[Ward-based clinical pharmacists in intensive care medicine: an economic evaluation]. / Stationsapotheker:innen in der Intensivmedizin: ökonomische Nutzenanalyse.

BACKGROUND: The positive impact of pharmaceutical care in improving medication safety is considered proven. Little is known about the economic benefit of clinical pharmaceutical services in Germany. OBJECTIVE: In 2020, a pilot project was started at the Ernst von Bergmann Hospital to introduce ward-based clinical pharmacists in intensive care medicine, also in order to determine the economic benefit of the medication management offered. METHODS: By a team of experienced intensive care physicians and clinical pharmacists on the basis of a consensus principle, each pharmaceutical intervention (PI) was assigned a probability score (Nesbit probability score) with which an adverse drug event (ADE) would have occurred. Assuming that each ADE results in an increased length of stay, the costs of intensive care treatment/day were used as potential savings. The model thereby combines the findings of two international publications to enable an economic analysis of pharmaceutical services. RESULTS: During the study period, 177 pharmaceutical interventions were evaluated and corresponding probability scores for the occurrence of ADE were determined. From this, annual savings of €â€¯80,000 through avoided costs were calculated. CONCLUSION: In this project, the economic benefit of pharmaceutical services in intensive care medicine was proven. Ward-based clinical pharmacists are now an integral part of the intensive care treatment team at the Ernst von Bergmann Hospital.

[Present practise patterns of renal replacement therapy in German intensive care medicine]. / Aktueller Stand der Durchführung von Nierenersatztherapien auf deutschen Intensivstationen.

About 50% of all critically ill patients develop acute kidney injury (AKI) and approximately 15% receive renal replacement therapy (RRT). Although RRT is frequently used in intensive care units in Germany, it is currently unknown which RRT procedures are available, which qualification the involved staff has, which anticoagulation strategies are used and how RRT doses are prescribed. To investigate quality and structural characteristics of the performance of RRT in intensive care units throughout Germany, the German Interdisciplinary Society of Intensivists (Deutsche Interdisziplinäre Vereinigung für Intensiv- und Notfallmedizin [DIVI]) performed an inquiry among their members. A total of 897 members participated in the survey in which practical aspects were queried. In 69.1% of the cases, RRT was performed in hospitals with more than 400 beds and in 74.5% in university hospitals or other primary care hospitals. Furthermore, 93.3% of clinics are equipped with continuous and 75.8% with intermittent renal replacement devices. In 91.9%, indication for initiation of RRT was performed by trained physicians specialized in intensive care medicine or nephrologists. Intermittent as well as continuous modalities are both present in three-quarters of cases, which allows for individualized therapy. However, the documentation of dialysis dose needs to be improved.

[Crystalloids and colloids: fluid homeostasis and toxicity]. / Kristalloide und Kolloide: Flüssigkeitshomöostase und Toxizität.

Fluid balance is crucial in critically ill patients because mechanisms to counteract fluid dysbalances are limited. Therefore, an extremely important task of ICU staff is to assess and maintain fluid status. Fluid overload has been shown to have deleterious consequences for patients. Infusion fluids may be divided into colloid and crystalloid solutions. Within the crystalloids, balanced solutions have been shown to be superior over 0.9% saline with respect to acidosis, acute kidney injury, and mortality. The most widespread used colloid is hydroyethyl starch (HES). Compared to crystalloids, HES has a much greater volume effect. Despite this advantage, precautions must be undertaken with the use of HES. Side effects such as anaphylactic reactions and acute kidney injury are not uncommon; thus, critically ill patients and those at risk of kidney dysfunction should only receive HES preparations after careful consideration.

Use of IFNγ/IL10 Ratio for Stratification of Hydrocortisone Therapy in Patients With Septic Shock.

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.

[Quality improvement measures in the care of critically ill intensive care patients with renal replacement therapy for acute kidney injury : Position paper of the Kidney Section of DIVI in collaboration with DGAI and DGIIN]. / Qualitätsverbessernde Maßnahmen in der Versorgung von kritisch kranken Intensivpatienten mit Nierenersatztherapie bei akuter Nierenschädigung : Positionspapier der Sektion Niere der DIVI unter Mitarbeit von DGAI und DGIIN.

Renal replacement therapy is after mechanical ventilation one of the most important and frequently used organ replacement therapies in daily routine intensive care practice. In contrast to mechanical ventilation, quality standards for renal replacement therapy are less well known and defined. In this position paper of the German Interdisciplinary Association for Intensive Care and Emergency Medicine, we describe quality standards of renal replacement procedures in order to improve therapy of patients with severe acute kidney injury.

Procalcitonin (PCT)-guided antibiotic stewardship: an international experts consensus on optimized clinical use.

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.

Effect of Hydrocortisone on Development of Shock Among Patients With Severe Sepsis: The HYPRESS Randomized Clinical Trial.

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.

Neutropenic Sepsis in the ICU: Outcome Predictors in a Two-Phase Model and Microbiology Findings.

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.

Timing of renal replacement therapy in acute kidney injury.

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.

Comparison between B·R·A·H·M·S PCT direct, a new sensitive point-of-care testing device for rapid quantification of procalcitonin in emergency department patients and established reference methods - a prospective multinational trial.

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.

Effect of empirical treatment with moxifloxacin and meropenem vs meropenem on sepsis-related organ dysfunction in patients with severe sepsis: a randomized trial.

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.

Artificial extracorporeal liver support therapy in patients with severe liver failure.

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.

Inferior vena cava diameter correlates with invasive hemodynamic measures in mechanically ventilated intensive care unit patients with sepsis.

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.

Extracorporeal liver support therapy with Prometheus in patients with liver failure in the intensive care unit.

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.

Corticosteroids in the treatment of severe sepsis and septic shock in adults: a systematic review.

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.

Practice and perception--a nationwide survey of therapy habits in sepsis.

OBJECTIVE: To simultaneously determine perceived vs. practiced adherence to recommended interventions for the treatment of severe sepsis or septic shock. DESIGN: One-day cross-sectional survey. SETTING: Representative sample of German intensive care units stratified by hospital size. PATIENTS: Adult patients with severe sepsis or septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Practice recommendations were selected by German Sepsis Competence Network (SepNet) investigators. External intensivists visited intensive care units randomly chosen and asked the responsible intensive care unit director how often these recommendations were used. Responses "always" and "frequently" were combined to depict perceived adherence. Thereafter patient files were audited. Three hundred sixty-six patients on 214 intensive care units fulfilled the criteria and received full support. One hundred fifty-two patients had acute lung injury or acute respiratory distress syndrome. Low-tidal volume ventilation < or = 6 mL/kg/predicted body weight was documented in 2.6% of these patients. A total of 17.1% patients had tidal volume between 6 and 8 mL/kg predicted body weight and 80.3% > 8 mL/kg predicted body weight. Mean tidal volume was 10.0 +/- 2.4 mL/kg predicted body weight. Perceived adherence to low-tidal volume ventilation was 79.9%. Euglycemia (4.4-6.1 mmol/L) was documented in 6.2% of 355 patients. A total of 33.8% of patients had blood glucose levels < or = 8.3 mmol/L and 66.2% were hyperglycemic (blood glucose > 8.3 mmol/L). Among 207 patients receiving insulin therapy, 1.9% were euglycemic, 20.8% had blood glucose levels < or = 8.3 mmol/L, and 1.0% were hypoglycemic. Overall, mean maximal glucose level was 10.0 +/- 3.6 mmol/L. Perceived adherence to strict glycemic control was 65.9%. Although perceived adherence to recommendations was higher in academic and larger hospitals, actual practice was not significantly influenced by hospital size or university affiliation. CONCLUSIONS: This representative survey shows that current therapy of severe sepsis in German intensive care units complies poorly with practice recommendations. Intensive care unit directors perceive adherence to be higher than it actually is. Implementation strategies involving all intensive care unit staff are needed to overcome this gap between current evidence-based knowledge, practice, and perception.

Hyperosmotic stress enhances cytokine production and decreases phagocytosis in vitro.

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.