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Abstract Background Recent data from the randomized SUSTAIN CSX trial could not confirm clinical benefits from perioperative selenium treatment in high-risk cardiac surgery patients. Underlying reasons may involve inadequate biosynthesis of glutathione peroxidase (GPx3), which is a key mediator of selenium's antioxidant effects. This secondary analysis aimed to identify patients with an increase in GPx3 activity following selenium treatment. We hypothesize that these responders might benefit from perioperative selenium treatment. Methods Patients were selected based on the availability of selenium biomarker information. Four subgroups were defined according to the patient's baseline status, including those with normal kidney function, reduced kidney function, selenium deficiency, and submaximal GPx3 activity. Results Two hundred and forty-four patients were included in this analysis. Overall, higher serum concentrations of selenium, selenoprotein P (SELENOP) and GPx3 were correlated with less organ injury. GPx3 activity at baseline was predictive of 6-month survival (AUC 0.73; p = 0.03). While selenium treatment elevated serum selenium and SELENOP concentrations but not GPx3 activity in the full patient cohort, subgroup analyses revealed that GPx3 activity increased in patients with reduced kidney function, selenium deficiency and low to moderate GPx3 activity. Clinical outcomes did not vary between selenium treatment and placebo in any of these subgroups, though the study was not powered to conclusively detect differences in outcomes. Conclusions The identification of GPx3 responders encourages further refined investigations into the treatment effects of selenium in high-risk cardiac surgery patients. Graphical Abstract

Abstract Background Sepsis and septic shock are frequently accompanied by coagulopathy. Since the sepsis-induced coagulopathy (SIC) score was first described, subsequent studies from Asia revealed a SIC prevalence of 40–60%. In Europe, however, SIC prevalence in patients fulfilling sepsis criteria according to the third international consensus definition (SEPSIS-3) has not yet been evaluated. Methods The Critical Care Trials Group of the German Sepsis Competence Network (SepNet) conducted a secondary analysis of two randomized controlled trials. Only patients fulfilling sepsis criteria according SEPSIS-3 were included in this secondary analysis. In a two step approach, SIC prevalence was determined in 267 patients with sepsis but not septic shock (at the time of inclusion) from the “Effect of Hydrocortisone on Development of Shock Among Patients With Severe Sepsis” (HYPRESS) trial. Then, we estimated SIC prevalence in 1,018 patients from the “Effect of Sodium Selenite Administration and Procalcitonin-Guided Therapy on Mortality in Patients With Severe Sepsis or Septic Shock” (SISPCT) trial using a simplified SIC score based on the platelet-SIC-subscore (PSSC). Study aims were to assess (i) the prevalence of SIC in patients with SEPSIS-3, (ii) the association of SIC with 90-day mortality and morbidity, (iii) the time when patients become SIC positive during the course of sepsis, and (iv) the value of the PSSC for predicting SIC. Results In the HYPRESS trial, SIC prevalence was 22.1% (95% confidence interval [CI] 17.5–27.5%). The estimated SIC prevalence in the SISPCT trial was 24.2% (95% CI 21.6–26.9%). In the HYPRESS trial, SIC was associated with significantly higher 90-day mortality (13.9% vs. 26.8%, p = 0.027) and morbidity. Logistic regression analysis adjusted for age, sex, treatment arm, and (SIC-adapted) SOFA score confirmed the negative association of SIC with survival (p = 0.011). In the SISPCT trial, increased PSSCs were associated with higher 90-day mortality (PSSC 0: 34.4%, PSSC 1: 40.5%, PSSC 2: 53.3%; p

Abstract Background The clinical significance of vitamin D administration in critically ill patients remains inconclusive. The purpose of this systematic review with meta-analysis was to investigate the effect of vitamin D and its metabolites on major clinical outcomes in critically ill patients, including a subgroup analysis based on vitamin D status and route of vitamin D administration. Methods Major databases were searched through February 9, 2022. Randomized controlled trials of adult critically ill patients with an intervention group receiving vitamin D or its metabolites were included. Random-effect meta-analyses were performed to estimate the pooled risk ratio (dichotomized outcomes) or mean difference (continuous outcomes). Risk of bias assessment included the Cochrane tool for assessing risk of bias in randomized trials. Results Sixteen randomized clinical trials with 2449 patients were included. Vitamin D administration was associated with lower overall mortality (16 studies: risk ratio 0.78, 95% confidence interval 0.62–0.97, p = 0.03; I 2 = 30%), reduced intensive care unit length of stay (12 studies: mean difference − 3.13 days, 95% CI − 5.36 to − 0.89, n = 1250, p = 0.006; I 2 = 70%), and shorter duration of mechanical ventilation (9 studies: mean difference − 5.07 days, 95% CI − 7.42 to − 2.73, n = 572, p

Background: Prehabilitation is gaining increasing interest and shows promising effects on short- and long-term outcomes among patients undergoing major surgery. The effect of multimodal, interdisciplinary prehabilitation has not yet been studied in patients with severe heart failure scheduled for the implantation of a left-ventricular assist device (LVAD). Methods: This randomized controlled multi-center study evaluates the effect of preoperative combined optimization of nutritional and functional status. Patients in the intervention group are prescribed daily in-bed cycling and oral nutrition supplements (ONS) from study inclusion until the day before LVAD-implantation. Patients in the control group receive standard of care treatment. The primary outcomes for the pilot study that involves 48 patients are safety (occurrence of adverse events), efficacy (group separation regarding the intake of macronutrients), feasibility of the trial protocol (compliance (percentage of received interventions) and confirmation of recruitment rates. Secondary outcomes include longitudinal measurements of muscle mass, muscle strength, physical function and quality of life, next to traditional clinical outcomes (30-day mortality, hospital and ICU length of stay, duration of mechanical ventilation and number of complications and infections). If the pilot study is successful, a larger confirmatory, international multicenter study is warranted.

Abstract Background Medical nutrition therapy may be associated with clinical outcomes in critically ill patients with prolonged intensive care unit (ICU) stay. We wanted to assess nutrition practices in European intensive care units (ICU) and their importance for clinical outcomes. Methods Prospective multinational cohort study in patients staying in ICU ≥ 5 days with outcome recorded until day 90. Macronutrient intake from enteral and parenteral nutrition and non-nutritional sources during the first 15 days after ICU admission was compared with targets recommended by ESPEN guidelines. We modeled associations between three categories of daily calorie and protein intake (low: 20 kcal/kg; > 1.2 g/kg) and the time-varying hazard rates of 90-day mortality or successful weaning from invasive mechanical ventilation (IMV). Results A total of 1172 patients with median [Q1;Q3] APACHE II score of 18.5 [13.0;26.0] were included, and 24% died within 90 days. Median length of ICU stay was 10.0 [7.0;16.0] days, and 74% of patients could be weaned from invasive mechanical ventilation. Patients reached on average 83% [59;107] and 65% [41;91] of ESPEN calorie and protein recommended targets, respectively. Whereas specific reasons for ICU admission (especially respiratory diseases requiring IMV) were associated with higher intakes (estimate 2.43 [95% CI: 1.60;3.25] for calorie intake, 0.14 [0.09;0.20] for protein intake), a lack of nutrition on the preceding day was associated with lower calorie and protein intakes (− 2.74 [− 3.28; − 2.21] and − 0.12 [− 0.15; − 0.09], respectively). Compared to a lower intake, a daily moderate intake was associated with higher probability of successful weaning (for calories: maximum HR 4.59 [95% CI: 1.5;14.09] on day 12; for protein: maximum HR 2.60 [1.09;6.23] on day 12), and with a lower hazard of death (for calories only: minimum HR 0.15, [0.05;0.39] on day 19). There was no evidence that a high calorie or protein intake was associated with further outcome improvements. Conclusions Calorie intake was mainly provided according to the targets recommended by the active ESPEN guideline, but protein intake was lower. In patients staying in ICU ≥ 5 days, early moderate daily calorie and protein intakes were associated with improved clinical outcomes. Trial registration NCT04143503 , registered on October 25, 2019. Graphical abstract

Abstract Background Oscillometric, non-invasive blood pressure measurement (NIBP) is the first choice of blood pressure monitoring in the majority of low and moderate risk surgeries. In patients with morbid obesity, however, it is subject to several limitations. The aim was to compare arterial pressure monitoring by NIBP and a non-invasive finger-cuff technology (Nexfin®) with the gold-standard invasive arterial pressure (IAP). Methods In this secondary analysis of a prospective observational, single centre cohort study, systolic (SAP), diastolic (DAP) and mean arterial pressure (MAP) were measured at 16 defined perioperative time points including posture changes, fluid bolus administration and pneumoperitoneum (PP) in patients undergoing laparoscopic bariatric surgery. Absolute arterial pressures by NIBP, Nexfin® and IAP were compared using correlation and Bland Altman analyses. Interchangeability was defined by a mean difference ≤ 5 mmHg (SD ≤8 mmHg). Percentage error (PE) was calculated as an additional statistical estimate. For hemodynamic trending, concordance rates were analysed according to the Critchley criterion. Results Sixty patients (mean body mass index of 49.2 kg/m2) were enrolled and data from 56 finally analysed. Pooled blood pressure values of all time points showed a significant positive correlation for both NIPB and Nexfin® versus IAP. Pooled PE for NIBP versus IAP was 37% (SAP), 35% (DAP) and 30% (MAP), for Nexfin versus IAP 23% (SAP), 26% (DAP) and 22% (MAP). Correlation of MAP was best and PE lowest before induction of anesthesia for NIBP versus IAP (r = 0.72; PE 24%) and after intraoperative fluid bolus administration for Nexfin® versus IAP (r = 0.88; PE: 17.2%). Concordance of MAP trending was 90% (SAP 85%, DAP 89%) for NIBP and 91% (SAP 90%, DAP 86%) for Nexfin®. MAP trending was best during intraoperative ATP positioning for NIBP (97%) and at induction of anesthesia for Nexfin® (97%). Conclusion As compared with IAP, interchangeability of absolute pressure values could neither be shown for NIBP nor Nexfin®, however, NIBP showed poorer overall correlation and precision. Overall trending ability was generally high with Nexfin® surpassing NIBP. Nexfin® may likely render individualized decision-making in the management of different hemodynamic stresses during laparoscopic bariatric surgery, particularly where NIBP cannot be reliably established. Trial registration The non-interventional, observational study was registered retrospectively at ( NCT03184285 ) on June 12, 2017.

Abstract Background Proteins are an essential part of medical nutrition therapy in critically ill patients. Guidelines almost universally recommend a high protein intake without robust evidence supporting its use. Methods Using a large international database, we modelled associations between the hazard rate of in-hospital death and live hospital discharge (competing risks) and three categories of protein intake (low: 1.2 g/kg per day) during the first 11 days after ICU admission (acute phase). Time-varying cause-specific hazard ratios (HR) were calculated from piece-wise exponential additive mixed models. We used the estimated model to compare five different hypothetical protein diets (an exclusively low protein diet, a standard protein diet administered early (day 1 to 4) or late (day 5 to 11) after ICU admission, and an early or late high protein diet). Results Of 21,100 critically ill patients in the database, 16,489 fulfilled inclusion criteria for the analysis. By day 60, 11,360 (68.9%) patients had been discharged from hospital, 4,192 patients (25.4%) had died in hospital, and 937 patients (5.7%) were still hospitalized. Median daily low protein intake was 0.49 g/kg [IQR 0.27–0.66], standard intake 0.99 g/kg [IQR 0.89– 1.09], and high intake 1.41 g/kg [IQR 1.29–1.60]. In comparison with an exclusively low protein diet, a late standard protein diet was associated with a lower hazard of in-hospital death: minimum 0.75 (95% CI 0.64, 0.87), and a higher hazard of live hospital discharge: maximum HR 1.98 (95% CI 1.72, 2.28). Results on hospital discharge, however, were qualitatively changed by a sensitivity analysis. There was no evidence that an early standard or a high protein intake during the acute phase was associated with a further improvement of outcome. Conclusions Provision of a standard protein intake during the late acute phase may improve outcome compared to an exclusively low protein diet. In unselected critically ill patients, clinical outcome may not be improved by a high protein intake during the acute phase. Study registration ID number ISRCTN17829198

Abstract Background Parenteral lipid emulsions in critical care are traditionally based on soybean oil (SO) and rich in pro-inflammatory omega-6 fatty acids (FAs). Parenteral nutrition (PN) strategies with the aim of reducing omega-6 FAs may potentially decrease the morbidity and mortality in critically ill patients. Methods A systematic search of MEDLINE, EMBASE, CINAHL and CENTRAL was conducted to identify all randomized controlled trials in critically ill patients published from inception to June 2021, which investigated clinical omega-6 sparing effects. Two independent reviewers extracted bias risk, treatment details, patient characteristics and clinical outcomes. Random effect meta-analysis was performed. Results 1054 studies were identified in our electronic search, 136 trials were assessed for eligibility and 26 trials with 1733 critically ill patients were included. The median methodologic score was 9 out of 14 points (95% confidence interval [CI] 7, 10). Omega-6 FA sparing PN in comparison with traditional lipid emulsions did not decrease overall mortality (20 studies; risk ratio [RR] 0.91; 95% CI 0.76, 1.10; p = 0.34) but hospital length of stay was substantially reduced (6 studies; weighted mean difference [WMD] − 6.88; 95% CI − 11.27, − 2.49; p = 0.002). Among the different lipid emulsions, fish oil (FO) containing PN reduced the length of intensive care (8 studies; WMD − 3.53; 95% CI − 6.16, − 0.90; p = 0.009) and rate of infectious complications (4 studies; RR 0.65; 95% CI 0.44, 0.95; p = 0.03). When FO was administered as a stand-alone medication outside PN, potential mortality benefits were observed compared to standard care. Conclusion Overall, these findings highlight distinctive omega-6 sparing effects attributed to PN. Among the different lipid emulsions, FO in combination with PN or as a stand-alone treatment may have the greatest clinical impact. Trial registration PROSPERO international prospective database of systematic reviews (CRD42021259238). Graphical abstract

Purpose The role of positive endexpiratory pressure (PEEP) for successful cannulation of the subclavian vein (SCV) remains inconclusive. The aim of our study was to assess the effect of different levels of PEEP on distance from SCV to parietal pleura (DVP) and on the cross-sectional area (CSA) of the SCV. Methods Invasive mechanically ventilated adult patients with a clinical indication for a stepwise PEEP-trial (0, 5, 10, and 15 cm H2O) were included in this prospective observational single-center study. Ultrasound examinations of SCV were performed with a linear ultrasound probe using the infraclavicular view. DVP and CSA were measured on the right and left bodyside. Examinations were repeated at each PEEP step. Results 27 patients were enrolled (12 female; 60±21 years; BMI 24.6±4.9 kg/m2; 20 patients on controlled, 7 on assisted ventilation). A statistically significant increase of DVP in the in-plane view was found on the left side which was not clinically relevant. No significant differences of DVP were observed in all other views. PEEP induced changes in CSAs were statistically significant but clinically not relevant on both sides. The largest change in CSA (2mm2) was observed when comparing PEEP 10 with PEEP 0 cm H2O. Conclusion A stepwise PEEP increase was not associated with clinically relevant changes of the DVP and CSA. Thus, a PEEP-optimization for the cannulation of the subclavian vein is not indicated.

Abstract Background Ultrasound education is propagated already during medical school due to its diagnostic importance. Courses are usually supervised by experienced faculty staff (FS) with patient bedside examinations or students among each other but often overbooked due to limited FS availability. To overcome this barrier, use of teaching videos may be advantageous. Likewise, peer teaching concepts solely with trained student tutors have shown to be feasible and effective. The aim was to evaluate 1) objective learning outcomes of a combined video-based, student-tutor (ViST) as compared to a FS-led course without media support, 2) acceptance and subjective learning success of the videos. Methods Two ultrasound teaching videos for basic and advanced abdominal ultrasound (AU) and transthoracic echocardiography (TTE) were produced and six students trained as tutors. Fourth-year medical students (N = 96) were randomized to either the ViST- or FS course (6 students per tutor). Learning objectives were defined equally for both courses. Acquired practical basic and advanced ultrasound skills were tested in an objective structured clinical examination (OSCE) using modified validated scoring sheets with a maximum total score of 40 points. Acceptance and subjective learning success of both videos were evaluated by questionnaires based on Kirkpatrick’s evaluation model with scale-rated closed and open questions. Results 79 of 96 medical students completed the OSCE and 77 could be finally analyzed. There was no significant difference in the mean total point score of 31.3 in the ViST (N = 42) and 32.7 in the FS course (N = 35, P = 0.31) or in any of the examined basic or advanced ultrasound skill subtasks. Of the 42 ViST participants, 29 completed the AU and 27 the TTE video questionnaire. Acceptance and subjective learning success of both videos was rated positively in 14–52% and 48–88% of the rated responses to each category, respectively. Attendance of either the student or faculty tutor was deemed necessary in addition to the videos. Conclusions A ViST versus FS teaching concept was able to effectively teach undergraduate students in AU and TTE, albeit acceptance of the teaching videos alone was limited. However, the ViST concept has the potential to increase course availability and FS resource allocation.

Abstract Background In morbidly obese patients undergoing laparoscopic bariatric surgery, the combination of obesity-related comorbidities, pneumoperitoneum and extreme posture changes constitutes a high risk of perioperative hemodynamic complications. Thus, an advanced hemodynamic monitoring including continuous cardiac index (CI) assessment is desirable. While invasive catheterization may bear technical difficulties, transesophageal echocardiography is contraindicated due to the surgical procedure. Evidence on the clinical reliability of alternative semi- or non-invasive cardiac monitoring devices is limited. The aim was to compare the non-invasive vascular unloading to a semi-invasive pulse contour analysis reference technique for continuous CI measurements in bariatric surgical patients. Methods This prospective observational study included adult patients scheduled for elective, laparoscopic bariatric surgery after obtained institutional ethics approval and written informed consent. CI measurements were performed using the vascular unloading technique (Nexfin®) and semi-invasive reference method (FloTrac™). At 10 defined measurement time points, the influence of clinically indicated body posture changes, passive leg raising, fluid bolus administration and pneumoperitoneum was evaluated pre- and intraoperatively. Correlation, Bland-Altman and concordance analyses were performed. Results Sixty patients (mean BMI 49.2 kg/m2) were enrolled into the study and data from 54 patients could be entered in the final analysis. Baseline CI was 3.2 ± 0.9 and 3.3 ± 0.8 l/min/m2, respectively. Pooled absolute CI values showed a positive correlation (rs = 0.76, P 92%). Conclusion Non-invasive as compared to semi-invasive CI measurements did not reach criteria of interchangeability for monitoring absolute and trending values of CI in morbidly obese patients undergoing bariatric surgery. Trial registration The study was registered retrospectively on June 12, 2017 with the registration number NCT03184272 .

Abstract Background Gastrointestinal (GI) dysfunction is frequent in the critically ill but can be overlooked as a result of the lack of standardization of the diagnostic and therapeutic approaches. We aimed to develop a research agenda for GI dysfunction for future research. We systematically reviewed the current knowledge on a broad range of subtopics from a specific viewpoint of GI dysfunction, highlighting the remaining areas of uncertainty and suggesting future studies. Methods This systematic scoping review and research agenda was conducted following successive steps: (1) identify clinically important subtopics within the field of GI function which warrant further research; (2) systematically review the literature for each subtopic using PubMed, CENTRAL and Cochrane Database of Systematic Reviews; (3) summarize evidence for each subtopic; (4) identify areas of uncertainty; (5) formulate and refine study proposals that address these subtopics; and (6) prioritize study proposals via sequential voting rounds. Results Five major themes were identified: (1) monitoring, (2) associations between GI function and outcome, (3) GI function and nutrition, (4) management of GI dysfunction and (5) pathophysiological mechanisms. Searches on 17 subtopics were performed and evidence summarized. Several areas of uncertainty were identified, six of them needing consensus process. Study proposals ranked among the first ten included: prevention and management of diarrhoea; management of upper and lower feeding intolerance, including indications for post-pyloric feeding and opioid antagonists; acute gastrointestinal injury grading as a bedside tool; the role of intra-abdominal hypertension in the development and monitoring of GI dysfunction and in the development of non-occlusive mesenteric ischaemia; and the effect of proton pump inhibitors on the microbiome in critical illness. Conclusions Current evidence on GI dysfunction is scarce, partially due to the lack of precise definitions. The use of core sets of monitoring and outcomes are required to improve the consistency of future studies. We propose several areas for consensus process and outline future study projects.

Abstract Metabolic alterations in the critically ill have been studied for more than a century, but the heterogeneity of the critically ill patient population, the varying duration and severity of the acute phase of illness, and the many confounding factors have hindered progress in the field. These factors may explain why management of metabolic alterations and related conditions in critically ill patients has for many years been guided by recommendations based essentially on expert opinion. Over the last decade, a number of randomized controlled trials have been conducted, providing us with important population-level evidence that refutes several longstanding paradigms. However, between-patient variation means there is still substantial uncertainty when translating population-level evidence to individuals. A cornerstone of metabolic care is nutrition, for which there is a multifold of published guidelines that agree on many issues but disagree on others. Using a series of nine questions, we provide a review of the latest data in this field and a background to promote efforts to address the need for international consistency in recommendations related to the metabolic care of the critically ill patient. Our purpose is not to replace existing guidelines, but to comment on differences and add perspective.

Abstract Background This study assessed the ability of mid-regional proadrenomedullin (MR-proADM) in comparison to conventional biomarkers (procalcitonin (PCT), lactate, C-reactive protein) and clinical scores to identify disease severity in patients with sepsis. Methods This is a secondary analysis of a randomised controlled trial in patients with severe sepsis or septic shock across 33 German intensive care units. The association between biomarkers and clinical scores with mortality was assessed by Cox regression analysis, area under the receiver operating characteristic and Kaplan-Meier curves. Patients were stratified into three severity groups (low, intermediate, high) for all biomarkers and scores based on cutoffs with either a 90% sensitivity or specificity. Results 1089 patients with a 28-day mortality rate of 26.9% were analysed. According to the Sepsis-3 definition, 41.2% and 58.8% fulfilled the criteria for sepsis and septic shock, with respective mortality rates of 20.0% and 32.1%. MR-proADM had the strongest association with mortality across all Sepsis-1 and Sepsis-3 subgroups and could facilitate a more accurate classification of low (e.g. MR-proADM vs. SOFA: N = 265 vs. 232; 9.8% vs. 13.8% mortality) and high (e.g. MR-proADM vs. SOFA: N = 161 vs. 155; 55.9% vs. 41.3% mortality) disease severity. Patients with decreasing PCT concentrations of either ≥ 20% (baseline to day 1) or ≥ 50% (baseline to day 4) but continuously high MR-proADM concentrations had a significantly increased mortality risk (HR (95% CI): 19.1 (8.0–45.9) and 43.1 (10.1–184.0)). Conclusions MR-proADM identifies disease severity and treatment response more accurately than established biomarkers and scores, adding additional information to facilitate rapid clinical decision-making and improve personalised sepsis treatment.

Abstract Nutrition support is a necessary therapy for critically ill cardiac surgery patients. However, conclusive evidence for this population, consisting of well-conducted clinical trials is lacking. To clarify optimal strategies to improve outcomes, an international multidisciplinary group of 25 experts from different clinical specialties from Germany, Canada, Greece, USA and Russia discussed potential approaches to identify patients who may benefit from nutrition support, when best to initiate nutrition support, and the potential use of pharmaco-nutrition to modulate the inflammatory response to cardiopulmonary bypass. Despite conspicuous knowledge and evidence gaps, a rational nutritional support therapy is presented to benefit patients undergoing cardiac surgery.

Introduction Observational studies have demonstrated an association between vitamin D deficiency and increased risk of morbidity and mortality in critically ill patients. Cohort studies and pilot trials have suggested promising beneficial effects of vitamin D replacement in the critical ill, at least in patients with severe vitamin D deficiency. As vitamin D is a simple, low-cost and safe intervention, it has potential to improve survival in critically ill patients.Methods and analysis In this randomised, placebo-controlled, double-blind, multicentre, international trial, 2400 adult patients with severe vitamin D deficiency (25-hydroxyvitamin D≤12 ng/mL) will be randomised in a 1:1 ratio by www.randomizer.at to receive a loading dose of 540 000 IU cholecalciferol within 72 hours after intensive care unit (ICU) admission, followed by 4000 IU daily for 90 days or placebo. Hypercalcaemia may occur as a side effect, but is monitored by regular checks of the calcium level. The primary outcome is all-cause mortality at 28 days after randomisation. Secondary outcomes are: ICU, hospital, 90-day and 1-year mortality; hospital and ICU length of stay, change in organ dysfunction on day 5 as measured by Sequential Organ Function Assessment (SOFA) score, number of organ failures; hospital and ICU readmission until day 90; discharge destination, self-reported infections requiring antibiotics until day 90 and health-related quality of life. Recruitment status is ongoing.Ethics and dissemination National ethical approval was obtained by the Ethics Committee of the University of Graz for Austria, Erasme University Brussels (Belgium) and University Hospital Frankfurt (Germany), and will further be gained according to individual national processes. On completion, results will be published in a peer-reviewed scientific journal. The study findings will be presented at national and international meetings with abstracts online.Trial registration NCT03188796, EudraCT-No: 2016-002460-13.

IntroductionElectrical impedance tomography (EIT) is an emerging clinical tool for monitoring ventilation distribution in mechanically ventilated patients, for which many image reconstruction algorithms have been suggested. We propose an experimental framework to assess such algorithms with respect to their ability to correctly represent well-defined physiological changes. We defined a set of clinically relevant ventilation conditions and induced them experimentally in 8 pigs by controlling three ventilator settings (tidal volume, positive end-expiratory pressure and the fraction of inspired oxygen). In this way, large and discrete shifts in global and regional lung air content were elicited.MethodsWe use the framework to compare twelve 2D EIT reconstruction algorithms, including backprojection (the original and still most frequently used algorithm), GREIT (a more recent consensus algorithm for lung imaging), truncated singular value decomposition (TSVD), several variants of the one-step Gauss-Newton approach and two iterative algorithms. We consider the effects of using a 3D finite element model, assuming non-uniform background conductivity, noise modeling, reconstructing for electrode movement, total variation (TV) reconstruction, robust error norms, smoothing priors, and using difference vs. normalized difference data.Results and conclusionsOur results indicate that, while variation in appearance of images reconstructed from the same data is not negligible, clinically relevant parameters do not vary considerably among the advanced algorithms. Among the analysed algorithms, several advanced algorithms perform well, while some others are significantly worse. Given its vintage and ad-hoc formulation backprojection works surprisingly well, supporting the validity of previous studies in lung EIT.

Acid sphingomyelinase is involved in lipid signalling pathways and regulation of apoptosis by the generation of ceramide and plays an important role during the host response to infectious stimuli. It thus has the potential to be used as a novel diagnostic marker in the management of critically ill patients. The objective of our study was to evaluate acid sphingomyelinase serum activity (ASM) as a diagnostic and prognostic marker in a mixed intensive care unit population before, during, and after systemic inflammation.40 patients admitted to the intensive care unit at risk for developing systemic inflammation (defined as systemic inflammatory response syndrome plus a significant procalcitonin [PCT] increase) were included. ASM was analysed on ICU admission, before (PCT before), during (PCT peak) and after (PCT low) onset of SIRS. Patients undergoing elective surgery served as control (N = 8). Receiver-operating characteristics curves were computed.ASM significantly increased after surgery in the eight control patients. Patients from the intensive care unit had significantly higher ASM on admission than control patients after surgery. 19 out of 40 patients admitted to the intensive care unit developed systemic inflammation and 21 did not, with no differences in ASM between these two groups on admission. In patients with SIRS and PCT peak, ASM between admission and PCT before was not different, but further increased at PCT peak in non-survivors and was significantly higher at PCT low compared to survivors. Survivors exhibited decreased ASM at PCT peak and PCT low. Receiver operating curve analysis on discrimination of ICU mortality showed an area under the curve of 0.79 for ASM at PCT low.In summary, ASM was generally higher in patients admitted to the intensive care unit compared to patients undergoing uncomplicated surgery. ASM did not indicate onset of systemic inflammation. In contrast to PCT however, it remained high in non-surviving ICU patients after systemic inflammation.

IntroductionLung-protective ventilation aims at using low tidal volumes (VT) at optimum positive end-expiratory pressures (PEEP). Optimum PEEP should recruit atelectatic lung regions and avoid tidal recruitment and end-inspiratory overinflation. We examined the effect of VT and PEEP on ventilation distribution, regional respiratory system compliance (C(RS)), and end-expiratory lung volume (EELV) in an animal model of acute lung injury (ALI) and patients with ARDS by using electrical impedance tomography (EIT) with the aim to assess tidal recruitment and overinflation.MethodsEIT examinations were performed in 10 anaesthetized pigs with normal lungs ventilated at 5 and 10 ml/kg body weight VT and 5 cmH2O PEEP. After ALI induction, 10 ml/kg VT and 10 cmH2O PEEP were applied. Afterwards, PEEP was set according to the pressure-volume curve. Animals were randomized to either low or high VT ventilation changed after 30 minutes in a crossover design. Ventilation distribution, regional C(RS) and changes in EELV were analyzed. The same measures were determined in five ARDS patients examined during low and high VT ventilation (6 and 10 (8) ml/kg) at three PEEP levels.ResultsIn healthy animals, high compared to low VT increased C(RS) and ventilation in dependent lung regions implying tidal recruitment. ALI reduced C(RS) and EELV in all regions without changing ventilation distribution. Pressure-volume curve-derived PEEP of 21±4 cmH2O (mean±SD) resulted in comparable increase in C(RS) in dependent and decrease in non-dependent regions at both VT. This implied that tidal recruitment was avoided but end-inspiratory overinflation was present irrespective of VT. In patients, regional C(RS) differences between low and high VT revealed high degree of tidal recruitment and low overinflation at 3±1 cmH2O PEEP. Tidal recruitment decreased at 10±1 cmH2O and was further reduced at 15±2 cmH(2)O PEEP.ConclusionsTidal recruitment and end-inspiratory overinflation can be assessed by EIT-based analysis of regional C(RS).