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Background: Pulse-contour analysis method (PCM) cardiac output (CO) monitors are increasingly used for CO monitoring during anaesthesia and in the critically ill. Very recently, several systems have been introduced that do not need calibration; among them the pressure recording analytical method (PRAM). Sparse data comparing the accuracy of the PRAM-CO with conventional thermodilution CO (ThD-CO) in cardiac surgery patients are available.Methods: In this prospective comparison study, paired CO measurements with a pulmonary artery catheter and a PRAM monitoring set were obtained 20-30 min apart (t1, t2) in 23 extubated patients on the first postoperative day after cardiac surgery. Data were analysed by the Bland-Altman method.Results: A total of 46 paired CO measurements (23 for each interval) were collected. The Bland-Altman analysis showed a mean difference (bias) of 0.0 litre min(-1) and limits of agreement (1.96 sd) of 4.53 to -4.54 litre min(-1) [upper 95% confidence interval (CI), 3.26-5.80; lower 95% CI, -5.8 to -3.27]. The percentage error (1.96 sd/mean of the reference method) was 87%.Conclusions: These results question the reliability of the PRAM technology for the determination of CO in postoperative cardiac surgery patients. [ABSTRACT FROM AUTHOR]

Initially introduced as a rheologic agent for use in intermittent claudication due to peripheral artery disease and in ischemic cerebrovascular disease, the methylxanthine derivative pentoxifylline (PTX) has been shown to possess several anti-inflammatory properties which make this drug an interesting immunomodulating adjunct for the management of patients undergoing cardiac surgery. As an unspecific phosphodiesterase inhibitor PTX ameliorates the inflammatory response following a septic stimulus and blunts organ dysfunction after ischemia-reperfusion injury. Apart from this several small clinical studies have shown that the use of PTX may blunt the inflammatory response induced by cardiac surgery using a cardiopulmonary bypass. Additionally it has been shown that the perioperative application of this drug may improve postoperative function of organs at risk, such as the kidneys and liver. [ABSTRACT FROM AUTHOR]

Background: Surviving sepsis can lead to chronic physical, psychological and cognitive impairments, which affect millions of patients worldwide, including survivors after COVID-19 viral sepsis. We aimed to characterize the magnitude and trajectory of functional dependence and new impairments post-sepsis., Methods: We conducted a prospective cohort study including sepsis survivors who had been discharged from five German intensive care units (ICUs), until 36 months post-discharge. Primary outcome was functional dependence, defined as ≥1 impaired activity of daily living (ADL; 10-item ADL score <100), self-reported nursing care dependence or nursing care level. Secondary outcome was post-sepsis morbidity in the physical, psychological or cognitive domain. We used a multistate, competing risk model to address competing events in the course of dependence, and conducted multiple linear regression analyses to identify predictors associated with the ADL score., Findings: Of 3210 sepsis patients screened, 1968 survived the ICU treatment (61.3%). A total of 753 were included in the follow-up assessments of the Mid-German Sepsis cohort. Patients had a median age of 65 (Q1-Q3 56-74) years, 64.8% (488/753) were male and 76.1% (573/753) had a septic shock. Considering competing risk modelling, the probability of still being functional dependent was about 25%, while about 30% regained functional independence and 45% died within the three years post-sepsis. Patients reported a high burden of new and often overlapping impairments until three years post-sepsis. In the subgroup of three-year survivors (n = 330), new physical impairments affected 91.2% (n = 301) while new cognitive and psychological impairments were reported by 57.9% (n = 191) and 40.9% (n = 135), respectively. Patients with pre-existing functional limitations and higher age were at risk for low ADL scores three years after sepsis., Interpretation: Sepsis survivorship was associated with a broad range of new impairments and led to functional dependence in around one quarter of patients. Targeted measures are needed to mitigate the burden of this Post-Sepsis-Syndrome and increase the proportion of patients that achieve functional improvements., Funding: This work was supported by the Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC) at the Jena University Hospital funded by the German Ministry of Education and Research and by the Rudolf Presl GmbH & Co, Kreischa, Germany., Competing Interests: Over the past 5 years, Sven Bercker was investigator in studies sponsored by BioMeriéux, Boehringer Ingelheim, AM-Pharma B.V., Roche, Takeda, Dompé, and he is member of a DSMB for a study sponsored by hemotune AG. He has not received any personal fees for lectures or as a consultant or any reimbursement of travel expenses outside the sponsored studies. Konrad Reinhart holds shares from InflaRx NV, which is based in Jena, Germany and listed at NASDQ. This company recently received emergency use authorization by the FDA for an antibody against C5a—Gohibic (vilobelimab)—to treat critically ill COVID-19 patients, which fulfill the criteria for viral sepsis. E. Wesley Ely received NIH/VA Grant support. Over the last 36 months, the institution of Heinrich Groesdonk has received fees for his lectures, for his consultant activities, for his work in an advisory board or reimbursement for personal travel expenses by Edwards Lifescience, Amomed, and he personally holds shares from Fresenius SE. All other authors declare no conflict of interest., (© 2024 The Author(s).)

Background: The intensive care unit (ICU) is a scarce resource in all health care systems, necessitating a well-defined utilization. Therefore, benchmarks are essential; and yet, they are limited due to heterogenous definitions of what an ICU is. This study analyzed the case distribution, patient characteristics, and hospital course and outcomes of 6,204,093 patients in the German Helios Hospital Group according to 10 derived ICU definitions. We aimed to set a baseline for the development of a nationwide, uniform ICU definition. Methods : We analyzed ten different ICU definitions: seven derived from the German administrative data set of claims data according to the German Hospital Remuneration Act, three definitions were taken from the Helios Hospital Group's own bed classification. For each ICU definition, the size of the respective ICU population was analyzed. Due to similar patient characteristics for all ten definitions, we selected three indicator definitions to additionally test statistically against IQM. Results : We analyzed a total of 5,980,702 completed hospital cases, out of which 913,402 referred to an ICU criterion (14.7% of all cases). A key finding is the significant variability in ICU population size, depending on definitions. The most restrictive definition of only mechanical ventilation (DOV definition) resulted in 111,966 (1.9%) cases; mechanical ventilation plus typical intensive care procedure codes (IQM definition) resulted in 210,147 (3.5%) cases; defining each single bed individually as ICU or IMC (ICUᴧIMC definition) resulted in 411,681 (6.9%) cases; and defining any coded length of stay at ICU (LOSi definition) resulted in 721,293 (12.1%) cases. Further testing results for indicator definitions are reported. Conclusions : The size of the population, utilization rates, outcomes, and capacity assumptions clearly depend on the definition of ICU. Therefore, the underlying ICU definition should be stated when making any comparisons. From previous studies, we anticipated that 25-30% of all ICU patients should be mechanically ventilated, and therefore, we conclude that the ICUᴧIMC definition is the most plausible approximation. We suggest a mandatory application of a clearly defined ICU term for all hospitals nationwide for improved benchmarking and data analysis.

The aim of this study was to investigate the pharmacokinetics of multiple-dose intravenous (i.v.) fosfomycin in critically ill patients during continuous venovenous hemodialysis (CVVHD). Non-compartmental analysis and population pharmacokinetic modeling were used to simulate different dosing regimens. We evaluated 15 critically ill patients with renal insufficiency and CVVHD undergoing anti-infective treatment with fosfomycin in our ICU. Five grams of fosfomycin were administered for 120 min every 6 h. Plasma concentrations were determined with and without CVVHD. Pharmacokinetic analysis and simulations were performed using non-linear mixed effects modelling (NONMEM). A two-compartment model with renal and dialysis clearance was most accurate in describing the pharmacokinetics of i.v. fosfomycin during CVVHD. Population parameter estimates were 18.20 L and 20.80 L for the central and peripheral compartment volumes, and 0.26 L/h and 5.08 L/h for renal and intercompartmental clearance, respectively. Urinary creatinine clearance (CL CR ) represented a considerable component of renal clearance. Central compartment volume increased over time after the first dose. For patients with CL CR  > 50 (90) mL/min and CVVHD, dosage should be increased to ≥ 15 (16) grams of i.v. fosfomycin across three (four) daily doses. Individual CL CR must be considered when dosing i.v. fosfomycin in critically ill patients during CVVHD., (© 2023. Springer Nature Limited.)

The inodilator levosimendan, in clinical use for over two decades, has been the subject of extensive clinical and experimental evaluation in various clinical settings beyond its principal indication in the management of acutely decompensated chronic heart failure. Critical care and emergency medicine applications for levosimendan have included postoperative settings, septic shock, and cardiogenic shock. As the experience in these areas continues to expand, an international task force of experts from 15 countries (Austria, Belgium, China, Croatia, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Spain, Sweden, Switzerland, and the USA) reviewed and appraised the latest additions to the database of levosimendan use in critical care, considering all the clinical studies, meta-analyses, and guidelines published from September 2019 to November 2021. Overall, the authors of this opinion paper give levosimendan a "should be considered" recommendation in critical care and emergency medicine settings, with different levels of evidence in postoperative settings, septic shock, weaning from mechanical ventilation, weaning from veno-arterial extracorporeal membrane oxygenation, cardiogenic shock, and Takotsubo syndrome, in all cases when an inodilator is needed to restore acute severely reduced left or right ventricular ejection fraction and overall haemodynamic balance, and also in the presence of renal dysfunction/failure., (© 2022. The Author(s).)

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.

Background: To assess the risk of aspiration, nutrient tolerance, and gastric emptying of patients in ICUs, gastric ultrasound can provide information about the gastric contents. Using established formulas, the gastric residual volume (GRV) can be calculated in a standardized way by measuring the gastric antrum. The purpose of this study was to determine the GRV in a cohort of enterally fed patients using a miniaturized ultrasound device to achieve knowledge about feasibility and the GRV over time during the ICU stay. The findings could contribute to the optimization of enteral nutrition (EN) therapy., Methods: A total of 217 ultrasound examinations with 3 measurements each (651 measurements in total) were performed twice daily (morning and evening) in a longitudinal observational study on 18 patients with EN in the interdisciplinary surgical ICU of Saarland University Medical Center. The measured values of the GRV were analyzed in relation to the clinical course, the nutrition, and other parameters., Results: Measurements could be performed without interrupting the flow of clinical care and without pausing EN. The GRV was significantly larger with sparsely auscultated bowel sounds than with normal and excited bowel sounds ( p < 0.01). Furthermore, a significantly larger GRV was present when using a high-caloric/low-protein nutritional product compared to an isocaloric product ( p = 0.02). The GRV at the morning and evening measurements showed no circadian rhythm. When comparing the first and last ultrasound examination of each patient, there was a tendency towards an increased GRV ( p = 0.07)., Conclusion: The GRV measured by miniaturized ultrasound devices can provide important information about ICU patients without restricting treatment procedures in the ICU. Measurements are possible while EN therapy is ongoing. Further studies are needed to establish gastric ultrasound as a management tool in nutrition therapy.

Background: The number of high-risk patients undergoing surgery is steadily increasing. In order to maintain and, if necessary, optimize perioperative hemodynamics as well as the oxygen supply to the organs (DO 2 ) in this patient population, a timely assessment of cardiac function and the underlying pathophysiological causes of hemodynamic instability is essential for the anesthesiologist. A variety of hemodynamic monitoring procedures are available for this purpose; however, due to method-immanent limitations they are often not able to directly identify the underlying cause of cardiovascular impairment., Objective: To present a stepwise algorithm for a perioperative echocardiography-based hemodynamic optimization in noncardiac surgery high-risk patients. In this context, echocardiography on demand according to international guidelines can be performed under certain conditions (hemodynamic instability, nonresponse to hemodynamic treatment) as well as in the context of a planned intraoperative procedure, mostly as a transesophageal echocardiography., Methods and Results: Hemodynamically focused echocardiography as a rapidly available bedside method, enables the timely diagnosis and assessment of cardiac filling obstructions, volume status and volume response, right and left heart function, and the function of the heart valves., Conclusion: Integrating all echocardiographic findings in a differentiated assessment of the patient's cardiovascular function enables a (patho)physiologically oriented and individualized hemodynamic treatment., (© 2021. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Cardiac surgery patients represent a high-risk cohort in intensive care units (ICUs). Central venous pressure (CVP) measurement seems to remain an integral part in hemodynamic monitoring, especially in cardio-surgical ICUs. However, its value as a prognostic marker for organ failure is still unclear. Therefore, we analyzed postoperative CVP values after adult cardiac surgery in a large cohort with regard to its prognostic value for morbidity and mortality., Methods: All adult patients admitted to our ICUs between 2006 and 2019 after cardiac surgery were eligible for inclusion in the study ( n = 11,198). We calculated the median initial CVP (miCVP) after admission to the ICU, which returned valid values for 9802 patients. An ROC curve analysis for optimal cut-off miCVP to predict ICU mortality was conducted with consecutive patient allocation into a (a) low miCVP (LCVP) group (≤11 mmHg) and (b) high miCVP (HCVP) group (>11 mmHg). We analyzed the impact of high miCVP on morbidity and mortality by propensity score matching (PSM) and logistic regression., Results: ICU mortality was increased in HCVP patients. In addition, patients in the HCVP group required longer mechanical ventilation, had a higher incidence of acute kidney injury, were more frequently treated with renal replacement therapy, and showed a higher risk for postoperative liver dysfunction, parametrized by a postoperative rise of ≥ 10 in MELD Score. Multiple regression analysis confirmed HCVP has an effect on postoperative ICU-mortality and intrahospital mortality, which seems to be independent., Conclusions: A high initial CVP in the early postoperative ICU course after cardiac surgery is associated with worse patient outcome. Whether or not CVP, as a readily and constantly available hemodynamic parameter, should promote clinical efforts regarding diagnostics and/or treatment, warrants further investigations.

(1) Background: Reliable ultrasonographic measurements of optic nerve sheath diameter (ONSD) to detect increased intracerebral pressure (ICP) has not been established in awake patients with continuous invasive ICP monitoring. Therefore, in this study, we included fully awake patients with and without raised ICP and correlated ONSD with continuously measured ICP values. (2) Methods: In a prospective study, intracranial pressure (ICP) was continuously measured in 25 patients with an intraparenchymatic P-tel probe. Ultrasonic measurements were carried out three times for each optic nerve in vertical and horizontal directions. ONSD measurements and ICP were correlated. Patients with ICP of 2.0-10.0 mmHg were compared with patients suffering from an ICP of 10.1-24.2 mmHg. (3) Results: In all patients, the ONSD vertical and horizontal measurement for both eyes correlated well with the ICP (Pearson R = 0.68-0.80). Both measurements yielded similar results (Bland-Altman: vertical bias: -0.09 mm, accuracy: ±0.66 mm; horizontal bias: -0.06 mm, accuracy: ±0.48 mm). For patients with an ICP of 2.0-10.0 mmHg compared to an ICP of 10.1-24.2, ROC (receiver operating characteristic) analyses showed that ONSD measurement accurately predicts elevated ICP (optimal cut-off value 5.05 mm, AUC of 0.91, sensitivity 92% and specificity 90%, p < 0.001). (4) Conclusions: Ultrasonographic measurement of ONSD in awake, spontaneously breathing patients provides a valuable method to evaluate patients with suspected increased ICP. Additionally, it provides a potential tool for rapid assessment of ICP at the bedside and to identify patients at risk for a poor neurological outcome.

Background: The reported mortality for sepsis and septic shock varies between 15% and 59% in international comparison. For Germany, the number of studies is limited. Previous estimations of mortality in Germany are outdated or based on claims data analyses. Various authors discuss whether lacking quality initiatives and treatment standards in Germany could cause higher mortality for sepsis. This contrasts with the internationally well-recognized performance of the German intensive care infrastructure during the COVID-19 pandemic., Objectives: The objectives of this systematic review and meta-analysis were to estimate 30-day and 90-day mortality of patients with sepsis and patients with septic shock in Germany and to compare the mortality with that of other industrialized regions (Europe, North America)., Material and Methods: A systematic literature search included interventional and observational studies published between 2009 and 2020 in PubMed and the Cochrane Library that analyzed adult patients with sepsis, severe sepsis and septic shock in Europe and North America. Studies with less than 20 patients were excluded. The 30-day and 90-day mortality for sepsis and septic shock were pooled separately for studies conducted in Germany, Europe (excluding Germany) and North America in a meta-analysis using a random effects model. Mortality over time was analyzed in a linear regression model., Results: Overall, 134 studies were included. Of these, 15 studies were identified for the estimation of mortality in Germany, covering 10,434 patients, the number of patients per study ranged from 28 to 4183 patients. The 30-day mortality for sepsis was 26.50% (95% confidence interval, CI: 19.86-33.15%) in Germany, 23.85% (95% CI: 20.49-27.21%) in Europe (excluding Germany) and 19.58% (95% CI: 14.03-25.14%) in North America. The 30-day mortality for septic shock was 30.48% (95% CI: 29.30-31.67%) in Germany, 34.57% (95% CI: 33.51-35.64%) in Europe (excluding Germany) and 33.69% (95% CI: 31.51-35.86%) in North America. The 90-day mortality for septic shock was 38.78% (95% CI: 32.70-44.86%) in Germany, 41.90% (95% CI: 38.88-44.91%) in Europe (excluding Germany) and 34.41% (95% CI: 25.66-43.16%) in North America. A comparable decreasing trend in sepsis 30-day mortality was observed in all considered regions since 2009., Conclusion: Our analysis does not support the notion that mortality related to sepsis and septic shock in Germany is higher in international comparison. A higher mortality would not be obvious either, since intensive care, for example also during the COVID-19 pandemic, is regarded as exemplary in Germany and the structural quality, such as the number of intensive care beds per 100,000 inhabitants, is high in international comparison. Nevertheless, deficits could also exist outside intensive care medicine. A comparison of international individual studies should take greater account of the structure of healthcare systems, the severity of disease and the limitations resulting from the data sources used., (© 2021. The Author(s).)

The number of high-risk patients undergoing surgery is growing. To maintain adequate hemodynamic functioning as well as oxygen delivery to the vital organs (DO 2 ) amongst this patient population, a rapid assessment of cardiac functioning is essential for the anesthesiologist. Pinpointing any underlying cardiovascular pathophysiology can be decisive to guide interventions in the intraoperative setting. Various techniques are available to monitor the hemodynamic status of the patient, however due to intrinsic limitations, many of these methods may not be able to directly identify the underlying cause of cardiovascular impairment. Hemodynamic focused echocardiography, as a rapid diagnostic method, offers an excellent opportunity to examine signs of filling impairment, cardiac preload, myocardial contractility and the function of the heart valves. We thus propose a 6-step-echocardiographic approach to assess high-risk patients in order to improve and maintain perioperative DO 2 . The summary of all echocardiographic based findings allows a differentiated assessment of the patient's cardiovascular function and can thus help guide a (patho)physiological-orientated and individualized hemodynamic therapy.

Hemodynamic conditions with reduced systemic vascular resistance commonly are observed in patients undergoing cardiac surgery and may range from moderate reductions in vascular tone, as a side effect of general anesthetics, to a profound vasodilatory syndrome, often referred to as vasoplegic shock. Therapy with vasopressors is an important pillar in the treatment of these conditions. There is limited guidance on the appropriate choice of vasopressors to restore and optimize systemic vascular tone in patients undergoing cardiac surgery. A panel of experts in the field convened to develop statements and evidence-based recommendations on clinically relevant questions on the use of vasopressors in cardiac surgical patients, using a critical appraisal of the literature following the GRADE system and a modified Delphi process. The authors unanimously and strongly recommend the use of norepinephrine and/or vasopressin for restoration and maintenance of systemic perfusion pressure in cardiac surgical patients; despite that, the authors cannot recommend either of these drugs with respect to the risk of ischemic complications. The authors unanimously and strongly recommend against using dopamine for treating post-cardiac surgery vasoplegic shock and against using methylene blue for purposes other than a rescue therapy. The authors unanimously and weakly recommend that clinicians consider early addition of a second vasopressor (norepinephrine or vasopressin) if adequate vascular tone cannot be restored by a monotherapy with either norepinephrine or vasopressin and to consider using vasopressin as a first-line vasopressor or to add vasopressin to norepinephrine in cardiac surgical patients with pulmonary hypertension or right-sided heart dysfunction., Competing Interests: Declaration of Competing Interest All authors received travel support and expense allowances for the participation in the consensus meetings in Vienna and Ghent. Additionally, F.G. reports honoraria for lectures, scientific advice, and travel support by Orion Pharma and Amomed Pharma outside this work; M. Ha. reports honoraria for lectures, scientific advice, and travel support by Edwards Lifesciences, and Amomed Pharma outside this work; S.T. received honoraria for lectures, scientific advice, and travel support by Edwards Lifesciences, scientific advice, and travel support by Orion Pharma, Medtronic, CSL Behring, Edwards Lifesciences, and Amomed Pharma outside this work. All other authors state that they have no further interest to declare., (Copyright © 2020 Elsevier Inc. All rights reserved.)

In recent years, inhaled sedation has been increasingly used in the intensive care unit (ICU). The aim of this prospective, controlled trial was to compare washout and awakening times after long term sedation with desflurane and isoflurane both administered with the Mirus™ system (TIM GmbH, Koblenz, Germany). Twenty-one consecutive critically ill patients were alternately allocated to the two study groups, obtaining inhaled sedation with either desflurane or isoflurane. After 24 h study sedation, anesthetic washout curves were recorded, and a standardized wake-up test was performed. The primary outcome measure was the time required to decrease the endtidal concentration to 50% (T50%). Secondary outcome measures were T80% and awakening times (all extremities moved, RASS -2). Decrement times (min) (desflurane versus isoflurane, median (1st quartile-3rd quartile)) (T50%: 0.3 (0.3-0.4) vs. 1.3 (0.4-2.3), log-rank test P = 0.002; P80%: 2.5 (2-5.9) vs. 12.1 (5.1-20.2), P = 0.022) and awakening times (to RASS -2: 7.5 (5.5-8.8) vs. 41.0 (24.5-43.0), P = 0.007; all extremities moved: 5.0 (4.0-8.5) vs. 13.0 (8.0-41.25), P = 0.037) were significantly shorter after desflurane compared to isoflurane. The use of desflurane with the Mirus™ system significantly shortens the washout times and leads to faster awakening after sedation of critically ill patients.

Fosfomycin is an antibiotic with a broad spectrum of activity against many multidrug-resistant bacterial strains. It is mainly excreted unchanged by the kidneys, and its half-life therefore depends on kidney function which varies considerably among individuals, and within individuals over time. Proper fosfomycin dosing thus depends on assaying blood concentration of the drug. We developed and validated a simple, sensitive and specific chromatography assay, which was coupled to electrospray ionization mass spectrometry for determination of fosfomycin. Separation of fosfomycin was based on the method of the hydrophilic interaction liquid chromatography; specifically, plasma and dialysate samples were acidified and the protein precipitated with acetonitrile. The calibration curves showed excellent coefficients of determination (R2 > 0.999) over the relevant concentration range of 25-700 μg/mL. Intraday precision was 1.1-1.2% and accuracy was -5.9% to 0.9% for quality control samples. Interday precision was 2.9-3.4% and accuracy was -3.7% to 5.5%. Extraction recovery was ≥87% and matrix effects ranged from 2.2% to 4.3%. After laboratory validation, the method was successfully applied to clinical samples., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Importance: The overall low survival rate of patients with lung cancer calls for improved detection tools to enable better treatment options and improved patient outcomes. Multivariable molecular signatures, such as blood-borne microRNA (miRNA) signatures, may have high rates of sensitivity and specificity but require additional studies with large cohorts and standardized measurements to confirm the generalizability of miRNA signatures., Objective: To investigate the use of blood-borne miRNAs as potential circulating markers for detecting lung cancer in an extended cohort of symptomatic patients and control participants., Design, Setting, and Participants: This multicenter, cohort study included patients from case-control and cohort studies (TREND and COSYCONET) with 3102 patients being enrolled by convenience sampling between March 3, 2009, and March 19, 2018. For the cohort study TREND, population sampling was performed. Clinical diagnoses were obtained for 3046 patients (606 patients with non-small cell and small cell lung cancer, 593 patients with nontumor lung diseases, 883 patients with diseases not affecting the lung, and 964 unaffected control participants). No samples were removed because of experimental issues. The collected data were analyzed between April 2018 and November 2019., Main Outcomes and Measures: Sensitivity and specificity of liquid biopsy using miRNA signatures for detection of lung cancer., Results: A total of 3102 patients with a mean (SD) age of 61.1 (16.2) years were enrolled. Data on the sex of the participants were available for 2856 participants; 1727 (60.5%) were men. Genome-wide miRNA profiles of blood samples from 3046 individuals were evaluated by machine-learning methods. Three classification scenarios were investigated by splitting the samples equally into training and validation sets. First, a 15-miRNA signature from the training set was used to distinguish patients diagnosed with lung cancer from all other individuals in the validation set with an accuracy of 91.4% (95% CI, 91.0%-91.9%), a sensitivity of 82.8% (95% CI, 81.5%-84.1%), and a specificity of 93.5% (95% CI, 93.2%-93.8%). Second, a 14-miRNA signature from the training set was used to distinguish patients with lung cancer from patients with nontumor lung diseases in the validation set with an accuracy of 92.5% (95% CI, 92.1%-92.9%), sensitivity of 96.4% (95% CI, 95.9%-96.9%), and specificity of 88.6% (95% CI, 88.1%-89.2%). Third, a 14-miRNA signature from the training set was used to distinguish patients with early-stage lung cancer from all individuals without lung cancer in the validation set with an accuracy of 95.9% (95% CI, 95.7%-96.2%), sensitivity of 76.3% (95% CI, 74.5%-78.0%), and specificity of 97.5% (95% CI, 97.2%-97.7%)., Conclusions and Relevance: The findings of the study suggest that the identified patterns of miRNAs may be used as a component of a minimally invasive lung cancer test, complementing imaging, sputum cytology, and biopsy tests.

Background: Despite an increasing incidence of patients suffering from acute coronary syndrome (ACS) under simultaneous treatment with direct oral anticoagulants (DOAC), neither sufficient scientific data nor uniform guidelines for the anticoagulation treatment of these patients are currently available., Objective: The aim of this study was to determine the current practice of preclinical treatment of ACS in patients under DOAC treatment., Material and Methods: An internet and paper-based survey of emergency physicians, specialists of internal medicine, anesthesiologists, emergency and intensive care physicians was performed concerning the prehospital treatment of ACS in patients under long-term DOAC treatment., Results: Overall, 284 questionnaires were answered. Substantial differences in the current treatment of ACS under long-term DOAC therapy were identified. While 39% of the respondents stated that they administer a combination treatment of heparin and acetylsalicylic acid (ASA), 36% renounced the administration of heparin. If a dose reduction was performed, 71% answered that they reduce the heparin dosage. Also, in cases of ST-segment elevation myocardial infarction 48% of the physicians renounced the administration of heparin., Conclusion: In Germany there is currently a heterogeneous practice of emergency treatment of ACS patients under DOAC therapy with respect to the administration of heparin and ASA. Therefore, guidelines of the specialist medical societies should address the prehospital emergency anticoagulation management of ACS in patients under therapy with DOAC, which correspond to the needs of patients and emergency physicians.

Background: Transthoracic echocardiography is the primary imaging modality for diagnosing cardiac conditions but medical education in this field is limited. We tested the hypothesis that a structured theoretical and supervised practical course of training in focused echocardiography in last year medical students results in a more accurate assessment and more precise calculation of left ventricular ejection fraction after ten patient examinations., Methods: After a theoretical introduction course 25 last year medical students performed ten transthoracic echocardiographic examination blocks in postsurgical patients. Left ventricular function was evaluated both with an eye-balling method and with the calculated ejection fraction using diameter and area of left ventricles. Each examination block was controlled by a certified and blinded tutor. Bias and precision of measurements were assessed with Bland and Altman method., Results: Using the eye-balling method students agreed with the tutor's findings both at the beginning (88%) but more at the end of the course (95.7%). The variation between student and tutor for calculation of area, diameter and ejection fraction, respectively, was significantly lower in examination block 10 than in examination block 1 (each p < 0.001). Students underestimated both the length and the area of the left ventricle at the outset, as complete imaging of the left heart in the ultrasound sector was initially unsuccessful., Conclusions: A structured theoretical and practical transthoracic echocardiography course of training for last year medical students provides a clear and measurable learning experience in assessing and measuring left ventricular function. At least 14 examination blocks are necessary to achieve 90% agreement of correct determination of the ejection fraction.

Background: Volatile anesthetics are increasingly used for sedation in intensive care units. The most common administration system is AnaConDa-100 mL (ACD-100; Sedana Medical, Uppsala, Sweden), which reflects volatile anesthetics in open ventilation circuits. AnaConDa-50 mL (ACD-50) is a new device with half the volumetric dead space. Carbon dioxide (CO2) can be retained with both devices. We therefore compared the CO2 elimination and isoflurane reflection efficiency of both devices., Methods: A test lung constantly insufflated with CO2 was ventilated with a tidal volume of 500 mL at 10 breaths/min. End-tidal CO2 (EtCO2) partial pressure was measured using 3 different devices: a heat-and-moisture exchanger (HME, 35 mL), ACD-100, and ACD-50 under 4 different experimental conditions: ambient temperature pressure (ATP), body temperature pressure saturated (BTPS) conditions, BTPS with 0.4 Vol% isoflurane (ISO-0.4), and BTPS with 1.2 Vol% isoflurane. Fifty breaths were recorded at 3 time points (n = 150) for each device and each condition. To determine device dead space, we adjusted the tidal volume to maintain normocapnia (n = 3), for each device. Thereafter, we determined reflection efficiency by measuring isoflurane concentrations at infusion rates varying from 0.5 to 20 mL/h (n = 3), for each device., Results: EtCO2 was consistently greater with ACD-100 than with ACD-50 and HME (ISO-0.4, mean ± standard deviations: ACD-100, 52.4 ± 0.8; ACD-50, 44.4 ± 0.8; HME, 40.1 ± 0.4 mm Hg; differences of means of EtCO2 [respective 95% confidence intervals]: ACD-100 - ACD-50, 8.0 [7.9-8.1] mm Hg, P < .001; ACD-100 - HME, 12.3 [12.2-12.4] mm Hg, P < .001; ACD-50 - HME, 4.3 [4.2-4.3] mm Hg, P < .001). It was greatest under ATP, less under BTPS, and least with ISO-0.4 and BTPS with 1.2 Vol% isoflurane. In addition to the 100 or 50 mL "volumetric dead space" of each AnaConDa, "reflective dead space" was 40 mL with ACD-100 and 25 mL with ACD-50 when using isoflurane. Isoflurane reflection was highest under ATP. Under BTPS with CO2 insufflation and isoflurane concentrations around 0.4 Vol%, reflection efficiency was 93% with ACD-100 and 80% with ACD-50., Conclusions: Isoflurane reflection remained sufficient with the ACD-50 at clinical anesthetic concentrations, while CO2 elimination was improved. The ACD-50 should be practical for tidal volumes as low as 200 mL, allowing lung-protective ventilation even in small patients.

Objective: The aim of this study was to develop clinical preoperative, intraoperative, and postoperative scores for early identification of patients who are at risk of nonocclusive mesenteric ischemia (NOMI)., Design: A retrospective analysis., Setting: Single center., Participants: From January 2008 to December 2014, all patients from the Department of Thoracic and Cardiovascular Surgery were included on the basis of the hospital database., Interventions: All mesenteric angiographically identified NOMI patients were compared with non-NOMI patients., Measurements and Main Results: The study population of 8,748 patients was randomized into a cohort for developing the scores (non-NOMI 4,214 and NOMI 235) and a cohort for control (non-NOMI 4,082 and NOMI 217). Risk factors were identified using forward and backward Wald test and were included in the predictive scores for the occurrence of NOMI. C statistic showed that the scores had a high discrimination for the prediction of NOMI preoperatively (C statistic 0.79; p < 0.001), intraoperatively (C statistic 0.68; p < 0.001), and postoperatively (C statistic 0.85; p < 0.001). A combination of the preoperative, intraoperative, and postoperative risk scores demonstrated the highest discrimination (C statistic 0.87; p < 0.001). The combined score included the following risk factors: renal insufficiency (preoperative); use of cardiopulmonary bypass and intra-aortic balloon pump support (intraoperative); and reexploration for bleeding, renal replacement therapy, and packed red blood cells ≥ 4 units (postoperative). The results were similar in the control group., Conclusions: These scores could be useful to identify patients at risk for NOMI and promote a rapid diagnosis and therapy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: In patients with hemodynamic instability echocardiography has been recommended as the preferred modality to evaluate the underlying pathophysiology. However, due to the fact that recent scientific data on the utilization of echocardiography in German Intensive Care Units (ICU) are scarce, we sought to investigate current practice., Methods: A structured, web-based, anonymized survey was performed from May until July 2015 among members of the German Interdisciplinary Association of Critical Care and Emergency Medicine (DIVI) consisting of 14 questions. Descriptive data analysis was performed., Results: One hundred four intensivists participated in the survey. Two-thirds of participants (66%) used echocardiography regularly for hemodynamic monitoring and stated that it changed the therapy in 26-50% of the cases irrespective of the time performed after ordering the examination. Transthoracic (TTE) were more frequently used than transesophageal (TEE) examinations. Twenty-six percent of the participants held an echocardiography certificate with a formal examination, 27% completed a structured training without an examination and almost half of the questioned ICU personnel (47%) did not complete a comprehensive training., Conclusions: The results of this survey demonstrate a widespread utilization of echocardiography as part of routine diagnostic on frequent number of operative ICUs. However, there might be a lack of structured echocardiographic training especially for anesthesiologists.

Background: The fourth edition of the German guideline for the assessment of brain death, published in 2015 by the German Medical Council (Bundesärztekammer), emphasizes the importance of an apnea test. It is also now required under all circumstances of extracorporeal life support., Objectives: This article is an instruction for the guideline-conforming performance of an apnea test in general and also in cases of extracorporeal life support in different configurations., Materials and Methods: A literature review was performed., Conclusions: The apnea test is an essential part of the bedside examination for the clinical diagnosis of brain death. It is required for all kinds of extracorporeal life support and can be easily performed without endangering the patient. More accurate recommendations for its performance should be considered for the next version of the German guideline for brain death assessment.

Objectives: To characterize volatile organic compounds in breath exhaled by ventilated care patients with acute kidney injury and changes over time during dialysis., Design: Prospective observational feasibility study., Setting: Critically ill patients on an ICU in a University Hospital, Germany., Patients: Twenty sedated, intubated, and mechanically ventilated patients with acute kidney injury and indication for dialysis., Interventions: Patients exhalome was evaluated from at least 30 minutes before to 7 hours after beginning of continuous venovenous hemodialysis., Measurements and Main Results: Expired air samples were aspirated from the breathing circuit at 20-minute intervals and analyzed using multicapillary column ion-mobility spectrometry. Volatile organic compound intensities were compared with a ventilated control group with normal renal function. A total of 60 different signals were detected by multicapillary column ion-mobility spectrometry, of which 44 could be identified. Thirty-four volatiles decreased during hemodialysis, whereas 26 remained unaffected. Forty-five signals showed significant higher intensities in patients with acute kidney injury compared with control patients with normal renal function. Among these, 30 decreased significantly during hemodialysis. Volatile cyclohexanol (23 mV; 2575th, 19-38), 3-hydroxy-2-butanone (16 mV, 9-26), 3-methylbutanal (20 mV; 14-26), and dimer of isoprene (26 mV; 18-32) showed significant higher intensities in acute kidney impairment compared with control group (12 mV; 10-16 and 8 mV; 7-14 and not detectable and 4 mV; 0-6; p < 0.05) and a significant decline after 7 hours of continuous venovenous hemodialysis (16 mV; 13-21 and 7 mV; 6-13 and 9 mV; 8-13 and 14 mV; 10-19)., Conclusions: Exhaled concentrations of 45 volatile organic compounds were greater in critically ill patients with acute kidney injury than in patients with normal renal function. Concentrations of two-thirds progressively decreased during dialysis. Exhalome analysis may help quantify the severity of acute kidney injury and to gauge the efficacy of dialysis.

Inhalation sedation is increasingly performed in intensive care units. For this purpose, two anaesthetic reflectors, AnaConDa™ and Mirus™ are commercially available. However, their internal volume (100 ml) and possible carbon dioxide reflection raised concerns. Therefore, we compared carbon dioxide elimination of both with a heat moisture exchanger (HME, 35 ml) in a test lung model. A constant flow of carbon dioxide was insufflated into the test lung, ventilated with 500 ml, 10 breaths per minute. HME, MIRUS and AnaConDa were connected successively. Inspired (insp-CO 2 ) and end-tidal carbon dioxide concentrations (et-CO 2 ) were measured under four conditions: ambient temperature pressure (ATP), body temperature pressure saturated (BTPS), BTPS with 0.4 Vol% (ISO-0.4), and 1.2 Vol% isoflurane (ISO-1.2). Tidal volume increase to maintain normocapnia was also determined. Insp-CO 2 was higher with AnaConDa compared to MIRUS and higher under ATP compared to BTPS. Isoflurane further decreased insp-CO 2 and abolished the difference between AnaConDa and MIRUS. Et-CO 2 showed similar effects. In addition to volumetric dead space, reflective dead space was determined as 198 ± 6/58 ± 6/35 ± 0/25 ± 0 ml under ATP/BTPS/ISO-0.4/ISO-1.2 conditions for AnaConDa, and 92 ± 6/25 ± 0/25 ± 0/25 ± 0 ml under the same conditions for MIRUS, respectively. Under BTPS conditions and with the use of moderate inhaled agent concentrations, reflective dead space is small and similar between the two devices.

Flavonifractor plautii (formerly Eubacterium plautii ) is an anaerobic gram positive rod shaped bacterium belonging to the family of Clostridiales, and a common member of the human gut microbiome. However, it is very rarely isolated from clinical human specimens, so data about its clinical significance are scarce. Here we report of a bloodstream infection due to F. plautii following gangrenous cholecystitis in a 69 year old man. After cholecystectomy and empirical antimicrobial treatment with ceftriaxone and metronidazole the patient recovered. F. plautii was the only bacterium detected in blood culture, suggesting that it might have been causative for cholecystitis. Antimicrobial resistance testing identified decreased susceptibilities against linezolid and penicillin indicating that a targeted therapy might be necessary. F. plautii can be considered a potential pathogen for cholecystitis.

With the AnaConDa™ and the MIRUS™ system, volatile anesthetics can be administered for inhalation sedation in intensive care units. Instead of a circle system, both devices use anesthetic reflectors to save on the anesthetic agent. We studied the efficiency of desflurane reflection with both devices using different tidal volumes (V T ), respiratory rates (RR), and 'patient' concentrations (C Pat ) in a bench study. A test lung was ventilated with four settings (volume control, RR × V T : 10 × 300 mL, 10 × 500 mL, 20 × 500 mL, 10 × 1000 mL). Two different methods for determination of reflection efficiency were established: First (steady state), a bypass flow carried desflurane into the test lung (flow in ), the input concentration (C in ) was varied (1-17 vol%), and the same flow (flow ex , C ex ) was suctioned from the test lung. After equilibration, C Pat was stored online and averaged; efficiency [%] was calculated [Formula: see text]. Second (washout), flow in and flow ex were stopped, the decline of C Pat was measured; efficiency was calculated from the decay constant of the exponential regression equation. Both measurement methods yielded similar results (Bland-Altman: bias: -0.9 %, accuracy: ±5.55 %). Efficiencies higher than 80 % (>80 % of molecules exhaled are reflected) could be demonstrated in the clinical range of C Pat and V T . Efficiency inversely correlates with the product of C Pat and V T which can be imagined as the volume of anesthetic vapor exhaled by the patient in one breath, but not with the respiratory frequency. Efficiency of the AnaConDa™ was higher for each setting compared with the MIRUS™. Desflurane is reflected by both reflectors with efficiencies high enough for clinical use.

The circle system has been in use for more than a 100 years, whereas the first clinical application of an anaesthetic reflector was reported just 15 years ago. Its functional basis relies on molecular sieves such as zeolite crystals or activated carbon. In a circle system, the breathing gas is rebreathed after carbon dioxide absorption; a reflector on the other hand specifically retains the anaesthetic during expiration and resupplies it during the next inspiration. Reflection systems can be used in conjunction with intensive care ventilators and do not need the permanent presence of trained qualified staff. Because of easy handling and better ventilatory capabilities of intensive care ventilators, reflection systems facilitate the routine use of volatile anaesthetics in intensive care units. Until now, there are three reflection systems commercially available: the established AnaConDa™ (Sedana Medical, Uppsala, Sweden), the new smaller AnaConDa-S™, and the Mirus™ (Pall Medical, Dreieich, Germany). The AnaConDa consists only of a reflector which is connected to a syringe pump for infusion of liquid sevoflurane or isoflurane. The Mirus represents a technical advancement; its control unit includes a gas and ventilation monitor as well as a gas dispensing unit. The functionality, specific features, advantages and disadvantages of both systems are discussed in the text.

AnaConDa-100 ml (ACD-100, Sedana Medical, Uppsala, Sweden) is well established for inhalation sedation in the intensive care unit. But because of its large dead space, the system can retain carbon dioxide (CO 2 ) and increase ventilatory demands. We therefore evaluated whether AnaConDa-50 ml (ACD-50), a device with half the internal volume, reduces CO 2 retention and ventilatory demands during sedation of invasively ventilated, critically ill patients. Ten patients participated in this cross-over protocol. After sedation with isoflurane via ACD-100 for 24 h, the 5-h observation period started. During the first hour, ACD-100 was used; for the next 2 h, ACD-50; and for the last 2 h, ACD-100 was used again. Sedation was titrated to Richmond Agitation and Sedation Scale (RASS) score - 3 to - 4 and a processed electroencephalogram (Narcotrend Index, Narcotrend-Gruppe, Hannover, Germany) was recorded. Minute ventilation, CO 2 elimination, and isoflurane consumption were compared. All patients were deeply sedated (Narcotrend Index, mean ± SD: 38 ± 10; RASS scores - 3 to - 5) and breathed spontaneously with pressure support throughout the observation period. Infusion rates of isoflurane and opioid, either remifentanil or sufentanil, as well as ventilator settings were unchanged. Minute ventilation and end-tidal CO 2 were significantly reduced with the ACD-50, respiratory rate remained unchanged, and tidal volume decreased by 66 ± 43 ml. End-tidal isoflurane concentrations were also slightly reduced while haemodynamic measures remained constant. The ACD-50 reduces the tidal volume needed to eliminate carbon dioxide without augmenting isoflurane consumption.

Objectives: To prospectively evaluate the relationship of established inflammatory markers and presepsin on nonocclusive mesenteric ischemia and to correlate presepsin levels to the occurrence and severity of nonocclusive mesenteric ischemia., Design: Patients were prospectively enrolled and blood samples taken, followed by a retrospective evaluation of laboratory values and angiographic findings. The study was ethics committee approved., Settings: Patients with clinical suspicion of nonocclusive mesenteric ischemia underwent catheter angiography of the superior mesenteric artery. Images were assessed by two experienced radiologists on consensus basis using a previously published standardized reporting system (Homburg-Nonocclusive Mesenteric Ischemia-Score). Two groups were formed according to the severity of nonocclusive mesenteric ischemia, mild and severe, patients without clinical signs of nonocclusive mesenteric ischemia formed the reference group. These data were correlated to inflammatory blood markers assessed pre- and postoperatively: C-reactive protein, leucocytes, procalcitonin, and presepsin as well as outcome data., Patients: Between January 2010 and March 2011, a total of 839 patients undergoing cardiovascular surgery participated in this study., Measurements and Main Results: Mild nonocclusive mesenteric ischemia was diagnosed in 4.5%, and severe nonocclusive mesenteric ischemia in 3.2%. Median postoperative presepsin concentrations were significantly greater in mild and severe nonocclusive mesenteric ischemia than in non-nonocclusive mesenteric ischemia. Statistics showed that postoperative presepsin better discriminated mild and severe nonocclusive mesenteric ischemia than any other tested biomarker., Conclusions: Elevated postoperative plasma presepsin concentrations are an independent predictor of mild and severe nonocclusive mesenteric ischemia. The established inflammatory blood markers significantly correlate with the development and severity of nonocclusive mesenteric ischemia.

Introduction: Isoflurane has shown better sedation control and potential benefits in patients with ARDS compared to propofol or midazolam, but the practical use during continuous lateral rotational therapy remains unknown. We therefore compared isoflurane with propofol and midazolam regarding sedation depth (per the Richmond Agitation-Sedation Scale), opioid consumption, lung function, and hemodynamics in patients treated with continuous lateral rotational therapy., Methods: 38 consecutive critically ill surgical subjects were retrospectively studied using a hospital database. All subjects suffered from ARDS and were treated with continuous lateral rotational therapy between May 2010 and September 2013. Nineteen subjects were sedated with propofol or midazolam and compared with 19 subjects sedated with isoflurane using the AnaConDa-system., Results: Isoflurane sedation resulted in significantly lower Richmond Agitation-Sedation Scale scores compared with propofol or midazolam. Despite deep isoflurane sedation, opioid consumption could be significantly reduced. Spontaneous breathing was possible in 90% of the subjects on isoflurane sedation compared with 16% of the subjects sedated with propofol or midazolam. The difference between peak inspiratory pressure and PEEP was significantly decreased after 24 h of isoflurane sedation. Oxygenation (P aO 2 /F IO 2 ) improved in both groups. Hemodynamics and need for vasopressor therapy were comparable between groups., Conclusions: This study supports the feasibility of isoflurane sedation using continuous lateral rotational therapy., (Copyright © 2018 by Daedalus Enterprises.)

Objective: To clarify whether reactivated cytomegalovirus (CMV) infections in critically ill patients lead to worse outcome or just identify more severely ill patients. If CMV has a pathogenic role, latently infected (CMV-seropositive) patients should have worse outcome than seronegative patients because only seropositive patients can experience a CMV reactivation., Design: Post-hoc analysis of a prospective observational study., Setting: Single university hospital., Participants: The study comprised 983 consecutive patients scheduled for on-pump surgery., Interventions: None., Measurements and Main Results: CMV antibodies were analyzed in preoperative plasma samples. Postoperative adverse events (reintubation, low cardiac output or reinfarction, dialysis, stroke) and 30-day and 1-year mortality were evaluated prospectively. The plasma of reintubated patients and matched control patients was tested for CMV deoxyribonucleic acid, and 618 patients were found to be seropositive for CMV (63%). Among these, the risk for reintubation was increased (10% v 4%, p = 0.001). This increase remained significant after correction for confounding factors (odds ratio 2.70, p = 0.003) and was detectable from the third postoperative day throughout the whole postoperative period. Other outcome parameters were not different. Reintubated seropositive patients were more frequently CMV deoxyribonucleic acid-positive than were matched control patients (40% v 8%, p<0.001)., Conclusions: CMV-seropositive patients had an increased risk of reintubation after cardiac surgery, which was associated with reactivations of their CMV infections. Additional studies should determine whether this complication may be prevented by monitoring of latently infected patients and administering antiviral treatment for reactivated CMV infections., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background  Sparse data are available on the prevalence of right ventricular dysfunction and/or pulmonary arterial hypertension in patients scheduled for cardiac surgery in Germany as well as on the intensity and modalities used for diagnosis, perioperative monitoring, and treatment of these comorbidities. Methods  A postal survey including questions on the prevalence of preoperative right ventricular dysfunction and/or pulmonary arterial hypertension in patients undergoing cardiac surgery in 2009 was sent to 81 German heart centers. Total 47 of 81 (58%) heart centers returned the questionnaires. The centers reported data on 51,095 patients, and 49.8% of the procedures were isolated coronary artery bypass grafting. Results  Data on the prevalence of preoperative pulmonary hypertension and/or right ventricular dysfunction were not available in 54% and 64.6% of centers. In the remaining hospitals, 19.5% of patients presented right heart dysfunction and 10% pulmonary arterial hypertension. Preoperative echocardiography was performed in only 45.3% of the coronary artery bypass grafting cases. Preoperative pharmacologic treatment of pulmonary hypertension or right ventricular dysfunction with oral sildenafil, inhaled prostanoids, or nitric oxide was initiated in 71% and 95.7% of the centers, respectively. Intra- and postoperative treatment was most frequently accomplished with phosphodiesterase-III inhibitors. Conclusion  The prevalence of preoperative right heart dysfunction and pulmonary arterial hypertension in cardiac surgical patients in Germany seems to be substantial. However, in more than 50% of the patients, no preoperative data on right ventricular function and pulmonary arterial pressure are available. This may lead to underestimation of perioperative risk and inappropriate management of this high-risk population., Competing Interests: Conflict of interest: None declared., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: As of 2009, anticoagulation with citrate was standard practice in continuous renal replacement therapy (CRRT) for critically ill patients at the University Medical Centre of Saarland, Germany. Partial hepatic metabolism of citrate means accumulation may occur during CRRT in critically ill patients with impaired liver function. The aim of this study was to evaluate the actual influence of hepatic function on citrate-associated complications during long-term CRRT., Methods: In a retrospective study conducted between January 2009 and November 2012, all cases of dialysis therapy performed in the interdisciplinary surgical intensive care unit were analysed. Inclusion criteria were CRRT and regional anticoagulation with citrate, pronounced liver dysfunction, and pathologically reduced indocyanine green plasma disappearance rate (ICG-PDR)., Results: A total of 1339 CRRTs were performed in 69 critically ill patients with liver failure. At admission, the mean Model for End-stage Liver Disease score was 19.2, and the mean ICG-PDR was 9.8%. Eight patients were treated with liver replacement therapy, and 30 underwent transplants. The mortality rate was 40%. The mean duration of dialysis was 19.4 days, and the circuit patency was 62.2 h. Accumulation of citrate was detected indirectly by total serum calcium/ionised serum calcium (tCa/iCa) ratio > 2.4. This was noted in 16 patients (23.2%). Dialysis had not to be discontinued for metabolic disorder or accumulation of citrate in any case. In 26% of cases, metabolic alkalosis occurred with pH > 7.5. Interestingly, no correlation between citrate accumulation and liver function parameters was detected. Moreover, most standard laboratory liver function parameters showed poor predictive capabilities for accumulation of citrate., Conclusions: Our findings indicate that extra-hepatic metabolism of citrate seems to exist, avoiding in most cases citrate accumulation in critically ill patients despite impaired liver function. Because the citric acid cycle is oxygen-dependent, disturbed microcirculation would result in inadequate citrate metabolism. Raising the tCa/iCa ratio would therefore be an indicator of severity of illness and mortality rather than of liver failure. However, further studies are warranted for confirmation.

Six patients suffering from acute respiratory distress syndrome with the need for extracorporeal membrane oxygenation (ECMO) therapy in deep sedation were included. Isoflurane sedation with the AnaConDa system was initiated within 24 hours after initiation of ECMO therapy and resulted in a satisfactory sedation (Richmond Agitation-Sedation Scale -4 to -5). Despite deep sedation, spontaneous breathing was possible in 6 of 6 patients. We observed a reduced need for vasopressor therapy and improved lung function (PaO2, PaCO2, delta P, and tidal volume) during isoflurane sedation. Opioid consumption could be reduced, and only very low doses of isoflurane were needed (1-3 mL/h). This small case series supports the feasibility of sedation using inhaled anesthetics concurrently with venovenous ECMO.

Background: Lipoprotein(a) concentrations in plasma are associated with cardiovascular risk in the general population. Whether lipoprotein(a) concentrations or LPA genetic variants predict long-term mortality in patients with established coronary heart disease remains less clear., Methods: We obtained data from 3313 patients with established coronary heart disease in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. We tested associations of tertiles of lipoprotein(a) concentration in plasma and two LPA single-nucleotide polymorphisms ([SNPs] rs10455872 and rs3798220) with all-cause mortality and cardiovascular mortality by Cox regression analysis and with severity of disease by generalised linear modelling, with and without adjustment for age, sex, diabetes diagnosis, systolic blood pressure, BMI, smoking status, estimated glomerular filtration rate, LDL-cholesterol concentration, and use of lipid-lowering therapy. Results for plasma lipoprotein(a) concentrations were validated in five independent studies involving 10 195 patients with established coronary heart disease. Results for genetic associations were replicated through large-scale collaborative analysis in the GENIUS-CHD consortium, comprising 106 353 patients with established coronary heart disease and 19 332 deaths in 22 studies or cohorts., Findings: The median follow-up was 9·9 years. Increased severity of coronary heart disease was associated with lipoprotein(a) concentrations in plasma in the highest tertile (adjusted hazard radio [HR] 1·44, 95% CI 1·14-1·83) and the presence of either LPA SNP (1·88, 1·40-2·53). No associations were found in LURIC with all-cause mortality (highest tertile of lipoprotein(a) concentration in plasma 0·95, 0·81-1·11 and either LPA SNP 1·10, 0·92-1·31) or cardiovascular mortality (0·99, 0·81-1·2 and 1·13, 0·90-1·40, respectively) or in the validation studies., Interpretation: In patients with prevalent coronary heart disease, lipoprotein(a) concentrations and genetic variants showed no associations with mortality. We conclude that these variables are not useful risk factors to measure to predict progression to death after coronary heart disease is established., Funding: Seventh Framework Programme for Research and Technical Development (AtheroRemo and RiskyCAD), INTERREG IV Oberrhein Programme, Deutsche Nierenstiftung, Else-Kroener Fresenius Foundation, Deutsche Stiftung für Herzforschung, Deutsche Forschungsgemeinschaft, Saarland University, German Federal Ministry of Education and Research, Willy Robert Pitzer Foundation, and Waldburg-Zeil Clinics Isny., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Presepsin (soluble cluster-of-differentiation 14 subtype [sCD14-ST]) is a humoral risk stratification marker for systemic inflammatory response syndrome and sepsis. It remains unknown whether presepsin can be used to stratify risk in elective cardiac surgery. The authors therefore determined the usefulness of presepsin for risk stratification in patients having elective cardiac surgery., Methods: Eight hundred fifty-six cardiac surgical patients were prospectively studied. Preoperative plasma concentrations of presepsin, procalcitonin, N-terminal pro-hormone natriuretic peptide, cystatin C, and the additive European System of Cardiac Operative Risk Evaluation 2 were compared to mortality at 30 days (primary outcome), 6 months, and 2 yr. Discrimination was assessed with C statistic. Logistic regression analysis was used to calculate univariable and multivariable odds ratios., Results: Thirty-day mortality was 3.2%, 6-month mortality was 6.1%, and 2-yr mortality was 10.4% across the population. Median preoperative presepsin concentrations were significantly greater in 30-day nonsurvivors than in survivors: 842 pg/ml (interquartile range, 306 to 1,246) versus 160 pg/ml (interquartile range, 122 to 234); difference, 167 pg/ml (interquartile range, 92 to 301; P < 0.001). The results were similar for 6-month and 2-yr mortality. Compared to the European System of Cardiac Operative Risk Evaluation 2, presepsin concentration provided better discrimination for postoperative mortality at all follow-up periods, including 30 days (C statistic 0.88 vs. 0.74), 6 months (0.87 vs. 0.76), and 2 yr (0.81 vs. 0.74). Presepsin also provided better discrimination than cystatin C, N-terminal pro-hormone natriuretic peptide, or procalcitonin. Elevated presepsin remained an independent risk predictor after adjustment for potential confounding factors., Conclusions: Elevated preoperative plasma presepsin concentration is an independent predictor of postoperative mortality in elective cardiac surgery patients and is a stronger predictor than several other commonly used assessments.

The circle system has been in use for more than 100 years, whereas the first clinical application of an anaesthetic reflector was reported just 15 years ago. In the circle system, all breathing gas is rebreathed after carbon dioxide absorption. A reflector, on the other hand, with the breathing gas flowing to and fro, specifically retains the anaesthetic during expiration and resupplies it during the next inspiration. A high reflection efficiency (number of molecules resupplied/number of molecules exhaled, RE 80-90%) decreases consumption. In analogy to the fresh gas flow of a circle system, pulmonary clearance ((1-RE) × minute ventilation) defines the opposition between consumption and control of the concentration.It was not until reflection systems became available that volatile anaesthetics were used routinely in some intensive care units. Their advantages, such as easy handling, and better ventilatory capabilities of intensive care versus anaesthesia ventilators, were basic preconditions for this. Apart from AnaConDa™ (Sedana Medical, Uppsala, Sweden), the new MIRUS™ system (Pall Medical, Dreieich, Germany) represents a second, more sophisticated commercially available system.Organ protective effects, excellent control of sedation, and dose-dependent deep sedation while preserving spontaneous breathing with hardly any accumulation or induction of tolerance, make volatile anaesthetics an interesting alternative, especially for patients needing deep sedation or when intravenous drugs are no longer efficacious.But obviously, the outcome is most important. We know that deep intravenous sedation increases mortality, whereas inhalational sedation could prove beneficial. We now need prospective clinical trials examining mortality, but also the psychological outcome of those most critically ill patients sedated by inhalation or intravenously.

Background: Even though bleeding and thromboembolic events are major complications of extracorporeal membrane oxygenation (ECMO), data on the incidence of venous thrombosis (VT) and thromboembolism (VTE) under ECMO are scarce. This study analyzes the incidence and predictors of VTE in patients treated with ECMO due to respiratory failure., Methods: Retrospective analysis of patients treated on ECMO in our center from 04/2010 to 11/2015. Patients with thromboembolic events prior to admission were excluded. Diagnosis was made by imaging in survivors and postmortem examination in deceased patients., Results: Out of 102 screened cases, 42 survivors and 21 autopsy cases [mean age 46.0 ± 14.4 years; 37 (58.7 %) males] fulfilling the above-mentioned criteria were included. Thirty-four patients (54.0 %) underwent ECMO therapy due to ARDS, and 29 patients (46.0 %) with chronic organ failure were bridged to lung transplantation. Despite systemic anticoagulation at a mean PTT of 50.6 ± 12.8 s, [VT/VTE 47.0 ± 12.3 s and no VT/VTE 53.63 ± 12.51 s (p = 0.037)], VT and/or VTE was observed in 29 cases (46.1 %). The rate of V. cava thrombosis was 15/29 (51.7 %). Diagnosis of pulmonary embolism prevailed in deceased patients [5/21 (23.8 %) vs. 2/42 (4.8 %) (p = 0.036)]. In a multivariable analysis, only aPTT and time on ECMO predicted VT/VTE. There was no difference in the incidence of clinically diagnosed VT in ECMO survivors and autopsy findings., Conclusions: Venous thrombosis and thromboembolism following ECMO therapy are frequent. Quality of anticoagulation and ECMO runtime predicted thromboembolic events.

Background: Procalcitonin (PCT) is a well-known prognostic marker after elective cardiac surgery. However, the impact of elevated PCT in patients with an initially uneventful postoperative course is still unclear. The aim of this study was to evaluate PCT levels as a prognostic tool for delayed complications after elective cardiac surgery., Methods: A prospective study was performed in 751 patients with an apparently uneventful postoperative course within the first 24 h after elective cardiac surgery. Serum PCT concentration was taken the morning after surgery. All patients were screened for the occurrence of delayed complications. Delayed complications were defined by in-hospital death, intensive care unit readmission, or prolonged length of hospital stay (>12 days). Odds ratios (OR) [with 95% confidence interval (CI)] were calculated by logistic regression analyses and adjusted for confounders. Predictive capacity of PCT for delayed complications was calculated by ROC analyses. The cutoff value of PCT was derived from the Youden Index calculation., Results: Among 751 patients with an initially uneventful postoperative course, 117 patients developed delayed complications. Serum PCT levels the first postoperative day were significantly higher in these 117 patients (8.9 ng/ml) compared to the remaining 634 (0.9 ng/ml; p < 0.001). ROC analyses showed that PCT had a high accuracy to predict delayed complications (optimal cutoff value of 2.95 ng/ml, AUC of 0.90, sensitivity 73% and specificity 97%). Patients with PCT levels above 2.95 ng/ml the first postoperative day had a highly increased risk of delayed complications (adjusted OR, 110.2; 95% CI 51.5-235.5; p < 0.001)., Conclusions: A single measurement of PCT seems to be a useful tool to identify patients at risk of delayed complications despite an initially uneventful postoperative course.

Background: Vasopressin is used as an adjunct to norepinephrine to support blood pressure in vasodilatory shock after cardiopulmonary bypass (CPB). In this study, we report our observation of vasopressin treatment in 11 patients with nonocclusive mesenteric ischemia (NOMI)., Methods: In an observational cohort study, 78 patients were studied after having been treated for NOMI with intraarterial iloprost infusion after elective cardiac operation. All patients received norepinephrine as vasopressor for marked vasodilation. In 11 patients mean arterial pressure could not be maintained with norepinephrine alone (≤0.4 μg · kg(-1) · min(-1)), and vasopressin was given in addition to norepinephrine as a rescue therapy. The 11 patients (Vaso) and the remaining 67 patients (Nor) were analyzed for clinical improvement after initiation of NOMI treatment, on the following days 1 and 2, and for hospital survival. Intestinal perfusion was controlled by mesenteric angiography., Results: Before initiation of NOMI treatment Vaso patients had significantly higher doses of norepinephrine than the Nor patients (Vaso, 0.65 ± 0.20 μg · kg(-1) · min(-1); Nor, 0.20 ± 0.13 μg · kg(-1) · min(-1); p < 0.001), and their diagnostic score of the angiography was higher (Vaso, 5.4 ± 1.1 points; Nor, 3.5 ± 2.1 points; p = 0.004). After 2 days of NOMI treatment, Vaso patients had improved intestinal perfusion in the control angiography (Vaso, 3.8 ± 1.5 points) and significantly lower doses of norepinephrine than the Nor patients (Vaso, 0.28 ± 0.12 μg · kg(-1) · min(-1); Nor, 0.53 ± 0.34 μg · kg(-1) · min(-1); p = 0.002). All patients survived in the Vaso group; in the Nor group, 17 of 67 patients died in the hospital., Conclusions: Vasopressin administration during NOMI treatment after CPB seems to improve small intestine perfusion and appears be to associated with improved hospital survival., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Acute kidney injury (AKI) is a prominent problem in hospitalized patients and associated with increased morbidity and mortality. Clinical medicine is currently hampered by the lack of accurate and early biomarkers for diagnosis of AKI and the evaluation of the severity of the disease. In 2010, we established a multivariate peptide marker pattern consisting of 20 naturally occurring urinary peptides to screen patients for early signs of renal failure. The current study now aims to evaluate if, in a different study population and potentially various AKI causes, AKI can be detected early and accurately by proteome analysis., Methods: Urine samples from 60 patients who developed AKI after cardiac surgery were analyzed by capillary electrophoresis-mass spectrometry (CE-MS). The obtained peptide profiles were screened by the AKI peptide marker panel for early signs of AKI. Accuracy of the proteomic model in this patient collective was compared to that based on urinary neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) ELISA levels. Sixty patients who did not develop AKI served as negative controls., Results: From the 120 patients, 110 were successfully analyzed by CE-MS (59 with AKI, 51 controls). Application of the AKI panel demonstrated an AUC in receiver operating characteristics (ROC) analysis of 0.81 (95 % confidence interval: 0.72-0.88). Compared to the proteomic model, ROC analysis revealed poorer classification accuracy of NGAL and KIM-1 with the respective AUC values being outside the statistical significant range (0.63 for NGAL and 0.57 for KIM-1)., Conclusions: This study gives further proof for the general applicability of our proteomic multimarker model for early and accurate prediction of AKI irrespective of its underlying disease cause.