Sepsis Current Awareness Bulletin March 2020

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Title: Sepsis-Associated Encephalopathy: From Delirium to Dementia? Citation: Journal of clinical medicine; Mar 2020; vol. 9 (no. 3) Author(s): Chung, Ha-Yeun; Wickel, Jonathan; Brunkhorst, Frank M; Geis, Christian Abstract: Sepsis is a major cause of death in intensive care units worldwide. The acute phase of sepsis is often accompanied by sepsis-associated encephalopathy, which is highly associated with increased mortality. Moreover, in the chronic phase, more than 50% of surviving patients suffer from severe and long-term cognitive deficits compromising their daily quality of life and placing an immense burden on primary caregivers. Due to a growing number of sepsis survivors, these long-lasting deficits are increasingly relevant. Despite the high incidence and clinical relevance, the pathomechanisms of acute and chronic stages in sepsis-associated encephalopathy are only incompletely understood, and no specific therapeutic options are yet available. Here, we review the emergence of sepsis-associated encephalopathy from initial clinical presentation to long-term cognitive impairment in sepsis survivors and summarize pathomechanisms potentially contributing to the development of sepsis-associated encephalopathy.

Title: Sepsis Management in the Emergency Department. Citation: The Nursing clinics of North America; Mar 2020; vol. 55 (no. 1); p. 71-79 Author(s): McVeigh, Sarah E Abstract: Sepsis is a deadly and costly condition, but effectively managing sepsis in the emergency department (ED) can help to improve patient outcomes. A key part of sepsis management is improving compliance with sepsis bundles, which can be challenging in the ED setting. Bedside nurses in the ED have a unique opportunity to facilitate early identification and treatment of patients with sepsis, which increases sepsis bundle compliance and improves patient outcomes. Interventions reviewed in this article can help to improve early identification and treatment, along with ways to standardize care, provide education, and implement feedback.

Title: Establishing the Therapeutic Index of Fluid Resuscitation in the Septic Patient: A Narrative Review and Meta-Analysis. Citation: Pharmacotherapy; Mar 2020; vol. 40 (no. 3); p. 256-269 Author(s): Reynolds, Paul M; Wells, Lauren; MacLaren, Robert; Scoular, Sarah K Abstract: This comprehensive review comparatively evaluates the safety and benefits of parenteral fluids used in resuscitation with a focus on sepsis. It also provides a random-effects meta-analysis of studies comparing restrictive resuscitation and usual care in sepsis with the primary outcome of mortality. In the septic patient, fluid therapy remains a complex interplay between fluid compartments in the body, the integrity of the endothelial barrier, and the inflammatory tone of the patient. Recent data have emerged describing the pharmacokinetics of fluid resuscitation that can be affected by the factors just listed, as well as mean arterial pressure, rate of infusion, volume of fluid infusate, nature of the fluid, and drug interactions. Fluid overload in sepsis has been associated with vasodilation, kidney injury, and increased mortality. Restrictive resuscitation after the initial septic insult is an emerging practice. Our search strategy of Medline databases revealed six randomized studies with 706 patients that examined restrictive resuscitation in sepsis. Results of this meta-analysis demonstrated no differences in mortality with restrictive resuscitation compared with usual care (30.6% vs 37.8%; risk ratio 0.83, 95% confidence interval 0.66-1.05, respectively) but was limited by the small number of studies and larger quantities of pre-randomization fluids. Another approach to address fluid overload is active (diuresis) de-resuscitation strategies that may shorten the need for mechanical ventilation and intensive care unit length of stay. Data suggest that colloids may confer mortality benefit over saline in the most severely ill septic patients. Compared with isotonic saline, balanced resuscitation fluids are associated with a lower incidence of acute kidney injury and mortality. The benefits of

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balanced resuscitation fluids are most evident when higher volumes of fluids are used for sepsis. Clinicians should consider these pharmacotherapeutic factors when selecting a fluid, its quantity, and rate of infusion.

Title: Perioperative Management of Patients with Sepsis and Septic Shock, Part II: Ultrasound Support for Resuscitation. Citation: Anesthesiology clinics; Mar 2020; vol. 38 (no. 1); p. 123-134 Author(s): Bughrara, Nibras; Diaz-Gomez, Jose L; Pustavoitau, Aliaksei Abstract: Point-of-care ultrasound is capable of identifying the precise causes of hemodynamic failure in patients with septic shock. Patients in shock demonstrate complex alterations in their circulation, including changes in loading conditions (preload and afterload), right and left ventricular function, and development of obstructive physiology, and some of them have a burden of underlying cardiac disease. Knowledge of underlying hemodynamic derangements in such situations allows targeted interventions, that is, fluids, vasoactive, and inotropic medications, to optimize patient's perfusion. One example of competing goals involves a patient with hypertrophic "thick" left ventricle (LV), which is easily identified using point-of-care ultrasound (POCUS). Such patients usually have diastolic dysfunction and commonly require higher filling pressures (mainly grade II and III diastolic dysfunction) to maintain adequate cardiac output. They are vulnerable to the effects of hypovolemia with the potential for dynamic LV outflow tract (LVOT) obstruction. The use of inotrope is harmful under these circumstances and could lead to worsening of the obstructive physiology because of systolic anterior motion of the mitral valve leaflet and mitral regurgitation with rapid progression toward a cardiac arrest. Recognizing the increasingly important role of POCUS in the perioperative arena, in this review, we highlight how POCUS allows anesthesiologists to recognize and manage hemodynamic derangements in patients with sepsis and septic shock. We provide a systematic approach to the evaluation of this patient population using qualitative assessment of myocardial performance, fluid responsiveness, and fluid tolerance. Our approach is based on a limited number of ultrasound views: subcostal, inferior vena cava (IVC), and lung views are obtained in rapid succession. A combination of findings in these views is grouped into distinct hemodynamic phenotypes, each of them requiring their own approach to management.

Title: Perioperative Management of Patients with Sepsis and Septic Shock, Part I: Systematic Approach. Citation: Anesthesiology clinics; Mar 2020; vol. 38 (no. 1); p. 107-122 Author(s): Bughrara, Nibras; Cha, Stephanie; Safa, Radwan; Pustavoitau, Aliaksei Abstract: Sepsis and septic shock are medical emergencies, with high associated mortality. The Surviving Sepsis Campaign has developed definitions and management guidelines, emphasizing the use of hour-1 care bundle. Anesthesiologists frequently encounter sepsis when source control is required. The authors summarize expected manifestations of organ dysfunction and state-of-the-art management of patients with sepsis and septic shock. They highlight an increasingly vital role point-of-care ultrasound examination in the recognition and management of hemodynamic derangements in this patient population. Supporting the role of anesthesiologists as perioperative physicians, the authors provide a framework for transitions of care between operating room and intensive care units.

Title: Interventions for rapid recognition and treatment of sepsis in the emergency department - A narrative review. Citation: Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases; Feb 2020

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Author(s): Uffen, Jan Willem; Oosterheert, Jan-Jelrik; Schweitzer, Valentijn; Thursky, Karin; Kaasjager, Karin; Ekkelenkamp, Miquel Background: Sepsis is a major cause of morbidity and mortality worldwide. Early recognition and treatment of sepsis is associated with improved outcome. Emergency departments (EDs) are the main department where patients with sepsis are presented. But recognition in the ED remains difficult. Different alert and triage systems, screening scores and intervention strategies have been developed to assist clinicians in early recognition of sepsis and to optimize management. Objectives: this narrative review describes currently applied interventions or interventions we can start using today such as screening scores, (automated) triage systems, sepsis teams, and clinical pathways in sepsis care, and summarizes evidence for the effect of implementation of these interventions in the ED on patient management and outcomes. Sources: A systematic literature search was conducted in PubMed resulting in 32 eligible studies. Content: The main sepsis interventions in the ED are (automated) triage systems, sepsis teams and clinical pathways, the most integrative being a clinical pathway. Implementation of any of these interventions in sepsis care, will generally lead to increased protocol adherence. Presumably, increased adherence to sepsis guidelines and bundles will lead to better patient outcomes, but the level of evidence to support this improvement is low, while implementation of interventions is often complex and costly. No studies comparing different interventions were identified. Essential factors for success of interventions in the ED are (1) obtaining the support from all professionals and (2) providing ongoing education. The vulnerability of these interventions resides in the lack of accurate tools to identify sepsis; diagnosing sepsis ultimately still relies on clinical assessments. A lack of specificity or sepsis alerts may lead to alert-tiredness and/or over-treatment. Implications: Severity and poor outcome of sepsis and the frequency of presentation in EDs. make a structured, protocolled approach towards these patients essential, preferably as part of a clinical pathway.

Title: Improving Sepsis Bundle Implementation Times: A Nursing Process Improvement Approach. Citation: Journal of Nursing Care Quality; Apr 2020; vol. 35 (no. 2); p. 135-139 Author(s): Threatt, David L. Background: Early recognition of sepsis in the emergency room (ER) has been shown to improve treatment intervention times and decrease mortality. Local Problem: Failure to recognize early signs and symptoms of sepsis in the ER has led to poor sepsis bundle completion times. Methods: A comparison of preintervention and postintervention data was performed to determine whether sepsis bundle implementation times, mortality, and length of stay (LOS) improved. Interventions: An ER Nurse Sepsis Identification Tool, leadership buy-in from key stakeholders, and systemic inflammatory response syndrome (SIRS) education were implemented. Results: Postintervention, average bundle compliance time decreased 458 minutes (P < .001), average antibiotic administration time decreased 101 minutes (P < .001), overall sepsis mortality decreased 5.9% (P = .074), and there was no change to LOS. Conclusions: The implementation of an ER early sepsis identification tool, leadership buy-in, and SIRS education can lead to improved bundle implementation times in the ER.

Title: Predictive value of C-reactive protein and NT-pro-BNP levels in sepsis patients older than 75 years: a prospective, observational study. Citation: Aging Clinical & Experimental Research; Mar 2020; vol. 32 (no. 3); p. 389-397 Author(s): Li, Han; Shan-shan, Zhang; Jian-qiang, Kang; Ling, Yang; Fang, Liu

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Introduction: Using biomarkers to predict mortality in patients with sepsis is important because these patients frequently have high mortality rates and unsatisfactory outcomes. The performance of N-terminal pro-brain natriuretic peptide (NT-pro-BNP) and C-reactive protein (CRP) to predict clinical outcomes in elderly sepsis patients is unimpressive. We aimed to assess the prognostic value of NT-pro-BNP, CRP and the combination of both in selected medical ICU sepsis patients more than 75 years old. Methods: In total, 245 consecutive patients were screened for eligibility and followed during their ICU stays. We collected the patients' baseline characteristics, including their Acute Physiology and Chronic Health Evaluation II (APACHE II) scores and NT-pro-BNP and CRP levels. The primary outcome was ICU mortality. Potential predictors were analyzed for their possible associations with the outcome. We also evaluated the ability of NT-pro-BNP and CRP levels combined with the APACHE II score to predict ICU mortality by calculating the C-index and net reclassification improvement (NRI). Results: Univariate regression revealed that CRP, NT-pro-BNP, APACHE II score, lactic acid level, NEU count(neutrophil count)and HCT level independently predicted ICU mortality (all P < 0.01). The C-index for the prediction of ICU mortality by the APACHE II score (0.847 ± 0.029; P < 0.001) was greater than that for NT-pro-BNP (0.673 ± 0.039; P < 0.01) or CRP (0.626 ± 0.039; P < 0.01) (all P < 0.01). Compared with the APACHE II score (0.847 ± 0.029; P < 0.001), the combination of CRP (0.849 ± 0.029; P < 0.01) or NT-pro-BNP (0.853 ± 0.028; P < 0.01) or both (0.853 ± 0.030; P 0.05). However, the addition of NT-pro-BNP to the APACHE II score gave an NRI of 8.6% (P = 0.000), the addition of CRP to the APACHE II score provided an NRI of 11.34% (P = 0.012), and the addition of both markers to the APACHE II score yielded an NRI of 29.0% (P = 0.000). In the MOF subgroup (N = 118), CRP (OR = 2.62, P 0.05) independently predicted ICU mortality, and the addition of CRP to the APACHE II score obviously increased its predictive ability (NRI = 13.88%, P = 0.000). In the non-MOF group (N = 127), neither CRP (OR = 5.447, P = 0.078) nor NT-pro-BNP (OR = 2.239, P = 0.016) was an independent predictor of ICU mortality. Conclusions: In sepsis patients older than 75 years, NT-pro-BNP and CRP can serve as independent predictors of mortality, and the addition of NT-pro-BNP or CRP or both to the APACHE II score significantly improves the ability to predict ICU mortality. CRP appears to be useful for predicting ICU outcomes in elderly sepsis patients with multiple-organ failure.

Title: Management of Sepsis in the Pediatric Patient. Citation: Journal of Radiology Nursing; Mar 2020; vol. 39 (no. 1); p. 24-31 Author(s): Rooney, Sara P.; Heffren, Joshua C.; Song, Boh L.; Sanchez, Alicia C. Abstract: Sepsis is a life-threatening condition requiring prompt recognition and aggressive, multidisciplinary treatment. This treatment consists of, but is not limited to, cardiovascular support via fluids and vasoactive medications plus systemic, broad-spectrum antibiotics. This article reviews the guidelines as well as supporting primary literature surrounding fluids, vasoactive medications, and antibiotic recommendations for pediatric sepsis. • This article reviews and fully summarizes up-to-date information, including primary literature and guidelines, regarding the multidisciplinary care and treatment necessary for severely ill septic pediatric patients.

Title: Role of procalcitonin use in the management of sepsis. Citation: Journal of Thoracic Disease; Feb 2020; vol. 12 (no. 1) Author(s): Gregoriano, Claudia; Heilmann, Eva; Molitor, Alexandra; Schuetz, Philipp Abstract: Important aspects of sepsis management include early diagnosis as well as timely and specific treatment in the first few hours of triage. However, diagnosis and differentiation from non-infectious causes often cause uncertainties and potential time delays. Correct use of antibiotics still represents a major challenge, leading to increased risk for opportunistic infections, resistances to multiple antimicrobial agents and toxic side effects, which in turn increase mortality and healthcare costs. Optimized procedures for reliable diagnosis and management of antibiotic therapy has great potential to improve patient care. Herein, biomarkers have been shown to improve infection diagnosis,

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help in early risk stratification and provide prognostic information which helps optimizing therapeutic decisions ("antibiotic stewardship"). In this context, the use of the blood infection marker procalcitonin (PCT) has gained much attention. There is still no gold standard for the detection of sepsis and use of conventional diagnostic approaches are restricted by some limitations. Therefore, additional tests are necessary to enable early and reliable diagnosis. PCT has good discriminatory properties to differentiate between bacterial and viral inflammations with rapidly available results. Further, PCT adds to risk stratification and prognostication, which may influence appropriate use of health-care resources and therapeutic options. PCT kinetics over time also improves the monitoring of critically ill patients with sepsis and thus influences decisions regarding de-escalation of antibiotics. Most importantly, PCT helps in guiding antibiotic use in patients with respiratory infection and sepsis by limiting initiation and by shortening treatment duration. To date, PCT is the best studied biomarker regarding antibiotic stewardship. Still, further research is needed to understand optimal use of PCT, also in combination with other remerging diagnostic tests for most efficient sepsis care.

Title: Fluid resuscitation in sepsis: the great 30 mL per kg hoax. Citation: Journal of Thoracic Disease; Feb 2020; vol. 12 (no. 1) Author(s): Marik, Paul E.; Byrne, Liam; van Haren, Frank Abstract: Large volume fluid resuscitation is currently viewed as the cornerstone of the treatment of septic shock. The surviving sepsis campaign (SSC) guidelines provide a strong recommendation to rapidly administer a minimum of 30 mL/kg crystalloid solution intravenously in all patients with septic shock and those with elevated blood lactate levels. However, there is no credible evidence to support this recommendation. In fact, recent findings from experimental, observational and randomized clinical trials demonstrate improved outcomes with a more restrictive approach to fluid resuscitation. Accumulating evidence suggests that aggressive fluid resuscitation is harmful. Paradoxically, excess fluid administration may worsen shock. In this review, we critically evaluate the scientific evidence for a weight-based fluid resuscitation approach. Furthermore, the potential mechanisms and consequences of harm associated with fluid resuscitation are discussed. Finally, we recommend an individualized, conservative and physiologic guided approach to fluid resuscitation.

Title: The origins of the Lacto-Bolo reflex: the mythology of lactate in sepsis. Citation: Journal of Thoracic Disease; Feb 2020; vol. 12 (no. 1) Author(s): Spiegel, Rory; Gordon, David; Marik, Paul E. Abstract: The use of lactate as a marker of the severity of circulatory shock was popularized by Dr. Weil in the 1970's. Dr. Weil promoted the idea that blood lactate concentration increased in circulatory shock due to anaerobic metabolism following decreased oxygen delivery. This concept becomes entrenched with 1992 ACCP/SCCM consensus conference definition of sepsis. Since then, the central role of lactate in the definition and management of septic shock has only been expanded and become more ingrained. This review will discuss the wisdom of such an approach, an updated model describing the origins of hyperlactatemia in sepsis, and how such improvements in our knowledge of the underlying physiology should change our approach to resuscitation in patients presenting with septic shock.

Title: Sepsis trends: increasing incidence and decreasing mortality, or changing denominator? Citation: Journal of Thoracic Disease; Feb 2020; vol. 12 (no. 1) Author(s): Rhee, Chanu; Klompas, Michael Abstract: Numerous studies suggest that the incidence of sepsis has been steadily increasing over the past several decades while mortality rates are falling. However, reliably assessing trends in sepsis epidemiology is challenging due to changing diagnosis and coding practices over time. Ongoing

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efforts by clinicians, administrators, policy makers, and patient advocates to increase sepsis awareness, screening, and recognition are leading to more patients being labeled with sepsis. Subjective clinical definitions and heterogeneous presentations also allow for wide discretion in diagnosing sepsis rather than specific infections alone or nonspecific syndromes. These factors create a potential ascertainment bias whereby the inclusion of less severely ill patients in sepsis case counts over time leads to a perceived increase in sepsis incidence and decrease in sepsis mortality rates. Analyses that rely on administrative data alone are further confounded by changing coding practices in response to new policies, financial incentives, and efforts to improve documentation. An alternate strategy for measuring sepsis incidence, outcomes, and trends is to use objective and consistent clinical criteria rather than administrative codes or registries to identify sepsis. This is feasible using data routinely found in electronic health record systems, such as blood culture draws and sustained courses of antibiotics to identify infection and laboratory values, vasopressors, and mechanical ventilation to measure acute organ dysfunction. Recent surveillance studies using this approach suggest that sepsis incidence and mortality rates have been essentially stable over the past decade. In this review, we summarize the major epidemiologic studies of sepsis trends, potential biases in these analyses, and the recent change in the surveillance paradigm toward using objective clinical data from electronic health records to more accurately characterize sepsis trends.

Title: Sepsis In The Context Of Nonventilator Hospital-Acquired Pneumonia. Citation: American Journal of Critical Care; Jan 2020; vol. 29 (no. 1); p. 9-14 Author(s): Giuliano, Karen K. Background: Sepsis is a leading cause of mortality among hospitalized patients and is the most expensive condition affecting the US health care system. Pneumonia is associated with about half of sepsis cases, yet limited research has described the incidence of sepsis in the context of nonventilator hospital-acquired pneumonia (NV-HAP). Persons with NV-HAP who are at risk for sepsis must be identified so that interventions to reduce the burden of NV-HAP and improve outcomes among patients with sepsis can be designed. Objectives: To determine the proportion of persons with NV-HAP in whom sepsis develops and to describe the demographic and clinical characteristics of persons with NV-HAP in whom sepsis develops. Methods: In this retrospective, population-based study, data were extracted from the National Inpatient Sample from the 2012 Healthcare Cost and Utilization Project dataset. International Classification of Diseases, Ninth Revision, Clinical Modification codes were used to identify adult patients at least 18 years of age who had a stay of at least 48 hours, had no documented diagnosis of ventilator- associated pneumonia, and had secondary diagnoses of both NV-HAP and sepsis, neither of which was present on admission. Results: In the 2012 calendar year, 119 075 adults had NV-HAP develop; sepsis developed in 36.3% of these cases. Male and black patients were overrepresented in the sample, and patients had a mean of 7 comorbid conditions (SD, 3.3). Conclusions: Sepsis in the context of NV-HAP is a key concern. Additional research is needed to identify factors associated with the development of sepsis among patients with NV-HAP.

Title: The Obesity Paradox in Sepsis: A Theoretical Framework. Citation: Biological research for nursing; Feb 2020 ; p. 1099800420905889 Author(s): Robinson, Jamie; Swift-Scanlan, Theresa; Salyer, Jeanne; Jones, Terry Abstract: Sepsis is a life-threatening syndrome that occurs in response to a severe infection. In recent years, the understanding of the pathobiology of sepsis has been refined, with research describing an altered host response as the underlying cause. Survivors of sepsis often have long hospital stays and suffer from subsequent frailty and long-term health consequences. Predicting attributes of sepsis survivors remains challenging; however, an obesity paradox exists, wherein obese individuals survive sepsis at higher rates than their normal-weight counterparts. We present a model

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that describes the relationships between sepsis and obesity, focusing on inflammation as a shared pathway for dysregulation in obese and healthy-weight adults. Understanding the interaction of these complex variables is an important first step toward developing interventions and treatments to augment sepsis survival.

Title: The Australasian Resuscitation In Sepsis Evaluation: Fluids or vasopressors in emergency department sepsis (ARISE FLUIDS), a multi-centre observational study describing current practice in Australia and New Zealand. Citation: Emergency medicine Australasia : EMA; Feb 2020 Author(s): Keijzers, Gerben; Macdonald, Stephen Pj; Udy, Andrew A; Arendts, Glenn; Bailey, Michael; Bellomo, Rinaldo; Blecher, Gabriel E; Burcham, Jonathon; Coggins, Andrew R; Delaney, Anthony; Fatovich, Daniel M; Fraser, John F; Harley, Amanda; Jones, Peter; Kinnear, Frances B; May, Katya; Peake, Sandra; Taylor, David McD; Williams, Patricia; ARISE FLUIDS Observational Study Group Objectives: To describe haemodynamic resuscitation practices in ED patients with suspected sepsis and hypotension. Methods: This was a prospective, multicentre, observational study conducted in 70 hospitals in Australia and New Zealand between September 2018 and January 2019. Consecutive adults presenting to the ED during a 30-day period at each site, with suspected sepsis and hypotension (systolic blood pressure <100 mmHg) despite at least 1000 mL fluid resuscitation, were eligible. Data included baseline demographics, clinical and laboratory variables and intravenous fluid volume administered, vasopressor administration at baseline and 6- and 24-h post-enrolment, time to antimicrobial administration, intensive care admission, organ support and in-hospital mortality. Results: A total of 4477 patients were screened and 591 were included with a mean (standard deviation) age of 62 (19) years, Acute Physiology and Chronic Health Evaluation II score 15.2 (6.6) and a median (interquartile range) systolic blood pressure of 94 mmHg (87-100). Median time to first intravenous antimicrobials was 77 min (42-148). A vasopressor infusion was commenced within 24 h in 177 (30.2%) patients, with noradrenaline the most frequently used (n = 138, 78%). A median of 2000 mL (1500-3000) of intravenous fluids was administered prior to commencing vasopressors. The total volume of fluid administered from pre-enrolment to 24 h was 4200 mL (3000-5661), with a range from 1000 to 12 200 mL. Two hundred and eighteen patients (37.1%) were admitted to an intensive care unit. Overall in-hospital mortality was 6.2% (95% confidence interval 4.4-8.5%). Conclusion: Current resuscitation practice in patients with sepsis and hypotension varies widely and occupies the spectrum between a restricted volume/earlier vasopressor and liberal fluid/later vasopressor strategy.

Title: Higher glycemic variability within the first day of ICU admission is associated with increased 30-day mortality in ICU patients with sepsis. Citation: Annals of intensive care; Feb 2020; vol. 10 (no. 1); p. 17 Author(s): Chao, Wen-Cheng; Tseng, Chien-Hua; Wu, Chieh-Liang; Shih, Sou-Jen; Yi, Chi-Yuan; Chan, Ming-Cheng Background: High glycemic variability (GV) is common in critically ill patients; however, the prevalence and mortality association with early GV in patients with sepsis remains unclear. Methods: This retrospective cohort study was conducted in a medical intensive care unit (ICU) in central Taiwan. Patients in the ICU with sepsis between January 2014 and December 2015 were included for analysis. All of these patients received protocol-based management, including blood sugar monitoring every 2 h for the first 24 h of ICU admission. Mean amplitude of glycemic excursions (MAGE) and coefficient of variation (CoV) were used to assess GV. Results: A total of 452 patients (mean age 71.4 ± 14.7 years; 76.7% men) were enrolled for analysis. They were divided into high GV (43.4%, 196/452) and low GV (56.6%, 256/512) groups using MAGE

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65 mg/dL as the cut-off point. Patients with high GV tended to have higher HbA1c (6.7 ± 1.8% vs. 5.9 ± 0.9%, p < 0.01) and were more likely to have diabetes mellitus (DM) (50.0% vs. 23.4%, p  65 mg/dL. Higher GV within 24 h of ICU admission was independently associated with increased 30-day mortality. These findings highlight the need to monitor GV in septic patients early during an ICU admission.

Title: Paediatric sepsis: timely management to save lives. Citation: The Lancet. Child & adolescent health; Feb 2020 Author(s): The Lancet Child Adolescent Health

Title: Validation of automated sepsis surveillance based on the Sepsis-3 clinical criteria against physician record review in a general hospital population: observational study using electronic health records data. Citation: BMJ quality & safety; Feb 2020 Author(s): Valik, John Karlsson; Ward, Logan; Tanushi, Hideyuki; Müllersdorf, Kajsa; Ternhag, Anders; Aufwerber, Ewa; Färnert, Anna; Johansson, Anders F; Mogensen, Mads Lause; Pickering, Brian; Dalianis, Hercules; Henriksson, Aron; Herasevich, Vitaly; Nauclér, Pontus Background: Surveillance of sepsis incidence is important for directing resources and evaluating quality-of-care interventions. The aim was to develop and validate a fully-automated Sepsis-3 based surveillance system in non-intensive care wards using electronic health record (EHR) data, and demonstrate utility by determining the burden of hospital-onset sepsis and variations between wards. Methods: A rule-based algorithm was developed using EHR data from a cohort of all adult patients admitted at an academic centre between July 2012 and December 2013. Time in intensive care units was censored. To validate algorithm performance, a stratified random sample of 1000 hospital admissions (674 with and 326 without suspected infection) was classified according to the Sepsis-3 clinical criteria (suspected infection defined as having any culture taken and at least two doses of antimicrobials administered, and an increase in Sequential Organ Failure Assessment (SOFA) score by >2 points) and the likelihood of infection by physician medical record review. Results: In total 82 653 hospital admissions were included. The Sepsis-3 clinical criteria determined by physician review were met in 343 of 1000 episodes. Among them, 313 (91%) had possible, probable or definite infection. Based on this reference, the algorithm achieved sensitivity 0.887 (95% CI: 0.799 to 0.964), specificity 0.985 (95% CI: 0.978 to 0.991), positive predictive value 0.881 (95% CI: 0.833 to 0.926) and negative predictive value 0.986 (95% CI: 0.973 to 0.996). When applied to the total cohort taking into account the sampling proportions of those with and without suspected infection, the algorithm identified 8599 (10.4%) sepsis episodes. The burden of hospital-onset sepsis (>48 hour after admission) and related in-hospital mortality varied between wards. Conclusions: A fully-automated Sepsis-3 based surveillance algorithm using EHR data performed well compared with physician medical record review in non-intensive care wards, and exposed variations in hospital-onset sepsis incidence between wards.

Title: Long-Term Courses of Sepsis Survivors: Effects of a Primary Care Management Intervention Citation: American Journal of Medicine; Mar 2020; vol. 133 (no. 3); p. 381 Author(s): Schmidt K.F.; Schwarzkopf D.; Freytag A.; Schneider N.; Worrack S.; Gensichen J.; Heintze C.; Reinhart K.; Baldwin L.-M.; Brunkhorst F.M.; von Korff M.; Wensing M. Background: Sepsis survivors face mental and physical sequelae even years after discharge from the intensive care unit. The aim of this study was to evaluate the long-term courses of sepsis survivors and the effects of a primary care management intervention in sepsis aftercare.

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Method(s): This study presents a 24-month follow-up of a randomized controlled trial that recruited 291 patients who survived sepsis (including septic shock) from nine German intensive care units. Participants were randomized to usual care (n=143) or to a 12-month-intervention (n=148). The intervention included training of patients and their primary care physicians (PCP) in evidence-based post-sepsis care, case management provided by trained nurses, and clinical decision support for PCPs by consulting physicians. Usual care was provided by PCPs in the control group. At the 24-month follow-up, 12 months after the 1-year-intervention, survival and measures of mental and physical health were collected by telephone interviews. Result(s): One hundred eighty-six (63.9%, 98 intervention, 88 control) of 291 patients completed the 24-month follow-up, showing both increased mortality and recovery from functional impairment. Unlike the intervention group, the control group showed a significant increase of posttraumatic stress symptoms according to the Posttraumatic Symptom Scale (difference between baseline and 24-months follow-up values, mean [standard deviation] 3.7 [11.8] control vs -0.7 [12.1] intervention; P =. 016). There were no significant differences in all other outcomes between the intervention and control groups. Conclusion(s): Twelve months after completion, a primary care management intervention among survivors of sepsis did not improve mental health-related quality of life. Patients in the intervention group showed less posttraumatic stress symptoms. Copyright © 2019 Elsevier Inc.

Title: Continuous EEG Monitoring in a Consecutive Patient Cohort with Sepsis and Delirium Citation: Neurocritical Care; Feb 2020; vol. 32 (no. 1); p. 121-130 Author(s): Nielsen R.M.; Moller K.; Olsen K.S.; Lauritsen A.O.; Eddelien H.S.; Urdanibia-Centelles O.; Vedel-Larsen E.; Lauritzen M.; Benedek K.; Thomsen K.J. Background: Delirium is common during sepsis, although under-recognized. We aimed to assess the value of continuous electroencephalography (cEEG) to aid in the diagnosis of delirium in septic patients. Method(s): We prospectively evaluated 102 consecutive patients in a medical intensive care unit (ICU), who had sepsis or septic shock, without evidence of acute primary central nervous system disease. We initiated cEEG recording immediately after identification. The median cEEG time per patient was 44 h (interquartile range 21-99 h). A total of 6723 h of cEEG recordings were examined. The Confusion Assessment Method for the ICU (CAM-ICU) was administered six times daily to identify delirium. We analyzed the correlation between cEEG and delirium using 1252 two-minute EEG sequences recorded simultaneously with the CAM-ICU scorings. Result(s): Of the 102 included patients, 66 (65%) had at least one delirium episode during their ICU stay, 30 (29%) remained delirium-free, and 6 (6%) were not assessable due to deep sedation or coma. The absence of delirium was independently associated with preserved high-frequency beta activity (> 13 Hz) (P < 10-7) and cEEG reactivity (P < 0.001). Delirium was associated with preponderance of low-frequency cEEG activity and absence of high-frequency cEEG activity. Sporadic periodic cEEG discharges occurred in 15 patients, 13 of whom were delirious. No patient showed clinical or electrographic evidence of non-convulsive status epilepticus. Conclusion(s): Our findings indicate that cEEG can help distinguish septic patients with delirium from non-delirious patients. Copyright © 2019, Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.

Title: Application of regression model combined with computer technology in the construction of early warning model of sepsis infection in children Citation: Journal of Infection and Public Health; Feb 2020; vol. 13 (no. 2); p. 253-259 Author(s): Yang J.; Ma Y.; Mao M.; Zhang P.; Gao H. Abstract: This paper uses computer technology combined with regression model to analyze the risk factors of children with sepsis, determine the relevant factors and establish a corresponding early warning model of sepsis, and then verify the clinical application value of the regression model. The

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paper collected severe infections and sepsis in children who came to our hospital from 2014 to 2018, including 129 patients with infection and 86 patients with sepsis. The general conditions, clinical symptoms, laboratory tests and other factors were used. Analysis, to identify the risk of infection development into sepsis, and use Logistic regression model combined with computer technology to construct an early warning model of sepsis. The experimental results show that early warning of sepsis is closely related to skin spots, platelets, procalcitonin, creatinine and international normalized ratio. The experiment demonstrates that the early warning model has higher sensitivity and specificity, and has higher accuracy for predicting whether infection develops into sepsis in advance, and has certain clinical value. Copyright © 2019 The Authors

Title: Implementation of an Evidence-Based, Nurse-Driven Sepsis Protocol to Reduce Acute Care Transfer Readmissions in the Inpatient Rehabilitation Facility Setting. Citation: Rehabilitation nursing : the official journal of the Association of Rehabilitation Nurses; ; vol. 45 (no. 2); p. 57-70 Author(s): Jacobs, Jenelle L Purpose: The aim of this study was to determine if implementing an evidence-based, nurse-driven sepsis protocol would reduce acute care transfer (ACT) readmissions from an inpatient rehabilitation facility compared to nonprotocolized or usual standard of care for adult sepsis patients undergoing physical rehabilitation. Design: This study used a preintervention and postintervention model for quality improvement, which involved comparing the nonprotocolized care of adult sepsis patients in the inpatient rehabilitation population to the application of an evidence-based, nurse-driven sepsis protocol to determine its effect on reducing ACT readmissions. Methods: Patients who screened positive for suspected sepsis and received protocolized interventions were analyzed to determine the occurrence of ACT readmission. Compliance with protocol elements was also evaluated. Findings: The sepsis-related ACT readmission rate decreased from 36.28% to 25% in 8 weeks, and compliance with protocolized sepsis interventions increased.CONCLUSIONSNurse-driven, protocolized assessment and treatment can improve the management and care of sepsis patients undergoing physical rehabilitation and can reduce ACT readmissions. Clinical Relevance: This review provides rehabilitation nurses an evidence-based, nurse-driven approach to the clinical management of sepsis patients in the inpatient rehabilitation setting and discusses how this approach can reduce ACT readmissions and improve clinical outcomes.

Title: Heart failure and sepsis: practical recommendations for the optimal management. Citation: Heart failure reviews; Mar 2020; vol. 25 (no. 2); p. 183-194 Author(s): Arfaras-Melainis, Angelos; Polyzogopoulou, Eftihia; Triposkiadis, Filippos; Xanthopoulos, Andrew; Ikonomidis, Ignatios; Mebazaa, Alexander; Parissis, John Abstract: Acute heart failure (AHF) is a common clinical challenge that a wide spectrum of physicians encounters in every practice. In many cases, AHF is due to decompensation of chronic heart failure. This decompensation may be triggered by various reasons, with sepsis being a notable one. Sepsis is defined as a life-threatening organ dysfunction caused by the dysregulated host response to infection and is associated with a very high mortality, which may reach 25%. Alarmingly, the increase in the mortality rate of patients with combined cardiac dysfunction and sepsis is extremely high (may reach 90%). Thus, these patients need urgent intervention. Management of patients with AHF and sepsis is challenging since cornerstone interventions for AHF may be contraindicated in sepsis and vice versa (e.g., diuretic treatment). Unfortunately, no relevant guidelines are yet available, and treatment remains empirical. This review attempts to shed light on the intricacies of the available interventions and suggests routes of action based on the existing bibliography.

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Title: Diagnostic and prognostic value of red blood cell distribution width in sepsis: A narrative review. Citation: Clinical biochemistry; Mar 2020; vol. 77 ; p. 1-6 Author(s): Hu, Zhi-De; Lippi, Giuseppe; Montagnana, Martina Abstract: Previous studies showed that red blood cell distribution width (RDW) can be used as a prognostic and diagnostic index in various non-hematological diseases, including severe infections and sepsis. Here, we provide a narrative review to summarize the findings of available studies investigating the relationship between RDW and sepsis. Current evidence suggests that increased RDW on admission, both in adults and neonates, may be associated with unfavorable outcomes on the short- and long-term. In patients with suspected sepsis, RDW has modest value for predicting positive blood culture. Accordingly, its diagnostic value for sepsis seems limited, whilts dynamic changes of RDW are associated with outcome of sepsis. Taken together, these results suggest that RDW could be used as a prognostic index in septic patients.

Title: Screening for early onset neonatal sepsis: NICE guidance-based practice versus projected application of the Kaiser Permanente sepsis risk calculator in the UK population. Citation: Archives of disease in childhood. Fetal and neonatal edition; Mar 2020; vol. 105 (no. 2); p. 118-122 Objective: To compare management recommendations of the National Institute for Health and Care Excellence (NICE) guidelines with the Kaiser Permanente sepsis risk calculator (SRC) for risk of early onset neonatal sepsis (EONS). Design: Multicentre prospective observational projection study.SETTINGEight maternity hospitals in Wales, UK. Patients: All live births ≥34 weeks gestation over a 3-month period (February-April 2018). Methods: Demographics, maternal and infant risk factors, infant's clinical status, antibiotic usage and blood culture results from first 72 hours of birth were collected. Infants were managed using NICE recommendations and decisions compared with that projected by SRC. Main Outcome Measure: Proportion of infants recommended for antibiotics on either tool.RESULTSOf 4992 eligible infants, complete data were available for 3593 (71.9%). Of these, 576 (16%) were started on antibiotics as per NICE recommendations compared with 156 (4.3%) projected by the SRC, a relative reduction of 74%. Of the 426 infants avoiding antibiotics, SRC assigned 314 (54.6%) to normal care only. There were seven positive blood cultures-three infants were recommended antibiotics by both, three were not identified in the asymptomatic stage by either; one was a contaminant. No EONS-related readmission was reported. Conclusion: The judicious adoption of SRC in UK clinical practice for screening and management of EONS could potentially reduce interventions and antibiotic usage in three out of four term or near-term infants and promote earlier discharge from hospital in >50%. We did not identify any EONS case missed by SRC when compared with NICE. These results have significant implications for healthcare resources.

Title: Fluid-limiting treatment strategies among sepsis patients in the ICU: a retrospective causal analysis. Citation: Critical care (London, England); Feb 2020; vol. 24 (no. 1); p. 62 Author(s): Shahn, Zach; Shapiro, Nathan I; Tyler, Patrick D; Talmor, Daniel; Lehman, Li-Wei H Objective: In septic patients, multiple retrospective studies show an association between large volumes of fluids administered in the first 24 h and mortality, suggesting a benefit to fluid restrictive strategies. However, these studies do not directly estimate the causal effects of fluid-restrictive

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strategies, nor do their analyses properly adjust for time-varying confounding by indication. In this study, we used causal inference techniques to estimate mortality outcomes that would result from imposing a range of arbitrary limits ("caps") on fluid volume administration during the first 24 h of intensive care unit (ICU) care. Design: Retrospective cohort study Setting: ICUs at the Beth Israel Deaconess Medical Center, 2008-2012 PATIENTS: One thousand six hundred thirty-nine septic patients (defined by Sepsis-3 criteria) 18 years and older, admitted to the ICU from the emergency department (ED), who received less than 4 L fluids administered prior to ICU admission Measurements And Main Results: Data were obtained from the Medical Information Mart for Intensive Care III (MIMIC-III). We employed a dynamic Marginal Structural Model fit by inverse probability of treatment weighting to obtain confounding adjusted estimates of mortality rates that would have been observed had fluid resuscitation volume caps between 4 L-12 L been imposed on the population. The 30-day mortality in our cohort was 17%. We estimated that caps between 6 and 10 L on 24 h fluid volume would have reduced 30-day mortality by - 0.6 to - 1.0%, with the greatest reduction at 8 L (- 1.0% mortality, 95% CI [- 1.6%, - 0.3%]). Conclusions: We found that 30-day mortality would have likely decreased relative to observed mortality under current practice if these patients had been subject to "caps" on the total volume of fluid administered between 6 and 10 L, with the greatest reduction in mortality rate at 8 L.

Title: Screening strategies to identify sepsis in the prehospital setting: a validation study. Citation: CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne; Mar 2020; vol. 192 (no. 10); p. E230 Author(s): Lane, Daniel J; Wunsch, Hannah; Saskin, Refik; Cheskes, Sheldon; Lin, Steve; Morrison, Laurie J; Scales, Damon C Background: In the prehospital setting, differentiating patients who have sepsis from those who have infection but no organ dysfunction is important to initiate sepsis treatments appropriately. We aimed to identify which published screening strategies for paramedics to use in identifying patients with sepsis provide the most certainty for prehospital diagnosis. Methods: We identified published strategies for screening by paramedics through a literature search. We then conducted a validation study in Alberta, Canada, from April 2015 to March 2016. For adult patients (≥ 18 yr) who were transferred by ambulance, we linked records to an administrative database and then restricted the search to patients with infection diagnosed in the emergency department. For each patient, the classification from each strategy was determined and compared with the diagnosis recorded in the emergency department. For all strategies that generated numeric scores, we constructed diagnostic prediction models to estimate the probability of sepsis being diagnosed in the emergency department. Results: We identified 21 unique prehospital screening strategies, 14 of which had numeric scores. We linked a total of 131 745 eligible patients to hospital databases. No single strategy had both high sensitivity (overall range 0.02-0.85) and high specificity (overall range 0.38-0.99) for classifying sepsis. However, the Critical Illness Prediction (CIP) score, the National Early Warning Score (NEWS) and the Quick Sepsis-Related Organ Failure Assessment (qSOFA) score predicted a low to high probability of a sepsis diagnosis at different scores. The qSOFA identified patients with a 7% (lowest score) to 87% (highest score) probability of sepsis diagnosis. Interpretation: The CIP, NEWS and qSOFA scores are tools with good predictive ability for sepsis diagnosis in the prehospital setting. The qSOFA score is simple to calculate and may be useful to paramedics in screening patients with possible sepsis.

Title: Serum 25-Hydroxyvitamin D and the risk of mortality in adult patients with Sepsis: a meta-analysis. Citation: BMC infectious diseases; Mar 2020; vol. 20 (no. 1); p. 189

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Author(s): Li, Yuye; Ding, Shifang Background: Vitamin D deficiency has been related to the risk of sepsis. However, previous studies showed inconsistent results regarding the association between serum 25-hydroxyvitamin D (25 (OH) D) and mortality risk in septic patients. We aimed to evaluate the relationship between serum 25 (OH) D at admission and mortality risk in adult patients in a meta-analysis. Methods: Follow-up studies that provided data of multivariate adjusted relative risk (RR) between serum 25 (OH) D and mortality risk in septic patients were retrieved via systematic search of PubMed and Embase databases. A random effect model was used to pool the results. Results: Eight studies with 1736 patients were included. Results of overall meta-analysis showed that lower 25 (OH) D at admission was independently associated with increased risk or mortality (adjusted RR: 1.93, p < 0.001; I2 = 63%) in patients with sepsis. Exploring subgroup association showed that patients with severe vitamin D deficiency (25 (OH) D < 10 ng/ml) was significantly associated with higher mortality risk (adjusted RR: 1.92, p < 0.001), but the associations were not significant for vitamin D insufficiency (25 (OH) D 20~30 ng/ml) or deficiency (25 (OH) D 10~20 ng/ml). Further analyses showed that the association between lower serum 25 (OH) D and higher mortality risk were consistent in studies applied different diagnostic criteria for sepsis (systemic inflammatory response syndrome, Sepsis-2.0, or Sepsis-3.0), short-term (within 1 month) and long-term studies (3~12 months), and in prospective and retrospective studies. Conclusions: Severe vitamin D deficiency may be independently associated with increased mortality in adult patients with sepsis. Large-scale prospective studies are needed to validate our findings.

Title: Challenges in developing a consensus definition of neonatal sepsis. Citation: Pediatric research; Mar 2020 Author(s): McGovern, Matthew; Giannoni, Eric; Kuester, Helmut; Turner, Mark A; van den Hoogen, Agnes; Bliss, Joseph M; Koenig, Joyce M; Keij, Fleur M; Mazela, Jan; Finnegan, Rebecca; Degtyareva, Marina; Simons, Sinno H P; de Boode, Willem P; Strunk, Tobias; Reiss, Irwin K M; Wynn, James L; Molloy, Eleanor J; Infection, Inflammation, Immunology and Immunisation (I4) section of the ESPR Abstract: Sepsis remains a leading cause of morbidity and mortality in the neonatal population, and at present, there is no unified definition of neonatal sepsis. Existing consensus sepsis definitions within paediatrics are not suited for use in the NICU and do not address sepsis in the premature population. Many neonatal research and surveillance networks have criteria for the definition of sepsis within their publications though these vary greatly and there is typically a heavy emphasis on microbiological culture. The concept of organ dysfunction as a diagnostic criterion for sepsis is rarely considered in neonatal literature, and it remains unclear how to most accurately screen neonates for organ dysfunction. Accurately defining and screening for sepsis is important for clinical management, health service design and future research. The progress made by the Sepsis-3 group provides a roadmap of how definitions and screening criteria may be developed. Similar initiatives in neonatology are likely to be more challenging and would need to account for the unique presentation of sepsis in term and premature neonates. The outputs of similar consensus work within neonatology should be twofold: a validated definition of neonatal sepsis and screening criteria to identify at-risk patients earlier in their clinical course. IMPACT: There is currently no consensus definition of neonatal sepsis and the definitions that are currently in use are varied. A consensus definition of neonatal sepsis would benefit clinicians, patients and researchers. Recent progress in adults with publication of Sepsis-3 provides guidance on how a consensus definition and screening criteria for sepsis could be produced in neonatology. We discuss common themes and potential shortcomings in sepsis definitions within neonatology. We highlight the need for a consensus definition of neonatal sepsis and the challenges that this task poses.

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Sources Used: The following databases are used in the creation of this bulletin: BNI, CINAHL, EMBASE & Medline. Disclaimer: The results of your literature search are based on the request that you made, and consist of a list of references, some with abstracts. Royal United Hospital Bath Healthcare Library will endeavour to use the best, most appropriate and most recent sources available to it, but accepts no liability for the information retrieved, which is subject to the content and accuracy of databases, and the limitations of the search process. The library assumes no liability for the interpretation or application of these results, which are not intended to provide advice or recommendations on patient care.