov, Valentin A.

2017-01-01

Sepsis, a complex disorder characterized by immune, metabolic, and neurological dysregulation, is the number one killer in the intensive care unit. Mortality remains alarmingly high even in among sepsis survivors discharged from the hospital. There is no clear strategy for managing this lethal chronic sepsis illness, which is associated with severe functional disabilities and cognitive deterioration. Providing insight into the underlying pathophysiology is desperately needed to direct new therapeutic approaches. Previous studies have shown that brain cholinergic signaling importantly regulates cognition and inflammation. Here, we studied the relationship between peripheral immunometabolic alterations and brain cholinergic and inflammatory states in mouse survivors of cecal ligation and puncture (CLP)-induced sepsis. Within 6 days, CLP resulted in 50% mortality vs. 100% survival in sham-operated controls. As compared to sham controls, sepsis survivors had significantly lower body weight, higher serum TNF, interleukin (IL)-1β, IL-6, CXCL1, IL-10, and HMGB1 levels, a lower TNF response to LPS challenge, and lower serum insulin, leptin, and plasminogen activator inhibitor-1 levels on day 14. In the basal forebrain of mouse sepsis survivors, the number of cholinergic [choline acetyltransferase (ChAT)-positive] neurons was significantly reduced. In the hippocampus and the cortex of mouse sepsis survivors, the activity of acetylcholinesterase (AChE), the enzyme that degrades acetylcholine, as well as the expression of its encoding gene were significantly increased. In addition, the expression of the gene encoding the M1 muscarinic acetylcholine receptor was decreased in the hippocampus. In parallel with these forebrain cholinergic alterations, microglial activation (in the cortex) and increased Il1b and Il6 gene expression (in the cortex), and Il1b gene expression (in the hippocampus) were observed in mouse sepsis survivors. Furthermore, microglial activation was

Pediatric Sepsis Guidelines: Summary for resource-limited countries

PubMed Central

Khilnani, Praveen; Singhi, Sunit; Lodha, Rakesh; Santhanam, Indumathi; Sachdev, Anil; Chugh, Krishan; Jaishree, M.; Ranjit, Suchitra; Ramachandran, Bala; Ali, Uma; Udani, Soonu; Uttam, Rajiv; Deopujari, Satish

2010-01-01

Justification: Pediatric sepsis is a commonly encountered global issue. Existing guidelines for sepsis seem to be applicable to the developed countries, and only few articles are published regarding application of these guidelines in the developing countries, especially in resource-limited countries such as India and Africa. Process: An expert representative panel drawn from all over India, under aegis of Intensive Care Chapter of Indian Academy of Pediatrics (IAP) met to discuss and draw guidelines for clinical practice and feasibility of delivery of care in the early hours in pediatric patient with sepsis, keeping in view unique patient population and limited availability of equipment and resources. Discussion included issues such as sepsis definitions, rapid cardiopulmonary assessment, feasibility of early aggressive fluid therapy, inotropic support, corticosteriod therapy, early endotracheal intubation and use of positive end expiratory pressure/mechanical ventilation, initial empirical antibiotic therapy, glycemic control, and role of immunoglobulin, blood, and blood products. Objective: To achieve a reasonable evidence-based consensus on the basis of published literature and expert opinion to formulating clinical practice guidelines applicable to resource-limited countries such as India. Recommendations: Pediatric sepsis guidelines are presented in text and flow chart format keeping resource limitations in mind for countries such as India and Africa. Levels of evidence are indicated wherever applicable. It is anticipated that once the guidelines are used and outcomes data evaluated, further modifications will be necessary. It is planned to periodically review and revise these guidelines every 3–5 years as new body of evidence accumulates. PMID:20606908

Extracorporeal blood treatment (EBT) methods in SIRS/Sepsis.

PubMed

Bellomo, R; Honoré, P M; Matson, J; Ronco, C; Winchester, J

2005-05-01

Extracorporeal blood purification treatment (EBT) methods have been used in the treatment of experimental and human SIRS/Sepsis in a variety of settings and with variable reports of efficacy and safety. Their role in the management of SIRS/Sepsis remains controversial. To develop consensus statements regarding important aspects of research, practice and technical management concerning EBT. Systematic review of published study. Evidence-based grading of information available. Consensus development regarding fundamental questions about EBT. Consensus was achieved on all questions posed during the conference. It was agreed that there is currently a clear biological rational for EBT in SIRS and Sepsis. It was agreed that conventional CVVH has sufficiently been shown not to be effective in SIRS/Sepsis in the absence of concomitant ARF and that other therapies such as plasmapheresis or high-volume hemofiltration or coupled plasma filtration adsorption appear more promising and should be tested in multicentre randomized controlled trials. Patients with ARF and SIRS/Sepsis should be treated differently from those with ARF alone even though current practice in this field is not well known. Patients with refractory septic shock should be considered for EBT. Appropriate end points for clinical trials can be defined and chosen according to the goals of the trial. Different technologies exist for EBT and better understanding of the merits and safety of each is needed as well as better standardization of methodology and dose. Broad consensus can be achieved on several aspects of EBT and can be used to inform clinical practice and to help guide the establishment of a future research agenda.

The New Sepsis Definitions: Implications for the Basic and Translational Research Communities.

PubMed

Coopersmith, Craig M; Deutschman, Clifford S

2017-03-01

New definitions of sepsis and septic shock were published in early 2016, updating old definitions that have not been revisited since 2001. These new definitions should profoundly affect sepsis research. In addition, these papers present clinical criteria for identifying infected patients who are highly likely to have or to develop sepsis or septic shock. In contrast to previous approaches, these new clinical criteria are evidence based. In this review, two of the authors of the new definitions detail the content of the papers and explore the implications for shock and sepsis researchers.

Elevated thrombopoietin in plasma of burned patients without and with sepsis enhances platelet activation.

PubMed

Lupia, E; Bosco, O; Mariano, F; Dondi, A E; Goffi, A; Spatola, T; Cuccurullo, A; Tizzani, P; Brondino, G; Stella, M; Montrucchio, G

2009-06-01

Thrombopoietin (TPO) is a humoral growth factor that does not induce platelet aggregation per se, but enhances platelet activation in response to several agonists. Circulating levels of TPO are increased in patients with sepsis and are mainly related to sepsis severity. To investigate the potential contribution of elevated TPO levels in platelet activation during burn injury complicated or not by sepsis. We studied 22 burned patients, 10 without and 12 with sepsis, and 10 healthy subjects. We measured plasma levels of TPO, as well as leukocyte-platelet binding and P-selectin expression. The priming activity of plasma from burned patients or healthy subjects on platelet aggregation and leukocyte-platelet binding, and the role of TPO in these effects were also studied in vitro. Burned patients without and with sepsis showed higher circulating TPO levels and increased monocyte-platelet binding compared with healthy subjects. Moreover, TPO levels, monocyte-platelet binding and P-selectin expression were significantly higher in burned patients with sepsis than in burned patients without sepsis. In vitro, plasma from burned patients without and with sepsis, but not from healthy subjects, primed platelet aggregation, monocyte-platelet binding and platelet P-selectin expression. The effect of plasma from burned patients with sepsis was significantly higher than that of plasma from burned patients without sepsis. An inhibitor of TPO prevented the priming effect of plasma from burned patients. Increased TPO levels may enhance platelet activation during burn injury and sepsis, potentially participating in the pathogenesis of multi-organ failure in these diseases.

T-cell proliferative responses following sepsis in neonatal rats.

PubMed

Dallal, Ousama; Ravindranath, Thyyar M; Choudhry, Mashkoor A; Kohn, Annamarie; Muraskas, Jonathan K; Namak, Shahla Y; Alattar, Mohammad H; Sayeed, Mohammed M

2003-01-01

Both experimental and clinical evidence suggest a suppression of T-cell function in burn and sepsis. The objective of the present study was to evaluate splenocyte and purified T-cell proliferative response and IL-2 production in septic neonatal rats. We also examined if alterations in T-cell proliferation and IL-2 production in neonatal sepsis is due to elevation in PGE2. PGE2 is known to play a significant role in T-cell suppression during sepsis in adults. Sepsis was induced in 15-day-old neonatal Sprague-Dawley rats by implanting 0.1 cm3 of fecal pellet impregnated with Escherichia coli (50 CFU) and Bacteroides fragilis (10(3) CFU). Animals receiving fecal pellets without the bacteria were designated as sterile. A group of septic and sterile rats were treated with PGE2 synthesis inhibitors, NS398 and resveratrol. These treatments of animals allowed us to evaluate the role of PGE2 in T-cell suppression during neonatal sepsis. Splenocytes as well as purified T cells were prepared and then proliferative response and IL-2 productive capacities were measured. A significant suppression of splenocyte proliferation and IL-2 production was noticed in both sterile and septic animals compared to the T cells from unoperated control rats. In contrast, the proliferation and IL-2 production by nylon wool purified T cells in sterile rats was not significantly different from control rats, whereas, a significant suppression in Con A-mediated T-cell proliferation and IL-2 production noticed in septic rat T cells compared to the sterile and control rat T cells. Such decrease in T-cell proliferation and IL-2 production was accompanied with 20-25% deaths in neonates implanted with septic pellets. No mortality was noted in sterile-implanted neonates. Treatment of animals with COX-1 inhibitor had no effect on T-cell proliferation response in both septic and sterile groups, whereas COX-2 inhibitor abrogated the decrease in T-cell proliferative response in the septic group. The treatment

Evaluation of oxidative stress and antioxidant status: Correlation with the severity of sepsis.

PubMed

Kumar, S; Gupta, E; Kaushik, S; Kumar Srivastava, V; Mehta, S K; Jyoti, A

2018-04-01

Sepsis is a condition caused by infection followed by unregulated inflammatory response which may lead to the organ dysfunction. During such condition, over-production of oxidants is one of the factors which contribute cellular toxicity and ultimately organ failure and mortality. Antioxidants having free radicals scavenging activity exert protective role in various diseases. This study has been designed to evaluate the levels of oxidative and antioxidative activity in sepsis patients and their correlation with the severity of the sepsis. A total of 100 sepsis patients and 50 healthy controls subjects were enrolled in this study from the period October 2016 to June 2017. The investigation included measurements of oxidative enzyme, myeloperoxidase (MPO), antioxidant enzymes including superoxide dismutase activity (SOD) and catalase activity (CAT) and cytokines (TNF-α, IL-8 and IFN-γ). Furthermore, the level of these activities was correlated with severity of sepsis. Augmented levels of oxidants were found in sepsis as demonstrated by DMPO nitrone adduct formation and plasma MPO level activity (1.37 ± 0.51 in sepsis vs 0.405 ± 0.16 in control subjects). Cytokines were also found to be increased in sepsis patients. However, plasma SOD and CAT activities were significantly attenuated (P < .001) in the sepsis patients compared with controls subjects. Moreover, inverse relation between antioxidant enzymes (SOD and CAT) and organ failure assessment (SOFA), physiological score (APACHE II), organ toxicity specific markers have been observed as demonstrated by Pearson's correlation coefficient. This study suggests that imbalance between oxidant and antioxidant plays key role in the severity of sepsis. © 2018 The Foundation for the Scandinavian Journal of Immunology.

Inter-alpha inhibitor protein administration improves survival from neonatal sepsis in mice.

PubMed

Singh, Kultar; Zhang, Ling Xiu; Bendelja, Kreso; Heath, Ryan; Murphy, Shaun; Sharma, Surendra; Padbury, James F; Lim, Yow-Pin

2010-09-01

Inter-alpha inhibitor proteins (IaIp) are serine proteases inhibitors that modulate endogenous protease activity and have been shown to improve survival in adult models of sepsis. We evaluated the effect of IaIp on survival and systemic responses to sepsis in neonatal mice. Sepsis was induced in 2-d-old mice with lipopolysaccharide (LPS), Escherichia coli, and group B Streptococci. Sepsis was associated with 75% mortality. IaIp, given by i.p. administration at doses between 15 and 45 mg/kg from 1 to 6 h after the onset of sepsis, improved survival to approximately 90% (p = 0.0159) in both LPS-induced sepsis and with live bacterial infections. The greatest effect was on reversal of hemorrhagic pneumonitis. The effects were dose and time dependent. Systemic cytokine profile and tissue histology were examined. Survival was compared in IL-10 knock out animals. Systemic cytokine levels including TNF-[alpha] and IL-10 were increased after induction of sepsis and modulated significantly after IaIp administration. Because the effect of IaIp was still demonstrable in IL-10 deficient mice, we conclude the beneficial effects of IaIp is because of suppression of proinflammatory cytokines such as TNF-[alpha] rather than augmentation of IL-10. IaIp may offer significant benefits as a therapeutic

Analysis of sepsis in allogeneic bone marrow transplant recipients: a single-center study.

PubMed

Mitsui, Hideki; Karasuno, Takahiro; Santo, Taisuke; Fukushima, Kentaro; Matsunaga, Hitomi; Nakamura, Hiroyuki; Hiraoka, Akira

2003-09-01

We reviewed the records of 235 consecutive recipients of allogeneic bone marrow transplantation (allo-BMT) at our center between February 1983 and October 2000. Sepsis occurred in 25 patients (10.6%) at a median of 10 days (range, 1-280 days) after BMT. Five of the 25 patients (20%) died of sepsis. Pathogens isolated from blood culture were gram-positive cocci in 19 patients, gram-negative rods in 7, fungi in 2, and others in 1 patient. Two pathogens were detected concomitantly in 4 patients. Univariate analysis revealed that risk factors for sepsis were selective gut decontamination using lomefloxacin hydrochloride and nystatin, an unrelated donor, HLA mismatched BMT, and stomatitis. Multivariate logistic regression analysis revealed that an unrelated donor was the only significant independent risk factor, with a relative risk of 5.432. In 12 of 25 patients with sepsis, the pathogens of sepsis were sensitive to antibiotics used for gut decontamination. Selective gut decontamination significantly increased the incidence of sepsis, especially that with gram-positive cocci, but not the mortality rate of sepsis, compared with total gut decontamination using vancomycin. We also found a significant relationship between pathogens isolated from blood culture and those isolated from surveillance cultures of stool, urine, and gargled water in the period before sepsis occurred. The present study revealed an independent risk factor for sepsis (unrelated donor), the feasibility of selective gut decontamination, and the importance of surveillance culture.

Evaluation of musculoskeletal sepsis with indium-111 white blood cell imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ouzounian, T.J.; Thompson, L.; Grogan, T.J.

The detection of musculoskeletal sepsis, especially following joint replacement, continues to be a challenging problem. Often, even with invasive diagnostic evaluation, the diagnosis of infection remains uncertain. This is a report on the first 55 Indium-111 white blood cell (WBC) images performed in 39 patients for the evaluation of musculoskeletal sepsis. There were 40 negative and 15 positive Indium-111 WBC images. These were correlated with operative culture and tissue pathology, aspiration culture, and clinical findings. Thirty-eight images were performed for the evaluation of possible total joint sepsis (8 positive and 30 negative images); 17 for the evaluation of nonarthroplasty-related musculoskeletalmore » sepsis (7 positive and 10 negative images). Overall, there were 13 true-positive, 39 true-negative, two false-positive, and one false-negative images. Indium-111 WBC imaging is a sensitive and specific means of evaluating musculoskeletal sepsis, especially following total joint replacement.« less

Associations between interleukin-1 gene polymorphisms and sepsis risk: a meta-analysis

PubMed Central

2014-01-01

Background Previous epidemiological studies have presented conflicting evidence regarding associations between interleukin-1 (IL-1) polymorphisms and sepsis susceptibility. We have performed a meta-analysis to evaluate possible associations between IL-1 polymorphisms and sepsis risk. Methods Eligible literature was retrieved from PubMed, Embase and Web of Knowledge databases until Jun 15, 2013. The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using random-effects model in the overall and subgroup analysis based on ethnicity, sepsis severity and quality score. Results Eighteen studies addressing five IL-1 polymorphisms were included in this meta-analysis. For IL-1A-889 (rs1800587) polymorphism, significant association was observed in overall comparison for allelic effect (OR = 1.47, 95% CI = 1.01-2.13, P = 0.04). There were no significant associations between either IL-1B-511 (rs16944) or IL-1B-31 (rs1143627) and sepsis susceptibility in overall or subgroup analyses. For IL-1B + 3594 (rs143634) polymorphism, genotype TT decreased sepsis risk in overall analysis (OR = 0.59, 95% CI = 0.36-0.97, P = 0.04), as well as in Caucasian (OR = 0.57, 95% CI = 0.34-0.95, P = 0.03) and sepsis (OR = 0.55, 95% CI = 0.31-0.97, P = 0.04) subgroup analysis. For IL-1RN VNTR polymorphism, significant association was observed in overall comparison for allelic effect (OR = 1.40, 95% CI = 1.01-1.95, P = 0.04). Furthermore, the effect sizes of IL-1RN VNTR on sepsis risk increased with disease severity (septic shock OR > severe sepsis OR > sepsis OR). Conclusions Our meta-analysis indicated that IL-1A-889, IL-1B + 3954 and IL-1RN VNTR might be associated with sepsis susceptibility. However, further studies with larger sample sizes and from homogenous populations would be necessary to validate these findings. PMID:24428862

[Sepsis with Staphylococcus aureus in immunocompromised patients].

PubMed

Petrache, Simona Magdalena; Miftode, Egidia; Vâţă, A; Petrovici, Cristina Mirela; Dorneanu, Olivia; Luca, V

2009-01-01

The aim of our study was to analyze clinical and biological characteristics of immunocompromised patients with staphylococcal sepsis and to compare with the same data in non-immunocompromised patients. The diagnosis of sepsis was made based on Bone criteria. MiniAPI system ID 32 STAPH was used for identification and antibiotic susceptibility was assessed by ATB STAPH method and by E-test for oxacillin and vancomycin. Among the 147 patients with Staphylococcus aureus sepsis--66.67% had concomitant immunosuppressive conditions (diabetes mellitus, liver diseases, renal failure, corticotherapy, etc). We have found a significant correlation between the immunosuppressed status and MRSA (methicillin-resistant Staphylococcus aureus) involvement (p = 0.0018) and also, between this group of patients and treatment failure (p = 0.0012). Because of the high rate of MRSA involvement in systemic infections in the Eastern region of Romania first intention treatment of patients with staphylococcal infections and conditions of immunosuppression must include antibiotics effective against methicillin-resistant strains.

Sepsis Definitions: The Search for Gold and What CMS Got Wrong.

PubMed

Kalantari, Annahieta; Mallemat, Haney; Weingart, Scott D

2017-08-01

On October 1, 2015, the United States Centers for Medicare and Medicaid Services (CMS) issued a core measure addressing the care of septic patients. These core measures are controversial among healthcare providers. This article will address that there is no gold standard definition for sepsis, severe sepsis or septic shock and the CMS-assigned definitions for severe sepsis and septic shock are premature and inconsistent with evidence-based definitions.

Trend and outcome of sepsis in children: A nationwide cohort study.

PubMed

Yo, Chia-Hung; Hsu, Tzu-Chun; Gabriel Lee, Meng-Tse; Porta, Lorenzo; Tsou, Po-Yang; Wang, Yu-Hsun; Lee, Wan-Chien; Chen, Szu-Ta; Lee, Chien-Chang

2018-02-09

The aim of this study was to investigate the trend of incidence and outcome of paediatric sepsis in a population-based database. Children with sepsis were identified from the 23 million nationwide health insurance claims database of Taiwan. Sepsis was defined by the presence of single ICD-9 code for severe sepsis or septic shock or a combination of ICD-9 codes for infection and organ dysfunction. We analysed the trend of incidence, mortality and source of infection in three age groups: infant (28 days to 1 year), child (1-9 years) and adolescent (10-18 years). From 2002 to 2012, we identified 38 582 paediatric patients with sepsis, of which 21.3% were infants, 52.8% were children and 25.8% were adolescents. The incidence of sepsis was 336.4 cases per 100 000 population in infants, 3.3 times higher than in children (101.5/100 000 cases) and 7.3 times higher than in adolescents (46.2/100 000 cases). While sepsis incidence decreased from 598.0 to 336.4 cases per 100 000 people in the infant population, it remained relatively unchanged in children and adolescents. For 90-day mortality, there were significant decreases in all three age groups (absolute decrease of 5.0% for infants, 3.7% for children and 14.4% for the adolescents). In the infant population, we observed a decrease in the incidence of lower respiratory tract infections, while the incidence of urinary tract infections remained unchanged. The incidence and mortality of sepsis among paediatric patients have decreased substantially between 2002 and 2012, especially among infants. The widespread use of Haemophilus influenzae and pneumococcal vaccines in infants could be a possible explanation. © 2018 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

Evaluation of procalcitonin for diagnosis of neonatal sepsis of vertical transmission

PubMed Central

López Sastre, José B; Solís, David Pérez; Serradilla, Vicente Roqués; Colomer, Belén Fernández; Cotallo, Gil D Coto

2007-01-01

Background The results of recent studies suggest the usefulness of PCT for early diagnosis of neonatal sepsis, with varying results. The aim of this prospective multicenter study was to determine the behavior of serum PCT concentrations in both uninfected and infected neonates, and to assess the value of this marker for diagnosis of neonatal sepsis of vertical transmission. Methods PCT was measured in 827 blood samples collected prospectively from 317 neonates admitted to 13 acute-care teaching hospitals in Spain over one year. Serum PCT concentrations were determined by a specific immunoluminometric assay. The diagnostic efficacy of PCT at birth and within 12–24 h and 36–48 h of life was evaluated calculating the sensitivity, specificity, and likelihood ratio of positive and negative results. Results 169 asymptomatic newborns and 148 symptomatic newborns (confirmed vertical sepsis: 31, vertical clinical sepsis: 38, non-infectious diseases: 79) were studied. In asymptomatic neonates, PCT values at 12–24 h were significantly higher than at birth and at 36–48 h of life. Resuscitation at birth and chorioamnionitis were independently associated to PCT values. Neonates with confirmed vertical sepsis showed significantly higher PCT values than those with clinical sepsis. PCT thresholds for the diagnosis of sepsis were 0.55 ng/mL at birth (sensitivity 75.4%, specificity 72.3%); 4.7 ng/mL within 12–24 h of life (sensitivity 73.8%, specificity 80.8%); and 1.7 ng/mL within 36–48 h of life (sensitivity 77.6%, specificity 79.2%). Conclusion Serum PCT was moderately useful for the detection of sepsis of vertical transmission, and its reliability as a maker of bacterial infection requires specific cutoff values for each evaluation point over the first 48 h of life. PMID:17324267

Long-term risk of seizures in adult survivors of sepsis.

PubMed

Reznik, Michael E; Merkler, Alexander E; Mahta, Ali; Murthy, Santosh B; Claassen, Jan; Kamel, Hooman

2017-10-03

To examine the association between sepsis and the long-term risk of seizures. We conducted a retrospective population-based cohort study using administrative claims data from all emergency department visits and hospitalizations at nonfederal acute care hospitals in California, Florida, and New York from 2005 to 2013. Using previously validated diagnosis codes, we identified all adult patients hospitalized with sepsis. Our outcome was any emergency department visit or hospitalization for seizure. Poisson regression and demographic data were used to calculate age-, sex-, and race-standardized incidence rate ratios (IRR). To confirm our findings, we used a matched cohort of hospitalized patients without sepsis for comparison and additionally assessed claims data from a nationally representative 5% sample of Medicare beneficiaries. We identified 842,735 patients with sepsis. The annual incidence of seizure was 1.29% (95% confidence interval [CI] 1.27%-1.30%) in patients with sepsis vs 0.16% (95% CI 0.16%-0.16%) in the general population (IRR 4.98; 95% CI 4.92-5.04). A secondary analysis using matched hospitalized patients confirmed these findings (IRR 4.33; 95% CI 4.13-4.55), as did a separate analysis of Medicare beneficiaries, in whom we found a similar strength of association (IRR 2.72; 95% CI 2.60-2.83), as we did in patients ≥65 years of age in our primary statewide data (IRR 2.83; 95% CI 2.78-2.88). We found that survivors of sepsis faced a significantly higher long-term risk of seizures than both the general population and other hospitalized patients. Our findings suggest that sepsis is associated with pathways that lead to permanent neurologic sequelae. © 2017 American Academy of Neurology.

Towards a consensus definition of maternal sepsis: results of a systematic review and expert consultation.

PubMed

Bonet, Mercedes; Nogueira Pileggi, Vicky; Rijken, Marcus J; Coomarasamy, Arri; Lissauer, David; Souza, João Paulo; Gülmezoglu, Ahmet Metin

2017-05-30

There is a need for a clear and actionable definition of maternal sepsis, in order to better assess the burden of this condition, trigger timely and effective treatment and allow comparisons across facilities and countries. The objective of this study was to review maternal sepsis definitions and identification criteria and to report on the results of an expert consultation to develop a new international definition of maternal sepsis. All original and review articles and WHO documents, as well as clinical guidelines providing definitions and/or identification criteria of maternal sepsis were included. A multidisciplinary international panel of experts was surveyed through an online consultation in March-April 2016 on their opinion on the existing sepsis definitions, including new definition of sepsis proposed for the adult population (2016 Third International Consensus Definitions for Sepsis and Septic Shock) and importance of different criteria for identification of maternal sepsis. The definition was agreed using an iterative process in an expert face-to-face consensus development meeting convened by WHO and Jhpiego. Standardizing the definition of maternal sepsis and aligning it with the current understanding of sepsis in the adult population was considered a mandatory step to improve the assessment of the burden of maternal sepsis by the expert panel. The literature review and expert consultation resulted in a new WHO consensus definition "Maternal sepsis is a life-threatening condition defined as organ dysfunction resulting from infection during pregnancy, child-birth, post-abortion, or post-partum period". Plans are in progress to validate the new WHO definition of maternal sepsis in a large international population. The operationalization of the new maternal sepsis definition requires generation of a set of practical criteria to identify women with sepsis. These criteria should enable clinicians to focus on the timely initiation of actionable elements of

Bacterial Sepsis in Brazilian Children: A Trend Analysis from 1992 to 2006

PubMed Central

Mangia, Cristina Malzoni Ferreira; Kissoon, Niranjan; Branchini, Otavio Augusto; Andrade, Maria Cristina; Kopelman, Benjamin Israel; Carcillo, Joe

2011-01-01

Background The objective of this study was to determine the epidemiology of hospitalized pediatric sepsis in Brazil (1992–2006) and to compare mortality caused by sepsis to that caused by other major childhood diseases. Methods and Findings We performed a retrospective descriptive study of hospital admissions using a government database of all hospital affiliated with the Brazilian health system. We studied all hospitalizations in children from 28 days through 19 years with diagnosis of bacterial sepsis defined by the criteria of the International Classification of Diseases (ICD), (Appendix S1). Based on the data studied from 1992 through 2006, the pediatric hospital mortality rate was 1.23% and there were 556,073 pediatric admissions with bacterial sepsis with a mean mortality rate of 19.9%. There was a case reduction of 67% over.1992–2006 (p<0.001); however, the mortality rate remained unchanged (from 1992–1996, 20.5%; and from 2002–2006, 19.7%). Sepsis-hospital mortality rate was substantially higher than pneumonia (0.5%), HIV (3.3%), diarrhea (0.3%), undernutrition (2.3%), malaria (0.2%) and measles (0.7%). The human development index (HDI) and mortality rates (MR) by region were: North region 0.76 and 21.7%; Northeast region 0.72 and 27.1%; Central-West 0.81 and 23.5%; South region 0.83 and 12.2% and Southeast region 0.82 and 14.8%, respectively. Conclusions We concluded that sepsis remains an important health problem in children in Brazil. The institution of universal primary care programs has been associated with substantially reduced sepsis incidence and therefore deaths; however, hospital mortality rates in children with sepsis remain unchanged. Implementation of additional health initiatives to reduce sepsis mortality in hospitalized patients could have great impact on childhood mortality rates in Brazil. PMID:21674036

Restorative Mechanisms Regulating Protein Balance in Skeletal Muscle During Recovery From Sepsis.

PubMed

Crowell, Kristen T; Soybel, David I; Lang, Charles H

2017-04-01

Muscle deconditioning is commonly observed in patients surviving sepsis. Little is known regarding the molecular mechanisms regulating muscle protein homeostasis during the recovery or convalescence phase. We adapted a sepsis-recovery mouse model that uses cecal ligation and puncture (CLP), followed 24 h later by cecal resection and antibiotic treatment, to identify putative cellular pathways regulating protein synthesis and breakdown in skeletal muscle. Ten days after CLP, body weight and food consumption did not differ between control and sepsis-recovery mice, but gastrocnemius weight was reduced. During sepsis-recovery, muscle protein synthesis was increased 2-fold and associated with enhanced mTOR kinase activity (4E-BP1 and S6K1 phosphorylation). The sepsis-induced increase in 4E-BP1 was associated with enhanced formation of the eIF4E-eIF4G active cap-dependent complex, while the increased S6K1 was associated with increased phosphorylation of downstream targets S6 and eIF4B. Proximal to mTOR, sepsis-recovery increased Akt and TSC2 phosphorylation, did not alter AMPK phosphorylation, and decreased REDD1 protein content. Despite the decreased mRNA content for the E3 ubiquitin ligases atrogin-1 and muscle RING-finger 1, proteasomal activity was increased 50%. In contrast, sepsis-recovery was associated with an apparent decrease in autophagy (e.g., increased ULK-1 phosphorylation, decreased LCB3-II, and increased p62). The mRNA content for IL-1β, IL-18, TNFα, and IL-6 in muscle was elevated in sepsis-recovery. During recovery after sepsis skeletal muscle responds with an increase in Akt-TSC2-mTOR-dependent protein synthesis and decreased autophagy, but full restoration of muscle protein content may be slowed by the continued stimulation of ubiquitin-proteasome activity.

Identification of MicroRNA as Sepsis Biomarker Based on miRNAs Regulatory Network Analysis

PubMed Central

Huang, Jie; Sun, Zhandong; Yan, Wenying; Zhu, Yujie; Lin, Yuxin; Chen, Jiajai; Shen, Bairong

2014-01-01

Sepsis is regarded as arising from an unusual systemic response to infection but the physiopathology of sepsis remains elusive. At present, sepsis is still a fatal condition with delayed diagnosis and a poor outcome. Many biomarkers have been reported in clinical application for patients with sepsis, and claimed to improve the diagnosis and treatment. Because of the difficulty in the interpreting of clinical features of sepsis, some biomarkers do not show high sensitivity and specificity. MicroRNAs (miRNAs) are small noncoding RNAs which pair the sites in mRNAs to regulate gene expression in eukaryotes. They play a key role in inflammatory response, and have been validated to be potential sepsis biomarker recently. In the present work, we apply a miRNA regulatory network based method to identify novel microRNA biomarkers associated with the early diagnosis of sepsis. By analyzing the miRNA expression profiles and the miRNA regulatory network, we obtained novel miRNAs associated with sepsis. Pathways analysis, disease ontology analysis, and protein-protein interaction network (PIN) analysis, as well as ROC curve, were exploited to testify the reliability of the predicted miRNAs. We finally identified 8 novel miRNAs which have the potential to be sepsis biomarkers. PMID:24809055

Angiopoietin-1, Angiopoietin-2 and Bicarbonate as Diagnostic Biomarkers in Children with Severe Sepsis

PubMed Central

Wang, Kun; Bhandari, Vineet; Giuliano, John S.; O′Hern, Corey S.; Shattuck, Mark D.; Kirby, Michael

2014-01-01

Severe pediatric sepsis continues to be associated with high mortality rates in children. Thus, an important area of biomedical research is to identify biomarkers that can classify sepsis severity and outcomes. The complex and heterogeneous nature of sepsis makes the prospect of the classification of sepsis severity using a single biomarker less likely. Instead, we employ machine learning techniques to validate the use of a multiple biomarkers scoring system to determine the severity of sepsis in critically ill children. The study was based on clinical data and plasma samples provided by a tertiary care center's Pediatric Intensive Care Unit (PICU) from a group of 45 patients with varying sepsis severity at the time of admission. Canonical Correlation Analysis with the Forward Selection and Random Forests methods identified a particular set of biomarkers that included Angiopoietin-1 (Ang-1), Angiopoietin-2 (Ang-2), and Bicarbonate (HCO) as having the strongest correlations with sepsis severity. The robustness and effectiveness of these biomarkers for classifying sepsis severity were validated by constructing a linear Support Vector Machine diagnostic classifier. We also show that the concentrations of Ang-1, Ang-2, and HCO enable predictions of the time dependence of sepsis severity in children. PMID:25255212

Sepsis and Critical Illness Research Center investigators: protocols and standard operating procedures for a prospective cohort study of sepsis in critically ill surgical patients.

PubMed

Loftus, Tyler J; Mira, Juan C; Ozrazgat-Baslanti, Tezcan; Ghita, Gabriella L; Wang, Zhongkai; Stortz, Julie A; Brumback, Babette A; Bihorac, Azra; Segal, Mark S; Anton, Stephen D; Leeuwenburgh, Christiaan; Mohr, Alicia M; Efron, Philip A; Moldawer, Lyle L; Moore, Frederick A; Brakenridge, Scott C

2017-08-01

Sepsis is a common, costly and morbid cause of critical illness in trauma and surgical patients. Ongoing advances in sepsis resuscitation and critical care support strategies have led to improved in-hospital mortality. However, these patients now survive to enter state of chronic critical illness (CCI), persistent low-grade organ dysfunction and poor long-term outcomes driven by the persistent inflammation, immunosuppression and catabolism syndrome (PICS). The Sepsis and Critical Illness Research Center (SCIRC) was created to provide a platform by which the prevalence and pathogenesis of CCI and PICS may be understood at a mechanistic level across multiple medical disciplines, leading to the development of novel management strategies and targeted therapies. Here, we describe the design, study cohort and standard operating procedures used in the prospective study of human sepsis at a level 1 trauma centre and tertiary care hospital providing care for over 2600 critically ill patients annually. These procedures include implementation of an automated sepsis surveillance initiative, augmentation of clinical decisions with a computerised sepsis protocol, strategies for direct exportation of quality-filtered data from the electronic medical record to a research database and robust long-term follow-up. This study has been registered at ClinicalTrials.gov, approved by the University of Florida Institutional Review Board and is actively enrolling subjects. Dissemination of results is forthcoming. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The role of heparin in sepsis: much more than just an anticoagulant.

PubMed

Li, Xu; Ma, Xiaochun

2017-11-01

Despite progress in antibiotic treatment, mechanical ventilation, fluid resuscitation and blood glucose maintenance, sepsis remains a cause of high mortality in the intensive care unit to date, there are no proven treatment strategies for the routine management of septic patients. The extensive interaction between inflammation and coagulation contributes to the basic pathophysiology of sepsis. Thus, the agents that attenuate the activation of both inflammation and coagulation may improve the outcome in sepsis. Apart from the well-known anticoagulant effects of heparin, it also possesses various immunomodulatory properties and protects glycocalyx from shedding. Hence, heparin seems to be such an agent. Immunothrombosis plays an important role in early host defence against bacterial dissemination, thus the proper timing for anticoagulant therapy should be determined. We review the available experimental and clinical data supporting the use of heparin in sepsis. At this time the use of heparin in the treatment of sepsis is conflicting. Future trials of heparin therapy for sepsis should concentrate on the very severely ill patients, in whom benefit is most likely to be demonstrated. © 2017 John Wiley & Sons Ltd.

An epidemiologic survey of pediatric sepsis in regional hospitals in China.

PubMed

Wang, Yuanyuan; Sun, Bo; Yue, Hongni; Lin, Xiaofei; Li, Bing; Yang, Xiaochun; Shan, Chunming; Fan, Yujin; Dong, Maotian; Zhang, Yixing; Lin, Wenlong; Zuo, Xiaofeng; Su, Ping; Heng, Yongbo; Xu, Jinzhong; Kissoon, Niranjan

2014-11-01

To determine the prevalence, treatment, and outcomes of sepsis at regional hospitals in Huai'an, Jiangsu, China. Prospective data registry using a descriptive clinical epidemiologic approach through a collaborative network. Pediatric departments in 11 regional city and county referral hospitals serving 843,000 children (exclusive of neonates). All admissions (n = 27,836) of patients from 28 days to 15 years old from September 1, 2010, to August 31, 2011. None. A total of 1,530 patients met the 2005 international consensus definition of sepsis, corresponding to an estimated incidence of 181/100,000 children, with 80% under 5 years old, and in 10% (153), severe sepsis or septic shock developed. The overall case fatality rate for sepsis was 3.5% (53/1,530) or 34.6% (53/153) in those in whom severe sepsis or septic shock developed. Treatment varied widely and in many instances did not conform to international guidelines as reflected by inadequate use of antibiotics, corticosteroids, vasoactive agents, and inotropes. We first report the prevalence and outcome of pediatric sepsis based on a regional hospital network in China. The diverse treatment approaches and practice at low-level clinics suggest the need for clinical implementation of internationally recognized strategy to improve the care standard in resource-limited regional hospitals.

Initial management of pneumonia and sepsis: factors associated with improved outcome.

PubMed

Menéndez, R; Torres, A; Reyes, S; Zalacain, R; Capelastegui, A; Aspa, J; Borderías, L; Martín-Villasclaras, J J; Bello, S; Alfageme, I; de Castro, F R; Rello, J; Molinos, L; Ruiz-Manzano, J

2012-01-01

Processes of care and adherence to guidelines have been associated with improved survival in community-acquired pneumonia (CAP). In sepsis, bundles of processes of care have also increased survival. We aimed to audit compliance with guideline-recommended processes of care and its impact on outcome in hospitalised CAP patients with sepsis. We prospectively studied 4,137 patients hospitalised with CAP in 13 hospitals. The processes of care evaluated were adherence to antibiotic prescription guidelines, first dose within 6 h and oxygen assessment. Outcome measures were mortality and length of stay (LOS). Oxygen assessment was measured in 3,745 (90.5%) patients; 3,024 (73.1%) patients received antibiotics according to guidelines and 3,053 (73.8%) received antibiotics within 6 h. In CAP patients with sepsis, the strongest independent factor for survival was antibiotic adherence (OR 0.4). In severe sepsis, only compliance to antibiotic adherence plus first dose within 6 h was associated with lower mortality (OR 0.60), adjusted for fine prognostic scale and hospital. Antibiotic adherence was related to shorter hospital stay. In sepsis, antibiotic adherence is the strongest protective factor of care associated with survival and LOS. In severe sepsis, combined antibiotic adherence and first dose within 6 h may reduce mortality.

A quality improvement project to improve early sepsis care in the emergency department.

PubMed

Gatewood, Medley O'Keefe; Wemple, Matthew; Greco, Sheryl; Kritek, Patricia A; Durvasula, Raghu

2015-12-01

Sepsis causes substantial morbidity and mortality in hospitalised patients. Although many studies describe the use of protocols in the management of patients with severe sepsis and septic shock, few have addressed emergency department (ED) screening and management for patients initially presenting with uncomplicated sepsis (ie, patients without organ failure or hypotension). A quality improvement task force at a large, quaternary care referral hospital sought to develop a protocol focusing on early identification of patients with uncomplicated sepsis, in addition to severe sepsis and septic shock. The three-tiered intervention consisted of (1) a nurse-driven screening tool and management protocol to identify and initiate early treatment of patients with sepsis, (2) a computer-assisted screening algorithm that generated a 'Sepsis Alert' pop-up screen in the electronic medical record for treating clinical healthcare providers and (3) automated suggested sepsis-specific order sets for initial workup and resuscitation, antibiotic selection and goal-directed therapy. A before and after retrospective cohort study was undertaken to determine the intervention's impact on compliance with recommended sepsis management, including serum lactate measured in the ED, 2 L of intravenous fluid administered within 2 h of triage, antibiotics administered within 3 h of triage and blood cultures drawn before antibiotic administration. Mortality rates for patients in the ED with a sepsis-designated ICD-9 code present on admission were also analysed. Overall bundle compliance increased by 154%, from 28% at baseline to 71% in the last quarter of the study (p<0.001). Bundle, antibiotic and intravenous fluid compliance all increased significantly after launch of the sepsis initiative (eg, bundle and intravenous fluid compliance increased by 74% and 54%, respectively; p<0.001). Bundle and antibiotic compliance both showed further significant increases after implementation of suggested

Genetic polymorphism in postoperative sepsis after open heart surgery in infants.

PubMed

Fakhri, Dicky; Djauzi, Samsuridjal; Murni, Tri Wahyu; Rachmat, Jusuf; Harahap, Alida Roswita; Rahayuningsih, Sri Endah; Mansyur, Muchtaruddin; Santoso, Anwar

2016-05-01

Sepsis is one of the complications following open heart surgery. Toll-like receptor 2 and toll-interacting protein polymorphism influence the immune response after open heart surgery. This study aimed to assess the genetic distribution of toll-like receptor 2 N199N and toll-interacting protein rs5743867 polymorphism in the development of postoperative sepsis. A prospective cohort study was conducted in 108 children <1-year old who underwent open heart surgery with a Basic Aristotle score ≥6. Patients with an accompanying congenital anomaly, human immunodeficiency virus infection, or history of previous open heart surgery were excluded. The patients' nutritional status and genetic polymorphism were assessed prior to surgery. The results of genetic polymorphism were obtained through genotyping. Patients' ages on the day of surgery and cardiopulmonary bypass times were recorded. The diagnosis of sepsis was established according to Surviving Sepsis Campaign criteria. Postoperative sepsis was observed in 21% of patients. There were 92.6% patients with toll-like receptor 2 N199N polymorphism and 52.8% with toll-interacting protein rs5743867 polymorphism. Toll-like receptor 2 N199N polymorphism tends to increase the risk of sepsis (odds ratio = 1.974; 95% confidence interval: 0.23-16.92; p = 0.504), while toll-interacting protein rs5743867 polymorphism tends to decrease the risk of sepsis (odds ratio = 0.496; 95% confidence interval: 0.19-1.27; p = 0.139) in infants <1-year old undergoing complex open heart surgery. © The Author(s) 2016.

Sepsis in general surgery: the 2005-2007 national surgical quality improvement program perspective.

PubMed

Moore, Laura J; Moore, Frederick A; Todd, S Rob; Jones, Stephen L; Turner, Krista L; Bass, Barbara L

2010-07-01

To document the incidence, mortality rate, and risk factors for sepsis and septic shock compared with pulmonary embolism and myocardial infarction in the general-surgery population. Retrospective review. American College of Surgeons National Surgical Quality Improvement Program institutions. General-surgery patients in the 2005-2007 National Surgical Quality Improvement Program data set. Incidence, mortality rate, and risk factors for sepsis and septic shock. Of 363 897 general-surgery patients, sepsis occurred in 8350 (2.3%), septic shock in 5977 (1.6%), pulmonary embolism in 1078 (0.3%), and myocardial infarction in 615 (0.2%). Thirty-day mortality rates for each of the groups were as follows: 5.4% for sepsis, 33.7% for septic shock, 9.1% for pulmonary embolism, and 32.0% for myocardial infarction. The septic-shock group had a greater percentage of patients older than 60 years (no sepsis, 40.2%; sepsis, 51.7%; and septic shock, 70.3%; P < .001). The need for emergency surgery resulted in more cases of sepsis (4.5%) and septic shock (4.9%) than did elective surgery (sepsis, 2.0%; septic shock, 1.2%) (P < .001). The presence of any comorbidity increased the risk of sepsis and septic shock 6-fold (odds ratio, 5.8; 95% confidence interval, 5.5-6.2) and increased the 30-day mortality rate 22-fold (odds ratio, 21.8; 95% confidence interval, 17.6-26.9). The incidences of sepsis and septic shock exceed those of pulmonary embolism and myocardial infarction. The risk factors for mortality include age older than 60 years, the need for emergency surgery, and the presence of any comorbidity. This study emphasizes the need for early recognition of patients at risk via aggressive screening and the rapid implementation of evidence-based guidelines.

Psychosocial stress as a risk factor for sepsis: a population-based cohort study.

PubMed

Ojard, Connor; Donnelly, John P; Safford, Monika M; Griffin, Russell; Wang, Henry E

2015-01-01

To characterize the relationship between stress and future risk of sepsis. We also evaluated the role of depression in this relationship. We used population-based data on 30,183 participants in the Reasons for Geographic and Racial Differences in Stroke cohort, characterizing stress using the Perceived Stress Scale (PSS) and depressive symptoms using the Center for Epidemiologic Studies Depression Scale (CES-D). We identified incident sepsis events as hospitalizations for a serious infection with the presence of at least two systemic inflammatory response syndrome criteria. We assessed associations between PSS and incidence of sepsis for 1 and 10 years of follow-up, adjusting for demographics and chronic medical conditions and assessing the role of health behaviors and CES-D in these relationships. In 2003 to 2012, 1500 participants experienced an episode of sepsis. Mean PSS and CES-D scores were 3.2 (2.9) and 1.2 (2.1). PSS was associated with increased 1-year adjusted incidence of sepsis (hazard ratio [HR] = 1.21 per PSS standard deviation, 95% confidence interval = 1.06-1.38); multivariable adjustment for health behaviors and CES-D did not change this association (1.20, 1.03-1.39). PSS was also associated with increased 10-year adjusted incidence of sepsis (HR = 1.07 per PSS standard deviation; 95% confidence interval = 1.02-1.13). Multivariable adjustment showed that health behaviors did not affect this long-term association, whereas the addition of CES-D reduced the association between PSS and sepsis during 10-year follow-up (HR = 1.04, 0.98-1.11). Increased stress was associated with higher 1-year adjusted incidence of sepsis, even after accounting for depressive symptoms. The association between stress and 10-year adjusted incidence of sepsis was also significant, but this association was reduced when adjusting for depressive symptoms. Reduction of stress may limit short-term sepsis risk.

Endothelial glycocalyx degradation is more severe in patients with non-pulmonary sepsis compared to pulmonary sepsis and associates with risk of ARDS and other organ dysfunction.

PubMed

Murphy, Laura S; Wickersham, Nancy; McNeil, J Brennan; Shaver, Ciara M; May, Addison K; Bastarache, Julie A; Ware, Lorraine B

2017-10-06

Disruption of the endothelial glycocalyx contributes to acute lung injury in experimental sepsis but has not been well studied in humans. To study glycocalyx degradation in sepsis-induced ARDS, we measured plasma levels of syndecan-1, a marker for glycocalyx degradation. The present study is a retrospective observational study of 262 ventilated medical ICU patients at risk of ARDS due to severe sepsis and APACHE II ≥ 25. Plasma syndecan-1 was measured at study enrollment. Primary analysis focused on the association between syndecan-1 levels and the development of ARDS, other organ dysfunction (Brussels criteria), or in-hospital mortality. Overall, 135 (52%) patients developed ARDS. In patients with non-pulmonary sepsis, syndecan-1 levels were associated with ARDS (p = 0.05). Regardless of etiology of sepsis, higher syndecan-1 levels were associated with hepatic (p < 0.001), renal (p = 0.003), coagulation (p = 0.001), and circulatory (p = 0.02) failure as well as in-hospital mortality (p = 0.001), and there was a significant association between syndecan-1 levels and the number of vasopressors required in the first 24 h (p < 0.001). In addition, elevated syndecan levels were independently predictive of mortality in multivariable logistic regression adjusted for age and APACHE II score (odds ratio 1.85 per log increase in syndecan-1, 95% CI 1.056-3.241, p = 0.03). The extent of endothelial glycocalyx degradation is associated with non-pulmonary organ dysfunction in subjects with sepsis and is associated with ARDS but only in the subgroup with non-pulmonary sepsis. Measurement of syndecan-1 levels in sepsis patients might be useful for identifying patients at high risk of organ dysfunction and mortality as well as those who could benefit from therapies targeted at protecting or restoring the glycocalyx.

Time for a neonatal–specific consensus definition for sepsis

PubMed Central

Wynn, James L.; Wong, Hector R.; Shanley, Thomas P.; Bizzarro, Matthew J.; Saiman, Lisa; Polin, Richard A.

2014-01-01

Objective To review the accuracy of the pediatric consensus definition of sepsis in term neonates and to determine the definition of neonatal sepsis used. Study selection The review focused primarily on pediatric literature relevant to the topic of interest. Conclusions Neonatal sepsis is variably defined based on a number of clinical and laboratory criteria that make the study of this common and devastating condition very difficult. Diagnostic challenges and uncertain disease epidemiology necessarily result from a variable definition of disease. In 2005, intensivists caring for children recognized that as new drugs became available, children would be increasingly studied and thus, pediatric-specific consensus definitions were needed. Pediatric sepsis criteria are not accurate for term neonates and have not been examined in preterm neonates for whom the developmental stage influences aberrations associated with host immune response. Thus, specific consensus definitions for both term and preterm neonates are needed. Such definitions are critical for the interpretation of observational studies, future training of scientists and practitioners, and implementation of clinical trials in neonates. PMID:24751791

Inter-Alpha Inhibitor Protein (IAIP) Administration Improves Survival From Neonatal Sepsis In Mice

PubMed Central

Singh, Kultar; Zhang, Ling Xiu; Bendelja, Kreso; Heath, Ryan; Murphy, Shaun; Sharma, Surendra; Padbury, James F.; Lim, Yow-Pin

2010-01-01

Inter-alpha Inhibitor proteins (IaIp) are serine proteases inhibitors which modulate endogenous protease activity and have been shown to improve survival in adult models of sepsis. We evaluated the effect of IaIp on survival and systemic responses to sepsis in neonatal mice. Sepsis was induced in 2-day-old mice with LPS, E. coli and Group B Streptococci. Sepsis was associated with 75% mortality. IaIp, given by intraperitoneal administration at doses between 15–45 mg/kg from 1–6 hours following the onset of sepsis improved survival to nearly 90% (p = 0.0159) in both LPS induced sepsis and with live bacterial infections. The greatest effect was on reversal of hemorrhagic pneumonitis. The effects were dose and time dependent. Systemic cytokine profile and tissue histology were examined. Survival was compared in interleukin 10 knock out animals. Systemic cytokine levels, including TNF-α and IL-10 were increased following induction of sepsis and modulated significantly following IaIp administration. Because the effect of IaIp was still demonstrable in IL-10 deficient mice, we conclude the beneficial effect(s) of IaIp is due to suppression of pro-inflammatory cytokines like TNF-α rather than augmentation of IL-10. IaIp may offer significant benefits as a therapeutic adjunct to treatment of sepsis in neonates and adults. PMID:20520583

The recognition and management of sepsis and septic shock: a guide for non-intensivists.

PubMed

Keeley, Alexander; Hine, Paul; Nsutebu, Emmanuel

2017-10-01

Sepsis is common, often fatal and requires rapid interventions to improve outcomes. While the optimal management of sepsis in the intensive care setting is the focus of extensive research interest, the mainstay of the recognition and initial management of sepsis will occur outside the intensive care setting. Therefore, it is key that institutions and clinicians remain well informed of the current updates in sepsis management and continue to use them to deliver appropriate and timely interventions to enhance patient survival. This review discusses the latest updates in sepsis care including the new consensus definition of sepsis, the outcome of the proCESS, ProMISe and ARISE trials of early goal directed therapy (EGDT), and the most recent guidelines from the Surviving Sepsis Campaign. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Accurate coding in sepsis: clinical significance and financial implications.

PubMed

Chin, Y T; Scattergood, N; Thornber, M; Thomas, S

2016-09-01

Sepsis is a major healthcare problem and leading cause of death worldwide. UK hospital mortality statistics and payments for patient episodes of care are calculated on clinical coding data. The accuracy of these data depends on the quality of coding. This study aimed to investigate whether patients with significant bacteraemia are coded for sepsis and to estimate the financial costs of miscoding. Of 54 patients over a one-month period with a significant bacteraemia, only 19% had been coded for sepsis. This is likely to lead to falsely high calculated hospital mortality. Furthermore, this resulted in an underpayment of £21,000 for one month alone. Copyright © 2016 The Healthcare Infection Society. All rights reserved.

Emodin alleviates jejunum injury in rats with sepsis by inhibiting inflammation response.

PubMed

Chen, Yi-Kun; Xu, Ying-Kun; Zhang, Hao; Yin, Jiang-Tao; Fan, Xin; Liu, Da-Dong; Fu, Hai-Yan; Wan, Bing

2016-12-01

Emodin is an anthraquinone derived from Chinese herb that exerts anti-inflammation effects. This study aimed to investigate whether emodin provides the protection for jejunum injury by inhibiting inflammation. We established a model of sepsis caused by cecal ligation and puncture. Forty-eight male Wistar rats were divided into four groups (n=12). Jejunum injury was assessed by pathological examination. The activity of pJAK1/pSTAT3 and protein levels of Bcl-2 and Bax were detected by Western blot analysis. Inflammatory factors IL-6, TNF-α and procalcitonin were detected by ELISA. Apoptosis was detected by TUNEL. We found that emodin alleviated jejunum damage and apoptosis induced by sepsis and decreased the levels of IL-6, TNF-α and procalcitonin in septic rats. Furthermore, we observed that emodin increased the levels of pJAK1 and of pSTAT3, which were decreased in rats with sepsis. In addition, emodin enhanced the expression of Bcl-2 which was downregulated by sepsis and decreased the expression of Bax which was upregulated by sepsis. In conclusion, these results indicate that emodin suppresses inflammatory response induced by sepsis. Emodin activates JAK1/STAT3 signaling pathway and regulates Bcl-2 and Bax expression to protect the jejunum in rats with sepsis. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Esmolol reduces apoptosis and inflammation in early sepsis rats with abdominal infection.

PubMed

Lu, Yang; Yang, Yang; He, Xin; Dong, Shangwen; Wang, Wanhua; Wang, Donghao; Zhang, Peng

2017-10-01

Esmolol is a highly selective beta 1 receptor blocker with various effects such as slowing heart rate, lowering blood pressure and reducing myocardial oxygen consumption. However, few studies have reported the use of beta blockers in sepsis with multiple organ dysfunctions. This study aimed to investigate the effects of esmolol on reducing apoptosis and inflammation in early sepsis rats with abdominal infection. Rats were randomly divided into sham operation group, sepsis group, antibiotic group, Esmolol + antibiotic group with low, median and high dose Esmolol (L group, M group and H group). Values between two or more groups were compared by independent t-tests. In the liver and kidney, we found inflammatory infiltration in sepsis group while pathological aspects reduced in L, M and H groups. Bcl-2 mRNA and protein levels increased while Bax mRNA and protein levels decreased in the liver and kidney of L, M and H groups. Serum IL-6, HMGB-1 and TNF-α levels decreased but IL-10 level increased in L, M and H groups, compared to sepsis group. Compared to sepsis and antibiotic groups, the levels of myocardial enzymes were lower in L, M and H groups. The administration of esmolol in early sepsis may reduce inflammation, inhibit apoptosis and protect key organs. Copyright © 2017 Elsevier Inc. All rights reserved.

Targeting IL-17A attenuates neonatal sepsis mortality induced by IL-18

PubMed Central

Wynn, James Lawrence; Wilson, Chris S.; Hawiger, Jacek; Scumpia, Philip O.; Marshall, Andrew F.; Liu, Jin-Hua; Zharkikh, Irina; Wong, Hector R.; Lahni, Patrick; Benjamin, John T.; Plosa, Erin J.; Weitkamp, Jörn-Hendrik; Sherwood, Edward R.; Moldawer, Lyle L.; Ungaro, Ricardo; Baker, Henry V.; Lopez, M. Cecilia; McElroy, Steven J.; Colliou, Natacha; Mohamadzadeh, Mansour; Moore, Daniel Jensen

2016-01-01

Interleukin (IL)-18 is an important effector of innate and adaptive immunity, but its expression must also be tightly regulated because it can potentiate lethal systemic inflammation and death. Healthy and septic human neonates demonstrate elevated serum concentrations of IL-18 compared with adults. Thus, we determined the contribution of IL-18 to lethality and its mechanism in a murine model of neonatal sepsis. We find that IL-18–null neonatal mice are highly protected from polymicrobial sepsis, whereas replenishing IL-18 increased lethality to sepsis or endotoxemia. Increased lethality depended on IL-1 receptor 1 (IL-1R1) signaling but not adaptive immunity. In genome-wide analyses of blood mRNA from septic human neonates, expression of the IL-17 receptor emerged as a critical regulatory node. Indeed, IL-18 administration in sepsis increased IL-17A production by murine intestinal γδT cells as well as Ly6G+ myeloid cells, and blocking IL-17A reduced IL-18–potentiated mortality to both neonatal sepsis and endotoxemia. We conclude that IL-17A is a previously unrecognized effector of IL-18–mediated injury in neonatal sepsis and that disruption of the deleterious and tissue-destructive IL-18/IL-1/IL-17A axis represents a novel therapeutic approach to improve outcomes for human neonates with sepsis. PMID:27114524

Stem cells in sepsis and acute lung injury.

PubMed

Cribbs, Sushma K; Matthay, Michael A; Martin, Greg S

2010-12-01

Sepsis and acute lung injury continue to be major causes of morbidity and mortality worldwide despite advances in our understanding of pathophysiology and the discovery of new management strategies. Recent investigations show that stem cells may be beneficial as prognostic biomarkers and novel therapeutic strategies in these syndromes. This article reviews the potential use of endogenous adult tissue-derived stem cells in sepsis and acute lung injury as prognostic markers and also as exogenous cell-based therapy. A directed systematic search of the medical literature using PubMed and OVID, with particular emphasis on the time period after 2002, was done to evaluate topics related to 1) the epidemiology and pathophysiology of sepsis and acute lung injury; and 2) the definition, characterization, and potential use of stem cells in these diseases. DATA SYNTHESIS AND FINDINGS: When available, preferential consideration was given to prospective nonrandomized clinical and preclinical studies. Stem cells have shown significant promise in the field of critical care both for 1) prognostic value and 2) treatment strategies. Although several recent studies have identified the potential benefit of stem cells in sepsis and acute lung injury, further investigations are needed to more completely understand stem cells and their potential prognostic and therapeutic value.

Comparison of Two Sepsis Recognition Methods in a Pediatric Emergency Department

PubMed Central

Balamuth, Fran; Alpern, Elizabeth R.; Grundmeier, Robert W.; Chilutti, Marianne; Weiss, Scott L.; Fitzgerald, Julie C.; Hayes, Katie; Bilker, Warren; Lautenbach, Ebbing

2015-01-01

Objectives To compare the effectiveness of physician judgment and an electronic algorithmic alert to identify pediatric patients with severe sepsis/septic shock in a pediatric emergency department (ED). Methods This was an observational cohort study of patients older than 56 days with fever or hypothermia. All patients were evaluated for potential sepsis in real time by the ED clinical team. An electronic algorithmic alert was retrospectively applied to identify patients with potential sepsis independent of physician judgment. The primary outcome was the proportion of patients correctly identified with severe sepsis/septic shock defined by consensus criteria. Test characteristics were determined and receiver operating characteristic (ROC) curves were compared. Results Of 19,524 eligible patient visits, 88 patients developed consensus-confirmed severe sepsis or septic shock. Physician judgment identified 159, and the algorithmic alert identified 3,301 patients with potential sepsis. Physician judgment had sensitivity of 72.7% (95% CI = 72.1% to 73.4%) and specificity 99.5% (95% CI = 99.4% to 99.6%); the algorithmic alert had sensitivity 92.1% (95% CI = 91.7% to 92.4%), and specificity 83.4% (95% CI = 82.9% to 83.9%) for severe sepsis/septic shock. There was no significant difference in the area under the ROC curve for physician judgment (0.86, 95% CI = 0.81 to 0.91) or the algorithm (0.88, 95% CI = 0.85 to 0.91; p = 0.54). A combination method using either positive physician judgment or an algorithmic alert improved sensitivity to 96.6% and specificity to 83.3%. A sequential approach, in which positive identification by the algorithmic alert was then confirmed by physician judgment, achieved 68.2% sensitivity and 99.6% specificity. Positive and negative predictive values for physician judgment vs. algorithmic alert were 40.3% vs. 2.5% and 99.88 % vs. 99.96%, respectively. Conclusions The electronic algorithmic alert was more sensitive but less specific than

Comparison of Two Sepsis Recognition Methods in a Pediatric Emergency Department.

PubMed

Balamuth, Fran; Alpern, Elizabeth R; Grundmeier, Robert W; Chilutti, Marianne; Weiss, Scott L; Fitzgerald, Julie C; Hayes, Katie; Bilker, Warren; Lautenbach, Ebbing

2015-11-01

The objective was to compare the effectiveness of physician judgment and an electronic algorithmic alert to identify pediatric patients with severe sepsis/septic shock in a pediatric emergency department (ED). This was an observational cohort study of patients older than 56 days with fever or hypothermia. All patients were evaluated for potential sepsis in real time by the ED clinical team. An electronic algorithmic alert was retrospectively applied to identify patients with potential sepsis independent of physician judgment. The primary outcome was the proportion of patients correctly identified with severe sepsis/septic shock defined by consensus criteria. Test characteristics were determined and receiver operating characteristic (ROC) curves were compared. Of 19,524 eligible patient visits, 88 patients developed consensus-confirmed severe sepsis or septic shock. Physician judgment identified 159 and the algorithmic alert identified 3,301 patients with potential sepsis. Physician judgment had sensitivity of 72.7% (95% confidence interval [CI] = 72.1% to 73.4%) and specificity of 99.5% (95% CI = 99.4% to 99.6%); the algorithmic alert had sensitivity of 92.1% (95% CI = 91.7% to 92.4%) and specificity of 83.4% (95% CI = 82.9% to 83.9%) for severe sepsis/septic shock. There was no significant difference in the area under the ROC curve for physician judgment (0.86, 95% CI = 0.81 to 0.91) or the algorithm (0.88, 95% CI = 0.85 to 0.91; p = 0.54). A combination method using either positive physician judgment or an algorithmic alert improved sensitivity to 96.6% and specificity to 83.3%. A sequential approach, in which positive identification by the algorithmic alert was then confirmed by physician judgment, achieved 68.2% sensitivity and 99.6% specificity. Positive and negative predictive values for physician judgment versus algorithmic alert were 40.3% versus 2.5% and 99.88% versus 99.96%, respectively. The electronic algorithmic alert was more sensitive but less

Interprofessional Collaboration to Improve Sepsis Care and Survival Within a Tertiary Care Emergency Department.

PubMed

Tedesco, Elizabeth R; Whiteman, Kimberly; Heuston, Melanie; Swanson-Biearman, Brenda; Stephens, Kimberly

2017-11-01

Sepsis is a leading cause of death in the United States; however, health care providers struggle with timely recognition, diagnosis, and treatment of patients. Both the Centers for Medicare and Medicaid Services and the National Quality Forum have identified this diagnosis as a priority. Presently, many patients with sepsis are identified late, resulting in significant morbidity and death. In this project, a collaborative, interprofessional approach was created for screening and early identification of ED patients with possible sepsis. The department has 38 beds with annual patient volumes of more than 40,000 visits. Education was provided about the symptoms and treatment of patients with sepsis. A screening and management algorithm tool was instituted that consisted of early identification triggers and how to intervene according to Surviving Sepsis Campaign recommendations. The tool allowed for assessment of the patient by the ED team; the team worked to determine if sepsis was present and the extent of the illness. During the first 4 months after implementation, more than 240 patients were screened, assessed, and treated according to the algorithm. Project outcomes resulted in an increase in staff knowledge of sepsis, a decrease in length of stay by 3 hours, and a significant decrease in mortality when compared with the previous year's coded data. This project demonstrates that sepsis education and team collaboration are an integral part of identifying and treating patients with sepsis. An interprofessional collaborative approach could be implemented in other institutions to combat the life-threatening complications of sepsis. Copyright © 2017 Emergency Nurses Association. Published by Elsevier Inc. All rights reserved.

The Atypical Chemokine Receptor ACKR2 is Protective Against Sepsis.

PubMed

Castanheira, Fernanda V E Silva; Borges, Vanessa; Sônego, Fabiane; Kanashiro, Alexandre; Donate, Paula B; Melo, Paulo H; Pallas, Kenneth; Russo, Remo C; Amaral, Flávio A; Teixeira, Mauro M; Ramalho, Fernando S; Cunha, Thiago M; Liew, Foo Y; Alves-Filho, José C; Graham, Gerard J; Cunha, Fernando Q

2018-06-01

Sepsis is a systemic inflammatory response as a result of uncontrolled infections. Neutrophils are the first cells to reach the primary sites of infection, and chemokines play a key role in recruiting neutrophils. However, in sepsis chemokines could also contribute to neutrophil infiltration to vital organs leading to multiple organ failure. ACKR2 is an atypical chemokine receptor, which can remove and degrade inflammatory CC chemokines. The role of ACK2 in sepsis is unknown. Using a model of cecal ligation and puncture (CLP), we demonstrate here that ACKR2 deficient () mice exhibited a significant reduction in the survival rate compared with similarly treated wild-type (WT) mice. However, neutrophil migration to the peritoneal cavity and bacterial load were similar between WT and ACKR2 mice during CLP. In contrast, ACKR2 mice showed increased neutrophil infiltration and elevated CC chemokine levels in the lung, kidney, and heart compared with the WT mice. In addition, ACKR2 mice also showed more severe lesions in the lung and kidney than those in the WT mice. Consistent with these results, WT mice under nonsevere sepsis (90% survival) had higher expression of ACKR2 in these organs than mice under severe sepsis (no survival). Finally, the lungs from septic patients showed increased number of ACKR2 cells compared with those of nonseptic patients. Our data indicate that ACKR2 may have a protective role during sepsis, and the absence of ACKR2 leads to exacerbated chemokine accumulation, neutrophil infiltration, and damage to vital organs.

Endothelial Progenitor Cell Mobilization in Preterm Infants With Sepsis Is Associated With Improved Survival.

PubMed

Siavashi, Vahid; Asadian, Simin; Taheri-Asl, Masoud; Keshavarz, Samaneh; Zamani-Ahmadmahmudi, Mohamad; Nassiri, Seyed Mahdi

2017-10-01

Microvascular dysfunction plays a key role in the pathology of sepsis, leading to multi-organ failure, and death. Circulating endothelial progenitor cells (cEPCs) are critically involved in the maintenance of the vascular homeostasis in both physiological and pathological contexts. In this study, concentration of cEPCs in preterm infants with sepsis was determined to recognize whether the EPC mobilization would affect the clinical outcome of infantile sepsis. One hundred and thirty-three preterm infants (81 with sepsis and 52 without sepsis) were enrolled in this study. The release of EPCs in circulation was first quantified. Thereafter, these cells were cultivated and biological features of these cells such as, proliferation and colony forming efficiency were analyzed. The levels of chemoattractant cytokines were also measured in infants. In mouse models of sepsis, effects of VEGF and SDF-1 as well as anti-VEGF and anti-SDF-1 were evaluated in order to shed light upon the role which the EPC mobilization plays in the overall survival of septic animals. Circulating EPCs were significantly higher in preterm infants with sepsis than in the non-sepsis group. Serum levels of VEGF, SDF-1, and Angiopoietin-2 were also higher in preterm infants with sepsis than in control non-sepsis. In the animal experiments, injection of VEGF and SDF-1 prompted the mobilization of EPCs, leading to an improvement in survival whereas injection of anti-VEGF and anti-SDF-1 was associated with significant deterioration of survival. Overall, our results demonstrated the beneficial effects of EPC release in preterm infants with sepsis, with increased mobilization of these cells was associated with improved survival. J. Cell. Biochem. 118: 3299-3307, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

[Risk Factors for Healthcare Associated Sepsis in Very Low Birth Weight Infants].

PubMed

Pereira, Helena; Grilo, Ema; Cardoso, Patrícia; Noronha, Natália; Resende, Cristina

2016-04-01

Healthcare associated infections in very low birth weight infants are associated with significant morbidity and mortality and are also a cause of increased length of stay and hospital costs. The objective of this study was to evaluate the rate of healthcare-associated sepsis and associated risk factors in very low birth weight infants. Retrospective observational study including very low birth weight infants hospitalized in a Neonatal Intensive Care Unit during ten years (2005-2014). We evaluated the association between several risk factors and healthcare-associated sepsis. 461 very low birth weight infants were admitted. There were 110 episodes of HS in 104 very low birth weight infants and 53 episodes of sepsis associated with central vascular catheter. The density of the sepsis was 7.5/1 000 days of hospitalization and the density of central vascular catheter - associated sepsis was 22.6/1 000 days of use. The infants with HS had lower average birth weight and gestational age (959 ± 228 g vs 1191 ± 249 g and 27.6 ± 2 vs 29.8 ± 2.2 weeks), p < 0.001. After adjusting for birth weight and gestational age we verified an association between healthcare-associated sepsis and antibiotic therapy in D1, the duration of parenteral nutrition and central vascular catheter. After logistic regression only the gestational age and duration of parenteral nutrition remained as independent significant risk factors for healthcare-associated sepsis. The independent factors for healthcare-associated sepsis are gestational age and duration of parenteral nutrition. For each extra week on gestational age the risk declined in 20% and for each day of NP the risk increased 22%.

Development of metabolic and inflammatory mediator biomarker phenotyping for early diagnosis and triage of pediatric sepsis.

PubMed

Mickiewicz, Beata; Thompson, Graham C; Blackwood, Jaime; Jenne, Craig N; Winston, Brent W; Vogel, Hans J; Joffe, Ari R

2015-09-09

The first steps in goal-directed therapy for sepsis are early diagnosis followed by appropriate triage. These steps are usually left to the physician's judgment, as there is no accepted biomarker available. We aimed to determine biomarker phenotypes that differentiate children with sepsis who require intensive care from those who do not. We conducted a prospective, observational nested cohort study at two pediatric intensive care units (PICUs) and one pediatric emergency department (ED). Children ages 2-17 years presenting to the PICU or ED with sepsis or presenting for procedural sedation to the ED were enrolled. We used the judgment of regional pediatric ED and PICU attending physicians as the standard to determine triage location (PICU or ED). We performed metabolic and inflammatory protein mediator profiling with serum and plasma samples, respectively, collected upon presentation, followed by multivariate statistical analysis. Ninety-four PICU sepsis, 81 ED sepsis, and 63 ED control patients were included. Metabolomic profiling revealed clear separation of groups, differentiating PICU sepsis from ED sepsis with accuracy of 0.89, area under the receiver operating characteristic curve (AUROC) of 0.96 (standard deviation [SD] 0.01), and predictive ability (Q(2)) of 0.60. Protein mediator profiling also showed clear separation of the groups, differentiating PICU sepsis from ED sepsis with accuracy of 0.78 and AUROC of 0.88 (SD 0.03). Combining metabolomic and protein mediator profiling improved the model (Q(2) =0.62), differentiating PICU sepsis from ED sepsis with accuracy of 0.87 and AUROC of 0.95 (SD 0.01). Separation of PICU sepsis or ED sepsis from ED controls was even more accurate. Prespecified age subgroups (2-5 years old and 6-17 years old) improved model accuracy minimally. Seventeen metabolites or protein mediators accounted for separation of PICU sepsis and ED sepsis with 95% confidence. In children ages 2-17 years, combining metabolomic and

Intraintestinal administration of ulinastatin protects against sepsis by relieving intestinal damage.

PubMed

Yang, Bingchang; Gao, Min; Wang, Kangkai; Jiang, Yu; Peng, Yue; Zhang, Huali; Yang, Mingshi; Xiao, Xianzhong

2017-05-01

Intravenous administration of ulinastatin (UTI), a broad spectral protease inhibitor, has been used on an experimental basis with severe sepsis patients in Asia. However, the effects of intraintestinal administration of UTI on intestinal and multiple organ damage in sepsis have not been reported. In this study, we established a sepsis model in rats using cecal ligation and puncture and compared the effects of intraintestinal administration of UTI through an artificial fistula of duodenum and intraperitoneal administration of UTI on the pathophysiological changes of sepsis. It was found that intraintestinal administration of UTI (1) significantly improved the survival of septic rats, (2) significantly reduced the serum levels of tumor necrosis factor-α, interleukin-1β, interleukin-6 as well as intestinal injury biomarkers diamine oxidase, D-lactic acid, and fluorescein isothiocyanate-dextran 4, and (3) significantly reduced intestinal microscopic and ultrastructural damage of septic rats. In addition, the protective effects of intraintestinal administration of UTI were significantly better than those of intraperitoneal administration of UTI. Overall, the present study for the first time revealed that intraintestinal administration of protease inhibitor UTI could reduce systemic inflammatory responses and multiple organ dysfunction in rats with sepsis by inhibiting autodigestion of intestinal wall due to proteases and provided new research ideas and experimental evidences for treatment of sepsis by intraintestinal administration of UTI. Copyright © 2016. Published by Elsevier Inc.

Parameters of oxidative metabolism in neonates suffering from sepsis and anemia.

PubMed

Sanodze, N; Uberi, N; Uberi, E; Kulumbegov, B

2006-11-01

Neonatal sepsis still remains as one of the actual problems in modern medicine due to its high morbidity and mortality rates determined by diagnostic difficulties and absence of sufficient evidence for effective therapy. Literature data have shown that essential role in pathogenesis of sepsis belongs to the cellular oxidation-reduction misballance and development of the oxidative stress. The aim of our work was to assess indices of pro- and antioxidant systems in term neonates with sepsis on the background of anemia and without it. A total of 41 neonates (17 male, 24 female) with the age range from 3 to 7 days, with early sepsis, and in 2003-2005 years treated at the department of neonates' therapy and intensive care unit of pediatric clinics of the Tbilisi State Medical University were under observation. The control group involved 17 practically healthy neonates of the same age range. In consequence of the analyses there was ascertained, that with anemia increases intensification free-radical oxidation process. At the same time, antioxidant system activity was not change significantly in the sepsis with anemia, than other one. Pathogenesis of anemia may was founded undergo hemolitic anemia results by oxidative stress. According to the results of investigations could be concluded that in case of anemia developed at neonatal sepsis supports intensify of oxidative stress and at the same time anemia is the result of the oxidative stress.

β-hydroxy-β-methylbutyrate (HMB) Prevents Sepsis-Induced Diaphragm Dysfunction in Mice

PubMed Central

Supinski, Gerald S.; Callahan, Leigh Ann

2014-01-01

Infections induce severe respiratory muscle weakness. Currently there are no treatments for this important clinical problem. We tested the hypothesis that β-hydroxy-β-methylbutyrate (HMB) would prevent sepsis-induced diaphragm weakness. Four groups of adult male mice were studied: controls (saline-injected), sepsis (intraperitoneal lipopolysaccharide), sepsis+HMB (injected intravenously), and HMB. Diaphragm force generation and indices of caspase 3, calpain, 20S proteasomal subunit, and double-stranded RNA-dependent protein kinase (PKR) activation were assessed after 24 hours. Sepsis elicited large reductions in diaphragm specific force generation at all stimulation frequencies. Endotoxin also activated caspase 3, calpain, the 20S proteasomal subunit and PKR in the diaphragm. HMB blocked sepsis-induced caspase 3, 20S proteasomal and PKR activation, but did not prevent calpain activation. Most importantly, HMB administration significantly attenuated sepsis-induced diaphragm weakness, preserving muscle force generation at all stimulation frequencies (p<0.01). We speculate that HMB may prove to be an important therapy in infected patients, with the potential to increase diaphragm strength, to reduce the duration of mechanical ventilation and to decrease mortality in this patient population PMID:24632527

β-hydroxy-β-methylbutyrate (HMB) prevents sepsis-induced diaphragm dysfunction in mice.

PubMed

Supinski, Gerald S; Callahan, Leigh A

2014-06-01

Infections induce severe respiratory muscle weakness. Currently there are no treatments for this important clinical problem. We tested the hypothesis that β-hydroxy-β-methylbutyrate (HMB) would prevent sepsis-induced diaphragm weakness. Four groups of adult male mice were studied: controls (saline-injected), sepsis (intraperitoneal lipopolysaccharide), sepsis+HMB (injected intravenously), and HMB. Diaphragm force generation and indices of caspase 3, calpain, 20S proteasomal subunit, and double-stranded RNA-dependent protein kinase (PKR) activation were assessed after 24h. Sepsis elicited large reductions in diaphragm specific force generation at all stimulation frequencies. Endotoxin also activated caspase 3, calpain, the 20S proteasomal subunit and PKR in the diaphragm. HMB blocked sepsis-induced caspase 3, 20S proteasomal and PKR activation, but did not prevent calpain activation. Most importantly, HMB administration significantly attenuated sepsis-induced diaphragm weakness, preserving muscle force generation at all stimulation frequencies (p<0.01). We speculate that HMB may prove to be an important therapy in infected patients, with the potential to increase diaphragm strength, to reduce the duration of mechanical ventilation and to decrease mortality in this patient population. Copyright © 2014 Elsevier B.V. All rights reserved.

Diagnostic accuracy and effectiveness of automated electronic sepsis alert systems: A systematic review.

PubMed

Makam, Anil N; Nguyen, Oanh K; Auerbach, Andrew D

2015-06-01

Although timely treatment of sepsis improves outcomes, delays in administering evidence-based therapies are common. To determine whether automated real-time electronic sepsis alerts can: (1) accurately identify sepsis and (2) improve process measures and outcomes. We systematically searched MEDLINE, Embase, The Cochrane Library, and Cumulative Index to Nursing and Allied Health Literature from database inception through June 27, 2014. Included studies that empirically evaluated 1 or both of the prespecified objectives. Two independent reviewers extracted data and assessed the risk of bias. Diagnostic accuracy of sepsis identification was measured by sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and likelihood ratio (LR). Effectiveness was assessed by changes in sepsis care process measures and outcomes. Of 1293 citations, 8 studies met inclusion criteria, 5 for the identification of sepsis (n = 35,423) and 5 for the effectiveness of sepsis alerts (n = 6894). Though definition of sepsis alert thresholds varied, most included systemic inflammatory response syndrome criteria ± evidence of shock. Diagnostic accuracy varied greatly, with PPV ranging from 20.5% to 53.8%, NPV 76.5% to 99.7%, LR+ 1.2 to 145.8, and LR- 0.06 to 0.86. There was modest evidence for improvement in process measures (ie, antibiotic escalation), but only among patients in non-critical care settings; there were no corresponding improvements in mortality or length of stay. Minimal data were reported on potential harms due to false positive alerts. Automated sepsis alerts derived from electronic health data may improve care processes but tend to have poor PPV and do not improve mortality or length of stay. © 2015 Society of Hospital Medicine.

Diagnostic Accuracy and Effectiveness of Automated Electronic Sepsis Alert Systems: A Systematic Review

PubMed Central

Makam, Anil N.; Nguyen, Oanh K.; Auerbach, Andrew D.

2015-01-01

Background Although timely treatment of sepsis improves outcomes, delays in administering evidence-based therapies are common. Purpose To determine whether automated real-time electronic sepsis alerts can: 1) accurately identify sepsis, and 2) improve process measures and outcomes. Data Sources We systematically searched MEDLINE, Embase, The Cochrane Library, and CINAHL from database inception through June 27, 2014. Study Selection Included studies that empirically evaluated one or both of the prespecified objectives. Data Extraction Two independent reviewers extracted data and assessed the risk of bias. Diagnostic accuracy of sepsis identification was measured by sensitivity, specificity, positive (PPV) and negative predictive values (NPV) and likelihood ratios (LR). Effectiveness was assessed by changes in sepsis care process measures and outcomes. Data Synthesis Of 1,293 citations, 8 studies met inclusion criteria, 5 for the identification of sepsis (n=35,423) and 5 for the effectiveness of sepsis alerts (n=6,894). Though definition of sepsis alert thresholds varied, most included systemic inflammatory response syndrome criteria ± evidence of shock. Diagnostic accuracy varied greatly, with PPV ranging from 20.5-53.8%, NPV 76.5-99.7%; LR+ 1.2-145.8; and LR- 0.06-0.86. There was modest evidence for improvement in process measures (i.e., antibiotic escalation), but only among patients in non-critical care settings; there were no corresponding improvements in mortality or length of stay. Minimal data were reported on potential harms due to false positive alerts. Conclusions Automated sepsis alerts derived from electronic health data may improve care processes but tend to have poor positive predictive value and do not improve mortality or length of stay. PMID:25758641

Sepsis and Acute Kidney Injury.

PubMed

Bilgili, Beliz; Haliloğlu, Murat; Cinel, İsmail

2014-12-01

Acute kindney injury (AKI) is a clinical syndrome which is generally defined as an abrupt decline in glomerular filtration rate, causing accumulation of nitrogenous products and rapid development of fluid, electrolyte and acid base disorders. In intensive care unit sepsis and septic shock are leading causes of AKI. Sepsis-induced AKI literally acts as a biologic indicator of clinical deterioration. AKI triggers variety of immune, inflammatory, metabolic and humoral patways; ultimately leading distant organ dysfunction and increases morbidity and mortality. Serial mesurements of creatinine and urine volume do not make it possible to diagnose AKI at early stages. Serum creatinine influenced by age, weight, hydration status and become apparent only when the kidneys have lost 50% of their function. For that reason we need new markers, and many biomarkers in the diagnosis of early AKI activity is assessed. Historically "Risk-Injury-Failure-Loss-Endstage" (RIFLE), "Acute Kidney Injury Netwok" (AKIN) and "The Kidney Disease/ Improving Global Outcomes" (KDIGO) classification systems are used for diagnosing easily in clinical practice and research and grading disease. Classifications including diagnostic criteria are formed for the identification of AKI. Neutrophil gelatinase associated lipocalin (NGAL), cystatin-C (Cys-C), kidney injury molecule-1 (KIM-1) and also "cell cycle arrest" molecules has been concerned for clinical use. In this review the pathophysiology of AKI, with the relationship of sepsis and the importance of early diagnosis of AKI is evaluated.

Use of Systematic Methods to Improve Disease Identification in Administrative Data: The Case of Severe Sepsis.

PubMed

Shahraz, Saeid; Lagu, Tara; Ritter, Grant A; Liu, Xiadong; Tompkins, Christopher

2017-03-01

Selection of International Classification of Diseases (ICD)-based coded information for complex conditions such as severe sepsis is a subjective process and the results are sensitive to the codes selected. We use an innovative data exploration method to guide ICD-based case selection for severe sepsis. Using the Nationwide Inpatient Sample, we applied Latent Class Analysis (LCA) to determine if medical coders follow any uniform and sensible coding for observations with severe sepsis. We examined whether ICD-9 codes specific to sepsis (038.xx for septicemia, a subset of 995.9 codes representing Systemic Inflammatory Response syndrome, and 785.52 for septic shock) could all be members of the same latent class. Hospitalizations coded with sepsis-specific codes could be assigned to a latent class of their own. This class constituted 22.8% of all potential sepsis observations. The probability of an observation with any sepsis-specific codes being assigned to the residual class was near 0. The chance of an observation in the residual class having a sepsis-specific code as the principal diagnosis was close to 0. Validity of sepsis class assignment is supported by empirical results, which indicated that in-hospital deaths in the sepsis-specific class were around 4 times as likely as that in the residual class. The conventional methods of defining severe sepsis cases in observational data substantially misclassify sepsis cases. We suggest a methodology that helps reliable selection of ICD codes for conditions that require complex coding.

[Evaluation of coagulation disorders with thrombelastography in patients with sepsis].

PubMed

Zhong, Shengjian; Zhang, Chunbao; Hu, Juntao; Tang, Zhanhong

2016-02-01

To compare the results of thrombelastography (TEG) and the conventional coagulability test in patients with sepsis, and to discuss the value of TEG in monitoring blood coagulation dysfunction in patients with sepsis. The clinical data of 92 adult patients with sepsis admitted to Department of Critical Care Medicine of the First Affiliated Hospital of Guangxi Medical University were retrospectively analyzed. The patients were divided into sequential organ failure assessment (SOFA) score ≥ 12 group (n = 47) and SOFA < 12 group (n = 45). Thirty-five non-sepsis adult patients with normal coagulation function served as control group. The venous blood was collected for conventional blood coagulation test and routine examination of blood, D-dimer, procalcitonin (PCT), and TEG, and the differences were compared among three groups. Correlations between SOFA and various indexes of patients with sepsis were analyzed by Spearman rank correlation method. As shown in the results of the conventional blood coagulation test, D-dimer was gradually increased with the aggravation of the disease, the values in non-sepsis, SOFA < 12, and SOFA ≥ 12 groups were 0.523 (0.273, 0.928), 0.863 (0.673, 4.221), and 4.118 (2.420, 5.653) mg/L respectively (Z = 25.163, P = 0.000). Platelet count (PLT) in SOFA ≥ 12 group was significantly lower than that of the SOFA < 12 group and non-sepsis group [×10(9)/L: 28.6 (12.8, 48.9) vs. 257.3 (152.6, 339.8), 182.0 (118.0, 229.0), both P < 0.01]. There was no significant difference in prothrombin time (PT) and international normalized ratio (INR) among three groups, and it indicated that the conventional blood coagulation test might not respond quickly to the change in coagulation status of sepsis patients. As shown in the results of TEG, the values of reaction time (R value) and kinetics time (K value) in SOFA < 12 group were lower than those of the non-sepsis group [R value (minutes): 4.4 (3.6, 6.1) vs. 6.3 (6.0, 6.7), P < 0.01; K value (minutes

[Relationship between highly sensitive cardiac troponin T and sepsis and outcome in critically ill patients].

PubMed

Wang, T T; Jiang, L

2017-10-01

Objective: To investigate the prognostic value of highly sensitive cardiac Troponin T (hs-cTn T) for sepsis in critically ill patients. Methods: Patients estimated to stay in the ICU of Fuxing Hospital for more than 24h were enrolled at from March 2014 to December 2014. Serum hs-cTn T was tested within two hours. Univariate and multivariate linear regression analyses were used to determine the association of variables with the hs-cTn T. Multivariable logistic regression analysis was used to evaluate the risk factors of 28-day mortality. Results: A total of 125 patients were finally enrolled including 68 patients with sepsis and 57 without. The levels of hs-cTn T in sepsis and non-sepsis groups were significantly different[52.0(32.5, 87.5) ng/L vs 14.0(6.5, 29.0) ng/L respectively, P <0.001]. In sepsis group, hs-cTn T among common sepsis, severe sepsis and septic shock were similar. Hs-cTn T was significantly higher in non-survivors than survivors [27(13, 52)ng/L vs 44.5(28.8, 83.5)ng/L, P <0.001]. Age, sepsis, serum creatinine were independent risk factors affecting hs-cTn T by multivariate linear regression analyses. But hs-cTn T was not a risk factor for death. Conclusion: Patients with sepsis had higher serum hs-cTn T than those without sepsis. but it was not found to be associated with the severity of sepsis.

Standardized Approach to Quantitatively Measure Residual Limb Skin Health in Individuals with Lower Limb Amputation.

PubMed

Rink, Cameron L; Wernke, Matthew M; Powell, Heather M; Tornero, Mark; Gnyawali, Surya C; Schroeder, Ryan M; Kim, Jayne Y; Denune, Jeffrey A; Albury, Alexander W; Gordillo, Gayle M; Colvin, James M; Sen, Chandan K

2017-07-01

Objective: (1) Develop a standardized approach to quantitatively measure residual limb skin health. (2) Report reference residual limb skin health values in people with transtibial and transfemoral amputation. Approach: Residual limb health outcomes in individuals with transtibial ( n  = 5) and transfemoral ( n  = 5) amputation were compared to able-limb controls ( n  = 4) using noninvasive imaging (hyperspectral imaging and laser speckle flowmetry) and probe-based approaches (laser doppler flowmetry, transcutaneous oxygen, transepidermal water loss, surface electrical capacitance). Results: A standardized methodology that employs noninvasive imaging and probe-based approaches to measure residual limb skin health are described. Compared to able-limb controls, individuals with transtibial and transfemoral amputation have significantly lower transcutaneous oxygen tension, higher transepidermal water loss, and higher surface electrical capacitance in the residual limb. Innovation: Residual limb health as a critical component of prosthesis rehabilitation for individuals with lower limb amputation is understudied in part due to a lack of clinical measures. Here, we present a standardized approach to measure residual limb health in people with transtibial and transfemoral amputation. Conclusion: Technology advances in noninvasive imaging and probe-based measures are leveraged to develop a standardized approach to quantitatively measure residual limb health in individuals with lower limb loss. Compared to able-limb controls, resting residual limb physiology in people that have had transfemoral or transtibial amputation is characterized by lower transcutaneous oxygen tension and poorer skin barrier function.

The Effect of Hospital Volume on Mortality in Patients Admitted with Severe Sepsis

PubMed Central

Shahul, Sajid; Hacker, Michele R.; Novack, Victor; Mueller, Ariel; Shaefi, Shahzad; Mahmood, Bilal; Ali, Syed Haider; Talmor, Daniel

2014-01-01

Importance The association between hospital volume and inpatient mortality for severe sepsis is unclear. Objective To assess the effect of severe sepsis case volume and inpatient mortality. Design Setting and Participants Retrospective cohort study from 646,988 patient discharges with severe sepsis from 3,487 hospitals in the Nationwide Inpatient Sample from 2002 to 2011. Exposures The exposure of interest was the mean yearly sepsis case volume per hospital divided into tertiles. Main Outcomes and Measures Inpatient mortality. Results Compared with the highest tertile of severe sepsis volume (>60 cases per year), the odds ratio for inpatient mortality among persons admitted to hospitals in the lowest tertile (≤10 severe sepsis cases per year) was 1.188 (95% CI: 1.074–1.315), while the odds ratio was 1.090 (95% CI: 1.031–1.152) for patients admitted to hospitals in the middle tertile. Similarly, improved survival was seen across the tertiles with an adjusted inpatient mortality incidence of 35.81 (95% CI: 33.64–38.03) for hospitals with the lowest volume of severe sepsis cases and a drop to 32.07 (95% CI: 31.51–32.64) for hospitals with the highest volume. Conclusions and Relevance We demonstrate an association between a higher severe sepsis case volume and decreased mortality. The need for a systems-based approach for improved outcomes may require a high volume of severely septic patients. PMID:25264788

Macrophage P2X4 receptors augment bacterial killing and protect against sepsis

PubMed Central

Csóka, Balázs; Németh, Zoltán H.; Szabó, Ildikó; Davies, Daryl L.; Varga, Zoltán V.; Pálóczi, János; Falzoni, Simonetta; Di Virgilio, Francesco; Muramatsu, Rieko; Pacher, Pál

2018-01-01

The macrophage is a major phagocytic cell type, and its impaired function is a primary cause of immune paralysis, organ injury, and death in sepsis. An incomplete understanding of the endogenous molecules that regulate macrophage bactericidal activity is a major barrier for developing effective therapies for sepsis. Using an in vitro killing assay, we report here that the endogenous purine ATP augments the killing of sepsis-causing bacteria by macrophages through P2X4 receptors (P2X4Rs). Using newly developed transgenic mice expressing a bioluminescent ATP probe on the cell surface, we found that extracellular ATP levels increase during sepsis, indicating that ATP may contribute to bacterial killing in vivo. Studies with P2X4R-deficient mice subjected to sepsis confirm the role of extracellular ATP acting on P2X4Rs in killing bacteria and protecting against organ injury and death. Results with adoptive transfer of macrophages, myeloid-specific P2X4R-deficient mice, and P2rx4 tdTomato reporter mice indicate that macrophages are essential for the antibacterial, antiinflammatory, and organ protective effects of P2X4Rs in sepsis. Pharmacological targeting of P2X4Rs with the allosteric activator ivermectin protects against bacterial dissemination and mortality in sepsis. We propose that P2X4Rs represent a promising target for drug development to control bacterial growth in sepsis and other infections. PMID:29875325

Cerebral blood flow is reduced in patients with sepsis syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bowton, D.L.; Bertels, N.H.; Prough, D.S.

The relationship between sepsis-induced CNS dysfunction and changes in brain blood flow remains unknown, and animal studies examining the influence of sepsis on cerebral blood flow (CBF) do not satisfactorily address that relationship. We measured CBF and cerebrovascular reactivity to CO/sub 2/ in nine patients with sepsis syndrome using the /sup 133/Xe clearance technique. Mean CBF was 29.6 +/- 15.8 (SD) ml/100 g.min, significantly lower than the normal age-matched value in this laboratory of 44.9 +/- 6.2 ml/100 g.min (p less than .02). This depression did not correlate with changes in mean arterial pressure. Despite the reduction in CBF, themore » specific reactivity of the cerebral vasculature to changes in CO/sub 2/ was normal, 1.3 +/- 0.9 ml/100 g.min/mm Hg. Brain blood flow is reduced in septic humans; the contribution of this reduction to the metabolic and functional changes observed in sepsis requires further study.« less

[Metabolic therapy and pulmonary disfunction in patients with obstetric sepsis].

PubMed

Iakovlev, A Iu; Zaĭtsev, P M; Zubeev, P S; Mokrov, K B; Balandina, A V; Gushchina, N N; Kucherenko, V E

2011-01-01

The role of reamberin, a succinate-containing infusion preparation in correlation of pulmonary metabolic and respiratory disturbances in patients with obstetric puerperal sepsis was estimated. The prospective randomized study enrolled 43 patients with puerperal obstetric sepsis complicated by polyorganic deficiency (SOFA 8-10). Nineteen patients of the 1st group and 24 patients of the 2nd group were additionally treated with reamberin in a dose of 800 ml/day for 8 days. The venous and arterial difference by glucose, lactate, pyruvate, diene conjugates, malondialdehyde and ceruloplasmin was investigated. The blood gases were determined with the Ciba Corning 45 apparatus. Lower metabolic activity of the lungs with prevalence of the glucose anaerobic metabolism and lower activity of the intrapulmonary antioxidant protection were observed in the patients with obstetric sepsis. The use of reamberin in the complex therapy of obstetric sepsis promoted maintenance of the initial balance and anaeroibic and aerobic pulmonary metabolism, thus providing shorter terms of the decompensation and recovery of the lungs respiratory function.

[CONTEMPORARY MOLECULAR-GENETIC METHODS USED FOR ETIOLOGIC DIAGNOSTICS OF SEPSIS].

PubMed

Gavrilov, S N; Skachkova, T S; Shipulina, O Yu; Savochkina, Yu A; Shipulin, G A; Maleev, V V

2016-01-01

Etiologic diagnostics of sepsis is one of the most difficult problems of contemporary medicine due to a wide variety of sepsis causative agents, many of which are components of normal human microflora. Disadvantages of contemporary "golden standard" of microbiologic diagnostics of sepsis etiology by seeding of blood for sterility are duration of cultivation, limitation in detection of non-cultivable forms of microorganisms, significant effect of preliminary empiric antibiotics therapy on results of the analysis. Methods of molecular diagnostics that are being actively developed and integrated during the last decade are deprived of these disadvantages. Main contemporary methods of molecular-biological diagnostics are examined in the review, actualdata on their diagnostic characteristic are provided. Special attention is given to methods of PCR-diagnostics, including novel Russian developments. Methods of nucleic acid hybridization and proteomic analysis are examined in comparative aspect. Evaluation of application and perspectives of development of methods of molecular diagnostics of sepsis is given.

Drotrecogin alfa (activated): a novel therapeutic strategy for severe sepsis

PubMed Central

Pastores, S

2003-01-01

Recent studies have highlighted the close link between activation of the coagulation system and the inflammatory response in the pathophysiology of severe sepsis. The protein C anticoagulant pathway plays an integral part in modulating the coagulation and inflammatory responses to infection. In patients with sepsis, endogenous protein C levels are decreased, shifting the balance toward greater systemic inflammation, coagulation, and cell death. On the basis of a single large randomised phase 3 trial, drotrecogin alfa (activated), a recombinant form of human activated protein C, was recently approved for the treatment of adult patients with severe sepsis and a high risk of death. Since its approval, several questions have been raised regarding the appropriate use of this agent. Given the increased risk of serious bleeding and the high cost of treatment, drotrecogin alfa (activated) should be reserved at this time for the most acutely ill patients with severe sepsis who meet the criteria that were used in the phase 3 trial. PMID:12566544

Risk of fever and sepsis evaluations after routine immunizations in the neonatal intensive care unit.

PubMed

Navar-Boggan, A M; Halsey, N A; Golden, W C; Escobar, G J; Massolo, M; Klein, N P

2010-09-01

Premature infants can experience cardiorespiratory events such as apnea after immunization in the neonatal intensive care unit (NICU). These changes in clinical status may precipitate sepsis evaluations. This study evaluated whether sepsis evaluations are increased after immunizations in the NICU. We conducted a retrospective cohort study of infants older than 53 days who were vaccinated in the NICU at the KPMCP (Kaiser Permanente Medical Care Program). Chart reviews were carried out before and after all immunizations were administered and for all sepsis evaluations after age 53 days. The clinical characteristics of infants on the day before receiving a sepsis evaluation were compared between children undergoing post-immunization sepsis evaluations and children undergoing sepsis evaluation at other times. The incidence rate of sepsis evaluations in the post-immunization period was compared with the rate in a control time period not following immunization using Poisson regression. A total of 490 infants met the inclusion criteria. The rate of fever was increased in the 24 h period after vaccination (2.3%, P<0.05). The incidence rate of sepsis evaluations was 40% lower after immunization than during the control period, although this was not statistically significant (P=0.09). Infants undergoing a sepsis evaluation after immunization were more likely to have an apneic, bradycardic or moderate-to-severe cardiorespiratory event in the day before the evaluation than were infants undergoing sepsis evaluations at other times (P<0.05). Despite an increase in fever and cardiorespiratory events after immunization in the NICU, routine vaccination was not associated with increased risk of receiving sepsis evaluations. Providers may be deferring immunizations until infants are clinically stable, or may have a higher threshold for initiating sepsis evaluations after immunization than at other times.

Programmed Cell Death-1/Programmed Death-ligand 1 Pathway: A New Target for Sepsis.

PubMed

Liu, Qiang; Li, Chun-Sheng

2017-04-20

Sepsis remains a leading cause of death in many Intensive Care Units worldwide. Immunosuppression has been a primary focus of sepsis research as a key pathophysiological mechanism. Given the important role of the negative costimulatory molecules programmed cell death-1 (PD-1) and programmed death-ligand 1 (PD-L1) in the occurrence of immunosuppression during sepsis, we reviewed literatures related to the PD-1/PD-L1 pathway to examine its potential as a new target for sepsis treatment. Studies of the association between PD-1/PD-L1 and sepsis published up to January 31, 2017, were obtained by searching the PubMed database. English language studies, including those based on animal models, clinical research, and reviews, with data related to PD-1/PD-L1 and sepsis, were evaluated. Immunomodulatory therapeutics could reverse the deactivation of immune cells caused by sepsis and restore immune cell activation and function. Blockade of the PD-1/PD-L1 pathway could reduce the exhaustion of T-cells and enhance the proliferation and activation of T-cells. The anti-PD-1/PD-L1 pathway shows promise as a new target for sepsis treatment. This review provides a basis for clinical trials and future studies aimed at revaluating the efficacy and safety of this targeted approach.

Relationship between gut and sepsis: Role of ghrelin

PubMed Central

Das, Undurti N

2011-01-01

Ghrelin is a growth hormone secretagogue produced by the gut, and is expressed in the hypothalamus and other tissues as well. Ghrelin not only plays an important role in the regulation of appetite, energy balance and glucose homeostasis, but also shows anti-bacterial activity, suppresses pro-inflammatory cytokine production and restores gut barrier function. In experimental animals, ghrelin has shown significant beneficial actions in preventing mortality from sepsis. In the critically ill, corticosteroid insufficiency as a result of dysfunction of the hypothalamic-pituitary-adrenal axis is known to occur. It is therefore possible that both gut and hypothalamus play an important role in the pathogenesis of sepsis by virtue of their ability to produce ghrelin, which, in turn, could be a protective phenomenon to suppress inflammation. It remains to be seen whether ghrelin and its analogues are of benefit in treating patients with sepsis. PMID:21537444

Does Infection Site Matter? A Systematic Review of Infection Site Mortality in Sepsis.

PubMed

Motzkus, Christine A; Luckmann, Roger

2017-09-01

Sepsis treatment protocols emphasize source control with empiric antibiotics and fluid resuscitation. Previous reviews have examined the impact of infection site and specific pathogens on mortality from sepsis; however, no recent review has addressed the infection site. This review focuses on the impact of infection site on hospital mortality among patients with sepsis. The PubMed database was searched for articles from 2001 to 2014. Studies were eligible if they included (1) one or more statistical models with hospital mortality as the outcome and considered infection site for inclusion in the model and (2) adult patients with sepsis, severe sepsis, or septic shock. Data abstracted included stage of sepsis, infection site, and raw and adjusted effect estimates. Nineteen studies were included. Infection sites most studied included respiratory (n = 19), abdominal (n = 19), genitourinary (n = 18), and skin and soft tissue infections (n = 11). Several studies found a statistically significant lower mortality risk for genitourinary infections on hospital mortality when compared to respiratory infections. Based on studies included in this review, the impact of infection site in patients with sepsis on hospital mortality could not be reliably estimated. Misclassification among infections and disease states remains a serious possibility in studies on this topic.

Prediction of pediatric sepsis mortality within 1 h of intensive care admission.

PubMed

Schlapbach, Luregn J; MacLaren, Graeme; Festa, Marino; Alexander, Janet; Erickson, Simon; Beca, John; Slater, Anthony; Schibler, Andreas; Pilcher, David; Millar, Johnny; Straney, Lahn

2017-08-01

The definitions of sepsis and septic shock have recently been revised in adults, but contemporary data are needed to inform similar approaches in children. Multicenter cohort study including children <16 years admitted with sepsis or septic shock to ICUs in Australia and New Zealand in the period 2012-2015. We assessed septic shock criteria at ICU admission to define sepsis severity, using 30-day mortality as outcome. Through multivariable logistic regression, a pediatric sepsis score was derived using variables available within 60 min of ICU admission. Of 42,523 pediatric admissions, 4403 children were admitted with invasive infection, including 1697 diagnosed as having sepsis/septic shock on admission. Mortality was 8.5% (144/1697) and 50.7% of deaths occurred within 48 h of admission. The presence of septic shock as defined by the 2005 consensus was sensitive but not specific in predicting mortality (AUC = 0.69; 95% CI 0.65-0.72). Combinations of hypotension, vasopressor therapy, and lactate >2 mmol/l discriminated poorly (AUC <0.60). Multivariate models showed that oxygenation markers, ventilatory support, hypotension, cardiac arrest, serum lactate, pupil responsiveness, and immunosuppression were the best-performing predictors (0.843; 0.811-0.875). We derived a pediatric sepsis score (0.817; 0.779-0.855), and every one-point increase was associated with a 28.5% (23.8-33.2%) increase in the odds of death. Children with a score ≥6 had 19.8% mortality and accounted for 74.3% of deaths. The sepsis score performed comparably when applied to all children admitted with invasive infection (0.810; 0.781-0.840). We observed mortality patterns specific to pediatric sepsis that support the need for specialized definitions of sepsis severity in children. We demonstrated the importance of lactate, cardiovascular, and respiratory derangements at ICU admission for the identification of children with substantially higher risk of sepsis mortality.

Decreased ADAMTS 13 Activity is Associated With Disease Severity and Outcome in Pediatric Severe Sepsis

PubMed Central

Lin, Jainn-Jim; Chan, Oi-Wa; Hsiao, Hsiang-Ju; Wang, Yu; Hsia, Shao-Hsuan; Chiu, Cheng-Hsun

2016-01-01

Abstract Decreased ADAMTS 13 activity has been reported in severe sepsis and in sepsis-induced disseminated intravascular coagulation. This study aimed to investigate the role of ADAMTS 13 in different pediatric sepsis syndromes and evaluate its relationship with disease severity and outcome. We prospectively collected cases of sepsis treated in a pediatric intensive care unit, between July 2012 and June 2014 in Chang Gung Children's Hospital in Taoyuan, Taiwan. Clinical characteristics and ADAMTS-13 activity were analyzed. All sepsis syndromes had decreased ADAMTS 13 activity on days 1 and 3 of admission compared to healthy controls. Patients with septic shock had significantly decreased ADAMTS 13 activity on days 1 and 3 compared to those with sepsis and severe sepsis. There was a significant negative correlation between ADAMTS 13 activity on day 1 and day 1 PRISM-II, PELOD, P-MOD, and DIC scores. Patients with mortality had significantly decreased ADAMTS 13 activity on day 1 than survivors, but not on day 3. Different pediatric sepsis syndromes have varying degrees of decreased ADAMTS 13 activity. ADAMTS 13 activity is strongly negatively correlated with disease severity of pediatric sepsis syndrome, whereas decreased ADAMTS 13 activity on day 1 is associated with increased risk of mortality. PMID:27100422

Decreased ADAMTS 13 Activity is Associated With Disease Severity and Outcome in Pediatric Severe Sepsis.

PubMed

Lin, Jainn-Jim; Chan, Oi-Wa; Hsiao, Hsiang-Ju; Wang, Yu; Hsia, Shao-Hsuan; Chiu, Cheng-Hsun

2016-04-01

Decreased ADAMTS 13 activity has been reported in severe sepsis and in sepsis-induced disseminated intravascular coagulation. This study aimed to investigate the role of ADAMTS 13 in different pediatric sepsis syndromes and evaluate its relationship with disease severity and outcome. We prospectively collected cases of sepsis treated in a pediatric intensive care unit, between July 2012 and June 2014 in Chang Gung Children's Hospital in Taoyuan, Taiwan. Clinical characteristics and ADAMTS-13 activity were analyzed. All sepsis syndromes had decreased ADAMTS 13 activity on days 1 and 3 of admission compared to healthy controls. Patients with septic shock had significantly decreased ADAMTS 13 activity on days 1 and 3 compared to those with sepsis and severe sepsis. There was a significant negative correlation between ADAMTS 13 activity on day 1 and day 1 PRISM-II, PELOD, P-MOD, and DIC scores. Patients with mortality had significantly decreased ADAMTS 13 activity on day 1 than survivors, but not on day 3. Different pediatric sepsis syndromes have varying degrees of decreased ADAMTS 13 activity. ADAMTS 13 activity is strongly negatively correlated with disease severity of pediatric sepsis syndrome, whereas decreased ADAMTS 13 activity on day 1 is associated with increased risk of mortality.

Maturity aggravates sepsis-associated skeletal muscle catabolism in growing pigs

USDA-ARS?s Scientific Manuscript database

Synthesis and accretion of muscle protein is elevated in neonates and decreases with development. During sepsis, muscle protein synthesis is reduced, but the effect of development on the metabolic response to sepsis in skeletal muscle is not well understood. Fasted 7- and 26-d-old pigs were infused ...

Procession to pediatric bacteremia and sepsis: covert operations and failures in diplomacy.

PubMed

Bateman, Stacey L; Seed, Patrick C

2010-07-01

Despite advances in diagnosis and treatment, bacterial sepsis remains a major cause of pediatric morbidity and mortality, particularly among neonates, the critically ill, and the growing immunocompromised patient population. Sepsis is the end point of a complex and dynamic series of events in which both host and microbial factors drive high morbidity and potentially lethal physiologic alterations. In this article we provide a succinct overview of the events that lead to pediatric bloodstream infections (BSIs) and sepsis, with a focus on the molecular mechanisms used by bacteria to subvert host barriers and local immunity to gain access to and persist within the systemic circulation. In the events preceding and during BSI and sepsis, Gram-positive and Gram-negative pathogens use a battery of factors for translocation, inhibition of immunity, molecular mimicry, intracellular survival, and nutrient scavenging. Gaps in understanding the molecular pathogenesis of bacterial BSIs and sepsis are highlighted as opportunities to identify and develop new therapeutics.

Artemisinin protects mice against burn sepsis through inhibiting NLRP3 inflammasome activation.

PubMed

Long, Huibao; Xu, Bincan; Luo, Yanling; Luo, Keqin

2016-05-01

NLRP3 inflammasome activation is recently reported to be linked to the pathogenesis of sepsis. Artemisinin is shown to play beneficial effects in sepsis. However, the impacts of artemisinin on burn sepsis have not been investigated. This study is designed to investigate the role of artemisinin in burn sepsis and the involvement of NLRP3 inflammasome activation. Male BALB/c mice were randomly divided into sham burn, burn, burn sepsis, and artemisinin treated groups. Inflammatory cytokines were measured by enzyme-linked immunosorbent assay. Adhesion molecules and neutrophil infiltration in lung and heart were detected by real-time polymerase chain reaction. Mortality rates were monitored. Artemisinin was added to Raw 264.7 cells that were stimulated with burn sepsis serum in the presence/absence of an inhibitor of NLRP3 inflammasome, 3, 4-methylenedioxy-β-nitrostyrene. Interleukin (IL) 1β and IL-18 messenger RNA expression as well as NLRP3 and caspase 1 protein were measured. Production of inflammatory cytokines in serum, levels of adhesion molecules and neutrophil infiltration in lung and heart, and mortality rate of burn septic mice were significantly higher than those of control. These effects were attenuated by artemisinin. Artemisinin down-regulated protein levels of NLRP3 and caspase 1 and inhibited the increases of IL-1β and IL-18 messenger RNA expression from Raw 264.7 cells that were stimulated with burn sepsis serum. These effects of artemisinin were not further strengthened in the presence of 4-methylenedioxy-β-nitrostyrene. Artemisinin protects mice from burn sepsis by attenuating the inflammatory response and alleviating inflammatory infiltration in vital organs, likely through inhibiting the activation of NLRP3 inflammasome. Copyright © 2016 Elsevier Inc. All rights reserved.

Age-related differences in biomarkers of acute inflammation during hospitalization for sepsis.

PubMed

Ginde, Adit A; Blatchford, Patrick J; Trzeciak, Stephen; Hollander, Judd E; Birkhahn, Robert; Otero, Ronny; Osborn, Tiffany M; Moretti, Eugene; Nguyen, H Bryant; Gunnerson, Kyle J; Milzman, David; Gaieski, David F; Goyal, Munish; Cairns, Charles B; Rivers, Emanuel P; Shapiro, Nathan I

2014-08-01

The authors aimed to evaluate age-related differences in inflammation biomarkers during the first 72 h of hospitalization for sepsis. This was a secondary analysis of a prospective observational cohort of adult patients (n = 855) from 10 urban academic emergency departments with confirmed infection and two or more systemic inflammatory response syndrome criteria. Six inflammation-related biomarkers were analyzed-chemokine (CC-motif) ligand-23, C-reactive protein, interleukin-1 receptor antagonist, neutrophil gelatinase-associated lipocalin (NGAL), peptidoglycan recognition protein, and tumor necrosis factor receptor-1a (TNFR-1a)-measured at presentation and 3, 6, 12, 24, 48, or 72 h later. The median age was 56 (interquartile range, 43 - 72) years, and sepsis severity was 38% sepsis, 16% severe sepsis without shock, and 46% septic shock; the overall 30-day mortality was 12%. Older age was associated with higher sepsis severity: 41% of subjects aged 18 to 34 years had severe sepsis or septic shock compared with 71% for those aged 65 years or older (P < 0.001). In longitudinal models adjusting for demographics, comorbidities, and infection source, older age was associated with higher baseline values for chemokine (CC-motif) ligand-23, interleukin-1 receptor antagonist, NGAL, and TNFR-1a (all P < 0.05). However, older adults had higher mean values during the entire 72-h period only for NGAL and TNFR-1a and higher final 72-h values only for TNFR-1a. Adjustment or stratification by sepsis severity did not change the age-inflammation associations. Although older adults had higher levels of inflammation at presentation and an increased incidence of severe sepsis and septic shock, these age-related differences in inflammation largely resolved during the first 72 h of hospitalization.

Association of Delayed Antimicrobial Therapy with One-Year Mortality in Pediatric Sepsis.

PubMed

Han, Moonjoo; Fitzgerald, Julie C; Balamuth, Fran; Keele, Luke; Alpern, Elizabeth R; Lavelle, Jane; Chilutti, Marianne; Grundmeier, Robert W; Nadkarni, Vinay M; Thomas, Neal J; Weiss, Scott L

2017-07-01

Delayed antimicrobial therapy in sepsis is associated with increased hospital mortality, but the impact of antimicrobial timing on long-term outcomes is unknown. We tested the hypothesis that hourly delays to antimicrobial therapy are associated with 1-year mortality in pediatric severe sepsis. Retrospective observational study. Quaternary academic pediatric intensive care unit (PICU) from February 1, 2012 to June 30, 2013. One hundred sixty patients aged ≤21 years treated for severe sepsis. None. We tested the association of hourly delays from sepsis recognition to antimicrobial administration with 1-year mortality using multivariable Cox and logistic regression. Overall 1-year mortality was 24% (39 patients), of whom 46% died after index PICU discharge. Median time from sepsis recognition to antimicrobial therapy was 137 min (IQR 65-287). After adjusting for severity of illness and comorbid conditions, hourly delays up to 3 h were not associated with 1-year mortality. However, increased 1-year mortality was evident in patients who received antimicrobials ≤1 h (aOR 3.8, 95% CI 1.2, 11.7) or >3 h (aOR 3.5, 95% CI 1.3, 9.8) compared with patients who received antimicrobials within 1 to 3 h from sepsis recognition. For the subset of patients who survived index PICU admission, antimicrobial therapy ≤1 h was also associated with increased 1-year mortality (aOR 5.5, 95% CI 1.1, 27.4), while antimicrobial therapy >3 h was not associated with 1-year mortality (aOR 2.2, 95% CI 0.5, 11.0). Hourly delays to antimicrobial therapy, up to 3 h, were not associated with 1-year mortality in pediatric severe sepsis in this study. The finding that antimicrobial therapy ≤1 h from sepsis recognition was associated with increased 1-year mortality should be regarded as hypothesis-generating for future studies.

Delayed antimicrobial therapy increases mortality and organ dysfunction duration in pediatric sepsis.

PubMed

Weiss, Scott L; Fitzgerald, Julie C; Balamuth, Fran; Alpern, Elizabeth R; Lavelle, Jane; Chilutti, Marianne; Grundmeier, Robert; Nadkarni, Vinay M; Thomas, Neal J

2014-11-01

Delayed antimicrobials are associated with poor outcomes in adult sepsis, but data relating antimicrobial timing to mortality and organ dysfunction in pediatric sepsis are limited. We sought to determine the impact of antimicrobial timing on mortality and organ dysfunction in pediatric patients with severe sepsis or septic shock. Retrospective observational study. PICU at an academic medical center. One hundred thirty patients treated for severe sepsis or septic shock. None. We determined if hourly delays from sepsis recognition to initial and first appropriate antimicrobial administration were associated with PICU mortality (primary outcome); ventilator-free, vasoactive-free, and organ failure-free days; and length of stay. Median time from sepsis recognition to initial antimicrobial administration was 140 minutes (interquartile range, 74-277 min) and to first appropriate antimicrobial was 177 minutes (90-550 min). An escalating risk of mortality was observed with each hour delay from sepsis recognition to antimicrobial administration, although this did not achieve significance until 3 hours. For patients with more than 3-hour delay to initial and first appropriate antimicrobials, the odds ratio for PICU mortality was 3.92 (95% CI, 1.27-12.06) and 3.59 (95% CI, 1.09-11.76), respectively. These associations persisted after adjustment for individual confounders and a propensity score analysis. After controlling for severity of illness, the odds ratio for PICU mortality increased to 4.84 (95% CI, 1.45-16.2) and 4.92 (95% CI, 1.30-18.58) for more than 3-hour delay to initial and first appropriate antimicrobials, respectively. Initial antimicrobial administration more than 3 hours was also associated with fewer organ failure-free days (16 [interquartile range, 1-23] vs 20 [interquartile range, 6-26]; p = 0.04). Delayed antimicrobial therapy was an independent risk factor for mortality and prolonged organ dysfunction in pediatric sepsis.

Validation of the Sepsis Severity Score Compared with Updated Severity Scores in Predicting Hospital Mortality in Sepsis Patients.

PubMed

Khwannimit, Bodin; Bhurayanontachai, Rungsun; Vattanavanit, Veerapong

2017-06-01

Recently, the Sepsis Severity Score (SSS) was constructed to predict mortality in sepsis patients. The aim of this study was to compare performance of the SSS with the Acute Physiology and Chronic Health Evaluation (APACHE) II-IV, Simplified Acute Physiology Score (SAPS) II, and SAPS 3 scores in predicting hospital outcome in sepsis patients. A retroprospective analysis was conducted in the medical intensive care unit of a tertiary university hospital. A total of 913 patients were enrolled; 476 of these patients (52.1%) had septic shock. The median SSS was 80 (range 20-137). The SSS presented good discrimination with an area under the receiver operating characteristic curve (AUC) of 0.892. However, the AUC of the SSS did not differ significantly from that of APACHE II (P = 0.07), SAPS II (P = 0.06), and SAPS 3 (P = 0.11). The APACHE IV score showed the best discrimination with an AUC of 0.948 and the overall performance by a Brier score of 0.096. The AUC of the APACHE IV score was statistically greater than the SSS, APACHE II, SAPS II, and SAPS 3 (P <0.0001 for all) and APACHE III (P = 0.0002). The calibration of all scores was poor with the Hosmer-Lemeshow goodness-of-fit H test <0.05. The SSS provided as good discrimination as the APACHE II, SAPS II, and SAPS 3 scores. However, the APACHE IV score had the best discrimination and overall performance in our sepsis patients. The SSS needs to be adapted and modified with new parameters to improve its performance.

A Severe Sepsis Mortality Prediction Model and Score for Use with Administrative Data

PubMed Central

Ford, Dee W.; Goodwin, Andrew J.; Simpson, Annie N.; Johnson, Emily; Nadig, Nandita; Simpson, Kit N.

2016-01-01

Objective Administrative data is used for research, quality improvement, and health policy in severe sepsis. However, there is not a sepsis-specific tool applicable to administrative data with which to adjust for illness severity. Our objective was to develop, internally validate, and externally validate a severe sepsis mortality prediction model and associated mortality prediction score. Design Retrospective cohort study using 2012 administrative data from five US states. Three cohorts of patients with severe sepsis were created: 1) ICD-9-CM codes for severe sepsis/septic shock, 2) ‘Martin’ approach, and 3) ‘Angus’ approach. The model was developed and internally validated in ICD-9-CM cohort and externally validated in other cohorts. Integer point values for each predictor variable were generated to create a sepsis severity score. Setting Acute care, non-federal hospitals in NY, MD, FL, MI, and WA Subjects Patients in one of three severe sepsis cohorts: 1) explicitly coded (n=108,448), 2) Martin cohort (n=139,094), and 3) Angus cohort (n=523,637) Interventions None Measurements and Main Results Maximum likelihood estimation logistic regression to develop a predictive model for in-hospital mortality. Model calibration and discrimination assessed via Hosmer-Lemeshow goodness-of-fit (GOF) and C-statistics respectively. Primary cohort subset into risk deciles and observed versus predicted mortality plotted. GOF demonstrated p>0.05 for each cohort demonstrating sound calibration. C-statistic ranged from low of 0.709 (sepsis severity score) to high of 0.838 (Angus cohort) suggesting good to excellent model discrimination. Comparison of observed versus expected mortality was robust although accuracy decreased in highest risk decile. Conclusions Our sepsis severity model and score is a tool that provides reliable risk adjustment for administrative data. PMID:26496452

Cellular and extracellular miRNAs are blood-compartment-specific diagnostic targets in sepsis.

PubMed

Reithmair, Marlene; Buschmann, Dominik; Märte, Melanie; Kirchner, Benedikt; Hagl, Daniel; Kaufmann, Ines; Pfob, Martina; Chouker, Alexander; Steinlein, Ortrud K; Pfaffl, Michael W; Schelling, Gustav

2017-10-01

Septic shock is a common medical condition with a mortality approaching 50% where early diagnosis and treatment are of particular importance for patient survival. Novel biomarkers that serve as prompt indicators of sepsis are urgently needed. High-throughput technologies assessing circulating microRNAs represent an important tool for biomarker identification, but the blood-compartment specificity of these miRNAs has not yet been investigated. We characterized miRNA profiles from serum exosomes, total serum and blood cells (leukocytes, erythrocytes, platelets) of sepsis patients by next-generation sequencing and RT-qPCR (n = 3 × 22) and established differences in miRNA expression between blood compartments. In silico analysis was used to identify compartment-specific signalling functions of differentially regulated miRNAs in sepsis-relevant pathways. In septic shock, a total of 77 and 103 miRNAs were down- and up-regulated, respectively. A majority of these regulated miRNAs (14 in serum, 32 in exosomes and 73 in blood cells) had not been previously associated with sepsis. We found a distinctly compartment-specific regulation of miRNAs between sepsis patients and healthy volunteers. Blood cellular miR-199b-5p was identified as a potential early indicator for sepsis and septic shock. miR-125b-5p and miR-26b-5p were uniquely regulated in exosomes and serum, respectively, while one miRNA (miR-27b-3p) was present in all three compartments. The expression of sepsis-associated miRNAs is compartment-specific. Exosome-derived miRNAs contribute significant information regarding sepsis diagnosis and survival prediction and could serve as newly identified targets for the development of novel sepsis biomarkers. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Surviving sepsis: a trust-wide approach. A multi-disciplinary team approach to implementing evidence-based guidelines.

PubMed

Gerber, Karin

2010-01-01

To share an experience of examining the true extent of the number of patients with severe sepsis being admitted, and the overall compliance with existing treatment guidelines in a district general hospital (DGH). Because of its aggressive, multi-factorial nature, sepsis is a rapid killer. Mortality associated with severe sepsis remains unacceptably high: 30-50%. When shock is present, mortality is reported to be even higher: 50-60%. The rapid diagnosis and management of sepsis is vital to successful treatment. The International Surviving Sepsis Campaign (SSC) was developed to help meet the challenges of sepsis and to improve its management, diagnosis and treatment. The overall aim is to reduce mortality from sepsis by 25% by 2009. Data on the number of patients admitted with severe sepsis to the DGH were previously unknown. The aim of the baseline audits was to determine the true extent of the problem and baseline mortality rates, resulting in an action plan to provide evidence-based care to patients with sepsis regardless of where in the hospital they were located. It was found that 11% of the patients audited presented with signs of severe sepsis and demonstrated elements of poor compliance with some elements of existing treatment guidelines as set out by the resuscitation component of the Surviving Sepsis Care Bundle. As an international campaign introduced predominantly within critical care, within this DGH the SSC teams' innovative approach has resulted in: * Better educated staff; * Objectives agreed within multi-disciplinary teams; * The appropriate assessment of resources; * Standardization of practice in terms of patients presenting with severe sepsis.

Effects of varying inter-limb spacing to limb length ratio in metachronal swimming

NASA Astrophysics Data System (ADS)

Lai, Hong Kuan; Merkel, Rachael; Santhanakrishnan, Arvind

2016-11-01

Crustaceans such as shrimp, krill and crayfish swim by rhythmic paddling of four to five pairs of closely spaced limbs. Each pair is phase-shifted in time relative to the neighboring pair, resulting in a metachronal wave that travels in the direction of animal motion. The broad goal of this study is to investigate how the mechanical design of the swimming limbs affect scalability of metachronal swimming in terms of limb-based Reynolds number (Re). A scaled robotic model of metachronal paddling was developed, consisting of four pairs of hinged acrylic plates actuated using stepper motors that were immersed in a rectangular tank containing water-glycerin fluid medium. 2D PIV measurements show that the propulsive jets transition from being primarily horizontal (thrust-producing direction) at Re of order 10 to angled vertically at Re of order 100. The ratio of inter-limb spacing to limb length among metachronal swimming organisms ranges between 0.2 to 0.65. 2D PIV will be used to examine the jets generated between adjacent limbs for varying inter-limb spacing to limb length ratios. The effect of increasing this ratio to beyond the biologically observed range will be discussed.

Antithyroid drug-induced agranulocytosis complicated by pneumococcal sepsis and upper airway obstruction.

PubMed

Ishimaru, Naoto; Ohnishi, Hisashi; Nishiuma, Teruaki; Doukuni, Ryota; Umezawa, Kanoko; Oozone, Sachiko; Kuramoto, Emi; Yoshimura, Sho; Kinami, Saori

2013-01-01

Streptococcus pneumoniae is a rare pathogen of sepsis in patients with antithyroid drug-induced agranulocytosis. We herein describe a case of antithyroid drug-induced agranulocytosis complicated by pneumococcal sepsis and upper airway obstruction. A 27-year-old woman who was previously prescribed methimazole for nine months presented with a four-day history of a sore throat. She nearly choked and was diagnosed with febrile agranulocytosis. She was successfully treated with intubation, intravenous antibiotics and granulocyte colony-stimulating factor. Her blood cultures yielded S. pneumoniae. Emergency airway management, treatment of sepsis and the administration of granulocyte colony-stimulating factor can improve the clinical course of antithyroid drug-induced pneumococcal sepsis in patients with airway obstruction.

Paramedic-Initiated CMS Sepsis Core Measure Bundle Prior to Hospital Arrival: A Stepwise Approach.

PubMed

Walchok, Jason G; Pirrallo, Ronald G; Furmanek, Douglas; Lutz, Martin; Shope, Colt; Giles, Brandi; Gue, Greta; Dix, Aaron

2017-01-01

To improve patient outcomes, the Center for Medicare and Medicaid Services (CMS) implemented core measures that outline the initial treatment of the septic patient. These measures include initial blood culture collection prior to antibiotics, adequate intravenous fluid resuscitation, and early administration of broad spectrum antibiotics. We sought to determine if Paramedics can initiate the CMS sepsis core measure bundle in the prehospital field reliably. This is a retrospective, case series from a 3rd service EMS system model in Greenville, South Carolina between November 17, 2014 and February 20, 2016. An adult Prehospital Sepsis Assessment Tool was created using the 2012 Surviving Sepsis guidelines: 2 of 3 signs of systemic inflammatory response (heart rate, respiratory rate, oral temperature) and a known or suspected source of infection. A "Sepsis Alert" was called by paramedics and upon IV access a set of blood cultures and blood for lactate analysis was collected prior to field antibiotic administration. The Sepsis Alert was compared to serum lactate levels and ICD 9 or 10 admitting diagnosis of Sepsis, Severe Sepsis, or Septic Shock. Blood culture contamination, serum lactate, and antibiotic match were determined by in-hospital laboratory analysis. A total of 120 trained paramedics called 1,185 "Sepsis Alerts" on 56,643 patients (50.3% Male, mean age 70). Patients with missing discharge diagnosis were eliminated (n = 31). The admitting diagnosis of sepsis overall was 73.5% (848/1154): Sepsis 50% (578/1154), Severe Sepsis 14.6% (169/1154), Septic Shock 8.9% (101/1154). A total of 946 blood cultures were collected in the prehospital setting, with a 95.04% (899/946) no contamination rate. Contamination was found in 4.96% (47/946). A total of 179 (18.9%) of the uncontaminated blood cultures were found to have positive growth with 720 (76.1%) having no growth. EMS administered antibiotics matched blood culture positive growth in 72% of patients. The lactate

The costs and cost-effectiveness of an integrated sepsis treatment protocol.

PubMed

Talmor, Daniel; Greenberg, Dan; Howell, Michael D; Lisbon, Alan; Novack, Victor; Shapiro, Nathan

2008-04-01

Sepsis is associated with high mortality and treatment costs. International guidelines recommend the implementation of integrated sepsis protocols; however, the true cost and cost-effectiveness of these are unknown. To assess the cost-effectiveness of an integrated sepsis protocol, as compared with conventional care. Prospective cohort study of consecutive patients presenting with septic shock and enrolled in the institution's integrated sepsis protocol. Clinical and economic outcomes were compared with a historical control cohort. Beth Israel Deaconess Medical Center. Overall, 79 patients presenting to the emergency department with septic shock in the treatment cohort and 51 patients in the control group. An integrated sepsis treatment protocol incorporating empirical antibiotics, early goal-directed therapy, intensive insulin therapy, lung-protective ventilation, and consideration for drotrecogin alfa and steroid therapy. In-hospital treatment costs were collected using the hospital's detailed accounting system. The cost-effectiveness analysis was performed from the perspective of the healthcare system using a lifetime horizon. The primary end point for the cost-effectiveness analysis was the incremental cost per quality-adjusted life year gained. Mortality in the treatment group was 20.3% vs. 29.4% in the control group (p = .23). Implementing an integrated sepsis protocol resulted in a mean increase in cost of approximately $8,800 per patient, largely driven by increased intensive care unit length of stay. Life expectancy and quality-adjusted life years were higher in the treatment group; 0.78 and 0.54, respectively. The protocol was associated with an incremental cost of $11,274 per life-year saved and a cost of $16,309 per quality-adjusted life year gained. In patients with septic shock, an integrated sepsis protocol, although not cost-saving, appears to be cost-effective and compares very favorably to other commonly delivered acute care interventions.

Sepsis risk factors in infants with congenital diaphragmatic hernia.

PubMed

Levy, Michaël; Le Sache, Nolwenn; Mokhtari, Mostafa; Fagherazzi, Guy; Cuzon, Gaelle; Bueno, Benjamin; Fouquet, Virginie; Benachi, Alexandra; Eleni Dit Trolli, Sergio; Tissieres, Pierre

2017-12-01

Congenital diaphragmatic hernia (CDH) is a rare congenital anomaly and remains among the most challenging ICU-managed disease. Beside severe pulmonary hypertension, lung hypoplasia and major abdominal surgery, infective complications remain major determinants of outcome. However, the specific incidence of sepsis as well as associated risk factors is unknown. This prospective, 4-year observational study took place in the pediatric intensive care and neonatal medicine department of the Paris South University Hospitals (Le Kremlin-Bicêtre, France), CDH national referral center and involved 62 neonates with CDH. During their ICU stay, 28 patients (45%) developed 38 sepsis episodes. Ventilator-associated pneumonia (VAP: 23/38; 31.9 VAP per 1000 days of mechanical ventilation) and central line-associated blood stream infections (CLABSI: 5/38; 5.5 per 1000 line days) were the most frequently encountered infections. Multivariate analysis showed that gestational age at birth and intra-thoracic position of liver were significantly associated with the occurrence of sepsis. Infected patients had longer duration of mechanical and noninvasive ventilation (16.2 and 5.8 days, respectively), longer delay to first feeding (1.2 days) and a longer length of stay in ICU (23 days), but there was no difference in mortality. Healthcare-associated infections, and more specifically VAP, are the main infective threat in children with CDH. Sepsis has a significant impact on the duration of ventilator support and ICU length of stay but does not impact mortality. Low gestational age and intra-thoracic localization of the liver are two independent risk factors associated with sepsis.

Attrition of memory CD8 T cells during sepsis requires LFA-1.

PubMed

Serbanescu, Mara A; Ramonell, Kimberly M; Hadley, Annette; Margoles, Lindsay M; Mittal, Rohit; Lyons, John D; Liang, Zhe; Coopersmith, Craig M; Ford, Mandy L; McConnell, Kevin W

2016-11-01

CD8 T cell loss and dysfunction have been implicated in the increased susceptibility to opportunistic infections during the later immunosuppressive phase of sepsis, but CD8 T cell activation and attrition in early sepsis remain incompletely understood. With the use of a CLP model, we assessed CD8 T cell activation at 5 consecutive time points and found that activation after sepsis results in a distinct phenotype (CD69 + CD25 int CD62L HI ) independent of cognate antigen recognition and TCR engagement and likely through bystander-mediated cytokine effects. Additionally, we observed that sepsis concurrently results in the preferential depletion of a subset of memory-phenotype CD8 T cells that remain "unactivated" (i.e., fail to up-regulate activation markers) by apoptosis. Unactivated CD44 HI OT-I cells were spared from sepsis-induced attrition, as were memory-phenotype CD8 T cells of mice treated with anti-LFA-1 mAb, 1 h after CLP. Perhaps most importantly, we demonstrate that attrition of memory phenotype cells may have a pathologic significance, as elevated IL-6 levels were associated with decreased numbers of memory-phenotype CD8 T cells in septic mice, and preservation of this subset after administration of anti-LFA-1 mAb conferred improved survival at 7 d. Taken together, these data identify potentially modifiable responses of memory-phenotype CD8 T cells in early sepsis and may be particularly important in the application of immunomodulatory therapies in sepsis. © Society for Leukocyte Biology.

Attrition of memory CD8 T cells during sepsis requires LFA-1

PubMed Central

Serbanescu, Mara A.; Ramonell, Kimberly M.; Hadley, Annette; Margoles, Lindsay M.; Mittal, Rohit; Lyons, John D.; Liang, Zhe; Coopersmith, Craig M.; Ford, Mandy L.; McConnell, Kevin W.

2016-01-01

CD8 T cell loss and dysfunction have been implicated in the increased susceptibility to opportunistic infections during the later immunosuppressive phase of sepsis, but CD8 T cell activation and attrition in early sepsis remain incompletely understood. With the use of a CLP model, we assessed CD8 T cell activation at 5 consecutive time points and found that activation after sepsis results in a distinct phenotype (CD69+CD25intCD62LHI) independent of cognate antigen recognition and TCR engagement and likely through bystander-mediated cytokine effects. Additionally, we observed that sepsis concurrently results in the preferential depletion of a subset of memory-phenotype CD8 T cells that remain “unactivated” (i.e., fail to up-regulate activation markers) by apoptosis. Unactivated CD44HI OT-I cells were spared from sepsis-induced attrition, as were memory-phenotype CD8 T cells of mice treated with anti-LFA-1 mAb, 1 h after CLP. Perhaps most importantly, we demonstrate that attrition of memory phenotype cells may have a pathologic significance, as elevated IL-6 levels were associated with decreased numbers of memory-phenotype CD8 T cells in septic mice, and preservation of this subset after administration of anti-LFA-1 mAb conferred improved survival at 7 d. Taken together, these data identify potentially modifiable responses of memory-phenotype CD8 T cells in early sepsis and may be particularly important in the application of immunomodulatory therapies in sepsis. PMID:27286793

Sepsis-Related Mortality of Very Low Birth Weight Brazilian Infants: The Role of Pseudomonas aeruginosa

PubMed Central

Pereira, Sylvia Maria Porto; Cardoso, Maria Helena Cabral de Almeida; Figuexeds, Ana Lucia; Mattos, Haroldo; Rozembaum, Ronaldo; Ferreira, Vanessa Isidoro; Portinho, Maria Antonieta; Gonçalves, Ana Cristina; da Costa, Elaine Sobral

2009-01-01

The aim of this study is to identify risk factors for sepsis-related mortality in low birth weight (<1500 g) infants. We performed retrospective cohort study to investigate risk factors for sepsis-related mortality in all neonates birth weight <1500 g admitted to Level III neonatal intensive care unit, Brazil, April 2001/September 2004. Of the 203 cases, 71 (35%) had sepsis. Of those, gram-positive was identified in 52/87 blood cultures (59.8%), the most common Coagulase-negative Staphylococcus (31/87; 35.5%). Gram-negative was present in 29 of the 87 positive blood cultures (33.3%), with Pseudomonas aeruginosa (8/87; 9.1%), the most frequent agent. Overall 21 of 71 infants with sepsis (29.6%) died. Risk factors for sepsis-related mortality were gestational age ≤28 weeks, birth weight ≤1000 g (9.6 times more often than birth weight >1000 g), five-minute Apgar ≤7, gram-negative sepsis, mechanical ventilation (6.7 times higher than no use), and intravascular catheter. Sepsis-related mortality was due, mainly, to Pseudomonas aeruginosa; birth weight ≤1000 g and mechanical ventilation were strong sepsis-related mortality predictors. PMID:20182631

The role of genetics and antibodies in sepsis

PubMed Central

Giamarellos-Bourboulis, Evangelos J.

2016-01-01

During the course of sepsis when immunosuppression predominates, the concentrations of circulating immunoglobulins (IGs) are decreased and this is associated with adverse outcomes. The production of IGs as response to invasive bacterial pathogens takes place through a complex pathway starting from the recognition of the antigen (Ag) by innate immune cells that process and present Ags to T cells. The orchestration of T-helper (Th) lymphocyte responses directs specific B cells and ends with the production of IGs by plasma cells. All molecules implicated in this process are encoded by genes bearing single nucleotide polymorphisms (SNPs). Meta-analysis of case-control studies have shown that the carriage of minor frequency SNPs of CD14, TLR2 and TNF is associated with increased sepsis risk. The ambiguity of results of clinical trials studying the clinical efficacy of exogenous IG administration in sepsis suggests that efficacy of treatment should be considered after adjustment for SNPs of all implicated genes in the pathway of IG production. PMID:27713886

The role of genetics and antibodies in sepsis.

PubMed

Giamarellos-Bourboulis, Evangelos J; Opal, Steven M

2016-09-01

During the course of sepsis when immunosuppression predominates, the concentrations of circulating immunoglobulins (IGs) are decreased and this is associated with adverse outcomes. The production of IGs as response to invasive bacterial pathogens takes place through a complex pathway starting from the recognition of the antigen (Ag) by innate immune cells that process and present Ags to T cells. The orchestration of T-helper (Th) lymphocyte responses directs specific B cells and ends with the production of IGs by plasma cells. All molecules implicated in this process are encoded by genes bearing single nucleotide polymorphisms (SNPs). Meta-analysis of case-control studies have shown that the carriage of minor frequency SNPs of CD14 , TLR2 and TNF is associated with increased sepsis risk. The ambiguity of results of clinical trials studying the clinical efficacy of exogenous IG administration in sepsis suggests that efficacy of treatment should be considered after adjustment for SNPs of all implicated genes in the pathway of IG production.

Correlation analysis of omega-3 fatty acids and mortality of sepsis and sepsis-induced ARDS in adults: data from previous randomized controlled trials.

PubMed

Chen, HuaiSheng; Wang, Su; Zhao, Ying; Luo, YuTian; Tong, HuaSheng; Su, Lei

2018-05-31

This study aimed to investigate the possible effect of omega-3 fatty acids on reducing the mortality of sepsis and sepsis-induced acute respiratory distress syndrome (ARDS) in adults. Medline, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI) database, WangFang database, and Chinese BioMedical Literature Database from their inception to March 6, 2017, were searched using systematic review researching methods. Five factors were analyzed to investigate the correlation between omega-3 fatty acids (either parenteral or enteral supplementation) and mortality rate. Forty randomized controlled trials (RCTs) were initially included, but only 25 of them assessed mortality. Of these RCTs, nine used enteral nutrition (EN) and 16 used parenteral nutrition (PN). The total mortality rate in the omega-3 fatty acid group was lower than that in the control group. However, the odds ratio (OR) value was not significantly different in the EN or PN subgroup. Eighteen RCTs including 1790 patients with similar severity of sepsis and ARDS were also analyzed. The OR value was not significantly different in the EN or PN subgroup. Omega-3 fatty acids did not show positive effect on improving mortality of sepsis-induced ARDS (p = 0.39). But in EN subgroup, omega-3 fatty acids treatment seemed to have some benefits in reducing mortality rate (p = 0.04). In the RCTs including similar baseline patients, partial correlation analysis found that the concentration ratio of n-6 to n-3 fatty acids had positive correlation with reduction of mortality (RM) (γ = 0.60, P = 0.02), whereas the total number of each RCT had negative correlation with RM (γ = - 0.54, P = 0.05). This review found that omega-3 fatty acid supplementation could reduce the mortality rate of sepsis and sepsis-induced ARDS. However, further investigation based on suitable concentrations and indications is needed to support the findings.

Muscle Mass Depletion Associated with Poor Outcome of Sepsis in the Emergency Department.

PubMed

Lee, YoonJe; Park, Hyun Kyung; Kim, Won Young; Kim, Myung Chun; Jung, Woong; Ko, Byuk Sung

2018-05-08

Muscle mass depletion has been suggested to predict morbidity and mortality in various diseases. However, it is not well known whether muscle mass depletion is associated with poor outcome in sepsis. We hypothesized that muscle mass depletion is associated with poor outcome in sepsis. Retrospective observational study was conducted in an emergency department during a 9-year period. Medical records of 627 patients with sepsis were reviewed. We divided the patients into 2 groups according to 28-day mortality and compared the presence of muscle mass depletion assessed by the cross-sectional area of the psoas muscle at the level of the third lumbar vertebra on abdomen CT scans. Univariate and multivariate logistic regression analyses were conducted to examine the association of scarcopenia on the outcome of sepsis. A total of 274 patients with sepsis were finally included in the study: 45 (16.4%) did not survive on 28 days and 77 patients (28.1%) were identified as having muscle mass depletion. The presence of muscle mass depletion was independently associated with 28-day mortality on multivariate logistic analysis (OR 2.79; 95% CI 1.35-5.74, p = 0.01). Muscle mass depletion evaluated by CT scan was associated with poor outcome of sepsis patients. Further studies on the appropriateness of specific treatment for muscle mass depletion with sepsis are needed. © 2018 S. Karger AG, Basel.

Getting the invite list right: a discussion of sepsis severity scoring systems in severe complicated intra-abdominal sepsis and randomized trial inclusion criteria.

PubMed

Tolonen, Matti; Coccolini, Federico; Ansaloni, Luca; Sartelli, Massimo; Roberts, Derek J; McKee, Jessica L; Leppaniemi, Ari; Doig, Christopher J; Catena, Fausto; Fabian, Timothy; Jenne, Craig N; Chiara, Osvaldo; Kubes, Paul; Kluger, Yoram; Fraga, Gustavo P; Pereira, Bruno M; Diaz, Jose J; Sugrue, Michael; Moore, Ernest E; Ren, Jianan; Ball, Chad G; Coimbra, Raul; Dixon, Elijah; Biffl, Walter; MacLean, Anthony; McBeth, Paul B; Posadas-Calleja, Juan G; Di Saverio, Salomone; Xiao, Jimmy; Kirkpatrick, Andrew W

2018-01-01

Severe complicated intra-abdominal sepsis (SCIAS) is a worldwide challenge with increasing incidence. Open abdomen management with enhanced clearance of fluid and biomediators from the peritoneum is a potential therapy requiring prospective evaluation. Given the complexity of powering multi-center trials, it is essential to recruit an inception cohort sick enough to benefit from the intervention; otherwise, no effect of a potentially beneficial therapy may be apparent. An evaluation of abilities of recognized predictive systems to recognize SCIAS patients was conducted using an existing intra-abdominal sepsis (IAS) database. All consecutive adult patients with a diffuse secondary peritonitis between 2012 and 2013 were collected from a quaternary care hospital in Finland, excluding appendicitis/cholecystitis. From this retrospectively collected database, a target population (93) of those with either ICU admission or mortality were selected. The performance metrics of the Third Consensus Definitions for Sepsis and Septic Shock based on both SOFA and quick SOFA, the World Society of Emergency Surgery Sepsis Severity Score (WSESSSS), the APACHE II score, Manheim Peritonitis Index (MPI), and the Calgary Predisposition, Infection, Response, and Organ dysfunction (CPIRO) score were all tested for their discriminant ability to identify this subgroup with SCIAS and to predict mortality. Predictive systems with an area under-the-receiving-operating characteristic (AUC) curve > 0.8 included SOFA, Sepsis-3 definitions, APACHE II, WSESSSS, and CPIRO scores with the overall best for CPIRO. The highest identification rates were SOFA score ≥ 2 (78.4%), followed by the WSESSSS score ≥ 8 (73.1%), SOFA ≥ 3 (75.2%), and APACHE II ≥ 14 (68.8%) identification. Combining the Sepsis-3 septic-shock definition and WSESSS ≥ 8 increased detection to 80%. Including CPIRO score ≥ 3 increased this to 82.8% (Sensitivity-SN; 83% Specificity-SP; 74%. Comparatively, SOFA �

MiRNA-21 has effects to protect kidney injury induced by sepsis.

PubMed

Fu, Dian; Dong, Jie; Li, Ping; Tang, Chaopeng; Cheng, Wen; Xu, Zhenyu; Zhou, Wenquan; Ge, Jingping; Xia, Chen; Zhang, Zhengyu

2017-10-01

To investigate the miRNA-21 over-expression in the acute kidney injury induced by sepsis, we developed a sepsis induced in vitro model by lip polysaccharide (LPS) and in vovo model by cecal ligation and puncture (CLP) surgery. LPS or CLP surgery induced kidney cell apoptosis increasing. However, the kidney injury indexes of miRNA groups which were transfected with miRNA-21 were significantly suppressed. In further study, the relative proteins expressions were evaluated to explain the miRNA-21 mechanism to improve sepsis induced kidney cell apoptosis. The results were shown that miRNA-21 over-expression had effects to protect kidney cell apoptosis induced by sepsis via PTEN/PI3K/AKT signaling pathway. Copyright © 2017. Published by Elsevier Masson SAS.

Recent advances in prevention of sepsis in the premature neonates in NICU.

PubMed

Manzoni, P; Rizzollo, S; Decembrino, L; Ruffinazzi, G; Rossi Ricci, A; Gallo, E; Stolfi, I; Mostert, M; Stronati, M; Farina, D

2011-03-01

Sepsis-related morbidity and mortality are major problems in NICU. Preterm neonates display clinical characteristics that make them prone to infections. Due to the high frequency of severe neurodevelopmental sequelae in survivors, the best possible strategy to manage sepsis in NICU is to prevent them. Hygiene, cohorting, stewardship on use of H2-blockers, steroids and broad-spectrum antibiotic are mandatory, as well as proper management of central venous accesses and surgical devices. In addition, clinical research offers the opportunity of adopting pharmacological preventative strategies such as use of palivizumab to prevent RSV infection, use of fluconazole to prevent fungal sepsis, use of probiotics and lactoferrin to enhance the innate immunity, and use of pagibaximab to prevent staphylococcal sepsis. Copyright © 2011 Elsevier Ltd. All rights reserved.

Differentiating sepsis from non-infectious systemic inflammation based on microvesicle-bacteria aggregation

NASA Astrophysics Data System (ADS)

Herrmann, I. K.; Bertazzo, S.; O'Callaghan, D. J. P.; Schlegel, A. A.; Kallepitis, C.; Antcliffe, D. B.; Gordon, A. C.; Stevens, M. M.

2015-08-01

Sepsis is a severe medical condition and a leading cause of hospital mortality. Prompt diagnosis and early treatment has a significant, positive impact on patient outcome. However, sepsis is not always easy to diagnose, especially in critically ill patients. Here, we present a conceptionally new approach for the rapid diagnostic differentiation of sepsis from non-septic intensive care unit patients. Using advanced microscopy and spectroscopy techniques, we measure infection-specific changes in the activity of nano-sized cell-derived microvesicles to bind bacteria. We report on the use of a point-of-care-compatible microfluidic chip to measure microvesicle-bacteria aggregation and demonstrate rapid (<=1.5 hour) and reliable diagnostic differentiation of bacterial infection from non-infectious inflammation in a double-blind pilot study. Our study demonstrates the potential of microvesicle activities for sepsis diagnosis and introduces microvesicle-bacteria aggregation as a potentially useful parameter for making early clinical management decisions.Sepsis is a severe medical condition and a leading cause of hospital mortality. Prompt diagnosis and early treatment has a significant, positive impact on patient outcome. However, sepsis is not always easy to diagnose, especially in critically ill patients. Here, we present a conceptionally new approach for the rapid diagnostic differentiation of sepsis from non-septic intensive care unit patients. Using advanced microscopy and spectroscopy techniques, we measure infection-specific changes in the activity of nano-sized cell-derived microvesicles to bind bacteria. We report on the use of a point-of-care-compatible microfluidic chip to measure microvesicle-bacteria aggregation and demonstrate rapid (<=1.5 hour) and reliable diagnostic differentiation of bacterial infection from non-infectious inflammation in a double-blind pilot study. Our study demonstrates the potential of microvesicle activities for sepsis diagnosis and

Optical detection of sepsis markers using liquid crystal based biosensors

NASA Astrophysics Data System (ADS)

McCamley, Maureen K.; Artenstein, Andrew W.; Opal, Steven M.; Crawford, Gregory P.

2007-02-01

A liquid crystal based biosensor for the detection and diagnosis of sepsis is currently in development. Sepsis, a major clinical syndrome with a significant public health burden in the US due to a large elderly population, is the systemic response of the body to a localized infection and is defined as the combination of pathologic infection and physiological changes. Bacterial infections are responsible for 90% of cases of sepsis in the US. Currently there is no bedside diagnostic available to positively identify sepsis. The basic detection scheme employed in a liquid crystal biosensor contains attributes that would find value in a clinical setting, especially for the early detection of sepsis. Utilizing the unique properties of liquid crystals, such as birefringence, a bedside diagnostic is in development which will optically report the presence of biomolecules. In a septic patient, an endotoxin known as lipopolysaccharide (LPS) is released from the outer membrane of Gram-negative bacteria and can be found in the blood stream. It is hypothesized that this long chained molecule will cause local disruptions to the open surface of a sensor containing aligned liquid crystal. The bulk liquid crystal ampli.es these local changes at the surface due to the presence of the sepsis marker, providing an optical readout through polarizing microscopy images. Liquid crystal sensors consisting of both square and circular grids, 100-200 μm in size, have been fabricated and filled with a common liquid crystal material, 5CB. Homeotropic alignment was confirmed using polarizing microscopy. The grids were then contacted with either saline only (control), or saline with varying concentrations of LPS. Changes in the con.guration of the nematic director of the liquid crystal were observed through the range of concentrations tested (5mg/mL - 1pg/mL) which have been confirmed by a consulting physician as clinically relevant levels.

[Peritonitis: main reason of severe sepsis in surgical intensive care].

PubMed

Weiss, G; Steffanie, W; Lippert, H

2007-04-01

Aim of the study was to determine the epidemiology of sepsis in an university surgical intensive care unit. We were mainly interested in getting information about incidence, reason and clinical course of peritonitis. The results should give more information about diagnostic and therapy of sepsis in the surgical intensive care. We analyzed our 2 676 ICU-patients from 2000 to 2002 with infection as main diagnosis. By means of medical report we analyzed the kind of infection and the clinical course of 561 (21 %) patients. For 356 (13.3 %) patients with peritonitis we observed the kind, the reason and the severity of infection and further the special events in the clinical course. The incidence of severe sepsis was 14.8 %. With 63 % the peritonitis is the main infectiological diagnosis on admission to ICU. 33.8 % of infections are hospital acquired. 71.3 % of patients with peritonitis developed a severe sepsis or septic shock during the clinical course. On average 4.7 further abdominal surgical interventions and 5.1 new occurring nosocomial infections marked a difficult surgical and infectious treatment course. Hospital acquired infections (70 %), high value of scoring and inadequate surgical treatment (23.7 %) have proved to be a good prognostic instrument for the development of tertiary peritonitis. With a share of 17 % from patients with peritonitis and a mortality of 35 % they have a strong influence on the ICU-mortality. Peritonitis is the main reason of severe sepsis on the surgical ICU. Hospital acquired infections especially the tertiary peritonitis have the highest mortality. High mortality is the consequence from the large number of difficult clinical courses and high rates of severe sepsis and septic shock. "Second hits" play a crucial role for the therapy and the prognosis of these patients. To decline the mortality future studies must more consider the problem of hospital acquired and tertiary abdominal infections.

VIP as a potential therapeutic agent in gram negative sepsis.

PubMed

Ibrahim, Hiba; Barrow, Paul; Foster, Neil

2012-12-01

Gram negative sepsis remains a high cause of mortality and places a great burden on public health finance in both the developed and developing world. Treatment of sepsis, using antibiotics, is often ineffective since pathology associated with the disease occurs due to dysregulation of the immune system (failure to return to steady state conditions) which continues after the bacteria, which induced the immune response, have been cleared. Immune modulation is therefore a rational approach to the treatment of sepsis but to date no drug has been developed which is highly effective, cheap and completely safe to use. One potential therapeutic agent is VIP, which is a natural peptide and is highly homologous in all vertebrates. In this review we will discuss the effect of VIP on components of the immune system, relevant to gram negative sepsis, and present data from animal models. Furthermore we will hypothesise on how these studies could be improved in future and speculate on the possible different ways in which VIP could be used in clinical medicine.

Therapeutic Intervention in Sepsis with Antibody to Endotoxin: Is There a Future

DTIC Science & Technology

1994-01-01

Within the last 24 months a number of studies that tested thle efficacy of immunologic reagents in the treat- ment of sepsis were concluded. Amonug...raised the question whlethier the usc of anti-eIlndotxinl alltil)(Idit. il tfie treatient of sepsis was still a1 viable concept. 5The question was...intervention in sepsis with antibody to endotoxin: is there a future? , olity Codes Avail and/or Dist Special A. S. Cross. S. Opal -/ Department of

Severe Maternal Sepsis in the UK, 2011–2012: A National Case-Control Study

PubMed Central

Acosta, Colleen D.; Kurinczuk, Jennifer J.; Lucas, D. Nuala; Tuffnell, Derek J.; Sellers, Susan; Knight, Marian

2014-01-01

Background In light of increasing rates and severity of sepsis worldwide, this study aimed to estimate the incidence of, and describe the causative organisms, sources of infection, and risk factors for, severe maternal sepsis in the UK. Methods and Findings A prospective case-control study included 365 confirmed cases of severe maternal sepsis and 757 controls from all UK obstetrician-led maternity units from June 1, 2011, to May 31, 2012. Incidence of severe sepsis was 4.7 (95% CI 4.2–5.2) per 10,000 maternities; 71 (19.5%) women developed septic shock; and five (1.4%) women died. Genital tract infection (31.0%) and the organism Escherichia coli (21.1%) were most common. Women had significantly increased adjusted odds ratios (aORs) of severe sepsis if they were black or other ethnic minority (aOR = 1.82; 95% CI 1.82–2.51), were primiparous (aOR = 1.60; 95% CI 1.17–2.20), had a pre-existing medical problem (aOR = 1.40; 95% CI 1.01–1.94), had febrile illness or were taking antibiotics in the 2 wk prior to presentation (aOR = 12.07; 95% CI 8.11–17.97), or had an operative vaginal delivery (aOR = 2.49; 95% CI 1.32–4.70), pre-labour cesarean (aOR = 3.83; 95% CI 2.24–6.56), or cesarean after labour onset (aOR = 8.06; 95% CI 4.65–13.97). Median time between delivery and sepsis was 3 d (interquartile range = 1–7 d). Multiple pregnancy (aOR = 5.75; 95% CI 1.54–21.45) and infection with group A streptococcus (aOR = 4.84; 2.17–10.78) were associated with progression to septic shock; for 16 (50%) women with a group A streptococcal infection there was <2 h—and for 24 (75%) women, <9 h—between the first sign of systemic inflammatory response syndrome and a diagnosis of severe sepsis. A limitation of this study was the proportion of women with sepsis without an identified organism or infection source (16.4%). Conclusions For each maternal sepsis death, approximately 50 women have life-threatening morbidity from