Explore the vast range of titles available.

BackgroundMulti-organ dysfunction in critical illness is common and frequently involves the lungs and kidneys, often requiring organ support such as invasive mechanical ventilation (IMV), renal replacement therapy (RRT) and/or extracorporeal membrane oxygenation (ECMO).MethodsA consensus conference on the spectrum of lung–kidney interactions in critical illness was held under the auspices of the Acute Disease Quality Initiative (ADQI) in Innsbruck, Austria, in June 2018. Through review and critical appraisal of the available evidence, the current state of research, and both clinical and research recommendations were described on the following topics: epidemiology, pathophysiology and strategies to mitigate pulmonary dysfunction among patients with acute kidney injury and/or kidney dysfunction among patients with acute respiratory failure/acute respiratory distress syndrome. Furthermore, emphasis was put on patients receiving organ support (RRT, IMV and/or ECMO) and its impact on lung and kidney function.ConclusionThe ADQI 21 conference found significant knowledge gaps about organ crosstalk between lung and kidney and its relevance for critically ill patients. Lung protective ventilation, conservative fluid management and early recognition and treatment of pulmonary infections were the only clinical recommendations with higher quality of evidence. Recommendations for research were formulated, targeting lung–kidney interactions to improve care processes and outcomes in critical illness.

We investigated the occurrence and outcome of respiratory failure and ARDS in critically ill patients with liver cirrhosis. This is a retrospective analysis of patients with liver cirrhosis at an ICU during an 8-Year period. An assessment of acute on chronic liver failure as well as the presence and grade of ARDS within the first 72 h of admission to the ICU was performed. A total of 735 patients during the study period. Median age was 58 (50–69) years and 61% ( n  = 447) were male. 57% ( n  = 421) of the patients received mechanical ventilation (MV). Liver specific as well as ICU scores on admission were significantly higher in patients with MV. Necessity of vasopressor support (86%vs.25%, p  < 0.001) and RRT (50%vs.11%, p  < 0.001) was more frequent in patients with MV. The incidence of ARDS within the first 72 h of admission was 8% ( n  = 61). We observed a 28-day mortality or liver transplantation rate of 54% ( n  = 196) and 66% ( n  = 66%) in patients with MV and ARDS, respectively. After 90-days 63% ( n  = 226) with MV and 70% ( n  = 43) with ARDS were dead or received liver transplantation. ARDS is a prognostic factor for mortality in patients with liver cirrhosis admitted to the ICU. One out of ten critically ill cirrhotic patients develop ARDS within 72 h after admission. Although mortality rates are high initially critical care therapy should not be withheld and must be reevaluated regularly.

Several case series have highlighted the ADVOS hemodialysis system's efficacy in eliminating water-soluble and protein-bound substances across diverse patient populations, such as multiorgan failure, acute-on-chronic liver failure (ACLF), acidosis, and even COVID-19. The EMOS-Registry, a non-interventional, multi-center patient registry, amassed real-world evidence, culminating in the largest patient cohort treated with ADVOS to date. This study aims to present and analyze the final performance and safety outcomes from the entire dataset comprising 282 participants. Data spanning from January 18, 2017, to August 31, 2020, were collected from five German hospitals, encompassing subsets of patients with acidosis and ACLF grade 3. Performance and safety were assessed through vital signs, clinical laboratory parameters and blood gas analyses. The SOFA Score-Standardized Mortality Ratio (SMR) served to evaluate patient outcomes in the absence of a control group. Participants, with a median age of 58 years, predominantly male (64%), exhibited a high requirement for mechanical ventilation (68%) and vasopressors (82%) with a median SOFA Score of 15. Notably, a median of 3 (IQR 2, 5) ADVOS sessions per patient were administered. Following the initial treatment, significant reductions were observed in bilirubin (-1.9 [CI 95% -1.3, -2.5]), creatinine (-0.5 [-0.4, -0.6]), and blood urea nitrogen (-13.1 mg/dL [-10.3, -16.0]) levels. Moreover, there were marked improvements in blood pH (7.34 vs. 7.41, p < 0.001), HCO3- (19.4 vs. 24.6 mmol/l, p < 0.001) and base excess (-5.6 vs. 0.2 mmol/l, p < 0.001). The observed mortality rate (66%) was notably lower than the expected rate based on SOFA Score (84%), resulting in a SMR of 0.79 (95% CI: 0.66-0.93), with a calculated number needed to treat (NNT) of 5.8. This study emphasizes the ADVOS system's efficacy in eliminating water-soluble and protein-bound substances and correcting acid-base imbalances across a diverse cohort with multiorgan failure. However, further validation through randomized controlled trials is warranted to solidify these findings. DRKS00017068. Registered 29 April 2019 - Retrospectively registered, https://drks.de/search/en/trial/DRKS00017068.

Phosphate imbalances or disorders have a high risk of morbidity and mortality in patients with chronic kidney disease. It is unknown if this finding extends to mortality in patients presenting at an emergency room with or without normal kidney function. This cross sectional analysis included all emergency room patients between 2010 and 2011 at the Inselspital Bern, Switzerland. A multivariable cox regression model was applied to assess the association between phosphate levels and in-hospital mortality up to 28 days. 22,239 subjects were screened for the study. Plasma phosphate concentrations were measured in 2,390 patients on hospital admission and were included in the analysis. 3.5% of the 480 patients with hypophosphatemia and 10.7% of the 215 patients with hyperphosphatemia died. In univariate analysis, phosphate levels were associated with mortality, age, diuretic therapy and kidney function (all p<0.001). In a multivariate Cox regression model, hyperphosphatemia (OR 3.29, p<0.001) was a strong independent risk factor for mortality. Hypophosphatemia was not associated with mortality (p>0.05). Hyperphosphatemia is associated with 28-day in-hospital mortality in an unselected cohort of patients presenting in an emergency room.

Hepatic dysfunction and jaundice are traditionally viewed as late features of sepsis and portend poor outcomes. We hypothesized that changes in liver function occur early in the onset of sepsis, yet pass undetected by standard laboratory tests. In a long-term rat model of faecal peritonitis, biotransformation and hepatobiliary transport were impaired, depending on subsequent disease severity, as early as 6 h after peritoneal contamination. Phosphatidylinositol-3-kinase (PI3K) signalling was simultaneously induced at this time point. At 15 h there was hepatocellular accumulation of bilirubin, bile acids, and xenobiotics, with disturbed bile acid conjugation and drug metabolism. Cholestasis was preceded by disruption of the bile acid and organic anion transport machinery at the canalicular pole. Inhibitors of PI3K partially prevented cytokine-induced loss of villi in cultured HepG2 cells. Notably, mice lacking the PI3Kγ gene were protected against cholestasis and impaired bile acid conjugation. This was partially confirmed by an increase in plasma bile acids (e.g., chenodeoxycholic acid [CDCA] and taurodeoxycholic acid [TDCA]) observed in 48 patients on the day severe sepsis was diagnosed; unlike bilirubin (area under the receiver-operating curve: 0.59), these bile acids predicted 28-d mortality with high sensitivity and specificity (area under the receiver-operating curve: CDCA: 0.77; TDCA: 0.72; CDCA+TDCA: 0.87). Liver dysfunction is an early and commonplace event in the rat model of sepsis studied here; PI3K signalling seems to play a crucial role. All aspects of hepatic biotransformation are affected, with severity relating to subsequent prognosis. Detected changes significantly precede conventional markers and are reflected by early alterations in plasma bile acids. These observations carry important implications for the diagnosis of liver dysfunction and pharmacotherapy in the critically ill. Further clinical work is necessary to extend these concepts into clinical practice. Please see later in the article for the Editors' Summary.

Purpose Hypoxic hepatitis (HH) is a frequent cause of acute hepatocellular damage at the intensive care unit. Although mortality is reported to be high, risk factors for mortality in this population are unknown. Methods One-hundred and seventeen consecutive patients with HH were studied prospectively at three medical intensive care units of a university hospital. Results The main causes of hypoxic hepatitis were low cardiac output and septic shock, and most patients (74%) had more than one underlying factor. Peak aspartate transaminase ( P  = 0.02), lactate dehydrogenase ( P  = 0.03), INR ( P  < 0.001) and lactate ( P  < 0.01) were higher in non-survivors. Prolonged duration of HH caused higher overall mortality rate ( P  = 0.03). INR > 2 ( P  = 0.02), septic shock ( P  = 0.01) and SOFA score >10 ( P  = 0.04) were risk factors of mortality in the regression model. Conclusions Hypoxic hepatitis is the consequence of multiorgan injury. Outcome is influenced by the severity of liver impairment and the etiology and severity of the basic disease.

Background Critically ill patients in the intensive care unit (ICU) are at high risk for developing Clostridioides difficile infections (CDI). Risk factors predicting their mortality or standardized treatment recommendations have not been defined for this cohort. Our goal is to determine outcome and mortality associated risk factors for patients at the ICU with CDI by evaluating clinical characteristics and therapy regimens. Methods A retrospective single-centre cohort study. One hundred forty-four patients (0.4%) with CDI-associated diarrhoea were included (total 36.477 patients admitted to 12 ICUs from January 2010 to September 2015). Eight patients without specific antibiotic therapy were excluded, so 132 patients were analysed regarding mortality, associated risk factors and therapy regimens using univariate and multivariate regression. Results Twenty-eight-day mortality was high in patients diagnosed with CDI (27.3%) compared to non-infected ICU patients (9%). Patients with non CDI-related sepsis ( n  = 40/132; 30.3%) showed further increase in 28-day mortality (45%; p  = 0.003). Initially, most patients were treated with a single CDI-specific agent ( n  = 120/132; 90.9%), either metronidazole (orally, 35.6%; or IV, 37.1%) or vancomycin (18.2%), or with a combination of antibiotics ( n  = 12/132; 9.1%). Patients treated with metronidazole IV showed significantly longer duration of diarrhoea > 5 days ( p  = 0.006). In a multivariate regression model, metronidazole IV as initial therapy was an independent risk factor for delayed clinical cure. Immunosuppressants ( p  = 0.007) during ICU stay lead to increased 28-day mortality. Conclusion Treatment of CDI with solely metronidazole IV leads to a prolonged disease course in critically ill patients.

Background: The prone position (PP) is increasingly used in mechanically ventilated coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS) patients. However, studies investigating the influence of the PP are currently lacking in these patients. This is the first study to investigate the influence of the PP on the oxygenation and decarboxylation in COVID-19 patients. Methods: A prospective bicentric study design was used, and in mechanically ventilated COVID-19 patients, PP was indicated from a partial pressure of oxygen in arterial blood (PaO2)/fraction of inspired oxygen (FIO2) ratio of <200. Patients were left prone for 16 h each. Pressure levels, FIO2, were adjusted to ensure a PaO2 greater than 60 mmHg. Blood gas analyses were performed before (baseline 0.5 h), during (1/2/5.5/9.5/13 h), and after being in the PP (1 h), the circulatory/ventilation parameters were continuously monitored, and lung compliance (LC) was roughly calculated. Responders were defined compared to the baseline value (PaO2/FIO2 ratio increase of ≥15%; partial pressure of carbon dioxide (PaCO2) decrease of ≥2%). Results: 13 patients were included and 36 PP sessions were conducted. Overall, PaO2/FIO2 increased significantly in the PP (p < 0.001). Most PaO2/FIO2 responders (29/36 PP sessions, 77%) were identified 9.5 h after turning prone (14% slow responders), while most PaCO2 responders (15/36 PP sessions, 42%) were identified 13 h after turning prone. A subgroup of patients (interval intubation to PP ≥3 days) showed less PaO2/FIO2 responders (16% vs. 77%). An increase in PaCO2 and minute ventilation in the PP showed a significant negative correlation (p < 0.001). LC (median before the PP = 38 mL/cm H2O; two patients with LC >80 mL/cm H2O) showed a significant positive correlation with the 28 day survival of patients (p = 0.01). Conclusion: The PP significantly improves oxygenation in COVID-19 ARDS patients. The data suggest that they also benefit most from an early PP. A decrease in minute ventilation may result in fewer PaCO2 responders. LC may be a predictive outcome parameter in COVID-19 patients. Trial registration: Retrospectively registered.

Infection and sepsis are a main cause of acute-on-chronic liver failure (ACLF). Besides bacteria, molds play a role. Voriconazole (VRC) is recommended but its pharmacokinetics (PK) may be altered by ACLF. Because ACLF patients often suffer from concomitant acute renal failure, we studied the PK of VRC in patients receiving continuous renal replacement therapy (RRT) with ACLF and compared it to PK of VRC in critically ill patients with RRT without concomitant liver failure (NLF). In this prospective cohort study, patients received weight-based VRC. Pre- and post-dialysis membrane, and dialysate samples obtained at different time points were analyzed by high-performance liquid chromatography. An integrated dialysis pharmacometric model was used to model the available PK data. The recommended, 50% lower, and 50% higher doses were analyzed by Monte-Carlo simulation (MCS) for day 1 and at steady-state with a target trough concentration (TC) of 0.5–3mg/L. Fifteen patients were included in this study. Of these, 6 patients suffered from ACLF. A two-compartment model with linear clearance described VRC PK. No difference for central (V1) or peripheral (V2) volumes of distribution or clearance could be demonstrated between the groups. V1 was 80.6L (95% confidence interval: 62.6–104) and V2 106L (65–166) with a body clearance of 4.7L/h (2.87–7.81) and RRT clearance of 1.46L/h (1.29–1.64). MCS showed TC below/within/above target of 10/74/16% on day 1 and 9/39/52% at steady-state for the recommended dose. A 50% lower dose resulted in 26/72/1% (day 1) and 17/64/19% at steady-state and 7/57/37% and 7/27/67% for a 50% higher dose. VRC pharmacokinetics are not significantly influenced by ACLF in critically ill patients who receive RRT. Maintenance dose should be adjusted in both groups. Due to the high interindividual variability, therapeutic drug monitoring seems inevitable.