The Association between the rs3747406 Polymorphism in the Glucocorticoid-Induced Leucine Zipper Gene and Sepsis Survivals Depends on the SOFA Score.

The variability in mortality in sepsis could be a consequence of genetic variability. The glucocorticoid system and the intermediate TSC22D3 gene product-glucocorticoid-induced leucine zipper-are clinically relevant in sepsis, which is why this study aimed to clarify whether TSC22D3 gene polymorphisms contribute to the variance in sepsis mortality. Blood samples for DNA extraction were obtained from 455 patients with a sepsis diagnosis according to the Sepsis-III criteria and from 73 control subjects. A SNP TaqMan assay was used to detect single-nucleotide polymorphisms (SNPs) in the TSC22D3 gene. Statistical and graphical analyses were performed using the SPSS Statistics and GraphPad Prism software. C-allele carriers of rs3747406 have a 2.07-fold higher mortality rate when the sequential organ failure assessment (SOFA) score is higher than eight. In a multivariate COX regression model, the SNP rs3747406 with a SOFA score ≥ 8 was found to be an independent risk factor for 30-day survival in sepsis. The HR was calculated to be 2.12, with a p-value of 0.011. The wild-type allele was present in four out of six SNPs in our cohort. The promoter of TSC22D3 was found to be highly conserved. However, we discovered that the C-allele of rs3747406 poses a risk for sepsis mortality for SOFA Scores higher than 6.

AQP3 and AQP9-Contrary Players in Sepsis?

Sepsis involves an immunological systemic response to a microbial pathogenic insult, leading to a cascade of interconnected biochemical, cellular, and organ-organ interaction networks. Potential drug targets can depict aquaporins, as they are involved in immunological processes. In immune cells, AQP3 and AQP9 are of special interest. In this study, we tested the hypothesis that these aquaporins are expressed in the blood cells of septic patients and impact sepsis survival. Clinical data, routine laboratory parameters, and blood samples from septic patients were analyzed on day 1 and day 8 after sepsis diagnosis. AQP expression and cytokine serum concentrations were measured. AQP3 mRNA expression increased over the duration of sepsis and was correlated with lymphocyte count. High AQP3 expression was associated with increased survival. In contrast, AQP9 expression was not altered during sepsis and was correlated with neutrophil count, and low levels of AQP9 were associated with increased survival. Furthermore, AQP9 expression was an independent risk factor for sepsis lethality. In conclusion, AQP3 and AQP9 may play contrary roles in the pathophysiology of sepsis, and these results suggest that AQP9 may be a novel drug target in sepsis and, concurrently, a valuable biomarker of the disease.

The Aquaporin 3 Polymorphism (rs17553719) Is Associated with Sepsis Survival and Correlated with IL-33 Secretion.

Sepsis is a common life-threatening disease caused by dysregulated immune response and metabolic acidosis which lead to organ failure. An abnormal expression of aquaporins plays an important role in organ failure. Additionally, genetic variants in aquaporins impact on the outcome in sepsis. Thus, we investigated the polymorphism (rs17553719) and expression of aquaporin-3 (AQP3) and correlated these measurements with the survival of sepsis patients. Accordingly, we collected blood samples on several days (plus clinical data) from 265 sepsis patients who stayed in different ICUs in Germany. Serum plasma, DNA, and RNA were then separated to detect the promotor genotypes of AQP3 mRNA expression of AQP3 and several cytokines. The results showed that the homozygote CC genotype exhibited a significant decrease in 30-day survival (38.9%) compared to the CT (66.15%) and TT genotypes (76.3%) (p = 0.003). Moreover, AQP3 mRNA expression was significantly higher and nearly doubled in the CC compared to the CT (p = 0.0044) and TT genotypes (p = 0.018) on the day of study inclusion. This was accompanied by an increased IL-33 concentration in the CC genotype (day 0: p = 0.0026 and day 3: p = 0.008). In summary, the C allele of the AQP3 polymorphism (rs17553719) shows an association with increased AQP3 expression and IL-33 concentration accompanied by decreased survival in patients with sepsis.

Blood taken immediately after fatal resuscitation attempts yields higher quality DNA for genetic studies as compared to autopsy samples.

BACKGROUND: The out-of-hospital cardiac arrest (OHCA) in the young may be associated with a genetic predisposition which is relevant even for genetic counseling of relatives. The identification of genetic variants depends on the availability of intact genomic DNA. DNA from autopsy may be not available due to low autopsy frequencies or not suitable for high-throughput DNA sequencing (NGS). The emergency medical service (EMS) plays an important role to save biomaterial for subsequent molecular autopsy. It is not known whether the DNA integrity of samples collected by the EMS is better suited for NGS than autopsy specimens. MATERIAL AND METHODS: DNA integrity was analyzed by standardized protocols. Fourteen blood samples collected by the EMS and biomaterials from autopsy were compared. We collected 172 autopsy samples from different tissues and blood with postmortem intervals of 14-168 h. For comparison, DNA integrity derived from blood stored under experimental conditions was checked against autopsy blood after different time intervals. RESULTS: DNA integrity and extraction yield were higher in EMS blood compared to any autopsy tissue. DNA stability in autopsy specimens was highly variable and had unpredictable quality. In contrast, collecting blood samples by the EMS is feasible and delivered comparably the highest DNA integrity. CONCLUSIONS: Isolation yield and DNA integrity from blood samples collected by the EMS is superior in comparison to autopsy specimens. DNA from blood samples collected by the EMS on scene is stable at room temperature or even for days at 4 °C. We conclude that the EMS personnel should always save a blood sample of young fatal OHCA cases died on scene to enable subsequent genetic analysis.

Hemoadsorption with CytoSorb® and the early course of linezolid plasma concentration during septic shock.

Hemoadsorption with CytoSorb® becomes increasingly established in treatment of various, predominantly inflammation-associated diseases. In septic shock, results suggest improvements in hemodynamics and organ function. However, little is known about the in vivo adsorption properties for various antibiotics. We present the case of a 61-year-old female patient with known Ulrich Turner syndrome who treated supportively with CytoSorb® and with linezolid due to a Staphylococcus epidermidis bloodstream infection as part of her intensive care treatment for septic shock. After establishment of a new adsorber, 600 mg of linezolid administered over 1 h. Linezolid levels measured before adsorber inlet (cpre) and after adsorber outlet (cpost) at 0, 15, 60, 120 and 480 min after starting infusion. Out of the ten samples, only the cpre samples 60 min (3.25 mg/l) and 120 min (4.7 mg/l) showed sufficiently high linezolid levels (therapeutic range 3-9 mg/l). After 480 min, cpre decreased to 2.8 mg/l, cpost increased to 1.85 mg/l, and thus clearance decreased to 67.86 ml/min (from 200 ml/min at 60 min), with greatly reduced adsorption capacity of CytoSorb® after 8 h. A loading dose (additional 600 mg) would have been urgently needed. Linezolid therapy under hemadsorption with CytoSorb® requires a clear indication and close monitoring of levels to avoid underdosing.

Therapeutic Modulation of the Host Defense by Hemoadsorption with CytoSorb®-Basics, Indications and Perspectives-A Scoping Review.

The "normal" immune response to an insult triggers a highly regulated response determined by the interaction of various immunocompetent cells with pro- and anti-inflammatory cytokines. Under pathologic conditions, the massive elevation of cytokine levels ("cytokine storm") could not be controlled until the recent development of hemoadsorption devices that are able to extract a variety of different DAMPs, PAMPs, and metabolic products from the blood. CytoSorb® has been approved for adjunctive sepsis therapy since 2011. This review aims to summarize theoretical knowledge, in vitro results, and clinical findings to provide the clinician with pragmatic guidance for daily practice. English-language and peer-reviewed literature identified by a selective literature search in PubMed and published between January 2016 and May 2021 was included. Hemoadsorption can be used successfully as adjunct to a complex therapeutic regimen for various conditions. To the contrary, this nonspecific intervention may potentially worsen patient outcomes in complex immunological processes. CytoSorb® therapy appears to be safe and useful in various diseases (e.g., rhabdomyolysis, liver failure, or intoxications) as well as in septic shock or cytokine release syndrome, although a conclusive assessment of treatment benefit is not possible and no survival benefit has yet been demonstrated in randomized controlled trials.

Outcome of acute respiratory distress syndrome in university and non-university hospitals in Germany.

BACKGROUND: This study investigates differences in treatment and outcome of ventilated patients with acute respiratory distress syndrome (ARDS) between university and non-university hospitals in Germany. METHODS: This subanalysis of a prospective, observational cohort study was performed to identify independent risk factors for mortality by examining: baseline factors, ventilator settings (e.g., driving pressure), complications, and care settings-for example, case volume of ventilated patients, size/type of intensive care unit (ICU), and type of hospital (university/non-university hospital). To control for potentially confounding factors at ARDS onset and to verify differences in mortality, ARDS patients in university vs non-university hospitals were compared using additional multivariable analysis. RESULTS: Of the 7540 patients admitted to 95 ICUs from 18 university and 62 non-university hospitals in May 2004, 1028 received mechanical ventilation and 198 developed ARDS. Although the characteristics of ARDS patients were very similar, hospital mortality was considerably lower in university compared with non-university hospitals (39.3% vs 57.5%; p = 0.012). Treatment in non-university hospitals was independently associated with increased mortality (OR (95% CI): 2.89 (1.31-6.38); p = 0.008). This was confirmed by additional independent comparisons between the two patient groups when controlling for confounding factors at ARDS onset. Higher driving pressures (OR 1.10; 1 cmH2O increments) were also independently associated with higher mortality. Compared with non-university hospitals, higher positive end-expiratory pressure (PEEP) (mean ± SD: 11.7 ± 4.7 vs 9.7 ± 3.7 cmH2O; p = 0.005) and lower driving pressures (15.1 ± 4.4 vs 17.0 ± 5.0 cmH2O; p = 0.02) were applied during therapeutic ventilation in university hospitals, and ventilation lasted twice as long (median (IQR): 16 (9-29) vs 8 (3-16) days; p < 0.001). CONCLUSIONS: Mortality risk of ARDS patients was considerably higher in non-university compared with university hospitals. Differences in ventilatory care between hospitals might explain this finding and may at least partially imply regionalization of care and the export of ventilatory strategies to non-university hospitals.

End-of-life perceptions among physicians in intensive care units managed by anesthesiologists in Germany: a survey about structure, current implementation and deficits.

BACKGROUND: Structural aspects and current practice about end-of-life (EOL) decisions in German intensive care units (ICUs) managed by anesthesiologists are unknown. A survey among intensive care anesthesiologists has been conducted to explore current practice, barriers and opinions on EOL decisions in ICU. METHODS: In November 2015, all members of the German Society of Anesthesiology and Intensive Care Medicine (DGAI) and the Association of German Anesthesiologists (BDA) were asked to participate in an online survey to rate the presence or absence and the importance of 50 items. Answers were grouped into three categories considering implementation and relevance: Category 1 reflects high implementation and high relevance, Category 2 low and low, and Category 3 low and high. RESULTS: Five-hundred and forty-one anesthesiologists responded. Only four items reached ≥90% agreement as being performed "yes, always" or "mostly", and 29 items were rated "very" or "more important". A profound discrepancy between current practice and attributed importance was revealed. Twenty-eight items attributed to Category 1, six to Category 2 and sixteen to Category 3. Items characterizing the most urgent need for improvement (Category 3) referred to patient outcome data, preparation of health care directives and interdisciplinary discussion, standard operating procedures, implementation of practical instructions and inclusion of nursing staff and families in the process. CONCLUSION: The present survey affirms an urgent need for improvement in EOL practice in German ICUs focusing on advanced care planning, distinct aspects of changing goals of care, implementation of standard operating procedures, continuing education and reporting of outcome data.

Isoflurane, like sepsis, decreases CYP1A2 liver enzyme activity in intensive care patients: a clinical study and network model.

PURPOSE: Liver function of intensive care patients is routinely monitored by static blood pathology. For specific indications, liver specific cytochrome activity may be measured by the commercially available maximum liver function capacity (LiMAx) test via quantification of the cytochrome P450 1A2 (CYP1A2) dependent C-methacetin metabolism. Sedation with the volatile anesthetic isoflurane was suspected to abrogate the correlation of LiMAx test with global liver function. We hypothesized that isoflurane has a CYP1A2-activity and LiMAx test result decreasing effect. METHODS: In this monocentric, observational clinical study previously liver healthy intensive care patients, scheduled to be changed from propofol to isoflurane sedation, were enrolled. LiMAx testing was done before, during and after termination of isoflurane sedation. RESULTS: The mean LiMAx value decreased during isoflurane sedation. Septic patients (n = 11) exhibited lower LiMAx values compared to non-septic patients (n = 11) at all time points. LiMAx values decreased with isoflurane from 140 ± 82 to 30 ± 34 µg kg-1 h-1 in the septic group and from 253 ± 92 to 147 ± 131 µg kg-1 h-1 in the non-septic group while laboratory markers did not imply significant hepatic impairment. Lactate increased during isoflurane inhalation without clinical consequence. CONCLUSION: Sepsis and isoflurane have independently demonstrated an effect on reducing the hepatic CYP1A2-activity. A network model was constructed that could explain the mechanism through the influence of isoflurane on hypoxia inducible factor (HIF-1α) by upregulation of the hypoxia-inducible pathway and the downregulation of CYP1A2-activity via the ligand-inducible pathway. Thus, the increased anaerobic metabolism may result in lactate accumulation. The influence of isoflurane sedation on the validated correlation of global liver function with CYP1A2-activity measured by LiMAx testing needs to be investigated in more detail.

Assessing SOFA score trajectories in sepsis using machine learning: A pragmatic approach to improve the accuracy of mortality prediction.

INTRODUCTION: An increasing amount of longitudinal health data is available on critically ill septic patients in the age of digital medicine, including daily sequential organ failure assessment (SOFA) score measurements. Thus, the assessment in sepsis focuses increasingly on the evaluation of the individual disease's trajectory. Machine learning (ML) algorithms may provide a promising approach here to improve the evaluation of daily SOFA score dynamics. We tested whether ML algorithms can outperform the conventional ΔSOFA score regarding the accuracy of 30-day mortality prediction. METHODS: We used the multicentric SepsisDataNet.NRW study cohort that prospectively enrolled 252 sepsis patients between 03/2018 and 09/2019 for training ML algorithms, i.e. support vector machine (SVM) with polynomial kernel and artificial neural network (aNN). We used the Amsterdam UMC database covering 1,790 sepsis patients for external and independent validation. RESULTS: Both SVM (AUC 0.84; 95% CI: 0.71-0.96) and aNN (AUC 0.82; 95% CI: 0.69-0.95) assessing the SOFA scores of the first seven days led to a more accurate prognosis of 30-day mortality compared to the ΔSOFA score between day 1 and 7 (AUC 0.73; 95% CI: 0.65-0.80; p = 0.02 and p = 0.05, respectively). These differences were even more prominent the shorter the time interval considered. Using the SOFA scores of day 1 to 3 SVM (AUC 0.82; 95% CI: 0.68 0.95) and aNN (AUC 0.80; 95% CI: 0.660.93) led to a more accurate prognosis of 30-day mortality compared to the ΔSOFA score (AUC 0.66; 95% CI: 0.58-0.74; p < 0.01 and p < 0.01, respectively). Strikingly, all these findings could be confirmed in the independent external validation cohort. CONCLUSIONS: The ML-based algorithms using daily SOFA scores markedly improved the accuracy of mortality compared to the conventional ΔSOFA score. Therefore, this approach could provide a promising and automated approach to assess the individual disease trajectory in sepsis. These findings reflect the potential of incorporating ML algorithms as robust and generalizable support tools on intensive care units.

Lung-Protective Ventilation Attenuates Mechanical Injury While Hypercapnia Attenuates Biological Injury in a Rat Model of Ventilator-Associated Lung Injury.

Background and Objective: Lung-protective mechanical ventilation is known to attenuate ventilator-associated lung injury (VALI), but often at the expense of hypoventilation and hypercapnia. It remains unclear whether the main mechanism by which VALI is attenuated is a product of limiting mechanical forces to the lung during ventilation, or a direct biological effect of hypercapnia. Methods: Acute lung injury (ALI) was induced in 60 anesthetized rats by the instillation of 1.25 M HCl into the lungs via tracheostomy. Ten rats each were randomly assigned to one of six experimental groups and ventilated for 4 h with: 1) Conventional HighV E Normocapnia (high VT, high minute ventilation, normocapnia), 2) Conventional Normocapnia (high VT, normocapnia), 3) Protective Normocapnia (VT 8 ml/kg, high RR), 4) Conventional iCO 2 Hypercapnia (high VT, low RR, inhaled CO2), 5) Protective iCO 2 Hypercapnia (VT 8 ml/kg, high RR, added CO2), 6) Protective endogenous Hypercapnia (VT 8 ml/kg, low RR). Blood gasses, broncho-alveolar lavage fluid (BALF), and tissue specimens were collected and analyzed for histologic and biologic lung injury assessment. Results: Mild ALI was achieved in all groups characterized by a decreased mean PaO2/FiO2 ratio from 428 to 242 mmHg (p < 0.05), and an increased mean elastance from 2.46 to 4.32 cmH2O/L (p < 0.0001). There were no differences in gas exchange among groups. Wet-to-dry ratios and formation of hyaline membranes were significantly lower in low VT groups compared to conventional tidal volumes. Hypercapnia reduced diffuse alveolar damage and IL-6 levels in the BALF, which was also true when CO2 was added to conventional VT. In low VT groups, hypercapnia did not induce any further protective effect except increasing pulmonary IL-10 in the BALF. No differences in lung injury were observed when hypercapnia was induced by adding CO2 or decreasing minute ventilation, although permissive hypercapnia decreased the pH significantly and decreased liver histologic injury. Conclusion: Our findings suggest that low tidal volume ventilation likely attenuates VALI by limiting mechanical damage to the lung, while hypercapnia attenuates VALI by limiting pro-inflammatory and biochemical mechanisms of injury. When combined, both lung-protective ventilation and hypercapnia have the potential to exert an synergistic effect for the prevention of VALI.

Immunomodulation by Hemoadsorption-Changes in Hepatic Biotransformation Capacity in Sepsis and Septic Shock: A Prospective Study.

BACKGROUND: Sepsis is often associated with liver dysfunction, which is an indicator of poor outcomes. Specific diagnostic tools that detect hepatic dysfunction in its early stages are scarce. So far, the immune modulatory effects of hemoadsorption with CytoSorb® on liver function are unclear. METHOD: We assessed the hepatic function by using the dynamic LiMAx® test and biochemical parameters in 21 patients with sepsis or septic shock receiving CytoSorb® in a prospective, observational study. Points of measurement: T1: diagnosis of sepsis or septic shock; T2 and T3: 24 h and 48 h after the start of CytoSorb®; T4: 24 h after termination of CytoSorb®. RESULTS: The hepatic biotransformation capacity measured by LiMAx® was severely impaired in up to 95 % of patients. Despite a rapid shock reversal under CytoSorb®, a significant improvement in LiMAx® values appeared from T3 to T4. This decline and recovery of liver function were not reflected by common parameters of hepatic metabolism that remained mostly within the normal range. CONCLUSIONS: Hepatic dysfunction can effectively and safely be diagnosed with LiMAx® in ventilated ICU patients under CytoSorb®. Various static liver parameters are of limited use since they do not adequately reflect hepatic dysfunction and impaired hepatic metabolism.

Case report: Early detection of mesenteric ischemia by intravital microscopy in a patient with septic shock.

Gut ischemia is a frequent but underdiagnosed complication, especially in critically ill intensive care patients, and represents a special diagnostic challenge that can only be solved in an interdisciplinary manner. We report a case of a 54-year-old woman with acute mesenteric ischemia (AMI) as a cause of septic shock diagnosed by intravital microscopy (IVM) 2 days before visible necrotic changes in a multimodality approach. We show that intravital microscopy can be a serious alternative for the early diagnosis of mesenteric ischemia in the hands of the skilled. We use this case to discuss the value and clinical perspective of IVM in the intensive care setting.

Hemoadsorption in the critically ill-Final results of the International CytoSorb Registry.

The aim of the current paper is to summarize the results of the International CytoSorb Registry. Data were collected on patients of the intensive care unit. The primary endpoint was actual in-hospital mortality compared to the mortality predicted by APACHE II score. The main secondary endpoints were SOFA scores, inflammatory biomarkers and overall evaluation of the general condition. 1434 patients were enrolled. Indications for hemoadsorption were sepsis/septic shock (N = 936); cardiac surgery perioperatively (N = 172); cardiac surgery postoperatively (N = 67) and "other" reasons (N = 259). APACHE-II-predicted mortality was 62.0±24.8%, whereas observed hospital mortality was 50.1%. Overall SOFA scores did not change but cardiovascular and pulmonary SOFA scores decreased by 0.4 [-0.5;-0.3] and -0.2 [-0.3;-0.2] points, respectively. Serum procalcitonin and C-reactive protein levels showed significant reduction: -15.4 [-19.6;-11.17] ng/mL; -17,52 [-70;44] mg/L, respectively. In the septic cohort PCT and IL-6 also showed significant reduction: -18.2 [-23.6;-12.8] ng/mL; -2.6 [-3.0;-2.2] pg/mL, respectively. Evaluation of the overall effect: minimal improvement (22%), much improvement (22%) and very much improvement (10%), no change observed (30%) and deterioration (4%). There was no significant difference in the primary outcome of mortality, but there were improvements in cardiovascular and pulmonary SOFA scores and a reduction in PCT, CRP and IL-6 levels. Trial registration: ClinicalTrials.gov Identifier: NCT02312024 (retrospectively registered).

What on earth is APRV?

Partial ventilatory support modalities are ill defined and different perceptions about these modes might depend on geographic region. Exemplary on two recent publications investigating airway pressure release ventilation (APRV) in an adult ICU population, the question is investigated whether research in ventilation modes can be performed with the current definitions. The lack of precise definitions precludes drawing meaningful conclusions from these studies, as it remains unclear how these patients were actually ventilated and whether or how much spontaneous breathing was factitiously preserved. An argument is made to develop a new taxonomy of ventilation modes.

Physiologic and biologic characteristics of three experimental models of acute lung injury in rats.

BACKGROUND: Strategies to attenuate ventilator-associated lung injury have been tested in various experimental methods of acute lung injury (ALI). Conclusions are often drawn from physiologic and biologic effects, but the influence of the model on these results is not known. Our aim in this study was to characterize frequently used models of experimental ALI. METHODS: Twenty Sprague Dawley rats were anesthetized and their lungs mechanically ventilated for 5 hours. Three models of ALI (surfactant washout, acid aspiration, and high tidal volume ventilation) were investigated with regard to hemodynamics, respiratory mechanics, gas exchange, lung pathology, and inflammatory reactions. Animals without ALI served as controls. RESULTS: Five animals in each group were analyzed. Dynamic compliance and Pao(2)/fraction of inspired oxygen ratio decreased by at least 50% in all groups after 1 hour. Whereas compliance remained decreased in all models, oxygenation returned to baseline values in the lavage group after 5 hours. Diffuse alveolar damage was worse in the high tidal volume model and was not different between the control and lavage animals. Interleukin-6 was increased in bronchoalveolar lavage fluid in the aspiration and high tidal volume models. CONCLUSIONS: Although comparable physiologic effects meeting acute respiratory distress syndrome criteria were achieved in all models, the biologic responses varied among lung injury models. The acid aspiration model created both respiratory and inflammatory responses typically seen in ALI; these data suggest that it may be the most clinically applicable model to study the intermediate-term effects of ventilator-associated lung injury in rats.

High-dose CytoSorb hemoadsorption is associated with improved survival in patients with septic shock: A retrospective cohort study.

BACKGROUND AND PURPOSE: Hemoadsorption with CytoSorb® offers a possible therapeutic approach in septic shock, but modes of application and dosing are still undetermined. MATERIALS AND METHODS: Data from surgical patients with septic shock, treated with hemoadsorption adjunctive to renal replacement therapy were analyzed retrospectively. The 28-day mortality was compared to predicted mortality. RESULTS: In 70 patients (70.6 ± 13.3 years), hemoadsorption was applied for 85.6 ± 53.8 h. The APACHE ll (30.2 ± 6.3) calculated to a predicted mortality of 73.3%, while the observed mortality was significantly lower (50%, p < 0.05). The amount of blood purified was higher in survivors than in non-survivors (8.5 ± 4.4 vs. 6.1 ± 3.6 l/kgBW, p = 0.017). We identified three clusters of <6 l/kgBW, 6-13 l/kgBW and ≥ 13 l/kgBW with a linear dose-response relation between blood purification volume and survival, which was best in the highest volume cluster (83.3%; p = 0.045). CONCLUSIONS: The application of CytoSorb® seems to be effective in various conditions of septic shock. In a cohort of most severely ill patients the observed mortality was lower than predicted and decreased linearly with blood purification volumes inadvertently exceeding 6 l/kg BW. These results suggest that hemoadsorption might improve survival provided that the applied dose is high enough.

Profound decrease of liver maximum function capacity test of isoflurane sedated patients: A report of three cases.

LiMAx 13C-methacetin breath test results should be interpreted with caution in patients sedated with isoflurane.

Pericarditis Caused by Enterococcus faecium with Acute Liver Failure Treated by a Multifaceted Approach including Antimicrobials and Hemoadsorption.

BACKGROUND: Sepsis and septic shock are still life-threatening diseases with a high mortality rate. We report a complex case of peritonitis with pericarditis and acute liver failure caused by septic shock. Potentially hepatotoxic antibiotic therapy levels were monitored using the liver maximum capacity (LiMAx®) test, and standard treatment was supplemented by adjunctive hemoadsorption with CytoSorb®. Case Presentation. The case features a 29-year-old woman with a history of Crohn's disease and cachexia. Peritonitis caused by Enterococcus faecium was diagnosed later due to an ileum perforation. The hematogenic spread led to pericarditis. In addition, sepsis-related acute liver failure complicated antimicrobial therapy further. The combination of standard therapy, anti-infective medication, and blood purification was associated with inflammation control, hemodynamic stabilization, and a concomitant decrease in vasopressor support. An efficient, sustained reduction in plasma bilirubin levels was achieved while maintaining liver function. CONCLUSIONS: This case shows how complex infectious diseases with an atypical infectious focus resulting in septic shock can be successfully treated. A combination of antimicrobial (tigecycline and caspofungin) and long-term adjunctive hemoadsorption therapy was administered while hepatotoxic antibiotic medication was monitored by liver function testing.