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The most commonly used fluids for volume therapy are crystalloids and colloids. Crystalloids comprise 0.9% sodium chloride and balanced crystalloids (BC). Colloids can be divided into artificial colloids and human albumin (a natural colloid). Large studies show advantages for BC over 0.9% NaCl with respect to renal endpoints, probably due to the unphysiologically high chloride content of 0.9% NaCl. However, other studies, such as the BaSICS and PLUS trials, showed no significant differences in mortality in a heterogeneous population. Despite this, meta-analyses suggest advantages for BC. Therefore, BC should be preferred, especially in patients at increased risk of acute kidney injury, with acidemia and/or hyperchloremia. Except for specific indications (e.g., in patients with cirrhosis, sepsis resuscitation after initial volume therapy with BC), albumin should not be used. There is clear evidence of harm from hydroxyethyl starch in intensive care patients., (© 2024. The Author(s).)

Background: Coagulopathy is part of the pathological host response to infection in sepsis. Higher plasma concentrations of both tissue factor (TF) and tissue factor pathway inhibitor (TFPI) are associated with occurrence of disseminated intravascular coagulation (DIC), multi-organ dysfunction and increased mortality in patients with sepsis. Currently no treatment approaches specifically targeting this axis are available. We hypothesize that therapeutic plasma exchange (TPE) might limit this coagulopathy by restoring the balance of plasma proteins., Methods: This was a pooled post-hoc biobank analysis including 51 patients with early (shock onset < 24 h) and severe (norepinephrine dose > 0.4 μg/kg/min) septic shock, who were either receiving standard of care treatment (SOC, n = 14) or SOC + one single TPE (n = 37). Plasma concentrations of TF and TFPI were measured both at- and 6 h after study inclusion. The effect of TPE on concentrations of TF and TFPI was investigated and compared to SOC patients. Further, baseline TF and TFPI concentrations were used to modulate and predict clinical response to adjunctive TPE, indicated by longitudinal reduction of lactate concentrations over the first 24 h following study inclusion., Results: TPE led to a significant reduction in circulating concentrations of both TF and TFPI while no difference was observed in the SOC group. Relative change of TF within 6 h was + 14 (-0.8 to + 30.4) % (p = 0.089) in the SOC and -18.3 (-32.6 to -2.2) % (p < 0.001) in the TPE group (between group p < 0.001). Similarly, relative change of TFPI was + 14.4 (-2.3 to + 30.9) % (p = 0.076) in the SOC and -20 (-32.8 to -7.9) % (p < 0.001) in the TPE group (between group p = 0.022). The ratio of TF to TFPI remained unchanged in both SOC and TPE groups. SOC patients exhibited an increase in lactate over the initial 24 h when TF and TFPI concentrations were higher at baseline. In contrast, patients undergoing TPE experienced a sustained longitudinal reduction of lactate concentrations across all levels of baseline TF and TFPI elevations. In a multivariate mixed-effects model, higher baseline TF (p = 0.003) and TFPI (p = 0.053) levels led to greater longitudinal lactate concentration reduction effects in the TPE group., Conclusions: Adjunctive TPE in septic shock is associated with a significant removal of both TF and TFPI, which may contribute to the early hemodynamic improvement observed in septic shock patients receiving TPE. Higher baseline TF (and TFPI) plasma concentrations were identified as a putative predictor of treatment response that could be useful for predictive enrichment strategies in future clinical trials., (© 2024. The Author(s).)

Background: Sepsis-induced disseminated intravascular coagulopathy (DIC) remains a challenging clinical entity associated with significant morbidity and mortality. Endothelial injury or activation and extracellular vesicles (EV) are postulated as important determinants of DIC., Objectives: The aim of this study was to test the discriminatory ability of E-selectin, EV, tissue factor (TF) and TF pathway inhibitor (TFPI) in sepsis-induced coagulopathy., Methods: In this prospective, single-center study, we collected plasma samples within 24 hours after sepsis diagnosis and followed these patients for 5 consecutive days. Overt DIC was determined by the International Society on Thrombosis and Haemostasis (ISTH) DIC score. Eighty-seven sepsis patients were recruited (35 with overt DIC) who presented with increased levels of EV, EV-associated TF procoagulant activity (TF-PCA), E-selectin, TF, and TFPI at admission compared with healthy subjects., Results: Only TFPI levels and TF-PCA discriminated between sepsis patients with or without DIC (area under the curve = 0.76; P  = .0002). Increased TF-PCA was not sensitive in detecting sepsis-associated DIC; however, levels above 1.38 pg/mL showed high specificity in this cohort (sensitivity 27%, specificity 95%). The hazard ratio to progress to DIC over 5 days was 1.14 (95% CI, 0.64-2.07) for TF-PCA levels of 0.5 pg/mL or higher and 3.18 (95% CI, 1.74-5.79) for TFPI levels of 22.28 ng/mL or higher at admission., Conclusion: These findings highlight the pivotal roles of TF-PCA and TFPI in an early phase of sepsis-induced DIC. Only EV-associated and functionally active TF and not TF antigen levels showed a predictive potential regarding DIC. These novel results might support the improvement of diagnostic or even therapeutic strategies to mitigate the devastating consequences of DIC in septic patients., (© 2024 The Author(s).)

Coagulopathy, microvascular alterations and concomitant organ dysfunctions are hallmarks of sepsis. Attempts to attenuate coagulation activation with an inhibitor of tissue factor (TF), i.e. tissue factor pathway inhibitor (TFPI), revealed no survival benefit in a heterogenous group of sepsis patients, but a potential survival benefit in patients with an international normalized ratio (INR) < 1.2. Since an increased TF/TFPI ratio determines the procoagulant activity specifically on microvascular endothelial cells in vitro, we investigated whether TF/TFPI ratio in blood is associated with INR alterations, organ dysfunctions, disseminated intravascular coagulation (DIC) and outcome in septic shock. Twenty-nine healthy controls (HC) and 89 patients with septic shock admitted to a tertiary ICU were analyzed. TF and TFPI in blood was analyzed and related to organ dysfunctions, DIC and mortality. Patients with septic shock had 1.6-fold higher levels of TF and 2.9-fold higher levels of TFPI than HC. TF/TFPI ratio was lower in septic shock compared to HC (0.003 (0.002-0.005) vs. 0.006 (0.005-0.008), p < 0.001). Non-survivors had higher TFPI levels compared to survivors (43038 (29354-54023) vs. 28041 (21675-46582) pg/ml, p = 0.011). High TFPI levels were associated with acute kidney injury, liver dysfunction, DIC and disease severity. There was a positive association between TF/TFPI ratio and troponin T (b = 0.531 (0.309-0.754), p < 0.001). A high TF/TFPI ratio is exclusively associated with myocardial injury but not with other organ dysfunctions. Systemic TFPI levels seem to reflect disease severity. These findings point towards a pathophysiologic role of TF/TFPI in sepsis-induced myocardial injury., (© 2024. The Author(s).)

Introduction: Acute kidney injury is a frequent complication in critically ill patients with and without COVID-19. The aim of this study was to evaluate the incidence of, and risk factors for, acute kidney injury and its effect on clinical outcomes of critically ill COVID-19 patients in Tyrol, Austria., Methods: This multicenter prospective registry study included adult patients with a SARS-CoV-2 infection confirmed by polymerase chain reaction, who were treated in one of the 12 dedicated intensive care units during the COVID-19 pandemic from February 2020 until May 2022., Results: In total, 1042 patients were included during the study period. The median age of the overall cohort was 66 years. Of the included patients, 267 (26%) developed acute kidney injury during their intensive care unit stay. In total, 12.3% (n = 126) required renal replacement therapy with a median duration of 9 (IQR 3-18) days. In patients with acute kidney injury the rate of invasive mechanical ventilation was significantly higher with 85% (n = 227) compared to 41% (n = 312) in the no acute kidney injury group (p < 0.001). The most important risk factors for acute kidney injury were invasive mechanical ventilation (OR = 4.19, p < 0.001), vasopressor use (OR = 3.17, p < 0.001) and chronic kidney disease (OR = 2.30, p < 0.001) in a multivariable logistic regression analysis. Hospital and intensive care unit mortality were significantly higher in patients with acute kidney injury compared to patients without acute kidney injury (Hospital mortality: 52.1% vs. 17.2%, p < 0.001, ICU-mortality: 47.2% vs. 14.7%, p < 0.001)., Conclusion: As in non-COVID-19 patients, acute kidney injury is clearly associated with increased mortality in critically ill COVID-19 patients. Among known risk factors, invasive mechanical ventilation has been identified as an independent and strong predictor of acute kidney injury., (© 2023. The Author(s).)

Background: Widely varying mortality rates of critically ill Coronavirus disease 19 (COVID-19) patients in the world highlighted the need for local surveillance of baseline characteristics, treatment strategies and outcome. We compared two periods of the COVID-19 pandemic to identify important differences in characteristics and therapeutic measures and their influence on the outcome of critically ill COVID-19 patients., Methods: This multicenter prospective register study included all patients with a SARS-CoV‑2 infection confirmed by polymerase chain reaction, who were treated in 1 of the 12 intensive care units (ICU) from 8 hospitals in Tyrol, Austria during 2 defined periods (1 February 2020 until 17 July: first wave and 18 July 2020 until 22 February 2021: second wave) of the COVID-19 pandemic., Results: Overall, 508 patients were analyzed. The majority (n = 401) presented during the second wave, where the median age was significantly higher (64 years, IQR 54-74 years vs. 72 years, IQR 62-78 years, p < 0.001). Invasive mechanical ventilation was less frequent during the second period (50.5% vs 67.3%, p = 0.003), as was the use of vasopressors (50.3% vs. 69.2%, p = 0.001) and renal replacement therapy (12.0% vs. 19.6%, p = 0.061), which resulted in shorter ICU length of stay (10 days, IQR 5-18 days vs. 18 days, IQR 5-31 days, p < 0.001). Nonetheless, ICU mortality did not change (28.9% vs. 21.5%, p = 0.159) and hospital mortality even increased (22.4% vs. 33.4%, p = 0.039) in the second period. Age, frailty and the number of comorbidities were significant predictors of hospital mortality in a multivariate logistic regression analysis of the overall cohort., Conclusion: Advanced treatment strategies and learning effects over time resulted in reduced rates of mechanical ventilation and vasopressor use in the second wave associated with shorter ICU length of stay. Despite these improvements, age appears to be a dominant factor for hospital mortality in critically ill COVID-19 patients., (© 2021. The Author(s).)

Introduction: Inflammation induces a procoagulant phenotype of endothelial cells (EC) with the exposure of tissue factor (TF), a potent initiator of the extrinsic coagulation cascade. Although systemic inflammation affects the whole vascular system, thrombotic lesions occur particularly in microcirculation. This raises the question of whether TF-procoagulant activity (TF-PCA) differs between EC from arterial, venous, and microvascular beds., Materials and Methods: Functional coagulation tests, including TF-PCA, and inflammatory responses were investigated on arterial, venous and microvascular endothelial cells. Interleukin-6 (IL-6) and TF-levels were determined in cohort of 59 septic patients., Results: We found that tumor necrosis factor alpha (TNFα), lipopolysaccharide, and interleukin-1β induce a solid, dose-dependent increase in TF-PCA, which is highest in microvascular EC. A positive correlation of interleukin-6 (IL-6) with TF levels was observed in a cohort of 59 septic patients. In contrast, TF-PCA was independent of IL-6 concentrations in vitro. Re-analysis of publicly available gene expression data revealed that among the top 50 genes annotated to coagulation, TF is one of three regulated genes common to the three investigated EC subtypes. The response to inflammatory stimuli in terms of exposure of leukocyte-endothelial- and platelet-endothelial adhesion molecules (E-selectin and PECAM-1), remodeling of adherens junctions, co-exposure of negatively charged surfaces nor breakdown of the glycocalyx was comparable between the EC subtypes and did not explain the higher TF-PCA on microvascular cells. We found that the ratio of TF and TFPI exposure on the endothelial membrane significantly differs between the EC subtypes., Conclusions: These findings indicate that the ratio of TF to its inhibitor TFPI is a determinant of endothelial TF-PCA, which is most pronounced on microvascular endothelial cells and might explain why the microvascular system is particularly susceptible to inflammation-induced thrombosis., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Metabolic alkalosis is a frequently occurring problem during continuous veno-venous hemofiltration (CVVH) with regional citrate anticoagulation (RCA). This study aimed to evaluate the effectiveness of switching from high to low bicarbonate (HCO 3 - ) replacement fluid in alkalotic critically ill patients with acute kidney injury treated by CVVH and RCA., Methods: A retrospective-comparative study design was applied. Patients who underwent CVVH with RCA in the ICU between 09/2016 and 11/2017 were evaluated. Data were available from the clinical routine. A switch of the replacement fluid Phoxilium ® (30 mmol/l HCO 3 - ) to Biphozyl ® (22 mmol/l HCO 3 - ) was performed as blood HCO 3 - concentration persisted ≥ 26 mmol/l despite adjustments of citrate dose and blood flow. Data were collected from 72 h before the switch of the replacement solutions until 72 h afterwards., Results: Of 153 patients treated with CVVH during that period, 45 patients were switched from Phoxilium ® to Biphozyl ® . Forty-two patients (42 circuits) were available for statistical analysis. After switching the replacement fluid from Phoxilium ® to Biphozyl ® the serum HCO 3 - concentration decreased significantly from 27.7 mmol/l (IQR 26.9-28.9) to 25.8 mmol/l (IQR 24.6-27.7) within 24 h (p < 0.001). Base excess (BE) decreased significantly from 4.0 mmol/l (IQR 3.1-5.1) to 1.8 mmol/l (IQR 0.2-3.4) within 24 h (p < 0.001). HCO 3 - and BE concentration remained stable from 24 h till the end of observation at 72 h after the replacement fluid change (p = 0.225). pH and PaCO 2 did not change significantly after the switch of the replacement fluid until 72 h., Conclusions: This retrospective analysis suggests that for patients developing refractory metabolic alkalosis during CVVH with RCA the use of Biphozyl ® reduces external HCO 3 - load and sustainably corrects intracorporeal HCO 3 - and BE concentrations. Future studies have to prove whether correcting metabolic alkalosis during CVVH with RCA in critically ill patients is of relevance in terms of clinical outcome.

Background: Critically ill coronavirus disease 2019 (COVID-19) patients present with a hypercoagulable state with high rates of macrovascular and microvascular thrombosis, for which hypofibrinolysis might be an important contributing factor., Methods: We retrospectively analysed 20 critically ill COVID-19 patients at Innsbruck Medical University Hospital whose coagulation function was tested with ClotPro® and compared with that of 60 healthy individuals at Augsburg University Clinic. ClotPro is a viscoelastic whole blood coagulation testing device. It includes the TPA test, which uses tissue factor (TF)-activated whole blood with added recombinant tissue-derived plasminogen activator (r-tPA) to induce fibrinolysis. For this purpose, the lysis time (LT) is measured as the time from when maximum clot firmness (MCF) is reached until MCF falls by 50%. We compared COVID-19 patients with prolonged LT in the TPA test and those with normal LT., Results: Critically ill COVID-19 patients showed hypercoagulability in ClotPro assays. MCF was higher in the EX test (TF-activated assay), IN test (ellagic acid-activated assay), and FIB test (functional fibrinogen assay) with decreased maximum lysis (ML) in the EX test (hypofibrinolysis) and highly prolonged TPA test LT (decreased fibrinolytic response), as compared with healthy persons. COVID-19 patients with decreased fibrinolytic response showed higher fibrinogen levels, higher thrombocyte count, higher C-reactive protein levels, and decreased ML in the EX test and IN test., Conclusion: Critically ill COVID-19 patients have impaired fibrinolysis. This hypofibrinolytic state could be at least partially dependent on a decreased fibrinolytic response., Competing Interests: Declarations of interest MB has received research funding and travel grants from LFB Biomedicaments, Baxter GmbH, CSL Behring GmbH, Mitsubishi Tanabe and non-financial support from TEM International outside the submitted work. MJ reported receiving grants from Baxter; grants and personal fees from Fresenius Kabi; and speaking, consulting honoraria, or both from Sphingotec, CLS-Behring, Fresenius and Astute Medical outside the submitted work. CT reports grants and personal fees from BrainLab, grants and personal fees from DePuySynthes, grants and personal fees from Intrinsic Therapeutics, grants from TETEC AG, personal fees from Aesculap, grants and personal fees from Signus Medizintechnik, grants and personal fees from Medtronic, grants and personal fees from Icotec AG, grants and personal fees from Edge Therapeutics, grants from BIT-Pharma, outside the submitted work. DF has received study funding, honoraria for consultancy and board activity from Astra Zeneca, AOP orphan, Baxter, Bayer, BBraun, Biotest, CSL Behring, Delta Select, Dade Behring, Edwards, Fresenius, Glaxo, Haemoscope, Hemogem, Lilly, LFB, Mitsubishi Pharma, NovoNordisk, Octapharm, Pfizer, Tem-Innovation outside the submitted work. The other authors declare no conflicts of interest., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: On February 25, 2020, the first 2 patients were tested positive for severe acute respiratory syndrome coronavirus‑2 (SARS-CoV-2) in Tyrol, Austria. Rapid measures were taken to ensure adequate intensive care unit (ICU) preparedness for a surge of critically ill coronavirus disease-2019 (COVID-19) patients., Methods: This cohort study included all COVID-19 patients admitted to an ICU with confirmed or strongly suspected COVID-19 in the State of Tyrol, Austria. Patients were recorded in the Tyrolean COVID-19 intensive care registry. Date of final follow-up was July 17, 2020., Results: A total of 106 critically ill patients with COVID-19 were admitted to 1 of 13 ICUs in Tyrol from March 9 to July 17, 2020. Median age was 64 years (interquartile range, IQR 54-74 years) and the majority of patients were male (76 patients, 71.7%). Median simplified acute physiology score III (SAPS III) was 56 points (IQR 49-64 points). The median duration from appearance of first symptoms to ICU admission was 8 days (IQR 5-11 days). Invasive mechanical ventilation was required in 72 patients (67.9%) and 6 patients (5.6%) required extracorporeal membrane oxygenation treatment. Renal replacement therapy was necessary in 21 patients (19.8%). Median ICU length of stay (LOS) was 18 days (IQR 5-31 days), median hospital LOS was 27 days (IQR 13-49 days). The ICU mortality was 21.7% (23 patients), hospital mortality was 22.6%. There was no significant difference in ICU mortality in patients receiving invasive mechanical ventilation and in those not receiving it (18.1% vs. 29.4%, p = 0.284). As of July 17th, 2020, two patients are still hospitalized, one in an ICU, one on a general ward., Conclusion: Critically ill COVID-19 patients in Tyrol showed high severity of disease often requiring complex treatment with increased lengths of ICU and hospital stay. Nevertheless, the mortality was found to be remarkably low, which may be attributed to our adaptive surge response providing sufficient ICU resources.

Background: Sepsis, a dysregulated host response following infection, is associated with massive immune activation and high mortality rates. There is still a need to define further risk factors and laboratory parameters predicting the clinical course. Iron metabolism is regulated by both, the body's iron status and the immune response. Iron itself is required for erythropoiesis but also for many cellular and metabolic functions. Moreover, iron availability is a critical determinant in infections because it is an essential nutrient for most microbes but also impacts on immune function and intravascular oxidative stress. Herein, we used a prospective study design to investigate the putative impact of serum iron parameters on the outcome of sepsis., Methods: Serum markers of iron metabolism were measured in a prospective cohort of 61 patients (37 males, 24 females) with sepsis defined by Sepsis-3 criteria in a medical intensive care unit (ICU) and compared between survivors and non-survivors. Regulation of iron parameters in patients stratified by focus of infection and co-medication as well as association of the markers with sepsis severity scores and survival were investigated with linear and logistic regression corrected for sex and age effects., Results: Positive correlations of increased serum iron and ferritin concentrations upon ICU admission with the severity of organ failure (SOFA score) and with mortality were observed. Moreover, high TF-Sat, elevated ferritin and serum iron levels and low transferrin concentrations were associated with reduced survival. A logistic regression model consisting of SOFA and transferrin saturation (SOFA-TF-Sat) had the best predictive power for survival in septic ICU patients. Of note, administration of blood transfusions prior to ICU admission resulted in increased TF-Sat and reduced survival of septic patients., Conclusions: Our study could show an important impact of serum iron parameters on the outcome of sepsis. Furthermore, we identified transferrin saturation as a stand-alone predictor of sepsis survival and as a parameter of iron metabolism which may in a combined model improve the prediction power of the SOFA score., Trial Registration: The study was carried out in accordance with the recommendations of the Declaration of Helsinki on biomedical research. The study was approved by the institutional ethics review board of the Medical University Innsbruck (study AN2013-0006)., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

Oliguria is often observed in critically ill patients. However, different thresholds in urine output (UO) have raised discussion as to the clinical importance of a transiently reduced UO of less than 0.5 ml/kg/h lasting for at least 6 h. While some studies have demonstrated that isolated oliguria without a concomitant increase in serum creatinine is associated with higher mortality rates, different underlying pathophysiological mechanisms suggest varied clinical importance of reduced UO, as some episodes of oliguria may be fully reversible. We aim to explore the clinical relevance of oliguria in critically ill patients and propose a clinical pathway for the diagnostic and therapeutic management of an oliguric, critically ill patient.

Interactions between lung and kidney can significantly affect the course of acute diseases, a phenomenon that was first observed in the 1950s by describing pulmonary dysfunction in uremic patients. From animal experiments there is ample evidence for remote lung injury following acute kidney injury (AKI), with an increased risk for the development of pulmonary edema and acute respiratory distress syndrome (ARDS). Coincident ARDS and AKI are associated with higher rates of intubation and mechanical ventilation, significantly prolonged weaning from mechanical ventilation and increased mortality. On the other hand, acute lung diseases and mechanical ventilation can promote the development of AKI and are associated with increased mortality when AKI is also present. These bidirectional interactions may include hemodynamic adverse effects during mechanical ventilation or volume overload as well as the release or decreased clearance and metabolism of proinflammatory mediators (e.g., interleukin-6 and tumor necrosis factor-α), which may induce and aggravate distant organ injury. The aim of this work is to examine the interactions between lung and the kidney in critically ill patients, as well as discuss potential preventive approaches.

Purpose: Acute kidney injury (AKI) frequently occurs in critically ill patients and often precipitates use of renal replacement therapy (RRT). However, the ideal circumstances for whether and when to start RRT remain unclear. We performed evidence synthesis of the available literature to evaluate the value of biomarkers to predict receipt of RRT for AKI., Methods: We conducted a PRISMA-guided systematic review and meta-analysis including all trials evaluating biomarker performance for prediction of RRT in AKI. A systematic search was applied in MEDLINE, Embase, and CENTRAL databases from inception to September 2017. All studies reporting an area under the curve (AUC) for a biomarker to predict initiation of RRT were included., Results: Sixty-three studies comprising 15,928 critically ill patients (median per study 122.5 [31-1439]) met eligibility. Forty-one studies evaluating 13 different biomarkers were included. Of these biomarkers, neutrophil gelatinase-associated lipocalin (NGAL) had the largest body of evidence. The pooled AUCs for urine and blood NGAL were 0.720 (95% CI 0.638-0.803) and 0.755 (0.706-0.803), respectively. Blood creatinine and cystatin C had pooled AUCs of 0.764 (0.732-0.796) and 0.768 (0.729-0.807), respectively. For urine biomarkers, interleukin-18, cystatin C, and the product of tissue inhibitor of metalloproteinase-2 and insulin growth factor binding protein-7 showed pooled AUCs of 0.668 (0.606-0.729), 0.722 (0.575-0.868), and 0.857 (0.789-0.925), respectively., Conclusion: Though several biomarkers showed promise and reasonable prediction of RRT use for critically ill patients with AKI, the strength of evidence currently precludes their routine use to guide decision-making on when to initiate RRT.

Background: Microvesicles (MV) are extracellular vesicles known to be associated with cellular activation and inflammation. Hemofiltration is an effective blood purification technique for patients with renal failure and possibly also eliminates inflammatory mediators in the setting of sepsis. On the other hand, proinflammatory stimuli are induced by blood contacting the artificial membrane during extracorporeal blood purification. In chronic dialysis patients a systemic increase in MV has been described. The aim of the study was to investigate whether hemofilter passage of blood in continuous veno-venous hemofiltration (CVVH) alters MV composition and levels in critically ill patients with sepsis., Methods: Pre- and postfilter bloods as well as ultrafiltrate samples from intensive care unit patients with severe sepsis were obtained during CVVH with regional citrate anticoagulation. MV subtypes in blood were analyzed by high-sensitivity flow cytometry. Additionally, tissue factor (TF) levels and MV-associated TF activities as well as MV activities were quantified. All parameters were corrected for hemoconcentration applied during CVVH., Results: Twelve patients were analyzed. A significant increase in presumably mostly leukocyte-derived CD31+/CD41- MV (1.32 (1.09-1.93)-fold [median (25th-75th quartiles)], p = 0.021) was observed post- to prefilter, whereas platelet-derived MV as well as AnnexinV-binding MV were unaltered. Increments of AnnexinV+, CD42b+ and CD31+/CD41- MV post- to prefilter correlated with filtration fraction (FF) (all p < 0.05). Significant reductions in MV activity [0.72 (0.62-0.84)-fold, p = 0.002] and TF level [0.95 (0.87-0.99)-fold, p = 0.0093] were detected postfilter compared to prefilter. No MV activity was measurable in ultrafiltrate samples., Conclusions: Despite clearing a fraction of small PS-exposing MV CVVH does not eliminate larger MV. Concurrently, CVVH induces the release of CD31+/CD4- MV that indicate leukocyte activation during hemofilter passage in septic patients. Increments of several MV subtypes within the hemofilter correlate with FF, which supports common recommendations to keep FF low. A fraction of TF is being cleared by CVVH via ultrafiltration.

Purpose: Endothelial pathology is considered to play a key role in septic shock. Since endothelial-derived microvesicles (MV) are elevated in various diseases associated with endothelial pathology, they are considered surrogate markers of the endothelial state. By analyzing the signature of circulating MV with high-sensitivity flow cytometry (hsFC), we wanted to test the hypothesis whether endothelial-derived MV are increased in septic shock., Methods: MV in blood from healthy volunteers and patients with septic shock treated in a medical intensive care unit were quantified by hsFC, which has an improved detection limit of approximately 0.3 μm., Results: Patients with septic shock (n = 30) showed 3-fold higher levels of CD31+/CD41- MV (58.5 (26.4-101.2) [median (25th-75th percentile)] vs. 19.5 (12.8-25.4) MV/μL; P <0.001) compared with healthy volunteers (n = 18). Absolute counts of CD144+, CD62E+, and CD106+ MV, specific for endothelial-derived MV, were low in all groups. The number of CD31+/CD41- MV correlated significantly with leukocyte count (rs = 0.64; P <0.001). Platelet-derived CD41+ MV were significantly elevated in the group dying within 48 h after inclusion (639.1 (321.3-969.7) vs. 221.5 (119.5-456.9) MV/μL; P = 0.037). Patients dying within 48 h had also significantly higher levels of CD31+/CD41-/AnnexinV- MV (51.9 (24.9-259.8) vs. 18.9 (9.7-31) MV/μL; P = 0.028)., Conclusions: Despite an improved detection limit for MV by using hsFC, counts of endothelial-specific MV are unexpectedly low in patients with septic shock. Increased amounts of CD41+ and CD31+/CD41-/AnnexinV- MV indicate release by activated platelets and possibly leukocytes correlating with unfavorable outcome.

Oliguria is a common phenomenon that is found in hospitalized patients . Although a rapid reduction in urine excretion rate may reflect a precipitous fall in the glomerular filtration rate, in many cases it may not. Given the common physiological finding of oliguria, we explore the relationship between the functional biomarker of renal injury (oliguria) with the increasing number of markers of renal injury to see if this combination may aid in risk stratification. © 2016 S. Karger AG, Basel.

Objective: To evaluate the prognostic potential of serum C-terminal provasopressin (CT-proAVP or Copeptin) and midregional pro-A-type natriuretic peptide (MR-proANP) to predict neurological outcome following resuscitation from cardiac arrest., Methods: In this prospective observational study, we employed novel ultra sensitive immunoassay technology to examine serial serum samples from 134 cardiac arrest patients. Patients were either allocated to mild therapeutic hypothermia using an endovascular device or normothermia. Serial blood samples were obtained from resuscitated cardiac arrest survivors during their first 7 days in an intensive care unit, and serum Copeptin and MR-proANP were measured. Cerebral function assessments were made using cerebral performance categorization (CPC) at discharge from hospital. Copeptin and MR-proANP data were analyzed using dichotomized CPC scores (1-2 versus 3-5)., Results: Sixty-nine patients (51%) had a poor outcome (CPC 3-5) at hospital discharge. MR-proANP and Copeptin peaked on day 1 (i.e. 0-24h) with the medians being 249.3pmol/L and 77.2pmol/L, respectively. In the first 48h maximum levels of MR-proANP and Copeptin showed an AUC in the ROC of 0.743 (95% CI: 0.658-0.828) and 0.677 (95% CI: 0.583-0.771). Binary logistic regression revealed MR-proANP and Copeptin within 48h after ROSC being significantly associated with functional outcome (p<0.05). Copeptin within 48h was also associated with outcome in the hypothermia group (p<0.05)., Conclusion: Systemic levels of MR-proANP and Copeptin peak early in cardiac arrest patients in the 48h post-resuscitation period. MR-proANP and Copeptin were highly predictive for poor outcome in comatose resuscitated patients., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Purpose: The neuropeptide secretoneurin (SN) shows widespread distribution in the brain. We evaluated whether SN is elevated after cardiopulmonary resuscitation (CPR) and could serve as a potential new biomarker for hypoxic brain injury after CPR., Methods: This was a prospective observational clinical study. All patients admitted to a tertiary medical intensive care unit after successful CPR with expected survival of at least 24 h were consecutively enrolled from September 2008 to April 2013. Serum SN and neuron-specific enolase were determined in 24 h intervals starting with the day of CPR for 7 days. Neurological outcome was assessed with the Cerebral Performance Categories Scale (CPC) at hospital discharge., Results: A total of 134 patients were included with 49 % surviving to good neurological outcome (CPC 1-2). SN serum levels peaked within the first 24 h showing on average a sixfold increase above normal. SN levels were significantly higher in patients with poor (CPC 3-5) than in patients with good neurological outcome [0-24 h: 75 (43-111) vs. 38 (23-68) fmol/ml, p < 0.001; 24-48 h: 45 (24-77) vs. 23 (16-39) fmol/ml, p < 0.001]. SN determined within the first 48 h showed a receiver operating characteristic (ROC) area under the curve (AUC) of 0.753 (0.665-0.841). NSE in the first 72 h had a ROC-AUC of 0.881 (0.815-0.946). When combining the two biomarkers an AUC of 0.925 (0.878-0.972) for outcome prediction could be reached., Conclusions: SN is a promising early biomarker for hypoxic brain injury. Further studies will be required for confirmation of these results.

Background: High volume hemofiltration (HVHF) has been proposed as method for blood purification, especially under the condition of systemic inflammatory syndromes. Our goal was to evaluate the effects of HVHF in critically ill patients., Methods: A systematic review and meta-analysis was conducted of randomized controlled trials containing original data comparing HVHF defined by a dose of >50 mL/kg/h versus standard volume hemofiltration in critically ill patients. The primary outcome assessed was mortality. Additional endpoints assessed were renal recovery, vasopressor dependency, cytokine reduction and adverse events., Results: Four studies investigating continuous HVHF and three studies examining pulse high volume hemofiltration (PHVHF) using prescribed doses between 62 and 85 mL/kg/h met the criteria for this systematic review and provided data eligible for meta-analysis on a total of 558 patients. Meta-analyses did not show an effect of continuous HVHF (odds ratio, OR: 0.85; 95% confidence interval [CI]: 0.50-1.45; 4 trials; N.=473) or PHVHF (OR: 0.62; 95% CI: 0.22-1.74; 3 trials; N.=85) on mortality (both combined: OR: 0.85; 95% CI: 0.60-1.22; 7 trials; N.=558). Continuous HVHF had no significant beneficial effect on renal recovery of survivors (OR: 0.62; 95% CI: 0.17-1.97; 3 trials; N.=445). Inconsistent reports of a more rapid hemodynamic stabilization or improved cytokine clearance were mainly restricted to PHVHF., Conclusion: No clear overall beneficial effect of HVHF or PHVHF compared to standard volume hemofiltration can be detected.

Purpose: Early clinical signs of heparin induced thrombocytopenia (HIT) are nonspecific and include a sudden drop in the number of platelets as well as formation of arterial and venous thromboses. Regional citrate anticoagulation (RCA) is increasingly used as a very effective modality to prevent filter clotting during renal replacement therapy (RRT). We report the first case where repeated premature filter clotting despite RCA indicated a manifestation of HIT., Materials and Methods: A 71-year old woman admitted to the ICU for a compartment syndrome of the leg developed septic shock with acute kidney injury requiring continuous veno-venous hemodialysis (CVVHD). Because of unexpected and repeated premature filter clotting during CVVHD using RCA, HIT was suspected., Results: The diagnosis of HIT was confirmed by the presence of IgG antibodies against heparin and platelet factor (PF) 4 complexes and six points in the 4T score. Discontinuation of heparin administration and initiation of systemic anticoagulation with danaparoid sodium resulted in the normalization of platelet count and hemofilter lifetime., Conclusion: RCA does not seem to be sufficient to prevent hemofilter clotting during HIT. Thus, in case of repeated premature filter clotting despite RCA, one should suspect HIT and prompt diagnostic workup as well as a switch to alternative anticoagulation., (© 2014 S. Karger AG, Basel.)

Purpose of Review: End-of-life care and communication deficits are important sources of conflicts within ICU teams and with patients or families. This narrative review describes recent studies on how to improve palliative care and surrogate decision-making in ICUs and compares the results with previously published literature on this topic., Recent Findings: Awareness and use of end-of-life recommendations is still low. Education about end-of-life is beneficial for end-of-life decisions. Residency and nurses training programmes start to integrate palliative care education in critical care. Integration of palliative care consults is recommended and probably cost-effective. Projects that promote direct contact of care team members with patients/families may be more likely to improve care than educational interventions for caregivers only. The family's response to critical illness includes adverse psychological outcome ('postintensive care syndrome-family'). Information brochures and structured communication protocols are likely to improve engagement of family members in surrogate decision-making; however, validation of outcome effects of their use is needed., Summary: Optimizing palliative care and communication skills is the current challenge in ICU end-of-life care. Intervention strategies should be interdisciplinary, multiprofessional and family-centred in order to quickly reach these goals.

Monitoring of organ function is one of the core tasks of intensive care medicine. Although various monitoring devices and parameters have already been established for some organs, there are no or only few conditionally useful parameters or scores available for the kidneys, liver, gastrointestinal tract, and blood coagulation. Therefore, specific biomarkers and scores as well as combinations of both are currently investigated for better monitoring of these organs. This article gives a critical overview of currently used as well as investigational biomarkers, tests and scores in general, and shows some examples of the implications for common diseases, clinical situations and constellations in the intensive care unit.