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Current Opinion in Anaesthesiology Apr 2022Advances in the treatment of septic shock have historically focused on resuscitation endpoints, mainly mean arterial pressure and cardiac output. As the definitions of... (Review)
Review
PURPOSE OF REVIEW
Advances in the treatment of septic shock have historically focused on resuscitation endpoints, mainly mean arterial pressure and cardiac output. As the definitions of sepsis and septic shock have shifted to focus on the diversity of causes of dysregulated host-response we have seen an emerging phenotype where tissue hypoxia persists despite adequate macrocirculatory parameters. Interest in the topic of microcirculation is re-emerging as validated bedside techniques for hemodynamic monitoring, such as video microscopes, are becoming available. We review the current understanding of how sepsis induced hypoperfusion with a focus on recent advances in monitoring the microcirculation, and how a proliferation of biomarkers and emerging therapeutic targets may impact future research.
RECENT FINDINGS
Conventional hemodynamic monitoring systems fail to assess the microcirculation, and it's response to treatment. Lactate and venous oxygen saturations often drive biomarker-guided sepsis management. Visual assessments such as mottling and capillary refill time are often associated with predicting outcomes, but sometimes can have issues with inter-provider reliability. Microcirculatory damage can be observed sublingually and appears to have prognostic value.
SUMMARY
Sepsis is associated with changes in the microcirculation that can lead to tissue hypoxia and organ dysfunction. Further studies are needed to validate the usefulness of microcirculatory bedside tools in guiding resuscitative efforts.
Topics: Hemodynamics; Humans; Microcirculation; Reproducibility of Results; Resuscitation; Sepsis; Shock, Septic
PubMed: 35081058
DOI: 10.1097/ACO.0000000000001098 -
JPEN. Journal of Parenteral and Enteral... Nov 2021Septic shock is a public health burden and defined as a subset of sepsis whereby abnormalities in microcirculatory and cellular metabolism manifest as acute circulatory... (Review)
Review
Septic shock is a public health burden and defined as a subset of sepsis whereby abnormalities in microcirculatory and cellular metabolism manifest as acute circulatory failure. At the level of the gut, septic shock impairs epithelial barrier function (EBF), and the gut initiates proinflammatory responses contributing to multiple organ dysfunction syndrome. The timing and dose of enteral nutrition (EN) in septic shock remains a conundrum. On the one hand, early EN preserves EBF. On the other hand, serious gastrointestinal complications such as bowel necrosis may limit EN initiation in septic shock. We (1) describe the pathophysiologic conundrum septic shock poses for EN initiation, (2) outline guideline-based recommendations for EN in septic shock, (3) identify the role of parenteral nutrition in septic shock, and (4) identify and appraise postguideline literature on the timing, dose, and titration of EN in septic shock.
Topics: Enteral Nutrition; Humans; Microcirculation; Parenteral Nutrition; Parenteral Nutrition, Total; Shock, Septic
PubMed: 34897735
DOI: 10.1002/jpen.2246 -
Acta Bio-medica : Atenei Parmensis Jul 2022Septic shock is a main cause of morbidity and mortality in neonates. Septic shock evolves from compensated to uncompensated through 3 distinct phases. Prompt diagnosis... (Review)
Review
Septic shock is a main cause of morbidity and mortality in neonates. Septic shock evolves from compensated to uncompensated through 3 distinct phases. Prompt diagnosis is challenging, since neonatal septic shock may overlap with the physiological changes occurring at birth. The outcome of septic shock depends on a prompt recognition of symptoms and a strict adherence to cardiopulmonary resuscitation guidelines. Fluid administration plays a major role in the initial management of septic shock. If there is no response to volume filling, inotropes must be infused within one hour of onset (dopamine, dobutamine, adrenaline). Life-threatening infections require immediate and aggressive empiric use of antimicrobials. In the pediatric age, delay in antibiotic initiation for treating septic shock is associated with poor outcome and increased risk of mortality. There is a gap regarding first line interventions in neonatal septic shock. This review addresses initial interventions in the treatment of neonatal septic shock and discusses currently available evidences., These interventions may allow to improve the outcome if they are promptly carried out.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Child; Humans; Infant, Newborn; Resuscitation; Shock, Septic
PubMed: 35775767
DOI: 10.23750/abm.v93i3.12577 -
Molekuliarnaia Biologiia 2019An extensive network of regulation of systemic inflammation makes development of a reproducible experimental model of sepsis a complex task. There is no single mouse... (Review)
Review
An extensive network of regulation of systemic inflammation makes development of a reproducible experimental model of sepsis a complex task. There is no single mouse model that can capture all clinical aspects of this complicated pathology. However, a combination of existing approaches can go a long way towards analysis of specific mechanisms of sepsis development and to the design of novel therapeutic approaches. This review describes the popular mouse models of sepsis and septic shock, as well as their limitations and development strategies.
Topics: Animals; Disease Models, Animal; Inflammation; Mice; Sepsis; Shock, Septic
PubMed: 31661479
DOI: 10.1134/S0026898419050100 -
Gaceta Medica de Mexico 2020Sepsis is one of the main reasons for consultation at emergency departments.
INTRODUCTION
Sepsis is one of the main reasons for consultation at emergency departments.
OBJECTIVE
To identify the prevalence of sepsis in emergency departments of Mexico.
METHOD
Cross-sectional study with a 30-day follow-up of patients diagnosed with sepsis or septic shock; demographic variables, management and outcomes were analyzed.
RESULTS
In 68 emergency departments analyzed, 2379 patients were attended to, out of whom 307 had sepsis. The prevalence of sepsis was 12.9 %, and overall mortality was 16.93 %, which in the cases of sepsis was 9.39 %, and in those of septic shock, 65.85 %; no significant differences were identified in demographic variables or type of hospital. A significantly higher fluid balance was observed within the first three hours in those patients who died, as well as a lack of adherence to international resuscitation recommendations.
CONCLUSIONS
A high prevalence of sepsis was found in Mexican emergency departments. Mortality of patients with septic shock was similar and even higher than that internationally reported.
INTRODUCCIÓN
La sepsis es una de las principales causas de consulta en los servicios de urgencias médicas.
OBJETIVO
Identificar la prevalencia de la sepsis en servicios de urgencias médicas de México.
MÉTODO
Estudio transversal con seguimiento a 30 días de los pacientes con diagnóstico de sepsis o choque séptico; se analizaron las variables demográficas, el manejo y los desenlaces.
RESULTADOS
En 68 servicios de urgencias médicas analizados se atendió a 2379 pacientes, de los cuales 307 presentaron sepsis. La prevalencia de la sepsis fue de 12.9 %, con mortalidad global de 16.93 %, que en los casos de sepsis fue de 9.39 % y en los de choque séptico, de 65.85 %; no se identificaron diferencias significativas en las variables demográficas o tipo de hospital. Se observó balance hídrico alto en las primeras tres horas y falta de apego a las recomendaciones internacionales de reanimación superior en los pacientes que fallecieron.
CONCLUSIONES
Se encontró alta prevalencia de la sepsis en los servicios de urgencias médicas mexicanos. La mortalidad de los pacientes con choque séptico fue similar e, incluso, mayor a la reportada internacionalmente.
Topics: Cross-Sectional Studies; Emergency Service, Hospital; Female; Follow-Up Studies; Guideline Adherence; Humans; Male; Mexico; Middle Aged; Prevalence; Resuscitation; Sepsis; Severity of Illness Index; Shock, Septic
PubMed: 33877101
DOI: 10.24875/GMM.M21000492 -
International Journal of Molecular... Aug 2022The treatment of sepsis and septic shock remains a major public health issue due to the associated morbidity and mortality. Despite an improvement in the understanding... (Review)
Review
The treatment of sepsis and septic shock remains a major public health issue due to the associated morbidity and mortality. Despite an improvement in the understanding of the physiological and pathological mechanisms underlying its genesis and a growing number of studies exploring an even higher range of targeted therapies, no significant clinical progress has emerged in the past decade. In this context, mesenchymal stem cells (MSCs) appear more and more as an attractive approach for cell therapy both in experimental and clinical models. Pre-clinical data suggest a cornerstone role of these cells and their secretome in the control of the host immune response. Host-derived factors released from infected cells (i.e., alarmins, HMGB1, ATP, DNA) as well as pathogen-associated molecular patterns (e.g., LPS, peptidoglycans) can activate MSCs located in the parenchyma and around vessels to upregulate the expression of cytokines/chemokines and growth factors that influence, respectively, immune cell recruitment and stem cell mobilization. However, the way in which MSCs exert their beneficial effects in terms of survival and control of inflammation in septic states remains unclear. This review presents the interactions identified between MSCs and mediators of immunity and tissue repair in sepsis. We also propose paradigms related to the plausible roles of MSCs in the process of sepsis and septic shock. Finally, we offer a presentation of experimental and clinical studies and open the way to innovative avenues of research involving MSCs from a prognostic, diagnostic, and therapeutic point of view in sepsis.
Topics: Cell- and Tissue-Based Therapy; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Sepsis; Shock, Septic
PubMed: 36012544
DOI: 10.3390/ijms23169274 -
Critical Care Medicine Feb 2024To identify research priorities in the management, epidemiology, outcome, and pathophysiology of sepsis and septic shock.
OBJECTIVES
To identify research priorities in the management, epidemiology, outcome, and pathophysiology of sepsis and septic shock.
DESIGN
Shortly after publication of the most recent Surviving Sepsis Campaign Guidelines, the Surviving Sepsis Research Committee, a multiprofessional group of 16 international experts representing the European Society of Intensive Care Medicine and the Society of Critical Care Medicine, convened virtually and iteratively developed the article and recommendations, which represents an update from the 2018 Surviving Sepsis Campaign Research Priorities.
METHODS
Each task force member submitted five research questions on any sepsis-related subject. Committee members then independently ranked their top three priorities from the list generated. The highest rated clinical and basic science questions were developed into the current article.
RESULTS
A total of 81 questions were submitted. After merging similar questions, there were 34 clinical and ten basic science research questions submitted for voting. The five top clinical priorities were as follows: 1) what is the best strategy for screening and identification of patients with sepsis, and can predictive modeling assist in real-time recognition of sepsis? 2) what causes organ injury and dysfunction in sepsis, how should it be defined, and how can it be detected? 3) how should fluid resuscitation be individualized initially and beyond? 4) what is the best vasopressor approach for treating the different phases of septic shock? and 5) can a personalized/precision medicine approach identify optimal therapies to improve patient outcomes? The five top basic science priorities were as follows: 1) How can we improve animal models so that they more closely resemble sepsis in humans? 2) What outcome variables maximize correlations between human sepsis and animal models and are therefore most appropriate to use in both? 3) How does sepsis affect the brain, and how do sepsis-induced brain alterations contribute to organ dysfunction? How does sepsis affect interactions between neural, endocrine, and immune systems? 4) How does the microbiome affect sepsis pathobiology? 5) How do genetics and epigenetics influence the development of sepsis, the course of sepsis and the response to treatments for sepsis?
CONCLUSIONS
Knowledge advances in multiple clinical domains have been incorporated in progressive iterations of the Surviving Sepsis Campaign guidelines, allowing for evidence-based recommendations for short- and long-term management of sepsis. However, the strength of existing evidence is modest with significant knowledge gaps and mortality from sepsis remains high. The priorities identified represent a roadmap for research in sepsis and septic shock.
Topics: Humans; Shock, Septic; Sepsis; Resuscitation; Respiration, Artificial; Critical Care
PubMed: 38240508
DOI: 10.1097/CCM.0000000000006135 -
Medizinische Klinik, Intensivmedizin... Dec 2023The Surviving Sepsis Campaign (SSC) International Guidelines for the Management of Sepsis and Septic Shock provide recommendations on the care of hospitalized adult... (Review)
Review
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.
Topics: Adult; Humans; Shock, Septic; Sepsis; Intensive Care Units; Fluid Therapy; Vasoconstrictor Agents
PubMed: 37286842
DOI: 10.1007/s00063-023-01028-5 -
Frontiers in Immunology 2021To date, there are no studies regarding the lactylation profile and its role in critically ill patients. Thus, we aimed to examine expression of histone H3 lysine 18... (Clinical Trial)
Clinical Trial
OBJECTIVE
To date, there are no studies regarding the lactylation profile and its role in critically ill patients. Thus, we aimed to examine expression of histone H3 lysine 18 (H3K18) lactylation and its role in patients with septic shock.
METHODS
Thirteen healthy volunteers and 35 critically ill patients from the Department of Surgical Intensive Care Medicine, Beijing Hospital were enrolled in our study. Baseline information and clinical outcomes were obtained prospectively. Lactylation levels of all proteins and H3K18 from peripheral blood mononuclear (PBMC) were determined by western blotting and serum levels of inflammatory cytokines by flow cytometry. Arginase-1 () and Krüppel-like factor-4 () mRNA expression was evaluated by quantitative real-time PCR (qRT-PCR).
RESULTS
Lactylation was found to be an all-protein post-translational modification and was detected in PBMCs from both healthy volunteers and critically ill patients, with a significantly higher relative density in shock patients (=2.172, =0.045). H3K18la was expressed in all subjects, including healthy volunteers, with the highest level in septic shock patients (compared with non-septic shock patients, critically ill without shock patients and healthy volunteers =0.033, 0.000 and 0.000, respectively). Furthermore, H3K18la protein expression correlated positively with APACHE II scores, SOFA scores on day 1, ICU stay, mechanical ventilation time and serum lactate (=0.42, 0.63, 0.39, 0.51 and 0.48, respectively, =0.012, 0.000, 0.019, 0.003 and 0.003, respectively). When we matched patients with septic shock and with non-septic shock according to severity, we found higher H3K18la levels in the former group (=-2.208, =0.040). Moreover, H3K18la exhibited a close correlation with procalcitonin levels (=0.71, =0.010). Patients with high H3K18la expression showed higher IL-2, IL-5, IL-6, IL-8, IL-10, IL-17, IFN-α levels (=0.33, 0.37, 0.62, 0.55, 0.65, 0.49 and 0.374 respectively, =0.024, 0.011, 0.000, 0.000, 0.000 and 0.000 respectively). H3K18la expression also displayed a positive correlation with the level of mRNA (=0.561, =0.005).
CONCLUSIONS
Lactylation is an all-protein post-translational modification occurring in both healthy subjects and critically ill patients. H3K18la may reflect the severity of critical illness and the presence of infection. H3K18la might mediate inflammatory cytokine expression and overexpression and stimulate the anti-inflammatory function of macrophages in sepsis.
Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Female; Histones; Humans; Male; Middle Aged; Patient Acuity; Protein Processing, Post-Translational; Shock, Septic
PubMed: 35069560
DOI: 10.3389/fimmu.2021.786666 -
Seminars in Respiratory and Critical... Oct 2021Despite decades of research, the mortality rate of sepsis and septic shock remains unacceptably high. Delays in diagnosis, identification of an infectious source, and... (Review)
Review
Despite decades of research, the mortality rate of sepsis and septic shock remains unacceptably high. Delays in diagnosis, identification of an infectious source, and the challenge of providing patient-tailored resuscitation measures routinely result in suboptimal patient outcomes. Bedside ultrasound improves a clinician's ability to both diagnose and manage the patient with sepsis. Indeed, multiple point-of-care ultrasound (POCUS) protocols have been developed to evaluate and treat various subsets of critically ill patients. These protocols mostly target patients with undifferentiated shock and have been shown to improve clinical outcomes. Other studies have shown that POCUS can improve a clinician's ability to identify a source of infection. Once a diagnosis of septic shock has been made, serial POCUS exams can be used to continuously guide resuscitative efforts. In this review, we advocate that the patient with suspected sepsis or septic shock undergo a comprehensive POCUS exam in which sonographic information across organ systems is synthesized and used in conjunction with traditional data gleaned from the patient's history, physical exam, and laboratory studies. This harmonization of information will hasten an accurate diagnosis and assist with hemodynamic management.
Topics: Hemodynamics; Humans; Resuscitation; Sepsis; Shock, Septic; Ultrasonography
PubMed: 34544181
DOI: 10.1055/s-0041-1733896