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Coronavirus disease 2019 (COVID-19) can lead to pneumonia and hyperinflammation. Here we show a sensitive method to measure polyclonal T cell activation by downstream effects on responder cells like basophils, plasmacytoid dendritic cells, monocytes and neutrophils in whole blood. We report a clear T cell hyporeactivity in hospitalized COVID-19 patients that is pronounced in ventilated patients, associated with prolonged virus persistence and reversible with clinical recovery. COVID-19-induced T cell hyporeactivity is T cell extrinsic and caused by plasma components, independent of occasional immunosuppressive medication of the patients. Monocytes respond stronger in males than females and IL-2 partially restores T cell activation. Downstream markers of T cell hyporeactivity are also visible in fresh blood samples of ventilated patients. Based on our data we developed a score to predict fatal outcomes and identify patients that may benefit from strategies to overcome T cell hyporeactivity., Perturbed T cell responses and disturbed cytokine secretion have been shown during SARS-CoV2 infection in patients. Here the authors show reduced polyclonal T cell activity in COVID-19 patients that is caused by plasma factors and linked to poor prognosis and viral persistence.

ObjectiveThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic challenges national health systems and the global economy. Monitoring of infection rates and seroprevalence can guide public health measures to combat the pandemic. This depends on reliable tests on active and former infections. Here, we set out to develop and validate a specific and sensitive enzyme linked immunosorbent assay (ELISA) for detection of anti-SARS-CoV-2 antibody levels.MethodsIn our ELISA, we used SARS-CoV-2 receptor-binding domain (RBD) and a stabilized version of the spike (S) ectodomain as antigens. We assessed sera from patients infected with seasonal coronaviruses, SARS-CoV-2 and controls. We determined and monitored IgM-, IgA- and IgG-antibody responses towards these antigens. In addition, for a panel of 22 sera, virus neutralization and ELISA parameters were measured and correlated.ResultsThe RBD-based ELISA detected SARS-CoV-2-directed antibodies, did not cross-react with seasonal coronavirus antibodies and correlated with virus neutralization (R2 = 0.89). Seroconversion started at 5 days after symptom onset and led to robust antibody levels at 10 days after symptom onset. We demonstrate high specificity (99.3%;N = 1000) and sensitivity (92% for IgA, 96% for IgG and 98% for IgM; > 10 days after PCR-proven infection;N = 53) in serum.ConclusionsWith the described RBD-based ELISA protocol, we provide a reliable test for seroepidemiological surveys. Due to high specificity and strong correlation with virus neutralization, the RBD ELISA holds great potential to become a preferred tool to assess thresholds of protective immunity after infection and vaccination.

Background: Extracorporeal photopheresis (ECP) is an effective immunomodulatory therapy for various diseases. Autologous leukocytes are collected, photoactivated with a photosensitizer (8-methoxypsoralen, 8-MOP) and UVA light, and subsequently reinfused back to the patient. Leukapheresis and UVA irradiation systems can be integrated into one device (inline) or handled by two separate devices (offline). ECP works via intercalation of 8-MOP into DNA helices and UVA-based interactions to inhibit DNA replication. 8-MOP is known to adhere to plastic materials, which might reduce its availability for intercalation. In the present study we examined the bioavailability of 8-MOP when different plastic materials and solvents are used as matrices. Methods: Varying amounts of shredded ethylene vinyl acetate (EVA) and polyvinylchloride (PVC) from the MacoGenic irradiation bag (EVA1), UVA PIT irradiation bag (EVA2), UVA PIT recirculation bag (PVC A) and UVA PIT tubing (PVC B) by MacoPharma and PIT Medical Systems, respectively, were incubated with 200 ng mL−1 8-MOP dissolved in diisopropyl ether (DIPE) plus toluene 90/10 vol%, deionized water or plasma. After 2 h 8-MOP concentrations were determined by GC-MS. Results: After incubation, 8-MOP concentrations varied depending on the amount and type of plastic (PVC > EVA) and solvent (water > plasma > DIPE/toluene). Absorption to 200 mg EVA1 or EVA2 resulted in 8-MOP concentrations of 57% or 32% in water, 91% or 80% in plasma, and 93% or 92% in DIPE/toluene, while 200 mg PVC A and PVC B yielded recovery rates of 26% and 10% in water, 76% and 75% in plasma, and 55% and 30% in DIPE/toluene, respectively. Remaining 8-MOP differed significantly between container materials (EVA vs. PVC; p < 0.022) but not manufacturers (MacoPharma vs. PIT Medical Systems). Conclusion: Absorption loss of 8-MOP depends on the type of plastic and solvent and is more pronounced with water than with plasma. As the DNA binding effect of 8-MOP is dose-dependent, ECP starting doses should be adjusted to ensure that a sufficient concentration of free bioavailable 8-MOP is present during UV irradiation.

Acceleromyography is characterised by an increase of the twitch response T1 (first twitch of the train-of-four [TOF]) during first 30 min of monitoring known as the staircase phenomenon. In adults the staircase phenomenon can be avoided by tetanic prestimulation. This study examined, if tetanic prestimulation eliminates the staircase phenomenon in children. After written informed consent, the neuromuscular function of 80 children, 10 in each age group ( 6 months, 6-12 months, 12-24 months, 2-3 years, 3-6 years, 6-12 years, 12-18 years, and ≥ 18 years) was measured on both arms simultaneously over 30 min under general anaesthesia. The ulnaris nerve was stimulated using the TOF technique every 15 s. The twitch response (T1, TOF ratio [TOFR]) was measured by acceleromyography. Before calibration, tetanic prestimmulation (50 Hz for 5 s) was administered to one randomly selected arm. The effect of tetanic prestimulation and age was analysed using general linear models based on the normalized T1 and TOFRs of both arms. Tetanic prestimulation significantly affected T1 values avoiding the staircase phenomenon (p 0.0001). After 5.8 min [1.0-17.2 min] the normalized T1 values increased to 117% [102-147%] without prestimulation (p 0.0001) independent of the age group (p = 0.539). The normalized TOFR was stable throughout the observation period of 30 min 100% [95-107%]. Infants ( 12 weeks), children, and young adults ( 18 years) develop similar characteristics of the staircase phenomenon than adults. Tetanic prestimulation prevents the staircase phenomenon in these age groups. The stability of the TOFR reading confirms its value to monitor neuromuscular function over time.Registration: The study was registered as NCT02552875 on Clinical Trials.gov on July 29, 2014.

Background: The facilitation of early recovery of acute kidney injury (AKI) is an important step to improve outcome, particularly because of the limited therapeutic interventions currently available for AKI. The combination of an electronic alert and biomarker-guided kidney-protection strategy implemented in the routine care may have an impact on the incidence of early complete reversal of AKI after major non-cardiac surgery. Methods: We studied 294 patients in two cohorts before (n = 151) and after protocol implementation (n = 143). Data collection required 6 months for each cohort. The kidney-protection protocol included an electronic alert to detect patients who were eligible for urinary biomarker [TIMP2 × IGFBP7]-guided kidney-protection intervention. Intervention was stratified according to three levels of immediate AKI risk: low, moderate, and high. After intervention, postoperative changes in the glomerular filtration rate (eGFR) were identified with a tracking software that included an alert for nephrology consultation if the eGFR had declined by &gt, 25% from the preoperative reference value. Primary outcome was early AKI recovery, i.e., the complete reversal of any AKI stage to absence of AKI within the first 7 postoperative days. Results: Protocol implementation significantly increased the recovery of AKI (36/46, 78% compared to control 27/48, 56%, (p = 0.025)) and reduced the length of the ICU stay (p &lt, 0.001). There was no significant difference in the overall incidence of all AKI and moderate and severe AKI in the first 7 postoperative days: 46/143 (32%) and 12/151 (8%) in the protocol implementation group compared to 48/151 (32%) and 18/151 (12%) in the historical control group. Patients with AKI reversal within the first 7 postoperative days had lower in-hospital mortality than patients without AKI reversal. Conclusions: Implementing a combined electronic alert and biomarker-guided kidney-protection strategy in routine care improved early recovery of AKI after major surgery.

Background Extracorporeal cardiopulmonary resuscitation (ECPR) performed at the emergency scene in out-of-hospital cardiac arrest (OHCA) can minimize low-flow time. Target temperature management (TTM) after cardiac arrest can improve neurological outcome. A combination of ECPR and TTM, both implemented as soon as possible on scene, appears to have promising results in OHCA. To date, it is still unknown whether the implementation of TTM and ECPR on scene affects the time course and value of neurological biomarkers. Methods 69 ECPR patients were examined in this study. Blood samples were collected between 1 and 72 h after ECPR and analyzed for S100, neuron-specific enolase (NSE), lactate, D-dimers and interleukin 6 (IL6). Cerebral performance category (CPC) scores were used to assess neurological outcome after ECPR upon hospital discharge. Resuscitation data were extracted from the Regensburg extracorporeal membrane oxygenation database and all data were analyzed by a statistician. The data were analyzed using non-parametric methods. Diagnostic accuracy of biomarkers was determined by area under the curve (AUC) analysis. Results were compared to the relevant literature. Results Non-hypoxic origin of cardiac arrest, manual chest compression until ECPR, a short low-flow time until ECPR initiation, low body mass index (BMI) and only a minimal need of extra-corporeal membrane oxygenation support were associated with a good neurological outcome after ECPR. Survivors with good neurological outcome had significantly lower lactate, IL6, D-dimer, and NSE values and demonstrated a rapid decrease in the initial S100 value compared to non-survivors. Conclusions A short low-flow time until ECPR initiation is important for a good neurological outcome. Hypoxia-induced cardiac arrest has a high mortality rate even when ECPR and TTM are performed at the emergency scene. ECPR patients with a higher BMI had a worse neurological outcome than patients with a normal BMI. The prognostic biomarkers S100, NSE, lactate, D-dimers and IL6 were reliable indicators of neurological outcome when ECPR and TTM were performed at the emergency scene.

Background Data of critically ill COVID-19 patients are being evaluated worldwide, not only to understand the various aspects of the disease and to refine treatment strategies but also to improve clinical decision-making. For clinical decision-making in particular, prognostic factors of a lethal course of the disease would be highly relevant. Methods In this retrospective cohort study, we analyzed the first 59 adult critically ill Covid-19 patients treated in one of the intensive care units of the University Medical Center Regensburg, Germany. Using uni- and multivariable regression models, we extracted a set of parameters that allowed for prognosing in-hospital mortality. Results Within the cohort, 19 patients died (mortality 32.2%). Blood pH value, mean arterial pressure, base excess, troponin, and procalcitonin were identified as highly significant prognostic factors of in-hospital mortality. However, no significant differences were found for other parameters expected to be relevant prognostic factors, like low arterial partial pressure of oxygen or high lactate levels. In the multivariable logistic regression analysis, the pH value and the mean arterial pressure turned out to be the most influential prognostic factors for a lethal course.

Background Postoperative vasoplegia with minimal responsiveness to vasopressors is common after cardiac surgery. Called cardiac vasoplegic syndrome (CVS), it is caused by multiple factors. Treating CVS involves a high dose of fluids and catecholamines, however high doses of catecholamines and fluids are associated with serious side effects. There is evidence that new therapeutic strategies can lead to a reduction in norepinephrine doses and mortality in CVS. Specifically, the use of non-adrenergic vasopressors such as methylene blue (MB) can be beneficial. Methods We retrospectively analyzed the electronic records of 8716 adult cardiac surgery patients from November 2008 to December 2016. Medication, hemodynamic and outcome parameter data were analyzed for CVS until discharge. We determined CVS according to the following parameters: a postoperative onset of ≤24 h, a reduced mean arterial pressure (MAP) of − 1 and a continuously increasing need for catecholamine, without ventricular dysfunction. Results We identified 513 patients with CVS. Perioperative risk factors were higher in patients treated with methylene blue (MB). Before MB administration patients had a significantly higher dose of norepinephrine, and MAP increased after MB administration. Norepinephrine could be reduced after MB administration and MAP remained stable at the same level even after the reduction of norepinephrine. Conclusions CVS patients have a severe systemic disease accompanied by significant operative stress and a high catecholamine requirement. The administration of MB in addition to standard treatment for CVS in the first 24 h was accompanied by an increase in MAP followed by a decrease in vasopressor requirement, indicating that early MB administration can be beneficial.

Background: Data of critically ill COVID-19 patients are being evaluated worldwide, not only to understand the various aspects of this disease and to refine treatment strategies but also to improve clinical decision-making. For the last aspect in particular, predictors of a lethal course of disease would be highly relevant.Methods:In this retrospective cohort study, we analyzed the first 59 adult critically ill Covid-19 patients treated in one of the intensive care units of the University Medical Center Regensburg, Germany. Using uni- and multivariable regression models, we extracted a set of parameters that allowed predictions of in-hospital mortality.Results:Blood pH value, mean arterial pressure, base excess, troponin, and procalcitonin were identified as highly significant predictors (p < 0.001) of in-hospital mortality. In the multivariable logistic regression analysis, the pH value and the mean arterial pressure turned out to be the most influential predictors and thus predisposing factors for a lethal course.Conclusions:We developed a formula that enables the easy calculation of the probability of a fatal outcome in COVID-19 intensive care patients. Currently a follow-up study with a larger group of patients is in progress to re-evaluate the established predictors.

Background From a public health perspective, effective containment strategies for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) should be balanced with individual liberties. Methods We collected 79 respiratory samples from 59 patients monitored in an outpatient center or in the intensive care unit of the University Hospital Regensburg. We analyzed viral load by quantitative real-time polymerase chain reaction, viral antigen by point-of-care assay, time since onset of symptoms, and the presence of SARS-CoV-2 immunoglobulin G (IgG) antibodies in the context of virus isolation from respiratory specimens. Results The odds ratio for virus isolation increased 1.9-fold for each log10 level of SARS-CoV-2 RNA and 7.4-fold with detection of viral antigen, while it decreased 6.3-fold beyond 10 days of symptoms and 20.0-fold with the presence of SARS-CoV-2 antibodies. The latter was confirmed for B.1.1.7 strains. The positive predictive value for virus isolation was 60.0% for viral loads >107 RNA copies/mL and 50.0% for the presence of viral antigen. Symptom onset before 10 days and seroconversion predicted lack of infectivity with negative predictive values of 93.8% and 96.0%. Conclusions Our data support quarantining patients with high viral load and detection of viral antigen and lifting restrictive measures with increasing time to symptom onset and seroconversion. Delay of antibody formation may prolong infectivity.

Die postoperative, neuromuskulare Restblockade („train of four ratio“

Anesthesia services outside central surgical facilities (nonoperating room anesthesia, NORA) have become more important. Nonoperating room anesthesia is a challenging field with a wide range of patient ages and interventions. The anesthesiologist is caught between the existing expertise in sedation, respiratory and emergency management and the fact that it may be a potentially avoidable cost factor. The efforts of some specialist departments to carry out sedation themselves even with more complex interventions have therefore increased. In order to permanently establish anesthesia here, apart from the pure anesthesiological expertise, a pronounced willingness to interdisciplinary communication and cooperation is necessary. Only in this way can the participating specialist disciplines be convinced of the anesthesiological added value for the patient. Groups of patients requiring special attention include pediatric patients. The care especially for children under 2 years old also requires the particular anesthesiological expertise of the supervising anesthesiologist; however, profound knowledge, for example in cardiac anesthesia, is also required if special interventions are decentrally managed in the cardiac catheterization laboratory.

Background: Numerous experimental studies show that anesthetics are potentially toxic to the immature brain. Even though benzodiazepines are widely used in pediatric anesthesia and intensive care m...

Metabolic pathways regulate immune responses and disrupted metabolism leads to immune dysfunction and disease. Coronavirus disease 2019 (COVID-19) is driven by imbalanced immune responses, yet the role of immunometabolism in COVID-19 pathogenesis remains unclear. By investigating 87 patients with confirmed SARS-CoV-2 infection, 6 critically ill non���COVID-19 patients, and 47 uninfected controls, we found an immunometabolic dysregulation in patients with progressed COVID-19. Specifically, T cells, monocytes, and granulocytes exhibited increased mitochondrial mass, yet only T cells accumulated intracellular reactive oxygen species (ROS), were metabolically quiescent, and showed a disrupted mitochondrial architecture. During recovery, T cell ROS decreased to match the uninfected controls. Transcriptionally, T cells from severe/critical COVID-19 patients showed an induction of ROS-responsive genes as well as genes related to mitochondrial function and the basigin network. Basigin (CD147) ligands cyclophilin A and the SARS-CoV-2 spike protein triggered ROS production in T cells in vitro. In line with this, only PCR-positive patients showed increased ROS levels. Dexamethasone treatment resulted in a downregulation of ROS in vitro and T cells from dexamethasone-treated patients exhibited low ROS and basigin levels. This was reflected by changes in the transcriptional landscape. Our findings provide evidence of an immunometabolic dysregulation in COVID-19 that can be mitigated by dexamethasone treatment.

Background: The role of venovenous extracorporeal membrane oxygenation (VV ECMO) in patients with COVID-19-induced acute respiratory distress syndrome (ARDS) still remains unclear. Our aim was to investigate the clinical course and outcome of those patients and to identify factors associated with the need for prolonged ECMO therapy. Methods: A retrospective single-center study on patients with VV ECMO for COVID-19-associated ARDS was performed. Baseline characteristics, ventilatory and ECMO parameters, and laboratory and virological results were evaluated over time. Six months follow-up was assessed. Results: Eleven of 16 patients (68.8%) survived to 6 months follow-up with four patients requiring short-term (2O vs 18.7 (17.7–25.0) ml/cmH2O, p = 0.030). Mechanical ventilation before ECMO was longer (19 (16–23) days vs 5 (5–9) days, p = 0.002) and SOFA score was higher (12.0 (10.5–17.0) vs 10.0 (9.0–10.0), p = 0.002) in non-survivors compared to survivors. Low viral load during the first days on ECMO tended to indicate worse outcomes. Seroconversion against SARS-CoV-2 occurred in all patients, but did not affect outcome. Conclusions: VV ECMO support for COVID-19-induced ARDS is justified if initiated early and at an experienced ECMO center. Prolonged ECMO therapy might be required in those patients. Although no relevant predictive factors for the duration of ECMO support were found, the decision to stop therapy should not be made dependent of the length of ECMO treatment.

During the coronavirus disease 2019 (COVID-19) pandemic, outbreaks in inpatient care facilities, which grow into a large-scale emergency scenario, are frequently observed. A standardized procedure analogous to algorithms for mass casualty incidents (MCI) is lacking.Based on a case report and the literature, the authors present a management strategy for infectious MCI during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and distinguish it from traumatic MCI deployment tactics.This management strategy can be divided into three phases, beginning with the acute emergency response including triage, stabilization of critical patients, and transport of patients requiring hospitalization. Phase 2 involves securing the facility's operational readiness, or housing residents elsewhere in case staff are infected or quarantined to a relevant degree. Phase 3 marks the return to regular operations.Phase 1 is based on usual MCI principles, phase 2 on hospital crisis management. Avoiding evacuation of residents to relieve hospitals is an important operational objective. The lack of mission and training experience with such situations, the limited applicability of established triage algorithms, and the need to coordinate a large number of participants pose challenges.This strategic model offers a practical, holistic approach to the management of infectious mass casualty scenarios in nursing facilities.HINTERGRUND: Während der Corona Virus Disease-2019(COVID-19)-Pandemie sind gehäuft Ausbrüche in stationären Pflege- und Betreuungseinrichtungen zu beobachten, die die ambulanten Strukturen überfordern und zu einer rettungsdienstlichen Großschadenslage aufwachsen. Standardisierte einsatztaktische Vorgaben wie für den Massenanfall von Verletzten (MANV) fehlen.Anhand eines konkreten Fallberichts und der Literatur stellen die Autoren eine Managementstrategie für den Massenanfall von Erkrankten bzw. Infizierten (MANE/MANI) während der Severe Acute Respiratory Syndrome Corona Virus‑2(SARS-CoV‑2)-Pandemie vor und grenzen diese zur MANV-Einsatztaktik ab.Das Vorgehen bei MANI lässt sich in 3 Phasen einteilen und beginnt mit der akuten Gefahrenabwehr mit Sichtung, Stabilisierung kritischer Patienten und Transport der hospitalisierungspflichtigen Patienten. In Phase 2 werden die Betriebsbereitschaft der Einrichtung gesichert oder die Bewohner anderweitig untergebracht, falls das Personal in relevantem Ausmaß infiziert oder in Quarantäne ist. Die 3. Phase markiert die Rückkehr zum Regelbetrieb.Phase 1 orientiert sich an MANV-Grundsätzen, Phase 2 am Krankenhauskrisenmanagement. Die Vermeidung einer Evakuierung der Bewohner zur Entlastung der Krankenhäuser stellt dabei ein wichtiges Einsatzziel dar. Mangelnde Einsatz- und Übungspraxis mit derartigen Lagen, die begrenzte Anwendbarkeit von etablierten Vorsichtungsalgorithmen sowie der hohe Koordinationsbedarf stellen die Führungskräfte vor Herausforderungen.Das vorgestellte Phasenmodell stellt einen praktikablen, ganzheitlichen Ansatz zum erweiterten notfallmedizinischen Management von MANI-Einsatzlagen dar.

Background Orthotopic liver transplantation (OLT) is the treatment option for early-stage hepatocellular carcinoma (HCC). OLT is often associated with high blood loss, requiring blood transfusion. Retransfusion of autologous blood is a key part of blood conservation. There are, however, concerns that the retransfusion of salvaged blood might cause the spread of cancer cells and induce metastasis. Irradiation of salvaged blood before retransfusion eliminates viable cancer cells. Here, we analyzed the incidence of tumor recurrence in patients with HCC undergoing OLT who received irradiated cell-salvaged blood during transplant surgery. Methods We retrospectively analyzed patients undergoing OLT for HCC between 2002 and 2018 at our center. We compared the tumour recurrence in patients who received no retransfusion of autologous blood with patients who received autologous blood with or without preceding irradiation of the blood. Results Fifty-one (40 male, 11 female) patients were included in the analysis; 10 patients developed tumor recurrence within a time period of 2.45 ± 2.0 years. Statistical analysis revealed that there was no significant difference in tumor recurrence between patients who received autologous blood with or without irradiation. Conclusion Intraoperative transfusion of cell-salvaged blood did not increase tumor recurrence rates. Cell salvage should be used in liver transplantation of HCC patients as part of a blood conservation strategy. The effect of blood irradiation on tumor recurrence could not be definitively evaluated.

Coronavirus disease 2019 (COVID-19) can lead to severe pneumonia and hyperinflammation. So far, insufficient or excessive T cell responses were described in patients. We applied novel approaches to analyze T cell reactivity and showed that T anergy is already present in non-ventilated COVID-19 patients, very pronounced in ventilated patients, strongly associated with virus persistence and reversible with clinical recovery. T cell activation was measured by downstream effects on responder cells like basophils, plasmacytoid dendritic cells, monocytes and neutrophils in whole blood and proved to be much more meaningful than classical readouts with PBMCs. Monocytes responded stronger in males than females and IL-2 partially reversed T cell anergy. Downstream markers of T cell anergy were also found in fresh blood samples of critically ill patients with severe T cell anergy. Based on our data we were able to develop a score to predict fatal outcomes and to identify patients that may benefit from strategies to overcome T cell anergy.

BACKGROUND Kidney injury is a complication among children undergoing liver transplantation (pLTx). Cystatin C serum concentration seems to be superior to creatinine-based determination of kidney injury in adults and children. Near-infrared spectroscopy (NIRS) technology provides non-invasive and real-time measurement of renal tissue oxygenation. Here, we compared renal tissue oximetry (rSrO₂) with conventional diagnostic criteria cystatin C and creatinine concentration in children undergoing pLTx. MATERIAL AND METHODS rSrO₂ was measured intraoperatively in children undergoing pLTx over the left kidney, and was statistically compared with pre- and postoperative serum creatinine and cystatin C concentrations. RESULTS rSrO₂ was affected by hemoglobin concentration, bilirubin concentration, and FiO₂. Statistical analysis demonstrated that rSrO₂ was significantly reduced in children with preoperative pathologic increased cystatin C concentrations compared to children without (63.7±4.3 vs. 53.4±4.9, p

Background Bleeding is a major adverse effect of veno-venous extracorporeal membrane oxygenation (vvECMO) therapy in surgical patients. This study retrospectively describes the amount of transfused packed red blood cells (PRBC) and coagulation parameters of patients requiring surgery during vvECMO therapy. Methods We included patients who underwent at least one surgical procedure during vvECMO therapy and analyzed hemoglobin levels, coagulation parameters, blood gas parameters and transfused blood products. Patients with perioperative transfusion of less than two PRBC during the perioperative period (group A) were compared to those who were given two or more PRBCs (group B). Results Seventy-three patients (group A: 42 patients, group B: 31 patients) were included. Activated PTT (54.7 vs. 56.2 sec), Quick test (61.5% vs. 60.0%), Platelet count (91 vs 72 / nL, P=0.322) and mortality (40.5 vs. 45.2%; P=0.689) were not different between both groups. Fibrinogen was significantly decreased in group B (245 mg/dL) compared to group A (353 mg/dL; P=0.004). Conclusions In patients requiring surgery during vvECMO therapy with perioperative transfusion of two or more PRBCs preoperative fibrinogen levels were significantly reduced compared to patients with transfusion of less than two PRBCs. No other analyzed lab value showed any predictive qualities in terms of bleeding.

To determine the impact of renal biomarker-guided implementation of the Kidney Disease Improving Global Outcomes (KDIGO) care bundle on the incidence of acute kidney injury (AKI) after major noncardiac surgery in a single-center unblinded randomized clinical trial.Early optimization of volume status and discontinuation of nephrotoxic medication before the occurrence of AKI may be the crucial step to reduce preventable AKI.The urinary biomarker-triggered KDIGO care bundle (early optimization of fluid status, maintenance of perfusion pressure, discontinuation of nephrotoxic agents) was compared to standard intensive care unit (ICU) care in 121 patients with an increased AKI risk after major abdominal surgery that was determined by urinary biomarker (inhibitor of metalloproteinase-2 × insulin-like growth factor-binding protein 7)0.3. Incidence of overall AKI, severity of AKI, length of stay, major kidney events at discharge, and cost effectiveness were evaluated.The overall stages of AKI were not statistically different between the 2 groups, but in patients with inhibitor of metalloproteinase-2 × insulin-like growth factor-binding protein 7 values of 0.3 to 2.0 a subgroup analysis demonstrated a significantly reduced incidence of AKI 13/48 (27.1%) in the intervention group compared to control 24/50 (48.0%, P = 0.03). Incidence of moderate and severe AKI (P = 0.04), incidence of creatinine increase25% of baseline value (P = 0.01), length of ICU, and hospital stay (P = 0.04) were significantly lower in the intervention group. Intervention was associated with cost reduction. There were no significant differences regarding renal replacement therapy, in-hospital mortality, or major kidney events at hospital discharge.Early biomarker-based prediction of imminent AKI followed by implementation of KDIGO care bundle reduced AKI severity, postoperative creatinine increase, length of ICU, and hospital stay in patients after major noncardiac surgery.

Die Hypnose stellt ein sehr altes und effektives Heilverfahren dar. In den letzten Jahrzehnten war die moderne Hypnose vor allem eine Domane der Psychotherapie. Jedoch gewinnt die Hypnose als therapeutisches Verfahren in der Medizin wieder zunehmend an Bedeutung. Hypnose kann bei einer Vielzahl von medizinischen Indikationen eingesetzt werden. In der Literatur finden sich zahlreiche Beweise fur ihre Wirksamkeit. Ziel war es, die Effektivitat der Hypnose in der stationaren Therapie chronischer Schmerzpatienten aufzuzeigen und ein Selbsthypnoseprogramm darzustellen, welches gut in die Schmerztherapie integriert werden kann. Eingeschlossen wurden alle stationaren chronischen Schmerzpatienten von Oktober 2012 bis April 2013 (Gruppe 1: Nichthypnosegruppe; Gruppe 2: Hypnosegruppe). Fur die Gruppe 2 wurde ein Protokoll fur Hypnosetherapie zusatzlich zum standardisierten schmerztherapeutischen Programm integriert. Das Hauptziel der Hypnosetherapie war vor allem ein Selbsthypnosetraining, damit eine hausliche weitere Umsetzung gewahrleistet werden konnte. Mittels standardisierter Testverfahren (u. a. Gesundheitsfragebogen fur Patienten [PHQ-9], Pain Disability Index [PDI], Generalized Anxiety Disorder [GAD-7] und numerische Rating-Skalen [NRS] zum Schmerz und allgemeinen Wohlbefinden) wurden die Daten vor und nach der Schmerztherapie ausgewertet. Die pra- und poststationaren standardisierten Testverfahren von 30 chronischen Schmerzpatienten konnten ausgewertet werden (17 Patienten ohne Hypnose, 13 Patienten mit Hypnose). Die Hauptdiagnose nach ICD-10 war bei allen Patienten „chronische Schmerzerkrankung“ (F45.41) mit einem MPSS-Stadium III. Der PDI war in der Hypnosegruppe signifikant gebessert (p = 0,019). Die weiteren Items zeigten alle einen Trend zur Besserung in der Hypnosegruppe (Ausnahme GAD-7) ohne eine statistische Signifikanz (p > 0,05). Die vorliegende Arbeit konnte in einem ersten kleinen Patientenkollektiv zeigen, dass die Integration der modernen Hypnosetherapie in die Behandlung von chronischen Schmerzpatienten im stationaren Setting ein weiterer sinnvoller therapeutischer Aspekt sein kann. Insbesondere die Anleitung zum Erlernen selbststandig durchzufuhrender Hypnosetechniken erscheint aufgrund der begrenzten stationaren Zeit sinnvoll zu sein. Es bedarf weiterer Untersuchungen, um diese ersten Ergebnisse zu unterstutzen.

Ein niedriger soziookonomischer Status (SES) ist bei schweren Erkrankungen mit einer hoheren Morbiditat und Mortalitat assoziiert. Ob neben dem SES weitere individuelle Faktoren (Geschlecht, Versichertenstatus, Wohnortgrose) mit der Erkrankungsschwere und intensivmedizinischen Behandlungsdauer verknupft sind, wurde in einer weiteren Analyse der ECSSTASI-Daten untersucht. Im Rahmen der ECSSTASI-Studie wurden 996 Patienten einer operativen Intensivstation rekrutiert. Nach der Primaranalyse untersuchten wir zusatzlich den Einfluss von Geschlecht, Versichertenstatus und Wohnortgrose auf gesundheitsrelevante Verhaltensweisen, die Erkrankungsschwere, die Intensivbehandlungs- und Beatmungsdauer („28 ventilator-free days score“, 28-VFDS) sowie die soziale Unterstutzung durch Angehorige. Es wurden multivariate adjustierte logistische Regressionsanalysen durchgefuhrt. Alle „odds ratios“ (OR) wurden als 95%-Konfidenzintervalle dargestellt. Bei Aufnahme auf die Intensivstation war der Schweregrad der Erkrankung (SOFA-Score >5) bei Frauen signifikant geringer (OR 0,62; 95 %-KI 0,45–0,87). Eine steigende Wohnortgrose der Patienten war im Vergleich zu kleinen Wohnorten mit einer signifikant kurzeren Behandlungsdauer auf der Intensivstation verknupft (OR 0,54; 95%-KI 0,32-0,91). Eine steigende Anzahl von Personen im Haushalt bedeutete ein signifikant erhohtes Risiko, langer beatmet zu werden, verglichen mit Einpersonenhaushalten (p fur Trend = 0,028). Privatversicherte Patienten (OR 1,87; 95%-KI 1,28–2,70), Patienten aus Haushalten mit ≥4 Personen (OR 1,92; 95%-KI 1,1–3,33) und Patienten ohne deutsche Staatsburgerschaft (OR 2,56; 95%-KI 1,39–4,55) wurden signifikant haufiger von Angehorigen besucht. Neben dem SES sind weitere soziodemografische Merkmale des einzelnen Patienten mit dem Behandlungsverlauf in der Intensivmedizin assoziiert. Das Ausmas sozialer Unterstutzung durch Angehorige hangt von interkulturellen und individuellen Patientenmerkmalen ab. Eine zunehmende Wohnortgrose und der private Krankenversichertenstatus beeinflussen die Intensivtherapie positiv. Um diese Daten zu bewerten, sind weitere epidemiologische Studien in der Intensivmedizin erforderlich.

BACKGROUND The right to adequate outpatient palliative care has existed for several years in Germany. In recent years outpatient palliative care has developed very positively. Nevertheless, in emergency situations paramedics and emergency physicians were often included in the care of palliative care of patients. The aim of our study was to investigate the cooperation between outpatient palliative care teams and the emergency medical services. Another aim was to identify structural realities and based on these to discuss the possibilities in the optimization of outpatient palliative medical emergency situations. METHODS A standardized self-designed questionnaire was distributed to specialized outpatient palliative care teams (SPCS) in Germany. For this purpose, closed and open questions (mixed methods) were used. The evaluation was carried out according to the questionnaire categories in quantitative and qualitative forms. The questionnaire was subdivided into general information and specific questions. RESULTS The survey response rate was 79% from a total of 81 SPCS in 2011. The following standards in palliative emergency care were recommended: (1) early integration of outpatient palliative care services and basic outpatient palliative care systems, (2) end-of-life discussions, (3) defined emergency medical documents, emergency drug boxes, do not attempt resuscitation orders and (4) emergency medical training (physicians and paramedics). CONCLUSION Outpatient palliative care in Germany has developed very positively during the last years; however, there are still deficits in terms of optimal patient care, one of which refers to the treatment of palliative care emergencies. In this context, optimization in the cooperation between outpatient palliative care services and emergency medical services should be discussed.

Background: Prehospital emergency physicians (EP) are often confronted with the acute care of palliative care patients. Dyspnoea is a frequent acute symptom and its causes often differ from the generally known emergency medical causes. Till now, there have been no relevant concepts for emergency care of palliative care patients for their specific symptoms.Methods: Over a 24-month period, the authors retrospectively investigated all out-of-hospital emergency medical services for palliative care patients with acute dyspnoea at four emergency physician support points. The evaluation of these services was followed retrospectively on the basis of the therapy carried out by the EP (Group 1: therapy with morphine and oxygen; Group 2: therapy with morphine, bronchodilator effective drugs and oxygen; Group 3: therapy with bronchodilator effective drugs and oxygen; Group 4: therapy with oxygen; Group 5: no medical treatment). Moreover, EPs were interviewed about their actions and their uncertainties in the treatment of palliative care patients.Results: The diagnosis of acute dyspnoea in palliative care patients occurred 121 times (116 patients were integrated in the present investigation) within the defined period. In total, 116 patients were included (Group 1: 21, Group 2: 29, Group 3: 31, Group 4: 28, and Group 5: 7). Dyspnoea was satisfactorily treated in 41 percent of the patients (Group 1: 67 percent, Group 2: 52 percent, Group 3: 22 percent, Group 4: 18 percent, and Group 5: 71 percent). Most EPs (70 percent) revealed uncertainties in emergency medical therapy for patients at the end of life.Conclusions: The current investigation showed a significant relief of acute dyspnoea when using opioids, in contrast with the established out-of-hospital emergency medical therapy for acute dyspnoea. Therefore, opioids should be recommended for emergency medical therapy of dyspnoea in palliative care patients. Clinical studies that recommend the use of effective opioids for the treatment of dyspnoea in palliative care patients are supported by the current retrospective study. Most EPs felt uncertain in the treatment of palliative care patients. Therefore, advanced training in palliative care medicine and endof-life care should be integrated into emergency medical training.

Background: Paramedics, arriving on emergency cases first, have to make end-of-life decisions almost on a daily basis. Faith shapes attitudes toward the meaning and worth of life itself and therefore influences decision-making. Objective: The objective of this study was to detect whether or not religious and spiritual beliefs influence paramedics in their workday life concerning end-of-life decisions, and whether it is legally possible for them to act according to their conscience. Methods and Design: This is a literature review of prior surveys on the topic using five key words and questionnaire-based investigation using a self-administered online survey instrument. Settings/Participants: Paramedics all over Germany were given the opportunity to participate in this online questionnaire-based study. Measurements: Two databases were searched for prior studies for literature review. Participants were asked about their religiosity, how it affects their work, especially in end-of-life situations, how experienced they are, and whether or not they have any legal latitude to withhold resuscitation. Results: A total of 429 paramedics answered the questionnaire. Religious paramedics would rather hospitalize a patient holding an advance directive than leave him/her at home (P = 0.036) and think death is less a part of life than the nonreligious (P = 0.001). Otherwise, the Spearman's rho correlation was statistically insignificant for all tests regarding resuscitation. Conclusions: The paramedic's religiosity is not the prime factor in his/her decision-making regarding resuscitation.

Das Pramedikationsgesprach als Risikoevaluation vor einem operativen Eingriff ist ein wichtiges Element der perioperativen Betreuung. Bisher liegen wenige Arbeiten vor, die sich mit der Analyse der Ablaufe und Probleme in Pramedikationsambulanzen befassen. Es sollte prospektiv durch Erfassung samtlicher Pramedikationsgesprache vor elektiven Eingriffen in der Pramedikationsambulanz in einem Zeitraum von mehreren Wochen ein groser Datenpool generiert und dieser im Hinblick auf Moglichkeiten einer Prozessoptimierung analysiert werden. An 38 Werktagen wurde in der Pramedikationsambulanz des Universitatsklinikums Regensburg eine Erfassung der Wartezeiten und der Dauer des Pramedikationsgesprachs durchgefuhrt. Zudem wurden Patientenalter, ASA-Score (Klassifikation der American Society of Anesthesiologists), operierende Fachabteilung, Risikoklassifikation des operativen Eingriffs, Berufserfahrung des pramedizierenden Arztes, geplanter Zeitpunkt des operativen Eingriffs und Freigabestatus dokumentiert. Bei dem Pramedikationsgesprach auftretende Probleme wurden mithilfe eines Fragebogens registriert. Insgesamt konnten 2233 Pramedikationsgesprache analysiert werden. Die Zahl der in der Pramedikationsambulanz vorgestellten Patienten differierte im Tagesverlauf stark und nahm am Ende der Woche insgesamt ab. Von Anasthesisten mit einer Berufserfahrung von mehr als 5 Jahren bzw. Facharzten wurden Patienten signifikant haufiger freigegeben als von jungeren Kollegen. Haufigster Grund fur eine Freigabe mit Einschrankung oder keine Freigabe war das Fehlen von Laborbefunden oder Elektrokardiogramm (EKG). Als haufigster Grund fur Probleme beim Pramedikationsgesprach wurde das Fehlen von Unterlagen genannt, die gemas hausinternem Standard hatten vorliegen sollen. Die mittlere Wartezeit fur die Patienten betrug 58,6 ± 30,3 min; Durchsicht der mitgebrachten Unterlagen und das Gesprach mit dem Patienten dauerten zusammen im Mittel 33,6 ± 16,3 min. Anasthesisten mit einer Berufserfahrung von 2 bis 5 Jahren benotigten fur die Durchsicht der Unterlagen und das Pramedikationsgesprach signifikant kurzer als Berufsanfanger und erfahrene Kollegen. Zudem korrelierte die Dauer mit dem ASA-Score und dem Risiko des operativen Eingriffs. Optionen zur Prozessoptimierung in der Pramedikationsambulanz stellen die Einfuhrung von Reglementierungen zur Schaffung eines homogenen Patientenaufkommens im Tagesverlauf und das Einwirken auf die zuweisenden Kliniken, dass Patienten im Regelfall nur mit vollstandigen Unterlagen gemas Pramedikationsstandard vorgestellt werden, dar.

Antibiotic stewardship (ABS) programs intend to improve outcomes of nosocomial infections and to counteract the emergence of further antimicrobial resistances. At the anesthesiologic-neurosurgical intensive care unit (ICU) of the University Medical Center Regensburg (Germany) we implemented a standard operating procedure (SOP) with clear instructions for the preanalytical handling and storage of microbiological samples. We intended to find out whether the instructions given in the SOP led to a higher rate of ideal material being sent to the laboratory and to overall better quality of the received results.We retraced retrospectively all samples taken in cases of suspected pneumonia, urinary tract infection, bloodstream infection, catheter infection associated with a central venous or arterial catheter and ventriculitis due to external ventricular drainage as well as all smears taken for the screening for multi-resistant bacteria within a time period of 1 year before to 1 year after the implementation of the SOP.In the case of suspected pneumonia and urinary tract infection, large amounts of ideal material were sent to the microbiological laboratory. A remarkable improvement after the implementation of the SOP, however, could only be observed regarding the number of urine samples taken from older urinary catheters, which was significantly lower in the "SOP group". Samples for microbiological diagnostics were taken much more often in the daytime, although storage of the probes did not lead to worse results.Concrete instructions enable adequate preanalytical handling of microbiological probes. However, we could not recognize substantial improvements probably due to a preexisting high process quality on the ICU. Microbiological diagnostics during the night shift has to be improved.

Candidemia is frequent in critically ill patients, especially in combination with an acute kidney injury (AKI). Echinocandins generally are recommended for therapy of such infections. Recent studies found no need for dosage adjustment in patients with end-stage renal disease receiving hemodialysis, or patients with AKI receiving continuous venovenous hemofiltration. The aim of this in vitro study was to examine the adsorption of anidulafungin to the surface of the hemofilter during continuous venovenous hemodialysis (CVVHD) and its effect on anidulafungin concentrations. The concentration of anidulafungin in the dialyzed fluid, and the dialysate during CVVHD in vitro was examined using three different dialyzed fluids (saline; saline with 40 g/L human albumin; and a mixture of human erythrocytes and fresh frozen plasma). After the end of dialysis, the hemofilter was opened and portions of the filter capillaries were also analyzed to determine the amount of anidulafungin adsorbed. When dialyzing saline, about 99% of the anidulafungin used adsorbed to the hemofilter capillaries; in the experiments with saline with 40 g/L albumin, about 60% adsorbed to the hemofilter's surface, and when blood was dialyzed, 35% was found adsorbed after analyzing the filter capillaries. Anidulafungin was not detectable in the dialysate of any of the experiments, consequently the dialysis clearance was 0 mL/min. In conclusion, during CVVHD in vitro we found remarkable adsorption of anidulafungin to the hemofilter's surface, yet the effect on the tissue concentration needs further examination.

Patienten unter peripherer venoarterieller extrakorporaler Membranoxygenierung haben ein hohes Risiko, eine Ischamie der unteren Extremitat zu erleiden. Im Allgemeinen erfolgt die regelmasige Kontrolle anhand klinischer und laborchemischer Parameter, um Komplikationen schnell erkennen und beheben zu konnen. Diese Kontrollen sind aufgrund von Schockzustanden, nichtpulsatilem Fluss und Vasopressortherapie nicht einfach. Als zusatzliches Monitoring wird in der Literatur die Anwendung einer Nahinfrarotspektroskopie (NIRS) zur Ischamiedetektion mit grosem Erfolg beschrieben. Der vorliegende Artikel beschreibt den Einsatz und mogliche Limitationen der NIRS zur peripheren Ischamiediagnostik.

Long-term continuous intra-arterial nimodipine infusion (CIAN) is a rescue therapy option in cases of severe refractory cerebral vasospasm (CV) following acute non-traumatic subarachnoid hemorrhage (SAH). However, CIAN therapy can be associated with relevant side effects. Available studies focus on intracerebral complications, whereas extracerebral side effects are rarely examined. Aim of the present study was to generate descriptive data on the clinical course during CIAN therapy and expectable extracerebral side effects. All patients treated with CIAN therapy for at least 5 days between May 2011 and December 2015 were included. We retrospectively extracted data from the patient data management system regarding the period between 2 days before the beginning and 5 days after the termination of CIAN therapy to analyze the course of ventilation parameters and pulmonary gas exchange, hemodynamic support, renal and liver function, integrity of the gastrointestinal tract, and the occurrence of infectious complications. In addition, we recorded the mean daily values of intracranial pressure (ICP) and intracerebral problems associated with CIAN therapy. Data from 28 patients meeting inclusion criteria were analyzed. The mean duration of long-term CIAN therapy was 10.5 ± 4.5 days. Seventeen patients (60.7%) reached a good outcome level (Glasgow Outcome Scale [GOS] 4–5) 6 months after SAH. An impairment of the pulmonary gas exchange occurred only at the very beginning of CIAN therapy. The required vasopressor support with norepinephrine was significantly higher on all days during and the first day after CIAN therapy compared to the situation before starting CIAN therapy. Two patients required short-time resuscitation due to cardiac arrest during CIAN therapy. Acute kidney injury was observed in four patients, and one of them required renal replacement therapy with sustained low-efficiency daily dialysis. During CIAN therapy, 23 patients (82.1%) needed the escalation of a previous antiinfective therapy or the onset of antibiotics which was in line with a significant increase of C-reactive protein and white blood cell count. Obstipation was observed in 22 patients (78.6%). Ten patients (35.7%) even showed insufficient defecation on at least seven consecutive days. Compared to the situation before, ICP was significantly higher during the whole period of CIAN therapy. Long-term CIAN therapy is associated with diverse side effects. The leading problems are an impairment of the hemodynamic situation and cardiac problems, an increase in infectious complications, a worsening of the motility of the gastrointestinal tract, and rising ICP values. Teams on neurointensive care units must be aware of these side effects to avoid that the beneficial effects of CIAN therapy on CV reported elsewhere are foiled by the problems this technique can be associated with.

ZusammenfassungEs wird von einem Patienten berichtet, der nach einem Suizidversuch mittels Kohlenmonoxidintoxikation einen raumfordernden Kleinhirninfarkt und konsekutiven okklusiven Hydrozephalus entwickelte. Durch das rechtzeitige Detektieren der intrazerebralen Läsion konnte ein Überleben des Patienten ohne schwerwiegendes neurologisches Defizit ermöglicht werden.

SUMMARYBackground and objectives Cell salvage plays a key role in blood conservation. To maintain high performance, quality management is recommended. Accordingly, a new-generation autotransfusion device was tested for its performance and compared with its predecessor. Two different calculations of quality parameters were applied. Materials and methods In an experimental study, the continuous autotransfusion devices CATSmart and Continuous Autotransfusion System (C.A.T.S) plus were tested using banked blood adjusted to a haematocrit of 20% and anticoagulated with heparin 5 U/L. Test blood was processed using an emergency programme, a high-quality programme/smart wash programme and a low-volume wash programme. Samples were taken after the production of 200 mL of red blood cells (RBC) and after the final emptying of the separation chamber. In an additional set of tests, blood containing 1·25% fat was processed with both devices to examine fat removal. Results Both devices demonstrated an equally high performance with regards to product hematocrit (Hct); RBC recovery; and elimination rates of protein, heparin and fat. The high fat elimination rate (>99·8%) reported for C.A.T.S plus was confirmed for CATSmart, regardless of the used programme. Samples taken during the ongoing process show a higher haematocrit and RBC recovery rate than samples taken after the final emptying of the separation chamber. Interface sensors were not affected by fat in the blood. Conclusions The new-generation autotransfusion device CATSmart is not inferior to its predecessor and shows high performance with regards to RBC recovery, plasma and fat elimination in all programme modes. Samples for quality controls should be taken during blood processing.

Resumo Justificativa A intubacao guiada por fibra optica (IGFO) atraves de dispositivo supraglotico (DSG) tem sido descrita como um procedimento seguro e facil para o manejo de via aerea dificil. No entanto, a visibilizacao da abertura da glote e essencial para a IGFO. Varios DSGs diferentes estao comercialmente disponiveis e podem oferecer diferentes condicoes para a IGFO. O objetivo deste estudo foi comparar a melhor visao obtida da abertura da glote com o uso de diferentes DSGs. Metodos Com a aprovacao do Comite de Etica local, 52 pacientes adultos submetidos a anestesia eletiva foram randomicamente designados para um dos DSGs: tubo laringeo (TL), mascara laringea (ML) I‐Gel, ML Unique, ML Supreme, ML AuraOnce. Apos a inducao padronizada da anestesia, o DSG foi colocado de acordo com as recomendacoes do fabricante. Apos ventilacao bem‐sucedida, a posicao do DSG em relacao a abertura da glote foi examinada com um endoscopio flexivel. Uma abertura da glote total ou parcialmente visivel foi considerada como adequada para a IGFO. A adequacao para a IGFO foi comparada entre os grupos (teste‐H, teste‐U; p Resultados Os dados demograficos nao foram diferentes entre os grupos. A colocacao do DSG e a ventilacao adequada foram bem‐sucedidas em todas as tentativas. A visao da glote adequada para a IGFO diferiu entre os dispositivos, variou de 40% para o TL, 66% para a ML Supreme, 70% para a ML I‐Gel e 90% para ambas as mascaras laringeas Unique e AuraOnce. Conclusao Nenhum dos DSG usados ofereceu uma visao total ou parcial da glote em todos os casos. Porem, as mascaras laringeas Unique e AuraOnce pareceram mais adequadas para a IGFO em comparacao com os outros dispositivos.

Wir berichten uber einen Patienten mit Thoraxtrauma, der nach operativer Versorgung auf die Intensivstation aufgenommen wurde. Nach Erfullung entsprechender Protokollkriterien wurde er am 7. postoperativen Tag extubiert, musste aber trotz intermittierender nicht-invasiver Beatmung am 10. Tag bei progressiver Hyperkapnie re-intubiert werden. Wir entschieden uns zu einer extrakorporalen CO2-Elimination (ECCO2‑R) anstelle einer Tracheotomie. Mit einem Blutfluss von 1,5 l/min gelang eine suffiziente CO2-Elimination, sodass der Patient bereits wenige Stunden spater extubiert werden konnte. Nach funf Tagen an ECCO2‑R konnte der Patient vom System entwohnt und stabil auf Normalstation verlegt werden.

Background/aim For patients undergoing cancer surgery, the risk for cancer progression is enhanced during the perioperative period. To what extent the type of anesthetic can affect the metastatic process and finally the outcome of patients with cancer is under debate. For this reason, the aim of this study was to investigate the effects of the volatile anesthetics sevoflurane and desflurane on colon cancer cells in vitro. Materials and methods SW480 colon carcinoma cells were exposed for 3 or 6 h to sevoflurane (1 or 2.5 vol%) or desflurane (6 or 12 vol%). Cell cycle distribution was analyzed by flow cytometry after a 24-72 h recovery and apoptosis was detected by annexin V staining after a 0-48 h recovery. Viability was tested by measuring ATP content after 0 and 24 h recovery. Results Treatment with sevoflurane or desflurane caused no or only slight changes in cell-cycle distribution and apoptosis rate. Desflurane at 12vol% significantly reduced cell viability by 17±25% and 11±22% after 3 and 6 h incubation and 24 h recovery, respectively, while 2.5 vol% sevoflurane slightly increased viability. Conclusion At clinically relevant concentrations, sevoflurane and desflurane had only slight effects on SW480 colon cancer cells in vitro.

Background Pancreatic adenocarcinoma is one of the most lethal cancers worldwide with very poor long-term survival. The treatment of choice next to chemotherapy or radiation treatment is surgical removal of the tumor. However, medication, surgery, and perioperative immunosuppression induce the constitutive activation of important signaling pathways and change the regulation of transcription factors, which may facilitate tumor progression and metastasis. Recent research has identified the transcription factors NFATc2 and Sp1 as key regulators in the carcinogenesis of pancreatic carcinoma. It is still unclear to what extent the transcription factors NFATc2 and Sp1 are influenced by analgesics given via peridural anesthetics or lidocaine infusions administered in perioperative settings or as postoperative pain therapy.Aims To conduct an in vitro analysis of the impact of clinically achievable dosages of ketamine, s-ketamine, metamizole, and paracetamol as well as of sufentanil, ropicavaine, and lidocaine on pancreatic carcinoma cells in dependency of NFATc2 and Sp1.Methods Analgesic stimulation and its effects on the expression of NFATc2 and Sp1 were investigated with immunoblot. Cell proliferation was measured with the ELISA BrdU assay.Results In PaTu8988t pancreatic carcinoma cells, 48h stimulation with ketamine and s-ketamine significantly inhibited proliferation and contemporaneously decreased endogen expression of NFATc2 in the nucleus. The addition of metamizole and lidocaine to PaTu8988t cells reduced proliferation after 48h.Conclusions New treatment concepts target the efficient modulation of specific signaling and transcription pathways. The extent to which drugs influence these mechanisms in vulnerable phases of pancreatic carcinoma cells needs to be investigated in future studies. The basis of novel therapeutic approaches to any disease is detailed knowledge of the carcinogenesis and profound molecular and biological understanding of the mechanisms.

Oral nimodipine is used for prophylaxis and treatment of delayed cerebral ischemia in patients with aneurysmal or perimesencephalic subarachnoid hemorrhage (SAH). In cases of serious refractory cerebral vasospasm, a continuous intra-arterial (IA) infusion of nimodipine (CIAN) may be required to avoid cerebral ischemia. Nimodipine can cause arterial hypotension requiring either a dosage reduction or its discontinuation. Aim of the present study was to examine the effect of different nimodipine formulations on arterial blood pressure in aneurysmal or perimesencephalic SAH patients and to measure the plasma levels after both, peroral administration as tablet or solution and IA infusion. In a prospective setting, over a 1-year observation period, data on the course of arterial blood pressure and nimodipine dosage were collected for 38 patients undergoing treatment for aneurysmal or perimesencephalic SAH in an intensive care unit. In addition, plasma concentrations of nimodipine were measured by liquid chromatography–tandem mass spectrometry. The intended full dose of 60 mg of nimodipine given orally every 4 h could only be administered on 57.2% of the examined days. Ninety-seven episodes of relevant arterial hypotension probably caused by the administration of nimodipine were observed within the first 14 days of treatment. Drops in blood pressure occurred about three times as often after administration of nimodipine as oral solution than as tablet. However, there were no differences in nimodipine plasma levels between the two formulations. In patients suffering from higher-grade SAH, arterial hypotension and consequent dosage reduction or discontinuation of nimodipine were more frequent than in patients with lower-grade SAH. Plasma concentrations of nimodipine during CIAN did not exceed those achieved by oral administration. Dosage reduction or discontinuation of oral nimodipine is often necessary in patients with higher-grade SAH. Oral nimodipine solutions cause drops in blood pressure more frequently than tablets. Intra-arterial infusion rates of less than 1 mg/h result in venous plasma concentrations of nimodipine similar to those observed after oral application of 60 mg every 4 h.