Purpose: Sepsis contributes considerably to global morbidity and mortality, while reasons for its increasing incidence remain unclear. We assessed risk adjusted secular trends in sepsis and infection epidemiology in Germany. Methods: Retrospective cohort study using nationwide German hospital discharge data. We assessed incidence, outcomes and trends of hospital-treated sepsis and infections between 2010 and 2015. Sepsis was identified by explicit ICD-10 sepsis codes. As sensitivity analysis, results were compared with sepsis cases identified by implicit sepsis coding (combined infection and organ dysfunction codes). Results: Among 18 664 877 hospital admissions in 2015, 4 213 116 (22.6%) patients had at least one infection code. There were 320 198 patients that had explicit sepsis codes including 136 542 patients with severe sepsis and septic shock; 183 656 patients were coded as sepsis without organ dysfunction. For patients with explicitly coded sepsis (including severe sepsis), or with severe sepsis alone, mortality rates over the period 2010-2015 decreased from 26.6 to 23.5%, and from 47.8 to 41.7%, respectively. Conclusions: Sepsis and infection remain significant causes of hospital admission and death in Germany. Sepsis-related mortality is higher and has declined to a lesser degree than in other high-income countries. Although infection rates steadily increased, the observed annual increase of sepsis cases seems to result, to a considerable degree, from improved coding of sepsis. Weniger anzeigen

Objective: To investigate the impact of a quality improvement initiative for severe sepsis and septic shock focused on the resuscitation bundle on 90-day mortality. Furthermore, effects on compliance rates for antiinfective therapy within the recommended 1-hour interval are evaluated. Design: Prospective observational before-after cohort study. Setting: Tertiary university hospital in Germany. Patients: All adult medical and surgical ICU patients with severe sepsis and septic shock. Intervention: Implementation of a quality improvement program over 7.5 years. Measurements: The primary endpoint was 90-day mortality. Secondary endpoints included ICU and hospital mortality rates and length of stay, time to broad-spectrum antiinfective therapy, and compliance with resuscitation bundle elements. Main results: A total of 14,115 patients were screened. The incidence of severe sepsis and septic shock was 9.7%. Ninety-day mortality decreased from 64.2% to 45.0% (p < 0.001). Hospital length of stay decreased from 44 to 36 days (p < 0.05). Compliance with resuscitation bundle elements was significantly improved. Antibiotic therapy within the first hour after sepsis onset increased from 48.5% to 74.3% (p < 0.001). Multivariate analysis revealed blood cultures before antibiotic therapy (hazard ratio, 0.60-0.84; p < 0.001), adequate calculated antibiotic therapy (hazard ratio, 0.53-0.75; p < 0.001), 1-2 L crystalloids within the first 6 hours (hazard ratio 0.67-0.97; p = 0.025), and greater than or equal to 6 L during the first 24 hours (hazard ratio, 0.64-0.95; p = 0.012) as predictors for improved survival. Conclusions: The continuous quality improvement initiative focused on the resuscitation bundle was associated with increased compliance and a persistent reduction in 90-day mortality over a 7.5-year period. Based on the observational study design, a causal relationship cannot be proven, and respective limitations need to be considered. Weniger anzeigen

Purpose: Guidelines recommend administering antibiotics within 1 h of sepsis recognition but this recommendation remains untested by randomized trials. This trial was set up to investigate whether survival is improved by reducing the time before initiation of antimicrobial therapy by means of a multifaceted intervention in compliance with guideline recommendations. Methods: The MEDUSA study, a prospective multicenter cluster-randomized trial, was conducted from July 2011 to July 2013 in 40 German hospitals. Hospitals were randomly allocated to receive conventional continuous medical education (CME) measures (control group) or multifaceted interventions including local quality improvement teams, educational outreach, audit, feedback, and reminders. We included 4183 patients with severe sepsis or septic shock in an intention-to-treat analysis comparing the multifaceted intervention (n = 2596) with conventional CME (n = 1587). The primary outcome was 28-day mortality. Results: The 28-day mortality was 35.1% (883 of 2596 patients) in the intervention group and 26.7% (403 of 1587 patients; p = 0.01) in the control group. The intervention was not a risk factor for mortality, since this difference was present from the beginning of the study and remained unaffected by the intervention. Median time to antimicrobial therapy was 1.5 h (interquartile range 0.1-4.9 h) in the intervention group and 2.0 h (0.4-5.9 h; p = 0.41) in the control group. The risk of death increased by 2% per hour delay of antimicrobial therapy and 1% per hour delay of source control, independent of group assignment. Conclusions: Delay in antimicrobial therapy and source control was associated with increased mortality but the multifaceted approach was unable to change time to antimicrobial therapy in this setting and did not affect survival. Weniger anzeigen

Importance: Survivors of sepsis face long-term sequelae that diminish health-related quality of life and result in increased care needs in the primary care setting, such as medication, physiotherapy, or mental health care. Objective: To examine if a primary care-based intervention improves mental health-related quality of life. Design, setting, and participants: Randomized clinical trial conducted between February 2011 and December 2014, enrolling 291 patients 18 years or older who survived sepsis (including septic shock), recruited from 9 intensive care units (ICUs) across Germany. Interventions: Participants were randomized to usual care (n = 143) or to a 12-month intervention (n = 148). Usual care was provided by their primary care physician (PCP) and included periodic contacts, referrals to specialists, and prescription of medication, other treatment, or both. The intervention additionally included PCP and patient training, case management provided by trained nurses, and clinical decision support for PCPs by consulting physicians. Main outcomes and measures: The primary outcome was change in mental health-related quality of life between ICU discharge and 6 months after ICU discharge using the Mental Component Summary (MCS) of the 36-Item Short-Form Health Survey (SF-36 [range, 0-100; higher ratings indicate lower impairment; minimal clinically important difference, 5 score points]). Results: The mean age of the 291 patients was 61.6 years (SD, 14.4); 66.2% (n = 192) were men, and 84.4% (n = 244) required mechanical ventilation during their ICU stay (median duration of ventilation, 12 days [range, 0-134]). At 6 and 12 months after ICU discharge, 75.3% (n = 219 [112 intervention, 107 control]) and 69.4% (n = 202 [107 intervention, 95 control]), respectively, completed follow-up. Overall mortality was 13.7% at 6 months (40 deaths [21 intervention, 19 control]) and 18.2% at 12 months (53 deaths [27 intervention, 26 control]). Among patients in the intervention group, 104 (70.3%) received the intervention at high levels of integrity. There was no significant difference in change of mean MCS scores (intervention group mean at baseline, 49.1; at 6 months, 52.9; change, 3.79 score points [95% CI, 1.05 to 6.54] vs control group mean at baseline, 49.3; at 6 months, 51.0; change, 1.64 score points [95% CI, -1.22 to 4.51]; mean treatment effect, 2.15 [95% CI, -1.79 to 6.09]; P = .28). Conclusions and relevance: Among survivors of sepsis and septic shock, the use of a primary care-focused team-based intervention, compared with usual care, did not improve mental health-related quality of life 6 months after ICU discharge. Further research is needed to determine if modified approaches to primary care management may be more effective. Trial registration: isrctn.org Identifier: ISRCTN61744782. Weniger anzeigen

Objective: To implement a statewide program for the early recognition and treatment of sepsis in New South Wales, Australia. Setting: Ninety-seven emergency departments in NSW hospitals. Intervention: A quality improvement program (SEPSIS KILLS) that promoted intervention within 60 minutes of recognition, including taking of blood cultures, measuring serum lactate levels, administration of intravenous antibiotics, and fluid resuscitation. Main outcome measures: Time to antibiotics and fluid resuscitation; mortality rates and length of stay. Results: Data for 13 567 patients were entered into the database. The proportion of patients receiving intravenous antibiotics within 60 minutes of triage increased from 29.3% in 2009-2011 to 52.2% in 2013. The percentage for whom a second litre of fluid was started within 60 minutes rose from 10.6% to 27.5% (each P < 0.001). The proportion of patients classed as Australasian Triage Scale (ATS) 1 increased from 2.3% in 2009-2011 to 4.2% in 2013, and the proportion classed as ATS 2 rose from 40.7% in 2009-2011 to 60.7% in 2013 (P < 0.001). There was a linear decrease in mortality from 19.3% in 2009-2011 to 14.1% in 2013; there was also a significant decline in time in intensive care and total length of stay (each P < 0.0001). The mortality rate for patients with severe sepsis (serum lactate ≥ 4 mmol/L or systolic blood pressure [SBP] < 90 mmHg) was 19.7%. The mortality rates for patients with severe sepsis admitted to intensive care and for those admitted to a ward did not change significantly over time. The proportion of patients with uncomplicated sepsis (SBP ≥ 90 mmHg, serum lactate < 4 mmol/L) transferred to a ward increased, and the mortality rate after transfer increased from 3.2% in 2009-2011 to 6.2% in 2013 (P < 0.05). The survival benefit was greatest for patients with evidence of haemodynamic instability (SBP < 90 mmHg) but normal lactate levels (P = 0.03). Conclusions: The SEPSIS KILLS program has improved the process of care for patients with sepsis in NSW hospitals. The program has focused attention on sepsis management in the wards. Weniger anzeigen

Background: Although sepsis is a major health problem, data on sepsis epidemiology are scarce. The aim of this study was to assess the incidence of sepsis, based on clinical findings in all adult patients treated with intravenous antibiotic in all parts of all hospitals in an entire population. Methods: This is a retrospective chart review of patients ≥18 years, living in 2 regions in Sweden, who were started on an intravenous antibiotic therapy on 4 dates, evenly distributed over the year of 2015. The main outcome was the incidence of sepsis with organ dysfunction. The mean population ≥18 years at 2015 in the regions was 1275753. Five hundred sixty-three patients living in the regions were started on intravenous antibiotic treatment on the dates of the survey. Patients who had ongoing intravenous antibiotic therapy preceding the inclusion dates were excluded, if sepsis was already present. Results: Four hundred eighty-two patients were included in the study; 339 had a diagnosed infection, of those, 96 had severe sepsis according to the 1991/2001 sepsis definitions, and 109 had sepsis according to the sepsis-3. This is equivalent to an annual incidence of traditional severe sepsis of 687/100000 persons (95% confidence interval [CI], 549-824) or according to the sepsis-3 definition of 780/100000 persons (95% CI, 633-926). Seventy-four patients had sepsis according to both definitions. Conclusions: The incidence of sepsis with organ dysfunction is higher than most previous estimates independent of definition. The inclusion of all inpatients started on intravenous antibiotic treatment of sepsis in a population makes an accurate assessment of sepsis incidence possible. Keywords: SIRS., incidence, qSOFA, sepsis Weniger anzeigen

Purpose: To estimate the incidence density, point prevalence and outcome of severe sepsis and septic shock in German intensive care units (ICUs). Methods: In a prospective, multicentre, longitudinal observational study, all patients already on the ICU at 0:00 on 4 November 2013 and all patients admitted to a participating ICU between 0:00 on 4 November 2013 and 23:59 hours on 1 December 2013 were included. The patients were followed up for the occurrence of severe sepsis or septic shock (SEPSIS-1 definitions) during their ICU stay. Results: A total of 11,883 patients from 133 ICUs at 95 German hospitals were included in the study, of whom 1503 (12.6 %) were diagnosed with severe sepsis or septic shock. In 860 cases (57.2 %) the infections were of nosocomial origin. The point prevalence was 17.9 % (95 % CI 16.3-19.7). The calculated incidence rate of severe sepsis or septic shock was 11.64 (95 % CI 10.51-12.86) per 1000 ICU days. ICU mortality in patients with severe sepsis/septic shock was 34.3 %, compared with 6 % in those without sepsis. Total hospital mortality of patients with severe sepsis or septic shock was 40.4 %. Classification of the septic shock patients using the new SEPSIS-3 definitions showed higher ICU and hospital mortality (44.3 and 50.9 %). Conclusions: Severe sepsis and septic shock continue to be a frequent syndrome associated with high hospital mortality. Nosocomial infections play a major role in the development of sepsis. This study presents a pragmatic, affordable and feasible method for the surveillance of sepsis epidemiology. Implementation of the new SEPSIS-3 definitions may have a major effect on future epidemiological data. Weniger anzeigen

Objectives: To examine the frequency of acute stress disorder and posttraumatic stress disorder in chronically critically ill patients with a specific focus on severe sepsis, to classify different courses of stress disorders from 4 weeks to 6 months after transfer from acute care hospital to postacute rehabilitation, and to identify patients at risk by examining the relationship between clinical, demographic, and psychological variables and stress disorder symptoms. Design: Prospective longitudinal cohort study, three assessment times within 4 weeks, 3 months, and 6 months after transfer to postacute rehabilitation. Setting: Patients were consecutively enrolled in a large rehabilitation hospital (Clinic Bavaria, Kreischa, Germany) admitted for ventilator weaning from acute care hospitals. Patients: We included 90 patients with admission diagnosis critical illness polyneuropathy or critical illness myopathy with or without severe sepsis, age between 18 and 70 years with a length of ICU stay greater than 5 days. Interventions: None. Measurements and main results: Acute stress disorder and posttraumatic stress disorder were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, criteria by a trained and experienced clinical psychologist using a semistructured clinical interview for Diagnostic and Statistical Manual of Mental Disorders. We further administered the Acute Stress Disorder Scale and the Posttraumatic Symptom Scale-10 to assess symptoms of acute stress disorder and posttraumatic stress disorder. Three percent of the patients had an acute stress disorder diagnosis 4 weeks after transfer to postacute rehabilitation. Posttraumatic stress disorder was found in 7% of the patients at 3-month follow-up and in 12% after 6 months, respectively. Eighteen percent of the patients showed a delayed onset of posttraumatic stress disorder. Sepsis turned out to be a significant predictor of posttraumatic stress disorder symptoms at 3-month follow-up. Conclusions: A regular screening of post-ICU patients after discharge from hospital should be an integral part of aftercare management. The underlying mechanisms of severe sepsis in the development of posttraumatic stress disorder need further examination. Weniger anzeigen

Background: 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. Methods: We conducted a pragmatic randomized trial with an integrated cost-effectiveness analysis in 56 hospitals in England. Patients were randomly assigned to receive either EGDT (a 6-hour resuscitation protocol) or usual care. The primary clinical outcome was all-cause mortality at 90 days. Results: We enrolled 1260 patients, with 630 assigned to EGDT and 630 to usual care. By 90 days, 184 of 623 patients (29.5%) in the EGDT group and 181 of 620 patients (29.2%) in the usual-care group had died (relative risk in the EGDT group, 1.01; 95% confidence interval [CI], 0.85 to 1.20; P=0.90), for an absolute risk reduction in the EGDT group of -0.3 percentage points (95% CI, -5.4 to 4.7). Increased treatment intensity in the EGDT group was indicated by increased use of intravenous fluids, vasoactive drugs, and red-cell transfusions and reflected by significantly worse organ-failure scores, more days receiving advanced cardiovascular support, and longer stays in the intensive care unit. There were no significant differences in any other secondary outcomes, including health-related quality of life, or in rates of serious adverse events. On average, EGDT increased costs, and the probability that it was cost-effective was below 20%. Conclusions: In patients with septic shock who were identified early and received intravenous antibiotics and adequate fluid resuscitation, hemodynamic management according to a strict EGDT protocol did not lead to an improvement in outcome. (Funded by the United Kingdom National Institute for Health Research Health Technology Assessment Programme; ProMISe Current Controlled Trials number, ISRCTN36307479.). Weniger anzeigen

Background: Several reports suggest that implementation of the Surviving Sepsis Campaign (SSC) guidelines is associated with mortality reduction in sepsis. However, adherence to the guideline-based resuscitation and management sepsis bundles is still poor. Objective: To perform a systematic review of studies evaluating the impact of performance improvement programs on compliance with Surviving Sepsis Campaign (SSC) guideline-based bundles and/or mortality. Data sources: Medline (PubMed), Scopus and Intercollegiate Studies Institute Web of Knowledge databases from 2004 (first publication of the SSC guidelines) to October 2014. Study selection: Studies on adult patients with sepsis, severe sepsis or septic shock that evaluated changes in compliance to individual/combined bundle targets and/or mortality following the implementation of performance improvement programs. Interventions may consist of educational programs, process changes or both. Data extraction: Data from the included studies were extracted independently by two authors. Unadjusted binary data were collected in order to calculate odds ratios (OR) for compliance to individual/combined bundle targets. Adjusted (if available) or unadjusted data of mortality were collected. Random-effects models were used for the data synthesis. Results: Fifty observational studies were selected. Despite high inconsistency across studies, performance improvement programs were associated with increased compliance with the complete 6-hour bundle (OR = 4.12 [95% confidence interval 2.95-5.76], I(2) = 87.72%, k = 25, N = 50,081) and the complete 24-hour bundle (OR = 2.57 [1.74-3.77], I(2) = 85.22%, k = 11, N = 45,846) and with a reduction in mortality (OR = 0.66 [0.61-0.72], I(2) = 87.93%, k = 48, N = 434,447). Funnel plots showed asymmetry. Conclusions: Performance improvement programs are associated with increased adherence to resuscitation and management sepsis bundles and with reduced mortality in patients with sepsis, severe sepsis or septic shock. Weniger anzeigen