[Epistemology in the intensive care unit-what is the purpose of a definition? : Paradigm shift in sepsis research]. / Erkenntnistheorie auf der Intensivstation ­ Welchen Zweck erfüllt eine Definition? : Paradigmenwechsel in der Sepsisforschung.

The adoption of the new sepsis definition in early 2016 introduced a new paradigm for the clinical picture of sepsis. Up until now, sepsis was defined as a systemic inflammatory reaction (systemic inflammatory response syndrome, SIRS) to an infection. Based on a better understanding of the molecular mechanisms, the focus of the new definition is no longer the inflammatory response, but rather the tissue damage and impairment of organ function which this induces. The paradigm thus moves away from the infection and the systemic inflammatory response, and toward that which makes sepsis so dangerous in terms of both disease dynamics and outcome: organ failure due to a dysregulated host response to an infection. This change of perspective or paradigm enables patients with an increased risk of developing sepsis to be recognized and treated earlier in clinical routine, even outside of the intensive care unit. The new definition also promotes development of new treatment strategies with improved ability to treat sepsis causally.

[Sepsis-3 : What has been confirmed in therapy?] / Sepsis-3 : Was ist gesichert in der Therapie?

Hugo Schottmüller realized already over 100 years ago that sepsis is a syndrome that occurs as a consequence of an infection defined by a systemic overreaction to a periodic invasion of bacilli. Consistent with this old concept, the term "systemic inflammatory response syndrome" (SIRS) was coined about 25 years ago and has been regularly used ever since. In 2016, a sepsis task force was formed to re-evaluate the current definition on a scientific basis. The task force suggested a third definition (sepsis-3) of the disease that now focuses both on the pathological host response and on organ dysfunction as obligatory key features to diagnose sepsis. In this review article, the definition is explained in detail and we summarize the novel international sepsis guideline from 2017 with personal commentaries.

[Hemophagocytic lymphohistiocytosis : A diagnostic challenge on the ICU]. / Hämophagozytische Lymphohistiozytose : Diagnostische Herausforderung auf der ITS.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) has well been studied as a genetic disorder in children (primary HLH). Mutations in the regulatory complex of the cellular immune synapse lead to a loss of function of cytotoxic T­cells and natural killer cells with excessive inflammation based on a cytokine storm. During the last decade, an increasing number of adult HLH patients without a family history of HLH (secondary or acquired HLH) have been reported. Various triggers - infections, malignancies or autoimmune diseases - result in an acquired loss of function of these cells and a sepsis-like disease. Missed or late diagnosis is believed to be a major cause of the high mortality. OBJECTIVES: To describe the current knowledge on HLH and to raise awareness. MATERIALS AND METHODS: Analysis of case reports, current studies, and expert recommendations. RESULTS: Increased vigilance in identifying the adult form of HLH resulted in an increasing number of case reports over the past few years. HLH patients typically present with a clinical phenotype resembling severe sepsis or septic shock with fever, cytopenia, and organomegaly, which do not or insufficiently respond to anti-infective treatment. Early recognition of HLH distinction from sepsis, and prompt initiation of treatment - which is fundamentally different from sepsis - are crucial for improved outcome. A promising diagnostic parameter is ferritin, which has gained sufficient specificity, but only in the context of the triad of fever, cytopenia, and organomegaly. Treatment of adult HLH patients requires immunosuppression, with strict therapeutic guidance derived from the triggering disease. CONCLUSIONS: Because of the similar clinical presentation to that of sepsis, HLH is often not recognized, resulting in a fatal outcome. In "sepsis" patients on the ICU with deterioration despite a standard of care, HLH needs to be considered by testing for ferritin when considering differential diagnoses. The complexity of the illness requires interdisciplinary patient care with specific integration of the hematologist in the diagnostic workup and therapeutic management, because of the frequent use of chemotherapy-based immunosuppression.

Delay in the administration of appropriate antimicrobial therapy in Staphylococcus aureus bloodstream infection: a prospective multicenter hospital-based cohort study.

OBJECTIVES: Early broad-spectrum antimicrobial treatment reduces mortality in patients with septic shock. In a multicenter, prospective observational study, we explored whether delayed appropriate antimicrobial therapy (AAT) influences outcome in Staphylococcus aureus bloodstream infection (SAB). METHODS: Two hundred and fifty-six patients with SAB from ten German study centers were enrolled and followed for 3 months. Predisposing factors, clinical features, diagnostic procedures, antimicrobial therapy, and outcome were recorded. The appropriateness of antimicrobial therapy was judged by a trained physician based on in vitro activity, dosage, and duration of therapy. Therapy was considered to be delayed when more than 24 h elapsed between the first positive blood culture and the start of appropriate therapy. The association of delayed therapy with overall mortality and SAB-related events (i.e., attributable mortality or late SAB-related complications) was assessed by crosstabulation and propensity score-based logistic regression. RESULTS: One hundred and sixty-eight patients received AAT during their hospital stay, of whom 42 (25%) received delayed AAT. The overall mortality and the occurrence of severe sepsis or septic shock were lower in patients with delayed AAT, pointing towards confounding by indication. Adjusted 90-day mortality (adjusted odds ratio [OR] 0.91, 95% confidence interval [CI] [0.39-2.13], p 0.82) and SAB-related events (adjusted OR 1.46, 95% CI [0.47-4.51], p 0.52) also failed to show a significant impact of delayed AAT on outcome. CONCLUSION: In patients with SAB, early AAT may not improve survival. However, confounding by indication is a major challenge when analyzing and interpreting observational studies on the impact of delayed AAT.

Ventilatory strategies in septic patients. Results from a nationwide observational trial.

BACKGROUND: Mortality in intensive care unit (ICU) patients is affected by multiple variables. The possible impact of the mode of ventilation has not yet been clarified; therefore, a secondary analysis of the "epidemiology of sepsis in Germany" study was performed. The aims were (1) to describe the ventilation strategies currently applied in clinical practice, (2) to analyze the association of the different modes of ventilation with mortality and (3) to investigate whether the ratio between arterial partial pressure of oxygen and inspired fraction of oxygen (PF ratio) and/or other respiratory variables are associated with mortality in septic patients needing ventilatory support. METHODS: A total of 454 ICUs in 310 randomly selected hospitals participated in this national prospective observational 1-day point prevalence of sepsis study including 415 patients with severe sepsis or septic shock according to the American College of Chest Physicians/Society of Critical Care Medicine criteria. RESULTS: Of the 415 patients, 331 required ventilatory support. Pressure controlled ventilation (PCV) was the most frequently used ventilatory mode (70.6 %) followed by assisted ventilation (AV 21.7 %) and volume controlled ventilation (VCV 7.7 %). Hospital mortality did not differ significantly among patients ventilated with PCV (57 %), VCV (71 %) or AV (51 %, p=0.23). A PF ratio equal or less than 300 mmHg was found in 83.2 % of invasively ventilated patients (n=316). In AV patients there was a clear trend to a higher PF ratio (204±70 mmHg) than in controlled ventilated patients (PCV 179±74 mmHg, VCV 175±75 mmHg, p=0.0551). Multiple regression analysis identified the tidal volume to pressure ratio (tidal volume divided by peak inspiratory airway pressure, odds ratio OR=0.94, 95 % confidence interval 95% CI=0.89-0.99), acute renal failure (OR=2.15, 95% CI=1.01-4.55) and acute physiology and chronic health evaluation (APACHE) II score (OR=1.09, 95% CI=1.03-1.15) but not the PF ratio (univariate analysis OR=0.998, 95 % CI=0.995-1.001) as independent risk factors for in-hospital mortality. CONCLUSIONS: This representative survey revealed that severe sepsis or septic shock was frequently associated with acute lung injury. Different ventilatory modes did not affect mortality. The tidal volume to inspiratory pressure ratio but not the PF ratio was independently associated with mortality.

[Bacteremia and sepsis]. / Bakteriämie und Sepsis.

Bacteremia and sepsis are common problems in clinical practice. Bacteremia is the presence of bacteria in the blood, hence a microbiological finding. Sepsis is a clinical diagnosis needing further specification regarding focus of infection and etiologic pathogen, whereupon clinicians, epidemiologists and microbiologists apply different definitions and terminology. Knowing these differences is important when reading and interpreting the literature. Studies show a pan-European increase in the rate of bacteremia, both Gram-negative and Gram-positive. Reasons for this are an increase in invasive diagnostics and therapy, going along with increasing age of patients. Bacteremic infections are frequently healthcare related. This article illustrates recent aspects in diagnosis and therapy of sepsis and bacteremia.

[Update: studies in intensive care medicine. Results of the last 12 months]. / Update: intensivmedizinische Studien. Ergebnisse der vergangenen 12 Monate.

Intensive care medicine plays an important role in the medical care of patients as well as the economic success of hospitals. Knowledge and implementation of recent relevant scientific evidence are prerequisites for high quality care in intensive care medicine. The aim of this review is to present an overview of the most important publications in intensive care medicine published in 2010 and the first half of the year 2011 and to comment on their attributable clinical relevance for intensive care practitioners. In 2010 and up to June 2011 many studies with high patient numbers have been published. The main topics were the treatment of respiratory failure, sepsis and investigations to improve analgosedation.

[Results of studies in critical care medicine in the year 2009 : update]. / Ergebnisse intensivmedizinischer Studien des Jahres 2009 : Update.

Critical care medicine plays an important role for the medical and economic success of hospitals. Knowledge and implementation of recent relevant studies are prerequisites for high quality intensive care medicine. The aim of the present manuscript is to present an overview of the most important publications in intensive care medicine in 2009 and comment on their clinical relevance. It has to be recognized that the cited studies are chosen according to the view of the authors. In 2009 many large randomized studies with high patient numbers were published. Main topics in 2009 were the therapy of lung failure, analgosedation and sepsis therapy. New trends are bedside echocardiography and telemedicine. Unfortunately, a magic bullet has not been identified last year. The focus is still on team education and guideline-assisted therapy.

[Prevention and follow-up care of sepsis. 1st revision of S2k guidelines of the German Sepsis Society (Deutsche Sepsis-Gesellschaft e.V., DSG) and the German Interdisciplinary Association of Intensive Care and Emergency Medicine (Deutsche Interdisziplinäre Vereinigung für Intensiv- und Notfallmedizin, DIVI)]. / Prävention und Nachsorge der Sepsis. 1. Revision der S2k-Leitlinien der Deutschen Sepsis-Gesellschaft e.V. (DSG) und der Deutschen Interdisziplinären Vereinigung für Intensiv- und Notfallmedizin (DIVI).

The 1st revision of the S2k guideline on the prevention and follow-up care of sepsis, provided by the German Sepsis Society in collaboration with 17 German medical scientific societies and one self-help group provides state-of-the-art information on the effective and appropriate medical care of critically ill patients with severe sepsis or septic shock. The guideline recommendations may not be applied under all circumstances. It rests with the clinician to decide whether a certain recommendation should be adopted or not, taking into consideration the unique set of clinical facts presented in connection with each individual patient as well as the available resources.

Promoting Global Research Excellence in Severe Sepsis (PROGRESS): lessons from an international sepsis registry.

BACKGROUND: The PROGRESS Registry (Promoting Global Research Excellence in Severe Sepsis) was designed to provide comparative data reflecting everyday clinical practice, thereby allowing participating institutions to explore and benchmark medical interventions in severe sepsis. MATERIALS AND METHODS: PROGRESS was an international, noninterventional, prospective, observational registry collecting data that describe the management and outcomes of severe sepsis patients in intensive care units (ICUs). Patients were enrolled who had been diagnosed with severe sepsis (suspected or proven infection and >or= 1 acute sepsis-induced organ dysfunction) at the participating institutions, where de-identified data were entered directly into a secured website. PROGRESS was governed by an independent international medical advisory board. RESULTS: PROGRESS took place in 276 ICUs in 37 countries, and 12,881 patients were identified as having severe sepsis. There was considerable variation among countries in enrollment levels, provision of standard treatment and supportive therapies, and ICU and hospital outcomes. Eight countries accounted for 65.2% of the enrolled patients. Males (59.3%) and Caucasian (48.6%) patients predominated the patient cohort. Diagnosis of severe sepsis was prior to ICU admission in 45.7% of patients, at ICU admission in 29.1% of patients, and after ICU admission in the remainder. Globally, ICU and hospital mortality rates were 39.2% and 49.6%, respectively. The mean length of ICU and hospital stay was 14.6 days and 28.2 days, respectively. CONCLUSIONS: The PROGRESS international sepsis registry demonstrates that a large web-based sepsis registry is feasible. Wide variations in outcomes and use of sepsis therapies were observed between countries. These results also suggest that additional opportunities exist across countries to improve severe sepsis outcomes.

[Diagnosis and causal treatment of sepsis]. / Diagnose und kausale Therapie der Sepsis.

The high mortality and morbidity of severe sepsis and septic shock had not been reduced during the two recent decades, despite a number of advances in the field of supportive and adjunctive sepsis therapies. The reason might be that important steps towards overcoming of sepsis - early diagnosis, the surgical resection of the infectious focus and an adequate antibiotic treatment - at present are still suboptimal and have to be improved. However, worldwide growing resistances of pathogens against the common antibiotics are detected. In opposite, no major progress in the development of new antibiotics, mainly for the treatment of Gram-negative non-fermenter infections like Pseudomonas aeruginosa, can be predicted for the next years. Therefore, sepsis treatment must be focused on prevention of infection, and on an optimised application of current antibiotic substances. The key factors are a broad, high dose, and early applicated initial treatment, a de-escalation strategy according to the clinical course supported by the application of novel molecular markers, and - with exceptions - a limitation of treatment to 7 to 10 days. A closer cooperation between microbiologists, infection control specialists and clinical infectious disease consultants may be a key factor to overcome the raising problems in the future.

[Supportive and adjunctive sepsis therapy]. / Supportive und adjunktive Therapie der Sepsis.

Severe sepsis and septic shock have an increasing incidence but an unchanged mortality. It has been demonstrated that the time until the start of supportive therapy affects the progress of multiorgan failure and patient outcome. Early goal-directed therapy guided by central venous oxygen saturation is associated with a significant reduction in mortality, as is the use of lung-protective mechanical ventilation and recombinant activated protein C (rhAPC) in eligible patients. The use of starches for volume resuscitation, low-dose dopamine and hydrocortison as well as an intensive insulin protocol for restoration of euglycemia is not recommended. The German Competence Network Sepsis (SepNet) is currently studying further relevant questions.

Effectiveness of a hospital-wide infection control programme on the incidence of healthcare-associated infections and associated severe sepsis and septic shock: a prospective interventional study.

OBJECTIVES: To evaluate whether a hospital-wide infection control programme (ICP) is effective at reducing the burden of healthcare-associated infections (HAIs) and associated severe sepsis/septic shock or death (severe HAIs). METHODS: Prospective, quasi-experimental study with two surveillance periods (September 2011 to August 2012; May 2013 to August 2014). Starting October 2012, the ICP included hand hygiene promotion and bundle implementation for common HAIs. We applied segmented mixed-effects Poisson regression and multi-state models. We reported adjusted incidence rate ratios (aIRR) and adjusted hazard ratios (aHR) with 95% confidence intervals (CI). RESULTS: Overall, 62 154 patients were under surveillance, with 1568 HAIs identified in 1170 patients (4.3 per 100 admissions) in the first and 2336 HAIs identified in 1711 patients (4.9 per 100 admissions) in the second surveillance period. No differences were found in the overall HAI incidence rates between the periods in the general wards (aIRR 1.29, 95% CI 0.78-2.15) and intensive care units (ICUs) (aIRR 0.59, 95% CI 0.27-1.31). However, the HAI incidence rate was declining in the ICUs after starting the ICP (aIRR 0.98, 95% CI 0.97-1.00 per 1-week increment), in contrast to general wards (aIRR 1.01, 95% CI 1.00-1.02). A reduction in severe HAIs (aIRR 0.13, 95% CI 0.05-0.32) and a lower probability of HAI-associated in-hospital deaths (aHR 0.56, 95% CI 0.31-0.99) were observed in the second period in the ICUs. CONCLUSIONS: There was no overall reduction in HAIs after implementation of the ICP. However, there was a significant reduction in severe HAIs in ICUs. Whether this difference was a consequence of the ICP or improvement in HAI case management is not clear.

International registry on the use of the CytoSorb® adsorber in ICU patients : Study protocol and preliminary results.

INTRODUCTION: The aim of this clinical registry is to record the use of CytoSorb® adsorber device in critically ill patients under real-life conditions. METHODS: The registry records all relevant information in the course of product use, e. g., diagnosis, comorbidities, course of the condition, treatment, concomitant medication, clinical laboratory parameters, and outcome (ClinicalTrials.gov Identifier: NCT02312024). Primary endpoint is in-hospital mortality as compared to the mortality predicted by the APACHE II and SAPS II score, respectively. RESULTS: As of January 30, 2017, 130 centers from 22 countries were participating. Data available from the start of the registry on May 18, 2015 to November 24, 2016 (122 centers; 22 countries) were analyzed, of whom 20 centers from four countries provided data for a total of 198 patients (mean age 60.3 ± 15.1 years, 135 men [68.2%]). In all, 192 (97.0%) had 1 to 5 Cytosorb® adsorber applications. Sepsis was the most common indication for CytoSorb® treatment (135 patients). Mean APACHE II score in this group was 33.1 ± 8.4 [range 15-52] with a predicted risk of death of 78%, whereas the observed mortality was 65%. There were no significant decreases in the SOFA scores after treatment (17.2 ± 4.8 [3-24]). However interleukin-6 levels were markedly reduced after treatment (median 5000 pg/ml before and 289 pg/ml after treatment, respectively). CONCLUSIONS: This third interim report demonstrates the feasibility of the registry with excellent data quality and completeness from 20 study centers. The results must be interpreted with caution, since the numbers are still small; however the disease severity is remarkably high and suggests that adsorber treatment might be used as an ultimate treatment in life-threatening situations. There were no device-associated side effects.

[Sepsis therapy: present guidelines and their application]. / Sepsistherapie : Aktuelle Leitlinien und deren Umsetzung.

Severe sepsis and septic shock have an increasing incidence and unchanged high mortality. Early diagnosis is necessary to slow the progression of organ dysfunction and improve outcome. Early administration of broad-spectrum antimicrobial therapy, early and aggressive hemodynamic therapy, and surgical source control are the most promising therapeutic approaches. Norepinephrine is the first choice as a vasopressor. Starches for volume resuscitation, intensive insulin therapy (aiming at 80-110 mg/dl), and low-dose hydrocortisone are not recommended outside randomized trials. Recombinant activated protein C is one choice for certain patients. The German Sepsis Competence Network (SepNet) is currently investigating other open questions.

Effect of pre-operative octenidine nasal ointment and showering on surgical site infections in patients undergoing cardiac surgery.

OBJECTIVE: To evaluate the effect of pre-operative octenidine (OCT) decolonization on surgical site infection (SSI) rates. DESIGN: Before-and-after cohort study. PATIENTS: Patients undergoing an elective isolated coronary artery bypass graft (CABG) procedure: control group (1st January to 31st December 2013), N=475; intervention group (1st January to 31st December 2014), N=428. INTERVENTIONS: The intervention consisted of nasal application of OCT ointment three times daily, beginning on the day before surgery, and showering the night before and on the day of surgery with OCT soap. RESULTS: A median sternotomy was performed in 805 (89.1%) patients and a minimally invasive direct coronary artery bypass procedure was performed in 98 (10.9%) patients. Overall, there was no difference in SSI rates between the control and intervention groups (15.4% vs 13.3%, P=0.39). The rate of harvest site SSIs was significantly lower in patients in the intervention group (2.5% vs 0.5%, P=0.01). Patients who had undergone a median sternotomy in the intervention group had a significantly lower rate of organ/space sternal SSIs (1.9% vs 0.3%, P=0.04). However, there was a trend towards an increased rate of deep incisional sternal SSIs (1.2% vs 2.9%, P=0.08). Multi-variate analysis did not identify a significant protective effect of the intervention (odds ratio 0.79, 95% confidence interval 0.53-1.15, P=0.27). CONCLUSIONS: Pre-operative decolonization with OCT did not reduce overall SSI rates in patients undergoing an elective isolated CABG procedure, but significantly decreased harvest site and organ/space sternal SSIs. Randomized controlled trials, including controlled patient adherence to the intervention, are required to confirm these observations and to determine the clinical utility of OCT in pre-operative decolonization.

Study on the utility of a statewide counselling programme for improving mortality outcomes of patients with Staphylococcus aureus bacteraemia in Thuringia (SUPPORT): a study protocol of a cluster-randomised crossover trial.

INTRODUCTION: Staphylococcus aureus bacteraemia (SAB) is a frequent infection with high mortality rates. It requires specific diagnostic and therapeutic management such as prolonged intravenous administration of antibiotics and aggressive search for and control of infectious sources. Underestimation of disease severity frequently results in delayed or inappropriate management of patients with SAB leading to increased mortality rates. According to observational studies, patient counselling by infectious disease consultants (IDC) improves survival and reduces the length of hospital stay as well as complication rates. In many countries, IDC are available only in some tertiary hospitals. In this trial, we aim to demonstrate that the outcome of patients with SAB in small and medium size hospitals that do not employ IDC can be improved by unsolicited ID phone counselling. The SUPPORT trial will be the first cluster-randomised controlled multicentre trial addressing this question. METHODS AND ANALYSIS: SUPPORT is a single-blinded, multicentre interventional, cluster-randomised, controlled crossover trial with a minimum of 15 centres that will include 250 patients with SAB who will receive unsolicited IDC counselling and 250 who will receive standard of care. Reporting of SAB will be conducted by an electronic real-time blood culture registry established for the German Federal state of Thuringia (ALERTSNet) or directly by participating centres in order to minimise time delay before counselling. Mortality, disease course and complications will be monitored for 90 days with 30-day all-cause mortality rates as the primary outcome. Generalised linear mixed modelling will be used to detect the difference between the intervention sequences. We expect improved outcome of patients with SAB after IDC. ETHICS AND DISSEMINATION: We obtained ethics approval from the Ethics committee of the Jena University Hospital and from the Ethics committee of the State Chamber of Physicians of Thuringia. Results will be published in a peer-reviewed journal and additionally disseminated through public media. TRIAL REGISTRATION NUMBER: DRKS00010135.

ESPEN Guidelines on Enteral Nutrition: Cardiology and pulmonology.

These guidelines are intended to give evidence-based recommendations for the use of enteral nutrition (EN) in patients with chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD). They were developed by an interdisciplinary expert group in accordance with officially accepted standards and are based on all relevant publications since 1985. They have been discussed and accepted in a consensus conference. EN by means of oral nutritional supplements (ONS) or tube feeding (TF) enables nutritional intake to be maintained or increased when normal oral intake is inadequate. No data are yet available concerning the effects of EN on cachexia in CHF patients. However, EN is recommended to stop or reverse weight loss on the basis of physiological plausibility. In COPD patients, EN in combination with exercise and anabolic pharmacotherapy has the potential to improve nutritional status and function. Frequent small amounts of ONS are preferred in order to avoid postprandial dyspnoea and satiety as well as to improve compliance.