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.

The effect of peer review on mortality rates.

OBJECTIVE: Lowering of mortality rates in hospitals with mortality rates higher than accepted reference values for acute myocardial infarction (AMI), congestive heart failure (CHF), pneumonia, stroke, mechanical ventilation (MV) and colorectal surgery by using an external peer review process that identifies areas requiring rectification and implements protocols directed at improving these areas. DESIGN: Retrospective, observational, quality management study using administrative data to compare in-hospital mortality rates (pre and post an external peer review process that included adoption of improvement protocols) with reference values. SETTING: German general hospitals of a large, private group. PARTICIPANTS: Hospitals with mortality rates higher than reference values. INTERVENTIONS: Peer review of medical records by experienced, outside physicians triggered by in-hospital mortality rates higher than expected. Inadequacies were identified, improvement protocols enforced and mortality rates subsequently re-examined. MAIN OUTCOME MEASURES: Mortality rates 1 year before and 1 year after peer review and protocol use. RESULTS: For AMI, CHF, pneumonia, stroke, MV and colorectal surgery, the mortality rates 1 year post-peer review were significantly decreased as compared to pre-peer review mortality rates. The standardized mortality ratio for all of the above diagnoses was 1.45, 1 year before peer review, and 0.97, 1 year after peer review. The absolute risk reduction of 7.3% translates into 710 deaths in this population which could have been prevented. CONCLUSIONS: Peer review triggered and conducted in the manner described here is associated with a significant lowering of in-hospital mortality rates in hospitals that previously had higher than expected mortality rates.

Prevention, diagnosis, therapy and follow-up care of sepsis: 1st revision of S-2k guidelines of the German Sepsis Society (Deutsche Sepsis-Gesellschaft e.V. (DSG)) and the German Interdisciplinary Association of Intensive Care and Emergency Medicine (Deutsche Interdisziplinäre Vereinigung für Intensiv- und Notfallmedizin (DIVI)).

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.

[Effects of a mandatory guideline that prohibit hospital doctors from accepting any form of benefits in any form from the pharmaceutical industry]. / Der Einfluss einer krankenhausinternen Richtlinie auf die Einstellung von Arzten zur pharmazeutischen Industrie.

BACKGROUND AND OBJECTIVE: Several hospitals have issued their own guidelines that regulate the conduct of staff members toward the pharmaceutical industry. The effect of theses guidelines on the attitude of the doctors toward the pharmaceutical industry in Germany has so far been unknown. This study investigated whether hospital doctors with guidelines and those without guidelines differ in their attitude toward the pharmaceutical industry. METHODS: A retrospective analysis was undertaken to determine the influence of hospital guidelines on the attitude of doctors toward the pharmaceutical industry. In May 2008 all doctors in intensive care of a hospital with and one without guidelines were asked anonymously by a questionnaire about their dealings with the pharmaceutical industry. The response rate was 64.9 % (37/57) and 55.1 % (59/107) respectively. The cooperation rate in both groups was 100 %. RESULTS: In the hospital with guidelines every doctor was on average carrying 0.56 +/- 0.64 pharmaceutical advertising gifts with a company logo, while the average in the institution without guidelines was 1.2 +/- 0.61 advertising gifts (p = 0.026). Whereas 49 % of doctors with guidelines considered the acceptance of advertising gifts as not questionable, 81 % without guidelines did (p = 0.001; RRR = 0.65; 95 % CI = 0.48-0.91). Furthermore, 70 % of doctors in the institution with guidelines compared with 92 % of those doctors in the hospital without guidelines believed that the advertising practices of the pharmaceutical industry had no influence on their prescribing behaviour (p = 0.010; RRR = 3.6; 95 % CI = 1.36-9.52). Both groups of doctors are convinced that other doctors are more influenced by the pharmaceutical industry than they are themselves (51 % with and 37 % without guidelines, p = 0.207). 70 % and 90 %, respectively of all participants considered hospital guidelines setting standards of conduct toward the pharmaceutical industry and those not sponsored by industry to have a positive effect. Every other doctor additionally stated the advice by the pharmaceutical industry was not helpful for his work. CONCLUSIONS: Hospital guidelines on relations with the pharmaceutical industry appear to further a critical attitude by physicians regarding the pharmaceutical industry.

[Study protocol of the VISEP study. Response of the SepNet study group]. / Studienprotokoll der VISEP-Studie. Entgegnung der SepNet-Studiengruppe.

In the commentary by Zander et al. the authors appear concerned about the methods and results of our, at that time, unpublished sepsis trial evaluating hydroxyethyl starch (HES) and insulin therapy. Unfortunately, the authors' concerns are based on false assumptions about the design, conduct and modes of action of the compounds under investigation. For instance, in our study the HES solution was not used for maintenance of daily fluid requirements, so that the assumption of the authors that this colloid was used "exclusively" is wrong. Moreover, the manufacturer of Hemohes, the HES product we used, gives no cut-off value for creatinine, thus the assumption that this cut-off value was "doubled" in our study is also incorrect. Other claims by the authors such as that lactated solutions cause elevated lactate levels, iatrogenic hyperglycemia and increase O(2) consumption are unfounded. There is no randomized controlled trial supporting such a claim - this claim is neither consistent with our study data nor with any credible published sepsis guidelines or with routine practice worldwide. We fully support open scientific debate. Our study methods and results have now been published after a strict peer-reviewing process and this data is now open to critical and constructive reviewing. However, in our opinion this premature action based on wrong assumptions and containing comments by representatives of pharmaceutical companies does not contribute to a serious, unbiased scientific discourse.

[Diagnosis and therapy of sepsis: guidelines of the German Sepsis Society Inc. and the German Interdisciplinary Society for Intensive and Emergency Medicine]. / Diagnose und therapie der sepsis: S2-Leitlinien der Deutschen Sepsis-Gesellschaft e.V. (DSG) und der Deutschen Interdisziplinären Vereinigung für Intensiv- und Notfallmedizin (DIVI).

A recent survey conducted by the publicly funded Competence Network Sepsis (SepNet) reveals that severe sepsis and/or septic shock occurs in 75,000 inhabitants (110 out of 100,000) and sepsis in 79,000 inhabitants (116 out of 100,000) in Germany annually. This illness is responsible for approximately 60,000 deaths and ranges as the third most frequent cause of death after acute myocardial infarction. Direct costs for the intensive care of patients with severe sepsis alone amount to approximately 1.77 billion euros, which means that about 30% of the budget in intensive care is used to treat severe sepsis. However, until now German guidelines for the diagnosis and therapy of severe sepsis did not exist. Therefore, the German Sepsis Society initiated the development of guidelines which are based on international recommendations by the International Sepsis Forum (ISF) and the Surviving Sepsis Campaign (SSC) and take into account the structure and organization of the German health care system. Priority was given to the following guideline topics: a) diagnosis, b) prevention, c) causative therapy, d) supportive therapy, e) adjunctive therapy. The guidelines development process was carefully planned and strictly adhered to the requirements of the Working Group of Scientific Medical Societies (AWMF).

[Diagnosis and therapy of sepsis]. / Diagnose und Therapie der Sepsis - S-2 Leitlinien der Deutschen Sepsis-Gesellschaft e.V. (DSG) und der Deutschen Interdisziplinären Vereinigung für Intensiv- und Notfallmedizin (DIVI).

A recent survey conducted by the publicly funded Competence Network Sepsis (Sep- Net) reveals that severe sepsis and/or septic shock occurs in 75,000 inhabitants (110 out of 100,000) and sepsis in 79,000 inhabitants (116 out of 100,000) in Germany annually. This illness is responsible for approx. 60,000 deaths and ranges as the third most frequent cause of death after acute myocardial infarction. Direct costs for the intensive care of patients with severe sepsis alone amount to approx. 1.77 billion euros, which means that about 30% of the budget in intensive care is used to treat severe sepsis. However, until now German guidelines for the diagnosis and therapy of severe sepsis did not exist. Therefore, the German Sepsis Society initiated the development of guidelines which are based on international recommendations by the International Sepsis Forum (ISF) and the Surviving Sepsis Campaign (SSC) and take into account the structure and organisation of the German health care system. Priority was given to the following guideline topics: a) diagnosis, b) prevention, c) causative therapy, d) supportive therapy, e) adjunctive therapy. The guidelines development process was carefully planned and strictly adhered to according to the requirements of the Working Group of Scientific Medical Societies (AWMF).

[Diagnosis and therapy of sepsis. Guidelines of the German Sepsis Society Inc. and the German Interdisciplinary Society for Intensive and Emergency Medicine]. / Diagnose und Therapie der Sepsis. S2-Leitlinien der Deutschen Sepsis-Gesellschaft e.V. (DSG) und der Deutschen Interdisziplinären Vereinigung für Intensiv- und Notfallmedizin (DIVI).

A recent survey conducted by the publicly funded Competence Network Sepsis (SepNet) reveals that severe sepsis and/or septic shock occurs in 75,000 inhabitants (110 out of 100,000) and sepsis in 79,000 inhabitants (116 out of 100,000) in Germany annually. This illness is responsible for approximately 60,000 deaths and ranges as the third most frequent cause of death after acute myocardial infarction. Direct costs for the intensive care of patients with severe sepsis alone amount to approximately 1.77 billion euros, which means that about 30% of the budget in intensive care is used to treat severe sepsis. However, until now German guidelines for the diagnosis and therapy of severe sepsis did not exist. Therefore, the German Sepsis Society initiated the development of guidelines which are based on international recommendations by the International Sepsis Forum (ISF) and the Surviving Sepsis Campaign (SSC) and take into account the structure and organization of the German health care system. Priority was given to the following guideline topics: a) diagnosis, b) prevention, c) causative therapy, d) supportive therapy, e) adjunctive therapy. The guidelines development process was carefully planned and strictly adhered to the requirements of the Working Group of Scientific Medical Societies (AWMF).

[Requirements and expectations for optimal volume replacement]. / Forderungen und Erwartungen an einen optimalen Volumenersatz.

A volume replacement should compensate a reduction in the intravascular volume and counteract a hypovolemia so that hemodynamics and vital functions can be maintained. For this therapy, a physiologically-based solution comprising both osmotically and colloid osmotically active components should be administered. A consensus is proposed for this purpose which takes into consideration the following aspects: The optimum colloid, the questionable use of albumin, the physiological electrolyte pattern encompassing sodium, potassium, chloride and phosphate and their contributions to osmolality, an eventual addition of glucose, the physiological acid-base status with bicarbonate or alternately with metabolisable anions, and the importance of a clear declaration of all ingredients. The consensus distinguishes between compulsory requirements derived from evidence-based medicine and physiological data and the potential expectations of an optimal volume replacement, including well-grounded wishes and aspirations for the future.

Post-operative hypoalbuminaemia and procalcitonin elevation for prediction of outcome in cardiopulmonary bypass surgery.

BACKGROUND: Because few studies have addressed postoperative hypoalbuminaemia in relation to hospital mortality, we evaluated this association and the prognostic value of increased procalcitonin (PCT) after cardiopulmonary bypass (CPB) surgery. METHODS: In 454 consecutive patients undergoing CPB, minimal serum albumin, colloid osmotic pressure (COP) and maximal PCT were retrospectively obtained from the 2nd to 10th postoperative day. Receiver operating characteristic (ROC) and multiple regression analyses determined independent predictive strength for 28-day mortality from preoperative albumin, Euroscore, postoperative minimal albumin and COP, and maximal PCT. Cut-off points for the four strongest predictors were calculated by the area under the curve (AUC) in the ROC for the 28-day mortality. RESULTS: Maximal PCT showed the largest AUC (0.85; 95% CI 0.79-0.90) and the highest relative risk (RR 12.17; 95%CI 5.26-28.16; P < 0.001), compared with postoperative albumin (AUC 0.72; 95% CI 0.62-0.81; RR 5.35; 95%CI 2.99-9.56; P < 0.001) and EuroSCORE (AUC 0.73; 95%CI 0.63-0.83; RR 4.48; 95%CI: 1.78-11.28; P < 0.01). By logistic regression, postoperative albumin was the strongest predictor of mortality (odds ratio 0.86; 95% CI 0.84-0.89). Cut-off values for predicting 28-day mortality were found for postoperative albumin and PCT at 17.8 g l(-1) and 2.5 ng l(-1), respectively. A slight but significant inverse correlation between PCT and albumin was found. Patients with albumin less than the cut-off showed significantly higher median values for PCT levels (2.5 vs. 1.0 g l-1), a higher 28-day mortality rate (20.8% vs. 4.5%), and a longer ICU stay (6 vs. 3 days) in comparison with patients with minimal albumin greater than 18 g l(-1). CONCLUSIONS: Post-operative serum albumin <18 g l(-1) and PCT >2.5 ng l(-1) are predictive for a higher 28-day mortality rate in cardiosurgical patients. Both peak PCT and minimal albumin were better outcome predictors than the Euroscore, which better represents the preoperative condition of the patient.

Equivalence of hydroxyethyl starch HES 130/0. 4 and HES 200/0. 5 for perioperative volume replacement in major gynaecological surgery.

BACKGROUND: Hydroxyethyl starch solutions (HES) are increasingly used for the compensation of surgical blood loss. The objective of this clinical trial was to compare a novel 6% HES 130/0.4 solution with a favourable pharmacological profile and a standard 6% HES 200/0.5 solution for maintenance of haemodynamic stability in major gynaecological surgery. METHODS: Sixty female patients aged 18-80 years undergoing major gynaecological surgery with indication for perioperative colloidal volume replacement were enrolled in this prospective, randomized double-blinded clinical study. The administration of study medication was dependent on individual requirements to maintain haemodynamic stability. The amount of study medication required from induction of anaesthesia until 6 h postoperatively served as the primary investigative parameter. RESULTS: The two one-sided test procedure by Westlake demonstrated equivalence of mean infused volumes between HES 130/0.4 and HES 200/0.5 during the study period (1224 +/- 544 ml and 1389 +/- 610 ml, respectively, P < 0.05). Perioperatively, haemodynamics did not differ significantly between treatment groups. While none of the mean values of coagulation parameters shifted outside the normal range, the degree of haemodilution revealed reduced haematocrit values in HES 200/0.5 treated patients at 6 h postoperatively (P < 0.05). Moreover, prothrombin time (PT) was higher and consequently international normalized ratio (INR) was lower at the same time point for patients who received HES 130/0.4 (P < 0.05). CONCLUSION: This clinical trial demonstrated therapeutic equivalence of this novel low-substituted HES 130/0.4 solution and a standard HES 200/0.5 solution for perioperative volume replacement. Moreover, both HES preparations were equally well-tolerated and safe.

Does the optimization of cardiac output by fluid loading increase splanchnic blood flow?

We studied the effects of increasing cardiac output by fluid loading on splanchnic blood flow in patients with haemodynamically stabilized septic shock. Eight patients (five female, 39-86 yr) were assessed using a transpulmonary thermo-dye-dilution technique for the measurement of cardiac index (CI) intrathoracic blood volume (ITBV) as a marker of cardiac preload and total blood volume (TBV). Splanchnic blood flow was measured by the steady state indocyanine-green technique using a hepatic venous catheter. Gastric mucosal blood flow was estimated by regional carbon dioxide tension (PRCO2). Hydroxyethyl starch was infused to increase cardiac output while mean arterial pressure was kept constant. In parallel, mean norepinephrine dosage could be reduced from 0.59 to 0.33 microg kg(-1) min(-1). Mean (SD) TBV index increased from 2549 (365) to 3125 (447) ml m(-2), as did ITBV index from 888 (167) to 1075 (266) ml m(-2) and CI from 3.6 (1.0) to 4.6 (1.0) litre min(-1) m(-2). Despite marked individual differences, splanchnic blood flow did not change significantly neither absolutely (from 1.09 (0.96) to 1.19 (0.91) litre min(-1) m(-2)) nor fractionally as part of CI (from 28.4 (19.5) to 24.9 (16.3)%). Gastric mucosal PRCO2 increased from 7.7 (2.6) to 8.3 (3.1) kPa. The PCO2-gap, the difference between regional and end-tidal PCO2, increased slightly from 3.2 (2.7) to 3.4 (3.1) kPa. Thus, an increase in cardiac output as a result of fluid loading is not necessarily associated with an increase in splanchnic blood flow in patients with stabilized septic shock.

Variability of splanchnic blood flow in patients with sepsis.

OBJECTIVES: Previous studies on therapeutic interventions in sepsis have assumed stability of the measure of splanchnic blood flow throughout the study. We assessed the variability of splanchnic blood flow during stable global hemodynamics in eight patients with sepsis requiring treatment with dobutamine and/or norepinephrine. DESIGN AND SETTING: Prospective clinical study in an intensive care unit of a university hospital. MEASUREMENTS AND RESULTS: Global and regional hemodynamics were measured at baseline, 2 h later, and 4 h later. Cardiac output was measured by transpulmonary thermodilution, intrathoracic blood volume as an indicator of cardiac preload, and total blood volume by the double indicator (thermo-dye) dilution technique. Total body oxygen consumption was assessed by indirect calorimetry using a metabolic cart. Splanchnic blood flow was measured by the continuous indocyanine green method, and gastric mucosal CO2 tension by gas tonometry. Neither absolute nor fractional splanchnic blood flow (as ratio of cardiac output) revealed significant global tendencies during the study period. However, variance component analysis showed that splanchnic blood flow determinations varied considerably within patients, for repeated measurements at 5-min intervals (standard error 31.1%) as well as for average values at 2-h intervals (25.6%). CONCLUSION: Stable global hemodynamics during a 4-h period in septic patients does not exclude marked changes in splanchnic blood measured by a hepatic venous catheter technique.