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Purpose The COVID-19 pandemic has led to global changes in healthcare systems. The purpose of this study was to investigate the effects on surgical care of patients. Methods We performed a retrospective analysis of routine data from the largest hospital group in Germany (68 acute hospitals). Included were inpatients who underwent cholecystectomy between March 19, 2020 (beginning of the first lockdown in Germany) and September 22, 2020. These patients were compared with those treated in the same interval in 2019. Results In the 2020 study period, 4035 patients met the inclusion criteria (2019: 4526 patients). During the first lockdown, there was a significant reduction in the number of cholecystectomies performed (51.1% decrease). More patients with a higher risk profile underwent urgent operations, which were accompanied by a significant increase in conversion from laparoscopic to open cholecystectomy. The patients were treated as inpatients for a longer duration than 2019, and the mortality rate increased significantly to 1.3% (2019: 0.1%). The complication rate also showed a significant increase. After the end of the first lockdown, daily admission rates normalized very quickly. However, it was not possible to fully address the backlog of operations. Conclusion There is still a “patient stagnation” 6 months after the first German lockdown. Extrapolated to the national level, this corresponds to almost 21,000 fewer cholecystectomies performed in Germany in 2020. It remains to be seen whether surgical rates will return to pre-pandemic levels and whether complications will arise in the future due to the lack of operations.

The impact of COVID-19 on urgent and involuntary inpatient admissions, as well as coercive measures, has not been assessed so far. A retrospective study was performed analyzing claims data for inpatient psychiatric admissions between 2018 and 2020 (total n = 64,502) from a large German Hospital network. Whilst the total number of urgent admissions decreased in 2020 (12,383) as compared to 2019 (13,493) and 2018 (13,469), a significant increase in the percentage of urgent admissions was observed in 2020 (62.9%) as compared to 2019 (60.6%) and 2018 (59.7%). Compared to this study period, Odds ratio (OR) for proportion were 0.87 (0.84, 0.91) and 0.91 (0.87, 0.95) for 2018 and 2019, respectively (both p

ZusammenfassungCOVID-19 hat zu umfassenden Veränderungen der Welt, wie wir sie bisher kannten, geführt. Durch den starken Anstieg intensivpflichtiger COVID-Patienten wurden beispielsweise elektive Aufnahmen und Eingriffe verschoben. Aber auch Notfälle wie Myokardinfarkte gingen zurück. Die hier vorliegende Studie hat sich mit den Auswirkungen der COVID-Pandemie auf viszeralchirurgische Notfälle anhand von 5 Indikatoroperationen beschäftigt. Dafür wurden Routinedaten aus 73 Akutkrankenhäusern der Helios-Gruppe ausgewertet. Eingeschlossen wurden die Eingriffe, die zwischen dem 13.03.2020 und 12.03.2021 durchgeführt wurden. Verglichen wurden die Daten mit dem Zeitraum vom 13.03.2019 bis zum 12.03.2020.Die Anzahl der Eingriffe bei schwerwiegenden Notfällen (Ileus, mesenteriale Ischämie und Ulkusperforation) sind konstant geblieben. Die Liegedauer im Krankenhaus war im Pandemiejahr 2020 jedoch signifikant kürzer als im Vergleichsjahr 2019. Die Anzahl der Cholezystektomien und Appendektomien war im Pandemiejahr signifikant geringer als im Vergleichsjahr 2019. Die Outcome-Parameter intensivmedizinische Betreuung, invasive Beatmung und Krankenhausmortalität waren zwischen den beiden Zeiträumen für die untersuchten Eingriffe vergleichbar.

Aims Digital health technologies have the potential to improve patient care sustainably. A digital capturing of patient-reported outcome measures (PROMs) could facilitate patients’ surveillance and endpoint assessment within clinical trials especially in heart failure (HF) patients. However, data regarding the availability of digital infrastructure and patients’ willingness to use digital health solutions are scarce. Therefore, we conducted a survey as part of a digital-based HF registry. Methods and results The Helios Heart registry (H2-registry) has been introduced as a prospective registry being based on digitally augmented processes throughout the whole trial conduction from patients’ selection to data collection and follow-up (FU). Patient-reported outcome measures are captured paper-based at recruitment, but patients are offered two digital solutions for FU. Overall, 125 patients (mean age 67.8 years, 34.4% female) were included in the single-centre run-in phase of 16 weeks. Of them, 52.0% were not interested in any digital contact as part of the FU. If digital PROM capturing was conceivable, a web-based solution (70.0%) was preferred to an application-based approach (30.0%). Discrepancies occurred regarding the availability of email accounts and smartphones. Patients in the non-digital group were older (72.0 years vs. 63.2 years, P Conclusions Our survey illustrated difficulties of implementing a digital FU to record PROMs in a contemporary HF cohort in particular among older patients. Further research is required to specify reasons in case of patients’ unwillingness and to better tailor digital health solutions to patients’ specific needs.

Aims Several reports indicate lower rates of emergency admissions in the cardiovascular sector and reduced admissions of patients with chronic diseases during the Coronavirus SARS-CoV-2 (COVID-19) pandemic. The aim of this study was therefore to evaluate numbers of admissions in incident and prevalent atrial fibrillation and flutter (AF) and to analyse care pathways in comparison to 2019.Methods A retrospective analysis of claims data of 74 German Helios hospitals was performed to identify consecutive patients hospitalized with a main discharge diagnosis of AF. A study period including the start of the German national protection phase (13 March 2020 to 16 July 2020) was compared to a previous year control cohort (15 March 2019 to 18 July 2019), with further sub-division into early and late phase. Incidence rate ratios (IRRs) were calculated. Numbers of admission per day (A/day) for incident and prevalent AF and care pathways including readmissions, numbers of transesophageal echocardiogram (TEE), electrical cardioversion (CV), and catheter ablation (CA) were analysed.Results During the COVID-19 pandemic, there was a significant decrease in total AF admissions both in the early (44.4 vs. 77.5 A/day, IRR 0.57 [95% confidence interval (CI) 0.54–0.61], P Conclusion During the COVID-19 pandemic, AF admission rates declined significantly, with a more pronounced reduction in incident than in prevalent AF. Overall AF care was maintained during early and late pandemic phases with only minor changes, namely less frequent use of TEE. Confirmation of these findings in other study populations and identification of underlying causes are required to ensure optimal therapy in patients with AF during the COVID-19 pandemic.

AIMS: The coronavirus disease 2019 (COVID-19) pandemic has led to changes in health care utilization for different acute cardiovascular diseases. Whether hospitalization rates and in-hospital mortality were affected by the pandemic in patients with acute symptomatic heart failure (HF) was investigated in this study. METHODS AND RESULTS: Administrative data provided by 67 German Helios hospitals were examined for patients with a main discharge diagnosis of HF using ICD codes. Urgent hospital admissions per day were compared for a study period (13 March-21 May 2020) with control intervals in 2020 (1 January-12 March) and 2019 (13 March-21 May), resulting in a total of 13 484 patients excluding all patients with laboratory-proven COVID-19 infection. Incidence rate ratios (IRR) were calculated using Poisson regression. Generalized linear mixed models were used for univariable and multivariable analysis to identify predictors of in-hospital mortality. The number of admissions per day was lower in the study period compared to the same year [IRR 0.69, 95% confidence interval (CI) 0.67-0.73, P < 0.01] and the previous year control group (IRR 0.73, 95% CI 0.70-0.76, P < 0.01). Age was similar throughout the intervals, but case severity increased in terms of distribution within New York Heart Association (NYHA) classes and comorbidities. Within the study period, 30-day rates for urgent hospital readmissions were higher compared to the same year but not the previous year control group. In-hospital mortality was 7.3% in the study period, 6.1% in the same year (P = 0.03) and 6.0% in the previous year control group (P = 0.02). In multivariable analysis, age, NYHA class and other predictors of fatal outcome were identified but hospitalization during the study period was not independently associated with mortality. CONCLUSION: Our data showed a significant reduction of urgent hospital admissions for HF with increased case severity and concomitant in-hospital mortality during the COVID-19 pandemic in Germany. Identifying causes of reduced inpatient treatment rates is essential for the understanding and valuation with regard to future optimal management of patients with HF.

Background The aim of our study was to assess the impact the impact of gender and age on reactogenicity to three COVID-19 vaccine products: Biontech/Pfizer (BNT162b2), Moderna (mRNA-1273) and AstraZeneca (ChAdOx). Additional analyses focused on the reduction in working capacity after vaccination and the influence of the time of day when vaccines were administered. Methods We conducted a survey on COVID-19 vaccinations and eventual reactions among 73,000 employees of 89 hospitals of the Helios Group. On May 19th, 2021 all employees received an email, inviting all employees who received at least 1 dose of a COVID-19 to participate using an attached link. Additionally, the invitation was posted in the group’s intranet page. Participation was voluntary and non-traceable. The survey was closed on June 21st, 2021. Results 8375 participants reported on 16,727 vaccinations. Reactogenicity was reported after 74.6% of COVID-19 vaccinations. After 23.0% vaccinations the capacity to work was affected. ChAdOx induced impairing reactogenicity mainly after the prime vaccination (70.5%), while mRNA-1273 led to more pronounced reactions after the second dose (71.6%). Heterologous prime-booster vaccinations with ChAdOx followed by either mRNA-1273 or BNT162b2 were associated with the highest risk for impairment (81.4%). Multivariable analyses identified the factors older age, male gender and vaccine BNT162b as independently associated with lower odds ratio for both, impairing reactogenicity and incapacity to work. In the comparison of vaccine schedules, the heterologous combination ChAdOx + BNT162b or mRNA-1273 was associated with the highest and the homologue prime-booster vaccination with BNT162b with the lowest odds ratios. The time of vaccination had no significant influence. Conclusions Around 75% of the COVID-19 vaccinations led to reactogenicity and nearly 25% of them led to one or more days of work loss. Major risk factors were female gender, younger age and the administration of a vaccine other than BNT162b2. When vaccinating a large part of a workforce against COVID-19, especially in professions with a higher proportion of young and women such as health care, employers and employees must be prepared for a noticeable amount of absenteeism. Assuming vaccine effectiveness to be equivalent across the vaccine combinations, to minimize reactogenicity, employees at risk should receive a homologous prime-booster immunisation with BNT162b2. Trial registration: The study was approved by the Ethic Committee of the Aerztekammer Berlin on May 27th, 2021 (Eth-37/21) and registered in the German Clinical Trials Register (DRKS 00025745). The study was supported by the Helios research grant HCRI-ID 2021-0272.

Males have a higher risk for an adverse outcome of COVID-19. The aim of the study was to analyze sex differences in the clinical course with focus on patients who received intensive care. Research was conducted as an observational retrospective cohort study. A group of 23,235 patients from 83 hospitals with PCR-confirmed infection with SARS-CoV-2 between 4 February 2020 and 22 March 2021 were included. Data on symptoms were retrieved from a separate registry, which served as a routine infection control system. Males accounted for 51.4% of all included patients. Males received more intensive care (ratio OR = 1.61, 95% CI = 1.51–1.71) and mechanical ventilation (invasive or noninvasive, OR = 1.87, 95% CI = 1.73–2.01). A model for the prediction of mortality showed that until the age 60 y, mortality increased with age with no substantial difference between sexes. After 60 y, the risk of death increased more in males than in females. At 90 y, females had a predicted mortality risk of 31%, corresponding to males of 84 y. In the intensive care unit (ICU) cohort, females of 90 y had a mortality risk of 46%, equivalent to males of 72 y. Seventy-five percent of males over 90 died, but only 46% of females of the same age. In conclusion, the sex gap was most evident among the oldest in the ICU. Understanding sex-determined differences in COVID-19 can be useful to facilitate individualized treatments.

Summary Background Staphylococcus aureus remains a common cause of ventilator-associated pneumonia, with little change in incidence over the past 15 years. We aimed to evaluate the efficacy of suvratoxumab, a monoclonal antibody targeting the α toxin, in reducing the incidence of S aureus pneumonia in patients in the intensive care unit (ICU) who are on mechanical ventilation. Methods We did a multicentre, randomised, double-blind, placebo-controlled, parallel-group, phase 2 pilot trial at 31 hospitals in Belgium, the Czech Republic, France, Germany, Greece, Hungary, Portugal, Spain, and Switzerland. Eligible patients were in the ICU, aged ≥18 years, were intubated and on mechanical ventilation, were positive for S aureus colonisation of the lower respiratory tract, as assessed by quantitative PCR (qPCR) analysis of endotracheal aspirate, and had not been diagnosed with new-onset pneumonia. Patients were excluded if they had confirmed or suspected acute ongoing staphylococcal disease; had received antibiotics for S aureus infection for more than 48 h within 72 h of randomisation; had a Clinical Pulmonary Infection Score of 6 or higher; had an acute physiology and chronic health evaluation II score of 25 or higher with a Glasgow coma scale (GCS) score of more than 5, or an acute physiology and chronic health evaluation II score of at least 30 with a GCS score of 5 or less; had a Sequential Organ Failure Assessment score of 9 or higher; or had active pulmonary disease that would impair the ability to diagnose pneumonia. Colonised patients were randomly assigned (1:1:1), by use of an interactive voice or web response system, to receive either a single intravenous infusion of suvratoxumab 2000 mg, suvratoxumab 5000 mg, or placebo. Randomisation was done in blocks of size four, stratified by country and by whether patients had received systemic antibiotics for S aureus infection. Patients, investigators, and study staff involved in the treatment or clinical evaluation of patients were masked to patient assignment. The primary efficacy endpoint was the incidence of S aureus pneumonia at 30 days, as determined by a masked independent endpoint adjudication committee, in all patients who received their assigned treatment (modified intention-to-treat [ITT] population). Primary safety endpoints were the incidence of treatment-emergent adverse events at 30 days, 90 days, and 190 days after treatment, and the incidence of treatment-emergent serious adverse events, adverse events of special interest, and new-onset chronic disease at 190 days after treatment. All primary safety endpoints were assessed in the modified ITT population. This trial is registered with ClinicalTrials.gov ( NCT02296320 ) and the EudraCT database (2014-001097-34). Findings Between Oct 10, 2014, and April 1, 2018, 767 patients were screened, of whom 213 patients with confirmed S aureus colonisation of the lower respiratory tract were randomly assigned to the suvratoxumab 2000 mg group (n=15), the suvratoxumab 5000 mg group (n=96), or the placebo group (n=102). Two patients in the placebo group did not receive treatment after randomisation because their clinical conditions changed and they no longer met the eligibility criteria for dosing. As adjudicated by the data monitoring committee at an interim analysis, the suvratoxumab 2000 mg group was discontinued on the basis of predefined pharmacokinetic criteria. At 30 days after treatment, 17 (18%) of 96 patients in the suvratoxumab 5000 mg group and 26 (26%) of 100 patients in the placebo group had developed S aureus pneumonia (relative risk reduction 31·9% [90% CI −7·5 to 56·8], p=0·17). The incidence of treatment-emergent adverse events at 30 days were similar between the suvratoxumab 5000 mg group (87 [91%]) and the placebo group (90 [90%]). The incidence of treatment-emergent serious adverse events at 30 days were also similar between the suvratoxumab 5000 mg group (36 [38%]) and the placebo group (32 [32%]). No significant difference in the incidence of treatment-emergent adverse events between the two groups at 90 days (89 [93%] in the suvratoxumab 5000 mg group vs 92 [92%] in the placebo group) and at 190 days (93 [94%] vs 93 [93%]) was observed. 40 (40%) patients in the placebo group and 50 (52%) in the suvratoxumab 5000 mg group had a serious adverse event at 190 days. In the suvratoxumab 5000 mg group, one (1%) patient reported at least one treatment-emergent serious adverse event related to treatment, two (2%) patients reported an adverse event of special interest, and two (2%) reported a new-onset chronic disease. Interpretation In patients in the ICU receiving mechanical ventilation with qPCR-confirmed S aureus colonisation of the lower respiratory tract, the incidence of S aureus pneumonia at 30 days was not significantly lower following treatment with 5000 mg suvratoxumab than with placebo. Despite these negative results, monoclonal antibodies still represent one promising therapeutic option to reduce antibiotic consumption that require further exploration and studies. Funding AstraZeneca, with support from the Innovative Medicines Initiative Joint Undertaking.

Objectives It has been suggested that pregnant women were affected more severely during the late wave, as opposed to the early wave of the coronavirus disease 2019 (COVID-19) pandemic. The aim of our study was to compare the proportion of pregnant women among hospitalized women of childbearing age, their rate of intensive care (ICU) admission, need for mechanical ventilation and mortality during the waves. Methods The study is a retrospective analysis of claims data on women of childbearing age (16–49 years) admitted to 76 hospitals with a laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection. The observation period was divided into first wave (7 March 2020 to 30 September 2020) and second wave (1 October to 17 April 2021). Co-morbidities derived from claims data were summarized in the Elixhauser Co-morbidity Index (ECI). Results A total of 1879 women were included, 532 of whom were pregnant. During the second wave, the proportion of pregnant women was higher (29.3% (484/1650) versus 21.0% (48/229), p

BackgroundAfter the first Covid-19 infection wave, a constant increase of pulmonary embolism (PE) hospitalizations not linked with active PCR-confirmed Covid-19 has been observed but potential contributors to this observation are unclear. Therefore, we analyzed associations between changes in PE hospitalizations and (1) the incidence of non-Covid-19 pneumonia, (2) the use of computed tomography pulmonary angiography (CTPA), (3) volume depletion and (4) preceding Covid-19 infection numbers in Germany.MethodsClaims data of Helios hospitals in Germany were used and consecutive cases with a hospital admission between May 6 and December 15, 2020 (PE surplus period) were analyzed and compared to corresponding periods covering the same weeks in 2016–2019 (control period). We analyzed the number of PE cases in the target period with multivariable Poisson general linear mixed models (GLMM) including (a) cohorts of 2020 versus 2016– 2019, (b) the number of cases with pneumonia, (c) CTPA, and (d) volume depletion and adjusted for age and sex. In order to associate the daily number of PE cases in 2020 with the number of preceding SARS-CoV-2 infections in Germany, we calculated the average number of daily infections (divided by 10,000) occurring 14 up to 90 days with increasing window sizes before PE cases and modelled the data with Poisson regression.ResultsThere were 2,404 PE hospitalizations between May 6 and December 15, 2020 as opposed to 2,112 – 2,236 (total 8,717) in the corresponding 2016 – 2019 control periods. (crude rate ratio [CRR] 1.10, 95% CI 1.05 – 1.15, PPPPPConclusionsThere is an increase in PE cases since early May 2020 compared to corresponding periods in 2016 – 2019. This surplus was significant even when controlling for changes in potential modulators such as demographics, volume depletion, non-Covid-19 pneumonia, CTPA use and preceding Covid-19 infections. Future studies are needed (1) to investigate a potential causal link for increased risk of delayed PE with preceding SARS-CoV-2 infection, and (2) to define optimal screening for SARS-CoV-2 in patients presenting with pneumonia and PE.

BackgroundThere is discussion evolving around the emergence of different phenotypes of Covid-19-associated thromboembolic disease, i.e. acute pulmonary embolism vs pulmonary thrombosis and different phenotypes of in situ thrombosis. With this study, we wish to provide hospitalization, treatment and in-hospital outcome data for pulmonary embolism during the 2020 Covid-19 pandemic and a corresponding 2016 – 2019 control period.MethodsWe performed a retrospective analysis of claims data of Helios hospitals in Germany. Consecutive cases with a hospital admission between January 1 and December 15, 2020 and pulmonary embolism as primary discharge diagnosis were analyzed and compared to a corresponding period covering the same weeks in 2016 – 2019.ResultsAs previously reported for other emergent medical conditions, there was a hospitalization deficit coinciding with the 1st pandemic wave. Beginning with the 12-week interval May 6 – July 28, there was a stable surplus of hospital admissions in 2020. During this surplus period (May 6 – December 15, 2020), there were 2,449 hospitalizations including 45 PCR-confirmed Covid-19 cases (1.8%) as opposed to 8,717 in 2016 – 2019 (IRR 1.12, 95% CI 1.07 – 1.18, PPP=0.28), the presence of thrombosis (46.1 vs 45.4%, P=0.55) and surgery (3.8 vs. 4.3%, P=0.33) were comparable, coagulopathy (3.3 vs 4.5%, P=0.01) and metastatic cancer (3.0 vs 4.0%, P=0.03) as contributing factors were less frequently observed during the 2020 surplus. Interventional treatments (thrombolytic therapy, thrombectomy or inferior vena cava filter placement) were less frequently used (4.7 vs 6.6%, OR 0.72, 95% CI 0.58 − 0.89, P< 0.01). Similarly, intensive care (35.1 vs 38.8%, OR 0.83, 95% CI 0.75 − 0.92, P< 0.01) and mechanical ventilation utilization (7.2 vs 8.1%, OR 0.88, 95% CI 0.74 – 1.04, P=0.14) as well as in-hospital-mortality rates (7.8 vs 9.8%, OR 0.76, 95% CI 0.64 − 0.90, P< 0.01) were lower in 2020 compared with 2016 – 2019. This was associated with a shorter length of hospital stay (6.4 ±5.4 vs. 7.2 ±5.7 days, P< 0.01) during the 2020 surplus period.ConclusionsOnly a minority of cases were associated with PCR-confirmed Covid-19 but this does not rule out preceding or undetected SARS-CoV-2 infection. Although there is a shift towards milder disease course, the increased incidence of hospitalizations for pulmonary embolism requires immediate attention, close surveillance and further studies.

BackgroundWhile there are numerous reports that describe emergency care during the early Covid-19 pandemic, there is scarcity of data for later stages. This study analyzes hospitalization rates for 37 emergency-sensitive conditions in the largest German-wide hospital network during different pandemic phases.MethodsUsing claims data of 80 hospitals, consecutive cases between January 1 and November 17, 2020 were analyzed and compared to a corresponding period in 2019. Incidence-rate ratios (IRR) comparing the both periods were calculated using Poisson regression to model the number of hospitalizations per day.ResultsThere was a hospitalization deficit between March 12 and June 13, 2020 (coinciding with the 1st pandemic wave) with 32,807 hospitalizations as opposed to 39,379 in 2019 (IRR 0.83, 95% CI 0.82 – 0.85, Pnd wave), hospitalizations were reduced from 63,799 in 2019 to 59,910 in 2020, but this reduction was not that pronounced (IRR 0.94, 95% CI 0.93 – 0.95, Pst wave during which hospitalizations had been reduced for those conditions. In contrast, hospitalizations for sepsis, pneumonia, obstructive pulmonary disease, and intracranial injuries were reduced during the entire pandemic.ConclusionsThere was an overall reduction of hospitalizations for emergency-sensitive conditions in Germany during the Covid-19 pandemic with heterogeneous effects on different disease categories. The increase of hospitalizations for acute myocardial infarction, aortic aneurism/dissection and pulmonary embolism is an alarming signal that requires attention and further studies.KEY MESSAGESWhat is already known on this subjectThere has been a reduction in emergency room visits and hospital admissions for several emergent medical and surgical conditions during the early Covid-19 pandemic (1st wave).What this study addsUsing claims data of 80 German-wide Helios hospitals, we found an overall reduction of hospitalizations for emergency-sensitive conditions in Germany during the Covid-19 pandemic until mid November 2020 with heterogeneous effects on different disease categories. While hospitalizations for sepsis, pneumonia, obstructive pulmonary disease, and intracranial injuries were reduced during the entire pandemic. There was an alarming increase of hospitalizations for acute myocardial infarction, aortic aneurism/dissection and pulmonary embolism after the 1st wave.

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

Summary Objectives The coronavirus disease 2019 (COVID-19) pandemic situation in Germany is unique among large European countries in that incidence and case fatality rate are distinctly lower. We describe the clinical course and examine factors associated with outcomes among patients hospitalized with COVID-19 in Germany. Methods In this retrospective cohort study we included patients with COVID-19 admitted to a national network of German hospitals between February 12, and June 12, 2020. We examined demographic characteristics, comorbidities and clinical outcomes. Results We included 1904 patients with a median age of 73 years, and 48.5% (924/1904) were female. The mortality rate was 17% (317/1835; 95% confidence interval [CI] 16-19), the rate of admission to the intensive care unit (ICU) 21% (399/1860; 95% CI 20–23), and the rate of invasive mechanical ventilation 14% (250/1850: 95% CI 12–15). The most prominent risk factors for death were male sex (hazard ratio [HR] 1.45; 95% CI 1.2-1.8), preexisting lung disease (HR 1.61; 95% CI 1.20-2.16), and increased patient age (HR 4.1 [95% CI 2.6–6.6] for age >79 years versus

Purpose Psychiatric emergency hospital admissions for distinct psychiatric disorders and length of inpatient stay in the hospital during the Coronavirus disease 2019 (COVID-19) outbreak have not been thoroughly assessed. Methods A retrospective study was performed analyzing claims data from a large German Hospital network during the COVID-19 outbreak (study period: March 13–May 21, 2020) as compared to periods directly before the outbreak (same year control: January 1–March 12, 2020) and one year earlier (previous year control: March 13–May 21, 2019). Results A total of 13,151 emergency hospital admissions for psychiatric diagnoses were included in the analysis. For all psychiatric diagnoses combined, emergency admissions significantly decreased during the study period with mean (interquartile range) incidence rate ratios (IRRs) of 0.68 (0.65, 0.71) and 0.70 (0.67, 0.73) as compared to the same and previous year controls, respectively (both p

Adrenomedullin (ADM) regulates vascular tone and endothelial permeability during sepsis. Levels of circulating biologically active ADM (bio-ADM) show an inverse relationship with blood pressure and a direct relationship with vasopressor requirement. In the present prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock 1 (, AdrenOSS-1) study, we assessed relationships between circulating bio-ADM during the initial intensive care unit (ICU) stay and short-term outcome in order to eventually design a biomarker-guided randomized controlled trial.AdrenOSS-1 was a prospective observational multinational study. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use, and need for renal replacement therapy. AdrenOSS-1 included 583 patients admitted to the ICU with sepsis or septic shock.Circulating bio-ADM levels were measured upon admission and at day 2. Median bio-ADM concentration upon admission was 80.5 pg/ml [IQR 41.5-148.1 pg/ml]. Initial SOFA score was 7 [IQR 5-10], and 28-day mortality was 22%. We found marked associations between bio-ADM upon admission and 28-day mortality (unadjusted standardized HR 2.3 [CI 1.9-2.9]; adjusted HR 1.6 [CI 1.1-2.5]) and between bio-ADM levels and SOFA score (p0.0001). Need of vasopressor/inotrope, renal replacement therapy, and positive fluid balance were more prevalent in patients with a bio-ADM70 pg/ml upon admission than in those with bio-ADM ≤ 70 pg/ml. In patients with bio-ADM70 pg/ml upon admission, decrease in bio-ADM below 70 pg/ml at day 2 was associated with recovery of organ function at day 7 and better 28-day outcome (9.5% mortality). By contrast, persistently elevated bio-ADM at day 2 was associated with prolonged organ dysfunction and high 28-day mortality (38.1% mortality, HR 4.9, 95% CI 2.5-9.8).AdrenOSS-1 shows that early levels and rapid changes in bio-ADM estimate short-term outcome in sepsis and septic shock. These data are the backbone of the design of the biomarker-guided AdrenOSS-2 trial.ClinicalTrials.gov, NCT02393781 . Registered on March 19, 2015.

Background: Pseudomonas aeruginosa infections are a serious threat in intensive care units (ICUs). The aim of this confirmatory, randomized, multicenter, placebo-controlled, double-blind, phase 2/3 study was to assess the efficacy, immunogenicity, and safety of IC43 recombinant Pseudomonas aeruginosa vaccine in non-surgical ICU patients. Methods: Eight hundred patients aged 18 to 80 years admitted to the ICU with expected need for mechanical ventilation for ≥ 48 h were randomized 1:1 to either IC43 100 μg or saline placebo, given in two vaccinations 7 days apart. The primary efficacy endpoint was all-cause mortality in patients 28 days after the first vaccination. Immunogenicity and safety were also evaluated. Findings: All-cause mortality rates at day 28 were 29.2% vs 27.7% in the IC43 and placebo groups, respectively (P =.67). Overall survival (Kaplan-Meier survival estimates, P =.46) and proportion of patients with ≥ one confirmed P. aeruginosa invasive infection or respiratory tract infection also did not differ significantly between both groups. The geometric mean fold increase in OprF/I titers was 1.5 after the first vaccination, 20 at day 28, after the second vaccination, and 2.9 at day 180. Significantly more patients in the placebo group (96.5%) had ≥ one adverse event (AE) versus the IC43 100 μg group (93.1%) (P =.04). The most frequently reported severe AEs in the IC43 and placebo groups were respiratory failure (6.9% vs 5.7%, respectively), septic shock (4.1% vs 6.5%), cardiac arrest (4.3% vs 5.7%), multiorgan failure (4.6% vs 5.5%), and sepsis (4.6% vs 4.2%). No related serious AEs were reported in the IC43 group. Interpretation: The IC43 100 μg vaccine was well tolerated in this large population of medically ill, mechanically ventilated patients. The vaccine achieved high immunogenicity but provided no clinical benefit over placebo in terms of overall mortality. Trial registration: https://clinicaltrials.gov (NCT01563263). Registration was sent to ClinicalTrials.gov on March 14, 2012, but posted by ClinicalTrials.gov on March 26, 2012. The first subject was included in the trial on March 22, 2012., SCOPUS: ar.j, info:eu-repo/semantics/published

Objective We report on the effect of hemoadsorption therapy to reduce cytokines in septic patients with respiratory failure. Methods This was a randomized, controlled, open-label, multicenter trial. Mechanically ventilated patients with severe sepsis or septic shock and acute lung injury or acute respiratory distress syndrome were eligible for study inclusion. Patients were randomly assigned to either therapy with CytoSorb hemoperfusion for 6 hours per day for up to 7 consecutive days (treatment), or no hemoperfusion (control). Primary outcome was change in normalized IL-6-serum concentrations during study day 1 and 7. Results 97 of the 100 randomized patients were analyzed. We were not able to detect differences in systemic plasma IL-6 levels between the two groups (n = 75; p = 0.15). Significant IL-6 elimination, averaging between 5 and 18% per blood pass throughout the entire treatment period was recorded. In the unadjusted analysis, 60-day-mortality was significantly higher in the treatment group (44.7%) compared to the control group (26.0%; p = 0.039). The proportion of patients receiving renal replacement therapy at the time of enrollment was higher in the treatment group (31.9%) when compared to the control group (16.3%). After adjustment for patient morbidity and baseline imbalances, no association of hemoperfusion with mortality was found (p = 0.19). Conclusions In this patient population with predominantly septic shock and multiple organ failure, hemoadsorption removed IL-6 but this did not lead to lower plasma IL-6-levels. We did not detect statistically significant differences in the secondary outcomes multiple organ dysfunction score, ventilation time and time course of oxygenation.

The aim of this clinical registry is to record the use of CytoSorb® adsorber device in critically ill patients under real-life conditions. 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. 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). 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.

Guidelines recommend administering antibiotics within 1 h of sepsis recognition but this recommendation remains untested by randomized trials. This trial was set up to investigate whether survival is improved by reducing the time before initiation of antimicrobial therapy by means of a multifaceted intervention in compliance with guideline recommendations. The MEDUSA study, a prospective multicenter cluster-randomized trial, was conducted from July 2011 to July 2013 in 40 German hospitals. Hospitals were randomly allocated to receive conventional continuous medical education (CME) measures (control group) or multifaceted interventions including local quality improvement teams, educational outreach, audit, feedback, and reminders. We included 4183 patients with severe sepsis or septic shock in an intention-to-treat analysis comparing the multifaceted intervention (n = 2596) with conventional CME (n = 1587). The primary outcome was 28-day mortality. The 28-day mortality was 35.1% (883 of 2596 patients) in the intervention group and 26.7% (403 of 1587 patients; p = 0.01) in the control group. The intervention was not a risk factor for mortality, since this difference was present from the beginning of the study and remained unaffected by the intervention. Median time to antimicrobial therapy was 1.5 h (interquartile range 0.1–4.9 h) in the intervention group and 2.0 h (0.4–5.9 h; p = 0.41) in the control group. The risk of death increased by 2% per hour delay of antimicrobial therapy and 1% per hour delay of source control, independent of group assignment. Delay in antimicrobial therapy and source control was associated with increased mortality but the multifaceted approach was unable to change time to antimicrobial therapy in this setting and did not affect survival.

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.

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.

Die Stellungnahme von Zander et al. nimmt fur sich in Anspruch, Methodik und Ergebnisse der zu diesem Zeitpunkt noch nicht publizierten VISEP-Studie zum Stellenwert von Hydroxyathylstarke (HES) und Insulin in der Therapie der schweren Sepsis kritisch zu evaluieren. Bedauerlicherweise gehen die Autoren von einer Reihe falscher Annahmen zu Protokoll, Durchfuhrung und Wirkweise der untersuchten Substanzen aus. Unter anderem wurde in der Studie HES nicht zur Deckung des taglichen Flussigkeitsbedarfs verwendet; die Annahme der Autoren, dass HES „exklusiv“ eingesetzt wurde, ist deshalb falsch. Ferner gibt es fur das von uns verwandte Hemohes® keine Kreatiningrenzwerte in der Fachinformation des Herstellers. Deshalb ist die Behauptung der Autoren, wir hatten die Einschlusskriterien fur Kreatininwerte gegenuber den Herstellerangaben verdoppelt, nicht richtig. Andere Aussagen der Autoren, wie z. B. dass laktathaltige Losungen erhohte Laktatspiegel, eine iatrogene Hyperglykamie bzw. einen erhohten O2-Verbrauch verursachen, sind durch unsere Studienergebnisse widerlegt und stehen im Widerspruch zu anerkannten Leitlinien zur Sepsistherapie und zur weltweiten klinischen Praxis. Wir begrusen eine offene wissenschaftliche Debatte. Die Studienmethodik und -ergebnisse haben einen strengen „Peer-review“-Prozess passiert, sind mittlerweile veroffentlicht und damit offen fur eine kritische Evaluierung. In dieser vorschnellen und auf falschen Annahmen basierenden Stellungnahme jedoch, der durch Kommentare von HES-Herstellern erganzt ist, konnen wir keinen Beitrag zu einem seriosen und vorurteilsfreien wissenschaftlichen Diskurs erkennen.

Sepsis is associated with an increase in reactive oxygen species and low endogenous antioxidative capacity. We postulated that high-dose supplementation of sodium-selenite would improve the outcome of patients with severe sepsis and septic shock.Prospective randomized, placebo-controlled, multiple-center trial.Eleven intensive care units in Germany.Patients were 249 patients with severe systemic inflammatory response syndrome, sepsis, and septic shock and an Acute Physiology and Chronic Health Evaluation (APACHE) III score70.Patients received 1000 microg of sodium-selenite as a 30-min bolus injection, followed by 14 daily continuous infusions of 1000 microg intravenously, or placebo.The primary end point was 28-day mortality; secondary end points were survival time and clinical course of APACHE III and logistic organ dysfunction system scores. In addition, selenium levels in serum, whole blood, and urine as well as serum glutathione-peroxidase-3 activity were measured. From 249 patients included, 11 patients had to be excluded. The intention-to-treat analysis of the remaining 238 patients revealed a mortality rate of 50.0% in the placebo group and 39.7% in the selenium-treated group (p = .109; odds ratio, 0.66; confidence interval, 0.39-1.1). A further 49 patients had to be excluded before the final analysis because of severe violations of the study protocol. In the remaining 92 patients of the study group, the 28-day mortality rate was significantly reduced to 42.4% compared with 56.7% in 97 patients of the placebo group (p = .049, odds ratio, 0.56; confidence interval, 0.32-1.00). In predefined subgroup analyses, the mortality rate was significantly reduced in patients with septic shock with disseminated intravascular coagulation (n = 82, p = .018) as well as in the most critically ill patients with an APACHE III scoreor =102 (75% quartile, n = 54, p = .040) or in patients with more than three organ dysfunctions (n = 83, p = .039). Whole blood selenium concentrations and glutathione peroxidase-3 activity were within the upper normal range during selenium treatment, whereas they remained significantly low in the placebo group. There were no side effects observed due to high-dose sodium-selenite treatment.The adjuvant treatment of patients with high-dose sodium-selenite reduces mortality rate in patients with severe sepsis or septic shock.

Nach neuesten Erhebungen des vom BMBF geforderten Kompetenznetzwerkes Sepsis (SepNet) erkranken in Deutschland pro Jahr 75 000 Einwohner (110 von 100 000) an einer schweren Sepsis bzw. septischem Schock und 79 000 (116 von 100 000) an einer Sepsis. Mit ca. 60 000 Todesfallen stellen septische Erkrankungen die dritthaufigste Todesursache nach dem akuten Myokardinfarkt dar. Die direkten anteiligen Kosten, die allein fur die intensivmedizinische Behandlung von Patienten mit schwerer Sepsis anfallen, liegen bei ca. 1,77 Milliarden Euro. Ca. 30% des Budgets fur Intensivmedizin werden damit in die Behandlung der Sepsis investiert. Im Kontrast hierzu, existierten bisher jedoch keine deutsche Leitlinien zur Diagnose und Therapie der schweren Sepsis. Auf Initiative der Deutschen Sepsis-Gesellschaft wurden daher in Anlehnung an die internationalen Empfehlungen des International Sepsis Forum (ISF) und der Surviving Sepsis Campaign (SSC) Leitlinien erarbeitet, welche die Versorgungsstrukturen im deutschen Gesundheitssystem berucksichtigen. Folgende Leitlinienthemen wurden als vorrangig eingestuft: a) Diagnose, b) Pravention, c) kausale Therapie, d) supportive Therapie, e) adjunktive Therapie. Die Leitlinien sind nach einem sorgfaltig geplanten und streng eingehaltenen Prozess nach den Vorgaben der Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF) entstanden.

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).

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).

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.

An initial phase II trial to investigate the safety and therapeutic effect of the endotoxin adsorber system EN 500 in septic patients suffering from presumed Gram-negative infection.Open, controlled, prospective, randomized, multiple-center, parallel-group clinical trial.Intensive care units of 31 university-affiliated and community hospitals in Europe.One hundred forty-five patients with a clinical diagnosis of severe sepsis or septic shock due to suspected Gram-negative infection.Patients were randomized to receive either standard therapy alone for sepsis (n = 76) or standard therapy plus extracorporeal endotoxin adsorption (n = 67) daily for the first 4 days following study entry.The primary end point was the proportion of responders (defined as a decrease in Acute Physiology and Chronic Health Evaluation II score byor =4 points from study entry to day 4). Secondary outcomes were the Sequential Organ Failure Assessment score and its components, length of intensive care unit stay, survival rate, and safety of the adsorber treatment. Patient characteristics at entry were well balanced between the two treatment groups, except for a higher Sequential Organ Failure Assessment score in the adsorber group. On all-subjects-treated analysis, 65% of the adsorber group were responders vs. 57% for the standard (p =.389). A planned interim analysis restricted further enrollment to patients with peritonitis, in whom a slightly higher proportion of responders was observed with the adsorber treatment (69%) vs. standard treatment (54%, p =.159). There were no differences in survival, but adsorption treatment in peritonitis patients was associated with trends toward a reduction in length of intensive care unit stay and a more rapid decline in plasma endotoxin concentrations. There was a significantly greater reduction in platelet count with the adsorber; however, this did not require extra treatment.The endotoxin adsorber system did not result in a significantly improved primary end point in patients with presumed Gram-negative sepsis. In patients with peritonitis, the adsorber treatment likewise did not result in significantly improved Acute Physiology and Chronic Health Evaluation II scores. There were no clinically important side effects. These results provide encouragement for further study of adsorber treatment in patients with high likelihood of Gram-negative sepsis (e.g., peritonitis).

The purpose of this analysis of health economic studies in the field of intensive and critical care was to investigate whether any relationship could be established between type of sponsorship and (1) type of economic analysis, (2) health technology assessed, (3) sensitivity analysis performed, (4) publication status, and (5) qualitative cost assessment. Using the terms critical careor intensive care, all health economics publications in the field of critical and intensive care were identified in the Health Economic Evaluations Database (HEED, Version 1995-2001) on the basis of sponsorship and comparative studies. This search yielded a total of 42 eligible articles. Their evaluations were prepared independently by 2 investigators on the basis of specific criteria. When evaluators disagreed, a third investigator provided a deciding evaluation. There was no statistically demonstrable relationship between types of sponsorship and sensitivity analysis performed, publication status, types of economic analysis, or qualitative cost assessment.

Objective: To evaluate plasma amino acid concentrations and markers of inflammation in the early stage and the course of septic encephalopathy. Design: Prospective, case series of patients with well-defined septic encephalopathy. Setting: Surgical department and intensive care unit of a university hospital. Patients: Seventeen patients with sepsis according to the ACCP/SCCM consensus conference criteria and encephalopathy based on neuropsychological tests, compared to a control group undergoing uncomplicated thoracic surgery. Interventions: None. Measurements and results: SOFA score, blood samples for plasma amino acids, procalcitonin and interleukin-6. Sepsis was determined to be the cause of encephalopathy in 14 of the 17 patients. Six patients developed septic shock, four died within the study period of 28 days. Within 12 h of the onset of septic encephalopathy, mean values of PCT and IL-6 were elevated (p

OBJECTIVE: To test the hypothesis that dopexamine reduces postoperative mortality and morbidity in high-risk, major abdominal surgery patients, when given to fluid-resuscitated patients starting before the operation and continued for 24 hrs after surgery. DESIGN: Prospective, randomized, controlled, double-blind multicenter trial. SETTING: Intensive care units in 13 hospitals from six European countries. PATIENTS: A total of 412 patients with predefined high-risk criteria, undergoing major abdominal surgery with an expected duration of at least 1.5 hrs. INTERVENTIONS: The patients received placebo (n = 140), dopexamine at 0.5 microg/kg/min (n = 135), or dopexamine at 2.0 microg/kg/ min (n = 137) starting after preoperative hemodynamic stabilization and continued for 24 hrs after surgery. MEASUREMENTS AND MAIN RESULTS: The primary outcome variable was mortality at 28 days. Analysis was by intention to treat. Dopexamine had no effect on mortality (at 28 days, 13%, 7%, and 15%, for the groups receiving placebo, dopexamine at 0.5 microg/kg/ min, and dopexamine at 2.0 microg/kg/min, respectively), despite the expected dose-dependent hemodynamic responses. No effect was observed on the occurrence of organ dysfunction, duration of intensive care unit stay, or length of hospital stay. CONCLUSION: We conclude that dopexamine in doses that result in increased cardiac output and oxygen delivery after preoperative stabilization with fluids does not improve outcome after major abdominal surgery compared with fluids alone. Based on post hoc subgroup analysis and stratification according to the number of risk factors, we suggest that the concept should be further tested in patients at higher risk of complications or undergoing emergency surgery.

Objective: Transpulmonary double-indicator dilution is a useful monitoring technique for measurement of intrathoracic blood volume (ITBV) and extravascular lung water (EVLW). In this study, we compared a simpler approach using single arterial thermodilution derived measurements of ITBV and EVLW with the double-indicator dilution technique.¶Design: Prospective observational clinical study.¶Setting: Surgical intensive care units of two university hospitals.¶Patients and methods: Global end-diastolic volume (GEDV) derived from single thermodilution was used for calculation of ITBV. Structural regression analysis of the first two thermo-dye dilution measurements in a derivation population of 57 critically ill patients (38 male, 19 female, 18–79 years, 56 ± 15 years) revealed ITBV = (1.25 · GEDV)–28.4 (ml). This equation was then applied to all first measurements in a validation population of 209 critically ill patients (139 male, 70 female, 10–88 years, mean 53 ± 19 years), and single-thermodilution ITBV (ITBVST) and EVLW (EVLWST) was calculated and compared to thermo-dye dilution derived values (ITBVTD, EVLWTD). For inter-individual comparison, absolute values for ITBV and EVLW were normalised as indexed by body surface area (ITBVI) and body weight (EVLWI), respectively.¶Measurements and results: Linear regression analysis yielded a correlation of ITBVIST = (1.05 · ITBVITD)–58.0 (ml/m2), r = 0.97, P < 0.0001. Bias between ITBVITD and ITBVIST was 7.6 (ml/m2) with a standard deviation of 57.4 (ml/m2). Single-thermodilution EVLWI (EVLWIST) was calculated using ITBVIST and revealed the correlation EVLWIST = (0.83 · EVLWITD) + 1.6 (ml/kg), r = 0.96, P < 0.0001. Bias between EVLWITD and EVLWIST was –0.2 (ml/kg) with a standard deviation of 1.4 (ml/kg). In detail, EVLWIST systematically overestimated EVLWITD at low-normal values for EVLWI and underestimated EVLWI at higher values (above 12 ml/kg).¶Conclusion: Determinations of ITBV and EVLW by single thermodilution agreed closely with the corresponding values from the double-indicator technique. Since transpulmonary single thermodilution is simple to apply, less invasive and cheaper, all these features make it a promising technique for the bedside. Nevertheless, further validation studies are needed in the future.

Laparoscopic techniques for surgery are gradually becoming established in paediatric surgery. Technical aspects, such as the maximum safe gas insufflation pressure, are still open to discussion. We used transoesophageal echocardiography to study the haemodynamic changes in eight small children undergoing laparoscopic herniorrhaphy, with two different levels of intra-abdominal pressure (IAP), 6 and 12 mm Hg. End-tidal carbon dioxide tension was maintained constant at 4.3-4.7 kPa. After baseline measurements, an IAP of 12 mm Hg was applied for 10 min. Next, IAP was decreased to 6 mm Hg, followed by a second period of 12 mm Hg. Haemodynamic measurements were obtained at each stage. A further measurement was obtained 10 min after abdominal deflation at the end of surgery while anaesthesia was unchanged. Cardiac index (CI) decreased significantly only after the first 12 mm Hg level of IAP. The subsequent decrease in IAP to 6 mm Hg caused return of CI to baseline levels. The second increase in IAP did not cause any reduction in CI. The initial reduction in CI, although statistically significant, did not appear to be clinically important. We conclude that an IAP of up to 12 mm Hg appeared to be safe in healthy small children undergoing laparoscopic herniorrhaphy.

Objectives To determine correlations and predictive strength of surrogate markers (body temperature, leukocyte count, C-reactive protein [CRP], and procalcitonin [PCT]) with elevated levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in septic patients. Design Prospective consecutive case series. Setting Surgical intensive care unit (ICU) of a university hospital. Patients A total of 175 patients experiencing intensive care unit stays >48 hrs categorized for sepsis according to ACCP/ SCCM Consensus Conference criteria. Measurements and main results CRP and PCT were both significantly correlated with TNF-alpha and IL-6. Based on the area-under-the-curve of the receiver operating characteristics curves, predicting capability was highest for PCT (0.814 for TNF-alpha >40 pg/mL and 0.794 for IL-6 >500 pg/mL), moderate with CRP (0.732 and 0.716, respectively), and lowest for leukocyte count (0.493 and 0.483, respectively) and body temperature (0.587 and 0.589, respectively). Sensitivity, specificity, positive, and negative predictive values and test effectiveness all followed this same pattern of being highest for PCT followed by CRP, with leukocyte count and body temperature being lowest. Conclusion PCT may be an early and better marker of elevated cytokines than the more classic criteria of inflammation.

OBJECTIVE In critically ill patients, the adjustment of target peak and trough levels of tobramycin was investigated because aminoglycoside pharmacokinetics can be changed by multiple influences. Sufficient but not too high peak serum concentrations and low trough levels, however, should be achieved to ensure a therapeutic effect and to minimize toxicity. METHODS 70 critically ill patients of 51 +/- 18 years were monitored daily during their aminoglycoside treatment on the intensive care unit targeting a peak of about 12 micrograms/ml 30 minutes after infusion and a trough level below 1 to 2 micrograms/ml. Dose recommendations were given daily, taking into consideration serum levels, dose predictions (Bayesian method, ABBOTTBASE), creatinine clearance and clinical findings. Creatinine clearance was estimated according to the Cockcroft-Gault-formula as well as directly by the urine collection method. RESULTS The standardized initial dose of 400 mg tobramycin led to average peak serum levels of 14.2 +/- 3.9 micrograms/ml in the patients with an apparent distribution volume of 0.345 +/- 0.074 L/kg. In 95% of the patients, the initial peak was higher than 8.5 micrograms/ml; levels higher than 20 micrograms/ml were observed in 7%, extremely low concentrations (below 5 micrograms/ml) in 2%. With individually adjusted doses between 160 and 560 mg, a mean peak of 11.5 +/- 2.7 micrograms/ml was measured subsequently. The levels amounted to 96 +/- 23% of the predicted values, deviations greater than 50% occurred in 5%. The target trough level was achieved in 99%, in less than 3% the dosing interval was extended up to 72 hours. A tobramycin clearance below 80 ml/min/1.73 m2 was associated with average 80% and 33% higher creatinine clearance values according to the Cockcroft-method and the direct method, respectively. CONCLUSION Target peak and trough aminoglycoside levels are adjustable even in critically ill patients. Reduced tobramycin clearance can be associated with normal creatinine clearance. Assuming an exact methodology, a reduced "direct" creatinine clearance, however, indicates a reduced drug clearance.

Die Anwendung der transpulmonalen Indikatorverdunnungsmethode erlaubt es, einen haufig in der Therapie kritisch kranker Patienten erforderlichen Kompromis zwischen adaquater Volumentherapie zur Aufrechterhaltung einer suffizienten regionalen Perfusion einerseits und einer Vermeidung eines pulmonalen Odems andererseits an den Parametern “intrathorakales Blutvolumen” und “extravaskulares Lungenwasser” auszurichten. Da fur die Anwendung dieser Methode lediglich ein 3F- oder 4F-Katheter in der A. femoralis notwendig ist, ist die Methode im Vergleich zum Pulmonalarterienkatheter weniger invasiv. Daruberhinaus ist eine Steuerung der Volumentherapie entlang des pulmonalkapillaren Verschlusdruckes bei beatmeten Patienten mit erheblichen methodischen Schwachen verbunden, so das insbesondere bei kritisch Kranken das intrathorakale Blutvolumen zur Abschatzung der kardialen Vorlast dem pulmonalkapillaren Verschlusdruck uberlegen zu sein scheint. Daruberhinaus liefert die Methode bei Anwendung der Doppelindikatortechnik mit der Indocyaninclearance einen wertvollen Parameter zur Einschatzung der Leberfunktion.

Procalcitonin (PCT), ein aus 116 Aminosauren bestehendes Glykoprotein, wurde als neuer Parameter der schweren Infektion inauguriert. Sein Syntheseort in diesem Zusammenhang ist nicht bekannt. Mittels immunoluminometrischen Assays kann die PCT-Konzentration innerhalb von ca. 2 h aus 40 µl Serum oder Plasma bestimmt werden. PCT-Erhohungen sind u.a. mit Lipopolysaccharid und mit den Zytokinen TNF-α und IL-6 assoziiert. Bakterielle, parasitare und pilzbedingte generalisierte Infektionen weisen im Gegensatz zu lokal begrenzten Infekten haufig einen Wert uber 2 ng/ml auf, wobei die Spezifitat des Parameters mit der Hohe des Werts steigt. Therapeutische Masnahmen, die zur lokalen Begrenzung der Infektion fuhren, resultieren in einem Abfall von PCT. In den ersten Tagen nach grosen Operationen, Polytrauma, bei wenigen malignen Erkrankungen, Hitzschlag wie auch im Rahmen spezieller Behandlungen hamatologischer Krankheiten kann der Parameter erhoht sein, ohne das eine Sepsis oder schwere Infektion vorliegt. Bisherige Studien legen nahe, das PCT bei Patienten mit Sepsis im Vergleich zu traditionellen Entzundungs- bzw. Sepsisparametern Vorteile besitzt, wobei an erster Stelle die Eigenschaft, eine generalisierte Infektion anzuzeigen, zu nennen ist.

Tissue hypoxia, especially in the splanchnic area, is still considered to be an important cofactor in the pathogenesis of multiple organ failure. Thus, in the treatment of septic shock the specific effects of ino-tropic drugs on the splanchnic perfusion are of particular interest. To give strict recommendations for monitoring and for therapeutic strategies in the treatment of gastrointestinal failure in patients with sepsis is difficult not only due to the lack of data on clinical outcome and organ dysfunction, but also due to some limitations in the methods applied to assess splanchnic perfusion and oxygenation. A reasonable approach in the management of splanchnic underperfusion in septic patients includes: Measurement of gastric mucosal pH or CO2-gap because it is the only method for the assessment of splanchnic perfusion which can be useful in the clinical routine. Adequate volume loading likely is the most important step in the supportive treatment of patients with septic shock. Unfortunately, what kind of fluids, endpoints, and monitoring techniques should be used is still controversial. Nevertheless, techniques allowing us to achieve and tightly control volume loading and regional perfusion, e.g. the measurement of pHi or CO2-gap, may be helpful. Patients with high DO2 have had better outcome. However, measurement of parameters assessing global and regional oxygenation may be superior than to guide therapy by DO2. To maximize DO2 by the use of very high dosages of catecholamines can be harmful. The recommendation to use dobutamine as catecholamine of first choice seems to be justified. In critically ill patients, no negative effects of norepinephrine on regional perfusion have been demonstrated provided the patient is adequately volume resuscitated and the DO2 is normal or slightly elevated. Therefore, after volume resuscitation and treatment with dobutamine, norepinephrine should be used for achieving an adequate perfusion pressure. Epinephrine and dopamine should be avoided because they seem to restribute blood flow away from the splanchnic region. There are no convincing data yet to support the routine use of low dose dopamine or dopexamine in patients with sepsis. These recommendations are limited by the lack of outcome studies and optimal methods for the assessment of splanchnic perfusion/oxygenation.