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Purpose To describe the clinical characteristics and outcomes of coronavirus disease-2019 (COVID-19)-associated pulmonary thromboembolism (PTE). Materials and methods A case series of five patients, representing the clinical spectrum of COVID-19 associated PTE. Patients were admitted to four hospitals in Germany, Italy, and France. Infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was confirmed using a real-time reverse transcription polymerase chain reaction test. Results The onset of PTE varied from 2 to 4 weeks after the occurrence of the initial symptoms of SARS-CoV-2 infection and led to deterioration of the clinical picture in all cases. PTE was the primary reason for hospital admission after a 2-week period of self-isolation at home (1 patient) and hospital readmission after initial uncomplicated hospital discharge (2 patients). Three of the patients had no past history of clinically relevant risk factors for venous thromboembolism (VTE). Severe disease progression was associated with concomitant increases in IL-6, ferritin, and D-Dimer levels. The outcome from PTE was related to the extent of vascular involvement, and associated complications. Conclusion PTE is a potential life-threatening complication, which occurs frequently in patients with COVID-19. Intermediate therapeutic dose of anticoagulants and extend thromboprophylaxis are necessary after meticulous risk-benefit assessment., Highlights • Pulnonary thromboembolism (PTE) is a frequent life-threatening complication in patients with coronavirsus disease-2019 (COVID-19). • The onset of PTE varies from 2 to 4 weeks after the occurrence of the initial symptoms and may occur during home self-isolation or after hospital discharge of primarily uncomplicated hospital admission. • PTE may occur in patients without clinically relevant past history of risk factors for venous thromboembolism and in those receiving standard prophylactic anticoagulation. • Intermediate therapeutic dose of anticoagulants and extend thromboprophylaxis are necessary in these patients after meticulous risk-benefit assessment.

Background & Aims: Retention of bile acids in the blood is a hallmark of liver failure. Recent studies have shown that increased serum bile acid levels correlate with bacterial infection and increased mortality. However, the mechanisms by which circulating bile acids influence patient outcomes still are elusive. Methods: Serum bile acid profiles in 33 critically ill patients with liver failure and their effects on Takeda G-protein–coupled receptor 5 (TGR5), an immunomodulatory receptor that is highly expressed in monocytes, were analyzed using tandem mass spectrometry, novel highly sensitive TGR5 bioluminescence resonance energy transfer using nanoluciferase (NanoBRET, Promega Corp, Madison, WI) technology, and in vitro assays with human monocytes. Results: Twenty-two patients (67%) had serum bile acids that led to distinct TGR5 activation. These TGR5-activating serum bile acids severely compromised monocyte function. The release of proinflammatory cytokines (eg, tumor necrosis factor α or interleukin 6) in response to bacterial challenge was reduced significantly if monocytes were incubated with TGR5-activating serum bile acids from patients with liver failure. By contrast, serum bile acids from healthy volunteers did not influence cytokine release. Monocytes that did not express TGR5 were protected from the bile acid effects. TGR5-activating serum bile acids were a risk factor for a fatal outcome in patients with liver failure, independent of disease severity. Conclusions: Depending on their composition and quantity, serum bile acids in liver failure activate TGR5. TGR5 activation leads to monocyte dysfunction and correlates with mortality, independent of disease activity. This indicates an active role of TGR5 in liver failure. Therefore, TGR5 and bile acid metabolism might be promising targets for the treatment of immune dysfunction in liver failure.

Introduction Severe COVID-19 constitutes a form of viral sepsis. Part of the specific pathophysiological pattern of this condition is the occurrence of cardiovascular events. These include pulmonary embolism, arrhythmias and cardiomyopathy as manifestations of extra-pulmonary organ dysfunction. Hitherto, the prognostic impact of these cardiovascular events and their predisposing risk factors remains unclear. This study aims to explore this question in two cohorts of viral sepsis–COVID-19 and influenza–in order to identify new theragnostic strategies to improve the short- and long-term outcome of these two diseases. Methods and analysis In this prospective multi-centre cohort study, clinical assessment will take place during the acute and post-acute phase of sepsis and be complemented by molecular laboratory analyses. Specifically, echocardiography and cardiovascular risk factor documentation will be performed during the first two weeks after sepsis onset. Aside from routine haematological and biochemical laboratory tests, molecular phenotyping will comprise analyses of the metabolome, lipidome and immune status. The primary endpoint of this study is the difference in 3-month mortality of patients with and without septic cardiomyopathy in COVID-19 sepsis. Patients will be followed up until 6 months after onset of sepsis via telephone interviews and questionnaires. The results will be compared with a cohort of patients with influenza sepsis as well as previous cohorts of patients with bacterial sepsis and healthy controls. Ethics and dissemination Approval was obtained from the Ethics Committee of the Friedrich Schiller University Jena (2020-2052-BO). The results will be published in peer-reviewed journals and presented at appropriate conferences. Trial registration DRKS00024162.

Die neu aufgetretene Atemwegserkrankung „coronavirus disease 2019“ (COVID-19) hat Deutschland erreicht. Die Erkrankung verlauft in den meisten Fallen leicht, aber der kleinere Anteil an schwer Erkrankten wird stationar und auch intensivmedizinisch behandelt werden. Im Gegensatz zu anderen akuten Infektionskrankheiten zeigen die schweren Verlaufe eine langsame Progredienz von den ersten Symptomen bis zur lebensbedrohlichen Verschlechterung. Die Diagnosestellung erfolgt mithilfe der Polymerase-Kettenreaktion (PCR) aus Proben des Respirationstrakts. Ein schweres „acute respiratory distress syndrome“ (ARDS) ist charakteristisch fur die kritischen Verlaufe. Der Vermeidung nosokomialer Infektionen, insbesondere durch korrekte Anwendung der Schutzausrustung, und der Aufrechterhaltung des Krankenhausbetriebs kommen zentrale Bedeutung zu. Auch in der Anasthesie und Notfallmedizin ist mit erheblichen Herausforderungen zu rechnen.

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).

Intraoperative vasopressor and fluid application are common strategies against hypotension. Use of processed electroencephalographic monitoring (pEEG) may reduce vasopressor application, a known risk factor for organ dysfunction, in elective cardiac surgery patients. Randomized single-centre clinical trial at Jena University Hospital. Adult patients operated on cardiopulmonary bypass or off-pump coronary artery bypass grafting were randomised to receive anesthesia with visible or blinded pEEG using Narcotrend™. In blinded-Narcotrend (NT) depth of anesthesia was extrapolated from clinical signs, hemodynamic response and anesthetic concentration, supplemented by target indices between 37 and 64 in the visible-NT group. Intraoperative norepinephrine requirement (primary endpoint), fluid balance, extubation time, delirium occurrence and adverse events were evaluated. Patients of the intent-to-treat population (visible-NT: n = 123, blinded-NT: n = 122) had similar patient and procedural characteristics. Adjusted for type of surgery intraoperative Norepinephrine application was significantly reduced in visible-NT (n = 120, robust mean of cumulative dose 4.71 µg/kg bodyweight) compared to blinded-NT patients (n = 119, 6.14 µg/kg bodyweight) (adjusted robust mean difference 1.71 (95% CI 0.33-3.10) µg/kg bodyweight). Although reduction in patients operated on cardiopulmonary bypass was higher the interaction was not significant in post-hoc subgroup analysis. Intraoperative fluid balance was similar among both groups and strata. Extubation time was non-significantly lower in visible than in blinded-NT group. Overall postoperative delirium risk was 16.4% without differences among the groups. Adverse events-sudden movement/coughing, perspiration or hypertension-occurred more often with visible-NT, while one blinded-NT patient experienced intraoperative awareness. Titration of depth of anesthesia in elective cardiac surgery patients using pEEG allows to reduce application of norepinephrine.

The current outbreak of coronavirus disease (COVID-19) has reached Germany. The majority of people infected present with mild disease, but there are severe cases that need intensive care. Unlike other acute infectious diseases progressing to sepsis, the severe courses of COVID19 seemingly show prolonged progression from onset of first symptoms to life-threatening deterioration of (primarily) lung function. Diagnosis relies on PCR using specimens from the respiratory tract. Severe ARDS reflects the hallmark of a critical course of the disease. Preventing nosocomial infections (primarily by correct use of personal protective equipment) and maintenance of hospitals' operational capability are of utmost importance. Departments of Anaesthesia, Intensive Care and emergency medicine will envisage major challenges.Die neu aufgetretene Atemwegserkrankung „coronavirus disease 2019“ (COVID-19) hat Deutschland erreicht. Die Erkrankung verläuft in den meisten Fällen leicht, aber der kleinere Anteil an schwer Erkrankten wird stationär und auch intensivmedizinisch behandelt werden. Im Gegensatz zu anderen akuten Infektionskrankheiten zeigen die schweren Verläufe eine langsame Progredienz von den ersten Symptomen bis zur lebensbedrohlichen Verschlechterung. Die Diagnosestellung erfolgt mithilfe der Polymerase-Kettenreaktion (PCR) aus Proben des Respirationstrakts. Ein schweres „acute respiratory distress syndrome“ (ARDS) ist charakteristisch für die kritischen Verläufe. Der Vermeidung nosokomialer Infektionen, insbesondere durch korrekte Anwendung der Schutzausrüstung, und der Aufrechterhaltung des Krankenhausbetriebs kommen zentrale Bedeutung zu. Auch in der Anästhesie und Notfallmedizin ist mit erheblichen Herausforderungen zu rechnen.

Extracorporeal albumin dialysis (ECAD) represents a supplemental therapy for patients with liver failure. Most experience was gained with the molecular adsorbent recirculating system (MARS). However, the ADVanced Organ Support (ADVOS) system was recently introduced. This study aims to compare effects of MARS and ADVOS on biochemical and clinical parameters in critically ill patients with liver failure using a retrospective analysis of ECAD at Jena University Hospital. Laboratory parameters, health scoring values, and need for transfusion were recorded before and after treatment. Generalized estimating equations were used to account for repeated measurements of multiple ECAD cycles per patient. Between 2012 and 2017, n = 75 MARS and n = 58 ADVOS cycles were evaluated. Although ADVOS runs significantly longer, both devices provided comparable reduction rates of bilirubin (MARS: -48 [-80.5 to -18.5] μmol/L vs ADVOS: -35 [-87.8 to -2.0] μmol/L, P = .194), a surrogate for detoxification capacity, while urea and lactate levels were more significantly lowered by the ADVOS system. In cycles with similar treatment times, both systems provided comparable reduction rates for bilirubin, renal replacement, coagulation, and metabolic parameters. Citrate was the preferred anticoagulant in case of bleeding. Neither bleeding tendency nor fibrinogen levels or platelets were altered by the type of anticoagulation. No adverse events were reported, but two sessions (one MARS and one ADVOS) were terminated early due to filter clotting. Experience is needed in the application of ADVOS and more prospective trials comparing the detoxification capacity of ECAD devices are needed to support and enlarge the findings of the current evaluation.

IMPORTANCE: Although current guidelines suggest the use of regional citrate anticoagulation (which involves the addition of a citrate solution to the blood before the filter of the extracorporeal dialysis circuit) as first-line treatment for continuous kidney replacement therapy in critically ill patients, the evidence for this recommendation is based on few clinical trials and meta-analyses. OBJECTIVE: To determine the effect of regional citrate anticoagulation, compared with systemic heparin anticoagulation, on filter life span and mortality. DESIGN, SETTING, AND PARTICIPANTS: A parallel-group, randomized multicenter clinical trial in 26 centers across Germany was conducted between March 2016 and December 2018 (final date of follow-up, January 21, 2020). The trial was terminated early after 596 critically ill patients with severe acute kidney injury or clinical indications for initiation of kidney replacement therapy had been enrolled. INTERVENTIONS: Patients were randomized to receive either regional citrate anticoagulation (n = 300), which consisted of a target ionized calcium level of 1.0 to 1.40 mg/dL, or systemic heparin anticoagulation (n = 296), which consisted of a target activated partial thromboplastin time of 45 to 60 seconds, for continuous kidney replacement therapy. MAIN OUTCOMES AND MEASURES: Coprimary outcomes were filter life span and 90-day mortality. Secondary end points included bleeding complications and new infections. RESULTS: Among 638 patients randomized, 596 (93.4%) (mean age, 67.5 years; 183 [30.7%] women) completed the trial. In the regional citrate group vs systemic heparin group, median filter life span was 47 hours (interquartile range [IQR], 19-70 hours) vs 26 hours (IQR, 12-51 hours) (difference, 15 hours [95% CI, 11 to 20 hours]; P

Common pathophysiologic states in critically ill patients, such as systemic inflammation or shock, lead to profound alterations in liver function with a reprogramming of protein synthesis referred to as ‘acute phase response’. In parallel, a disruption of phase I and II biotransformation and bile transport is frequently observed. Complex mechanisms to regulate liver blood flow might be impaired, leading to hypoperfusion, shunting and ultimately to cell death primarily in the pericentral region. The incidence and severity of liver impairment is underestimated when exclusively traditional “static” biomarkers, such as bilirubin and serum transaminases, are used while “dynamic” tests evaluating excretory or metabolic functions, such as plasma disappearance rate of indocyanine green or methacetin breath test, are more sensitive. Nevertheless, even slight elevations of bilirubin are associated with worse outcome in critical care patients. Changes in liver function lead to unpredictable changes in pharmacokinetics and pharmacodynamics, particularly in multidrug therapy frequently initiated in the critically ill. For some drugs, such as sedatives or analgesics, careful clinical assessment might be sufficient. Whenever possible, therapeutic monitoring should be performed. Sometimes, liver function tests and scoring systems can be helpful to adapt dosage. In principal, drugs solely metabolized via phase II metabolism should be preferred as this pathway is often less impaired. In contrast, the hepatobiliary excretory machinery appears exceptionally sensitive to inflammation. Hepatotoxic drugs should be avoided whenever possible to prevent additional liver damage.

End-of-life (EOL) decision-making is stressful. We conducted a quality improvement initiative to EOL decision-making and reduce stress for clinicians and patients’ relatives. A before–after study running from 2010–2014 at four interdisciplinary intensive care units (ICU) in a German university hospital was performed. Between periods, a multifaceted intervention was implemented to improve timeliness, clinician involvement, and organisational support. Consecutive patients with severe sepsis and therapy limitations were included. Relatives were interviewed by telephone after 90 days to assess their psychological symptoms. Clinician burnout was assessed by staff surveys in each period. Participation in the pre- and postintervention period was 84/145 and 90/159 among relatives, and 174/284 and 122/297 among ICU clinicians. Staff judged intervention elements as mostly helpful, but implementation of intervention elements was heterogeneous. From pre- to postintervention, relatives’ risk of posttraumatic stress, depression and anxiety did not change (all p ≥ 0.464). Clinicians’ risk of burnout increased (29% vs. 41%, p = 0.05). Relatives were highly satisfied in both periods (median of 9 vs. 9.2 on a 1–10 scale each). Attendings involved residents and nurses more often (both p ≤ 0.018). Nurses more often had sufficient information to talk with relatives (41% vs. 62%, p = 0.002). Time to first EOL decision as well as barriers and facilitators of EOL decision-making did not change. The intervention may have increased involvement in EOL decision-making, but was accompanied by an increased risk of clinician burnout maybe due to lack of improving communication skills and organisational support. More research is needed to understand which interventions can decrease clinician burnout.

Hepatic cirrhosis is a severe chronic disease of the liver accompanied by massive changes in the physiology of the cells constituting the hepatic tissue. Success or failing of a therapeutic effort is difficult to recognize because of its late manifestation in the tissue morphology. In this study, the complex course of hepatic cirrhosis and its regression is followed in a rodent carbon tetrachloride model. Raman spectroscopy, which senses molecular vibrations and reflects the molecular composition of a sample, was applied to gain label- and destruction-free insights into the process of cirrhosis and to conclude on the hepatic disease state on the cellular level. Hematoxylin and eosin staining and immunofluorescence labeling were used to obtain complementary information. False color images derived from maps of Raman spectra by spectral unmixing revealed individual nucleus positions giving structural information. Spectral data unraveled chemical changes associated with liver damage on the cellular level. Upon carbon tetrachloride treatment, a higher lipid content and the presence of catabolic products indicated cirrhosis in tissue samples. Furthermore, 77 % of the Raman spectra recorded from treated rats were classified as diseased, whereas 96 % of the Raman spectra recorded from untreated rats were classified as healthy. Importantly, samples from rats that experienced a recovery period revealed a chemical composition highly similar to the ones from healthy rats while morphologically clear signs of tissue damage were still obvious. Eighty-three percent of their Raman spectra were classified as healthy. The vibrational fingerprint of tissue provides characteristic information that might serve as prognostic biomarker. Graphical Abstract Images of hematoxylin and eosin stained tissue slices together with an average Raman spectrum belonging to healthy and cirrhotic rat liver, respectively, visualize morphological and spectral differences between the two states of the liver.

Background The aim of our study was the identification of genetic variants associated with postoperative complications after cardiac surgery. Methods We conducted a prospective, double-blind, multicenter, randomized trial (RIPHeart). We performed a genome-wide association study (GWAS) in 1170 patients of both genders (871 males, 299 females) from the RIPHeart-Study cohort. Patients undergoing non-emergent cardiac surgery were included. Primary endpoint comprises a binary composite complication rate covering atrial fibrillation, delirium, non-fatal myocardial infarction, acute renal failure and/or any new stroke until hospital discharge with a maximum of fourteen days after surgery. Results A total of 547,644 genotyped markers were available for analysis. Following quality control and adjustment for clinical covariate, one SNP reached genome-wide significance (PHLPP2, rs78064607, p = 3.77 × 10− 8) and 139 (adjusted for all other outcomes) SNPs showed promising association with p

PURPOSE: It is unknown how sepsis survivors conceptualize health-related quality of life (HRQL). We aimed to identify important HRQL domains for this population. METHODS: A literature search was performed to inform an interview guide. Open-ended interviews were held with 15 purposefully sampled sepsis survivors. Interview transcripts were analyzed by interpretative phenomenological analysis to allow themes to develop organically. Resulting codes were reviewed by an independent expert. The preliminary list of domains was rated in a two-round Delphi consensus procedure with therapists and survivors. RESULTS: Eleven domains emerged as critically important: Psychological impairment, Fatigue, Physical impairment, Coping with daily life, Return to normal living, Ability to walk, Cognitive impairment, Self-perception, Control over one’s life, Family support and Delivery of health care. Sepsis survivors want a “normal life”, to walk again, to regain control without cognitive impairment. Family support is essential to overcome sepsis aftermaths. CONCLUSIONS: Survivors described many HRQL domains which are not captured by the QoL instruments that have traditionally been used to study ICU survivorship (i.e. SF-36 and EQ-5D). Future studies of QoL in ICU survivors should consider using both a traditional instrument so that results are comparable to previous research, as well as a more holistic QoL measurement instrument like the WHOQOL-BREF.

Simultaneous assessment of excretory liver and kidney function is still an unmet need in experimental stress models as well as in critical care. The aim of the study was to characterize two polymethine-dyes potentially suitable for this purpose in vivo. Plasma disappearance rate and elimination measurements of simultaneously injected fluorescent dyes DY-780 (hepato-biliary elimination) and DY-654(renal elimination) were conducted using catheter techniques and intravital microscopy in animals subjected to different organ injuries, i.e. polymicrobial sepsis by peritoneal contamination and infection, ischemia-reperfusion-injury and glycerol-induced acute kidney-injury. DY-780 and DY-654 showed organ specific and determined elimination routes in both healthy and diseased animals. They can be measured simultaneously using near-infrared imaging and spectrophotometry. Plasma-disappearance rates of DY-780 and DY-654 are superior to conventional biomarkers in indicating hepatic or kidney dysfunction in different animal models. Greatest impact on liver function was found in animals with polymicrobial sepsis whereas glomerular damage due to glycerol-induced kidney-injury had strongest impact on DY-654 elimination. We therefore conclude that hepatic elimination and renal filtration can be assessed in rodents measuring plasma-disappearance rates of both dyes. Further, assessment of organ dysfunction by polymethine dyes correlates with, but outperforms conventional biomarkers regarding sensitivity and the option of spatial resolution if biophotonic strategies are applied. Polymethine-dye clearance thereby allows sensitive point-of-care assessment of both organ functions simultaneously.

Background Taurolidine has been used for peritonitis, oncological and catheter-lock treatment because of its anti-inflammatory properties. It has been suggested that taurolidine has no severe side-effects, but after long-term use morphological and functional changes of the liver were reported. The aim of this study was to investigate the effect of short-term use of taurolidine on the liver. Methods In HepaRG cell cultures and on a novel liver biochip dose-dependent effects of taurolidine treatment on hepatocyte adherence and cell viability was investigated. Furthermore, liver enzymes and interleukin- (IL-) 6 were measured in supernatants. Male rats were treated with low- or high-dose taurolidine, respectively, and compared to controls with physiological saline solution administration regarding blood serum parameters and histology. Results In HepaRG cell cultures, hepatocyte adherence was significantly decreased, cell death and cleaved caspase-3 were significantly increased after administration of taurolidine in a dose-dependent manner. High-dose application of taurolidine led to elevated liver enzymes and IL-6 secretion in hepatic organoid. After 24 h a significant increase of serum GLDH and ASAT was observed in rats treated with high-dose taurolidine treatment. Conclusions Our results suggest that taurolidine caused liver injury after short-term use in in vitro and in vivo models probably due to direct toxic effects on hepatocytes. Therefore, the taurolidine dose should be titrated in further investigations regarding liver injury and inflammation. Electronic supplementary material The online version of this article (doi:10.1186/s40360-017-0168-z) contains supplementary material, which is available to authorized users.

Infective endocarditis (IE) is often associated with multiorgan dysfunction and mortality. The impact of perioperative liver dysfunction (LD) on outcome remains unclear and little is known about factors leading to postoperative LD. We performed a retrospective, single-center analysis on 285 patients with left-sided IE without pre-existing chronic liver disease referred to our center between 2007 and 2013 for valve surgery. Sequential organ failure assessment (SOFA) score was used to evaluate organ dysfunction. Chi-square, Cox regression, and multivariate analyses were used for evaluation. Preoperative LD (Bilirubin >20 μmol/L) was present in 68 of 285 patients. New, postoperative LD occurred in 54 patients. Hypoxic hepatitis presented the most common origin of LD, accompanied with high short-term mortality. In-hospital mortality was higher in patients with preoperative and postoperative LD compared to patients without LD (51.5, 24.1, and 10.4%, respectively, p

Background Little is known about the incidence of severe critical events in children undergoing general anaesthesia in Europe. We aimed to identify the incidence, nature, and outcome of severe critical events in children undergoing anaesthesia, and the associated potential risk factors. Methods The APRICOT study was a prospective observational multicentre cohort study of children from birth to 15 years of age undergoing elective or urgent anaesthesia for diagnostic or surgical procedures. Children were eligible for inclusion during a 2-week period determined prospectively by each centre. There were 261 participating centres across 33 European countries. The primary endpoint was the occurence of perioperative severe critical events requiring immediate intervention. A severe critical event was defined as the occurrence of respiratory, cardiac, allergic, or neurological complications requiring immediate intervention and that led (or could have led) to major disability or death. This study is registered with ClinicalTrials.gov, number NCT01878760. Findings Between April 1, 2014, and Jan 31, 2015, 31 127 anaesthetic procedures in 30 874 children with a mean age of 6·35 years (SD 4·50) were included. The incidence of perioperative severe critical events was 5·2% (95% CI 5·0–5·5) with an incidence of respiratory critical events of 3·1% (2·9–3·3). Cardiovascular instability occurred in 1·9% (1·7–2·1), with an immediate poor outcome in 5·4% (3·7–7·5) of these cases. The all-cause 30-day in-hospital mortality rate was 10 in 10 000. This was independent of type of anaesthesia. Age (relative risk 0·88, 95% CI 0·86–0·90; p

In der Allgemein- und Viszeralchirurgie reicht die Bandbreite der Operationen von kleineren Eingriffen mit geringem perioperativen Risiko, wie bei Leistenhernien-Operationen, bis hin zu sehr grosen Operationen mit hohem perioperativen Risiko wie bei der thorakoabdominellen Osophagusresektion. Der zunehmende Anteil alterer Patienten mit erheblicher Komorbiditat und groser Operation stellt eine besondere perioperative Herausforderung dar. Eingriffe mit dringlicher oder Notfallindikation konnen das perioperative Risiko zusatzlich erhohen. Diese Aspekte werden in diesem Kapitel erortert.

Kidney injury with concomitant hemodialysis is a common finding in perioperative care of liver transplant patients. The aim of this study was to evaluate disturbances in acid-base status, electrolyte balance and citrate accumulation during hemodialysis with regional citrate anticoagulation in perioperative care of liver transplant recipients. A retrospective, single center evaluation was conducted of patients with severe liver dysfunction receiving renal replacement therapy in the perioperative care of liver transplantation in a multidisciplinary ICU of a university hospital. Within 5 days of ICU stay, 89 patients undergoing liver transplantation received regional citrate anticoagulation for hemodialysis. During the study period pH (7.39 [7.33/7.43] vs. 7.44 [7.39/7.47], P-value = 0.014), base excess values (−0.9 [−5.08/2.35] vs. 4.3 [1.93/8.21], P-value = 0.001) and standard bicarbonate (23.6 [20/26.9] vs. 28.2 [26.2/32.2], P-value = 0.001) significantly increased, whereas lactate levels (2.6 [1.60/4.45] vs. 1.25 [0.98/1.9], P-value = 0.071) and Catot/Caion-ratio decreased or remained below the upper reference. Hypocalcemia appeared mostly within 48 h after dialysis initiation. Although sodium levels increased during the observation, rates of hypernatremia were comparable between hemodialysis days 1 and 5. Hemodialysis using regional citrate anticoagulation remains a challenge in the perioperative care of liver transplant recipients. Major attention must be paid to acid-base disturbances and citrate accumulation within 48 h after dialysis initiation. Nevertheless, regional citrate anticoagulation in liver dysfunction is a feasible and valuable tool, when limitations and pitfalls are adequately considered.

Eine hepatische Dysfunktion stellt den Intensivmediziner vor diagnostische und therapeutische Herausforderungen. Neben einem Leberversagen sui generis kommen u. a. die hypoxische Hepatitis, eine Sepsis oder die (sekundar-)sklerosierende Cholangitis als auslosendes Agens einer Leberdysfunktion bei chirurgischen Patienten in Betracht. Nicht selten munden diese Krankheitsentitaten in ein Multiorganversagen und sind somit fur den Patienten pro-gnoselimitierend. Als diagnostische Hilfsmittel stehen dem Intensivmediziner neben den „statischen“ auch „dynamische“ Leberfunktionsparameter zur Verfugung, um eine hepatische Dysfunktion erkennen und rechtzeitig behandeln zu konnen. Ziel des vorliegenden Beitrags ist es, Aspekte des Leberfunktionsmonitorings darzustellen und einen klinischen Leitfaden zur Diagnostik haufiger Leberfunktionsstorungen auf der Intensivstation zu vermitteln.

Purpose The purposes of this study were to calculate attributable costs of candidemia in patients with severe sepsis and to obtain preliminary data regarding the potential effects of polymerase chain reaction–based pathogen detection on antifungal therapy for these patients. Methods Patients treated between 2004 and 2010 because of severe sepsis were included into this retrospective analysis. The hospital management provided annual fixed costs per patient-day; data for variable intensive care unit costs were taken from the literature. Multiplex polymerase chain reaction (PCR) was used (VYOO®, SIRS-Lab, Jena, Germany) for pathogen detection in the blood. Results Thirty-two patients with candidemia were identified. Of 874 patients with sepsis, propensity score matching found 32 corresponding patients with sepsis but without candida infection but similar risk factors for developing candidemia. Attributable costs of candidemia were 7713.79 Euro (cost increase, 19.4%). Initiation of antifungal therapy was reduced from 67.5 (52.4, 90) hours in the group, where candida infection was determined by blood culture, to 31.0 (28.0, 37.5; P Conclusions Candidemia increases costs of care in patients with septic shock. Polymerase chain reaction–based pathogen detection significantly reduces the time to initiation of antifungal therapy. This might impact on the clinical course of the disease but need to be confirmed in further trials.

During infection, the human pathogenic fungus Candida albicans undergoes a yeast-to-hypha transition, secretes numerous proteins for invasion of host tissues, and modulates the host's immune response. Little is known about the interplay of C. albicans secreted proteins and the host adaptive immune system. Here, we applied a combined 2D gel- and LC-MS/MS-based approach for the characterization of C. albicans extracellular proteins during the yeast-to-hypha transition, which led to a comprehensive C. albicans secretome map. The serological responses to C. albicans extracellular proteins were investigated by a 2D-immunoblotting approach combined with MS for protein identification. On the basis of the screening of sera from candidemia and three groups of noncandidemia patients, a core set of 19 immunodominant antibodies against secreted proteins of C. albicans was identified, seven of which represent potential diagnostic markers for candidemia (Xog1, Lip4, Asc1, Met6, Tsa1, Tpi1, and Prx1). Intriguingly, some secreted, strongly glycosylated protein antigens showed high cross-reactivity with sera from noncandidemia control groups. Enzymatic deglycosylation of proteins secreted from hyphae significantly impaired sera antibody recognition. Furthermore, deglycosylation of the recombinantly produced, secreted aspartyl protease Sap6 confirmed a significant contribution of glycan epitopes to the recognition of Sap6 by antibodies in patient's sera.

Development of a dysregulated immune response discriminates sepsis from uncomplicated infection. Currently used biomarkers fail to describe simultaneously occurring pro- and anti-inflammatory responses potentially amenable to therapy. Marker candidates were screened by microarray and, after transfer to a platform allowing point-of-care testing, validated in a confirmation set of 246 medical and surgical patients. We identified up-regulated pathways reflecting innate effector mechanisms, while down-regulated pathways related to adaptive lymphocyte functions. A panel of markers composed of three up- (Toll-like receptor 5; Protectin; Clusterin) and 4 down-regulated transcripts (Fibrinogen-like 2; Interleukin-7 receptor; Major histocompatibility complex class II, DP alpha1; Carboxypeptidase, vitellogenic-like) described the magnitude of immune alterations. The created gene expression score was significantly greater in patients with definite as well as with possible/probable infection than with no infection (median (Q25/Q75): 80 (60/101)) and 81 (58/97 vs. 49 (27/66), AUC-ROC = 0.812 (95%-CI 0.755–0.869), p, Highlights • Pro- and anti-inflammatory signaling occurs simultaneously in the host response to infection. • This response is currently monitored using biomarkers restricted to the pro-inflammatory component of innate immunity. • We developed a biomarker panel consisting of 7 transcripts that can assess both facets at the point of care. The concept that a selective, overwhelming systemic inflammation, the “Systemic Inflammatory Response Syndrome (SIRS)”, triggers organ failure subsequent to infection has lately been abandoned as it neglects parallel occurring anti-inflammatory responses or defects in the adaptive immune system. The present findings suggest that a compound panel of nucleic acid biomarkers that was developed in independent training and verification cohorts and transferred to a point-of-care platform can more comprehensively describe the host response. Quantification of an enhanced innate immunity might inform studies of anti-inflammatory therapies, while measurement of derangements in specific immunity might guide strategies to restore immune effector functions.

The liver with its parenchymal and non-parenchymal cells plays a key role in the organism with manifold functions of metabolism, synthesis, detoxification, excretion, and host response. This requires a portfolio of different tests to obtain an overview of hepatic function. In the critically ill hepatic dysfunction is common and potentially leading to extrahepatic organ dysfunctions culminating in multi-organ failure. Conventional laboratory measures are used to evaluate hepatocellular damage, cholestasis, or synthesis. They provide valuable (differential) diagnostic data and can yield prognostic information in chronic liver diseases, especially when used in scoring systems such as the ‘model for end-stage liver disease’. However, they have short-comings in the critically ill in assessing rapid changes in hepatic function and liver blood flow. In contrast, dynamic quantitative liver function tests measure current liver function with respect to the ability to eliminate and/or metabolize a specific substance. In addition, they are dependent on sinusoidal blood flow. Liver function tests have prognostic significance in the critically ill and may be used to guide therapy.

Impaired hepatic function is a common event in intensive care unit patients and as the liver plays a central role in drug metabolism and excretion this may lead to profound changes in pharmacokinetics. Underlying mechanisms are altered enzyme function of phase I and phase II metabolism, altered transporter protein function together with cholestasis and hepatic perfusion disorders. Moreover, multidrug therapy may lead to induction and inhibition of these enzymes and transporter proteins. In addition, changes in plasma protein binding and volumes of distribution of drugs are common. Altogether, these changes may not only lead to sometimes unpredictable plasma levels of xenobiotics, but also to drug-induced liver injury when hepatocellular accumulation of noxious substances occurs. Concomitant renal dysfunction may further complicate this situation. Pharmacodynamic alterations might also occur. In conclusion, the clinician must carefully evaluate medication given to patients with hepatic failure. Therapeutic drug monitoring should be performed wherever available to guide therapy.

Background Many of the concepts describing molecular mechanisms of sepsis-induced liver failure are derived from endotoxin models. However, the biological significance of such models is questionable as the complexity of clinical sepsis and associated organ failure is only partially replicated. Aims Comparison of cytokine response, leucocyte recruitment, oxidative stress and markers of hepatic organ dysfunction in rat models of endotoxaemia or peritoneal contamination and infection (PCI). Methods Endotoxemia and polymicrobial sepsis were induced in rats by intraperitoneal injection of lipopolysaccharide (LPS) or stool suspension, respectively. Results Both insults produced clinical and laboratory signs of multiple organ dysfunction, including hepatic excretory dysfunction. However, TNF alpha, oxidative stress responses and the degree of cell death were significantly higher in endotoxaemia compared to PCI (e.g. serum TNF levels (pg/ml) at 1.5 h post-insult: sham 5 ± 1.4, LPS 1 mg/kg bw 2176.92 ± 373.78, sepsis below detection limit; P P

Purpose The purpose of this study was to investigate possible differences in characteristics and mortality rates between early- and late-onset severe sepsis in surgical intensive care unit (ICU) patients. Materials and Methods Prospectively collected data from all adult patients (>18 years) admitted to our 50-bed surgical ICU between 1st March 2004 and 30th July 2006 were analyzed retrospectively. Results Of 5925 patients admitted during the study period, 234 patients (3.9%) had severe sepsis: 74 (31.6%) early onset and 160 (68.4%) late onset. Respiratory infections (48.1 versus 27.0%, P = .002) and infections of unknown origin (21.9 versus 12.2%, P = .005) were recorded more frequently in patients with late-onset than in those with early-onset severe sepsis; abdominal infections were more frequent in early-onset than in late-onset severe sepsis (20.3% versus 7.5%, P = .005). Gram-positive infections were more frequent in late-onset than in early-onset severe sepsis (63.1 versus 51.4%, P = .036). The time of onset of severe sepsis was not independently associated with an increased risk of ICU (early versus late: odds ratio, 1.1; confidence interval, 0.78-0.59; P = .786) or in-hospital (early versus late: odds ratio, 0.68; 95% confidence interval, 0.36-1.29; P = .689) death. Conclusions Patterns of infection are different in patients with early-onset and those with late-onset severe sepsis. The time of onset of severe sepsis in surgical ICU patients has no impact on mortality. These data may be important in risk stratification and may be useful in resource allocation in the ICU.

To characterize incidence of low, normal and “supranormal” central venous oxygen saturation (ScvO2) and the relation to markers of tissue hypoxia, course and outcome in cardiac surgery patients. Prospective, observational study in a university multidisciplinary 50-bed intensive care unit including 205 consecutive patients undergoing elective cardiac surgery. Data were split into training and test data sets and subjected to 50 replications of fivefold cross-validation to estimate lower and upper bounds of ScvO2 indicative of impaired tissue oxygenation. Both low (≤60.8%) and supranormal (≥77.4%) ScvO2 were associated with an unfavorable course, while the logistic EuroSCORE for risk adjustment was comparable between groups. Incidences of abnormal ScvO2 were 13.2% low and 30.7% supranormal. Patients with low ScvO2 and an uneventful course initially presented with normal lactate levels, whereas patients with supranormal ScvO2 displayed consistently higher serum lactate levels. High ScvO2 values were associated with the use of β-mimetics and signs of systemic inflammation. Mortality rates were comparable for patient populations presenting either low (14.8%) or supranormal ScvO2 (7.9%) and higher than normals (0%, p

Background: Infective endocarditis (IE) is a dangerous disease with high mortality (20-40%). A leading cause of death is multi-organ failure (MODS) with liver dysfunction (LD) as major contributor. Data on LD in IE patients are scarce. We assessed the impact of preoperative - and newly occurring LD on in-hospital mortality and long-term survival in IE patients. Methods: We retrospectively reviewed our database for surgery of left-sided endocarditis between 1/07 and 4/13. We used the hepatic Sepsis-related Organ Failure Assessment (hSOFA) score to assess the degree of LD. We performed Chi-Square, Cox regression and multivariate analyses. Results: The 308 patients had a mean age of 62 ±13.9. Preoperative LD (hSOFA > 0, Bilirubin > 32 μmol/L) was present in 1/4 (n=81) of patients and was associated with severely elevated in-hospital mortality (51.9% vs.14.6% without preoperative LD, p

BACKGROUND: Remote ischemic preconditioning (RIPC) is reported to reduce biomarkers of ischemic and reperfusion injury in patients undergoing cardiac surgery, but uncertainty about clinical outcomes remains. METHODS: We conducted a prospective, double-blind, multicenter, randomized, controlled trial involving adults who were scheduled for elective cardiac surgery requiring cardiopulmonary bypass under total anesthesia with intravenous propofol. The trial compared upper-limb RIPC with a sham intervention. The primary end point was a composite of death, myocardial infarction, stroke, or acute renal failure up to the time of hospital discharge. Secondary end points included the occurrence of any individual component of the primary end point by day 90. RESULTS: A total of 1403 patients underwent randomization. The full analysis set comprised 1385 patients (692 in the RIPC group and 693 in the sham-RIPC group). There was no significant between-group difference in the rate of the composite primary end point (99 patients [14.3%] in the RIPC group and 101 [14.6%] in the sham-RIPC group, P=0.89) or of any of the individual components: death (9 patients [1.3%] and 4 [0.6%], respectively; P=0.21), myocardial infarction (47 [6.8%] and 63 [9.1%], P=0.12), stroke (14 [2.0%] and 15 [2.2%], P=0.79), and acute renal failure (42 [6.1%] and 35 [5.1%], P=0.45). The results were similar in the per-protocol analysis. No treatment effect was found in any subgroup analysis. No significant differences between the RIPC group and the sham-RIPC group were seen in the level of troponin release, the duration of mechanical ventilation, the length of stay in the intensive care unit or the hospital, new onset of atrial fibrillation, and the incidence of postoperative delirium. No RIPC-related adverse events were observed. CONCLUSIONS: Upper-limb RIPC performed while patients were under propofol-induced anesthesia did not show a relevant benefit among patients undergoing elective cardiac surgery. (Funded by the German Research Foundation; RIPHeart ClinicalTrials.gov number, NCT01067703.). peerReviewed

Sepsis is characterized by disrupted inflammatory homeostasis due to infection. While a localized and controlled inflammatory reaction helps to eliminate and control infection, a dysregulated host response triggers multiple organ failure determining course and prognosis. Consequent surgical source control paralleled by adequate and early antibiotic therapy remains the cornerstone of care. Nevertheless, mortality remains as high as 50–60% for severe sepsis and septic shock. As the molecular mechanisms are becoming increasingly better defined, interventions aiming to interfere with the host response to infection have been undertaken, largely with disappointing results. Thus, many evidence-based recommendations suggest waiving of resource-consuming interventions, such as supplementation of antithrombin or immunoglobulins. Nevertheless, several seminal studies have indicated that meticulous supportive care according to pathophysiological principles, most notably early goal-directed therapy, low-dose hydrocortisone and activated protein C, can disrupt dysfunctional cascades favorably influencing the course of the disease. In parallel, there is increasing evidence from national and international surveys that therapy of severe sepsis on ICUs worldwide is generally in poor compliance with current guidelines, while personal perception of the physicians in charge would suggest high rates of adherence to evidence-based recommendations. Thus, strategies of change management, such as implementation of ‘sepsis bundles’, are warranted to achieve better standards of care toward the aim of the “surviving sepsis campaign”, i.e. a reduction of mortality rates by 25% within the next years.

Kidney injury with concomitant hemodialysis is a common finding in perioperative care of liver transplant patients. The aim of this study was to evaluate disturbances in acid-base status, electrolyte balance and citrate accumulation during hemodialysis with regional citrate anticoagulation in perioperative care of liver transplant recipients. A retrospective, single center evaluation was conducted of patients with severe liver dysfunction receiving renal replacement therapy in the perioperative care of liver transplantation in a multidisciplinary ICU of a university hospital. Within 5 days of ICU stay, 89 patients undergoing liver transplantation received regional citrate anticoagulation for hemodialysis. During the study period pH (7.39 [7.33/7.43] vs. 7.44 [7.39/7.47], P-value = 0.014), base excess values (-0.9 [-5.08/2.35] vs. 4.3 [1.93/8.21], P-value = 0.001) and standard bicarbonate (23.6 [20/26.9] vs. 28.2 [26.2/32.2], P-value = 0.001) significantly increased, whereas lactate levels (2.6 [1.60/4.45] vs. 1.25 [0.98/1.9], P-value = 0.071) and Catot /Caion -ratio decreased or remained below the upper reference. Hypocalcemia appeared mostly within 48 h after dialysis initiation. Although sodium levels increased during the observation, rates of hypernatremia were comparable between hemodialysis days 1 and 5. Hemodialysis using regional citrate anticoagulation remains a challenge in the perioperative care of liver transplant recipients. Major attention must be paid to acid-base disturbances and citrate accumulation within 48 h after dialysis initiation. Nevertheless, regional citrate anticoagulation in liver dysfunction is a feasible and valuable tool, when limitations and pitfalls are adequately considered.

Hepatic stellate cells (HSCs) surround liver sinusoids and store retinol while they are quiescent. During fibrotic liver diseases and acute-on-chronic liver failure they change to the activated state in which they proliferate, lose their retinol content and deposit extracellular matrix molecules. The process of HSC activation is of utmost interest, but so far only insufficiently understood, because there is a lack of techniques to address the function of single HSCs in the tissue context. In this contribution, the potential of Raman micro-spectroscopy for the label-free detection of HSCs in mouse liver samples is demonstrated. First, culture-induced activation of primary mouse HSCs is followed in vitro and characterized by means of Raman spectroscopy. The HSC activation state is confirmed by immunofluorescence labeling of glial fibrillary acidic protein (GFAP) and α-smooth muscle actin (ASMA). As expected, the unique Raman spectrum of retinol in quiescent HSCs is lost during activation. Nevertheless, successful discrimination of HSCs from primary hepatocytes is possible during all states of activation. A classification model based on principal component analysis followed by linear discriminant analysis (PCA–LDA) of the lipid droplet Raman data yields a prediction accuracy of 99%. The in vitro results are transferred to fresh liver slices and freshly sampled livers. Quiescent HSCs and a HSC transforming from quiescent to activated state are identified based on their Raman signature. This provides valuable information on HSC activation state in the liver.

Renal failure is a common complication among critically ill patients. Timing, dosage, and mode of renal replacement (RRT) are under debate, but also anticoagulation strategies and vascular access interfere with dialysis success. We present a retrospective, five-year evaluation of patients requiring RRT on a multidisciplinary 50-bed surgical intensive care unit of a university hospital with special regard to anticoagulation strategies and vascular access. Anticoagulation was preferably performed with unfractionated heparin or regional citrate application (RAC). Bleeding and suspected HIT-II were most common causes for RAC. In CVVHD mode filter life span was significantly longer under RAC compared to heparin or other anticoagulation strategies (P=0.001). Femoral vascular access was associated with reduced filter life span (P=0.012), especially under heparin anticoagulation (P=0.015). Patients on RAC had higher rates of metabolic alkalosis (P=0.001), required more transfusions (P=0.045), and showed higher illness severity measured by SOFA scores (P=0.001). RRT with unfractionated heparin represented the most common anticoagulation strategy in this study population. However, patients with bleeding risk and severe organ dysfunction were more likely placed on RAC. Citrate provided longer filter life spans regardless of vascular access site. Attention has to be paid to metabolic disturbances.

Eine 50-jahrige Patientin wird nach einem Sturz aus 8 m Hohe in den Schockraum gebracht. Sie war am Unfallort hypoton (Blutdruck 90/50 mmHg), tachykard (130/min), der GCS betrug 12 Punkte. Sie wurde vom Notarzt intubiert und beatmet und hat bei einem Pneumothorax eine Thoraxdrainage erhalten. Die Patientin wird wahrend der Ubergabe reanimationspflichtig. Unter forcierter Volumentherapie, u. a. mit 250 ml HyperHAES und mehreren ungekreuzten Erythrozytenkonzentraten der Blutgruppe Null Rhesus negativ, kann der Kreislauf wiederhergestellt werden. Im Spiral-CT zeigt sich folgendes Verletzungsmuster: kleine traumatische Subarachnoidalblutung, Thoraxtrauma mit Rippenserienfraktur, Pneumothorax und erheblichen Lungenkontusionen, Leberruptur, Lendenwirbelkorperfraktur sowie komplexe Beckenringfraktur. Die Patientin wird direkt operativ versorgt; das Becken wird stabilisiert und bei erheblicher Blutung mit Bauchtuchern gepackt; ebenfalls erfolgt ein Packing im Bereich der Leber. Bis zu diesem Zeitpunkt hat die Patientin 12 EK, 400 ml maschinelles Autotransfusionsblut, 10 FFP, 2 TK, 5 g Fibrinogen sowie 2 g Tranexamsaure erhalten und wird auf die Intensivstation gebracht. Trotz kontinuierlicher Volumentherapie ist die Patientin hoch katecholaminpflichtig; es besteht eine ausgepragte metabolische Azidose (pH-Wert < 7,1) und Hyperlaktatamie, sodass eine Pufferung mit Natriumbikarbonat und TRIS-Puffer erfolgt. Innerhalb einer weiteren Stunde werden weitere 10 EK, 10 FFP und 4 TK sowie 8 g Fibrinogen gegeben. Bei zunehmender Oxygenierungsstorung (paO70 mmHg bei FiO0,8) wird sie in ein Bett zur kontinuierlichen lateralen Rotationstherapie gelagert.

BACKGROUND: Monitoring hepatic blood flow and function might be crucial in treating critically ill patients. Intra-abdominal hypertension is associated with decreased abdominal blood flow, organ dysfunction, and increased mortality. The plasma disappearance rate (PDR) of indocyanine green (ICG) is considered to be a compound marker for hepatosplanchnic perfusion and hepatocellular membrane transport and correlates well with survival in critically ill patients. However, correlation between PDRICG and intra-abdominal pressure (IAP) remains poorly understood. The aim of this retrospective study was to investigate the correlation between PDRICG and classic liver laboratory parameters, IAP and abdominal perfusion pressure (APP). The secondary goal was to evaluate IAP, APP, and PDRICG as prognostic factors for mortality. METHODS: A total of 182 paired IAP and PDRICG measurements were performed in 40 critically ill patients. The mean values per patient were used for comparison. The IAP was measured using either a balloon-tipped stomach catheter connected to an IAP monitor (Spiegelberg, Hamburg, Germany, or CiMON, Pulsion Medical Systems, Munich, Germany) or a bladder FoleyManometer (Holtech Medical, Charlottenlund, Denmark). PDRICG was measured at the bedside using the LiMON device (Pulsion Medical Systems, Munich, Germany). Primary endpoint was hospital mortality. RESULTS: There was no significant correlation between PDRICG and classic liver laboratory parameters, but PDRICG did correlate significantly with APP (R = 0.62) and was inversely correlated with IAP (R = -0.52). Changes in PDRICG were associated with significant concomitant changes in APP (R = 0.73) and opposite changes in IAP (R = 0.61). The IAP was significantly higher (14.6 ± 4.6 vs. 11.1 ± 5.3 mmHg, p = 0.03), and PDRICG (10 ± 8.3 vs. 15.9 ± 5.2%, p = 0.02) and APP (43.6 ± 9 vs. 57.9 ± 12.2 mmHg, p < 0.0001) were significantly lower in non-survivors. CONCLUSIONS: PDRICG is positively correlated to APP and inversely correlated to IAP. Changes in APP areassociated with significant concomitant changes in PDRICG, while changes in IAP are associated with opposite changes in PDRICG, suggesting that an increase in IAP may compromise hepatosplanchnic perfusion. Both PDRICG and IAP are correlated with outcome. Measurement of PDRICG may be a useful additional clinical tool to assess the negative effects of increased IAP on liver perfusion and function.

BACKGROUND: Treatment of septic shock relies on appropriate antimicrobial therapy. Current culture based methods deliver final results after days, which may delay potentially lifesaving adjustments in antimicrobial therapy. This study was undertaken to compare PCR with blood culture results under routine conditions regarding 1. impact on antimicrobial therapy, and 2. time to result, in patients with presumed sepsis. METHODOLOGY/PRINCIPAL FINDINGS: This was an observational study in a 50 beds ICU of a university hospital. In 245 patients with suspected sepsis, 311 concomitant blood cultures and blood for multiplex PCR (VYOO(®)) were obtained. 45 of 311 blood cultures (14.5%) and 94 of 311 PCRs (30.1%) were positive. However, blood culture or microbiological sampling from the presumed site of infection rarely confirmed PCR results and vice versa. Median time to positivity and interquartile range were 24.2 (18.0, 27.5) hours for the PCR and 68 (52.2, 88.5) hours for BC (p

The liver comprises a multitude of parenchymal and nonparenchymal cells with diverse metabolic, hemodynamic and immune functions. Available monitoring options consist of 'static' laboratory parameters, quantitative tests of liver function based on clearance, elimination or metabolite formation and scores, most notably the 'model for end-stage liver disease'. This review aims at balancing conventional markers against 'dynamic' tests in the critically ill.There is emerging evidence that conventional laboratory markers, most notably bilirubin, and the composite model for end-stage liver disease are superior to assess cirrhosis and their acute decompensation, while dynamic tests provide information in the absence of preexisting liver disease. Bilirubin and plasma disappearance rate of indocyanine green reflecting static and dynamic indicators of excretory dysfunction prognosticate unfavorable outcome, both, in the absence and presence of chronic liver disease better than other functions or indicators of injury. Although dye excretion is superior to conventional static parameters in the critically ill, it still underestimates impaired canalicular transport, an increasingly recognized facet of excretory dysfunction.Progress has been made in the last year to weigh static and dynamic tests to monitor parenchymal liver functions, whereas biomarkers to assess nonparenchymal functions remain largely obscure.

Purpose The aim of this study was to investigate the epidemiology of and outcome from heparin-induced thrombocytopenia type II (HIT) in surgical intensive care unit (ICU) patients. Patients and Methods All 13 948 patients admitted to a university hospital surgical ICU between January 2004 and March 2008 were included in this retrospective cohort study. Results Of 349 patients with a clinical suspicion of HIT, 88 patients had platelet factor 4/heparin antibodies using enzyme-linked immunosorbent assay. The prevalence and incidence of HIT were 0.82% and 0.63%, respectively. The complication rate was 43.5%, and the ICU and hospital mortality rates were 23.9% and 33%, respectively. In a multivariable analysis, the nadir platelet count (odds ratio, 1.03; 95% confidence interval, 1.01-1.05; P = .048) was the only factor independently associated with risk of death in these patients. In a nested matched case-control analysis, mortality rates were similar in patients with HIT and in the matched controls. However, complication rates were higher, and ICU and hospital lengths of stay were longer in patients with HIT compared with those of the control group. Conclusions In this cohort of surgical ICU patients, HIT was associated with increased morbidity but not mortality rates compared with a nested matched control group. The nadir platelet count was independently associated with a higher risk of inhospital death in these patients.