UNASSIGNED: Sepsis remains a complex and costly disease with high morbidity and mortality. This article discusses Sepsis-2 and Sepsis-3 definitions, highlighting the 2021 Surviving Sepsis International guidelines as well as the regulatory requirements and reimbursement for the Severe Sepsis and Septic Shock Management Bundle (SEP-1) measure.

Sepsis is a leading cause of death among children worldwide. Current pediatric-specific criteria for sepsis were published in 2005 based on expert opinion. In 2016, the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) defined sepsis as life-threatening organ dysfunction caused by a dysregulated host response to infection, but it excluded children.
To update and evaluate criteria for sepsis and septic shock in children.
The Society of Critical Care Medicine (SCCM) convened a task force of 35 pediatric experts in critical care, emergency medicine, infectious diseases, general pediatrics, nursing, public health, and neonatology from 6 continents. Using evidence from an international survey, systematic review and meta-analysis, and a new organ dysfunction score developed based on more than 3 million electronic health record encounters from 10 sites on 4 continents, a modified Delphi consensus process was employed to develop criteria.
Based on survey data, most pediatric clinicians used sepsis to refer to infection with life-threatening organ dysfunction, which differed from prior pediatric sepsis criteria that used systemic inflammatory response syndrome (SIRS) criteria, which have poor predictive properties, and included the redundant term, severe sepsis. The SCCM task force recommends that sepsis in children be identified by a Phoenix Sepsis Score of at least 2 points in children with suspected infection, which indicates potentially life-threatening dysfunction of the respiratory, cardiovascular, coagulation, and/or neurological systems. Children with a Phoenix Sepsis Score of at least 2 points had in-hospital mortality of 7.1% in higher-resource settings and 28.5% in lower-resource settings, more than 8 times that of children with suspected infection not meeting these criteria. Mortality was higher in children who had organ dysfunction in at least 1 of 4-respiratory, cardiovascular, coagulation, and/or neurological-organ systems that was not the primary site of infection. Septic shock was defined as children with sepsis who had cardiovascular dysfunction, indicated by at least 1 cardiovascular point in the Phoenix Sepsis Score, which included severe hypotension for age, blood lactate exceeding 5 mmol/L, or need for vasoactive medication. Children with septic shock had an in-hospital mortality rate of 10.8% and 33.5% in higher- and lower-resource settings, respectively.
The Phoenix sepsis criteria for sepsis and septic shock in children were derived and validated by the international SCCM Pediatric Sepsis Definition Task Force using a large international database and survey, systematic review and meta-analysis, and modified Delphi consensus approach. A Phoenix Sepsis Score of at least 2 identified potentially life-threatening organ dysfunction in children younger than 18 years with infection, and its use has the potential to improve clinical care, epidemiological assessment, and research in pediatric sepsis and septic shock around the world.

New evidence is available examining the use of corticosteroids in sepsis, acute respiratory distress syndrome (ARDS) and community-acquired pneumonia (CAP), warranting a focused update of the 2017 guideline on critical illness-related corticosteroid insufficiency.
To develop evidence-based recommendations for use of corticosteroids in hospitalized adults and children with sepsis, ARDS, and CAP.
The 22-member panel included diverse representation from medicine, including adult and pediatric intensivists, pulmonologists, endocrinologists, nurses, pharmacists, and clinician-methodologists with expertise in developing evidence-based Clinical Practice Guidelines. We followed Society of Critical Care Medicine conflict of interest policies in all phases of the guideline development, including task force selection and voting.
After development of five focused Population, Intervention, Control, and Outcomes (PICO) questions, we conducted systematic reviews to identify the best available evidence addressing each question. We evaluated the certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach and formulated recommendations using the evidence-to-decision framework.
In response to the five PICOs, the panel issued four recommendations addressing the use of corticosteroids in patients with sepsis, ARDS, and CAP. These included a conditional recommendation to administer corticosteroids for patients with septic shock and critically ill patients with ARDS and a strong recommendation for use in hospitalized patients with severe CAP. The panel also recommended against high dose/short duration administration of corticosteroids for septic shock. In response to the final PICO regarding type of corticosteroid molecule in ARDS, the panel was unable to provide specific recommendations addressing corticosteroid molecule, dose, and duration of therapy, based on currently available evidence.
The panel provided updated recommendations based on current evidence to inform clinicians, patients, and other stakeholders on the use of corticosteroids for sepsis, ARDS, and CAP.

BACKGROUND: Sepsis-related mortality is decreasing over time after the introduction of \"Surviving Sepsis Campaign\" Guidelines in 2004. The last Guidelines version collects 93 recommendations, but several interventions supported by randomized evidence of mortality reduction are not included.
METHODS: We performed a systematic review of all randomized controlled trials reporting a statistically significant mortality reduction in septic patients and compared the identified studies to the Surviving Sepsis Campaign Guidelines 2021 to highlight discrepancies.
RESULTS: We identified 83 randomized controlled trials (58 interventions) influencing mortality in sepsis. Only 9/58 of these interventions were included in the Guidelines: lactate measurement and lactate-guided hemodynamic management, procalcitonin-guided antibiotics discontinuation, balanced crystalloids as first choice fluids, albumin infusion, avoidance of starches, noradrenaline as first line vasopressor, vasopressin as an adjunctive vasopressor to noradrenaline, neuromuscular blocking agents in moderate-severe sepsis-associated acute respiratory distress syndrome, and corticosteroids use. Only 11/93 Guidelines recommendations were supported by randomized evidence with mortality difference. Five of the interventions with survival benefit in literature (vitamin C, terlipressin, polymyxin B, liberal transfusion strategy and immunoglobulins) were recommended to avoid in the Guidelines, while 44 interventions were not mentioned, including three interventions (esmolol, omega 3, and external warming) with at least two randomized controlled trials with a documented survival benefit.
CONCLUSIONS: Several discrepancies exist between the randomized controlled trials with mortality difference in septic patients and the latest Surviving Sepsis Campaign Guidelines. This systematic review can be of help for improving future guidelines and may guide research on specific promising topics.

The time to administration of broad-spectrum antibiotics and (secondarily) to the initiation of hemodynamic stabilization are the most important factors influencing survival of patients with sepsis and septic shock; however, the basic prerequisite for the initiation of an adequate treatment is that a suspected diagnosis of sepsis is made first. Therefore, the treatment of sepsis, even before it has begun, is an interdisciplinary and interprofessional task. This article provides an overview of the current state of the art in sepsis treatment and points towards new evidence that has the potential to change guideline recommendations in the coming years. In summary, the following points are critical: (1) sepsis must be diagnosed as soon as possible and the implementation of a source control intervention (in case of a controllable source) has to be implemented as soon as (logistically) possible. (2) In general, intravenous broad-spectrum antibiotics should be given within the first hour after diagnosis if sepsis or septic shock is suspected. In organ dysfunction without shock, where sepsis is a possible but unlikely cause, the results of focused advanced diagnostics should be awaited before a decision to give broad-spectrum antibiotics is made. If it is not clear within 3 h whether sepsis is the cause, broad-spectrum antibiotics should be given when in doubt. Administer beta-lactam antibiotics as a prolonged (or if therapeutic drug monitoring is available, continuous) infusion after an initial loading dose. (3) Combination treatment with two agents for one pathogen group should remain the exception (e.g. multidrug-resistant gram-negative pathogens). (4) In the case of doubt, the duration of anti-infective treatment should rather be shorter than longer. Procalcitonin can support the clinical decision to stop (not to start!) antibiotic treatment! (5) For fluid treatment, if hypoperfusion is present, the first (approximately) 2L (30 ml/kg BW) of crystalloid solution is usually safe and indicated. After that, the rule is: less is more! Any further fluid administration should be carefully weighed up with the help of dynamic parameters, the patient\'s clinical condition and echo(cardio)graphy.
Die Zeiten bis zur Gabe eines Breitbandantibiotikums und (nachgeordnet) bis zum Beginn der hämodynamischen Stabilisierung sind die wichtigsten Einflussfaktoren für das Überleben von Patienten mit Sepsis und septischem Schock. Grundvoraussetzung für den Beginn einer adäquaten Therapie ist jedoch zunächst, dass die Verdachtsdiagnose „Sepsis“ gestellt wird. Die Behandlung der Sepsis ist daher, noch bevor sie begonnen hat, eine interdisziplinäre und interprofessionelle Aufgabe. Der vorliegende Artikel gibt eine Übersicht über den aktuellen „State of the Art“ der Sepsistherapie und weist auf neue Evidenz hin, die das Potenzial hat, die Leitlinienempfehlungen in den nächsten Jahren zu verändern.

BACKGROUND: The generalizability of the Surviving Sepsis Campaign (SSC) guidelines to various patient populations and hospital settings has been debated. A quantitative assessment of the diversity and representation in the clinical evidence supporting the guidelines would help evaluate the generalizability of the recommendations and identify strategic research goals and priorities. In this study, we evaluated the diversity of patients in the original studies, in terms of sex, race/ethnicity, and geographical location. We also assessed diversity in sex and geographical representation among study first and last authors.
METHODS: All clinical studies cited in support of the 2021 SSC adult guideline recommendations were identified. Original clinical studies were included, while editorials, reviews, non-clinical studies, and meta-analyses were excluded. For eligible studies, we recorded the proportion of male patients, percentage of each represented racial/ethnic subgroup (when available), and countries in which they were conducted. We also recorded the sex and location of the first and last authors. The World Bank classification was used to categorize countries.
RESULTS: The SSC guidelines included six sections, with 85 recommendations based on 351 clinical studies. The proportion of male patients ranged from 47 to 62%. Most studies did not report the racial/ ethnic distribution of the included patients; when they did so, most were White patients (68-77%). Most studies were conducted in high-income countries (77-99%), which included Europe/Central Asia (33-66%) and North America (36-55%). Moreover, most first/last authors were males (55-93%) and from high-income countries (77-99%).
CONCLUSIONS: To enhance the generalizability of the SCC guidelines, stakeholders should define strategies to enhance the diversity and representation in clinical studies. Though there was reasonable representation in sex among patients included in clinical studies, the evidence did not reflect diversity in the race/ethnicity and geographical locations. There was also lack of diversity among the first and last authors contributing to the evidence.

The current international sepsis guidelines from 2021 are based on the work of a panel of 60 international experts from various fields. They include a total of 93 recommendations, some of which include new aspects compared to the 2016 version of the guidelines. This article provides a subjective compilation by two internal medicine intensivists who highlight some aspects, especially of changes within the guidelines compared to the previous version. The focus is on the fields of screening, sepsis bundles, fluid and vasopressor treatment and adjuvant treatment. In addition, for the first time these guidelines address the important issue of long-term sequelae for sepsis survivors and their environment.
UNASSIGNED: Die aktuelle internationale Sepsisleitlinie aus dem Jahr 2021 basiert auf der Arbeit eines Panels von 60 internationalen Experten aus verschiedenen Bereichen. Sie beinhaltet insgesamt 93 Empfehlungen, wobei einige Empfehlungen verglichen mit der Leitlinienversion von 2016 neue Aspekte beinhalten. Der vorliegende Beitrag bietet eine subjektive Zusammenstellung zweier internistischer Intensivmediziner, die einige Aspekte aufzeigen, insbesondere Veränderungen innerhalb der Leitlinie im Vergleich zur vorherigen Version. Der Fokus liegt auf den Bereichen Screening, Sepsis-Campaign-Bündel, Flüssigkeits- und Vasopressorentherapie und adjuvante Therapien. Zudem wird in dieser Leitlinie erstmalig das wichtige Thema der Langzeitfolgen für Sepsisüberlebende und deren Umfeld angesprochen.

In 2021, the Society of Critical Care Medicine (SCCM) and the European Society of Intensive Care Medicine (ESICM) jointly released the Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock 2020 with 93 recommendations. In the same year, the Japanese Society of Intensive Care Medicine (JSICM) and the Japanese Association for Acute Medicine (JAAM) also cooperated to publish the Japanese clinical practice guidelines for management of sepsis and septic shock 2020, covering 118 clinical issues in 22 areas. In this paper, 50 items in the contents of the two guidelines are compared in accordance with the order of international guidelines, including screening, initial resuscitation, mean arterial pressure, transfer to intensive care unit (ICU), diagnosis of infection, timing of antimicrobial administration, biomarkers for initiation of antimicrobial therapy, selection of antibiotic, antifungal therapy, antiviral therapy, infusion of antibiotic, pharmacokinetics and pharmacodynamics, source of infection control, antimicrobial de-escalation strategy, course of antimicrobial administration, biomarkers for discontinuation of antibiotic, fluid management, vasoactive agents, positive inotropic agents, monitoring and intravenous access, fluid balance, oxygenation targets, high-flow nasal cannula oxygen therapy, noninvasive ventilation, protective ventilation in acute respiratory distress syndrome (ARDS), low tidal volume in respiratory failure patients with non-ARDS, lung recruitment maneuvers, prone position ventilation, muscle relaxants, extracorporeal membrane oxygenation (ECMO), glucocorticoids, blood purification, red blood cell (RBC) transfusion, immunoglobulin, stress ulcer prevention, prevention of venous thromboembolism (VTE), renal replacement therapy, glycemic management, vitamin C, sodium bicarbonate therapy, nutrition, treatment goals, palliative care, peer support groups, transition of care, screening economic and social support, education for the knowledge about sepsis to the patients and their families, common decision-making, discharge planning, cognitive therapy and follow-up after discharge. It is convenient for everyone to understand some views in the field of sepsis and septic shock, and deepen their understanding.

The Surviving Sepsis Campaign (SSC) International Guidelines for the Management of Sepsis and Septic Shock provide recommendations on the care of hospitalized adult patients with (or at risk for) sepsis. This review discusses what is new or different in the 2021 SSC adult sepsis guidelines compared to 2016. The guidelines include new weak recommendations for use of balanced fluid over saline 0.9%, use of intravenous corticosteroids for septic shock when there is ongoing vasopressor requirement, and peripheral initiation of intravenous vasopressors over delaying initiation in order to obtain central venous access. As before, there is a strong recommendation to initiate antimicrobials within 1 h of sepsis and septic shock, but there are now additional recommendations when the diagnosis is uncertain. The recommendation for initial fluid resuscitation in septic shock of 30 mL/kg crystalloid has been downgraded from strong to weak. Finally, there are 12 new recommendations addressing long-term outcomes from sepsis, including strong recommendations to screen for economic and social support and to make referrals for follow-up where available; use shared decision-making in post-intensive care unit (ICU) and hospital discharge planning; reconcile medications at both ICU and hospital discharge; provide information about sepsis and its sequelae in written and verbal hospital discharge summary; and to provide assessment and follow-up for physical, cognitive, and emotional problems after hospital discharge.
UNASSIGNED: Die internationalen Leitlinien der Surviving Sepsis Campaign (SSC) für die Behandlung von Sepsis und septischem Schock enthalten Empfehlungen für die Versorgung von erwachsenen Patienten mit Sepsis (bzw. mit Sepsisrisiko) im Krankenhaus. In dieser Übersicht wird erläutert, was in den 2021 erarbeiteten SSC-Leitlinien für Sepsis bei Erwachsenen im Vergleich zu 2016 neu bzw. anders ist. Die Leitlinien enthalten neue schwache Empfehlungen für die Verwendung von balancierter Flüssigkeit anstelle von 0,9%iger Natriumchloridlösung, für den Einsatz intravenöser Kortikosteroide bei septischem Schock, wenn ein anhaltender Bedarf für Vasopressoren besteht, und dafür, intravenöse Vasopressoren schon peripher einzuleiten, statt erst verzögert, wenn ein zentralvenöser Zugang besteht. Nach wie vor wird dringend empfohlen, bei Sepsis und septischem Schock innerhalb von einer Stunde mit einer antimikrobiellen Therapie zu beginnen, doch gibt es nun zusätzliche Empfehlungen, wenn die Diagnose nicht sicher ist. Die Empfehlung für eine initiale Flüssigkeitszufuhr bei septischem Schock von 30 ml/kg Kristalloid wurde von stark auf schwach herabgestuft. Schließlich gibt es 12 neue Empfehlungen, die sich mit den Langzeitfolgen der Sepsis befassen, darunter die nachdrücklichen Empfehlungen, hinsichtlich finanzieller und sozialer Unterstützung zu screenen und, falls verfügbar, zur Nachsorge zu überweisen, bei der Planung der Verlegung von der Intensivstation (ICU) und der Entlassung aus der stationären Behandlung die gemeinsame Entscheidungsfindung zu nutzen, die Medikation sowohl auf der ICU als auch bei der Krankenhausentlassung abzustimmen, Informationen über die Sepsis und ihre Folgen in der schriftlichen und mündlichen Zusammenfassung der Entlassung aus dem Krankenhaus bereitzustellen und nach der Entlassung aus dem Krankenhaus ein Assessment der und eine Nachsorge für körperliche, kognitive und emotionale Probleme zu anzubieten.

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