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.

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.

[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.

[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.

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.

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.

[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.

[Treatment of acute renal failure in Germany: Analysis of current practice]. / Versorgung des akuten Nierenversagens auf deutschen Intensivstationen: Analyse der aktuellen Behandlungspraxis.

BACKGROUND AND OBJECTIVES: There are currently no reliable data on the differential use of renal replacement therapy (RRT) options for critically ill patients with acute renal failure in Germany. PATIENTS AND METHODS: A questionnaire-based survey was delivered to 2265 German intensive care units. The questionnaire contained 19 questions regarding RRT. RESULTS: A total of 423 German intensive care units participated in the survey. The offered modalities of RRT varied significantly: the smaller the facility, the fewer different RRT options were available. Intermittent dialysis procedures were available in only 35% of hospitals with up to 400 beds. In university hospitals, hemodynamically unstable patients were exclusively treated by continuous RRT, whereas in hospitals with up to 400 beds, intermittent RRT was also used. In addition, treatment practice was also dependent on the specialization of the treating physicians: Isolated acute renal failure was treated more often intermittently by nephrologists compared to anesthesiologists (79.7 vs. 43.3%). Nephrologists also used extracorporeal RRT more often in cardiorenal syndrome (54.3 vs. 35.8%), whereas anesthesiologists preferred them in sepsis (37.3 vs. 23.1%). The choice of anticoagulant varied as well: Hospitals with up to 400 beds offered regional citrate anticoagulation in only 50% compared to 90% of university hospitals. CONCLUSIONS: Currently, RRT treatment in acute renal failure on German intensive care units seems to be dependent on the size, local structures, and education of the intensivists rather than patient needs. Our results demonstrate the necessity to establish cross-disciplinary standards for the treatment of acute renal failure in German intensive care units.

[Sepsis - Knowledge of non-physician personnel in Africa. A cross-sectional study in Malawian district hospitals]. / Sepsis - Kenntnisstand des nichtärztlichen Personals in Afrika. Eine Querschnittstudie in malawischen Distriktkrankenhäusern.

BACKGROUND: Malawi has one of the worst human resource situations in the world and each clinically working doctor has to serve around 50,000 patients. There are almost no Malawian specialists physicians so that in the district hospitals it is usually non-medical staff (e.g. anesthesia clinical officer) who have the responsibility for severely sick patients with sepsis. At the Queen Elizabeth Central Hospital we have organized different courses over the years to support these colleagues. METHODS: Anonymous questionnaires with 10 multiple choice and 4 feedback-related questions were distributed to 115 participants in order to achieve an overview of the basic knowledge related to sepsis in the Malawian setting. RESULTS: In total 64.2 % of the questions were answered correctly with only minor differences between the 4 groups of participants from different professional backgrounds. Despite a relatively good knowledge in practical therapy the question concerning the therapeutic strategies of the Surviving Sepsis Campaign obtained the worst score with 6 %. After the course there was a 17 % increase in correctly answered questions. Besides an overview over the diagnostic and therapeutic situation for sepsis in the districts we received suggestions and critical comments for a better adjustment of our courses towards the reality of rural district hospitals. CONCLUSIONS: Healthcare workers in Malawi are not aware of key recommendations of the Surviving Sepsis Campaign. Guidelines have to be adapted to the specific healthcare structures in underdeveloped countries. We realized the wish and the desire of the participants for more training and more courses in Malawi. In order to be able to support these needs we would like to invite cooperation from interested institutions and colleagues for a special sepsis course on the occasion of the annual World Sepsis Days.

[Neurological and psychological long-term effects of sepsis]. / Neurologische und psychische Langzeitfolgen der Sepsis.

BACKGROUND: In addition to the limitations to the health-related quality of life that have been compiled with validated test instruments, a number of former sepsis patients suffer from functional impairments, which are categorized under the terms critical illness polyneuropathy (CIP) or critical illness myopathy (CIM), which have been in existence for over 20 years now. CURRENT FOCUS: The issues of delirium during intensive therapy and persistent residual neurocognitive impairments, posttraumatic stress disorder (PTSD) and states of depression related to perihospital functional development have increasingly attracted notice. FUTURE: The degree of functional deficits resulting from sepsis and the actual quality of life of those affected may, however, be influenced by taking appropriate rehabilitation measures. However, neither therapeutic rehabilitation standards nor any rehabilitation facilities tailored to the needs of these patients currently exist.

[Sepsis-associated Purpura Fulminans International Registry--Europe (SAPFIRE)]. / Ein europäisches Register für sepsisassoziierte Purpura fulminans (SAPFIRE).

BACKGROUND: Purpura fulminans is a rare life-threatening condition which is characterized by disseminated thrombosis in dermal and systemic microcirculation, cutaneous hemorrhages with progressing necrosis and multiple organ failure. The underlying pathogenesis is based on the disruption of the intrinsic anticoagulation cascade, with protein C deficiency being considered the leading factor in this process. In the majority of cases, the condition emerges as consumptive coagulopathy associated with severe sepsis. OBJECTIVES: Epidemiological data on sepsis-associated purpura fulminans (SAPF) are scarce and evidence-based treatment guidelines have not been established yet. While restoration of the balance in the coagulation cascade is a declared therapeutic goal, evaluations of the efficacy of different therapeutic approaches in randomized clinical trials are still lacking. The causal role of individual microbial pathogens also requires comprehensive evaluation. METHODS: A prospective multicenter Sepsis-Associated Purpura Fulminans International Registry-Europe (SAPFIRE) will be established in the first quarter of 2015. For the first time, participating centers will systematically collect information on etiology, clinical course, biomarkers, treatment, morbidity, and mortality of SAPF. RESULTS: The SAPFIRE data will be periodically evaluated and disseminated. Retrospective analysis of each center's data and regular access to aggregated information collected by other centers will enable the participants to monitor and update care quality standards.

[Treatment of acute renal failure in Germany: a structural analysis]. / Versorgung des akuten Nierenversagens in Deutschland--Eine strukturelle Analyse.

INTRODUCTION: There are no reliable data on the structure and practice of the care of critically ill patients with acute renal failure in Germany. METHODS: We carried out a detailed survey by sending a questionnaire to 2265 German Intensive Care Units. The questionnaire contained 19 questions regarding renal replacement therapy. RESULTS: 423 German intensive care units participated in the survey. Most of the ICUs are headed interdisciplinary (47%) or by anesthesiologists (30%), with significant differences depending on the size of the clinic, with primarily interdisciplinary management in smaller clinics. The offered type of renal replacement therapy varies significantly, the smaller the house the fewer methods are available. Thus, intermittent dialysis procedures are offered only in 35% of hospitals with up to 400 beds. The indication for the initiation of acute renal replacement therapy in intensive care is provided predominantly (53%) by an anesthesiologist. A nephrologist is only involved in 22% of all intensive care units. The indication is based primarily on a "clinical criteria", but these are poorly defined. CONCLUSION: Our results demonstrate the need for cross-disciplinary standards for the treatment of acute renal failure in German intensive care units.

[Dysphagia management of acute and long-term critically ill intensive care patients]. / Dysphagie-Management im Akut- und Langzeitverlauf bei kritisch kranken intensivpflichtigen Patienten.

Dysphagia is a severe complication in critically ill patients and affects more than half the patients in an intensive care unit. Dysphagia also has a strong impact on morbidity and mortality. Risk factors for the development of dysphagia are neurological diseases, age >55-70 years, intubation >7 days and sepsis. With increasing numbers of long-term survivors chronic dysphagia is becoming an increasing problem. There is not much knowledge on the influence of specific diseases, including the direct impact of sepsis on the development of dysphagia. Fiberoptic evaluation of swallowing is a standardized tool for bedside evaluation, helping to plan swallowing training during the acute phase and to decrease the rate of chronic dysphagia. For evaluation of chronic dysphagia even more extensive diagnostic tools as well as several options of stepwise rehabilitation using restitution, compensation and adaption strategies for swallowing exist. Currently it seems that these options are not being sufficiently utilized. In general, there is a need for controlled clinical trials analyzing specific swallowing rehabilitation concepts for former critically ill patients and long-term survivors.

[Effectiveness of a hospital-wide educational programme for infection control to reduce the rate of health-care associated infections and related sepsis (ALERTS)--methods and interim results]. / Nutzen eines krankenhausweiten Infektionspräventions-Programmes zur Reduktion nosokomialer Infektionen und assoziierter Sepsisfälle (ALERTS)--Methodik und Zwischenergebnisse.

BACKGROUND AND AIM: Health care associated infections (HAIs) are one of the most frequent complications of hospital care, associated with increased morbidity, mortality and considerable extra costs for the health care system. The overarching objective of the ALERTS study is to demonstrate the feasibility of a hospitalwide programme to reduce the burden of HAIs and related sepsis of at least 20 %. METHODS: Prospective, quasi-experimental study covering all acute care units (27 general wards, 4 ICUs, overall 809 beds) at Jena University Hospital. Surveillance for HAIs is performed by computerized antibiotic monitoring in patients with risk factors for HAIs (i. e. intravenous and urinary catheters, surgery) on a daily basis. Following the first surveillance period a multifaceted, pragmatic infection control programme, aimed at proper hand hygiene and bundles for the prevention of the four most common HAIs will be implemented. Subsequently, a second surveillance period lasting 18 months will be conducted to measure the effect of the infection control programme, starting in May 2013. RESULTS: Interim results for the first surveillance period (09/2011 to 08/2012) are presented. During this period, 30,631 patients were admitted to the participating departments. According to CDC definitions we identified 1,637 HAIs, resulting in an overall incidence of 5.3 %. Based on clinical evaluation only, irrespective of the CDC definitions, an additional 944 HAIs were detected (overall HAI rate, 8.4 % [n =2581]). A substantial proportion of patients had HAI associated severe sepsis or septic shock (lower respiratory tract infection, n = 279 [37 %]; surgical site infection, n = 114 [25 %]; primary sepsis, n = 110 [32 %]; urinary tract infection, n = 46 [8 %]; other, n = 87 [22 %]). CONCLUSION: Our numbers reveal that a high number of HAIs are missed using CDC-definitions and therefore the magnitude of the problem might be underestimated. Furthermore, a high percentage of HAIs progress from localized infection to severe sepsis or septic shock, requiring ICU treatment.

[Peripheral venous catheter-related E. faecalis sepsis with fatal outcome]. / Fatale Sepsis nach Abszess bei peripherem Venenkatheter durch E. faecalis.

HISTORY AND ADMISSION FINDINGS: A 82 year-old man was admitted with a facial Herpes zoster reactivation and a zoster-related meningoencephalitis. He was treated with Aciclovir over a peripheral venous catheter that was placed in the right elbow pit. The meningoencephalitis subsided without neurological deficits, but the patient developed a catheter-associated phlebitis. An oral cephalosporin was prescribed and the patient discharged. After developing a fever and general discomfort he was readmitted to hospital three days later. INVESTIGATIONS: A 3 × 3 cm abscess in the elbow pit was incised and drained, but no swab or blood cultures were taken. When the patient's condition got worse an echocardiogram was ordered. It showed vegetations on the aortic and mitral valves as well as on the cardiac pacemaker wires. TREATMENT AND COURSE: Blood cultures were positive for Enterococcus faecalis. Although a therapy with vancomycin and ampicillin was started, the patient's condition impaired. Surgical valve replacement was initiated, but the patient expired 5 weeks later due to septic multi-organ failure. CONCLUSION: The danger of peripheral venous catheter infections is frequently underrated, early identification of the causing pathogen, sensitivity testing and proper antibiotic treatment are of tremendous importance. Clinical sings of sepsis must under no circumstances be overlooked.