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Practice guidelines are systematically developed statements and recommendations that assist the physicians and patients in making decisions about appropriate health care measures for specific clinical circumstances taking into account specific national health care structures. The 1st revision of the S-2k guideline of the German Sepsis Society in collaboration with 17 German medical scientific societies and one self-help group provides state-of-the-art information (results of controlled clinical trials and expert knowledge) on the effective and appropriate medical care (prevention, diagnosis, therapy and follow-up care) of critically ill patients with severe sepsis or septic shock. The guideline had been developed according to the “German Instrument for Methodological Guideline Appraisal” of the Association of the Scientific Medical Societies (AWMF). In view of the inevitable advancements in scientific knowledge and technical expertise, revisions, updates and amendments must be periodically initiated. 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.

Context: Early appropriate antimicrobial therapy leads to lower mortality rates associated with severe sepsis. The role of empirical combination therapy comprising at least 2 antibiotics of different mechanisms remains controversial.Objective: To compare the effect of moxifloxacin and meropenem with the effect of meropenem alone on sepsis-related organ dysfunction.Design, Setting, and Patients: A randomized, open-label, parallel-group trial of 600 patients who fulfilled criteria for severe sepsis or septic shock (n = 298 for monotherapy and n = 302 for combination therapy). The trial was performed at 44 intensive care units in Germany from October 16, 2007, to March 23, 2010. The number of evaluable patients was 273 in the monotherapy group and 278 in the combination therapy group.Interventions: Intravenous meropenem (1 g every 8 hours) and moxifloxacin (400 mg every 24 hours) or meropenem alone. The intervention was recommended for 7 days and up to a maximum of 14 days after randomization or until discharge from the intensive care unit or death, whichever occurred first.Main Outcome Measure: Degree of organ failure (mean of daily total Sequential Organ Failure Assessment [SOFA] scores over 14 days; score range: 0-24 points with higher scores indicating worse organ failure); secondary outcome: 28-day and 90-day all-cause mortality. Survivors were followed up for 90 days.Results: Among 551 evaluable patients, there was no statistically significant difference in mean SOFA score between the meropenem and moxifloxacin group (8.3 points; 95% CI, 7.8-8.8 points) and the meropenem alone group (7.9 points; 95% CI, 7.5-8.4 points) (P = .36). The rates for 28-day and 90-day mortality also were not statistically significantly different. By day 28, there were 66 deaths (23.9%; 95% CI, 19.0%-29.4%) in the combination therapy group compared with 59 deaths (21.9%; 95% CI, 17.1%-27.4%) in the monotherapy group (P = .58). By day 90, there were 96 deaths (35.3%; 95% CI, 29.6%-41.3%) in the combination therapy group compared with 84 deaths (32.1%; 95% CI, 26.5%-38.1%) in the monotherapy group (P = .43).Conclusion: Among adult patients with severe sepsis, treatment with combined meropenem and moxifloxacin compared with meropenem alone did not result in less organ failure.Trial Registration: clinicaltrials.gov Identifier: NCT00534287. [ABSTRACT FROM AUTHOR]

Context: The benefit of corticosteroids in severe sepsis and septic shock remains controversial.Objective: We examined the benefits and risks of corticosteroid treatment in severe sepsis and septic shock and the influence of dose and duration.Data Sources: We searched the CENTRAL, MEDLINE, EMBASE, and LILACS (through March 2009) databases as well as reference lists of articles and proceedings of major meetings, and we contacted trial authors.Study Selection: Randomized and quasi-randomized trials of corticosteroids vs placebo or supportive treatment in adult patients with severe sepsis/septic shock per the American College of Chest Physicians/Society of Critical Care Medicine consensus definition were included.Data Extraction: All reviewers agreed on trial eligibility. One reviewer extracted data, which were checked by the other reviewers and by the trials' authors whenever possible. Some unpublished data were obtained from the trials' authors. The primary outcome for this review was 28-day mortality.Results: We identified 17 randomized trials (n = 2138) and 3 quasi-randomized trials (n = 246) that had acceptable methodological quality to pool in a meta-analysis. Twenty-eight-day mortality for treated vs control patients was 388/1099 (35.3%) vs 400/1039 (38.5%) in randomized trials (risk ratio [RR], 0.84; 95% confidence interval [CI], 0.71-1.00; P = .05; I(2) = 53% by random-effects model) and 28/121 (23.1%) vs 24/125 (19.2%) in quasi-randomized trials (RR, 1.05, 95% CI, 0.69-1.58; P = .83). In 12 trials investigating prolonged low-dose corticosteroid treatment, 28-day mortality for treated vs control patients was 236/629 (37.5%) vs 264/599 (44%) (RR, 0.84; 95% CI, 0.72-0.97; P = .02). This treatment increased 28-day shock reversal (6 trials; 322/481 [66.9%] vs 276/471 [58.6%]; RR, 1.12; 95% CI, 1.02-1.23; P = .02; I(2) = 4%) and reduced intensive care unit length of stay by 4.49 days (8 trials; 95% CI, -7.04 to -1.94; P < .001; I(2) = 0%) without increasing the risk of gastroduodenal bleeding (13 trials; 65/800 [8.1%] vs 56/764 [7.3%]; P = .50; I(2) = 0%), superinfection (14 trials; 184/998 [18.4%] vs 170/950 [17.9%]; P = .92; I(2) = 8%), or neuromuscular weakness (3 trials; 4/407 [1%] vs 7/404 [1.7%]; P = .58; I(2) = 30%). Corticosteroids increased the risk of hyperglycemia (9 trials; 363/703 [51.6%] vs 308/670 [46%]; P < .001; I(2) = 0%) and hypernatremia (3 trials; 127/404 [31.4%] vs 77/401 [19.2%]; P < .001; I(2) = 0%).Conclusions: Corticosteroid therapy has been used in varied doses for sepsis and related syndromes for more than 50 years, with no clear benefit on mortality. Since 1998, studies have consistently used prolonged low-dose corticosteroid therapy, and analysis of this subgroup suggests a beneficial drug effect on short-term mortality. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the effect of low-dose hydrocortisone on time to shock reversal, the cytokine profile, and its relation to adrenal function in patients with early septic shock.Design: Prospective, randomized, double-blind, single-center study.Setting: Medical intensive care unit of a university hospital.Patients: Forty-one consecutive patients with early hyperdynamic septic shock.Interventions: After inclusion and a short adrenocorticotropic hormone test, all patients were randomized to receive either low-dose hydrocortisone (50-mg bolus followed by a continuous infusion of 0.18 mg/kg body of weight/hr) or matching placebo. After shock reversal, the dose was reduced to 0.06 mg/kg/hr and afterward slowly tapered. Severity of illness was estimated using Acute Physiology and Chronic Health Evaluation II score and Sequential Organ Failure Assessment score.Measurements and Main Results: Time to cessation of vasopressor support (primary end point) was significantly shorter in hydrocortisone-treated patients compared with placebo (53 hrs vs. 120 hrs, p < .02). This effect was more profound in patients with impaired adrenal reserve. Irrespective of endogenous steroid production, cytokine production was reduced in the treatment group with lower plasma levels of interleukin-6 and a diminished ex vivo lipopolysaccharide-stimulated interleukin-1 and interleukin-6 production. Interleukin-10 levels were unaltered. Adverse events were not more frequent in the treatment group.Conclusions: Treatment with low-dose hydrocortisone accelerates shock reversal in early hyperdynamic septic shock. This was accompanied by reduced production of proinflammatory cytokines, suggesting both hemodynamic and immunomodulatory effects of steroid treatment. Hemodynamic improvement seemed to be related to endogenous cortisol levels, whereas immune effects appeared to be independent of adrenal reserve. [ABSTRACT FROM AUTHOR]

Background: Post-transplant lymphoproliferative disease (PTLD) is a life-threatening complication following organ transplantation. The greatest risk is seen in Epstein–Barr virus (EBV)-seronegative patients receiving allografts from EBV-seropositive donors. We demonstrate a new approach of pre-transplant prophylaxis of EBV-related PTLD, suggesting that, prior to living-related renal transplantation, blood transfusion from an EBV-seropositive donor to an EBV-seronegative recipient could induce primary EBV infection in the recipient, developing EBV immunity and decreasing risk of PTLD. Methods: Recipients underwent weekly donor-specific blood transfusion (3 × 100 mL) before transplantation. EBV-mRNA expression, viral load, serological tests, and clinical signs of EBV infection were assessed following blood transfusion. Results: We explored a new approach in 2 young EBV-seronegative renal allograft recipients. Both patients developed primary EBV infection following blood transfusion before transplantation and showed symptom-free seroconversion post-transplantation without persistent EBV activation. There were no signs of PTLD during 5-year follow-up. Conclusions: A new effective and inexpensive approach is suggested for development of EBV immunity and probably for prophylaxis of EBV-associated PTLD. [ABSTRACT FROM AUTHOR]

Objectives: To compare cortisol levels during "low-dose" hydrocortisone therapy to basal and ACTH-stimulated endogenous levels and to assess whether clinical course and the need for catecholamines depend on cortisol levels and/or pretreatment adrenocortical responsiveness.Design and Setting: Prospective observational study in a medical ICU of a university hospital.Patients: Twenty consecutive patients with septic shock and a cardiac index of 3.5 l/min or higher, started on "low-dose" hydrocortisone therapy (100 mg bolus, 10 mg/h for 7 days and subsequent tapering) within 72 h of the onset of shock.Measurements and Results: Basal total and free plasma cortisol levels ranged from 203 to 2169 and from 17 to 372 nmol/l. In 11 patients cortisol production was considered "inadequate" because there was neither a response to ACTH of at least 200 nmol/l nor a baseline level of at least 1000 nmol/l. Following the initiation of hydrocortisone therapy total and free cortisol levels increased 4.2- and 8.5-fold to median levels of 3,587 (interquartile range 2,679-5,220) and 1,210 (interquartile range 750-1,846) nmol/l on day 1, and thereafter declined to median levels of 1,310 nmol/l and 345 nmol/l on day 7. Patients with "inadequate" steroid production could be weaned from vasopressor therapy significantly faster, although their plasma free cortisol concentrations during the hydrocortisone treatment period did not differ.Conclusions: (a) During proposed regimens of "low-dose" hydrocortisone therapy, initially achieved plasma cortisol concentrations considerably exceed basal and ACTH stimulated levels. (b) Cortisol concentrations decline subsequently, despite continuous application of a constant dose. (c) "Inadequate" endogenous steroid production appears to sensitize patients to the hemodynamic effects of a "therapeutic rise" in plasma cortisol levels. [ABSTRACT FROM AUTHOR]

Problem/condition: Splash pads are recreational interactive water venues that spray or jet water on users. Splash pads are intended for children aged <5 years and designed so that water typically does not collect in areas accessible to users, thereby minimizing the risk for drowning. Splash pads were first found to be associated with waterborne disease outbreaks in 1997., Period Covered: 1997-2022., Description of System: Since 1971, waterborne disease outbreaks have been voluntarily reported to CDC by state, local, and territorial health departments using a standard paper form via the Waterborne Disease and Outbreak Surveillance System (WBDOSS). Beginning in 2009, WBDOSS reporting was made available exclusively through the National Outbreak Reporting System, a web-based platform. This report characterizes waterborne disease outbreaks associated with splash pads reported to CDC that occurred during 1997-2022., Results: During 1997-2022, public health officials from 23 states and Puerto Rico reported 60 waterborne disease outbreaks associated with splash pads. These reported outbreaks resulted in 10,611 cases, 152 hospitalizations, 99 emergency department visits, and no reported deaths. The 40 (67%) outbreaks confirmed to be caused, in part, by Cryptosporidium resulted in 9,622 (91%) cases and 123 (81%) hospitalizations. Two outbreaks suspected to be caused by norovirus resulted in 72 (73%) emergency department visits., Interpretation: Waterborne pathogens that cause acute gastrointestinal illness can be transmitted by ingesting water contaminated with feces from infected persons. Chlorine is the primary barrier to pathogen transmission in splash pad water. However, Cryptosporidium is tolerant to chlorine and is the most common cause of reported waterborne disease outbreaks associated with splash pads., Public Health Action: Public health officials and the aquatics sector can use the findings in this report to promote the prevention of splash pad-associated outbreaks (e.g., recommended user behaviors) and guide the construction, operation, and management of splash pads. Public health practitioners and the aquatics sector also can collaborate to voluntarily adopt CDC's Model Aquatic Health Code recommendations to prevent waterborne illness associated with splash pads., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Background: Influenza can be associated with nonrespiratory disease presentation, but these are less well documented due to the lack of routine testing for influenza in the healthcare system, especially if patients do not present with influenza-like illness (ILI). We aimed to measure the proportion of influenza cases seeking care at emergency department (ED) for a nontraumatic cause, to describe their clinical presentation and their ED-discharge diagnosis., Methods: The study was conducted at seven hospitals in France, Spain, Italy and Germany during the 2019-20 influenza season, for a period of 10 weeks. Patients (≥ 18 years) consulting for nontraumatic causes at the ED were invited to participate. Consenting patients provided upper respiratory swab samples for influenza testing by reverse transcription polymerase chain reaction. Clinical and demographic data were collected., Results: There were 8678 patients included, 50.7% were female and the median age was 57 years. Among them, 494 (5.7%) were laboratory-confirmed influenza (LCI) cases. Nonetheless, only 24.3% of LCI cases had an ED-discharge of influenza. Of all cases confirmed as influenza, 47.6% had a nonrespiratory discharge diagnosis, which frequency increased with age. ILI case definition from the European Centre for Disease Prevention and Control was the most frequently met among influenza cases (68.6%). Older patients (≥ 65 years) were less frequently identified based on any ILI signs/symptoms., Conclusion: Our findings indicate that the impact of influenza among patients seeking care at the ED cannot be easily assessed based on clinical presentation and medical records alone. Preventing influenza among adult population may reduce healthcare utilization., (© 2024 The Author(s). Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Large clinical trials testing hydrocortisone therapy in septic shock have produced conflicting results. Subgroups may benefit of hydrocortisone treatment depending on their individual immune response. We performed an exploratory analysis of the database from the international randomized controlled clinical trial Corticosteroid Therapy of Septic Shock (CORTICUS) employing machine learning to a panel of 137 variables collected from the Berlin subcohort comprising 83 patients including demographic and clinical measures, organ failure scores, leukocyte counts and levels of circulating cytokines. The identified theranostic marker was validated against data from a cohort of the Hellenic Sepsis Study Group (HSSG) ( n = 246), patients enrolled in the clinical trial of Sodium Selenite and Procalcitonin Guided Antimicrobial Therapy in Severe Sepsis (SISPCT, n = 118), and another, smaller clinical trial (Crossover study, n = 20). In addition, in vitro blood culture experiments and in vivo experiments in mouse models were performed to assess biological plausibility. A low serum IFNγ/IL10 ratio predicted increased survival in the hydrocortisone group whereas a high ratio predicted better survival in the placebo group. Using this marker for a decision rule, we applied it to three validation sets and observed the same trend. Experimental studies in vitro revealed that IFNγ/IL10 was negatively associated with the load of (heat inactivated) pathogens in spiked human blood and in septic mouse models. Accordingly, an in silico analysis of published IFNγ and IL10 values in bacteremic and non-bacteremic patients with the Systemic Inflammatory Response Syndrome supported this association between the ratio and pathogen burden. We propose IFNγ/IL10 as a molecular marker supporting the decision to administer hydrocortisone to patients in septic shock. Prospective clinical studies are necessary and standard operating procedures need to be implemented, particularly to define a generic threshold. If confirmed, IFNγ/IL10 may become a suitable theranostic marker for an urging clinical need., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 König, Kolte, Ahlers, Oswald, Krauss, Roell, Sommerfeld, Dimopoulos, Tsangaris, Antoniadou, Jaishankar, Bogatsch, Löffler, Rödel, Garcia-Moreno, Tuchscherr, Sprung, Singer, Brunkhorst, Oppert, Gerlach, Claus, Coldewey, Briegel, Giamarellos-Bourboulis, Keh and Bauer.)

Nursing is often hazardous work. Promoting safety and care requires nurses to apply knowledge, skill and creativity in patient encounters. Nurses' risk exposures are well documented, with research on student nurses' safety more limited. We studied final-year nursing students' risk perceptions using questionnaire-based vignettes involving four patient presentations on patient aggression, manipulating patient and resource risk factors. We found student nurses were most likely to ask for help and wait when managing high-risk patient aggression scenarios. Student nurses placed most importance on their own safety and patient condition in making decisions. Resource risk significantly interacted with gender, with male nurses more likely to seek help when risks were high. There is need to improve student nurse training on managing patient aggression by promoting creative approaches to problem solving and critical thinking using simulation techniques to enhance situation awareness and translate knowledge to practice., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background Procalcitonin (PCT)-guided antibiotic stewardship (ABS) has been shown to reduce antibiotics (ABxs), with lower side-effects and an improvement in clinical outcomes. The aim of this experts workshop was to derive a PCT algorithm ABS for easier implementation into clinical routine across different clinical settings. Methods Clinical evidence and practical experience with PCT-guided ABS was analyzed and discussed, with a focus on optimal PCT use in the clinical context and increased adherence to PCT protocols. Using a Delphi process, the experts group reached consensus on different PCT algorithms based on clinical severity of the patient and probability of bacterial infection. Results The group agreed that there is strong evidence that PCT-guided ABS supports individual decisions on initiation and duration of ABx treatment in patients with acute respiratory infections and sepsis from any source, thereby reducing overall ABx exposure and associated side effects, and improving clinical outcomes. To simplify practical application, the expert group refined the established PCT algorithms by incorporating severity of illness and probability of bacterial infection and reducing the fixed cut-offs to only one for mild to moderate and one for severe disease (0.25 μg/L and 0.5 μg/L, respectively). Further, guidance on interpretation of PCT results to initiate, withhold or discontinue ABx treatment was included. Conclusions A combination of clinical patient assessment with PCT levels in well-defined ABS algorithms, in context with continuous education and regular feedback to all ABS stakeholders, has the potential to improve the diagnostic and therapeutic management of patients suspected of bacterial infection, thereby improving ABS effectiveness.

With the expansion of couples' voluntary HIV counseling and testing (CVCT) in urban Zambia, there is a growing need to evaluate CVCT provider trainings to ensure that couples are receiving quality counseling and care. We evaluated provider knowledge scores, pre- and post-training and predictors of pre- and post-training test scores. Providers operating in 67 government clinics in four Copperbelt Province cities were trained from 2008 to 2013 in three domains: counseling, rapid HIV laboratory testing and data management. Trainees received pre- and post-training tests on domain-specific topics. Pre- and post-training test scores were tabulated by provider demographics and training type, and paired t-tests evaluated differences in pre- and post-training test scores. Multivariable ANCOVA determined predictors of pre- and post-training test scores. We trained 1226 providers, and average test scores increased from 68.8% pre-training to 83.8% post-training (p < 0.001). Test scores increased significantly for every demographic group and training type (p < 0.001) with one exception-test scores did not significantly increase for those receiving counseling or data management training who had less than a high school education. In multivariable analysis, higher educational level and having a medical background were predictive of a higher pre-test score; higher pre-test scores and having a medical background were predictive of higher post-test scores. Pre- and post-test assessments are critical to ensure quality services, particularly as task-shifting from medical to lay staff becomes more common. Assessments showed that our CVCT trainings are successful at increasing knowledge, and that those with lower education may benefit from repeat trainings.

Recent multinational disease outbreaks demonstrate the risk of disease spreading globally before public health systems can respond to an event. To ensure global health security, countries need robust multisectoral systems to rapidly detect and respond to domestic or imported communicable diseases. The US Centers for Disease Control and Prevention International Border Team works with the governments of Nigeria, Togo, and Benin, along with Pro-Health International and the Abidjan-Lagos Corridor Organization, to build sustainable International Health Regulations capacities at points of entry (POEs) and along border regions. Together, we strengthen comprehensive national and regional border health systems by developing public health emergency response plans for POEs, conducting qualitative assessments of public health preparedness and response capacities at ground crossings, integrating internationally mobile populations into national health surveillance systems, and formalizing cross-border public health coordination. Achieving comprehensive national and regional border health capacity, which advances overall global health security, necessitates multisectoral dedication to the aforementioned components.

Importance: Adjunctive hydrocortisone therapy is suggested by the Surviving Sepsis Campaign in refractory septic shock only. The efficacy of hydrocortisone in patients with severe sepsis without shock remains controversial., Objective: To determine whether hydrocortisone therapy in patients with severe sepsis prevents the development of septic shock., Design, Setting, and Participants: Double-blind, randomized clinical trial conducted from January 13, 2009, to August 27, 2013, with a follow-up of 180 days until February 23, 2014. The trial was performed in 34 intermediate or intensive care units of university and community hospitals in Germany, and it included 380 adult patients with severe sepsis who were not in septic shock., Interventions: Patients were randomly allocated 1:1 either to receive a continuous infusion of 200 mg of hydrocortisone for 5 days followed by dose tapering until day 11 (n = 190) or to receive placebo (n = 190)., Main Outcomes and Measures: The primary outcome was development of septic shock within 14 days. Secondary outcomes were time until septic shock, mortality in the intensive care unit or hospital, survival up to 180 days, and assessment of secondary infections, weaning failure, muscle weakness, and hyperglycemia (blood glucose level >150 mg/dL [to convert to millimoles per liter, multiply by 0.0555])., Results: The intention-to-treat population consisted of 353 patients (64.9% male; mean [SD] age, 65.0 [14.4] years). Septic shock occurred in 36 of 170 patients (21.2%) in the hydrocortisone group and 39 of 170 patients (22.9%) in the placebo group (difference, -1.8%; 95% CI, -10.7% to 7.2%; P = .70). No significant differences were observed between the hydrocortisone and placebo groups for time until septic shock; mortality in the intensive care unit or in the hospital; or mortality at 28 days (15 of 171 patients [8.8%] vs 14 of 170 patients [8.2%], respectively; difference, 0.5%; 95% CI, -5.6% to 6.7%; P = .86), 90 days (34 of 171 patients [19.9%] vs 28 of 168 patients [16.7%]; difference, 3.2%; 95% CI, -5.1% to 11.4%; P = .44), and 180 days (45 of 168 patients [26.8%] vs 37 of 167 patients [22.2%], respectively; difference, 4.6%; 95% CI, -4.6% to 13.7%; P = .32). In the hydrocortisone vs placebo groups, 21.5% vs 16.9% had secondary infections, 8.6% vs 8.5% had weaning failure, 30.7% vs 23.8% had muscle weakness, and 90.9% vs 81.5% had hyperglycemia., Conclusions and Relevance: Among adults with severe sepsis not in septic shock, use of hydrocortisone compared with placebo did not reduce the risk of septic shock within 14 days. These findings do not support the use of hydrocortisone in these patients., Trial Registration: clinicaltrials.gov Identifier: NCT00670254.

Background: Procalcitonin (PCT) is increasingly being used for the diagnostic and prognostic work up of patients with suspected infections in the emergency department (ED). Recently, B·R·A·H·M·S PCT direct, the first high sensitive point-of-care test (POCT), has been developed for fast PCT measurement on capillary or venous blood samples., Methods: This is a prospective, international comparison study conducted in three European EDs. Consecutive patients with suspicion of bacterial infection were included. Duplicate determination of PCT was performed in capillary (fingertip) and venous whole blood (EDTA), and compared to the reference method. The diagnostic accuracy was evaluated by correlation and concordance analyses., Results: Three hundred and three patients were included over a 6-month period (60.4% male, median age 65.2 years). The correlation between capillary or venous whole blood and the reference method was excellent: r2=0.96 and 0.97, sensitivity 88.1% and 93.0%, specificity 96.5% and 96.8%, concordance 93% and 95%, respectively at a 0.25 μg/L threshold. No significant bias was observed (-0.04 and -0.02 for capillary and venous whole blood) although there were 6.8% and 5.1% outliers, respectively. B·R·A·H·M·S PCT direct had a shorter time to result as compared to the reference method (25 vs. 144 min, difference 119 min, 95% CI 110-134 min, p<0.0001)., Conclusions: This study found a high diagnostic accuracy and a faster time to result of B·R·A·H·M·S PCT direct in the ED setting, allowing shortening time to therapy and a more wide-spread use of PCT.

Acute kidney injury (AKI) is a frequent finding in patients with critical illness. In many of these patients renal replacement therapy (RRT) is needed to support organ dysfunction. Although international guidelines on the management of AKI have been developed and are widely accepted, there is still considerable controversy on the optimal timing of RRT. The clinician is in a constant dilemma that level of evidence (on timing of acute RRT) is low and the issue is of high importance. Despite this paucity of high quality prospective data, this review will give the reader an idea on how to approach the difficult question of initiating RRT. Obviously, no general recommendation can be given covering every aspect of intensive care medicine. Therefore, general thoughts are displayed, followed by a focus on specific clinical situations. The role of "novel" biomarkers in the process of deciding when to start is also discussed.

Objective. Patients with neutropenic sepsis have a poor prognosis. We aimed to identify outcome predictors and generate hypotheses how the care for these patients may be improved. Methods. All 12.352 patients admitted between 2006 and 2011 to the medical ICUs of our tertiary university center were screened for neutropenia; out of 558 patients identified, 102 fulfilled the inclusion criteria and were analyzed. Severity markers and outcome predictors were assessed. Results. The overall ICU mortality was 54.9%. The severity of sepsis and the number of organ failures predicted survival of the primary septic episode (APACHE II 22.8 and 29.0; SOFA 7.3 and 10.1, resp.). In the recovery phase, persistent organ damage and higher persistent C-reactive protein levels were associated with a poor outcome. Blood transfusions and CMV infection correlated with an unfavorable prognosis. Ineffective initial antibiotic therapy, fungal infections, and detection of multiresistant bacteria displayed a particularly poor outcome. Infections with coagulase-negative staphylococci and enterococci were associated with a significantly higher mortality and a high degree of systemic inflammation. Conclusion. Patients with persistent organ dysfunction show an increased mortality in the further course of their ICU stay. Early antimicrobial treatment of Gram-positive cocci may improve the outcome of these patients.

Severe liver failure is common and carries a high mortality risk in patients with both acute and acute-on-chronic liver failure. The failing liver constitutes a medical emergency, and in many cases liver transplantation is the only definite treatment. Extracorporeal liver support can be employed as a strategy for bridging to transplantation or recovery. This article focuses on options for artificial (nonbiological) extracorporeal treatment: single-pass albumin dialysis, fractionated plasma separation and adsorption (Prometheus(®)) and the molecular adsorbent recirculatory system. Their different principles, potential advantages and indications are discussed. Despite proven biochemical efficacy, there are little data regarding clinical end points. Thus far, molecular adsorbent recirculatory system therapy in acute and acute-on-chronic liver failure showed no survival benefit compared with standard medical therapy. Prometheus therapy showed reduced mortality in subgroups of higher severity of disease compared with standard medical therapy. Nevertheless, the value of extracorporeal liver support remains to be corroborated by further clinical studies that include the optimal timing, mode, intensity and duration of this treatment.

Practice guidelines are systematically developed statements and recommendations that assist the physicians and patients in making decisions about appropriate health care measures for specific clinical circumstances taking into account specific national health care structures. The 1(st) revision of the S-2k guideline of the German Sepsis Society in collaboration with 17 German medical scientific societies and one self-help group provides state-of-the-art information (results of controlled clinical trials and expert knowledge) on the effective and appropriate medical care (prevention, diagnosis, therapy and follow-up care) of critically ill patients with severe sepsis or septic shock. The guideline had been developed according to the "German Instrument for Methodological Guideline Appraisal" of the Association of the Scientific Medical Societies (AWMF). In view of the inevitable advancements in scientific knowledge and technical expertise, revisions, updates and amendments must be periodically initiated. 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.

Early optimization of fluid status is of central importance in the treatment of critically ill patients. This study aims to investigate whether inferior vena cava (IVC) diameters correlate with invasively assessed hemodynamic parameters and whether this approach may thus contribute to an early, non-invasive evaluation of fluid status. Thirty mechanically ventilated patients with severe sepsis or septic shock (age 60 +/- 15 years; APACHE-II score 31 +/- 8; 18 male) were included. IVC diameters were measured throughout the respiratory cycle using transabdominal ultrasonography. Consecutively, volume-based hemodynamic parameters were determined using the single-pass thermal transpulmonary dilution technique. This was a prospective study in a tertiary care academic center with a 24-bed medical intensive care unit (ICU) and a 14-bed anesthesiological ICU. We found a statistically significant correlation of both inspiratory and expiratory IVC diameter with central venous pressure (p = 0.004 and p = 0.001, respectively), extravascular lung water index (p = 0.001, p < 0.001, respectively), intrathoracic blood volume index (p = 0.026, p = 0.05, respectively), the intrathoracic thermal volume (both p < 0.001), and the PaO(2)/FiO(2) oxygenation index (p = 0.007 and p = 0.008, respectively). In this study, IVC diameters were found to correlate with central venous pressure, extravascular lung water index, intrathoracic blood volume index, the intrathoracic thermal volume, and the PaO(2)/FiO(2) oxygenation index. Therefore, sonographic determination of IVC diameter seems useful in the early assessment of fluid status in mechanically ventilated septic patients. At this point in time, however, IVC sonography should be used only in addition to other measures for the assessment of volume status in mechanically ventilated septic patients., (Copyright 2010 Elsevier Inc. All rights reserved.)

Acute liver failure (ALF) and acute-on-chronic liver failure (AoCLF) are associated with a high mortality. In these patients an accumulation of both water-soluble and water-insoluble, protein-bound, metabolic waste products occurs. Conventional extracorporeal blood purification techniques based on diffusion and/or convection such as hemodialysis or hemofiltration may only eliminate small molecular weight, water-soluble compounds. In recent years, fractionated plasma separation and adsorption (FPSA) with the Prometheus system has been introduced for extracorporeal liver support therapy. To date, however, only limited data is available regarding the effect of this treatment on mortality and outcome of patients with advanced liver disease. Here we report on our experience with 23 patients with severe liver failure who were treated with Prometheus in our medical intensive care unit. Fourteen patients had AoCLF, and nine patients experienced ALF. The median bilirubin level at the start of Prometheus therapy was 30.5 mg/dL and the median Acute Physiology and Chronic Health Evaluation II (APACHE II) score was 26. During 40 individual treatment sessions lasting 5-6 h, Prometheus therapy reduced serum bilirubin levels from 23.7 mg/dL to 15.0 mg/dL (median values) (P < 0.001), and the overall survival was 26%. ALF patients had a better survival compared to AoCLF patients (44% vs. 22%; P = 0.022). Apart from one patient who developed hemodynamic instability during a treatment session, Prometheus therapy was well tolerated without relevant side-effects. In conclusion, extracorporeal liver support therapy with Prometheus is a novel and safe treatment option in patients with severe liver failure. In this series, patients with ALF showed a significantly better outcome with Prometheus therapy compared to AoCLF patients.

Background: Sound data about the prevalence of acute renal failure (ARF) among patients with severe sepsis and septic shock are lacking. Further, it is not known whether ARF is an independent risk factor for mortality in septic patients or merely an indicator of disease severity., Methods: A prospective cross-sectional one-day prevalence study was carried out in a representative sample of German ICUs, divided into five strata (< 200 beds; 201-400 beds; 401-600 beds; > 600 beds; university hospitals). 3877 patients were screened of whom 415 had severe sepsis and septic shock., Results: Fourteen patients (3.4%) had chronic dialysis-dependent RF and were excluded from analysis. Of the remaining 401 patients, 166 (41.4%) had ARF, as defined by a rise in creatinine above twice the upper limit of normal and/or a drop in urine output to < 0.5 ml/kg bodyweight. Median APACHE II score was 22 in patients with ARF and 16 in patients without ARF (p< 0.0001). Patients with severe sepsis/septic shock had an overall hospital mortality of 55.2%. Hospital mortality in patients with ARF was 67.3% and without ARF 42.8% (p< 0.0001). After adjustment for APACHE II score and age, ARF remained a significant independent risk factor for death [odds ratio (OR) 2.11, 95% confidence interval (CI) 1.27-3.52]. Mortality in septic patients was not associated with pre-existing, non-dialysis-dependent chronic kidney disease, whereas in dialysis-dependent patients with sepsis mortality increased to 86%., Conclusion: In this representative survey in patients with severe sepsis/septic shock, prevalence of ARF is high with 41.4%. ARF represents a significant independent risk factor for mortality in these patients.

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<0.001). However, at 28 days, there was no significant difference between the two groups in the rate of death or the mean score for organ failure. The rate of severe hypoglycemia (glucose level, < or = 40 mg per deciliter [2.2 mmol per liter]) was higher in the intensive-therapy group than in the conventional-therapy group (17.0% vs. 4.1%, P<0.001), as was the rate of serious adverse events (10.9% vs. 5.2%, P=0.01). HES therapy was associated with higher rates of acute renal failure and renal-replacement therapy than was Ringer's lactate., Conclusions: The use of intensive insulin therapy placed critically ill patients with sepsis at increased risk for serious adverse events related to hypoglycemia. As used in this study, HES was harmful, and its toxicity increased with accumulating doses. (ClinicalTrials.gov number, NCT00135473.), (2008 Massachusetts Medical Society)

Introduction: Persistent coma is a common finding after cardiac arrest and has profound ethical and economic implications. Evidence suggests that therapeutic hypothermia improves neurological outcome in these patients. In this analysis, we investigate whether therapeutic hypothermia influences the length of intensive care unit (ICU) stay and ventilator time in patients surviving out-of-hospital cardiac arrest., Methods: A prospective observational study with historical controls was conducted at our medical ICU. Fifty-two consecutive patients (median age 62.6 years, 43 males, 34 ventricular fibrillation) submitted to therapeutic hypothermia after out-of-hospital cardiac arrest were included. They were compared with a historical cohort (n = 74, median age 63.8 years, 53 males, 43 ventricular fibrillation) treated in the era prior to hypothermia treatment. All patients received the same standard of care. Neurological outcome was assessed using the Pittsburgh cerebral performance category (CPC) score. Univariate analyses and multiple regression models were used., Results: In survivors, therapeutic hypothermia and baseline disease severity (Acute Physiology and Chronic Health Evaluation II [APACHE II] score) were both found to significantly influence ICU stay and ventilator time (all P < 0.01). ICU stay was shorter in survivors receiving therapeutic hypothermia (median 14 days [interquartile range (IQR) 8 to 26] versus 21 days [IQR 15 to 30] in the control group; P = 0.017). ICU length of stay and time on ventilator were prolonged in patients with CPC 3 or 4 compared with patients with CPC 1 or 2 (P = 0.003 and P = 0.034, respectively). Kaplan-Meier analysis showed improved probability for 1-year survival in the hypothermia group compared with the controls (log-rank test P = 0.013)., Conclusion: Therapeutic hypothermia was found to significantly shorten ICU stay and time of mechanical ventilation in survivors after out-of-hospital cardiac arrest. Moreover, profound improvements in both neurological outcome and 1-year survival were observed.

Introduction: Hyperglycemia is associated with negative outcomes in various settings of critical illness; infectious complications, especially, seem to be increased. On the other hand, intensive insulin therapy (IIT) has been shown to improve outcome in clinical trials. Whether normoglycemia itself or the application of insulin is responsible for the observed findings is unknown. We therefore tested the effect of glucose and insulin on various immune functions in vitro., Methods: Human peripheral blood mononuclear cells (PBMCs) were incubated ex vivo with low doses of lipopolysaccharide (LPS). PBMCs were incubated with various osmotic agents, insulin, or a combination of both. Interleukin (IL)-6 and IL-1 cytokine response was measured by enzyme-linked immunosorbent assay. In addition, we investigated the effects of glucose on phagocytosis and oxidative burst in human granulocytes., Results: Increasing concentrations of both glucose and mannitol significantly enhanced LPS-induced cytokine production. Insulin alone did not alter cytokine production and had only a minor influence in combination with glucose. Phagocytosis and oxidative burst were significantly reduced with increasing concentrations of glucose and mannitol., Conclusion: Hyperglycemia may lead to inflammation by enhancing cytokine production via the direct effects of hyperosmotic stress. Impaired phagocytosis and oxidative burst under hyperglycemia may weaken defense mechanisms of the host. Our in vitro findings may help to explain the beneficial effects of IIT not only in diabetic but also in critically ill patients.

Objective: To determine the prevalence and mortality of ICU patients with severe sepsis in Germany, with consideration of hospital size., Design: Prospective, observational, cross-sectional 1-day point-prevalence study., Setting: 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)., Patients: 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., Measurements and Results: 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 (