Sepsis
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Guidelines 2 Sepsis guidelines (2021)
Disse rekommandationer retter sig mod voksne indlagt med mistænkt sepsis og septisk shock. På vegne af Dansk Selskab for Infektionsmedicin: Lars Skov Dalgaard, Michael Dalager, Christian Philip Fischer, Rikke Krogh-Madsen, Gitte Kronborg, Jannik Helweg Larsen, Stig Lønberg Nielsen, Christian Søborg, Lars Toft. Nye artikler 1 Sepsis assessment and management in critically Ill adults: A systematic review Mohammad Rababa, Dania Bani Hamad, Audai A. Hayajneh PLoS One Infectious Diseases, 1.07.2022 Tilføjet 2.07.2022 by Mohammad Rababa, Dania Bani Hamad, Audai A. Hayajneh Background Early assessment and management of patients with sepsis can significantly reduce its high mortality rates and improve patient outcomes and quality of life. Objectives The purposes of this review are to: (1) explore nurses’ knowledge, attitude, practice, and perceived barriers and facilitators related to early recognition and management of sepsis, (2) explore different interventions directed at nurses to improve sepsis management. Methods A systematic review method according to the PRISMA guidelines was used. An electronic search was conducted in March 2021 on several databases using combinations of keywords. Two researchers independently selected and screened the articles according to the eligibility criteria. Results Nurses reported an adequate of knowledge in certain areas of sepsis assessment and management in critically ill adult patients. Also, nurses’ attitudes toward sepsis assessment and management were positive in general, but they reported some misconceptions regarding antibiotic use for patients with sepsis, and that sepsis was inevitable for critically ill adult patients. Furthermore, nurses reported they either were not well-prepared or confident enough to effectively recognize and promptly manage sepsis. Also, there are different kinds of nurses’ perceived barriers and facilitators related to sepsis assessment and management: nurse, patient, physician, and system-related. There are different interventions directed at nurses to help in improving nurses’ knowledge, attitudes, and practice of sepsis assessment and management. These interventions include education sessions, simulation, decision support or screening tools for sepsis, and evidence-based treatment protocols/guidelines. Discussion Our findings could help hospital managers in developing continuous education and staff development training programs on assessing and managing sepsis in critical care patients. Conclusion Nurses have poor to good knowledge, practices, and attitudes toward sepsis as well as report many barriers related to sepsis management in adult critically ill patients. Despite all education interventions, no study has collectively targeted critical care nurses’ knowledge, attitudes, and practice of sepsis management. Læs mere Tjek på PubMed2 Physiology Is Vital to Precision Medicine in Acute Respiratory Distress Syndrome and Sepsis Ewan C. Goligher, Irene Telias, Sarina K. Sahetya, Elias Baedorf-Kassis, Bhakti K. Patel, Nadir Yehya, Jonathan A Silversides, Niall D. Ferguson, Laurent J. Brochard, Patrick R. Lawler, Ryan Zarychanski, Arthur S. Slutsky American Journal of Respiratory and Critical Care Medicine , 1.07.2022 Tilføjet 2.07.2022 American Journal of Respiratory and Critical Care Medicine, Volume 206, Issue 1, Page 14-16, July 1, 2022. Læs mere Tjek på PubMed3 Reply to Goligher et al.: Physiology Is Vital to Precision Medicine in Acute Respiratory Distress Syndrome and Sepsis Faraaz Ali Shah, Nuala Meyer, Derek C. Angus, Sachin Yende American Journal of Respiratory and Critical Care Medicine , 1.07.2022 Tilføjet 2.07.2022 American Journal of Respiratory and Critical Care Medicine, Volume 206, Issue 1, Page 121-122, July 1, 2022. Læs mere Tjek på PubMed4 Short- and long-term mortality in patients with urosepsis caused by Escherichia coli susceptible and resistant to 3rd generation cephalosporins BMC Infectious Diseases, 24.06.2022 Tilføjet 25.06.2022 Abstract
Background The aim of this study was to compare short- and long-term mortality among patients with urosepsis caused by Escherichia coli susceptibile (EC-SC) and resistant (EC-RC) to 3rd generation cephalosporins.
Methods A retrospective cohort study that included all patients with E. coli urosepsis admitted to a 700-bed hospital from January 2014 until December 2019. Mortality up to 30 days, 6 months and 1 year was assessed using logistic multivariate regression analysis and Cox regression analysis.
Results A total of 313 adult were included, 195 with EC-SC and 118 patients with EC-RC. 205 were females (74%), mean age was 79 (SD 12) years. Mean Charlson score was 4.93 (SD 2.18) in the EC-SC group and 5.74 (SD 1.92) in the EC-RC group. Appropriate empiric antibiotic therapy was initiated in 245 (78.3%) patients, 100% in the EC-SC group but only 42.5% in the EC-RC group. 30-day mortality occurred in 12 (6.3%) of EC-SC group and 15 (12.7%) in the EC-RC group. Factors independently associated with 30-day mortality were Charlson score, Pitt bacteremia score, fever upon admission and infection with a EC-RC. Appropriate antibiotic therapy was not independently associated with 30-day mortality. Differences in mortality between groups remained significant one year after the infection and were significantly associated with the Charlson co-morbidity score.
Conclusions Mortality in patients with urosepsis due to E. coli is highly affected by age and comorbidities. Although mortality was higher in the EC-RC group, we could not demonstrate an association with inappropriate empirical antibiotic treatment. Mortality remained higher at 6 months and 1 year long after the infection resolved but was associated mainly with co-morbidity.
Læs mere Tjek på PubMed 5 Short- and long-term mortality in patients with urosepsis caused by Escherichia coli susceptible and resistant to 3rd generation cephalosporins BMC Infectious Diseases, 24.06.2022 Tilføjet 28.06.2022 Abstract
Background The aim of this study was to compare short- and long-term mortality among patients with urosepsis caused by Escherichia coli susceptibile (EC-SC) and resistant (EC-RC) to 3rd generation cephalosporins.
Methods A retrospective cohort study that included all patients with E. coli urosepsis admitted to a 700-bed hospital from January 2014 until December 2019. Mortality up to 30 days, 6 months and 1 year was assessed using logistic multivariate regression analysis and Cox regression analysis.
Results A total of 313 adult were included, 195 with EC-SC and 118 patients with EC-RC. 205 were females (74%), mean age was 79 (SD 12) years. Mean Charlson score was 4.93 (SD 2.18) in the EC-SC group and 5.74 (SD 1.92) in the EC-RC group. Appropriate empiric antibiotic therapy was initiated in 245 (78.3%) patients, 100% in the EC-SC group but only 42.5% in the EC-RC group. 30-day mortality occurred in 12 (6.3%) of EC-SC group and 15 (12.7%) in the EC-RC group. Factors independently associated with 30-day mortality were Charlson score, Pitt bacteremia score, fever upon admission and infection with a EC-RC. Appropriate antibiotic therapy was not independently associated with 30-day mortality. Differences in mortality between groups remained significant one year after the infection and were significantly associated with the Charlson co-morbidity score.
Conclusions Mortality in patients with urosepsis due to E. coli is highly affected by age and comorbidities. Although mortality was higher in the EC-RC group, we could not demonstrate an association with inappropriate empirical antibiotic treatment. Mortality remained higher at 6 months and 1 year long after the infection resolved but was associated mainly with co-morbidity.
Læs mere Tjek på PubMed 6 Frequency and mortality of sepsis and septic shock in China: a systematic review and meta-analysis BMC Infectious Diseases, 21.06.2022 Tilføjet 22.06.2022 Abstract
Background Sepsis, a life-threatening organ dysfunction induced by infection, is a major public health problem. This study aimed to evaluate the frequency and mortality of sepsis, severe sepsis, and septic shock in China.
Methods We Searched MEDLINE, Embase, PubMed, and Cochrane Library from 1 January 1992 to 1 June 2020 for studies that reported on the frequency and mortality of sepsis, severe sepsis, and septic shock conducted in China. Random effects models were performed to estimate the pooled frequency and mortality of sepsis, severe sepsis, and septic shock.
Results Our search yielded 846 results, of which 29 studies were included in this review. The pooled frequency of sepsis was estimated at 33.6% (95% CI 25.9% to 41.3%, I2 = 99.2%; p < 0.001), and the pooled mortality of sepsis, severe sepsis and septic shock were 29.0% (95% CI 25.3%–32.8%, I2 = 92.1%; p = 0), 31.1% (95% CI 25.3% to 36.9%, I2 = 85.8%; p < 0.001) and 37.3% (95% CI 28.6%–46.0%, I2 = 93.5%; p < 0.001). There was significant heterogeneity between studies. With a small number of included studies and the changing definition of sepsis, trends in sepsis frequency and mortality were not sufficient for analysis. Epidemiological data on sepsis in the emergency department (ED) are severely lacking, and more research is urgently needed in this area is urgently needed.
Conclusions Our findings indicated that the frequency and mortality of sepsis and septic shock in China were much higher than North America and Europe countries. Based on our results, an extremely high incidence and mortality of sepsis and septic shock in China's mainland requires more healthcare budget support. Epidemiological data on sepsis and septic shock in ED are severely lacking, and more research is urgently needed in this area. Trial registration This systematic review was conducted according to the statement of the preferred reporting items for systematic review (PROSPERO CRD42021243325) and the meta-analysis protocols (PRISMA-P). Læs mere Tjek på PubMed 7 Frequency and mortality of sepsis and septic shock in China: a systematic review and meta-analysis BMC Infectious Diseases, 21.06.2022 Tilføjet 28.06.2022 Abstract
Background Sepsis, a life-threatening organ dysfunction induced by infection, is a major public health problem. This study aimed to evaluate the frequency and mortality of sepsis, severe sepsis, and septic shock in China.
Methods We Searched MEDLINE, Embase, PubMed, and Cochrane Library from 1 January 1992 to 1 June 2020 for studies that reported on the frequency and mortality of sepsis, severe sepsis, and septic shock conducted in China. Random effects models were performed to estimate the pooled frequency and mortality of sepsis, severe sepsis, and septic shock.
Results Our search yielded 846 results, of which 29 studies were included in this review. The pooled frequency of sepsis was estimated at 33.6% (95% CI 25.9% to 41.3%, I2 = 99.2%; p < 0.001), and the pooled mortality of sepsis, severe sepsis and septic shock were 29.0% (95% CI 25.3%–32.8%, I2 = 92.1%; p = 0), 31.1% (95% CI 25.3% to 36.9%, I2 = 85.8%; p < 0.001) and 37.3% (95% CI 28.6%–46.0%, I2 = 93.5%; p < 0.001). There was significant heterogeneity between studies. With a small number of included studies and the changing definition of sepsis, trends in sepsis frequency and mortality were not sufficient for analysis. Epidemiological data on sepsis in the emergency department (ED) are severely lacking, and more research is urgently needed in this area is urgently needed.
Conclusions Our findings indicated that the frequency and mortality of sepsis and septic shock in China were much higher than North America and Europe countries. Based on our results, an extremely high incidence and mortality of sepsis and septic shock in China's mainland requires more healthcare budget support. Epidemiological data on sepsis and septic shock in ED are severely lacking, and more research is urgently needed in this area. Trial registration This systematic review was conducted according to the statement of the preferred reporting items for systematic review (PROSPERO CRD42021243325) and the meta-analysis protocols (PRISMA-P). Læs mere Tjek på PubMed 8 Can the history of empiric antibiotic treatment for neonatal sepsis inform future global trials? Shamim Qazi, Paul Heath, Manica Balasegaram, Julia Bielicki, Mike Sharland, Emma Sharland Clinical Microbiology and Infection, 16.06.2022 Tilføjet 17.06.2022 Antimicrobial resistance is a major threat to the Sustainable Development Goal to reduce neonatal mortality to 12 per 1000 live births (1). Current global rates are at 17 per 1000 live births with variation between Læs mere Tjek på PubMed9 Intravenous Vitamin C in Adults with Sepsis in the Intensive Care Unit François Lamontagne, Marie-Hélène Masse, Julie Menard, Sheila Sprague, Ruxandra Pinto, Daren K. Heyland, Deborah J Cook, Marie-Claude Battista, Andrew G. Day, Gordon H. Guyatt, Salmaan Kanji, Rachael Parke, Shay P. McGuinness, Bharath-Kumar Tirupakuzhi Vijayaraghavan, Djillali Annane, Dian Cohen, Yaseen M. Arabi, Brigitte Bolduc, Nicole Marinoff, Bram Rochwerg, Tina Millen, Maureen O. Meade, Lori Hand, Irene Watpool, Rebecca Porteous, Paul J. Young, Frederick D’Aragon, Emilie P. Belley-Cote, Elaine Carbonneau, France Clarke, David M. Maslove, Miranda Hunt, Michaël Chassé, Martine Lebrasseur, François Lauzier, Sangeeta Mehta, Hector Quiroz-Martinez, Oleksa G. Rewa, Emmanuel Charbonney, Andrew J.E. Seely, Demetrios J. Kutsogiannis, Remi LeBlanc, Armand Mekontso-Dessap, Tina S. Mele, Alexis F. Turgeon, Gordon Wood, Sandeep S. Kohli, Jason Shahin, Pawel Twardowski, Neill K.J. Adhikari New England Journal of Medicine, 15.06.2022 Tilføjet 16.06.2022 10 PROcalcitonin and NEWS2 evaluation for Timely identification of sepsis and Optimal use of antibiotics in the emergency department (PRONTO): protocol for a multicentre, open-label, randomised controlled trial Euden, J., Thomas-Jones, E., Aston, S., Brookes-Howell, L., Carman, J., Carrol, E., Gilbert, S., Howard, P., Hood, K., Inada-Kim, M., Llewelyn, M., McGill, F., Milosevic, S., Niessen, L. W., Nsutebu, E., Pallmann, P., Schmidt, P., Taylor-Robinson, D., Welters, I., Todd, S., French, N., on behalf of the PRONTO team., Clarkstone, Hughes, Meister, Tabner, Barlow, Body, Bradburn, Daniels, Richards, Brain, Walker, Goodacre, Scarborough, O'Shea, James BMJ Open, 13.06.2022 Tilføjet 13.06.2022 Introduction Sepsis is a common, potentially life-threatening complication of infection. The optimal treatment for sepsis includes prompt antibiotics and intravenous fluids, facilitated by its early and accurate recognition. Currently, clinicians identify and assess severity of suspected sepsis using validated clinical scoring systems. In England, the National Early Warning Score 2 (NEWS2) has been mandated across all National Health Service (NHS) trusts and ambulance organisations. Like many clinical scoring systems, NEWS2 should not be used without clinical judgement to determine either the level of acuity or a diagnosis. Despite this, there is a tendency to overemphasise the score in isolation in patients with suspected infection, leading to the overprescription of antibiotics and potentially treatment-related complications and rising antimicrobial resistance. The biomarker procalcitonin (PCT) has been shown to be useful in specific circumstances to support appropriate antibiotics prescribing by identifying bacterial infection. PCT is not routinely used in the care of undifferentiated patients presenting to emergency departments (EDs), and the evidence base of its optimal usage is poor. The PROcalcitonin and NEWS2 evaluation for Timely identification of sepsis and Optimal (PRONTO) study is a randomised controlled trial (RCT) in adults with suspected sepsis presenting to the ED to compare standard clinical management based on NEWS2 scoring plus PCT-guided risk assessment with standard clinical management based on NEWS2 scoring alone and compare if this approach reduces prescriptions of antibiotics without increasing mortality. Methods and analysis PRONTO is a parallel two-arm open-label individually RCT set in up to 20 NHS EDs in the UK with a target sample size of 7676 participants. Participants will be randomised in a ratio of 1:1 to standard clinical management based on NEWS2 scoring or standard clinical management based on NEWS2 scoring plus PCT-guided risk assessment. We will compare whether the addition of PCT measurement to NEWS2 scoring can lead to a reduction in intravenous antibiotic initiation in ED patients managed as suspected sepsis, with at least no increase in 28-day mortality compared with NEWS2 scoring alone (in conjunction with local standard care pathways). PRONTO has two coprimary endpoints: initiation of intravenous antibiotics at 3 hours (superiority comparison) and 28-day mortality (non-inferiority comparison). The study has an internal pilot phase and group-sequential stopping rules for effectiveness and futility/safety, as well as a qualitative substudy and a health economic evaluation. Ethics and dissemination The trial protocol was approved by the Health Research Authority (HRA) and NHS Research Ethics Committee (Wales REC 2, reference 20/WA/0058). In England and Wales, the law allows the use of deferred consent in approved research situations (including ED studies) where the time dependent nature of intervention would not allow true informed consent to be obtained. PRONTO has approval for a deferred consent process to be used. Findings will be disseminated through peer-reviewed journals and presented at scientific conferences. Trial registration number ISRCTN54006056. Læs mere Tjek på PubMed 11 Sepsis-associated neuroinflammation in the spinal cord Akiko Hirotsu, Mariko Miyao, Kenichiro Tatsumi, Tomoharu Tanaka PLoS One Infectious Diseases, 13.06.2022 Tilføjet 13.06.2022 by Akiko Hirotsu, Mariko Miyao, Kenichiro Tatsumi, Tomoharu Tanaka Septic patients commonly present with central nervous system (CNS) disorders including impaired consciousness and delirium. Today, the main mechanism regulating sepsis-induced cerebral disorders is believed to be neuroinflammation. However, it is unknown how another component of the CNS, the spinal cord, is influenced during sepsis. In the present study, we intraperitoneally injected mice with lipopolysaccharide (LPS) to investigate molecular and immunohistochemical changes in the spinal cord of a sepsis model. After LPS administration in the spinal cord, pro-inflammatory cytokines including interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha mRNA were rapidly and drastically induced. Twenty-four-hour after the LPS injection, severe neuronal ischemic damage spread into gray matter, especially around the anterior horns, and the anterior column had global edematous changes. Immunostaining analyses showed that spinal microglia were significantly activated and increased, but astrocytes did not show significant change. The current results indicate that sepsis induces acute neuroinflammation, including microglial activation and pro-inflammatory cytokine upregulation in the spinal cord, causing drastic neuronal ischemia and white matter edema in the spinal cord. Læs mere Tjek på PubMed12 Early empiric anti-Mycobacterium tuberculosis therapy for sepsis in sub-Saharan Africa: a protocol of a randomised clinical trial Said, B., Nuwagira, E., Liyoyo, A., Arinaitwe, R., Gitige, C., Mushagara, R., Buzaare, P., Chongolo, A., Jjunju, S., Twesigye, P., Boulware, D. R., Conaway, M., Null, M., Thomas, T. A., Heysell, S. K., Moore, C. C., Muzoora, C., Mpagama, S. G. BMJ Open, 6.06.2022 Tilføjet 6.06.2022 Introduction Sub-Saharan Africa shoulders the highest burden of global sepsis and associated mortality. In high HIV and tuberculosis (TB) prevalent settings such as sub-Saharan Africa, TB is the leading cause of sepsis. However, anti-TB therapy is often delayed and may not achieve adequate blood concentrations in patients with sepsis. Accordingly, this multisite randomised clinical trial aims to determine whether immediate and/or increased dose anti-TB therapy improves 28-day mortality for participants with HIV and sepsis in Tanzania or Uganda. Methods and analysis This is a phase 3, multisite, open-label, randomised controlled clinical 2x2 factorial superiority trial of (1) immediate initiation of anti-TB therapy and (2) sepsis-specific dose anti-TB therapy in addition to standard of care antibacterials for adults with HIV and sepsis admitted to hospital in Tanzania or Uganda. The primary endpoint is 28-day mortality. A sample size of 436 participants will provide 80% power for testing each of the main effects of timing and dose on 28-day mortality with a two-sided significance level of 5%. The expected main effect for absolute risk reduction is 13% and the expected OR for risk reduction is 1.58. Ethics and dissemination This clinical trial will determine the optimal content, dosing and timing of antimicrobial therapy for sepsis in high HIV and TB prevalent settings. The study is funded by the National Institutes of Health in the US. Institutional review board approval was conferred by the University of Virginia, the Tanzania National Institute for Medical Research, and the Uganda National Council for Science and Technology. Study results will be published in peer-reviewed journals and in the popular press of Tanzania and Uganda. We will also present our findings to the Community Advisory Boards that we convened during study preparation. Trial registration number ClinicalTrials.gov (NCT04618198). Læs mere Tjek på PubMed 13 Trends in bacterial sepsis incidence and mortality in France between 2015 and 2019 based on National Health Data System (Systeme National des donnees de Sante (SNDS)): a retrospective observational study Pandolfi, F., Guillemot, D., Watier, L., Brun-Buisson, C. BMJ Open, 25.05.2022 Tilføjet 25.05.2022 Objective This study aims to provide a case definition of sepsis of presumed bacterial aetiology based on 10th revision of the International Classification of Diseases (ICD-10) codes, to assess trends in sepsis incidence and mortality between 2015 and 2019 in France, and to describe the characteristics of affected patients and hospital stays. Design Nationwide, population-based, retrospective observational study. Setting Metropolitan France between 2015 and 2019. Participants Between 2015 and 2019, 1 224 433 patients with sepsis of presumed bacterial aetiology were selected from the French National Hospital Discharge Database (Programme de Médicalisation des Systèmes d’Information) and were identified from corresponding ICD-10 codes for explicit sepsis or implicit sepsis. Main outcomes measures Annual overall and age-specific and gender-specific incidence and 95% CI, as well as trends in sepsis incidence and mortality, were estimated. Comorbidities, length of hospital stay and outcomes were described. Results The sex-standardised and age-standardised incidence per 100 000 (95% CI) increased from 357 (356.0 to 359.0) in 2015 to 403 (401.9 to 405.0) in 2019 and remained higher for males compared with females. Children under 1 year and patients over 75 years consistently had the highest incidence. The most common comorbidities were cancer and chronic heart failure. The median hospital length of stay was 12 days. Most patients came from home, but only half returned home after their hospital stay and approximately 15% were discharged to long-term care. In-hospital mortality was about 25% and declined along the study period. Conclusions Medico-administrative databases can be used to provide nationwide estimates of the in-hospital burden of bacterial sepsis. The results confirm the high burden of sepsis in France. These data should be complemented by estimating the additional burden associated with fungal and viral infections during the COVID-19 pandemic. Læs mere Tjek på PubMed 14 Human Monoclonal Antibodies to Escherichia coli Outer Membrane Protein A Porin Domain Cause Aggregation but Do Not Alter In Vivo Bacterial Burdens in a Murine Sepsis Model Benjamin D. Fowler, Nurgun Kose, Joseph X. Reidy, Laura S. Handal, Eric P. Skaar, James E. Crowe aDepartment of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Centergrid.412807.8, Nashville, Tennessee, USA bVanderbilt Vaccine Center, Vanderbilt University Medical Centergrid.412807.8, Nashville, Tennessee, USA cVanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Centergrid.412807.8, Nashville, Tennessee, USA dDepartment of Pediatrics, Vanderbilt University Medical Centergrid.412807.8, Nashville, Tennessee, USA, Andreas J. Bäumler Infection and Immunity, 18.05.2022 Tilføjet 18.05.2022 15 The protective effects of HIF-1α activation on sepsis induced intestinal mucosal barrier injury in rats model of sepsis Xiuzhen Lei, Wenbin Teng, Ying Fan, Yeke Zhu, Liuxu Yao, Yuhong Li, Shengmei Zhu PLoS One Infectious Diseases, 16.05.2022 Tilføjet 16.05.2022 by Xiuzhen Lei, Wenbin Teng, Ying Fan, Yeke Zhu, Liuxu Yao, Yuhong Li, Shengmei Zhu The integrity of the intestinal barrier is critical for protecting the host against the pathogen. The role of hypoxia-inducible factor-1α (HIF-1α) in the intestinal barrier disfunction related to sepsis remained unclear. The purpose of the present study is to investigate the role of HIF-1α on oxidative damage, the intestinal mucosal permeability, structural and morphological changes during sepsis. Twenty-four Sprague Dawley (SD) rats were randomly divided into four groups of 6 rats each: the sham group (sham), sepsis group (subjected to cecal ligation and perforation, CLP), sepsis + DMOG group (40 mg/kg of DMOG by intraperitoneal injection for 7 consecutive days before CLP), and sepsis + BAY 87–2243 group (9 mg/kg of BAY 87–2243 orally administered for 3 consecutive days before CLP). Sepsis increased plasma levels of inflammatory mediators, oxidative stress markers and HIF-1α expression; caused pathological damage; increased permeability (P < 0.05); and decreased TJ protein expression in the intestinal mucosa of rats with sepsis (P < 0.05). The addition of DMOG up-regulated HIF-1α, then decreased the plasma levels of inflammatory mediators, oxidative stress markers, alleviated pathological damage to the intestinal mucosa and decreased intestinal permeability (P < 0.05); while BAY 87–2243 treatment had the opposite effects. Our findings showed that HIF-1α protects the intestinal barrier function of septic rats by inhibiting intestinal inflammation and oxidative damage, our results provide a novel insight for developing sepsis treatment. Læs mere Tjek på PubMed16 Serum Vimentin Predicts Mortality in Pediatric Severe Sepsis: A Prospective Observational Study Huijie Miao, Yun Cui, Ye Lu, Ting Sun, Jiaying Dou, Yuqian Ren, Chunxia Wang, Yucai Zhang International Journal of Infectious Diseases, 11.05.2022 Tilføjet 11.05.2022 Vascular hyperpermeability by loss of endothelial barrier integrity is a hallmark of sepsis. Vimentin is involved in regulation of endothelial function and inflammatory response. However, the serum level of vimentin and its clinical relevance in pediatric severe sepsis (PSS) is remain unknown. Læs mere Tjek på PubMed17 Personalised immunotherapy in sepsis: a scoping review protocol Slim, M. A., van Mourik, N., Dionne, J. C., Oczkowski, S. J. W., Netea, M. G., Pickkers, P., Giamarellos-Bourboulis, E. J., Müller, M. C. A., van der Poll, T., Wiersinga, W. J., Vlaar, A. P. J., van Vught, L. A. BMJ Open, 9.05.2022 Tilføjet 9.05.2022 Introduction Sepsis, a life-threatening organ dysfunction syndrome occurring in the context of severe infections, remains a major burden on global health with high morbidity and high mortality rates. Despite recent advances in the understanding of its pathophysiology, the treatment of sepsis remains supportive of nature with few interventions specifically designed for treating this complex syndrome. The focus of sepsis trials has increasingly shifted towards targeting excessive inflammation and immunosuppression using immunomodulatory agents. However, it remains uncertain how to identify patients that could benefit from such treatment, whether treatments can be tailored to an individual’s immune profile, or at which stage of the disease the intervention should be initiated. In this scoping review, we provide a comprehensive overview of current available literature on immunostimulatory and immunosuppressive therapies against sepsis. Methods and analysis The aim of this scoping review is to describe and summarise current literature evaluating immunotherapy in adult patients with sepsis. The review will be performed using the framework formulated by Arksey and O’Malley. A comprehensive literature and study collection will be executed by searching PubMed, Embase, Cochrane CENTRAL and ClinicalTrials.gov to identify clinical trials and cohort studies concerning immunotherapy in adult patients with sepsis. Screening will be performed independently and in duplicate by two reviewers who will also independently extract data into prespecified spreadsheets. We will summarise evidence in tabular format with descriptive statistics. The reported evidence will convey knowledge on the types of immunotherapies studied, and currently being studied, in adult patients with sepsis. Ethics and dissemination Approval from a medical ethics committee is not required. Once completed, the review will be submitted for publication in a peer-reviewed journal. These results will be of value to clinicians and researchers with an interest in advancing sepsis care. Læs mere Tjek på PubMed 18 Chronic aspirin use and survival following sepsis – A propensity-matched, observational cohort study Inbar Lavie, Michael Lavie, Anat Gafter-Gvili, Erez Halperin, Hadar Abramovich-Yoffe, Tomer Avni Clinical Microbiology and Infection, 6.05.2022 Tilføjet 6.05.2022 The use of antiplatelet agents is postulated to lead to improved outcomes in sepsis. We aimed to evaluate whether chronic, pre-hospitalization aspirin usage, leads to improved outcomes in patients with sepsis. Læs mere Tjek på PubMed19 Laboratory Investigations in Patients with Community Acquired Sepsis and/or Pneumonia Caused by Burkholderia pseudomallei American Journal of Tropical Medicine and Hygiene, 4.05.2022 Tilføjet 4.05.2022
Journal Name: The American Journal of Tropical Medicine and HygieneVolume: 106Issue: 5Pages: 1560-1560 Læs mere Tjek på PubMed 20 Determinants of neonatal sepsis among neonates admitted to the neonatal intensive care unit of public hospitals in Hawassa City Administration, Sidama Region, Ethiopia, 2020: an unmatched, case-control study Bejitual, K., Fikre, R., Ashegu, T., Zenebe, A. BMJ Open, 3.05.2022 Tilføjet 3.05.2022 Objective This study was conducted to assess the determinants of neonatal sepsis in the neonatal intensive care units of public hospitals in Hawassa City Administration, Sidama Region, Ethiopia, in 2020. Design Institutional-based, unmatched, case–control study. Setting The study was conducted in three public hospitals (Hawassa University Teaching Hospital, Adare General Hospital and Hawela Tula Primary Hospital) of Hawassa City, Ethiopia. Participants A total of 331 (110 cases and 221 controls) neonates with their index mothers were included in the study from 1 August to 30 September 2020. Outcome measures A pretested, interviewer-administered questionnaire and data extraction checklist were used to collect data. Data were coded and entered into EpiData V.3.1 before being exported to SPSS V.20 for analysis. The factors associated with neonatal sepsis were assessed using bivariable and multivariable logistic regression analyses. P value of less than 0.05 was used to establish statistically significant association of variables. Results Caesarean section delivery (adjusted OR (AOR)=2.56, 95 % CI 1.3 to 5.00), maternal anaemia (AOR=2.58, 95 % CI 1.45 to 4.6) and lack of vaccination with tetanus toxoid (AOR=3.5, 95% CI 2.07 to 6.19) were all identified as factors significantly associated with neonatal sepsis. Conclusions Caesarean section delivery, maternal history of anaemia and lack of vaccination with tetanus toxoid were found to be risk factors for neonatal sepsis. Establishing preconception care practice, strengthening the quality of antenatal care and standardising infection prevention practice are needed to improve neonatal health. Læs mere Tjek på PubMed |
Referencer 1 Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med 2021; 47(11):1181-1247
Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, Machado FR, Mcintyre L, Ostermann M, Prescott HC, Schorr C, Simpson S, Wiersinga WJ, Alshamsi F, Angus DC, Arabi Y, Azevedo L, Beale R, Beilman G, Belley-Cote E, Burry L, Cecconi M, Centofanti J, Coz Yataco A, De Waele J, Dellinger RP, Doi K, Du B, Estenssoro E, Ferrer R, Gomersall C, Hodgson C, Møller MH, Iwashyna T, Jacob S, Kleinpell R, Klompas M, Koh Y, Kumar A, Kwizera A, Lobo S, Masur H, McGloughlin S, Mehta S, Mehta Y, Mer M, Nunnally M, Oczkowski S, Osborn T, Papathanassoglou E, Perner A, Puskarich M, Roberts J, Schweickert W, Seckel M, Sevransky J, Sprung CL, Welte T, Zimmerman J, Levy M
PMID: 34599691 2 Timing of norepinephrine initiation in patients with septic shock: a systematic review and meta-analysis. Crit Care 2020; 24(1):488
Li Y, Li H, Zhang D
The effect of the timing of norepinephrine initiation on clinical outcomes in patients with septic shock is uncertain. A systematic review and meta-analysis was performed to evaluate the impact of early and late start of norepinephrine support on clinical outcomes in patients with septic shock. PMID: 327627653 Procalcitonin to Reduce Long-Term Infection-associated Adverse Events in Sepsis. A Randomized Trial. Am J Respir Crit Care Med 2021; 203(2):202-210
Kyriazopoulou E, Liaskou-Antoniou L, Adamis G, Panagaki A, Melachroinopoulos N, Drakou E, Marousis K, Chrysos G, Spyrou A, Alexiou N, Symbardi S, Alexiou Z, Lagou S, Kolonia V, Gkavogianni T, Kyprianou M, Anagnostopoulos I, Poulakou G, Lada M, Makina A, Roulia E, Koupetori M, Apostolopoulos V, Petrou D, Nitsotolis T, Antoniadou A, Giamarellos-Bourboulis EJ
Although early antimicrobial discontinuation guided by procalcitonin (PCT) has shown decreased antibiotic consumption in lower respiratory tract infections, the outcomes in long-term sepsis sequelae remain unclear. To investigate if PCT guidance may reduce the incidence of long-term infection-associated adverse events in sepsis. In this multicenter trial, 266 patients with sepsis (by Sepsis-3 definitions) with lower respiratory tract infections, acute pyelonephritis, or primary bloodstream infection were randomized (1:1) to receive either PCT-guided discontinuation of antimicrobials or standard of care. The discontinuation criterion was ≥80% reduction in PCT levels or any PCT ≤0.5 μg/L at Day 5 or later. The primary outcome was the rate of infection-associated adverse events at Day 180, a composite of the incidence of any new infection by or multidrug-resistant organisms, or any death attributed to baseline or multidrug-resistant organism infection. Secondary outcomes included 28-day mortality, length of antibiotic therapy, and cost of hospitalization. The rate of infection-associated adverse events was 7.2% (95% confidence interval [CI], 3.8-13.1%; 9/125) versus 15.3% (95% CI, 10.1-22.4%; 20/131) (hazard ratio, 0.45; 95% CI, 0.20-0.98; = 0.045); 28-day mortality 15.2% (95% CI, 10-22.5%; 19/125) versus 28.2% (95% CI, 21.2-36.5%; 37/131) (hazard ratio, 0.51; 95% CI, 0.29-0.89; = 0.02); and median length of antibiotic therapy 5 (range, 5-7) versus 10 (range, 7-15) days ( < 0.001) in the PCT and standard-of-care arms, respectively. The cost of hospitalization was also reduced in the PCT arm. In sepsis, PCT guidance was effective in reducing infection-associated adverse events, 28-day mortality, and cost of hospitalization.Clinical trial registered with www.clinicaltrials.gov (NCT03333304). PMID: 327579634 Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study. Lancet 2020; 395(10219):200-211
Rudd KE, Johnson SC, Agesa KM, Shackelford KA, Tsoi D, Kievlan DR, Colombara DV, Ikuta KS, Kissoon N, Finfer S, Fleischmann-Struzek C, Machado FR, Reinhart KK, Rowan K, Seymour CW, Watson RS, West TE, Marinho F, Hay SI, Lozano R, Lopez AD, Angus DC, Murray CJL, Naghavi M
Sepsis is life-threatening organ dysfunction due to a dysregulated host response to infection. It is considered a major cause of health loss, but data for the global burden of sepsis are limited. As a syndrome caused by underlying infection, sepsis is not part of standard Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimates. Accurate estimates are important to inform and monitor health policy interventions, allocation of resources, and clinical treatment initiatives. We estimated the global, regional, and national incidence of sepsis and mortality from this disorder using data from GBD 2017. PMID: 319544655 Procalcitonin-Guided Antibiotic Discontinuation and Mortality in Critically Ill Adults: A Systematic Review and Meta-analysis. Chest 2019; 155(6):1109-1118
Pepper DJ, Sun J, Rhee C, Welsh J, Powers JH, Danner RL, Kadri SS
Procalcitonin (PCT)-guided antibiotic discontinuation appears to decrease antibiotic use in critically ill patients, but its impact on survival remains less certain. PMID: 307723866 The Surviving Sepsis Campaign Bundle: 2018 Update. Crit Care Med 2018; 46(6):997-1000 7 Balanced Crystalloids versus Saline in Noncritically Ill Adults. N Engl J Med 2018; 378(9):819-828
Self WH, Semler MW, Wanderer JP, Wang L, Byrne DW, Collins SP, Slovis CM, Lindsell CJ, Ehrenfeld JM, Siew ED, Shaw AD, Bernard GR, Rice TW,
Comparative clinical effects of balanced crystalloids and saline are uncertain, particularly in noncritically ill patients cared for outside an intensive care unit (ICU). PMID: 294859268 Balanced Crystalloids versus Saline in Critically Ill Adults. N Engl J Med 2018; 378(9):829-839
Semler MW, Self WH, Wanderer JP, Ehrenfeld JM, Wang L, Byrne DW, Stollings JL, Kumar AB, Hughes CG, Hernandez A, Guillamondegui OD, May AK, Weavind L, Casey JD, Siew ED, Shaw AD, Bernard GR, Rice TW,
Both balanced crystalloids and saline are used for intravenous fluid administration in critically ill adults, but it is not known which results in better clinical outcomes. PMID: 294859259 A Comparison of the Quick-SOFA and Systemic Inflammatory Response Syndrome Criteria for the Diagnosis of Sepsis and Prediction of Mortality: A Systematic Review and Meta-Analysis. Chest 2018; 153(3):646-655
Serafim R, Gomes JA, Salluh J, Póvoa P
Several studies were published to validate the quick Sepsis-related Organ Failure Assessment (qSOFA), namely in comparison with the systemic inflammatory response syndrome (SIRS) criteria. We performed a systematic review and meta-analysis with the aim of comparing the qSOFA and SIRS in patients outside the ICU. PMID: 2928968710 Application of the Third International Consensus Definitions for Sepsis (Sepsis-3) Classification: a retrospective population-based cohort study. Lancet Infect Dis 2017; 17(6):661-670
Donnelly JP, Safford MM, Shapiro NI, Baddley JW, Wang HE
The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) present clinical criteria for the classification of patients with sepsis. We investigated incidence and long-term outcomes of patients diagnosed with these classifications, which are currently unknown. PMID: 2826806711 Prognostic Accuracy of the SOFA Score, SIRS Criteria, and qSOFA Score for In-Hospital Mortality Among Adults With Suspected Infection Admitted to the Intensive Care Unit. JAMA 2017; 317(3):290-300
Raith EP, Udy AA, Bailey M, McGloughlin S, MacIsaac C, Bellomo R, Pilcher DV,
The Sepsis-3 Criteria emphasized the value of a change of 2 or more points in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score, introduced quick SOFA (qSOFA), and removed the systemic inflammatory response syndrome (SIRS) criteria from the sepsis definition. PMID: 2811455312 Restricting volumes of resuscitation fluid in adults with septic shock after initial management: the CLASSIC randomised, parallel-group, multicentre feasibility trial. Intensive Care Med 2016; 42(11):1695-1705
Hjortrup PB, Haase N, Bundgaard H, Thomsen SL, Winding R, Pettilä V, Aaen A, Lodahl D, Berthelsen RE, Christensen H, Madsen MB, Winkel P, Wetterslev J, Perner A, ,
We assessed the effects of a protocol restricting resuscitation fluid vs. a standard care protocol after initial resuscitation in intensive care unit (ICU) patients with septic shock. PMID: 2768634913 Suspected sepsis: summary of NICE guidance. BMJ 2016; 354:i4030 14 The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016; 315(8):801-10
Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC
Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination. PMID: 2690333815 Developing a New Definition and Assessing New Clinical Criteria for Septic Shock: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016; 315(8):775-87
Shankar-Hari M, Phillips GS, Levy ML, Seymour CW, Liu VX, Deutschman CS, Angus DC, Rubenfeld GD, Singer M,
Septic shock currently refers to a state of acute circulatory failure associated with infection. Emerging biological insights and reported variation in epidemiology challenge the validity of this definition. PMID: 2690333616 Assessment of Clinical Criteria for Sepsis: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016; 315(8):762-74
Seymour CW, Liu VX, Iwashyna TJ, Brunkhorst FM, Rea TD, Scherag A, Rubenfeld G, Kahn JM, Shankar-Hari M, Singer M, Deutschman CS, Escobar GJ, Angus DC
The Third International Consensus Definitions Task Force defined sepsis as "life-threatening organ dysfunction due to a dysregulated host response to infection." The performance of clinical criteria for this sepsis definition is unknown. PMID: 2690333517 Trial of early, goal-directed resuscitation for septic shock. N Engl J Med 2015; 372(14):1301-11
Mouncey PR, Osborn TM, Power GS, Harrison DA, Sadique MZ, Grieve RD, Jahan R, Harvey SE, Bell D, Bion JF, Coats TJ, Singer M, Young JD, Rowan KM,
Early, goal-directed therapy (EGDT) is recommended in international guidelines for the resuscitation of patients presenting with early septic shock. However, adoption has been limited, and uncertainty about its effectiveness remains. PMID: 2577653218 Goal-directed resuscitation for patients with early septic shock. N Engl J Med 2014; 371(16):1496-506
, , Peake SL, Delaney A, Bailey M, Bellomo R, Cameron PA, Cooper DJ, Higgins AM, Holdgate A, Howe BD, Webb SA, Williams P
Early goal-directed therapy (EGDT) has been endorsed in the guidelines of the Surviving Sepsis Campaign as a key strategy to decrease mortality among patients presenting to the emergency department with septic shock. However, its effectiveness is uncertain. PMID: 2527231619 A randomized trial of protocol-based care for early septic shock. N Engl J Med 2014; 370(18):1683-93
, Yealy DM, Kellum JA, Huang DT, Barnato AE, Weissfeld LA, Pike F, Terndrup T, Wang HE, Hou PC, LoVecchio F, Filbin MR, Shapiro NI, Angus DC
In a single-center study published more than a decade ago involving patients presenting to the emergency department with severe sepsis and septic shock, mortality was markedly lower among those who were treated according to a 6-hour protocol of early goal-directed therapy (EGDT), in which intravenous fluids, vasopressors, inotropes, and blood transfusions were adjusted to reach central hemodynamic targets, than among those receiving usual care. We conducted a trial to determine whether these findings were generalizable and whether all aspects of the protocol were necessary. PMID: 2463577320 Albumin replacement in patients with severe sepsis or septic shock. N Engl J Med 2014; 370(15):1412-21
Caironi P, Tognoni G, Masson S, Fumagalli R, Pesenti A, Romero M, Fanizza C, Caspani L, Faenza S, Grasselli G, Iapichino G, Antonelli M, Parrini V, Fiore G, Latini R, Gattinoni L,
Although previous studies have suggested the potential advantages of albumin administration in patients with severe sepsis, its efficacy has not been fully established. PMID: 2463577221 High versus low blood-pressure target in patients with septic shock. N Engl J Med 2014; 370(17):1583-93
Asfar P, Meziani F, Hamel JF, Grelon F, Megarbane B, Anguel N, Mira JP, Dequin PF, Gergaud S, Weiss N, Legay F, Le Tulzo Y, Conrad M, Robert R, Gonzalez F, Guitton C, Tamion F, Tonnelier JM, Guezennec P, Van Der Linden T, Vieillard-Baron A, Mariotte E, Pradel G, Lesieur O, Ricard JD, Hervé F, du Cheyron D, Guerin C, Mercat A, Teboul JL, Radermacher P,
The Surviving Sepsis Campaign recommends targeting a mean arterial pressure of at least 65 mm Hg during initial resuscitation of patients with septic shock. However, whether this blood-pressure target is more or less effective than a higher target is unknown. PMID: 2463577022 Severe sepsis and septic shock. N Engl J Med 2013; 369(9):840-51 23 Hydroxyethyl starch 130/0.42 versus Ringer's acetate in severe sepsis. N Engl J Med 2012; 367(2):124-34
Perner A, Haase N, Guttormsen AB, Tenhunen J, Klemenzson G, Åneman A, Madsen KR, Møller MH, Elkjær JM, Poulsen LM, Bendtsen A, Winding R, Steensen M, Berezowicz P, Søe-Jensen P, Bestle M, Strand K, Wiis J, White JO, Thornberg KJ, Quist L, Nielsen J, Andersen LH, Holst LB, Thormar K, Kjældgaard AL, Fabritius ML, Mondrup F, Pott FC, Møller TP, Winkel P, Wetterslev J, ,
Hydroxyethyl starch (HES) [corrected] is widely used for fluid resuscitation in intensive care units (ICUs), but its safety and efficacy have not been established in patients with severe sepsis. PMID: 2273808524 Procalcitonin-guided interventions against infections to increase early appropriate antibiotics and improve survival in the intensive care unit: a randomized trial. Crit Care Med 2011; 39(9):2048-58
Jensen JU, Hein L, Lundgren B, Bestle MH, Mohr TT, Andersen MH, Thornberg KJ, Løken J, Steensen M, Fox Z, Tousi H, Søe-Jensen P, Lauritsen AØ, Strange D, Petersen PL, Reiter N, Hestad S, Thormar K, Fjeldborg P, Larsen KM, Drenck NE, Ostergaard C, Kjær J, Grarup J, Lundgren JD,
For patients in intensive care units, sepsis is a common and potentially deadly complication and prompt initiation of appropriate antimicrobial therapy improves prognosis. The objective of this trial was to determine whether a strategy of antimicrobial spectrum escalation, guided by daily measurements of the biomarker procalcitonin, could reduce the time to appropriate therapy, thus improving survival. PMID: 2157232825 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med 2003; 31(4):1250-6
Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G,
In 1991, the American College of Chest Physicians (ACCP) and the Society of Critical Care Medicine (SCCM) convened a "Consensus Conference," the goals of which were "to provide a conceptual and a practical framework to define the systemic inflammatory response to infection, which is a progressive injurious process that falls under the generalized term 'sepsis' and includes sepsis-associated organ dysfunction as well." The general definitions introduced as a result of that conference have been widely used in practice and have served as the foundation for inclusion criteria for numerous clinical trials of therapeutic interventions. Nevertheless, there has been an impetus from experts in the field to modify these definitions to reflect our current understanding of the pathophysiology of these syndromes. PMID: 1268250026 American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 1992; 20(6):864-74 |
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