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We aimed to investigate predictors for long-term survival of in-hospital patients with medical emergency team (MET) consultation with or without in-hospital cardiac arrest (IHCA) in Austria's largest medical center.Data of patients, who needed an intervention of a MET between 01/2014 and 03/2020 were reviewed for this retrospective analysis.In total, 708 MET calls were analyzed. The minimum follow-up was 7 months, the maximum 6.2 years. The main MET indications were circulatory failure (63%) followed by respiratory failure (27.1%), and bleeding events (3.5%). IHCA with subsequent cardiopulmonary resuscitation (CPR) was experienced by 425 (60%) patients. Of those, 274 (64%) reached return of spontaneous circulation (ROSC), and 221 (52%) survived the first 24-hours (median survival: 146 days) and 22.1% the first year. After adjustment for potential confounders, age (p0.001), time to ROSC (p0.001), a non-shockable rhythm (p=0.041), chronic kidney disease (CKD, p=0.041), peak lactate levels (p0.001), and C-reactive protein (p=0.001) were associated with long-term all-cause mortality in IHCA patients in Cox regression analysis. The 283 MET calls (40%) which were due to other reasons than IHCA were associated with a much better 24-hours (93%) and 1-year survival (61.8%). Beside age (p0.001), the main risk factors associated with mortality in MET patients without IHCA were comorbidities such as chronic obstructive pulmonary disease (COPD, p=0.008), CKD (p=0.001), pulmonary hypertension/chronic thromboembolic pulmonary hypertension (PH/CTEPH, p=0.024), and cancer (p=0.040).Patients triggering MET calls have an increased mortality, especially those with IHCA. Predictors of mortality comprise age, comorbidities, and cardiac arrest-related parameters. A better characterization of MET call populations and their outcome might help to improve clinical decision making.

Continuous advances in resuscitation care have increased survival, but the rate of favorable neurological outcome remains low. We have shown the usefulness of proteomics in identifying novel biomarkers to predict neurological outcome. Neurofilament light chain (NfL), a marker of axonal damage, has since emerged as a promising single marker. The aim of this study was to assess the predictive value of NfL in comparison with and in addition to our established model. NfL was measured in plasma samples drawn at 48 h after cardiac arrest using single-molecule assays. Neurological function was recorded on the cerebral performance category (CPC) scale at discharge from the intensive care unit and after 6 months. The ability to predict a dichotomized outcome (CPC 1–2 vs. 3–5) was assessed with receiver operating characteristic (ROC) curves. Seventy patients were included in this analysis, of whom 21 (30%) showed a favorable outcome (CPC 1–2), compared with 49 (70%) with an unfavorable outcome (CPC 3–5) at discharge. NfL increased from CPC 1 to 5 (16.5 pg/ml to 641 pg/ml, p

Venoarterial-extracorporeal membrane oxygenation (VA-ECMO) is a life-saving method for patients with low-output failure after cardiac surgery. However, VA-ECMO therapy may increase left ventricular afterload due to retrograde blood flow in the aorta, which may lead to progression of pulmonary congestion. We examined the predictive value of pulmonary congestion in patients that need VA-ECMO support after cardiovascular surgery.We enrolled a total of 266 adult patients undergoing VA-ECMO support following cardiovascular surgery at a university-affiliated tertiary care centre into our single-center registry. Pulmonary edema was assessed on bedside chest X rays at day 0, 3, 5 after VA-ECMO implantation.Median age was 65 (57-72) years, 69% of patients were male and 30-day survival was 63%. At ICU-admission 20% of patients had mild, 54% had moderate and 26% showed severe pulmonary congestion. Pulmonary congestion at day 0 was not associated with outcome (adjusted HR 1.31; 95%-CI 0.89-1.93;P = 0.18), whereas pulmonary congestion at day 3 (adj. HR 2.81; 95%-CI 1.76-4.46;P0.001) and day 5 (adj. HR 3.01;95%-CI 1.84-4.93;P0.001) was significantly associated with survival. Linear regression revealed that out of left ventricular function, cardiac output, central venous saturation, maximum dobutamine and norepinephrine dose as well as fluid balance solely ECMO rotation was associated with the evolution of pulmonary congestion (P = 0.007).Pulmonary edema three and five days after ECMO implantation are associated with poor survival. Interestingly, a high VA-ECMO output was the most important determinant of worsening pulmonary congestion within the first five days.

Purpose: The question of whether cancer patients with severe respiratory failure benefit from veno-venous extracorporeal membrane oxygenation (vv-ECMO) remains unanswered. We, therefore, analyzed clinical characteristics and outcomes of a large cohort of cancer patients treated with vv-ECMO with the aim to identify prognostic factors. Methods: 297 cancer patients from 19 German and Austrian hospitals who underwent vv-ECMO between 2009 and 2019 were retrospectively analyzed. A multivariable cox proportional hazards analysis for overall survival was performed. In addition, a propensity score-matched analysis and a latent class analysis were conducted. Results: Patients had a median age of 56 (IQR 44–65) years and 214 (72%) were males. 159 (54%) had a solid tumor and 138 (47%) a hematologic malignancy. The 60-day overall survival rate was 26.8% (95% CI 22.1–32.4%). Low platelet count (HR 0.997, 95% CI 0.996–0.999; p = 0.0001 per 1000 platelets/µl), elevated lactate levels (HR 1.048, 95% CI 1.012–1.084; p = 0.0077), and disease status (progressive disease [HR 1.871, 95% CI 1.081–3.238; p = 0.0253], newly diagnosed [HR 1.571, 95% CI 1.044–2.364; p = 0.0304]) were independent adverse prognostic factors for overall survival. A propensity score-matched analysis with patients who did not receive ECMO treatment showed no significant survival advantage for treatment with ECMO. Conclusion: The overall survival of cancer patients who require vv-ECMO is poor. This study shows that the value of vv-ECMO in cancer patients with respiratory failure is still unclear and further research is needed. The risk factors identified in the present analysis may help to better select patients who may benefit from vv-ECMO.

Background: Patients treated at medical intensive care units suffer from various pathologies and often present with elevated troponin T (TnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Both markers may reflect different forms of cardiac involvement in critical illness. Therefore, the aim of our study was to examine the synergistic prognostic potential of NT-proBNP and high-sensitivity TnT (hs)TnT in unselected critically ill patients. Methods: We included all consecutive patients admitted to our intensive care unit within one year, excluding those suffering from acute myocardial infarction or undergoing cardiac surgery and measured NT-proBNP and TnT plasma levels on the day of admission and 72 hours thereafter. Results: Of the included 148 patients, 52% were male, mean age was of 64.2 ± 16.8 years and 30-day mortality was 33.2%. Non-survivors showed significantly higher NT-proBNP and TnT plasma levels as compared with survivors (p Conclusions: Our findings regarding the individual predictive properties of NT-proBNP and TnT are in line with literature. However, we were able to highlight that they exhibit additive prognostic potential which exceeds their individual value. This might be attributed to a difference in underlying pathomechanisms and an assessment of synergistic risk factors.

Objectives Neurologic outcome prediction in out-of-hospital cardiac arrest survivors is highly limited due to the lack of consistent predictors of clinically relevant brain damage. The present study aimed to identify novel biomarkers of neurologic recovery to improve early prediction of neurologic outcome. Design Prospective, single-center study, SETTING:: University-affiliated tertiary care center. Patients We prospectively enrolled 96 out-of-hospital cardiac arrest survivors into our study. Interventions None. Measurements and main results Neurologic outcome was assessed by the Cerebral Performance Categories score. To identify plasma biomarkers for poor neurologic outcome (Cerebral Performance Categories score ≥ 3), we performed a three-step proteomics strategy of preselection by shotgun analyses, crosschecking in brain tissue samples, and verification by targeted proteomic analyses using a multistep statistical modeling approach. Sixty-three patients (66%) had a poor neurologic outcome. Out of a total of 299 proteins, we identified α-enolase, 14-3-3 protein ζ/δ, cofilin-1, and heat shock cognate 71 kDa protein as novel biomarkers for poor neurologic outcome. The implementation of these biomarkers into a clinical multimarker model, consisting of previously identified covariates associated to outcome, resulted in a significant improvement of neurologic outcome prediction (C-index, 0.70; explained variation, 11.9%; p for added value, 0.019). Conclusions This study identified four novel biomarkers for the prediction of poor neurologic outcome in out-of-hospital cardiac arrest survivors. The implementation of α-enolase, 14-3-3 protein ζ/δ, cofilin-1, and heat shock cognate 71 kDa protein into a multimarker predictive model along with previously identified risk factors significantly improved neurologic outcome prediction. Each of the proteomically identified biomarkers did not only outperform current risk stratification models but may also reflect important pathophysiologic pathways undergoing during cerebral ischemia.

SummaryBackgroundMatrix metalloproteinases (MMPs) are involved in systemic inflammatory responses and organ failure. The aim of this study was to evaluate early circulating plasma levels of MMP‑2, MMP‑9 and their inhibitors TIMP‑1 and TIMP‑2 and their prognostic significance in critically ill patients on admission to the intensive care unit (ICU).MethodsIn a single center prospective study 120 consecutive patients (72.5% male, mean age 66.8 ± 13.3 years, mean simplified acute physiology score [SAPS II] score 52.9 ± 21.9) were enrolled on transfer to the ICU of a cardiology department. The most common underlying conditions were cardiac diseases (n = 42.5%), respiratory failure (n = 10.8%) and sepsis (n = 6.7%). Blood samples were taken within 12 h of ICU admission. The MMP‑2, MMP‑9, TIMP‑1 and TIMP‑2 levels in plasma were evaluated in terms of 30-day survival, underlying condition and clinical score.ResultsOn ICU admission 30-day survivors had significantly lower plasma MMP‑9 (odds ratio, OR 1.67 per 1 SD; 95% confidence interval, CI 1.10−2.53;p = 0.016) and TIMP‑1 (OR 2.15 per 1 SD; 95% CI 1.27−3.64;p = 0.004) levels than non-survivors; furthermore, MMP‑9 and TIMP‑1 correlated well with SAPS II (bothp p = 0.002) and TIMP‑1 (p = 0.01) were independent predictors of survival (Cox regression). No significant correlation was found between MMP‑2 and TIMP‑2 levels, MMP/TIMP ratios and 30-day mortality.ConclusionThe MMP‑9 and TIMP‑1 levels are significantly elevated in acute critical care settings with increased short-term mortality risk, especially in patients with underlying heart disease. These findings support the value of MMPs and TIMPs as prognostic markers and potential therapeutic targets in conditions leading to systemic inflammation and acute organ failure.

Early prognostication in post-cardiac arrest (CA) patients remains challenging and biomarkers have evolved as helpful tools in risk assessment. The stress-response cytokine growth differentiation factor-15 (GDF-15) is dramatically up-regulated during various kinds of tissue injury and predicts outcome in many pathological conditions. We aimed to assess the predictive value of circulating GDF-15 in post-CA patients.This prospective observational study included 128 consecutive patients (median age 60.3 years, 75.8% male) with return of spontaneous circulation after in- or out-of-hospital CA who were treated at a tertiary university hospital. GDF-15 serum levels were determined at admission.A total of 52 patients (40.6%) died during the 6-month follow-up. Median GDF-15 levels were significantly lower in survivors (1601 ng/L (interquartile range: 1114-2983 ng/L) than in non-survivors (3172 ng/L (1927-8340 ng/L); p 0.001). GDF-15 levels were also significantly lower in patients with favourable neurological 6-month outcome (cerebral performance category (CPC) 1-2) than in those with poor neurological outcome (CPC 3-5; p 0.001). GDF-15 significantly predicted 6-month mortality in univariate Cox regression analysis (hazard ratio (HR) per 1-standard deviation increase 1.76 [95% confidence interval (CI) 1.35-2.31; p 0.001] and remained significant after multivariable adjustment (HR 1.57 [95% CI 1.19-2.07; p = 0.001]). Subgroup analysis revealed that the association between GDF-15 and 6-month outcome was present both in patients with in- and out-of-hospital CA.GDF-15 predicts poor survival and neurological outcome in post-CA patients. GDF-15 may reflect the extent of hypoxic injury to the brain and other organs and might help to improve early risk stratification after CA.

Skeletal muscle area (SMA) in the computed tomography (CT) at the third lumbar vertebra (L3) level is a proxy for whole-body muscle mass but is only performed for clinical reasons. Ultrasound is a promising tool to determine muscle mass at the bedside. It is still unclear how well ultrasound and which ultrasound measuring points can predict CT L3 SMA.This prospective observational trial included 200 non-critically ill patients, who underwent an abdominal CT scan for any clinical reason within 48 h before the ultrasound examination. Ultrasound muscle thickness was evaluated at 3 measuring points on the thigh and 2 measuring points on the upper arm with minimal compression. On the CT scan, the entire L3 SMA was measured based on Hounsfield units. Using a model selection algorithm based on the Bayesian information criterion (BIC) and clinical considerations, a linear prediction model for CT L3 SMA based on the ultrasound muscle thickness and other independent variables was fitted and assessed with cross-validation.67,5% and 32,5% of the patients were from surgical and medical wards, respectively. Mean ultrasound muscle thickness values were between 2,2 and 3,6 cm on the thigh and between 1,4 and 2,8 cm on the upper arm. All ultrasound muscle thickness values were higher in men than in women (P 0,05). CT L3 SMA was 40 cmOne single ultrasound measuring point at the thigh together with sex, height and weight very well predicts CT L3 SMA across different clinical populations. Ultrasound is a safe and bedside method to measure muscle thickness longitudinally to monitor the effects of nutrition and physical therapy.

Extracorporeal membrane oxygenation (ECMO) has established as a cornerstone therapy in severe acute respiratory distress syndrome and refractory hemodynamic failure. As circuit integrity is crucial for adequate organ support, component failure may necessitate a system exchange. In this retrospective study, incidence and etiology of system exchanges during applications of venovenous, venoarterial ECMO, and extracorporeal CO2 removal were examined. Sixty-three (44.4%) of 142 patients were affected by one or more exchanges, totaling 105 replaced circuits. The predominant exchange reason was clotting (n = 20), followed by hemolysis (n = 19), systemic coagulation disorders (n = 13), reconfiguration (n = 13), impaired gas exchange (n = 10), mechanical complications (n = 8), bleeding (n = 6), failed weaning (n = 5), prophylactic exchange (n = 3), and undocumented/other (n = 8). Nineteen (18.1%) events were classified as acute and 70 (66.7%) events as elective exchanges. Patients with circuit exchanges more frequently underwent renal replacement therapy at ECMO initiation (49.2% vs. 29.1%; p = 0.023), had a longer ECMO treatment duration (18 vs. 7.5 days, p < 0.001), and lower hospital survival (29.5% vs. 57.1%; p = 0.002). Considering the high occurrence of coagulation complications, further optimization of coagulation management is deemed necessary.

Background Acute heart failure and cardiogenic shock are associated with an impaired intestinal perfusion, which may lead to a release of cytoplasmatic proteins by hypoxic epithelial injury. Intestinal fatty acid binding protein (iFABP), highly specific for the small bowel enterocyte, may pose a useful novel and very sensitive biomarker for predicting outcome of these patients.The aim of this study was to investigate whether circulating levels of iFABP are associated with mortality in patients with acute heart failure or cardiogenic shock requiring intensive care unit (ICU) admission. Methods We included 90 consecutive patients with cardiogenic shock (74.4%) or severe acute heart failure (25.6%) admitted to a cardiac ICU. Blood samples were taken at day 0 and day 3. Median age was 64.7 (49.4-74.3), 76.7% of patients were male and median NT-proBNP levels were 4,986 (1,525-23,842) pg/mL. 30-day survival was 64.4%. Results Patients with serum levels of iFABP at day 0 in the highest quartile (iFABP ≥ 588.4 pg/mL) had a 2.5-fold risk (P = 0.02) of dying independent of demographics, NT-proBNP levels, and vasopressor use. Extensively elevated admission levels of iFABP above the 90th percentile (iFABP ≥ 10208.4 pg/mL) were associated with an excessive mortality rate of 88.9%. In contrast, iFABP levels at day 3 were not associated with outcome. Conclusion Circulating levels of iFABP at admission predict mortality. This suggests that early inadequate perfusion of the small intestine may be associated with a dramatically decreased survival in patients with cardiogenic shock or severe acute heart failure.

Objective: Patients on extracorporeal membrane oxygenation are frequently in need for sedation. Use of propofol has been associated with impaired oxygenator function due to adsorption to the membrane as well as lipid load. The aim of our retrospective analysis was to compare two different sedation regimens containing either propofol or midazolam with respect to oxygenator running time. Methods: Midazolam was used in 73 patients whereas propofol was used in 49 patients, respectively. In the propofol group, veno-arterial–extracorporeal membrane oxygenation was used predominantly (84%), while veno-venous–extracorporeal membrane oxygenation was used more often in the midazolam group (64%). Results: Oxygenator running time until first exchange was 7 days in both groups ( p = 0.759). No statistically significant differences could be observed between the subgroup of patients receiving lipid-free (n = 24) and lipid-containing (n = 31) parenteral nutrition, respectively. Laboratory parameters like triglycerides, free hemoglobin, fibrinogen, platelets, and activated partial thromboplastin time were not significantly different between both sedation regimens ( p = 0.462, p = 0.489, p = 0.960, p = 0.134, and p = 0.843) and were not associated with oxygenator running time. Conclusion: The use of propofol as sedative seems suitable in patients undergoing extracorporeal membrane oxygenation therapy.

Background In patients with septic shock, the presence of an elevated heart rate (HR) after fluid resuscitation marks a subgroup of patients with a particularly poor prognosis. Several studies have shown that HR control in this population is safe and can potentially improve outcomes. However, all were conducted in a single-center setting. The aim of this multicenter study is to demonstrate that administration of the highly beta1-selective and ultrashort-acting beta blocker landiolol in patients with septic shock and persistent tachycardia (HR ≥ 95 beats per minute [bpm]) is effective in reducing and maintaining HR without increasing vasopressor requirements. Methods A phase IV, multicenter, prospective, randomized, open-label, controlled study is being conducted. The study will enroll a total of 200 patients with septic shock as defined by The Third International Consensus Definitions for Sepsis and Septic Shock criteria and tachycardia (HR ≥ 95 bpm) despite a hemodynamic optimization period of 24–36 h. Patients are randomized (1:1) to receive either standard treatment (according to the Surviving Sepsis Campaign Guidelines 2016) and continuous landiolol infusion to reach a target HR of 80–94 bpm or standard treatment alone. The primary endpoint is HR response (HR 80–94 bpm), the maintenance thereof, and the absence of increased vasopressor requirements during the first 24 h after initiating treatment. Discussion Despite recent studies, the role of beta blockers in the treatment of patients with septic shock remains unclear. This study will investigate whether HR control using landiolol is safe, feasible, and effective, and further enhance the understanding of beta blockade in patients with septic shock. Trial registration EU Clinical Trials Register; EudraCT, 2017-002138-22. Registered on 8 August 2017. Electronic supplementary material The online version of this article (10.1186/s13063-018-3024-6) contains supplementary material, which is available to authorized users.

Background: Out of hospital cardiac arrest (OHCA) is a life-threatening event. Continuous advances in management increased initial survival, but the rate of favorable neurological outcome remains low. We have previously shown the usefulness of proteomics to identify novel biomarkers to predict this outcome. Neurofilament light chain (NfL), a marker of axonal damage, has since emerged as a promising single marker. The aim of this study was thus to assess the predictive value of NfL and compare it to our established model.Methods: NfL was measured in plasma samples from OHCA drawn at 48 hours after the event using single molecule assays. Neurological function at discharge from ICU was recorded on the cerebral performance category (CPC) scale. Predictive ability was assessed for NfL and compared to an established multimarker model.Results: Seventy patients were included into this analysis, of whom 21 (30%) showed a favorable outcome (CPC 1-2) compared to 49 (70%) with an unfavorable outcome (CPC 3 - 5). NfL increased from CPC 1 to 5 (16.5 pg/ml to 641 pg/ml, p

International audience; Background: In view of the high mortality rate of immunocompromised patients with ARDS, it is important to identify targets for improvement.Research question: This study investigated factors associated with mortality in this specific ARDS population, including factors related to respiratory mechanics (plateau pressure [Pplat,rs], compliance [Crs], and driving pressure [ΔPrs]).Study design and methods: This study consisted of a predefined secondary analysis of the EFRAIM data. Overall, 789 of 1,611 patients met the Berlin criteria for ARDS, and Pplat,rs, ΔPrs, and Crs were available for 494 patients. A hierarchical model was used to assess factors at ARDS onset independently associated with hospital mortality.Results: Hospital mortality was 56.3%. After adjustment, variables independently associated with hospital mortality included ARDS of undetermined etiology (OR, 1.66; 95% CI, 1.01-2.72), need for vasopressors (OR, 1.91; 95% CI, 1.27-2.88), and need for renal replacement therapy (OR, 2.02; 95% CI, 1.37-2.97). ARDS severity according to the Berlin definition, neutropenia on admission, and the type of underlying disease were not significantly associated with mortality. Before adjustment, higher Pplat,rs, higher ΔPrs, and lower Crs were associated with higher mortality. Addition of each of these individual variables to the final hierarchical model revealed a significant association with mortality: ΔPrs (OR, 1.08; 95% CI, 1.05-1.12), Pplat,rs (OR, 1.07; 95% CI, 1.04-1.11), and Crs (OR, 0.97; 95% CI, 0.95-0.98). Tidal volume was not associated with mortality.Interpretation: In immunocompromised patients with ARDS, respiratory mechanics provide additional prognostic information to predictors of hospital mortality. Studies designed to define lung-protective ventilation guided by these physiological variables may be warranted in this specific population.

Background After successful cardiopulmonary resuscitation with return of spontaneous circulation (ROSC), many patients show signs of an overactive immune activation. Monocytes are a heterogenous cell population that can be distinguished into three subsets. Purpose The aim of this prospective, observational study was to analyze whether monocyte subset distribution is associated with mortality at 6 months in patients after cardiac arrest. Methods We included 53 patients admitted to our medical ICU after cardiac arrest. Blood was taken on admission and monocyte subset distribution was analyzed by flow cytometry and distinguished into classical monocytes (CM; CD14++CD16-), intermediate monocytes (IM; CD14++CD16+CCR2+) and non-classical monocytes (NCM; CD14+CD16++CCR2-). Results Median age was 64.5 (IQR 49.8–74.3) years and 75.5% of patients were male. Mortality at 6 months was 50.9% and survival with good neurological outcome was 37.7%. Of interest, monocyte subset distribution upon admission to the ICU did not differ according to survival. However, patients that died within 6 months showed a strong increase in the pro-inflammatory subset of intermediate monocytes (8.3% (3.8–14.6)% vs. 4.1% (1.5–8.2)%; p=0.025), and a decrease of classical monocytes (87.5% (79.9–89.0)% vs. 90.8% (85.9–92.7)%; p=0.036) 72 hours after admission. In addition, intermediate monocytes were predictive of outcome independent of initial rhythm and time to ROSC and correlated with the CPC-score at 6 months (R=0.32; p=0.043). Discussion Monocyte subset distribution is associated with outcome in patients surviving a cardiac arrest. This suggests that activation of the innate immune system may play a significant role in patient outcome after cardiac arrest. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): FWF - Fonds zur Förderung der wissenschaftlichen Forschung

Current guidelines suggest the use of epinephrine in patients with cardiac arrest (CA). However, evidence for increased survival in good neurological condition is lacking. In experimental settings, epinephrine-induced impairment of microvascular flow was shown. The aim of our study was to analyze the association between epinephrine treatment and intestinal injury in patients after CA.We have included 52 patients with return of spontaneous circulation (ROSC) after CA admitted to our medical intensive care unit (ICU). Blood was taken on admission and levels of circulating intestinal fatty acid binding protein (iFABP) were analyzed.Patients were 64 (49.8-73.8) years old and predominantly male (76.9%). After six months, 50% of patients died and 38.5% of patients had a cerebral performance category (CPC)-score of 1-2. iFABP levels were lower in survivors (234 IQR 90-399 pg/mL) as compared to non-survivors (283, IQR 86-11500 pg/mL; p 0.05). Plasma levels of iFABP were not associated with time to ROSC but correlated with epinephrine-dose (R = 0.32; p 0.05). 40% of patients receiving ≥3 mg of epinephrine as compared to 10.5% of patients treated with3 mg (p 0.05) developed iFABP plasma levels1500 pg/mL, which was associated with dramatically increased mortality (HR4.87, 95%CI 1.95-12.1; p 0.001). iFABP levels predicted mortality independent from time to ROSC and the disease severity score SAPS II. In contrast to mortality, iFABP plasma levels were not associated with neurological outcome.In this small, single centre study, cumulative dose of epinephrine used in cardiac arrest patients was associated with an increase in biomarker indicative of intestinal injury and 6-month mortality.

Hypoxic-ischemic brain injury can affect and disturb the autonomous nervous system (ANS), which regulates various visceral systems including the gastro-intestinal and emetic system. The present study aimed to analyze the predictive value of gastric regurgitation (GReg) for neurological outcome in out-of-hospital cardiac arrest (OHCA) survivors. In this prospective, single-center study, 79 OHCA survivors treated at a university-affiliated tertiary care centre were included and GReg was measured at the first day after successful cardiopulmonary resuscitation. Neurological outcome was assessed by the Cerebral Performance Categories score at discharge. Seventy-six percent of the study population had a poor neurological outcome. GReg was found to be associated with poor neurological outcome with an adjusted OR of 5.37 (95% CI 1.41–20.46; p = 0.01). The area under the ROC curve for GReg was 0.69 (95% CI, 0.56–0.81) for poor neurological outcome. GReg on the first day after OHCA is an early, strong and independent predictor for poor neurological outcome in comatose OHCA survivors. These results are particularly compelling because measurement of GReg is inexpensive and routinely performed in critical care units.

BACKGROUND Toll-like receptors (TLRs) play an important role in inflammatory processes in critically ill patients by binding to pathogen-associated molecular patterns and danger-associated molecular patterns (DAMPs). Whether neutrophil or monocyte TLR expression patterns are associated with outcome in critical illness is unknown. OBJECTIVES To answer this question, we conducted a prospective, observational study including 215 consecutive patients admitted to a medical ICU at a tertiary care center. METHODS Blood was drawn at admission and expression of TLR-2, TLR-4, and TLR-9 on neutrophils and monocytes were analyzed by flow cytometry. RESULTS Median Acute Physiology and Chronic Health Evaluation II (APACHE II) score was 19, and 30-day mortality was 26%. TLR-2 expression on neutrophils was associated with APACHE II, Simplified Acute Physiology Score II, and Sepsis-related Organ Failure Assessment score. TLR-2 (P

Background Inflammation is regarded as an important trigger for disease progression in heart failure (HF) and activation of the inflammatory system was implicated in the pathophysiology of acute heart failure (AHF). Toll-like receptors (TLRs) play an important role in acute inflammatory processes in critically ill patients by binding to pathogen associated molecular patterns (PAMP) and danger associated molecular patterns (DAMP). However, it is not known whether the expression patterns of TLRs on neutrophils and monocytes are associated with outcome in patients with severe AHF requiring intensive care unit (ICU) admission. The aim of this prospective, observational study was to analyze whether TLR-expression on monocytes or neutrophils is associated with 30-day survival in patients with severe AHF. Methods We included 84 patients with severe AHF admitted to a cardiac ICU. Blood was taken at admission and mean fluorescence activity (MFI) of TLR-2, TLR-4 and TLR-9 on monocytes and neutrophils was analyzed by flow cytometry. Results Median age was 64 (IQR 48–74) years and 76.2% of patients were male. Median NT-proBNP was 4941 (IQR 1298–12273) pg/mL and 30-day mortality was 33.3%. TLR-4 expression on monocytes in survivors (740 IQR 694–854) was significantly lower than in non-survivors (871 IQR 723–979; p Conclusion Monocyte TLR-4 expression predicts mortality in patients admitted to a cardiac ICU for severe acute heart failure. This suggests that activation of the innate immune system by TLR-binding of DAMPS may play a significant role in critically ill acute heart failure patients.

Patients admitted to a medical intensive care unit (ICU) are characterized by an activated immune system and exhibit a high mortality rate irrespective of the underlying cause of admission. Interleukin (IL)-33 has been shown to be protective in experimental sepsis models and it has been demonstrated that circulating levels of its "decoy" receptor soluble ST2 (sST2) are associated with outcome in critically ill patients. The aim of the present study was to investigate whether circulating IL-33 is associated with 30-day mortality in patients admitted to a medical ICU. In this prospective, observational study, both IL-33 and sST2 levels were assessed in 223 consecutive patients at ICU admission using specific enzyme-linked immunosorbent assays (ELISAs). During the 30-day follow-up, 58 patients (26%) died. Circulating IL-33 was detectable in 166 patients and in 57 patients, serum IL-33 was below the detection limit. Both detectable IL-33 and sST2 below the median were strong predictors of survival in critically ill patients independent of acute physiology and chronic health evaluation II (APACHE II) score. IL-33 and sST2 predicted risk independent from each other. Patients with both, non-detectable levels of IL-33 and sST2 levels above the median, showed a dramatically increased mortality risk (HR 6.9 95% CI 3.0-16.2; p

The generation of harmful reactive oxygen species (ROS), including hydrogen peroxide, in out-of-hospital cardiac arrest (OHCA) survivors causes systemic ischemia/reperfusion injury that may lead to multiple organ dysfunction and mortality. We hypothesized that the antioxidant enzyme catalase may attenuate these pathophysiological processes after cardiac arrest. Therefore, we aimed to analyze the predictive value of catalase levels for mortality in OHCA survivors. In a prospective, single-center study, catalase levels were determined in OHCA survivors 48 h after the return of spontaneous circulation. Thirty-day mortality was defined as the study end point. A total of 96 OHCA survivors were enrolled, of whom 26% (n = 25) died within the first 30 days after OHCA. The median plasma intensity levels (log2) of catalase were 8.25 (IQR 7.64–8.81). Plasma levels of catalase were found to be associated with mortality, with an adjusted HR of 2.13 (95% CI 1.07–4.23, p = 0.032). A Kaplan–Meier analysis showed a significant increase in 30-day mortality in patients with high catalase plasma levels compared to patients with low catalase levels (p = 0.012). High plasma levels of catalase are a strong and independent predictor for 30-day mortality in OHCA survivors. This indicates that ROS-dependent tissue damage is playing a crucial role in fatal outcomes of post-cardiac syndrome patients.

Background and aim of the study: Non-occlusive mesenteric ischaemia (NOMI) is characterised by hypoperfusion of the intestines without evidence of mechanical obstruction, potentially leading to extensive ischaemia and necrosis. Low cardiac output appears to be a major risk factor. Cardiopulmonary resuscitation aims at restoring blood flow after cardiac arrest. However, post restoration of spontaneous circulation, myocardial stunning limits immediate recovery of sufficient cardiac function. Since after successful cardiopulmonary resuscitation patients are often ventilated and sedated, NOMI might be underdiagnosed and potentially life-saving treatment delayed. Material and methods: A prospectively maintained multi-purpose cohort of out of hospital cardiac arrest survivors, who had successful restoration of spontaneous circulation, was used for this retrospective database analysis. Patients’ charts were screened for clinical, radiological or pathological evidence of NOMI and clinical data were collected. Results: Between 2000 and 2014, 1780 patients who were successfully resuscitated after out of hospital cardiac arrest were screened for NOMI. Twelve patients (0.68 %) suffered from NOMI and six of those died (50 %). Patients suffering from NOMI tended to have a longer duration until restoration of spontaneous circulation (27 vs. 20 min, p=0.128) and had significantly higher lactate (14 mmol/l vs. 8 mmol/l, p=0.002) and base deficit levels at admission (−17 vs. −10, p=0.012). Median leukocyte counts in NOMI patients peaked at the day of diagnosis. Conclusion: NOMI is a rare but life-threatening and potentially curable complication following successful cardiopulmonary resuscitation. Lactate and base deficit at admission could help to identify patients at risk for developing NOMI who might benefit from increased clinical attention.

Background: Inflammation is regarded as an important trigger for disease progression in heart failure. Particularly in severe acute heart failure, tissue hypoxia may lead to cellular damage and the release of intracellular mitochondrial DNA, which acts as an activator of the immune system due to its resemblance to bacterial DNA. It may therefore serve as a mediator of disease progression. The aim of this study was to determine circulating levels of mitochondrial DNA and its association with mortality in patients with heart failure in different presentations. Methods: Plasma levels of circulating mitochondrial DNA were measured in 90 consecutive patients with severe acute heart failure admitted to our medical intensive care unit as well as 109 consecutive chronic heart failure patients. Results: In patients admitted to our medical intensive care unit (median age 64 (49–74) years, median NT-pro-brain natriuretic peptide 4986 (1525–23,842) pg/mL, 30-day survival 64.4%), mitochondrial DNA levels were significantly higher in patients who died within 30 days after intensive care unit admission, and patients with plasma levels of mitochondrial DNA in the highest quartile had a 3.4-fold increased risk (P=0.002) of dying independent of renal function, vasopressor use and NT-pro-brain natriuretic peptide, troponin T, lactate levels or CardShock and acute physiology and chronic health evaluation II score. However, mitochondrial DNA did not provide incremental prognostic accuracy on top of the current gold standard acute physiology and chronic health evaluation II. Patients with severe acute heart failure showed significantly higher mitochondrial DNA levels (P Conclusions: The release of mitochondrial DNA into the circulation is associated with mortality in patients with severe acute heart failure but not in patients with chronic heart failure. The release of mitochondrial DNA may therefore play a role within the pathophysiology of acute heart failure, which warrants further research. However, the use of mitochondrial DNA as a biomarker for risk stratification in these patients is of limited utility.

Vitamin D deficiency is frequent in cancer patients and a risk factor for morbidity and mortality during critical illness. This single-center retrospective study analyzed 25-hydroxyvitamin D levels in critically ill cancer patients (n = 178, hematologic, n = 108, solid, n = 70) enrolled in a prospective ICU registry. The primary analysis was the prevalence of vitamin D deficiency (&lt, 20 ng/mL) and the severe deficiency (&le, 12 ng/mL). Secondary analyses included risk factors for vitamin D deficiency and its impact on ICU, hospital, and 1-year mortality. The prevalence of vitamin D deficiency and severe deficiency was 74% (95% CI: 67&ndash, 80%) and 54% (95% CI: 47&ndash, 61%). Younger age, relapsed/refractory disease, and a higher sepsis-related organ failure assessment (SOFA) score were independent risk factors for vitamin D deficiency (p &lt, 0.05). After adjusting for relapsed/refractory disease, infection, the SOFA score, and the early need for life-supporting interventions, severe vitamin D deficiency was an independent predictor of hospital mortality (OR: 2.21, 95% CI: 1.03&ndash, 4.72, p = 0.04) and 1-year mortality (OR: 3.40, 95% CI: 1.50&ndash, 7.71, p &lt, 0.01), but not of ICU mortality. Conclusion: Vitamin D deficiency is common in critically ill cancer patients requiring ICU admission, but its impact on short-term mortality in this group is uncertain. The observed association of severe vitamin D deficiency with the post-ICU outcome warrants clinical consideration and further study.

Background The impact of levosimendan treatment on clinical outcome in patients undergoing extracorporeal membrane oxygenation (ECMO) support after cardiovascular surgery is unknown. We hypothesized that the beneficial effects of levosimendan might improve survival when adequate end-organ perfusion is ensured by concomitant ECMO therapy. We therefore studied the impact of levosimendan treatment on survival and failure of ECMO weaning in patients after cardiovascular surgery. Methods We enrolled a total of 240 patients undergoing veno-arterial ECMO therapy after cardiovascular surgery at a university-affiliated tertiary care centre into our observational single-centre registry. Results During a median follow-up period of 37 months (interquartile range 19–67 months), 65% of patients died. Seventy-five per cent of patients received levosimendan treatment within the first 24 h after initiation of ECMO therapy. Cox regression analysis showed an association between levosimendan treatment and successful ECMO weaning [adjusted hazard ratio (HR) 0.41; 95% confience interval (CI) 0.22–0.80; P=0.008], 30 day mortality (adjusted HR 0.52; 95% CI 0.30–0.89; P=0.016), and long-term mortality (adjusted HR 0.64; 95% CI 0.42–0.98; P=0.04). Conclusions These data suggest an association between levosimendan treatment and improved short- and long-term survival in patients undergoing ECMO support after cardiovascular surgery.

OBJECTIVES Extracorporeal membrane oxygenation represents a valuable and rapidly evolving therapeutic option in patients with severe heart or lung failure following cardiovascular surgery. However, survival remains poor and accurate risk stratification challenging. Therefore, we evaluated the predictive value of urinary output within 24 hours after extracorporeal membrane oxygenation initiation on mortality in patients undergoing venoarterial extracorporeal membrane oxygenation support following cardiovascular surgery and aimed to improve established risk prediction models. DESIGN Single-center, observational registry. SETTING University-affiliated tertiary care center. PATIENTS We included 205 patients undergoing veno-arterial extracorporeal membrane oxygenation therapy following cardiovascular surgery at a university-affiliated tertiary-care center into our single-centre registry. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS During a median follow-up time of 35 months (interquartile range, 19-69), 64% of patients died. Twenty-four-hour urinary output was the strongest predictor of outcome among renal function variables with an adjusted hazard ratio per 1 SD of 0.55 (95% CI, 0.40-0.76; p < 0.001) for 30-day mortality and of 0.65 (95% CI, 0.53-0.86; p = 0.002) for 2-year long-term mortality. Most remarkably, 24-hour urinary output showed additional prognostic value beyond that achievable with the simplified acute physiology score-3 and sequential organ failure assessment score indicated by improvements in the category-free net reclassification index for 30-day mortality (simplified acute physiology score-3: 36%, p = 0.015; sequential organ failure assessment score: 36%, p = 0.02), as well as for 2-year mortality (simplified acute physiology score-3: 33%, p = 0.02; sequential organ failure assessment score: 43%, p = 0.005). CONCLUSIONS We identified 24-hour urinary output as a strong and easily available predictor of mortality in patients undergoing extracorporeal membrane oxygenation therapy following cardiovascular surgery. Implementation of 24-hour urinary output leads to a substantial improvement of established risk prediction models in this vulnerable patient population. These results are particularly compelling because measurement of urinary output is inexpensive and routinely performed in all critical care units.

Beta-blockers are a potential option to manage peri-operative atrial fibrillation. Landiolol is a new ultra-short beta-blocker with a half-life of only 4 minutes and very high beta-1 selectivity which has been used for treatment and prevention of atrial fibrillation in pulmonary surgery and gastro-intestinal surgery. Due to its limited negative inotropic effect and high beta-1 selectivity landiolol allows for control of heart rate with minimal impact on blood pressure. Landiolol is well tolerated by the respiratory system. Additional benefits are related to the regulation of the inflammatory response and blunting of the adrenergic pathway. There is a limited number of trials with total of 61 patients undergoing lung resection or oesophagectomy who developed post-operative atrial fibrillation and were treated with landiolol. The experience with landiolol for prevention is more documented than landiolol application for treatment of post-operative atrial fibrillation. There are 9 comparative studies with a total of 450 patients administered landiolol for prevention of post-operative atrial fibrillation. The use of low dosage (5-10mcg/kg/min) is usually sufficient to rapidly control heart rate which is associated with earlier and higher rate of conversion to sinus rhythm as compared to the controls. The excellent tolerance of landiolol at lower dosage (3-5mcg/kg/min) allows to initiate prophylactic use during surgery and postoperatively. Landiolol prophylaxis is associated with reduced incidence of post-operative atrial fibrillation without triggering adverse events related to a beta-blockade.

OBJECTIVES Although extracorporeal membrane oxygenation (ECMO) represents a rapidly evolving treatment option in patients with refractory heart or lung failure, survival remains poor and appropriate risk stratification challenging because established risk prediction models have not been validated for this specific population. METHODS This observational single-centre registry included a total of 240 patients treated with venoarterial ECMO therapy following cardiovascular surgery and analysed the discriminatory power of the European System of Cardiac Operative Risk Evaluation (EuroSCORE) additive, the EuroSCORE II, the Sequential Organ Failure Assessment (SOFA) score, the Simplified Acute Physiology Score (SAPS) II, the SAPS III, the Acute Physiology and Chronic Health Evaluation (APACHE) II, the Risk of renal failure, Injury to the kidney, Failure of kidney function, Loss of kidney function and End-stage renal failure (RIFLE) classification, the survival after venoarterial ECMO (SAVE) score, the prEdictioN of Cardiogenic shock OUtcome foR AMI patients salvaGed by VA-ECMO (ENCOURAGE) score and the Society of Thoracic Surgeons (STS) risk model for outcome prediction. RESULTS During a median follow-up time of 37 months (interquartile range 19–67), 65% of the patients died. Only the SAVE score and the SAPS II were significantly associated with the 30-day mortality rate with a hazard ratio (HR) of 1.06 [95% confidence interval (CI) 1.02–1.11; P = 0.002] for the SAVE score and an HR of 1.02 (95% CI 1.01–1.03; P = 0.004) for the SAPS II with a modest discriminatory power displayed by a C-index of 0.61 and 0.57, respectively. Seven out of 10 scoring systems revealed significant association with long-term mortality, with the SAVE score and the SAPS II remaining the strongest predictors of long-term mortality with an HR of 1.06 (95% CI 1.03–1.09; P CONCLUSIONS Risk assessment based on established risk models in patients with ECMO remains difficult. Only the SAPS II and the SAVE score were exclusively found to be suitable for short- and long-term outcome prediction in this specific vulnerable patient population.

Background Jaundice and cholestatic hepatic dysfunction are frequent findings in critically ill patients associated with increased mortality. Cholestasis in critically ill patients is closely associated with stimulation of pro-inflammatory cytokines resulting in impaired bile secretion and subsequent accumulation of bile acids. Aim of this study was to evaluate the clinical role of circulating bile acids in critically ill patients. Methods Total and individual serum bile acids were assessed via high-performance liquid chromatography in 320 critically ill patients and 19 controls. Results Total serum bile acids were threefold higher in septic than cardiogenic shock patients and sixfold higher than in post-surgical patients or controls (p

Background Acid–base disturbances are frequently observed in critically ill patients at the intensive care unit. To our knowledge, the acid–base profile of patients with acute-on-chronic liver failure (ACLF) has not been evaluated and compared to critically ill patients without acute or chronic liver disease. Results One hundred and seventy-eight critically ill patients with liver cirrhosis were compared to 178 matched controls in this post hoc analysis of prospectively collected data. Patients with and without liver cirrhosis showed hyperchloremic acidosis and coexisting hypoalbuminemic alkalosis. Cirrhotic patients, especially those with ACLF, showed a marked net metabolic acidosis owing to increased lactate and unmeasured anions. This metabolic acidosis was partly antagonized by associated respiratory alkalosis, yet with progression to ACLF resulted in acidemia, which was present in 62% of patients with ACLF grade III compared to 19% in cirrhosis patients without ACLF. Acidemia and metabolic acidosis were associated with 28-day mortality in cirrhosis. Patients with pH values

Durch die Verfugbarkeit verbesserter ECMO-Gerate mit einfacherer Implantation und einfacherem stabilerem Betrieb, findet die ECMO-Implantation zunehmende Verbreitung. Das vorliegende Positionspapier der Osterreichischen Kardiologischen Gesellschaft beleuchtet den Einsatz der ECMO bei erwachsenen kardiologischen nicht-postoperativen Patienten. In diesem Positionspapier werden nicht nur Indikationen und Kontraindikationen beleuchtet sondern auch Masnahmen wahrend des ECMO-Betriebes – Monitoring und Komplikationsmanagement sowie das ECMO weaning behandelt. Mit diesen detaillierten Leitlinien soll der Einsatz der ECMO osterreichweit verbessert, wenig erfahrenen Zentren eine Unterstutzung fur den eigenstandigen Aufbau eines ECMO-Programmes geliefert und nicht ECMO-Zentren eine Hilfestellung fur die Kontaktaufnahme mit ECMO-Zentren geboten werden.