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Reducing the global burden of sepsis, a recognized global health challenge, requires comprehensive data on the incidence and mortality on a global scale. To estimate the worldwide incidence and mortality of sepsis and identify knowledge gaps based on available evidence from observational studies. We systematically searched 15 international citation databases for population-level estimates of sepsis incidence rates and fatality in adult populations using consensus criteria and published in the last 36 years. The search yielded 1,553 reports from 1979 to 2015, of which 45 met our criteria. A total of 27 studies from seven high-income countries provided data for metaanalysis. For these countries, the population incidence rate was 288 (95% confidence interval [CI], 215-386; τ = 0.55) for hospital-treated sepsis cases and 148 (95% CI, 98-226; τ = 0.99) for hospital-treated severe sepsis cases per 100,000 person-years. Restricted to the last decade, the incidence rate was 437 (95% CI, 334-571; τ = 0.38) for sepsis and 270 (95% CI, 176-412; τ = 0.60) for severe sepsis cases per 100,000 person-years. Hospital mortality was 17% for sepsis and 26% for severe sepsis during this period. There were no population-level sepsis incidence estimates from lower-income countries, which limits the prediction of global cases and deaths. However, a tentative extrapolation from high-income country data suggests global estimates of 31.5 million sepsis and 19.4 million severe sepsis cases, with potentially 5.3 million deaths annually. Population-level epidemiologic data for sepsis are scarce and nonexistent for low- and middle-income countries. Our analyses underline the urgent need to implement global strategies to measure sepsis morbidity and mortality, particularly in low- and middle-income countries.

Gelatin is a widely used synthetic colloid resuscitation fluid. We undertook a systematic review and meta-analysis of adverse effects in randomized and nonrandomized studies comparing gelatin with crystalloid or albumin for treatment of hypovolemia. Multiple databases were searched systematically without language restrictions until August 2015. We assessed risk of bias of individual studies and certainty in evidence assessment by the Grading of Recommendations Assessment, Development, and Evaluation approach. Sixty studies were eligible, including 30 randomized controlled trials, 8 nonrandomized studies, and 22 animal studies. After gelatin administration, the risk ratios were 1.15 (95% confidence interval, 0.96-1.38) for mortality, 1.10 (0.86-1.41) for requiring allogeneic blood transfusion, 1.35 (0.58-3.14) for acute kidney injury, and 3.01 (1.27-7.14) for anaphylaxis. Well-performed nonrandomized trials found increased rates of hospital mortality and acute kidney injury or renal replacement therapy in the gelatin intervention periods. Between 17% and 31% of administered gelatin was taken up extravascularly. The mean crystalloid-to-colloid ratio was 1.4. Gelatin solutions increase the risk of anaphylaxis and may be harmful by increasing mortality, renal failure, and bleeding possibly due to extravascular uptake and coagulation impairment. Until well-designed randomized controlled trials show that gelatin is safe, we caution against the use of gelatins because cheaper and safer fluid alternatives are available.

Purpose Hydroxyethyl starch solutions (HES) are plasma volume expanders which affect hemostasis. Newer HES 130/0.4 is said to be safer. Reevaluation of published evidence is necessary after the recent retraction of studies. Methods Systematic review of studies assessing HES 130/0.4 effects on hemostasis by thrombelastography (TEG, ROTEM) or Sonoclot (SCR) in comparison with crystalloid or albumin control fluids was performed. Only studies which provided statistical comparisons between study fluids were analyzed. Studies were divided into in vitro or in vivo hemodilution studies. We assessed study quality, HES effects which differed significantly from controls, values outside normal range, degree of hemodilution, and cumulative HES dose. Results Seventeen in vitro and seven in vivo hemodilution studies were analyzed. Four studies reported quality control measures. Nineteen studies (all 15 ROTEM studies, 3 of 5 in vitro TEG, and 1 of 2 SCR studies) showed a significant hypocoagulatory effect of HES 130/0.4 on clot formation, while clotting time was not uniformly affected. Three in vivo TEG studies with low HES doses or cancer patients found mixed or nonsignificant results. In studies which provided normal ranges ( n  = 9), more values were outside normal ranges in the HES than in the control groups (87/122 vs. 58/122, p  < 0.001). Dose effects were apparent in the in vitro studies, which investigated higher dilutions up to 80%. In vivo studies were fewer and did not investigate doses >40 ml/kg. Conclusions HES 130/0.4 administration results in a weaker and smaller clot. Until results from well-designed clinical trials are available, safer fluids should be chosen for patients with impaired coagulation.

The purpose of the study was to determine whether treatment preferences in patients' advance directives (ADs) are associated with life-supporting treatments received during end-of-life care in the intensive care unit (ICU). This is a retrospective cohort study, including patients who died in 4 ICUs of a university hospital in Germany. Patients with ADs were matched with 2 patients each without ADs using propensity scores. Sixty-four (13%) of 477 patients had ADs, written a median of 109 weeks before admission. Five categories of applicability conditions were identified, most of them difficult to interpret in the ICU (eg, “advanced brain impairment” or “imminent death”). Advance directives contained a number of treatment refusals. Specifically, 63 of 64 refused “life-sustaining measures.” Compared to patients without ADs, patients with ADs were less likely to receive cardiopulmonary resuscitation (9% vs 23%, P = .029) and more likely to have do-not-resuscitate orders (77% vs 56%, P = .007). Therapy-limiting decisions and ICU length of stay did not differ between those with or without ADs. Patients with ADs are less likely to receive cardiopulmonary resuscitation but otherwise receive similar life-sustaining treatments compared to matched patients without ADs. More research is needed to explore reasons for potential noncompliance with patient preferences.

Aims Worldwide applications of extracorporeal circulation for mechanical support in cardiac and circulatory failure, which are referred to as extracorporeal life support (ECLS) or veno‐arterial extracorporeal membrane oxygenation (va‐ECMO), have dramatically increased over the past decade. In spite of the expanding use and the immense medical as well as socio‐economic impact of this therapeutic approach, there has been a lack of interdisciplinary recommendations considering the best available evidence for ECLS treatment. Methods and Results In a multiprofessional, interdisciplinary scientific effort of all scientific societies involved in the treatment of patients with acute cardiac and circulatory failure, the first evidence‐ and expert consensus‐based guideline (level S3) on ECLS/ECMO therapy was developed in a structured approach under regulations of the AWMF (Association of the Scientific Medical Societies in Germany) and under use of GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria. This article presents all recommendations created by the expert panel, addressing a multitude of aspects for ECLS initiation, continuation, weaning and aftercare as well as structural and personnel requirements. Conclusions This first evidence‐ and expert consensus‐based guideline (level S3) on ECLS/ECMO therapy should be used to apply the best available care nationwide. Beyond clinical practice advice, remaining important research aspects for future scientific efforts are formulated.

Sepsis survivors often suffer from new morbidities. Current rehabilitation therapies are not tailored to their specific needs. The perspective of sepsis survivors and their caregivers on rehabilitation and aftercare is insufficiently understood. We aimed to assess how sepsis survivors in Germany rated the suitability, extent and satisfaction with rehabilitation therapies that they underwent in the year following the acute sepsis episode. Prospective mixed-methods, multicenter study among a cohort of adult ICU-treated sepsis survivors and their caregivers. Interviews were conducted 6 and 12 months after ICU discharge by telephone and comprised closed as well as open-ended questions. Primary outcomes were the utilization and patient satisfaction with inpatient and outpatient rehabilitation and post-sepsis aftercare in general. Open-ended questions were analyzed according to the principles of content analysis. Foun hundred interviews were performed with 287 patients and/or relatives. At 6 months after sepsis, 85.0% of survivors had applied for and 70.0% had undergone rehabilitation. Among these, 97% received physical therapy, but only a minority reported therapies for specific ailments including pain, weaning from mechanical ventilation, cognitive deficits of fatigue. Survivors were moderately satisfied with the suitability, extent, and overall results of received therapies and perceived deficits in the timeliness, accessibility, and specificity of therapies as well as deficits in the structural support frameworks and patient education. From the perspective of survivors who undergo rehabilitation, therapies should already begin in hospital, be more appropriate for their specific ailments and include better patient and caregiver education. The general aftercare and structural support framework should be improved.

Long-term impairments after sepsis can impede the return to work in survivors. We aimed to describe rates of return to work 6 and 12 months postsepsis. This retrospective, population-based cohort study was based on health claims data of the German AOK health insurance of 23.0 million beneficiaries. We included 12-months survivors after hospital-treated sepsis in 2013/2014, who were ≤60 years at the time of the admission and were working in the year presepsis. We assessed the prevalence of return to work (RTW), persistent inability to work and early retirement. Among 7,370 working age sepsis survivors, 69.2% returned to work at 6 months postsepsis, while 22.8% were on sick leave and 8.0% retired early. At 12 months postsepsis, the RTW rate increased to 76.9%, whereas 9.8% were still on sick leave and 13.3% retired early. Survivors who returned to work had a mean of 70 (SD 93) sick leave days in the 12 months presepsis (median 28 days, IQR 108 days). One out of four working age sepsis survivors does not resume work in the year postsepsis. Specific rehabilitation and targeted aftercare may be opportunities to reduce barriers to RTW after sepsis.

PurposeThe Mid-German Sepsis Cohort (MSC) aims to investigate mid-term and long-term functional disabilities in sepsis survivors from intensive care unit (ICU) discharge until 1 year after. Secondary, post-acute mortality and morbidity, health-related quality of life and healthcare utilisation will be investigated.ParticipantsThe MSC comprises adult (aged ≥18 years) patients who were treated for (severe) sepsis or septic shock on ICU. The participants were recruited between 15 April 2016 and 30 November 2018 from five German centres. Three thousand two hundred and ten patients with sepsis were identified, of which 1968 survived their ICU stay and were eligible for enrolment in the follow-up cohort. Informed consent for follow-up assessment was provided by 907 patients (46.1% of eligible patients).Findings to dateThe recruitment of the participants for follow-up assessments and the baseline data collection is completed. Incidence of sepsis was 116.7 patients per 1000 ICU patients. In this cohort profile, we provide an overview of the demographics and the clinical characteristics of both the overall sepsis cohort and the ICU survivors who provided informed consent for follow-up assessment (907 out of 1968 ICU survivors (46.1%)).Future plansThe follow-ups are conducted 3, 6 and 12 months after ICU discharge. Another yearly follow-up up to 5 years after ICU discharge is pursued. Several cooperation and satellite projects were initiated. This prospective cohort offers a unique resource for research on long-term sequelae of sepsis survivors.Trial registration numberGerman Clinical Trials Registry (DRKS00010050).

Sepsis survival is associated with adverse outcomes. Knowledge about risk factors for adverse outcomes is lacking. We performed a population-based cohort study of 116,507 survivors of hospital-treated sepsis identified in health claims data of a German health insurance provider. We determined the development and risk factors for long-term adverse events: new dependency on chronic care, chronic dialysis, long-term respiratory support, and 12-month mortality. At-risk patients were defined by absence of these conditions prior to sepsis. Risk factors were identified using simple and multivariable logistic regression analyses. In the first year post-sepsis, 48.9% (56,957) of survivors had one or more adverse outcome, including new dependency on chronic care (31.9%), dialysis (2.8%) or respiratory support (1.6%), and death (30.7%). While pre-existing comorbidities adversely affected all studied outcomes (>4 comorbidities: OR 3.2 for chronic care, OR 4.9 for dialysis, OR 2.7 for respiratory support, OR 4.7 for 12-month mortality), increased age increased the odds for chronic care dependency and 12-month mortality, but not for dialysis or respiratory support. Hospital-acquired and multi-resistant infections were associated with increased risk of chronic care dependency, dialysis, and 12-month mortality. Multi-resistant infections also increased the odds of respiratory support. Urinary or respiratory infections or organ dysfunction increased the odds of new dialysis or respiratory support, respectively. Central nervous system infection and organ dysfunction had the highest OR for chronic care dependency among all infections and organ dysfunctions. Our results imply that patient- and infection-related factors have a differential impact on adverse life changing outcomes after sepsis. There is an urgent need for targeted interventions to reduce the risk.