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In view of the globally evolving coronavirus disease (COVID-19) pandemic, German hospitals rapidly expanded their intensive care capacities. However, it is possible that even with an optimal use of the increased resources, these will not suffice for all patients in need. Therefore, recommendations for the allocation of intensive care resources in the context of the COVID-19 pandemic have been developed by a multidisciplinary group of authors with the support of eight scientific medical societies. The recommendations for procedures and criteria for prioritisations in case of resource scarcity are based on scientific evidence, ethicolegal considerations and practical experience. Medical decisions must always be based on the need and the treatment preferences of the individual patient. In addition to this patient-centred approach, prioritisations in case of resource scarcity require a supraindividual perspective. In such situations, prioritisations should be based on the criterion of clinical prospect of success in order to minimize the number of preventable deaths due to resource scarcity and to avoid discrimination based on age, disabilities or social factors. The assessment of the clinical prospect of success should take into account the severity of the current illness, severe comorbidities and the patient’s general health status prior to the current illness.

The number of patients who survive sepsis is growing. However, two of three sepsis survivors suffer from new physical or mental sequelae. Cognitive deficits, depression or limitations of the activities of daily living can seriously impair quality of life and working ability. Sepsis sequelae cover a range of lesions; current rehabilitation therapies appear unsuited because they are focused on only one organ system. An interdisciplinary approach is necessary to evaluate and treat sepsis sequelae. Survivors and their relatives should be informed about sepsis and possible sequelae as early as possible. Further studies are needed to improve the understanding of pathomechanisms and effectivity of treatment interventions for sepsis sequelae.

PurposeTo quantify the frequency and co-occurrence of new diagnoses consistent with post-sepsis morbidity, mortality, new nursing care dependency, and total healthcare costs after sepsis.MethodsPopulation-based cohort study using healthcare claims data from 23 million beneficiaries of a German health insurance provider. We included adult patients with incident hospital-treated sepsis identified by ICD-10 codes in 2013-2014. New medical, psychological and cognitive diagnoses associated with post-sepsis morbidity; mortality; dependency on nursing care; and total health care costs in survivors were assessed to 3 years after hospital discharge.ResultsAmong 116,507 sepsis patients who survived hospitalization for sepsis, 74.3% had a new medical, psychological or cognitive diagnosis in the first year after discharge. 20.6% and 3.8% had new diagnoses in two and three domains, respectively. 31.5% were newly dependent on nursing care, and 30.7% died within the first year. In the second and third year, 65.8% and 59.4% of survivors had new diagnoses, respectively. Healthcare costs totaled an average 36,585 Euro/patient in three years, including index hospitalization costs. Occurrence of new diagnoses in predefined subgroups was: 73.7% (survivors of non-severe sepsis), 75.6% (severe sepsis), 78.3% (ICU-treated sepsis), 72.8% (non-ICU treated sepsis) and 68.5% (survivors without prior diagnoses).ConclusionsNew medical, psychological and cognitive diagnoses consistent with post-sepsis morbidity are common after sepsis, including among patients with less severe sepsis, no prior diagnoses, and younger age. This calls for more efforts to elucidate the underlying mechanisms, define optimal screening for common new diagnoses, and test interventions to prevent and treat post-sepsis morbidity.Trial RegistrationDRKS00016340Take home messageThis large population-based cohort of over 100,000 survivors of hospital-treated sepsis found high rates and a broad spectrum of new diagnoses consistent with post-sepsis morbidity, frequent new nursing care dependency, and high long-term mortality 1-3 years post sepsis. Post-sepsis morbidity was not limited to the oldest survivors or those with the most severe illness, but also affected younger survivors and those without pre-existing diagnoses.

BACKGROUND: The role of intensive insulin therapy in patients with severe sepsis is uncertain. Fluid resuscitation improves survival among patients with septic shock, but evidence is lacking to support the choice of either crystalloids or colloids. METHODS: In a multicenter, two-by-two factorial trial, we randomly assigned patients with severe sepsis to receive either intensive insulin therapy to maintain euglycemia or conventional insulin therapy and either 10% pentastarch, a low-molecular-weight hydroxyethyl starch (HES 200/0.5), or modified Ringer's lactate for fluid resuscitation. The rate of death at 28 days and the mean score for organ failure were coprimary end points. RESULTS: The trial was stopped early for safety reasons. Among 537 patients who could be evaluated, the mean morning blood glucose level was lower in the intensive-therapy group (112 mg per deciliter [6.2 mmol per liter]) than in the conventional-therapy group (151 mg per deciliter [8.4 mmol per liter], P

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. Electronic supplementary material The online version of this article (10.1007/s00134-018-5377-4) contains supplementary material, which is available to authorized users.

Hydroxyethyl starch is a colloid plasma expander that has recently been reviewed by the European Medicines Agency (EMA) following safety concerns in critically ill patients or in patients with sepsis. The EMA decided to restrict HES use in these patients but continues to allow its use in surgical and trauma patients who suffer from hypovolemia due to blood loss that cannot be corrected by crystalloids alone. This narrative review explains the basis for initial approval of HES, the presumed action of HES as plasma expander, and the mechanisms of its adverse effects on coagulation and on extravascular tissue uptake, especially in the kidneys with resulting renal failure, and presents an overview of recent important studies with a focus on surgery and trauma. No definitive, large-scale randomized controlled trials with patient-relevant outcomes and long-term follow-up exist in this population. Existing studies provide no assurance of a lower risk of coagulopathy, mortality, or kidney failure than in other critically ill patients. There are sufficient data to suggest that HES has similar risks also in these patients and should therefore be avoided.

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.

OBJECTIVE In this study, we aim to describe the post-sepsis syndrome from the perspective of the sepsis survivors. DESIGN AND SETTING The study is a prospective, observational online international survey. PARTICIPANTS Sepsis survivors enrolled via social media from 13 September 2014 to 13 September 2016. INTERVENTIONS None. MAIN OUTCOME MEASURES Physiologic, physical and psychological function post-sepsis; and patient satisfaction with sepsis-centered care. RESULTS 1731 completed surveys from 41 countries were analyzed, with 79.9% female respondents, age 47.6 ± 14.4 years. The majority of respondents (47.8%) had sepsis within the last year. Survivors reported an increase in sensory, integumentary, digestive, breathing, chest pain, kidney and musculoskeletal problems after sepsis (all P-value

Early detection and rapid treatment of tissue hypoxia are important goals. Venous oxygen saturation is an indirect index of global oxygen supply-to-demand ratio. Central venous oxygen saturation (ScvO2) measurement has become a surrogate for mixed venous oxygen saturation (SvO2). ScvO2 is measured by a catheter placed in the superior vena cava. After results from a single-center study suggested that maintaining ScvO2 values >70% might improve survival rates in septic patients, international practice guidelines included this target in a bundle strategy to treat early sepsis. However, a recent multicenter study with >1500 patients found that the use of central hemodynamic and ScvO2 monitoring did not improve long-term survival when compared to the clinical assessment of the adequacy of circulation. It seems that if sepsis is recognized early, a rapid initiation of antibiotics and adequate fluid resuscitation are more important than measuring venous oxygen saturation.

Background:Patients with sepsis syndrome commonly have low serum selenium levels. Several randomized controlled trials have examined the efficacy of selenium supplementation on mortality in patients with sepsis.Objective:To determine the efficacy and safety of high-dose selenium supplementation comp

Sepsis, the most severe manifestation of acute infection, can cause multi-organ failure and ends in death in 30–50% of cases (1, 2). According to the National Center for Health Statistics, the annual incidence of sepsis in the USA rose by 7–8% per year over a period of 8 years, from 221/100 000 persons in 2000 to 377/100 000 persons in 2008 (3). Despite a continual decline in mortality (4), more than 200 000 persons died of sepsis in the USA in 2007 (5). Sepsis is thus much more common in the USA than myocardial infarction, breast cancer, or colon cancer (6, 7). In 2011, sepsis took first place on the list of the most expensive disease conditions in the USA, with annual hospital costs of $22.2 billion (8). The rising incidence of documented cases of sepsis has been attributed to demographic changes, with a larger population of elderly, multimorbid patients, and to the expansion of treatment with drugs and with invasive medical and intensive-care measures that weaken the immune response (9). Increased coding of sepsis due to increased awareness and financial incentives associated with sepsis coding has also been mentioned as a possible cause (10). No aggregate data on sepsis are given in the health reports of the German Federal Ministry of Health (11). The reported data concern only the frequency of pathogen-based sepsis codes, even though clinical sepsis codes—R65.0! (sepsis), R65.1! (severe sepsis), and R57.2 (septic shock)—have been included in the World Health Organization’s International Classification of Diseases (ICD-10) since 2005 (the last of these three was included in 2010). The reason for including clinical codes was that a pathogen can be identified by blood culture in no more than 30–40% of patients with sepsis (1). Clinical criteria, in addition to microbiological criteria, have provided the basis for epidemiological studies of sepsis since the 1990s (2, 12). Because of the lack of robust data for Germany, the German Sepsis Competence Network (SEPNET) carried out a point-prevalence study in 2003 to estimate the incidence of sepsis in Germany according to the abovementioned criteria (2). Data were collected only from intensive care units and concerned only patients with severe sepsis; thus, cases of sepsis without organ dysfunction, most of which were treated on regular hospital wards rather than intensive care units (ICUs), were not recorded, and their incidence could only be roughly estimated. With this limitation, the study revealed 154 000 cases of sepsis and about 60 000 deaths from sepsis in 2003. A DRG system (DRG, diagnosis related groups) was introduced in Germany in 2004; since then, German hospitals have been required to report their patients’ ICD-coded diagnoses on discharge to an administrative body that oversees the hospital reimbursement system (Institut fur das Entgeltsystem im Krankenhaus, InEK). These data are then released in summarized form by the Federal Statistical Office in the form of diagnosis-related hospital statistics (DRG statistics). The purpose of our study is to use data from this source to examine secular trends in the incidence and mortality of sepsis over the years 2007–2013. The use of hospital discharge diagnoses enabled us to obtain nationwide epidemiological data on sepsis not only for intensive-care patients, but also for patients treated on regular hospital wards. Thus, the data we analyzed are not only representative for the entire country, but also take account of the many patients with sepsis (and even severe sepsis) who are treated on a regular ward rather than an ICU.

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.

Objectives: Hydroxyethyl starch 200 is associated with renal impairment in sepsis, but hydroxyethyl starch 130/0.4 and gelatin are considered to be less harmful. We hypothesized that fluid therapy with only crystalloids would decrease the incidence of acute kidney injury. Design: Prospective sequential comparison during intensive care unit stay. Setting: Surgical intensive care unit. Patients: Patients with severe sepsis. Interventions: Changes in standard fluid therapy, with predominantly 6% hydroxyethyl starch from January 2005 to June 2005, 4% gelatin from January 2006 to June 2006, and only crystalloids from September 2008 to June 2009. Measurements and Main Results: Acute kidney injury was defined by the presence of at least one RIFLE class; 118 patients received hydroxyethyl starch, 87 patients received gelatin, 141 patients received only crystalloids. Baseline serum creatinine values were similar. Patients received median cumulative doses of 46 (interquartile range, 18–92) mL/kg hydroxyethyl starch and 43 (interquartile range, 18–76) mL/kg gelatin. Total median fluid amounts were 649 (interquartile range, 275–1098) mL/kg in the hydroxyethyl starch group, 525 (237–868) mL/kg in the gelatin group, and 355 (173–911) mL/kg in the crystalloid group. The difference was statistically significant for hydroxyethyl starch after adjustment for multiple testing. Mean daily fluid intake and fluid balance were higher on days 0 and 1 in the crystalloid group. Acute kidney injury occurred in 70% of patients receiving hydroxyethyl starch (adjusted p = .002) and in 68% of patients receiving gelatin (adjusted p = .025) vs. 47% patients receiving crystalloids. Need for renal replacement therapy tended to be higher in the hydroxyethyl starch group (34%; adjusted p = .086) and in the gelatin group (34%; adjusted p = .162) in comparison to the crystalloid group (20%). Intensive care unit and hospital mortality were similar in each group (hydroxyethyl starch: 35% and 43%; gelatin: 26% and 31%; crystalloids: 30% and 37%). Conclusion: Fluid resuscitation with only crystalloids was equally effective, resulted in a more positive fluid balance only on the first 2 days, and was associated with a lesser incidence of acute kidney injury.

To describe the risk–benefit profile of hydroxyethyl starch (HES). Narrative review. (1) Efficacy: no single clinical study or systemic review has shown that administration of any HES solution confers a clinically relevant benefit compared to crystalloids in critically ill patients or surgical patients in need of volume replacement. Contrary to beliefs expecting a ratio of 4:1 or more for crystalloid to colloid volume need, recent studies of goal-directed resuscitation observed much lower ratios of between 1 and 1.6. (2) Safety: HES administration is associated with coagulopathy, nephrotoxicity, pruritus and increased long-term mortality. Clinical studies claiming that modern HES 130/0.4 is safe have serious methodological drawbacks and do not adequately address the safety concerns. Given the complete lack of superiority in clinical utility studies and the wide spectrum of severe side effects, the use of HES in the ICU should be stopped. The belief that four times as much crystalloid as colloid fluid volume is needed for successful resuscitation is being seriously questioned.

Sepsis is a life-threatening condition following acute infections. It is a global public health disaster. in Germany, epidemiological data on incidence, mortality and costs of sepsis is scarce.

IntroductionAn increasing number of patients survive sepsis; however, we lack valid data on the long-term impact on morbidity from prospective observational studies. Therefore, we designed an observational cohort to quantify mid-term and long-term functional disabilities after intensive care unit (ICU)-treated sepsis. Ultimately, findings for the Mid-German Sepsis Cohort (MSC) will serve as basis for the implementation of follow-up structures for patients with sepsis and help to increase quality of care for sepsis survivors.Methods and analysisAll patients surviving ICU-treated sepsis are eligible and are recruited from five study centres in Germany (acute care hospital setting in Jena, Halle/Saale, Leipzig, Bad Berka, Erfurt; large long-term acute care hospital and rehabilitation setting in Klinik Bavaria Kreischa). Screening is performed by trained study nurses. Data are collected on ICU management of sepsis. On written informed consent provided by patients or proxies, follow-up is carried out by trained research staff at 3, 6 and 12 months and yearly thereafter. The primary outcome is functional disability as assessed by (instrumental) activities of daily living. Other outcomes cover domains like mortality, cognitive, emotional and physical impairment, and resource use. The estimated sample size of 3000 ICU survivors is calculated to allow detection of relevant changes in the primary outcome in sepsis survivors longitudinally.Ethics and disseminationThe study is conducted according to the current version of theDeclaration of Helsinkiand has been approved by four local/federal responsible institutional ethics committees and by the respective federal data protection commissioners. Results of MSC will be fed back to the patients and published in peer-reviewed journals.Trial registration numberGerman Clinical Trials Registry DRKS00010050.

Objectives The objective was to develop and evaluate an early sepsis detection score for the prehospital setting. Methods A retrospective analysis of consecutive patients who were admitted by emergency medical services (EMS) to the emergency department of the Jena University Hospital was performed. Because potential predictors for sepsis should be based on consensus criteria, the following parameters were extracted from the EMS protocol for further analysis: temperature, heart rate (HR), respiratory rate (RR), oxygen saturation (SaO2), Glasgow Coma Scale score, blood glucose, and systolic blood pressure (sBP). Potential predictors were stratified based on inspection of Loess graphs. Backward model selection was performed to select risk factors for the final model. The Prehospital Early Sepsis Detection (PRESEP) score was calculated as the sum of simplified regression weights. Its predictive validity was compared to the Modified Early Warning Score (MEWS), the Robson screening tool, and the BAS 90-30-90. Results A total of 375 patients were included in the derivation sample; 93 (24.8%) of these had sepsis, including 60 patients with severe sepsis and 12 patients with septic shock. Backward model selection identified temperature, HR, RR, SaO2, and sBP for inclusion in the PRESEP score. Simplified weights were as follows: temperature > 38°C = 4, temperature 90 beats/min = 2, RR > 22 breaths/min = 1, SaO2 < 92% = 2, and sBP < 90 mm Hg = 2. The cutoff value for a possible existing septic disease based on maximum Youden's index was ≥4 (sensitivity 0.85, specificity 0.86, positive predictive value [PPV] 0.66, and negative predictive value [NPV] 0.95). The area under the receiver operating characteristic curve (AUC) of the PRESEP score was 0.93 (95% confidence interval [CI] = 0.89 to 0.96) and was larger than the AUC of the MEWS (0.93 vs. 0.77, p < 0.001). The PRESEP score surpassed MEWS and BAS 90-60-90 for sensitivity (0.74 and 0.62, respectively), specificity (0.75 and 0.83), PPV (0.45 and 0.51), and NPV (0.91 and 0.89). The Robson screening tool had a higher sensitivity and NPV (0.95 and 0.97), but its specificity and PPV were lower (0.43 and 0.32). Conclusions The PRESEP score could be a valuable tool for identifying septic patients in the prehospital setting in the case of suspected infection. It should be prospectively validated.

Many patients present with sepsis through emergency services [1]. Their outcome could be improved if sepsis could be detected already in the prehospital setting. This study aims to develop and evaluate a score to detect prehospital early sepsis.

Amiodarone is widely used in ventricular tachyarrhythmias and atrial fibrillation, known to prolong QT-intervals. Concurrent administration of drugs prolonging QT- time can induce life-threatening ventricular tachyarrhythmia.QT-interval changes following use of Iohexol contrast-medium for coronarangiography were observed comparing 21 patients taking long-term amiodarone therapy with 21 controls not taking amiodarone or QT-prolonging drugs retrospectively.Concurrent use of Iohexol and amiodarone was associated with significant prolongation of QTc-interval (433, 95%CI: 419-448 ms vs. 480, 95%CI: 422-483 ms, P0.001) the day after coronarangiograpgy. 6/21 patients showed severe prolonged QTc-interval of500 ms.Caution is advised until more is known about pro-arrhythmic effects of Iohexol.

SUMMARY Sepsis is among the most common causes of death in hospitals. It arises from the host response to infection. Currently, diagnosis relies on nonspecific physiological criteria and culture-based pathogen detection. This results in diagnostic uncertainty, therapeutic delays, the mis- and overuse of antibiotics, and the failure to identify patients who might benefit from immunomodulatory therapies. There is a need for new sepsis biomarkers that can aid in therapeutic decision making and add information about screening, diagnosis, risk stratification, and monitoring of the response to therapy. The host response involves hundreds of mediators and single molecules, many of which have been proposed as biomarkers. It is, however, unlikely that one single biomarker is able to satisfy all the needs and expectations for sepsis research and management. Among biomarkers that are measurable by assays approved for clinical use, procalcitonin (PCT) has shown some usefulness as an infection marker and for antibiotic stewardship. Other possible new approaches consist of molecular strategies to improve pathogen detection and molecular diagnostics and prognostics based on transcriptomic, proteomic, or metabolic profiling. Novel approaches to sepsis promise to transform sepsis from a physiologic syndrome into a group of distinct biochemical disorders and help in the development of better diagnostic tools and effective adjunctive sepsis therapies.

Summary Traditionally, fluid therapy in trauma patients favoured liberal replacement of intravascular fluids to correct fluid loss and optimise macro- and microcirculation. This narrative review examines the background for the changed approach to volume therapy, discusses important clinical studies and points out open questions for future research. Evidence is emerging that low volume resuscitation and permissive hypotension may be associated with improved outcomes. Crystalloids are safe as first line fluids. Colloids have no advantage over crystalloids and may be detrimental in patients with traumatic brain injury. Synthetic colloids may prolong bleeding and increase need for blood products. The role of hypertonic saline is unclear, as recent large-scale trials have been stopped for futility and some safety concerns.

Hydroxyethyl starches (HES) are widely used for intravascular volume therapy in surgical, emergency, and intensive care patients. There are safety concerns with regard to coagulopathy, renal failure, pruritus, tissue storage, and mortality. Third-generation HES 130/0.4 is considered to have an improved risk profile. A common rationale for the use of HES is the belief that 3 to 4 times more crystalloid than colloid volume is needed to achieve similar hemodynamic end points. Our goal was to assess whether published studies on HES 130/0.4 resuscitation are sufficiently well designed to draw conclusions about the safety of this compound. In addition, we wanted to assess crystalloid-to-colloid fluid ratios in studies with goal-directed fluid regimen.Systematic review of randomized controlled trials in which HES 130/0.4 is used for resuscitation.We identified 56 randomized controlled trials (RCTs) with HES 130/0.4 in. acute hypovolemia, mainly from the elective surgical setting (n = 45). Surgical studies were small-sized (median 25 patients in the HES groups, range 10 to 90) and of short duration (median 12 hours, range 0.5 to 144 hours). The median cumulative HES dose was 2465 mL (range 328 to 6229 mL), corresponding to 35 mL/kg in a 70-kg patient, the daily dose limit being 50 mL/kg. End points mostly addressed variable surrogate outcomes. Sixty percent of control fluids were other HES solutions, gelatins, or dextran, which have a similar risk profile. Without exception, these studies were not designed for clinically important safety outcomes, primarily because they were too small, used mostly inadequate control fluids, and had inappropriately short observation periods. Therefore, and also because of heterogeneity of patient groups and outcome definitions, results from these studies cannot be pooled. These studies do not allow any conclusion about the safety of HES 130/0.4. There is a common belief that 3 to 4 times more crystalloid than colloid volume is necessary to achieve similar hemodynamic effects. We found a considerably lower ratio in surgical studies (mean 1.8, SD 0.1).In summary, the extent of fluid load reduction that can be achieved by HES 130/0.4 is overestimated. Use of older HES solutions may be associated with serious side effects, and clinicians should be aware that there is no convincing evidence that third-generation HES 130/0.4 is safe in surgical, emergency, or intensive care patients despite publication of numerous clinical studies.

International audience; The use of biomarkers might help to avoid antibiotic misuse and overuse and to curb the rising incidence of microbial resistance. Among >100 biomarkers proposed for use as infection/sepsis markers, procalcitonin is the most frequently evaluated. It has been tested in 11 randomized controlled trials with more than 3500 patients and resulted in a considerable 35-70% reduction in antibiotic use without an apparent negative impact on patient outcome. Testing was carried out in hospital, intensive care unit, emergency and primary care settings; most of the patients had lower respiratory tract infections and only smaller studies exist in surgical patients with infectious complications, immunocompromised patients and patients with sepsis. There are, however, concerns-trials designed to show non-inferiority of procalcitonin to standard management allowed rather large differences for mortality rates, in the range of 7.5-10%, thus clinically relevant excess mortality by procalcitonin-guided antibiotic therapy cannot be completely ruled out. Marker panels derived from transcriptomic or proteomic profiling hold promise in overcoming the limitations of procalcitonin for differentiating non-infectious from infection-associated inflammation. However, the utility of these novel diagnostic tools in the clinical setting remains to be proven.

Disorders of fluid and electrolyte balance in the critically ill are volume-related, compositional, or both. Targeting 'normal' values for plasma volume, osmolality and electrolytes might not be optimal in conditions as diverse as intracranial trauma/haemorrhage, hepatic encephalopathy, abdominal hypertension, or major surgery, because a hyperosmolar state seems to favourably affect tissue (brain and intestinal) oedema formation. However, adequately powered studies regarding the impact of hypertonic saline on outcome are lacking. Isotonic crystalloids are the cornerstone of resuscitation and must be balanced against natural or artificial colloids and vasopressors. Crystalloid resuscitation is superior to vasopressors in shock associated with blunt trauma, and is at least not inferior to colloids in septic shock. Traditional rules of thumb indicating the need for three to four times the amount of crystalloids for the plasma volume to be replaced are probably erroneous and might have contributed to association of overly aggressive crystalloid resuscitation with poor outcome.

To compare the effects of predominantly hydroxyethyl starch (HES 6% 130/0.4)-based with predominantly gelatin 4%-based fluid therapy on renal function in surgical intensive care unit (ICU) patients.Before-after, retrospective, study of surgical ICU patients. All patients admitted from January to June 2005 formed the HES group, with HES 130/0.4 as the standard colloid of choice. All patients admitted from January to June 2006 formed the GEL group, with gelatin 4% as the primary colloid. Acute renal failure (ARF) was defined as new need for renal replacement therapy (RRT) or at least a two-fold increase in baseline creatinine.There were 1383 patients in the HES group and 1528 in the GEL group; 118 and 87, in each group respectively, had severe sepsis. The incidence of ARF and ICU and hospital mortality rates were similar in the two groups. In a post-hoc multivariable analysis, cumulative doses33 ml/kg of either HES (OR = 1.85, 95% CI: 1.01-3.41, p0.001) or gelatin (OR = 1.99, 95% CI: 1.05-3.79, p = 0.035) were associated with a higher risk of ARF.The incidence of ARF was similar in patients who received predominantly HES (6% 130/.04) fluid therapy and in those who received predominantly gelatin 4%. Moderate cumulative doses of modern HES or gelatin solutions may be associated with a higher risk of ARF.

To determine the prevalence and mortality of ICU patients with severe sepsis in Germany, with consideration of hospital size. Prospective, observational, cross-sectional 1-day point-prevalence study. 454 ICUs from a representative nationwide sample of 310 hospitals stratified by size. Data were collected via 1-day on-site audits by trained external study physicians. Visits were randomly distributed over 1 year (2003). Inflammatory response of all ICU patients was assessed using the ACCP/SCCM consensus conference criteria. Patients with severe sepsis were followed up after 3 months for hospital mortality and length of ICU stay. Main outcome measures were prevalence and mortality. A total of 3,877 patients were screened. Prevalence was 12.4% (95% CI, 10.9–13.8%) for sepsis and 11.0% (95% CI, 9.7–12.2%) for severe sepsis including septic shock. The ICU and hospital mortality of patients with severe sepsis was 48.4 and 55.2%, respectively, without significant differences between hospital size. Prevalence and mean length of ICU stay of patients with severe sepsis were significantly higher in larger hospitals and universities (≤ 200 beds: 6% and 11.5 days, universities: 19% and 19.2 days, respectively). The expected number of newly diagnosed cases with severe sepsis in Germany amounts to 76–110 per 100,000 adult inhabitants. To allow better comparison between countries, future epidemiological studies should use standardized study methodologies with respect to sepsis definitions, hospital size, and daily and monthly variability.

Th e CRYSTMAS trial compared resuscitation fl uids 6% HES 130/0.4 and 0.9% NaCl in patients with severe sepsis to fulfi l a postmarketing study commitment issued by the US Food and Drug Administration (FDA). However, published trial outcomes were selective. When the more complete data set is assessed and compared against previous data, it rather suggests that use of HES 130/0.4 does not lead to clinically relevant volume savings, and suggests similar negative eff ects on kidney function as were seen with an older HES solution and an increase in 90-day mortality by 6.8%. Th e CRYSTMAS trial by Guidet and colleagues [1] lacked power to address renal safety [2]. However, observed outcomes add to existing safety concerns [3]. Th e number of subjects undergoing renal replacement therapy (RRT) doubled in the hydroxyethylstarch (HES 130/0.4) arm [4] (Table 1); mean duration of RRT was 9.1 days versus 4.3 days [4]; and Kaplan-Meier curves for time to RRT showed a trend against HES (P = 0.06; Figure 1) [4]. Serious adverse events and serious adverse events leading to death numbered 53 versus 44 and 38 versus 32, respectively (HES versus saline) [4]. Mortality rates were all higher in the HES arm, and 90-day mortality rates were remarkably similar compared to a previous sepsis trial with 10% HES 200/0.5 [3] (Figure 2). Th ese study data were not published in the journal article. Withholding data from original publications - socalled publication bias - is a major problem [5]. Th ere was also other reporting bias. Th e primary outcome required fl uid volumes - was only reported for a post hoc subgroup of patients who reached hemodynamic stabilisation (174 of all 196 patients), misleadingly called the ‘full analysis set’. Th e numbers of patients available for safety outcomes was inconsistent. Publication and report ing bias can lead to overestimation of the treatment eff ect and underestimation of safety risks [5]. Our reading of the extended CRYSTMAS study data therefore leads to somewhat changed key messages: use of HES 130/0.4 does not lead to clinically relevant volume savings; and negative eff ects on kidney function and mortality after HES 130/0.4 were similar to those seen after an older HES solution.

Previous studies showed an increased risk for developing acute kidney injury in septic patients receiving synthetic colloids [1]. However, little is known about effects of synthetic colloids on other organs. Ginz and colleagues found altered organ morphology and considerable colloidal storage in parenchymal and reticuloendothelial cells of the liver, lung and kidney in a septic patient after synthetic colloid administration [2]. For this reason we analyzed the effects of HES and gelatin on kidney, liver and lung function in comparison with crystalloids in septic patients.

In a smaller sample of patients with severe sepsis, resuscitation with the synthetic colloids hydroxyethyl starch (HES) as well as gelatin (GEL) increased the occurrence of acute kidney injury (AKI) in comparison with crystalloids (CRYS). We now performed the analysis in a large-scale sample with over 1,100 septic patients on our ICU.

Hydroxyethyl starch (HES) is widely used for volume therapy in intensive care. In critically ill and sepsis patients, HES use was dose-dependently associated with increased renal failure, tissue storage with organ failure, and increased long-term mortality. There are other safety concerns with regard to coagulopathy, pruritus, and mortality. However, third-generation HES 130/0.4 is considered to have an improved risk profile. Therefore, we wanted to assess whether published studies on HES 130/0.4 resuscitation are sufficiently well designed to draw conclusions about the safety of this compound.

Sepsis is a global healthcare challenge. However, comprehensive information on sepsis morbidity and mortality across the world is scarce. We aimed to estimate the global burden of sepsis and to identify knowledge gaps based on available evidence from observational epidemiological studies.

In Germany, advance directives (AD) are written documents explaining what medical treatment the individual would prefer in the future, should that individual lack mental capacity. AD are legally binding. When a patient has lost mental capacity, the treating physician judges whether the AD is applicable or not. The AD is applicable if the patient's present condition matches the clinical scenario the patient specified in writing (in the following termed “applicability statement”). Common applicability statements are “in the event of a terminal illness” or “if I have irreversible organ failure”. It is unknown how ICU physicians judge the applicability of a given ADs.