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Acta Clinica Croatica Jun 2022Sepsis is a life-threatening organ dysfunction caused by an unregulated response of a host. Septic shock is its most severe form. It is manifested by a drop in blood... (Review)
Review
Sepsis is a life-threatening organ dysfunction caused by an unregulated response of a host. Septic shock is its most severe form. It is manifested by a drop in blood pressure, which decreases tissue perfusion pressure, causing hypoxia that is characteristic of shock. Sepsis is still one of the leading causes of mortality worldwide. Its incidence has increased since the first consensus definitions were established in 1991. Raising sepsis awareness, its significance and the need for better treatment, has led to an improvement in in defining sepsis and the development of guidelines for its treatment. The first guidelines were published in 2004, the second 2008, the third 2013, the fourth 2016, and the last revised guidelines appeared in 2021. This paper will describe the previous and new definitions of sepsis and septic shock, the previous guidelines for the recognition and treatment, and the latest recommendations for treatment. Timely diagnosis is crucial for the outcomes for patients with sepsis and septic shock. The fact is that the sepsis care bundles have been modified to increasingly shorter time determinants, which emphasizes the importance of emergency physicians, who frequently first recognize and begin emergency treatment of septic patients.
Topics: Humans; Shock, Septic; Sepsis; Critical Care; Blood Pressure; Time Factors
PubMed: 36304809
DOI: 10.20471/acc.2022.61.s1.11 -
Military Medical Research Oct 2022Sepsis is a common complication of combat injuries and trauma, and is defined as a life-threatening organ dysfunction caused by a dysregulated host response to... (Review)
Review
Sepsis is a common complication of combat injuries and trauma, and is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. It is also one of the significant causes of death and increased health care costs in modern intensive care units. The use of antibiotics, fluid resuscitation, and organ support therapy have limited prognostic impact in patients with sepsis. Although its pathophysiology remains elusive, immunosuppression is now recognized as one of the major causes of septic death. Sepsis-induced immunosuppression is resulted from disruption of immune homeostasis. It is characterized by the release of anti-inflammatory cytokines, abnormal death of immune effector cells, hyperproliferation of immune suppressor cells, and expression of immune checkpoints. By targeting immunosuppression, especially with immune checkpoint inhibitors, preclinical studies have demonstrated the reversal of immunocyte dysfunctions and established host resistance. Here, we comprehensively discuss recent findings on the mechanisms, regulation and biomarkers of sepsis-induced immunosuppression and highlight their implications for developing effective strategies to treat patients with septic shock.
Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents; Biomarkers; Cytokines; Humans; Immune Checkpoint Inhibitors; Immunosuppression Therapy; Sepsis
PubMed: 36209190
DOI: 10.1186/s40779-022-00422-y -
International Journal of Molecular... Oct 2019Sepsis is defined as "a life-threatening organ dysfunction caused by a host's dysfunctional response to infection". Although the treatment of sepsis has developed... (Review)
Review
Sepsis is defined as "a life-threatening organ dysfunction caused by a host's dysfunctional response to infection". Although the treatment of sepsis has developed rapidly in the past few years, sepsis incidence and mortality in clinical treatment is still climbing. Moreover, because of the diverse manifestations of sepsis, clinicians continue to face severe challenges in the diagnosis, treatment, and management of patients with sepsis. Here, we review the recent development in our understanding regarding the cellular pathogenesis and the target of clinical diagnosis of sepsis, with the goal of enhancing the current understanding of sepsis. The present state of research on targeted therapeutic drugs is also elaborated upon to provide information for the treatment of sepsis.
Topics: Autophagy; Biomarkers; Blood Coagulation Disorders; Endoplasmic Reticulum Stress; Humans; Incidence; Inflammation; Mitochondrial Diseases; Neuroendocrine Cells; Sepsis; Virulence
PubMed: 31671729
DOI: 10.3390/ijms20215376 -
Brazilian Journal of Medical and... 2019Sepsis remains a major cause of morbidity and mortality worldwide, with increased burden in low- and middle-resource settings. The role of the inflammatory response in... (Review)
Review
Sepsis remains a major cause of morbidity and mortality worldwide, with increased burden in low- and middle-resource settings. The role of the inflammatory response in the pathogenesis of the syndrome has supported the modern concept of sepsis. Nevertheless, a definition of sepsis and the criteria for its recognition is a continuous process, which reflects the growing knowledge of its mechanisms and the success and failure of diagnostic and therapeutic interventions. Here we review the evolving concepts of sepsis, from the "systemic inflammatory response syndrome triggered by infection" (Sepsis-1) to "a severe, potentially fatal, organic dysfunction caused by an inadequate or dysregulated host response to infection" (Sepsis-3). We focused in the pathophysiology behind the concept and the criteria for recognition and diagnosis of sepsis. A major challenge in evaluating the host response in sepsis is to characterize what is protective and what is harmful, and we discuss that, at least in part, the apparent dysregulated host response may be an effort to adapt to a hostile environment. The new criteria for recognition and diagnosis of sepsis were derived from robust databases, restricted, however, to developed countries. Since then, the criteria have been supported in different clinical settings and in different economic and epidemiological contexts, but still raise discussion regarding their use for the identification versus the prognostication of the septic patient. Clinicians should not be restricted to definition criteria when evaluating patients with infection and should wisely use the broad array of information obtained by rigorous clinical observation.
Topics: Humans; Lactic Acid; Medical Illustration; Organ Dysfunction Scores; Sepsis
PubMed: 30994733
DOI: 10.1590/1414-431X20198595 -
The New England Journal of Medicine Aug 2013
Review
Topics: Humans; Incidence; Resuscitation; Risk Factors; Sepsis; Shock, Septic
PubMed: 23984731
DOI: 10.1056/NEJMra1208623 -
American Family Physician Apr 2020Guidelines published in 2016 provide a revised definition of sepsis: life-threatening organ dysfunction caused by a dysregulated host response to infection. The...
Guidelines published in 2016 provide a revised definition of sepsis: life-threatening organ dysfunction caused by a dysregulated host response to infection. The guidelines define septic shock as sepsis with circulatory, cellular, and metabolic dysfunction that is associated with a higher risk of mortality. The measurement of serum lactate has been incorporated into the latest septic shock definition. The guidelines recommend the Sequential Organ Failure Assessment (original and quick versions) as an important tool for early diagnosis. Respiratory, gastrointestinal, genitourinary, and skin and soft tissue infections are the most common sources of sepsis. Pneumonia is the most common cause of sepsis. Although many patients with sepsis have fever, the clinical manifestation can be subtle, particularly in older patients and those who are immunocompromised. Initial evaluation of patients with suspected sepsis includes basic laboratory tests, cultures, imaging studies as indicated, and sepsis biomarkers such as procalcitonin and lactate levels. Fluid resuscitation is the priority in early management, including administering an intravenous crystalloid at 30 mL per kg within the first three hours. Antimicrobial therapy should also be initiated early. Most research indicates that antimicrobial therapy should be started within three hours of presentation. The latest guidelines recommend starting antimicrobials within one hour, but this is controversial. Vasopressor therapy is indicated if hypotension persists despite fluid administration. Future trials of sepsis management are focusing on improving long-term rates of readmission and death, physical disability, cognitive impairment, and quality of life.
Topics: Anti-Bacterial Agents; Biomarkers; Early Diagnosis; Fluid Therapy; Humans; Oxygen Inhalation Therapy; Quality of Life; Respiration, Artificial; Sepsis; Shock, Septic; Time Factors
PubMed: 32227831
DOI: No ID Found -
Polish Archives of Internal Medicine Aug 2022The 2021 Surviving Sepsis Campaign Guidelines provided evidence-based recommendations for adult patients with sepsis and septic shock. This iteration of the guidelines... (Review)
Review
The 2021 Surviving Sepsis Campaign Guidelines provided evidence-based recommendations for adult patients with sepsis and septic shock. This iteration of the guidelines placed increased emphasis on a diverse, global perspective, as well as on the long-term sequelae of sepsis experienced by patients and their families. The guidelines encompassed the following sections: 1) screening and early treatment; 2) infection; 3) hemodynamic management; 4) ventilation; 5) additional therapies; and 6) goals of care and long-term outcomes. In this review, we provide a summary of key recommendations of interest to the practicing clinician, which are either novel or require a change in practice, as well as those for which the evidence has substantially evolved in the 5 years since the 2016 iteration of the Guidelines. Rather than reviewing the underlying evidence, we emphasize the practical aspects of interpretation, dissemination, and implementation of these recommendations in the clinical setting.
Topics: Adult; Humans; Sepsis; Shock, Septic
PubMed: 35791800
DOI: 10.20452/pamw.16290 -
Critical Care Medicine Feb 2013To provide an update to the "Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock," last published in 2008.
OBJECTIVE
To provide an update to the "Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock," last published in 2008.
DESIGN
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.
METHODS
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.
RESULTS
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-escalation, when appropriate (1B); infection source control with attention to the balance of risks and benefits of the chosen method within 12 hrs of diagnosis (1C); initial fluid resuscitation with crystalloid (1B) and consideration of the addition of albumin in patients who continue to require substantial amounts of crystalloid to maintain adequate mean arterial pressure (2C) and the avoidance of hetastarch formulations (1C); initial fluid challenge in patients with sepsis-induced tissue hypoperfusion and suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (more rapid administration and greater amounts of fluid may be needed in some patients) (1C); fluid challenge technique continued as long as hemodynamic improvement, as based on either dynamic or static variables (UG); norepinephrine as the first-choice vasopressor to maintain mean arterial pressure ≥ 65 mm Hg (1B); epinephrine when an additional agent is needed to maintain adequate blood pressure (2B); vasopressin (0.03 U/min) can be added to norepinephrine to either raise mean arterial pressure to target or to decrease norepinephrine dose but should not be used as the initial vasopressor (UG); dopamine is not recommended except in highly selected circumstances (2C); dobutamine infusion administered or added to vasopressor in the presence of a) myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or b) ongoing signs of hypoperfusion despite achieving adequate intravascular volume and adequate mean arterial pressure (1C); avoiding use of intravenous hydrocortisone in adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability (2C); hemoglobin target of 7-9 g/dL in the absence of tissue hypoperfusion, ischemic coronary artery disease, or acute hemorrhage (1B); low tidal volume (1A) and limitation of inspiratory plateau pressure (1B) for acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure (PEEP) in ARDS (1B); higher rather than lower level of PEEP for patients with sepsis-induced moderate or severe ARDS (2C); recruitment maneuvers in sepsis patients with severe refractory hypoxemia due to ARDS (2C); prone positioning in sepsis-induced ARDS patients with a PaO2/FIO2 ratio of ≤ 100 mm Hg in facilities that have experience with such practices (2C); head-of-bed elevation in mechanically ventilated patients unless contraindicated (1B); a conservative fluid strategy for patients with established ARDS who do not have evidence of tissue hypoperfusion (1C); protocols for weaning and sedation (1A); minimizing use of either intermittent bolus sedation or continuous infusion sedation targeting specific titration endpoints (1B); avoidance of neuromuscular blockers if possible in the septic patient without ARDS (1C); a short course of neuromuscular blocker (no longer than 48 hrs) for patients with early ARDS and a Pao2/Fio2 < 150 mm Hg (2C); a protocolized approach to blood glucose management commencing insulin dosing when two consecutive blood glucose levels are > 180 mg/dL, targeting an upper blood glucose ≤ 180 mg/dL (1A); equivalency of continuous veno-venous hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1B); use of stress ulcer prophylaxis to prevent upper gastrointestinal bleeding in patients with bleeding risk factors (1B); oral or enteral (if necessary) feedings, as tolerated, rather than either complete fasting or provision of only intravenous glucose within the first 48 hrs after a diagnosis of severe sepsis/septic shock (2C); and addressing goals of care, including treatment plans and end-of-life planning (as appropriate) (1B), as early as feasible, but within 72 hrs of intensive care unit admission (2C). Recommendations specific to pediatric severe sepsis include: therapy with face mask oxygen, high flow nasal cannula oxygen, or nasopharyngeal continuous PEEP in the presence of respiratory distress and hypoxemia (2C), use of physical examination therapeutic endpoints such as capillary refill (2C); for septic shock associated with hypovolemia, the use of crystalloids or albumin to deliver a bolus of 20 mL/kg of crystalloids (or albumin equivalent) over 5 to 10 mins (2C); more common use of inotropes and vasodilators for low cardiac output septic shock associated with elevated systemic vascular resistance (2C); and use of hydrocortisone only in children with suspected or proven "absolute"' adrenal insufficiency (2C).
CONCLUSIONS
Strong agreement existed among a large cohort of international experts regarding many level 1 recommendations for the best care of patients with severe 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 this important group of critically ill patients.
Topics: Critical Care; Early Diagnosis; Humans; Intensive Care Units; Sepsis
PubMed: 23353941
DOI: 10.1097/CCM.0b013e31827e83af -
Romanian Journal of Internal Medicine =... Sep 2020Sepsis is an overwhelming reaction to infection that comes with high morbidity and mortality, which requires urgent interventions in order to improve outcomes. Surviving... (Review)
Review
Sepsis is an overwhelming reaction to infection that comes with high morbidity and mortality, which requires urgent interventions in order to improve outcomes. Surviving Sepsis is an international campaign that aims to improve sepsis outcomes. The 2016 guideline modifies the previous definition of sepsis and proposes some specific diagnostic and therapeutic measures, such as the protocolized use of fluid resuscitation and antibiotics. We aim to summarize the main recommendations of the 2016 guideline that are relevant to the internist and evidence-base update them to the year 2020. In the current context, this review doesn't address patients affected by SARS-COV2 induced disease.
Topics: Anti-Bacterial Agents; Biomarkers; Fluid Therapy; Humans; Practice Guidelines as Topic; Sepsis; Vasoconstrictor Agents
PubMed: 32396142
DOI: 10.2478/rjim-2020-0012 -
EBioMedicine Dec 2022Management of the patient with sepsis comprises three key branches: control of the underlying infection, haemodynamic stabilization, and modulation of the host response.... (Review)
Review
Management of the patient with sepsis comprises three key branches: control of the underlying infection, haemodynamic stabilization, and modulation of the host response. Each aspect should be considered in all patients and, when relevant, managed at the same time. Infection control is applicable to all patients with sepsis and will include antibiotic therapy and often surgical intervention to remove an infectious source. Haemodynamic support involves fluid administration in all patients and vasoactive agents in patients with associated circulatory shock. Noradrenaline is the first choice vasopressor agent; inotropic agents, usually dobutamine, may be added in case of myocardial depression. No interventions directed at individual components of the host response to sepsis have yet been shown to improve outcomes, but glucocorticoids and vasopressin have a global impact on the response and can thus be considered in this category. A move toward more personalized treatment is needed across all three arms of sepsis management.
Topics: Humans; Shock, Septic; Sepsis; Vasoconstrictor Agents; Hemodynamics; Anti-Bacterial Agents
PubMed: 36470828
DOI: 10.1016/j.ebiom.2022.104318