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.
Diagnostic value of maternal, cord blood and neonatal biomarkers for early onset sepsis: a systematic review and meta-analysis
Lisanne M. van Leeuwen, Elandri Fourie, Gerrie van den Brink, Vincent Bekker, Marlies A. van Houten
Clinical Microbiology and Infection, 10.03.2024
Tilføjet 10.03.2024
An accurate diagnosis of early onset sepsis (EOS) is challenging due to subtle symptoms and the lack of a good diagnostic tool, resulting in considerable antibiotic overtreatment. A biomarker, discriminating between infected and non-infected newborns early in the disease, could improve EOS prediction. Numerous biomarkers have been tested, but have never been compared directly.
Polymicrobial bloodstream infections per se do not increase mortality compared to monomicrobial bloodstream infections in sepsis patients: a Korean nationwide sepsis cohort study
BMC Infectious Diseases, 8.03.2024
Tilføjet 8.03.2024
Abstract Background There is limited information about the outcomes of polymicrobial bloodstream infections in patients with sepsis. We aimed to investigate outcomes of polymicrobial bloodstream infections compared to monomicrobial bloodstream infections. Methods This study used data from the Korean Sepsis Alliance Registry, a nationwide database of prospective observational sepsis cohort. Adult sepsis patients with bloodstream infections from September 2019 to December 2021 at 20 tertiary or university-affiliated hospitals in South Korea were analyzed. Results Among the 3,823 patients with bloodstream infections, 429 of them (11.2%) had polymicrobial bloodstream infections. The crude hospital mortality of patients with sepsis with polymicrobial bloodstream infection and monomicrobial bloodstream infection was 35.7% and 30.1%, respectively (p = 0.021). However, polymicrobial bloodstream infections were not associated with hospital mortality in the proportional hazard analysis (HR 1.15 [0.97–1.36], p = 0.11). The inappropriate use of antibiotics was associated with increased mortality (HR 1.37 [1.19–1.57], p
Deficits in blood culture collection in the emergency department if sepsis is suspected: results of a retrospective cohort study
Infection, 7.03.2024
Tilføjet 7.03.2024
Abstract Purpose Blood cultures (BCs) are key for pathogen detection in septic patients. We investigated the extent to which sampling was performed and what factors were associated with the absence of general or inadequate BC sampling. Methods We conducted a retrospective cohort study of hospitalized patients with sepsis admitted to one of three EDs in 2018. Primary outcome was the extent of general BC collection of at least 1 set. Secondary outcome was the extent of adequate BC sampling, defined as ≥ 2 sets before antibiotic therapy (AT). Multivariable logistic regression analysis was performed to identify factors associated with deficits in both outcomes. Results 1143 patients were analyzed. BCs were collected from 946 patients. Single BCs were taken from 520 patients, ≥ 2 sets from 426 patients. Overall, ≥ 2 BCs were taken from 349 patients before AT. BC sampling before AT occurred significantly more frequently when ≥ 2 BC sets were taken rather than a single one (81.9%, versus 68.4%, p
Claudin-2 upregulation enhances intestinal permeability, immune activation, dysbiosis, and mortality in sepsis
Takehiko OamiShabnam AbtahiTakashi ShimazuiChing-Wen ChenYan Y. SweatZhe LiangEileen M. BurdAlton B. FarrisJoe T. RolandSachiko TsukitaMandy L. FordJerrold R. TurnerCraig M. CoopersmithaDepartment of Surgery and Emory Critical Care Center, Emory University School of Medicine, Atlanta, GA 30322bDepartment of Emergency and Critical Care Medicine, Chiba University Graduate School of Medicine, Chiba 260-8670, JapancLaboratory of Mucosal Pathobiology, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115dDepartment of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322eEpithelial Biology Center, Department of Surgery, Vanderbilt University Medical Center, Nashville, TN 37240fAdvanced Comprehensive Research Organization, Teikyo University, Tokyo 173-0003, JapangDepartment of Surgery and Emory Transplant Center, Emory University School of Medicine, Atlanta, GA 30322
Proceedings of the National Academy of Sciences, 6.03.2024
Tilføjet 6.03.2024
Proceedings of the National Academy of Sciences, Volume 121, Issue 10, March 2024.
Deficits in blood culture collection in the emergency department if sepsis is suspected: results of a retrospective cohort study
Infection, 6.03.2024
Tilføjet 6.03.2024
Abstract Purpose Blood cultures (BCs) are key for pathogen detection in septic patients. We investigated the extent to which sampling was performed and what factors were associated with the absence of general or inadequate BC sampling. Methods We conducted a retrospective cohort study of hospitalized patients with sepsis admitted to one of three EDs in 2018. Primary outcome was the extent of general BC collection of at least 1 set. Secondary outcome was the extent of adequate BC sampling, defined as ≥ 2 sets before antibiotic therapy (AT). Multivariable logistic regression analysis was performed to identify factors associated with deficits in both outcomes. Results 1143 patients were analyzed. BCs were collected from 946 patients. Single BCs were taken from 520 patients, ≥ 2 sets from 426 patients. Overall, ≥ 2 BCs were taken from 349 patients before AT. BC sampling before AT occurred significantly more frequently when ≥ 2 BC sets were taken rather than a single one (81.9%, versus 68.4%, p
Polymicrobial bloodstream infections per se do not increase mortality compared to monomicrobial bloodstream infections in sepsis patients: a Korean nationwide sepsis cohort study
BMC Infectious Diseases, 5.03.2024
Tilføjet 5.03.2024
Abstract Background There is limited information about the outcomes of polymicrobial bloodstream infections in patients with sepsis. We aimed to investigate outcomes of polymicrobial bloodstream infections compared to monomicrobial bloodstream infections. Methods This study used data from the Korean Sepsis Alliance Registry, a nationwide database of prospective observational sepsis cohort. Adult sepsis patients with bloodstream infections from September 2019 to December 2021 at 20 tertiary or university-affiliated hospitals in South Korea were analyzed. Results Among the 3,823 patients with bloodstream infections, 429 of them (11.2%) had polymicrobial bloodstream infections. The crude hospital mortality of patients with sepsis with polymicrobial bloodstream infection and monomicrobial bloodstream infection was 35.7% and 30.1%, respectively (p = 0.021). However, polymicrobial bloodstream infections were not associated with hospital mortality in the proportional hazard analysis (HR 1.15 [0.97–1.36], p = 0.11). The inappropriate use of antibiotics was associated with increased mortality (HR 1.37 [1.19–1.57], p
Persistent high sepsis-induced coagulopathy and sequential organ failure assessment scores can predict the 28-day mortality of patients with sepsis: A prospective study
BMC Infectious Diseases, 5.03.2024
Tilføjet 5.03.2024
Abstract Background The performance of the sepsis-induced coagulopathy (SIC) and sequential organ failure assessment (SOFA) scores in predicting the prognoses of patients with sepsis has been validated. This study aimed to investigate the time course of SIC and SOFA scores and their association with outcomes in patients with sepsis. Methods This prospective study enrolled 209 patients with sepsis admitted to the emergency department. The SIC and SOFA scores of the patients were assessed on days 1, 2, and 4. Patients were categorized into survivor or non-survivor groups based on their 28-day survival. We conducted a generalized estimating equation analysis to evaluate the time course of SIC and SOFA scores and the corresponding differences between the two groups. The predictive value of SIC and SOFA scores at different time points for sepsis prognosis was evaluated. Results In the non-survivor group, SIC and SOFA scores gradually increased during the first 4 days (P < 0.05). In the survivor group, the SIC and SOFA scores on day 2 were significantly higher than those on day 1 (P < 0.05); however, they decreased on day 4, dropping below the levels observed on day 1 (P < 0.05). The non-survivors showed higher SIC scores on days 2 (P < 0.05) and 4 (P < 0.001) than the survivors, whereas no significant differences were found between the two groups on day 1 (P > 0.05). The performance of SIC scores on day 4 for predicting mortality was more accurate than that on day 2, with areas under the curve of 0.749 (95% confidence interval [CI]: 0.674–0.823), and 0.601 (95% CI: 0.524–0.679), respectively. The SIC scores demonstrated comparable predictive accuracy for 28-day mortality to the SOFA scores on days 2 and 4. Cox proportional hazards models indicated that SIC on day 4 (hazard ratio [HR] = 3.736; 95% CI: 2.025–6.891) was an independent risk factor for 28-day mortality. Conclusions The time course of SIC and SOFA scores differed between surviving and non-surviving patients with sepsis, and persistent high SIC and SOFA scores can predict 28-day mortality.
Conventional and unconventional T cell responses contribute to the prediction of clinical outcome and causative bacterial pathogen in sepsis patients
Clinical & Experimental Immunology, 2.03.2024
Tilføjet 2.03.2024
Abstract Sepsis is characterised by a dysfunctional host response to infection culminating in life-threatening organ failure that requires complex patient management and rapid intervention. Timely diagnosis of the underlying cause of sepsis is crucial, and identifying those at risk of complications and death is imperative for triaging treatment and resource allocation. Here, we explored the potential of explainable machine learning models to predict mortality and causative pathogen in sepsis patients. By using a modelling pipeline employing multiple feature selection algorithms, we demonstrate the feasibility to identify integrative patterns from clinical parameters, plasma biomarkers and extensive phenotyping of blood immune cells. Whilst no single variable had sufficient predictive power, models that combined five and more features showed a macro area under the curve (AUC) of 0.85 to predict 90 day mortality after sepsis diagnosis, and a macro AUC of 0.86 to discriminate between Gram-positive and Gram-negative bacterial infections. Parameters associated with the cellular immune response contributed the most to models predictive of 90 day mortality, most notably, the proportion of T cells among PBMCs, together with expression of CXCR3 by CD4+ T cells and CD25 by mucosal-associated invariant T (MAIT) cells. Frequencies of Vδ2+ γδ T cells had the most profound impact on the prediction of Gram-negative infections, alongside other T cell-related variables and total neutrophil count. Overall, our findings highlight the added value of measuring the proportion and activation patterns of conventional and unconventional T cells in the blood of sepsis patients in combination with other immunological, biochemical and clinical parameters.
Streptococcus pyogenes (Group A Streptococcus – GAS) is responsible for millions of infections and more than 500,000 deaths worldwide annually [1]. Generally, the primary site of GAS is the oropharynx with pharyngotonsillitis and scarlet fever as its most common “suppurative” manifestations, possibly complicated by “non-suppurative” autoimmune sequelae. However, an increase in invasive GAS (iGAS) infections with detectable bacteremia was reported throughout Europe since late 2022 [2]. Even if less frequently than Streptococcus agalactiae (Group B streptococcus - GBS) and Escherichia coli, GAS can occasionally colonize the female genital tract and cause serious complications including puerperal sepsis and early-onset neonatal sepsis (EOS) [3].
Context and Implications of the New Pediatric Sepsis Criteria
Journal of the American Medical Association, 1.03.2024
Tilføjet 1.03.2024
Sepsis has been recognized as an important cause of morbidity and mortality for more than 2800 years. Derived from the Greek word sepo (σηπω, translated as “I rot,”), sepsis appears in writings of Homer, Hippocrates, Aristotle, and Galen. Conceptually, sepsis denotes a “line in the sand” within the broad spectrum of host-microbe interactions. It indicates that not only is the microbe unwanted (in contrast to the many microbes that live on and within us and contribute to health and digestion), but the host’s attempts to eradicate the microbe are resulting in collateral damage.
Journal of the American Medical Association, 1.03.2024
Tilføjet 1.03.2024
Everyone must acknowledge the difficulty of distinguishing diseases…whoever denies this may as well deny that there is such a thing as medical art.William Cullen
International Consensus Criteria for Pediatric Sepsis and Septic Shock
Journal of the American Medical Association, 1.03.2024
Tilføjet 1.03.2024
This article revises criteria to identify sepsis in children after an exhaustive process that involved surveying clinicians, reviewing health record databases, conducting a systematic review and meta-analysis, and undergoing a Delphi consensus process.
Development and Validation of the Phoenix Criteria for Pediatric Sepsis and Septic Shock
Journal of the American Medical Association, 1.03.2024
Tilføjet 1.03.2024
This cohort study derives and validates novel criteria for diagnosis of pediatric sepsis and septic shock across high-resource and low-resource international settings.
Real-World Implications of Updated Surviving Sepsis Campaign Antibiotic Timing Recommendations
Taylor, Stephanie P.; Kowalkowski, Marc A.; Skewes, Sable; Chou, Shih-Hsiung
Critical Care Medicine, 28.02.2024
Tilføjet 28.02.2024
Objective: To evaluate real-world implications of updated Surviving Sepsis Campaign (SSC) recommendations for antibiotic timing. Design: Retrospective cohort study. Setting: Twelve hospitals in the Southeastern United States between 2017 and 2021. Patients: One hundred sixty-six thousand five hundred fifty-nine adult hospitalized patients treated in the emergency department for suspected serious infection. Interventions: None. Measurements and Main Results: We determined the number and characteristics of patients affected by updated SSC recommendations for initiation of antibiotics that incorporate a risk- and probability-stratified approach. Using an infection prediction model with a cutoff of 0.5 to classify possible vs. probable infection, we found that 30% of the suspected infection cohort would be classified as shock absent, possible infection and thus eligible for the new 3-hour antibiotic recommendation. In real-world practice, this group had a conservative time to antibiotics (median, 5.5 hr; interquartile range [IQR], 3.2–9.8 hr) and low mortality (2%). Patients categorized as shock absent, probable infection had a median time to antibiotics of 3.2 hours (IQR, 2.1–5.1 hr) and mortality of 3%. Patients categorized as shock present, the probable infection had a median time to antibiotics 2.7 hours (IQR, 1.7–4.6 hr) and mortality of 17%, and patients categorized as shock present, the possible infection had a median time to antibiotics 6.9 hours (IQR, 3.5–16.3 hr) and mortality of 12%. Conclusions: These data support recently updated SSC recommendations to align antibiotic timing targets with risk and probability stratifications. Our results provide empirical support that clinicians and hospitals should not be held to 1-hour targets for patients without shock and with only possible sepsis.
Knowledge, attitudes and practices towards the diagnosis and management of paediatric sepsis among paediatric physicians and nurses: a cross-sectional study of 21 hospitals in Hubei Province, China
Yue, J., Zhao, H., Li, J., Wu, J., Zheng, R.
BMJ Open, 28.02.2024
Tilføjet 28.02.2024
ObjectivesTo evaluate the knowledge, attitudes and practices towards diagnosing and managing paediatric sepsis among paediatric physicians and nurses. DesignA cross-sectional, questionnaire-based study. Setting21 hospitals in Hubei Province between February 2023 and March 2023. ParticipantsPaediatric physicians and nurses. InterventionsNone. Primary and secondary outcome measuresThe questionnaire contained 35 items across four dimensions (demographic information, knowledge, attitude and practice). ResultsThe study included 295 participants (173 women). The average knowledge, attitude and practice scores were 10.93±2.61 points (possible range, 0–20 points), 32.22±2.65 points (possible range, 7–35 points) and 36.54±5.24 points (possible range, 9–45 points), respectively. Knowledge had a direct influence on both attitude (β=0.240, 95% CI 0.136 to 0.365, p=0.009) and practice (β=0.278, 95% CI 0.084 to 0.513, p=0.010), which also indirectly influenced practice through attitude (β=0.162, 95% CI 0.078 to 0.290, p=0.007). Attitude directly influenced practice (β=0.677, 95% CI 0.384 to 0.902, p=0.025). A higher attitude score was associated with good practice (OR=1.392; 95% CI 1.231 to 1.576; p
Sepsis incidence, suspicion, prediction and mortality in emergency medical services: a cohort study related to the current international sepsis guideline
Infection, 26.02.2024
Tilføjet 26.02.2024
Abstract Purpose Sepsis suspicion by Emergency Medical Services (EMS) is associated with improved patient outcomes. This study assessed sepsis incidence and recognition by EMS and analyzed which of the screening tools recommended by the Surviving Sepsis Campaign best facilitates sepsis prediction. Methods Retrospective cohort study of claims data from health insurances (n = 221,429 EMS cases), and paramedics’ and emergency physicians’ EMS documentation (n = 110,419); analyzed outcomes were: sepsis incidence and case fatality compared to stroke and myocardial infarction, the extent of documentation for screening-relevant variables and sepsis suspicion, tools’ intersections for screening positive in identical EMS cases and their predictive ability for an inpatient sepsis diagnosis. Results Incidence of sepsis (1.6%) was similar to myocardial infarction (2.6%) and stroke (2.7%); however, 30-day case fatality rate was almost threefold higher (31.7% vs. 13.4%; 11.8%). Complete vital sign documentation was achieved in 8.2% of all cases. Paramedics never, emergency physicians rarely (0.1%) documented a sepsis suspicion, respectively septic shock. NEWS2 had the highest sensitivity (73.1%; Specificity:81.6%) compared to qSOFA (23.1%; Sp:96.6%), SIRS (28.2%; Sp:94.3%) and MEWS (48.7%; Sp:88.1%). Depending on the tool, 3.7% to 19.4% of all cases screened positive; only 0.8% in all tools simultaneously. Conclusion Incidence and mortality underline the need for better sepsis awareness, documentation of vital signs and use of screening tools. Guidelines may omit MEWS and SIRS as recommendations for prehospital providers since they were inferior in all accuracy measures. Though no tool performed ideally, NEWS2 qualifies as the best tool to predict the highest proportion of septic patients and to rule out cases that are likely non-septic.
Early Restrictive or Liberal Fluid Management for Sepsis-Induced Hypotension.
N Engl J Med 2023; 388(6):499-510
Shapiro NI, Douglas IS, Brower RG, Brown SM, Exline MC, Ginde AA, Gong MN, Grissom CK, Hayden D, Hough CL, Huang W, Iwashyna TJ, Jones AE, Khan A, Lai P, Liu KD, Miller CD, Oldmixon K, Park PK, Rice TW, Ringwood N, Semler MW, Steingrub JS, Talmor D, Thompson BT, Yealy DM, Self WH
Intravenous fluids and vasopressor agents are commonly used in early resuscitation of patients with sepsis, but comparative data for prioritizing their delivery are limited.
Restriction of Intravenous Fluid in ICU Patients with Septic Shock.
N Engl J Med 2022; 386(26):2459-2470
Meyhoff TS, Hjortrup PB, Wetterslev J, Sivapalan P, Laake JH, Cronhjort M, Jakob SM, Cecconi M, Nalos M, Ostermann M, Malbrain M, Pettilä V, Møller MH, Kjær MN, Lange T, Overgaard-Steensen C, Brand BA, Winther-Olesen M, White JO, Quist L, Westergaard B, Jonsson AB, Hjortsø CJS, Meier N, Jensen TS, Engstrøm J, Nebrich L, Andersen-Ranberg NC, Jensen JV, Joseph NA, Poulsen LM, Herløv LS, Sølling CG, Pedersen SK, Knudsen KK, Straarup TS, Vang ML, Bundgaard H, Rasmussen BS, Aagaard SR, Hildebrandt T, Russell L, Bestle MH, Schønemann-Lund M, Brøchner AC, Elvander CF, Hoffmann SKL, Rasmussen ML, Martin YK, Friberg FF, Seter H, Aslam TN, Ådnøy S, Seidel P, Strand K, Johnstad B, Joelsson-Alm E, Christensen J, Ahlstedt C, Pfortmueller CA, Siegemund M, Greco M, Raděj J, Kříž M, Gould DW, Rowan KM, Mouncey PR, Perner A
Intravenous fluids are recommended for the treatment of patients who are in septic shock, but higher fluid volumes have been associated with harm in patients who are in the intensive care unit (ICU).
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
4
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.
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).
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.
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.
Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and meta-analysis.
Lancet 2018; 391(10131):1693-1705
Chu DK, Kim LH, Young PJ, Zamiri N, Almenawer SA, Jaeschke R, Szczeklik W, Schünemann HJ, Neary JD, Alhazzani W
Supplemental oxygen is often administered liberally to acutely ill adults, but the credibility of the evidence for this practice is unclear. We systematically reviewed the efficacy and safety of liberal versus conservative oxygen therapy in acutely ill adults.
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).
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.
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.
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.
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.
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.
Freitag A, Constanti M, O'Flynn N, Faust SN
PMID: 27514867
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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.
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.
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.
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.
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.
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.
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.
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.
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.
Procalcitonin-guided interventions against infections to increase early appropriate antibiotics and improve survival in the intensive care unit: a randomized trial.
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.
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.
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
To define the terms "sepsis" and "organ failure" in a precise manner.