To evaluate the association of body temperature with mortality in septic patients admitted to the ICU from the ward. In addition, we intend to investigate whether the timing of antibiotic administration was different between febrile and afebrile patients and whether this difference contributed to mortality. This is a retrospective cohort study that included sepsis patients admitted to the ICU from the ward between July 2017 and July 2019. Antibiotic administration was defined as the initiation of antimicrobial treatment or the expansion of the antimicrobial spectrum within 48 h prior to admission to the ICU. Regarding vital signs, the most altered vital sign in the 48 h prior to admission to the ICU was considered. Two hundred and eight patients were included in the final analysis. Antibiotic administration occurred earlier in patients with fever than in patients without fever. Antibiotic administration occurred before admission to the ICU in 27 (90.0%) patients with fever and in 101 (64.7%) patients without fever (p = 0.006). The mortality rate in the ICU was 88 in 176 (50.0%; 95% CI 42.5-57.5%) patients without fever and 7 in 32 (21.9%; 95% CI 6.7-37.0%) patients with fever (p = 0.004). In the multivariate analysis, absence of fever significantly increased the risk of ICU mortality (OR 3.462; 95% CI 1.293-9.272). We found an inverse association between body temperature and mortality in patients with sepsis admitted to the ICU from the ward. Although antibiotic administration was earlier in patients with fever and precocity was associated with reduced mortality, the time of antibiotic administration did not fully explain the lower mortality in these patients. Weniger anzeigen

Kommentar zu: Brunkhorst FM, Weigand MA, Pletz M et al. (2020) S3-Leitlinie Sepsis – Prävention, Diagnose, Therapie und Nachsorge. Med Klin Intensivmed Notfmed 115:37–109. 10.1007/s00063-020-00685-0. Die aktualisierte deutsche S3-Leitlinie „Sepsis – Prävention, Diagnose, Therapie und Nachsorge“ (AWMF-Registernummer: 079-001) wurde am 12.03.2020 auf der Webseite der AWMF veröffentlicht und liegt inzwischen als Publikation vor. Der Prozess der Evidenz- und Konsensfindung wurde bereits im Dezember 2018 abgeschlossen und somit stellt die aktuelle Leitlinie den Stand vom 31.12.2018 dar. Weniger anzeigen

Objective: Sepsis and septic shock are major challenges and economic burdens to healthcare, impacting millions of people globally and representing significant causes of mortality. Recently, a large number of quality improvement programs focused on sepsis resuscitation bundles have been instituted worldwide. These educational initiatives have been shown to be associated with improvements in clinical outcomes. We aimed to evaluate the impact of a multi-faceted quality implementing program (QIP) on the compliance of a „simplified 1-h bundle“ (Sepsis 6) and hospital mortality of severe sepsis and septic shock patients out of the intensive care unit (ICU). Methods: Emergency departments (EDs) and medical wards (MWs) of 12 academic and non-academic hospitals in the Lombardy region (Northern Italy) were involved in a multi-faceted QIP, which included educational and organizational interventions. Patients with a clinical diagnosis of severe sepsis or septic shock according to the Sepsis-2 criteria were enrolled in two different periods: from May 2011 to November 2011 (before-QIP cohort) and from August 2012 to June 2013 (after-QIP cohort). Measurements and main results: The effect of QIP on bundle compliance and hospital mortality was evaluated in a before-after analysis. We enrolled 467 patients in the before-QIP group and 656 in the after-QIP group. At the time of enrollment, septic shock was diagnosed in 50% of patients, similarly between the two periods. In the after-QIP group, we observed increased compliance to the „simplified rapid (1 h) intervention bundle“ (the Sepsis 6 bundle – S6) at three time-points evaluated (1 h, 13.7 to 18.7%, p = 0.018, 3 h, 37.1 to 48.0%, p = 0.013, overall study period, 46.2 to 57.9%, p < 0.001). We then analyzed compliance with S6 and hospital mortality in the before- and after-QIP periods, stratifying the two patients' cohorts by admission characteristics. Adherence to the S6 bundle was increased in patients with severe sepsis in the absence of shock, in patients with serum lactate <4.0 mmol/L, and in patients with hypotension at the time of enrollment, regardless of the type of admission (from EDs or MWs). Subsequently, in an observational analysis, we also investigated the relation between bundle compliance and hospital mortality by logistic regression. In the after-QIP cohort, we observed a lower in-hospital mortality than that observed in the before-QIP cohort. This finding was reported in subgroups where a higher adherence to the S6 bundle in the after-QIP period was found. After adjustment for confounders, the QIP appeared to be independently associated with a significant improvement in hospital mortality. Among the single S6 procedures applied within the first hour of sepsis diagnosis, compliance with blood culture and antibiotic therapy appeared significantly associated with reduced in-hospital mortality. Conclusion: A multi-faceted QIP aimed at promoting an early simplified bundle of care for the management of septic patients out of the ICU was associated with improved compliance with sepsis bundles and lower in-hospital mortality. Weniger anzeigen

Fever can be viewed as an adaptive response to infection. Temperature control in sepsis is aimed at preventing potential harms associated with high temperature (tachycardia, vasodilation, electrolyte and water loss) and therapeutic hypothermia may be aimed at slowing metabolic activities and protecting organs from inflammation. Although high fever (>39.5°C) control is usually performed in critically ill patients, available cohorts and randomized controlled trials do not support its use to improve sepsis prognosis. Finally, both spontaneous and therapeutic hypothermia are associated with poor outcomes in sepsis. Keywords: antipyretics, body temperature, fever, prognosis, sepsis, septic shock Weniger anzeigen

Rationale: Sepsis often leads to long-term functional deficits and increased mortality in survivors. Post-acute rehabilitation can decrease long-term sepsis mortality, but its impact on nursing care dependency, health care use and costs is insufficiently understood. Objective: To assess the short-term (7-12 months post-discharge) and long-term (13-36 months post-discharge) effect of inpatient rehabilitation within six months after hospitalization on mortality, nursing care dependency, health care use and costs. Methods: Observational cohort study using health claims data from the health insurer AOK (Allgemeine Ortskrankenkasse). Among 24.3 million AOK beneficiaries, we identified adult beneficiaries hospitalized with sepsis in 2013/14 by explicit ICD-10 codes. We included patients who were non-employed pre-sepsis, for whom rehabilitation is reimbursed by the AOK and thus included in the dataset, and who survived at least six months post-discharge. The effect of rehabilitation was estimated by statistical comparisons of patients with rehabilitation (treatment group) and those without (reference group). Possible differential effects were investigated for the subgroup of Intensive Care Unit (ICU)-treated sepsis survivors. We used inverse probability of treatment weighting based on propensity scores to adjust for differences in relevant covariates. Costs for rehabilitation in the six months post-sepsis were not included in the costs analysis. Results: Among 41,918 six-months sepsis survivors, 17.2% (n=7,224) received rehabilitation. There was no significant difference in short-term survival between survivors with and without rehabilitation. Long-term survival rates were significantly higher in the rehabilitation group (90.4% vs. 88.7% (odds ratio [OR]=1.2 95% confidence interval [CI], 1.1-1.3) p=0.003)). Survivors with rehabilitation had a higher mean number of hospital readmissions (7-12 months after sepsis, 0.82 vs. 0.76, p=0.014) and were more frequently dependent on nursing care (7-12 and 13-36 months after sepsis, 47.8% vs. 42.3%, OR=1.2 (95% CI, 1.2-1.3), p<0.001, and 52.5% vs. 47.5%, OR=1.2 (95% CI, 1.1-1.3), p<0.001, respectively) compared to those without rehabilitation, while total health care costs 7-36 months did not differ between groups. ICU-treated sepsis patients with rehabilitation had higher short and long-term survival rates (93.5% vs. 90.9%, OR=1.5 (95% CI, 1.2-1.7), p<0.001; 89.1% vs. 86.3%, OR= 1.3 (95% CI, 1.1-1.5), p<0.001, respectively) than ICU-treated sepsis patients without rehabilitation. Conclusion: Rehabilitation within the first 6 months after ICU- and non-ICU treated sepsis is associated with increased long-term survival within three years after sepsis without added total health care costs. Future work should aim to confirm and explain these exploratory findings. Weniger anzeigen

Importance Some individuals experience persistent symptoms after initial symptomatic SARS-CoV-2 infection (often referred to as Long COVID). Objective To estimate the proportion of males and females with COVID-19, younger or older than 20 years of age, who had Long COVID symptoms in 2020 and 2021 and their Long COVID symptom duration. Design, Setting, and Participants Bayesian meta-regression and pooling of 54 studies and 2 medical record databases with data for 1.2 million individuals (from 22 countries) who had symptomatic SARS-CoV-2 infection. Of the 54 studies, 44 were published and 10 were collaborating cohorts (conducted in Austria, the Faroe Islands, Germany, Iran, Italy, the Netherlands, Russia, Sweden, Switzerland, and the US). The participant data were derived from the 44 published studies (10 501 hospitalized individuals and 42 891 nonhospitalized individuals), the 10 collaborating cohort studies (10 526 and 1906), and the 2 US electronic medical record databases (250 928 and 846 046). Data collection spanned March 2020 to January 2022. Exposures Symptomatic SARS-CoV-2 infection. Main Outcomes and Measures Proportion of individuals with at least 1 of the 3 self-reported Long COVID symptom clusters (persistent fatigue with bodily pain or mood swings; cognitive problems; or ongoing respiratory problems) 3 months after SARS-CoV-2 infection in 2020 and 2021, estimated separately for hospitalized and nonhospitalized individuals aged 20 years or older by sex and for both sexes of nonhospitalized individuals younger than 20 years of age. Results A total of 1.2 million individuals who had symptomatic SARS-CoV-2 infection were included (mean age, 4-66 years; males, 26%-88%). In the modeled estimates, 6.2% (95% uncertainty interval [UI], 2.4%-13.3%) of individuals who had symptomatic SARS-CoV-2 infection experienced at least 1 of the 3 Long COVID symptom clusters in 2020 and 2021, including 3.2% (95% UI, 0.6%-10.0%) for persistent fatigue with bodily pain or mood swings, 3.7% (95% UI, 0.9%-9.6%) for ongoing respiratory problems, and 2.2% (95% UI, 0.3%-7.6%) for cognitive problems after adjusting for health status before COVID-19, comprising an estimated 51.0% (95% UI, 16.9%-92.4%), 60.4% (95% UI, 18.9%-89.1%), and 35.4% (95% UI, 9.4%-75.1%), respectively, of Long COVID cases. The Long COVID symptom clusters were more common in women aged 20 years or older (10.6% [95% UI, 4.3%-22.2%]) 3 months after symptomatic SARS-CoV-2 infection than in men aged 20 years or older (5.4% [95% UI, 2.2%-11.7%]). Both sexes younger than 20 years of age were estimated to be affected in 2.8% (95% UI, 0.9%-7.0%) of symptomatic SARS-CoV-2 infections. The estimated mean Long COVID symptom cluster duration was 9.0 months (95% UI, 7.0-12.0 months) among hospitalized individuals and 4.0 months (95% UI, 3.6-4.6 months) among nonhospitalized individuals. Among individuals with Long COVID symptoms 3 months after symptomatic SARS-CoV-2 infection, an estimated 15.1% (95% UI, 10.3%-21.1%) continued to experience symptoms at 12 months. Conclusions and Relevance This study presents modeled estimates of the proportion of individuals with at least 1 of 3 self-reported Long COVID symptom clusters (persistent fatigue with bodily pain or mood swings; cognitive problems; or ongoing respiratory problems) 3 months after symptomatic SARS-CoV-2 infection. Keywords: COVID-19, Long COVID symptoms Weniger anzeigen

A subset of patients has long-lasting symptoms after mild to moderate Coronavirus disease 2019 (COVID-19). In a prospective observational cohort study, we analyze clinical and laboratory parameters in 42 post-COVID-19 syndrome patients (29 female/13 male, median age 36.5 years) with persistent moderate to severe fatigue and exertion intolerance six months following COVID-19. Further we evaluate an age- and sex-matched postinfectious non-COVID-19 myalgic encephalomyelitis/chronic fatigue syndrome cohort comparatively. Most post-COVID-19 syndrome patients are moderately to severely impaired in daily live. 19 post-COVID-19 syndrome patients fulfill the 2003 Canadian Consensus Criteria for myalgic encephalomyelitis/chronic fatigue syndrome. Disease severity and symptom burden is similar in post-COVID-19 syndrome/myalgic encephalomyelitis/chronic fatigue syndrome and non-COVID-19/myalgic encephalomyelitis/chronic fatigue syndrome patients. Hand grip strength is diminished in most patients compared to normal values in healthy. Association of hand grip strength with hemoglobin, interleukin 8 and C-reactive protein in post-COVID-19 syndrome/non-myalgic encephalomyelitis/chronic fatigue syndrome and with hemoglobin, N-terminal prohormone of brain natriuretic peptide, bilirubin, and ferritin in post-COVID-19 syndrome/myalgic encephalomyelitis/chronic fatigue syndrome may indicate low level inflammation and hypoperfusion as potential pathomechanisms. Keywords: epidemiology, post-COVID-19, chronic fatigue syndrome Weniger anzeigen

Sepsis is associated with 11 million global deaths annually. Although serious consequences of sepsis can generally be avoided with prevention and early detection, research has not yet addressed the efficacy of evidence-based health information formats for different risk groups. This study examines whether two evidence-based health information formats-text based and graphical-differ in how well they foster informed choice and risk and health literacy and in how well they support different sepsis risk groups. Based on a systematic literature review, two one-page educative formats on sepsis prevention and early detection were designed-one text based and one graphical. A sample of 500 German participants was randomly shown one of the two formats; they were then assessed on whether they made informed choices and on their risk and health literacy. For both formats, >70% of participants made informed choices for sepsis prevention and >75% for early detection. Compared with the graphical format, the text-based format was associated with higher degrees of informed choice (p = 0.012, OR = 1.818) and risk and health literacy (p = 0.032, OR = 1.710). Both formats can foster informed choices and risk and health literacy on sepsis prevention and early detection, but the text-based format appears to be more effective. Weniger anzeigen

Background Vilobelimab, an anti-C5a monoclonal antibody, was shown to be safe in a phase 2 trial of invasively mechanically ventilated patients with COVID-19. Here, we aimed to determine whether vilobelimab in addition to standard of care improves survival outcomes in this patient population. Methods This randomised, double-blind, placebo-controlled, multicentre phase 3 trial was performed at 46 hospitals in the Netherlands, Germany, France, Belgium, Russia, Brazil, Peru, Mexico, and South Africa. Participants aged 18 years or older who were receiving invasive mechanical ventilation, but not more than 48 h after intubation at time of first infusion, had a PaO2/FiO2 ratio of 60–200 mm Hg, and a confirmed SARS-CoV-2 infection with any variant in the past 14 days were eligible for this study. Eligible patients were randomly assigned (1:1) to receive standard of care and vilobelimab at a dose of 800 mg intravenously for a maximum of six doses (days 1, 2, 4, 8, 15, and 22) or standard of care and a matching placebo using permuted block randomisation. Treatment was not continued after hospital discharge. Participants, caregivers, and assessors were masked to group assignment. The primary outcome was defined as all-cause mortality at 28 days in the full analysis set (defined as all randomly assigned participants regardless of whether a patient started treatment, excluding patients randomly assigned in error) and measured using KaplanMeier analysis. Safety analyses included all patients who had received at least one infusion of either vilobelimab or placebo. This study is registered with ClinicalTrials.gov, NCT04333420. Findings From Oct 1, 2020, to Oct 4, 2021, we included 368 patients in the ITT analysis (full analysis set; 177 in the vilobelimab group and 191 in the placebo group). One patient in the vilobelimab group was excluded from the primary analysis due to random assignment in error without treatment. At least one dose of study treatment was given to 364 (99%) patients (safety analysis set). 54 patients (31%) of 177 in the vilobelimab group and 77 patients (40%) of 191 in the placebo group died in the first 28 days. The all-cause mortality rate at 28 days was 32% (95% CI 25–39) in the vilobelimab group and 42% (35–49) in the placebo group (hazard ratio 0·73, 95% CI 0·50–1·06; p=0·094). In the predefined analysis without site-stratification, vilobelimab significantly reduced all-cause mortality at 28 days (HR 0·67, 95% CI 0·48–0·96; p=0·027). The most common TEAEs were acute kidney injury (35 [20%] of 175 in the vilobelimab group vs 40 [21%] of 189 in the placebo), pneumonia (38 [22%] vs 26 [14%]), and septic shock (24 [14%] vs 31 [16%]). Serious treatment-emergent adverse events were reported in 103 (59%) of 175 patients in the vilobelimab group versus 120 (63%) of 189 in the placebo group. Interpretation In addition to standard of care, vilobelimab improves survival of invasive mechanically ventilated patients with COVID-19 and leads to a significant decrease in mortality. Vilobelimab could be considered as an additional therapy for patients in this setting and further research is needed on the role of vilobelimab and C5a in other acute respiratory distress syndrome-causing viral infections. Weniger anzeigen

Background: Sepsis is one of the leading causes of preventable deaths in hospitals. This study presents the evaluation of a quality collaborative, which aimed to decrease sepsis-related hospital mortality. Methods: The German Quality Network Sepsis (GQNS) offers quality reporting based on claims data, peer reviews, and support for establishing continuous quality management and staff education. This study evaluates the effects of participating in the GQNS during the intervention period (April 2016-June 2018) in comparison to a retrospective baseline (January 2014-March 2016). The primary outcome was all-cause risk-adjusted hospital mortality among cases with sepsis. Sepsis was identified by International Classification of Diseases (ICD) codes in claims data. A controlled time series analysis was conducted to analyze changes from the baseline to the intervention period comparing GQNS hospitals with the population of all German hospitals assessed via the national diagnosis-related groups (DRGs)-statistics. Tests were conducted using piecewise hierarchical models. Implementation processes and barriers were assessed by surveys of local leaders of quality improvement teams. Results: Seventy-four hospitals participated, of which 17 were university hospitals and 18 were tertiary care facilities. Observed mortality was 43.5% during baseline period and 42.7% during intervention period. Interrupted time-series analyses did not show effects on course or level of risk-adjusted mortality of cases with sepsis compared to the national DRG-statistics after the beginning of the intervention period (p = 0.632 and p = 0.512, respectively). There was no significant mortality decrease in the subgroups of patients with septic shock or ventilation >24 h or predefined subgroups of hospitals. A standardized survey among 49 local quality improvement leaders in autumn of 2018 revealed that most hospitals did not succeed in implementing a continuous quality management program or relevant measures to improve early recognition and treatment of sepsis. Barriers perceived most commonly were lack of time (77.6%), staff shortage (59.2%), and lack of participation of relevant departments (38.8%). Conclusion: As long as hospital-wide sepsis quality improvement efforts will not become a high priority for the hospital leadership by assuring adequate resources and involvement of all pertinent stakeholders, voluntary initiatives to improve the quality of sepsis care will remain prone to failure. Weniger anzeigen