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BACKGROUND: After transfusion of senescent red blood cells (RBCs) a considerable fraction is rapidly cleared from the recipients' circulation. Thus, transfusion of senescent RBCs may be less effective in terms of increasing hemoglobin concentration (cHb) after transfusion. STUDY DESIGN AND METHODS: Data were retrospectively obtained in patients who underwent major abdominal surgery between 2006 and 2012. Patients were eligible if they received RBCs during surgery and had at least two arterial blood gas analyses performed. The primary endpoint was the increase of recipients' cHb related to the transfusion of 1 unit of RBCs with respect to different storage periods. Four storage periods were defined according to the distribution of RBC storage of the study population. General estimating equation was used for calculation of the primary endpoint and to adjust for confounding variables. RESULTS: A total of 598 arterial blood gas samples from 120 patients, receiving 429 RBC units, were analyzed. Mean (±SD) RBC storage was 21 (±9) days. RBC storage duration and the increase in recipients' cHb were inversely and gradually related; that is, the older the RBCs, the lower the increase in the recipients' cHb after transfusion (storage

BackgroundProlonged catheter use is controversial because of the risk of catheter-related infection, but the extent to which the risk increases over time remains unknown. We thus assessed the time-dependence of catheter-related infection risk up to 15 days.MethodsOur analysis was based on the German Network for Regional Anesthesia, which includes 25 centers. We considered 44,555 patients who had surgery between 2007 and 2014 and had continuous regional anesthesia as well as complete covariable details. Cox regression analysis was performed and adjusted for confounding covariables to examine the relationship between catheter duration and probability of infection-free catheter use.ResultsAfter adjustment for confounding factors, the probability of infection-free catheter use decreases with each day of peripheral and epidural catheter use. In peripheral catheters, it was 99% at day 4 of catheter duration, 96% at day 7, and 73% at day 15. In epidural catheters, it was 99% at day 4 of catheter duration, 95% at day 7, and 73% at day 15. Only 31 patients (0.07%) had severe infections that prompted surgical intervention. Among these were five catheters that initially had only mild or moderate signs of infection and were left in situ; all progressed to severe infections.ConclusionsInfection risk in catheter use increases over time, especially after four days. Infected catheters should be removed as soon as practical.

Extralegal factors may influence judicial outcomes. Here we investigated the experience of incidental haptic sensations on the harshness of punishment recommendations. Based on recent theories of embodiment, which claim that cognitive representations are structured by metaphorical mappings from sensory experience, we hypothesized that tactile priming with hard objects would cause subjects to recommend harsher sentences (to be ‘hard on crime’). Furthermore, the theory of embodiment predicts that this effect should be based on sensorimotor brain activation during the judging process. In order to test this we presented participants with scenarios that described various crimes while scanning their brain activity with fMRI. Participants were then asked to rate how severely they would sentence the delinquents. Before the scenarios, the participants were primed by touching either a hard or a soft object. Results revealed tha t hard priming led participants to recommend harder punishments. These results were accompanied by activation of somatosensory brain areas during the judging phase. This outcome is in line with simulation assumptions of the embodiment theory and proposes a central role of the sensorimotor cortices for embodied metaphors. Thus, incidental tactile experiences can influence our abstract cognitions and even how hard we are on criminals.

Summary Purpose Indirect calorimetry (IC) is the gold standard for measuring energy expenditure (EE). Due to O 2 uptake and CO 2 removal by both the extracorporeal lung support (ECLS) membrane and the lungs, a conventional IC is not feasible and no data available. Our MEEP (Measuring Energy Expenditure in ECLS Patients) protocol enables the determination of the REE in patients with ECLS, the comparison to patients without ECLS, and accuracy assessment of estimating equations. Methods In the MEEP protocol, a conventional IC is performed and extended by a calculation of the O 2 uptake and the CO 2 elimination by the ECLS membrane. Sum O 2 uptake and CO 2 elimination were used in the equation of Weir to calculate EE. We included 20 patients with ARDS on veno-venous (vv)-extracorporeal membrane oxygenation (ECMO) treatment, and 20 matched ARDS patients without ECLS as control. EE measurements were compared to the most prevalent predicting equations for EE. Results The new MEEP-protocol was shown to be feasible. None of the estimating equations matched the measured EE. Measured EE values did not significantly differ between the ARDS patients with vv-ECMO (2013 kcal/d [1786/2333]) and ARDS patients without ECLS (1857 kcal/d [1602/2085]) (p = 0.165). The blood flow through the vv-ECMO itself did not influence the EE. Conclusion Using the MEEP protocol, EE becomes easily measurable in patients with ECLS. We recommend the implementation of sequential measurements of EE in the critically ill, especially for patients with ECLS, but also for those without, in order to improve goal directed nourishment.

Background: Chronic alcohol consumption is a major cause of liver injury. However, the molecular mechanisms by which alcohol impairs hepatocellular function and induces cell death remain unclear. Macroautophagy (hereafter called 'autophagy') is a degradation pathway involved in the survival or death of cells during conditions of cellular stress. This study examines the effect of chronic alcohol consumption on hepatocellular autophagy in an animal model. Methods: During a 12-week period male Wistar rats were fed a Lieber-DeCarli diet containing 5% alcohol (EtOH group; n=10), or an isocaloric diet (control group; n=10). Hepatic expression of key regulatory autophagy proteins (e.g. Beclin-1, ATG-3, ATG-5, p62/SQSTM1 and LC3) were detected by real-time polymerase chain reaction and Western blot analysis. Markers of cellular stress and apoptotic cell death (e.g. HO-1, caspase-3, PARP-1 and Bcl-2) were determined, and levels of reduced and oxidized glutathione were measured. Results: Chronic alcohol consumption caused cellular and oxidative stress in the liver. Transcriptional and translational expression of Beclin-1 and ATG-5 was significantly impaired. The protein expression of LC3-I and LC3-II was significantly increased, while the ratio of LC3I/II remained unchanged in the EtOH group compared with controls. Hepatocellular expression of p62/SQSTM1 and markers of apoptotic cell death (such as cleaved caspase-3 and cleaved PARP-1) were significantly increased in the EtOH group indicating a disrupted autophagic flux and increased rate of apoptosis in the liver. Conclusions: In this model, chronic alcohol consumption impaired hepatocellular autophagy and induced apoptotic cell death. It appears that changes in autophagy might contribute to alcohol-induced structural and functional hepatocellular injury.

Background: Postoperative immune suppression, particularly a loss of cell-mediated immunity, is commonly seen after surgery and is associated with worse outcome, i.e. delayed wound healing, infections, sepsis, multiple-organ failure and cancer recurrence. However, the recovery of immune cells focusing on differences between innate and acquired immunity during severe postoperative immunosuppression is not investigated. Methods: In this retrospective randomized controlled trial (RCT) subgroup analysis, 10 postoperatively immune suppressed patients after esophageal or pancreatic resection were analyzed. Innate and acquired immune cells, the expression of human leukocyte antigen-D related on monocytes (mHLA-DR), lipopolysaccharide (LPS)-induced monocytic TNF-α and IL-10 secretion ex vivo, Concanavalin A (Con A)-induced IFN-γ, TNF-α, IL-2, IL-4, IL-5 and IL-10 release were measured preoperatively (od) until day 5 after surgery (pod5). Recovery of immune cells was defined by a significant decrease respectively increase after a significant postoperative alteration. Statistical analyses were performed using nonparametric statistical procedures. Results: Postoperative alterations of innate immune cells recovered on pod2 (eosinophils), pod3 (neutrophils) and pod5 (mHLA-DR, monocytic TNF-α and IL-10 secretion), whereas alterations of acquired immune cells (lymphocytes, T cells, T helper cells, and cytotoxic T cells) did not recover until pod5. Peripheral blood T cells showed an impaired production of the T helper (Th) 1 cytokine IFN-γ upon Con A stimulation on pod1, while Th2 specific cytokine release did not change until pod5. Conclusions: Innate immunity recovered earlier than acquired immunity during severe postoperative immunosuppression. Furthermore, we found a more anti- than pro-inflammatory T cell function on the first day after surgery, while T cell counts decreased.

ZusammenfassungPatienten mit Frailty sind anfälliger dafür, Komplikationen während und nach einer Operation zu entwickeln. Bei steigender Prävalenz dieses Syndroms werden das Erkennen sowie das spezielle Management von gebrechlichen Patienten in der perioperativen Phase wichtiger und könnte dazu beitragen, das perioperative Outcome dieser Patienten zu verbessern. Basierend auf aktueller Literatur und Leitlinien, präsentieren wir eine Zusammenstellung von grundlegenden Strategien, die eingesetzt werden können, um postoperative Komplikationen bei Patienten mit Frailty zu reduzieren. Aufgrund ihrer eingeschränkten Anpassungsmechanismen auf Stressoren werden besonders für Patienten mit Frailty potenzielle perioperative Gefahren identifiziert und diskutiert. Dazu gehören das Risiko von Dehydratation, Hypothermie, kardiovaskulärer Dekompensation, ungewöhnlicher Arzneimittelreaktionen und Delirium. Ebenso wird auf die Notwendigkeit von früher Mobilisierung und Ernährungsunterstützung eingegangen. Wenn Frailty präoperativ erkannt und dem Behandlerteam die erhöhte Komplikationsgefahr bewusst wird, gibt es Strategien, die in der perioperativen Versorgung umgesetzt werden können, um die Chancen einer erfolgreichen Erholung des Patienten zu erhöhen.

ZusammenfassungFrailty (Gebrechlichkeit) ist eine Einschränkung der physiologischen Reserve bei älteren Patienten mit schwerwiegenden individuellen und sozioökonomischen Folgen. Multiple Aspekte der Patientenbehandlung sowie das Outcome werden durch Frailty nachhaltig beeinflusst. Obwohl mehr als 60 Messinstrumente existieren, sind die Erfassung und Berücksichtigung funktioneller Assessments in der klinischen Routine unzureichend umgesetzt. Das interdisziplinäre und interprofessionelle Verständnis, warum und wie Frailty beurteilt werden sollte, ist die Grundlage für die dauerhafte Implementierung. Der Artikel zeigt die Auswirkungen von Frailty und Vorteile einer Früherkennung auf und gibt einen Überblick über die wichtigsten Instrumente, die in der Frailty-Erkennung und -Bewertung verwendet werden können. Die frühe präoperative Detektion bietet ein vielfältiges Optimierungspotenzial für die peri- und intraoperative Versorgung. Verschiedene Frailty-Assessment-Tools körperlicher, kognitiver und psychosozialer Domänen werden vorgestellt und diskutiert. Frailty-Assessments variieren immens in Bezug auf die erforderliche Zeit, die Ausrüstung und das Fachwissen zur Durchführung. Wir empfehlen mindestens einen Test für die einzelnen Dimensionen von Frailty, um ein holistisches Bild der geriatrischen Patienten zu erhalten. Die Bewertung von Frailty sollte übergreifend in die interdisziplinären Strukturen der klinischen Routine implementiert werden, um die Patientensicherheit sowie das kurz- und langfristige Outcome zu verbessern.

Objectives Dexamethasone has become the standard of care for severe coronavirus disease 2019 (COVID-19), but its virological impact is poorly understood. The objectives of this work were to characterize the kinetics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) concentration in the upper respiratory tract (URT) and the antibody response in patients with (D+) and without (D–) dexamethasone treatment. Methods Data and biosamples from hospitalized patients with severe COVID-19, enrolled between 4th March and 11th December 2020 in a prospective observational study, were analysed. SARS-CoV-2 virus concentration in serial URT samples was measured using RT-PCR. SARS-CoV-2-specific immunoglobulins A and G (IgA and IgG) were measured in serum samples using S1-ELISA. Results We compared 101 immunocompetent patients who received dexamethasone (according to the inclusion criteria and dosage determined in the RECOVERY trial) to 93 immunocompetent patients with comparable disease severity from the first months of the pandemic, who had not been treated with dexamethasone or other glucocorticoids. We found no inter-group differences in virus concentration kinetics, duration of presence of viral loads >106 viral copies/mL (D+ median 17 days (IQR 13–24), D– 19 days (IQR 13–29)), or time from symptom onset until seroconversion (IgA: D+ median 11.5 days (IQR 11–12), D– 14 days (IQR 11.5–15.75); IgG: D+ 13 days (IQR 12–14.5), D– 12 days (IQR 11–15)). Conclusion Dexamethasone does not appear to lead to a change in virus clearance or a delay in antibody response in immunocompetent patients hospitalized with severe COVID-19.

Background Grip strength measurement is a widely used method for clinical as well as scientific purposes. In hand surgery, it is an essential component in the diagnosis of disease, treatment sequences and assessment. In epidemiological studies, it is a good predictor of healthy ageing or disease progression. Problem Measurement results and their interpretation can be influenced by many factors. The historical development of dynamometry, measurement technology and the standard values in various population groups are presented. Comparisons with standard values should only be made using current tables because the grip strength has changed in recent decades. Assessment of the voluntarily submaximal grip strength remains problematic. Proposals are made for how to assess grip strength during the evaluation.

Eine 43-jahrige Patientin, mit Z. n. schwerer Sepsis und Entwicklung einer Critical-Illness-Myopathie/Polyneuropathie, stellt sich nach 5 Monaten mit einer akut aufgetretenen Allodynie/Hyperalgesie vor. Diese betrifft alle 4 Extremitaten distal, mit deutlicher Betonung im Versorgungsgebiet der Nn. ulnarii. Nach differenzialdiagnostischer Abklarung wird die Diagnose einer „Late-onset Small-Fiber-Neuropathie nach Critical Illness“ gestellt. Small-Fiber-Neuropathien, bei kritischer Erkrankung und auch im Follow-up, einhergehend mit neuropathischen Beschwerden, konnten in einigen neueren Studien gezeigt werden. Pathophysiologisch ist am ehesten eine Dysfunktion der spannungsabhangigen Natriumkanale, im Rahmen einer erhohten Insulinresistenz wahrend der kritischen Erkrankung, zu vermuten. Therapeutisch sind somit Kuhlung, Carbamazepin/Oxcarbazepin, trizyklische Antidepressiva und serielle Injektionen mit Lokalanasthetika am ehesten zu empfehlen.

Aim: Acute kidney injury (AKI) is diagnosed by a 50% increase in creatinine. For patients without a baseline creatinine measurement, guidelines suggest estimating baseline creatinine by back-calculation. The aim of this study was to evaluate different glomerular filtration rate (GFR) equations and different GFR assumptions for back-calculating baseline creatinine as well as the effect on the diagnosis of AKI.Methods: The Modification of Diet in Renal Disease, the Chronic Kidney Disease Epidemiology (CKD-EPI) and the Mayo quadratic (MQ) equation were evaluated to estimate baseline creatinine, each under the assumption of either a fixed GFR of 75 mL min(-1) 1.73 m(-2) or an ageadjusted GFR. Estimated baseline creatinine, diagnoses and severity stages of AKI based on estimated baseline creatinine were compared to measured baseline creatinine and corresponding diagnoses and severity stages of AKI.Results: The data of 34 690 surgical patients were analysed. Estimating baseline creatinine overestimated baseline creatinine. Diagnosing AKI based on estimated baseline creatinine had only substantial agreement with AKI diagnoses based on measured baseline creatinine [Cohen's kappa ranging from 0.66 (95% CI 0.65-0.68) to 0.77 (95% CI 0.76-0.79)] and overestimated AKI prevalence with fair sensitivity [ranging from 74.3% (95% CI 72.3-76.2) to 90.1% (95% CI 88.6-92.1)]. Staging AKI severity based on estimated baseline creatinine had moderate agreement with AKI severity based on measured baseline creatinine [Cohen's kappa ranging from 0.43 (95% CI 0.42-0.44) to 0.53 (95% CI 0.51-0.55)].Conclusion: Diagnosing AKI and staging AKI severity on the basis of estimated baseline creatinine in surgical patients is not feasible. Patients at risk for post-operative AKI should have a pre-operative creatinine measurement to adequately assess post-operative AKI.

Intensivmedizinische (ITS-)Behandlung hat langfristige Folgen, die in der Akutphase haufig noch nicht absehbar sind. Muskelschwache, kognitive Schaden und psychische Erkrankungen nach einer ITS-Behandlung werden unter dem Begriff „post-intensive care syndrome“ (PICS) zusammengefasst. Analgesie-, Sedierungs- und Delirmanagementprotokolle sowie nichtmedikamentose Praventions- und Therapieansatze reduzieren diese Komplikationen und verbessern langfristig das Uberleben. Das Prinzip der „early goal-directed therapy“ bildet die Versorgungsbasis. Hierbei wird ein Behandlungsziel definiert, durch validierte Monitoringverfahren erfasst und die Therapie angepasst. Die Datenlage fuhrte zu einem Paradigmenwechsel hin zum wachen, aufmerksamen und partizipativen Patienten. Individualisierte Analgesie- und (Nicht-)Sedierungskonzepte ermoglichen heute fur die uberwiegende Zahl der Patienten einen Richmond-Agitation-Sedation-Scale(RASS)-Zielwert von 0/−1. Ist eine Sedierung indiziert, soll eine Ubersedierung, speziell die fruhe tiefe Sedierung, vermieden werden.

Gaps and uncertainty exist regarding the understanding of optimal clinical goals for perioperative (ie, preoperative, intraoperative, and postoperative) blood pressure (BP) management in patients undergoing cardiac surgery and the consequences of achieving or failing to achieve those goals. In this setting, it is understood that preoperative hypertension is predictive of poor postoperative outcomes, with a growing appreciation that current, clinically acceptable changes in intraoperative BP also may be associated independently with adverse short- and long-term outcomes. In contrast, the impact of postoperative BP on outcomes after cardiac surgery remains less clear.This study was a retrospective outcome analysis.The study included all cardiac surgery patients cared for at a single institution over a 7-year period. Consequences of the success or failure of meeting postoperative BP targets on medical outcomes and health resource utilization were evaluated.The study comprised 5,225 patients. Hypertensive postoperative patients experienced a higher in-hospital mortality rate compared with matched-case normotensive patients (4.97% v 1.32%, p0.001) and a longer hospital stay (p = 0.024). In hypertensive patients, serum creatinine levels from postoperative day 1 through postoperative day 7 were increased compared with baseline and postoperative renal dysfunction according to the Kidney Disease: Improving Global Outcomes criteria occurred significantly more often (25.3% v 19.7%, p = 0.027).Postoperative hypertension is associated with compromised outcome as reflected by higher mortality, longer length of stay, and higher incidence of renal dysfunction.

Der demografische Wandel und die Zunahme der Komplexitat diagnostischer und chirurgischer Eingriffe haben dazu gefuhrt, dass akute Nierenschadigung eine postoperative Komplikation mit zunehmender Relevanz ist. Postoperative akute Nierenschadigung ist mit hoherer Mortalitat und Morbiditat sowie mit erhohten Behandlungskosten assoziiert. Ob postoperative akute Nierenschadigung tatsachlich kausal mit einem schlechteren chirurgischen Behandlungsergebnis verknupft ist, ist bisher nicht zweifelsfrei bewiesen. Dieser Artikel soll einen Uberblick uber das Phanomen postoperative akute Nierenschadigung geben, die Schwierigkeiten bei der Fuhrung des Kausalbeweises in biomedizinscher Forschung erortern und letztlich Argumente fur und gegen den kausalen Zusammenhang zwischen posto-perativer akuter Nierenschadigung und dem chirurgischem Behandlungsergebnis diskutieren.

Hintergrund Die Atiologie des Fibromyalgiesyndroms ist bislang nicht hinreichend geklart. Gegenwartig wird diskutiert, inwiefern sich durch eine Behandlung mit Gamma-Hydroxybuttersaure (GHB) endokrinologische Auffalligkeiten bei Fibromyalgiepatienten positiv beeinflussen lassen konnten.

To evaluate test validity of the Pediatric Confusion Assessment Method for the ICU, the Pediatric Anesthesia Emergence Delirium scale, and the newly developed severity scale for the Pediatric Confusion Assessment Method for the ICU; to prospectively assess covariates and their influence on test validity of the scores. Prospective observational cohort study. PICU of a tertiary care medical center. Critically ill patients 5 years old or older ventilated or nonventilated with an ICU length of stay of at least 24 hours. None. Patients were scored with the Pediatric Confusion Assessment Method for the ICU and the Pediatric Anesthesia Emergence Delirium scale once daily for a maximum of 21 days. Validity was determined by comparing scoring results with the evaluations of the delirium experts who used the criteria of the Diagnostic and Statistical Manual, 4th Edition, Text Revision, for delirium diagnosis. Sixty-four patients were enrolled and 214 assessments were conducted and included in data analysis. The first assessments within each patient revealed sensitivities of 69.2% for the Pediatric Anesthesia Emergence Delirium scale, 76.9% for the Pediatric Confusion Assessment Method for the ICU, and 84.9% for the severity scale for the Pediatric Confusion Assessment Method for the ICU. Specificities were 98% for all scores. Considering repeated measurements, sensitivities decreased to 35.9% for the Pediatric Anesthesia Emergence Delirium scale and to 52.3% for the Pediatric Confusion Assessment Method for the ICU. The sensitivity of the severity scale for the Pediatric Confusion Assessment Method for the ICU dropped to 71.8%, which was significantly higher compared to the Pediatric Anesthesia Emergence Delirium scale (p = 0.0008). Receiver operator characteristic regression unveiled that sedation and mechanical ventilation had a significant negative effect on the validity of the Pediatric Anesthesia Emergence Delirium scale and the severity scale for the Pediatric Confusion Assessment Method for the ICU. Age and gender had a significant impact on the receiver operator characteristic curve of the severity scale for the Pediatric Confusion Assessment Method for the ICU. The severity scale for the Pediatric Confusion Assessment Method for the ICU showed the best test validity when used in critically ill children of 5 years old or older. Nevertheless, validity of delirium screening itself depends on patient specific factors. These factors should be taken into consideration when choosing a delirium screening instrument.

Background Preoperative anemia and transfusion are associated with increased morbidity and mortality in cardiac surgery patients. It is unclear which of these factors plays the leading role in poor outcomes after cardiac surgery. The goal of this study was to analyze the influence of anemias of varying severity and intraoperative transfusion on long-term survival, and to characterize their interaction in cardiac surgery patients. Methods This was an observational cohort study conducted at a German university hospital. All patients undergoing cardiac surgery between 2006 and 2011 were screened for eligibility; duration of follow-up was 3 years. A total of 4494 patients were suitable for analysis; data on long-term survival were available for 3131 of these patients. The main outcome measure was survival at the 3-year follow-up. Length of stay and in-hospital mortality were assessed as secondary outcomes. Results Multivariate Cox regression analyses indicated that both the severity of preoperative anemia (mild anemia: hazard ratio [HR], 1.441; 95% confidence interval [CI], 1.201-1.728; severe anemia: HR, 1.805; 95% CI, 1.336-2.440) and intraoperative transfusion (HR, 1.340; 95% CI, 1.109-1.620) were associated with decreased long-term survival. Long-term survival was worse in anemic patients who received an intraoperative transfusion compared with those who did not receive an intraoperative transfusion. Conclusions Both preoperative anemia and transfusion are by themselves and in combination associated with decreased long-term survival. When anemic patients require transfusion, our results provide evidence that the risk of death after cardiac surgery may depend to a considerable extent on the severity of preoperative anemia.

OBJECTIVES: Mechanical ventilation can cause ventilator-induced brain injury via afferent vagal signaling and hippocampal neurotransmitter imbalances. The triggering mechanisms for vagal signaling during mechanical ventilation are unknown. The objective of this study was to assess whether pulmonary transient receptor potential vanilloid type-4 (TRPV4) mechanoreceptors and vagal afferent purinergic receptors (P2X) act as triggers of ventilator-induced brain injury. DESIGN: Controlled, human in vitro and ex vivo studies, as well as murine in vivo laboratory studies. SETTING: Research laboratory. SUBJECTS: Wild-type, TRPV4-deficient C57BL/6J mice, 8-10 weeks old. Human postmortem lung tissue and human lung epithelial cell line BEAS-2B. INTERVENTION: Mice subjected to mechanical ventilation were studied using functional MRI to assess hippocampal activity. The effects of lidocaine (a nonselective ion-channel inhibitor), P2X-purinoceptor antagonist (iso-PPADS), or genetic TRPV4 deficiency on hippocampal dopamine-dependent pro-apoptotic signaling were studied in mechanically ventilated mice. Human lung epithelial cells (BEAS-2B) were used to study the effects of mechanical stretch on TRPV4 and P2X expression and activation. TRPV4 levels were measured in postmortem lung tissue from ventilated and nonventilated patients. MEASUREMENTS AND MAIN RESULTS: Hippocampus functional MRI analysis revealed considerable changes in response to the increase in tidal volume during mechanical ventilation. Intratracheal lidocaine, iso-PPADS, and TRPV4 genetic deficiency protected mice against ventilationinduced hippocampal pro-apoptotic signaling. Mechanical stretch in both, BEAS-2B cells and ventilated wild-type mice, resulted in TRPV4 activation and reduced Trpv4 and P2x expression. Intratracheal replenishment of adenosine triphosphate in Trpv4 mice abrogated the protective effect of TRPV4 deficiency. Autopsy lung tissue from ventilated patients showed decreased lung TRPV4 levels compared with nonventilated patients. CONCLUSIONS: TRPV4 mechanosensors and purinergic receptors are involved in the mechanisms of ventilator-induced brain injury. Inhibition of this neural signaling, either using nonspecific or specific inhibitors targeting the TRPV4/adenosine triphosphate/P2X signaling axis, may represent a novel strategy to prevent or treat ventilator-induced brain injury.

BACKGROUND Different studies in adults reported significant outcome improvement for patients treated with high adherence to guidelines. The present study was initiated to evaluate the impact of adherence to antibiotic prescription guidelines on health outcomes of children on paediatric intensive care unit (PICU) suffering from pneumonia. METHODS This retrospective cohort study was conducted on a paediatric intensive care unit at Charite hospital Berlin. All patients with a length of stay (LOS) >24 hours, age

Empathy influences how we perceive, understand, and interact with our social environment. Previous studies suggested a network of different brain regions as a neural substrate for empathy, including, in particular, insula and anterior cingulate cortex (ACC). In addition, a contribution of the somatosensory cortices for this empathy related network has been suggested. This is remarkable, given that other recent studies have revealed a role for the somatosensory cortex in various social tasks. For example, in experiments using tactile priming, incidental haptic sensations are found to influence judgment recommendations. Here, we aimed to test if this engagement of the somatosensory cortices during tactile priming can be predicted by the participant's empathy personality traits. We assessed participant's empathy and personality traits by means of the Interpersonal Reactivity Index (IRI) and NEO-FFI and tested whether trait empathy is associated with the tactile priming effect in social judgments. Results revealed that empathy predicted the tactile priming effect negatively. This was accompanied by a reduced engagement of the somatosensory cortex, which has been shown to be associated with the priming effect. We conclude that empathy seems to protect people from tactile priming effects.

Background Illnesses that necessitate intensive care can impair cognitive function severely over the long term, leaving patients less able to cope with the demands of everyday living and markedly lowering their quality of life. There has not yet been any comprehensive study of the cognitive sequelae of critical illness among non- surgical patients treated in intensive care. The purpose of this review is to present the available study findings on cognitive deficits in such patients, with particular at- tention to prevalence, types of deficit, clinical course, risk factors, prevention, and treatment. Methods This review is based on pertinent publications retrieved by a selective search in MEDLINE. Results The literature search yielded 3360 hits, among which there were 14 studies that met our inclusion criteria. 17-78% of patients had cognitive deficits after dis- charge from the intensive care unit; most had never had a cognitive deficit before. Cognitive impairment often persisted for up to several years after discharge (0.5 to 9 years) and tended to improve over time. The only definite risk factor is delirium. Conclusion Cognitive dysfunction is a common sequela of the treatment of non-surgical patients in intensive care units. It is a serious problem for the affected persons and an increasingly important socio-economic problem as well. The effective management of delirium is very important. General conclusions are hard to draw from the available data because of heterogeneous study designs, varying methods of measurement, and differences among patient cohorts. Further studies are needed so that study designs and clinical testing procedures can be standard- ized and effective measures for prevention and treatment can be identified.

Background Hyperglycemia frequently occurs during major surgery and is associated with adverse postoperative outcomes. This study aimed to investigate the influence of intraoperative hyperglycemia on incidences of postoperative delirium (POD) and postoperative cognitive dysfunction (POCD). Methods Eighty-seven patients aged ≥65 years undergoing elective surgery were included in this prospective observational subproject of the BioCog study. Blood glucose (BG) levels were measured every 20 minutes intraoperatively. Hyperglycemia was defined as BG levels ≥150 mg·dL-1. Patients were assessed for POD twice daily until postoperative day 7. The occurrence of POCD was determined three months after surgery. Multivariable logistic regression was used to identify associations between hyperglycemia and POD as well as POCD. Secondary endpoints comprised duration of hyperglycemia, maximum glucose level (Glucosemax) and differences between diabetic and non-diabetic patients. Results POD occurred in 41 (47.1%), POCD in five (15.2%) patients. In two separate multivariable logistic regression models, hyperglycemia was significantly associated with POD (OR 3.86 [CI 95% 1.13, 39.49], P=0.044) but not POCD (3.59 [NaN, NaN], P=0.157). Relative duration of hyperglycemia was higher in POD patients compared to patients without POD (20 [0; 71] % versus 0 [0; 55] %, P=0.075), whereas the maximum glucose levels during surgery were similar between the two groups. Considering only non-diabetic patients, relative duration of hyperglycemia (P=0.003) and Glucosemax (P=0.015) were significantly higher in patients with POD. Conclusions Intraoperative hyperglycemia was independently associated with POD but not POCD. Relative duration of hyperglycemia appeared thereby to also play a role. Especially hyperglycemic non-diabetic patients might be at high risk for POD.

The radial arm maze (RAM) is a common behavioral test to assess spatial working and reference memory in mice. However, conventional RAM experiments require a substantial degree of manual handling and animals are usually subjected to prolonged periods of food or water deprivation to achieve sufficient learning motivation resulting in stress-induced confounding effects and unwanted intra- and inter-subject variation. In a proof-of-concept approach to improve reliability and repeatability of results by refining the conventional maze methodology, we developed a voluntary, fully automated 8-arm RAM and tested its feasibility and usability using both spatial working and combined working/reference memory paradigms in ten female C57BL/6J mice. We demonstrate that experimental procedures of up to 7 days duration could be conducted without any manual animal handling and that mice up to 18 months of age showed robust spatial learning performance without any food or water restrictions being applied. Therefore, a voluntary, automated 8-arm RAM can serve to minimize variation in experimental results by reducing an animal's distress, suffering, and pain, which, in turn, contributes to the comprehensive application of 3R principles.

Objective: To investigate the influence of midazolam premedication on the EEG-spectrum before and during general anesthesia in elderly patients. Methods: Patients aged ≥65 years, undergoing elective surgery were included in this prospective observational study. A continuous pre- and intraoperative frontal EEG was recorded in patients who received premedication with midazolam (Mid, n = 15) and patients who did not (noMid, n = 30). Absolute power within the delta (0.5–4 Hz), theta (4–8 Hz), alpha (8–12 Hz), and beta (12–25 Hz) frequency-bands was analyzed in EEG-sections before (pre-induction), and after induction of anesthesia with propofol (post-induction), as well as during general anesthesia with either propofol or volatile-anesthetics (intra-operative). Results: Pre-induction, α-power of Mid patients was lower compared with noMid-patients (α-power: Mid: −10.75 dB vs. noMid: −9.20 dB; p = 0.036). After induction of anesthesia Mid-patients displayed a stronger increase of frontal α-power resulting in higher absolute α-power at post-induction state, (α-power: Mid −3.56 dB vs. noMid: −6.69 dB; p = 0.004), which remained higher intraoperatively (α-power: Mid: −2.12 dB vs. noMid: −6.10 dB; p = 0.024). Conclusion: Midazolam premedication alters the intraoperative EEG-spectrum in elderly patients. Significance: This finding provides further evidence for the role of GABAergic activation in the induction of elevated, frontal α-power during general anesthesia. Keywords: Physiology (medical); Sensory Systems; Neurology; Clinical Neurology; Premedication; Benzodiazepines – midazolam; EEG; Geriatric anesthesia; Propofol anesthesia, Seventh Framework Programme (European Commission) (Grant HEALTH-F2-2014-60246)

Leptin and adiponectin are adipose-tissue derived hormones primarily involved in glucose, lipid, and energy metabolism, inflammation, and atherosclerosis. Both adipokines may cross the blood-brain barrier but evidence on their roles in cognitive impairment is limited and conflicting. Here, we determined associations of plasma adipokine concentration with cognitive impairment in older adults.Cross-sectional analysis of baseline data from 669 participants aged ≥65 years of the Biomarker Development for Postoperative Cognitive Impairment in the Elderly (BioCog) study were recruited 2014-2017 at study sites in Berlin, Germany and Utrecht, the Netherlands. Cognitive impairment was defined as the lowest tertile of a cognitive summary score derived from six neuropsychological tests.After adjustment for age, sex, fasting, BMI, diabetes, hypertension, cerebrovascular disease, and coronary heart disease, higher leptin concentrations and a higher leptin/adiponectin ratio (LAR) were associated with a higher odds of cognitive impairment (OR per 1 SD higher leptin concentration, 1.33; 95 % CI 1.05, 1.69; p = 0.02; OR per 1 SD higher LAR, 1.26; 95 % CI 1.01, 1.57; p = 0.04). Sensitivity analyses determined that these findings were driven by the non-obese group (BMI 30 kg/mWith leptin as a known promoter of atherosclerosis and inflammation, our findings point to a pathogenic role of leptin in age-related cognitive impairment that may be limited to non-obese individuals and warrants further investigation.

Background: General (GA)- and epidural-anesthesia may cause a drop in body-core-temperature (BCTdrop), and hypothermia, which may alter tissue oxygenation (StO2) and microperfusion after cytoreductive surgery for ovarian cancer. Cell metabolism of subcutaneous fat- or skeletal muscle cells, measured in microdialysis, may be affected. We hypothesized that forced-air prewarming during epidural catheter placement and induction of GA maintains normothermia and improves microperfusion. Methods: After ethics approval 47 women scheduled for cytoreductive surgery were prospectively enrolled. Women in the study group were treated with a prewarming of 43°C during epidural catheter placement. BCT (Spot on®, 3M) was measured before (T1), after induction of GA (T2) at 15 min (T3) after start of surgery, and until 2h after ICU admission (TICU2h). Primary endpoint was BCTdrop between T1 and T2. Microperfusion-, hemodynamic- and clinical outcomes were defined as secondary outcomes. Statistical analysis used the Mann-Whitney-U- and non-parametric-longitudinal tests. Results: BCTdrop was 0.35 °C with prewarming and 0.9 °C without prewarming (p< 0.005) and BCT remained higher over the observation period (ΔT4 = 0.9 °C up to ΔT7 = 0.95 °C, p

Frailty is a geriatric syndrome defined by coexistence of unintentional weight loss, low physical reserve, or activity and is associated with adverse health events. Neuroimaging studies reported structural white matter changes in frail patients. In the current study, we hypothesized that clinical frailty is associated also with functional changes in motion-related cortical areas, that is, (pre-)supplementary motor areas (SMA, pre-SMA). We expected that observed functional changes are related to motor-cognitive test performance. We studied a clinical sample of 143 cognitively healthy patients ≥65 years presenting for elective surgery, enrolled in the BioCog prospective multicentric cohort study on postoperative cognitive disorders. Participants underwent preoperative resting-state functional magnetic resonance imaging, motor-cognitive testing, and assessment of Fried’s modified frailty criteria. We analyzed functional connectivity associations with frailty and motor-cognitive test performance. Clinically robust patients (N = 60) showed higher connectivity in the SMA network compared to frail (N = 13) and prefrail (N = 70) patients. No changes were found in the pre-SMA network. SMA connectivity correlated with motor speed (Trail-Making-Test A) and manual dexterity (Grooved Pegboard Test). Our results suggest that diminished functional connectivity of the SMA is an early correlate of functional decline in the older adults . The SMA may serve as a potential treatment target in frailty.

Background Recent guidelines on postoperative delirium (POD) recommend POD screening in all patients, using a validated tool, starting in the recovery room. An operationalisation of the Confusion Assessment Method (CAM) criteria, the 3-Minute Diagnostic Interview for CAM-defined Delirium (3D-CAM), has been developed for use in general medical units. Objectives The aim of this study was to evaluate 3D-CAM performance in an adult patient population to detect POD in the recovery room. Design A prospective diagnostic study. Setting Recovery room of a tertiary care university hospital in Berlin, Germany, in 2017. Patients Patients at least 18 years of age undergoing elective surgery. Main outcome measures Patients were subjected to evaluation by blinded investigators using the 3D-CAM and the Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5, reference standard). Sensitivity, specificity and positive predictive value (PPV) and negative predictive value (NPV) were analysed for 3D-CAM, in addition to test-retest and inter-rater reliability analyses. Results Sixteen out of 176 patients (9.1%) developed POD. The 3D-CAM demonstrated strong test performance (specificity 0.88, sensitivity 1.0, area under the curve 0.94, PPV 0.44 and NPV 1.0), with a test-retest reliability of 90% (n = 10) and inter-rater reliability of 80% (n = 10). Conclusion In this diagnostic study, 3D-CAM showed strong performance for detection of POD in the recovery room. Due to the low training requirements, fast application and high sensitivity, it might be particularly appropriate for clinical staff with limited experience in the assessment of POD. Trial registration ClinicalTrials.gov Identifier: NCT02992717.

Biobanking of Mycobacterium tuberculosis (Mtb) sputum samples for future research activities recommends the use of -70°C or -80°C freezers. Infrastructure for biobanking is not readily available in the majority of low-income countries. This study aimed to assess the recovery rate of Mtb isolates stored at room temperature for more than 6 years in Zimbabwe.Census samples of all confirmed rifampicin-resistant/multidrug-resistant tuberculosis isolates that were stored in mycobacterial growth indicator tubes (MGITs) at room temperature from 2011 to 2016 were identified and retrieved. The samples were subcultured on MGIT and 7H10 solid media for the extraction of genomic deoxyribonucleic acid using the phenol/chloroform method followed by precipitation with isopropanol.A total of 248/400 (62%) isolates were successfully recovered. Recovery rates increased with declining time since the last culture, with 51% for samples stored for 6 years which increased to 77% for those stored for 1 year. The isolates that grew but were contaminated during the first subculture at the National Microbiology Reference Laboratory in Harare could not be recovered through decontamination because of limited resources. Decontamination was only possible during the second culture at the University of Stellenbosch.Storage of Mtb isolates at room temperature is a viable option in low-income countries where currently recommended biobanking procedures may not be available. This low-cost biobanking will facilitate research activities years later as new questions arise. Standard infection prevention and control when handling Mtb samples stored under room temperature for long periods is strongly recommended as these bacteria remain viable longer than previously reported.

Background Emergence-delirium is the most frequent brain dysfunction in children recovering from general anaesthesia, though the pathophysiological background remains unclear. The presented study analysed an association between emergence delirium and intraoperative burst suppression activity in the electroencephalogram, a period of very deep hypnosis during general anaesthesia. Methods In this prospective, observational cohort study at the Charité - university hospital in Berlin / Germany children aged 0.5 to 8 years old, undergoing planned surgery, were included between September 2015 and February 2017. Intraoperative bi-frontal electroencephalogram monitoring were recorded. Occurrence and duration of burst suppression periods were visually analysed. Emergence delirium was assessed with the Pediatric Assessment of Emergence Delirium Score. Results From 97 children being analysed within this study, 40 children developed emergence delirium, and 57 children did not. Overall 52% of the children displayed intraoperative burst suppression periods; however, occurrence and duration of burst suppression (Emergence delirium group 55% / 261+462sec vs. Non-emergence delirium group 49% / 318+531sec) did not differ in between both groups. Conclusions Our data reveal no correlation between the occurrence and duration of intraoperative burst suppression activity and the incidence of emergence delirium. Burst suppression occurrence is frequent; however, it does not seem to have an unfavourable impact on cerebral function at emergence from general anaesthesia in children.

BACKGROUND Skeletal muscle failure in critical illness (intensive care unit-acquired weakness) is a well-known complication developing early during intensive care unit stay. However, muscle weakness during the perioperative setting has not yet been investigated. METHODS We performed a subgroup investigation of a prospective observational trial to investigate perioperative muscle weakness. Eighty-nine patients aged 65 years or older were assessed for handgrip strength preoperatively, on the first postoperative day, at intensive care unit discharge, at hospital discharge, and at 3-month follow-up. Functional status was evaluated perioperatively via Barthel index, instrumental activities of daily living, Timed Up and Go test, and functional independence measure. After exclusion of patients with intensive care unit-acquired weakness or intensive care unit stay of ≥72 hours, 59 patients were included into our analyses. Of these, 14 patients had additional pulmonary function tests preoperatively and on postoperative day 1. Blood glucose was measured intraoperatively every 20 minutes. RESULTS Handgrip strength significantly decreased after surgery on postoperative day 1 by 16.4% (P < .001). Postoperative pulmonary function significantly decreased by 13.1% for vital capacity (P = .022) and 12.6% for forced expiratory volume in 1 second (P = .001) on postoperative day 1. Handgrip strength remained significantly reduced at hospital discharge (P = .016) and at the 3-month follow-up (P = .012). Perioperative glucose levels showed no statistically significant impact on muscle weakness. Instrumental activities of daily living (P < .001) and functional independence measure (P < .001) were decreased at hospital discharge, while instrumental activities of daily living remained decreased at the 3-month follow-up (P = .026) compared to preoperative assessments. CONCLUSIONS Perioperatively acquired weakness occurred, indicated by a postoperatively decreased handgrip strength, decreased respiratory muscle function, and impaired functional status, which partly remained up to 3 months.

BACKGROUND: Allogeneic red blood cells (RBCs) have the potential to impact the immunosurveillance of the recipient and may therefore increase the risk of recurrence after cancer surgery. In this article the relationship between perioperative RBC transfusion and the risk of recurrence after ovarian cancer surgery is examined. STUDY DESIGN AND METHODS: This is a retrospective cohort analysis of a prospective database of patients who underwent surgery due to primary ovarian cancer between 2006 and 2014 and who had no residual disease after surgery. Patients who did and did not receive perioperative RBC transfusion were compared. The primary endpoint was progression-free survival (PFS). Propensity score matching (PSM) and Cox proportional hazards regression (CPH) was used to control for between-group differences of prognostic determinants. RESULTS: A total of 529 patients with a median follow-up of 51.4 months (95% CI, 46.1-56.5) were eligible for analysis. Of those, 408 patients (77.1%) received allogeneic, leukoreduced RBCs with a median of 4 units (IQR, 2-6) per patient. There was a strong selection bias of prognostic determinants between patients with and without transfusion. In unadjusted analysis, transfusion of RBCs was associated with an increased risk of cancer recurrence (hazard ratio [HR] of PFS 2.71 [95% CI, 1.94-3.77], p < 0.001). After bias reduction, transfusion of RBCs was no longer associated with an increased risk of cancer recurrence, neither in PSM-adjusted (HR 1.03 [95% CI, 0.59-1.80], p = 0.91), nor in multivariable CPH-adjusted analysis (HR 1.26 [95% CI, 0.85-1.86], p = 0.23). CONCLUSION Perioperative transfusion of RBCs did not increase the risk of recurrence after ovarian cancer surgery.

Im operativ-chirurgischen Bereich besteht eine hohe Pravalenz von Suchterkrankungen. Substanzmissbrauch ist mit einer erhohten Morbiditat assoziiert. Dies bedingt einen haufigen Kontakt des klinisch tatigen Anasthesisten mit suchtkranken Patienten. Beim suchtkranken Patienten ist ein gezieltes diagnostisches Vorgehen erforderlich, da die Suchtdiagnose oft entweder erst anhand von Komplikationen im Verlauf gestellt wird oder die Intoxikation eine schwerwiegende Erkrankung verschleiert (z. B. Schadel-Hirn-Trauma und Alkoholintoxikation, Delir und Thiaminmangel, myokardiale Ischamie und Kokainabusus, Schmerzsyndrome und Opiatabusus). Viele Patienten nehmen mehr als eine Substanz ein (u. a. als Selbstmedikation bei Entzug oder psychiatrischen Erkrankungen). Die wichtigsten Aspekte werden in diesem Kapitel dargestellt.

Post-thoracotomy acute lung injury is one of the leading causes of mortality after thoracic surgery. Several trigger factors have been identified such as preoperative conditions, surgery-associated inflammation, fluid overload, ventilator-induced lung injury, one-lung ventilation, as well as transfusions. In severe cases the clinical presentation is an acute respiratory distress syndrome in adult patients with a high mortality rate. In the last decade, the concept of lung-“protective” ventilation strategies has been gaining importance in thoracic surgery.

BACKGROUND In the intensive care unit (ICU), continuous patient monitoring is essential to detect critical changes in patients’ health statuses and to guide therapy. The implementation of digital health technologies for patient monitoring may further improve patient safety. However, most monitoring devices today are still based on technologies from the 1970s. OBJECTIVE The aim of this study was to evaluate statements by ICU staff on the current patient monitoring systems and their expectations for future technological developments in order to investigate clinical requirements and barriers to the implementation of future patient monitoring. METHODS This prospective study was conducted at three intensive care units of a German university hospital. Guideline-based interviews with ICU staff—5 physicians, 6 nurses, and 4 respiratory therapists—were recorded, transcribed, and analyzed using the grounded theory approach. RESULTS Evaluating the current monitoring system, ICU staff put high emphasis on usability factors such as intuitiveness and visualization. Trend analysis was rarely used; inadequate alarm management as well as the entanglement of monitoring cables were rated as potential patient safety issues. For a future system, the importance of high usability was again emphasized; wireless, noninvasive, and interoperable monitoring sensors were desired; mobile phones for remote patient monitoring and alarm management optimization were needed; and clinical decision support systems based on artificial intelligence were considered useful. Among perceived barriers to implementation of novel technology were lack of trust, fear of losing clinical skills, fear of increasing workload, and lack of awareness of available digital technologies. CONCLUSIONS This qualitative study on patient monitoring involves core statements from ICU staff. To promote a rapid and sustainable implementation of digital health solutions in the ICU, all health care stakeholders must focus more on user-derived findings. Results on alarm management or mobile devices may be used to prepare ICU staff to use novel technology, to reduce alarm fatigue, to improve medical device usability, and to advance interoperability standards in intensive care medicine. For digital transformation in health care, increasing the trust and awareness of ICU staff in digital health technology may be an essential prerequisite. CLINICALTRIAL ClinicalTrials.gov NCT03514173; https://clinicaltrials.gov/ct2/show/NCT03514173 (Archived by WebCite at http://www.webcitation.org/77T1HwOzk)

Postoperative delirium (POD) is an acute change in the mental state with consciousness and attention deficits. It is a common complication after surgical procedures and can have serious consequences. Thus, the evidence- and consensus-based guidelines for POD appeals with the highest recommendation level that patients be regularly screened for delirium in the postoperative phase, from the recovery room to the fifth postoperative day and at least once per shift, using a validated test instrument for the detection of POD. In 2014, Marcantonio et al. published the 3D-CAM (3-Minute Diagnostic Interview for CAM-defined Delirium). In the 3D-CAM, the algorithm of the Confusion Assessment Method (CAM) is maintained by using individual elements that operationalize the evaluation of the criteria. Therefore, it requires less training, be faster to use, and, due to a standardized approach, has less interrater variability than the CAM, whereas the high sensitivity and specificity are maintained. Our goal was to translate the 3D-CAM from English to German, so as to make this instrument available to German-speaking countries. The translation of the 3D-CAM was based on the 2005 published guideline on Translation and Cultural Adaptation of Patient Reported Outcome Measures of the International Society for Pharmacoeconomics and Outcome Research. Three independent forward translations were harmonized to a preliminary translation, which then was translated back into the original language. Original authors reviewed the back translation. According to a cognitive debriefing, the translation was revised and in addition was adapted for use in the recovery room. Due to close contact with the original authors during the translation process, it was possible to ensure that the contents of the test instrument were remained intact during the translation process.Das postoperative Delir (POD) ist eine häufige und schwerwiegende Komplikation nach chirurgischen Eingriffen. Darum müssen Patienten postoperativ gezielt auf die Entwicklung eines POD untersucht werden. Hierfür steht die Weiterentwicklung des bekannten Delir-Testinstruments CAM, das 3D-CAM, nun auch in deutscher Fassung zur Verfügung.

The upcoming and ongoing debate on neurotoxicity of anesthetics at a young age put a new spotlight on the emergence delirium of children (paedED). The European Society for Anesthesiology published a consensus guideline on prevention and therapy in 2017 which can be a useful guidance in daily clinical practice. Patient data management systems with their clear documentation concerning pain/therapy of pain and paedED will be valuable tools in order to assess the real incidence of paedED. Differentiating between pain/agitation and paedED migth not always be easy. Age-adapted scores should always be applied. Main focus in the prevention of paedED is the reduction of anxiety. The way this is achieved by the dedicated pediatric anesthesia teams caring for children, e.g. by oral midazolam, clowns, music, smartphone induction, does not matter. Using αDas pädiatrische Emergence Delir rückt aufgrund der Debatte um Neurotoxizität von Anästhetika bei kleinen Kindern erneut in den Fokus. Die 2017 von der Europäischen Gesellschaft für Anästhesiologie (ESA) publizierte Leitlinie zu Prävention und Therapie kann eine sinnvolle Unterstützung der klinischen Tätigkeit sein. Insbesondere die zügige und konsequente Behandlung von Schmerzen bei kleinen Kindern und die konsequente Diagnose eines pädED mittels validierter Skale ermöglicht es- dank der Verbreitung von patient data management systemen- in Zukunft eine reelle Inzidenz des pädEDs anzugeben. In der Prävention des pädED liegt der Schwerpunkt auf der Reduktion der präoperativen Angst der Kinder, egal, ob dies durch ein auf das Kind fokussierte Kinderanästhesieteam zusammen mit den Eltern, Musik, Clowns, smartphones/tablets oder eine medikamentöse Prämedikation erzielt wird. Medikamentöse pädED-Prophylaxe durch perioperative Anwendung von alpha-2-Agonisten und die Verwendung von Propofol als Ausleitungsbolus oder TIVA erscheint gleichzeitg sinnvoll. Postoperativ ermöglicht eine ruhige Aufwachumgebung ein entspanntes delirfreies Aufwachen. Postanästhesiologische Visiten mit strukturiertem Erfassen von Veränderungen des kindlichen Verhaltens respektive schriftliche Fragebögen werden in Zukunft Auskunft über das pädED auf den Normalstationen geben. Strukturierte Nachbefragungen im Verlauf werden auch die Erfassung postoperativen unerwünschten Verhaltensänderungen und deren möglichen Zusammenhang zum pädED ermöglichen.

Background The cholinergic system is considered to play a key role in the development of postoperative delirium (POD), which is a common complication after surgery. Objectives To determine whether peri-operative acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities are associated with the development of POD in in-hospital surgical patients, and raise hypotheses on cholinergic regulatory mechanisms in POD. Design A prospective multicentre observational study by the Peripheral Cholinesterase-activity on Neurocognitive Dysfunctions in Surgical Patients (CESARO) study group. Setting Nine German hospitals. Patients Patients of at least 18 years of age scheduled for inpatient elective surgery for a variety of surgical procedures. A total of 650 patients (mean age 61.5 years, 52.8% male) were included. Methods Clinical variables, and peripheral AChE and BuChE activities, were assessed throughout the peri-operative period using bedside point-of-care measurements (one pre-operative and two postoperative measurements). POD screening was conducted postoperatively for at least 24 h and up to the third postoperative day using a validated screening tool (nursing delirium screening scale). Results In all, 179 patients (27.5%) developed POD within the early postoperative phase. There was a lower BuChE activity in patients with delirium compared with patients without delirium pre-operatively (Cohen's r = 0.07, P = 0.091), on postoperative day 1 (Cohen's r = 0.12, P = 0.003) and on postoperative day 2 (Cohen's r = 0.12, P = 0.002). In contrast, there was a significantly higher AChE activity in patients with delirium compared with patients without delirium pre-operatively (Cohen's r = 0.10, P = 0.012), on postoperative day 1 (Cohen's r = 0.11, P = 0.004) and on postoperative day 2 (Cohen's r = 0.13, P = 0.002). After adjusting for covariates in multiple logistic regression, a significant association between both BuChE and AChE activities and POD was not found. However, in the multivariable analysis using the Generalized Estimating Equation, cholinesterase activities showed that a decrease of BuChE activity by 100 U L increased the risk of a delirium by approximately 2.1% (95% CI 1.6 to 2.8%) and for each 1 U g of haemoglobin increase in AChE activity, there was a 1.4% (95% CI 0.6 to 2.2%) increased risk of POD. Conclusion Peri-operative peripheral cholinesterase activities may be related to the development of POD, but the clinical implications remain unclear. Further studies, in homogeneous patient groups with a strict protocol for measurement time points, are needed to investigate the relationship between cholinesterase activities and POD. Trial registration www.clinicaltrials.gov. Identifier NCT01964274.

Aims & objectives: Potentially transformative new tuberculosis (TB) drugs like bedaquiline are undergoing roll-out, however, this is largely in the absence of programmatic drug susceptibility testing (DST). We lack information on how susceptibility changes during treatment in patients on bedaquiline-containing regimens, especially in at risk patients who have complex treatment histories, are in programmatic rather than trial environments, and have a delayed treatment response (defined here as sustained culture-positivity). Methods: Serial isolates from 51 patients with drug resistant (DR-)TB who were culture-positive after ≥4 months of a programmatically administered bedaquiline-containing regimen, were collected. Bedaquiline phenotypic DST in MGIT 960 (1μg/ml), targeted deep sequencing (Rv0678, atpE, pepQ) and whole genome sequencing was done on paired isolates (pre-bedaquiline initiation, post-four-month). Results: 24/51 (47%) patients were phenotypically and genotypically resistant (39% acquired resistance). Excluding one patient with an unknown history, prior clofazimine exposure was associated with bedaquiline-resistance [21/24 (88%) bedaquiline resistant cases had prior clofazimine vs. 12/26 (46%) susceptibles; p=0.002]. Diverse combinations of single nucleotide polymorphisms (SNPs) and indels were in the Rv0678 promoter region and the Rv0678 and atpE genes. Examples of newly described resistance associated variants (RAVs) include Rv0678 -8 T/G and atpE 223 C/T. RAVs were not in defined hotspots and sometimes occurred concurrently with atpE RAVs. Discussion: The rate of bedaquiline resistance acquisition in this population is alarmingly high and associated with prior clofazimine exposure. The diverse RAVs pose challenges to molecular test development. This study highlights the existence of a potentially infectious pool of bedaquiline-resistant patients present under programmatic conditions in a resource-constrained setting and illustrates the danger of starting patients with complex histories on a novel drug without routinely available DST.

Purpose Although delirium monitoring is recommended in international guidelines, there is lacking evidence for improved outcome due to it. We hypothesized that adherence to routine delirium monitoring would improve clinical outcome in adult critically ill patients. Material and methods We present the results of a prospective, noninterventional, observational cohort study that was conducted on 2 intensive care units (ICUs) of a tertiary care medical center between July and October 2007 (International Standard Registered Clinical Trial Record identifier: 76100795). We assessed delirium-monitoring and outcome parameters on a daily basis. Besides multivariate logistic and robust linear regression to analyze the relationship between delirium monitoring and outcome, we used the doubly robust augmented inverse probability weighting method for observational data to estimate effect sizes. Results Of 355 screened patients, we included 185 surgical ICU patients into our final analysis, of which 87 were mechanically ventilated. We found an independent association between delirium-monitoring adherence and in-hospital mortality for ventilated patients (odds ratio, 0.973; P= .041). Estimating the effect size, delirium monitoring indicated a reduction of 22% of in-hospital mortality if conducted 50% or more of ICU days per patient. The average ICU length of stay of 46 days was estimated to be reduced by 19 days (P= .031) if patients were sufficiently monitored. Conclusion Our data suggest an improved outcome for mechanically ventilated patients being screened for delirium in clinical routine.

Background Hemophagocytic lymphohistiocytosis (HLH) has well been studied as a genetic disorder in children (primary HLH). Mutations in the regulatory complex of the cellular immune synapse lead to a loss of function of cytotoxic T‑cells and natural killer cells with excessive inflammation based on a cytokine storm. During the last decade, an increasing number of adult HLH patients without a family history of HLH (secondary or acquired HLH) have been reported. Various triggers - infections, malignancies or autoimmune diseases - result in an acquired loss of function of these cells and a sepsis-like disease. Missed or late diagnosis is believed to be a major cause of the high mortality. Objectives To describe the current knowledge on HLH and to raise awareness. Materials and methods Analysis of case reports, current studies, and expert recommendations. Results Increased vigilance in identifying the adult form of HLH resulted in an increasing number of case reports over the past few years. HLH patients typically present with a clinical phenotype resembling severe sepsis or septic shock with fever, cytopenia, and organomegaly, which do not or insufficiently respond to anti-infective treatment. Early recognition of HLH distinction from sepsis, and prompt initiation of treatment - which is fundamentally different from sepsis - are crucial for improved outcome. A promising diagnostic parameter is ferritin, which has gained sufficient specificity, but only in the context of the triad of fever, cytopenia, and organomegaly. Treatment of adult HLH patients requires immunosuppression, with strict therapeutic guidance derived from the triggering disease. Conclusions Because of the similar clinical presentation to that of sepsis, HLH is often not recognized, resulting in a fatal outcome. In "sepsis" patients on the ICU with deterioration despite a standard of care, HLH needs to be considered by testing for ferritin when considering differential diagnoses. The complexity of the illness requires interdisciplinary patient care with specific integration of the hematologist in the diagnostic workup and therapeutic management, because of the frequent use of chemotherapy-based immunosuppression.

Sleep-wake patterns are often significantly disturbed in critically ill patients. This disturbance is closely linked to secondary brain dysfunctions in these patients. Sedation not only impairs sleep quality in ICU patients but also has detrimental effects on short- and long-term outcome. In other contexts, light therapy has been proven to be effective in maintaining and resynchronizing circadian rhythmicity in humans. The objective of this systematic review was to analyse studies that investigated the effect of exposure to light or darkness on physiological measures and clinical outcomes of adult ICU patients. Studies were systematically identified by searching electronic bibliographic databases (The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, 2002) and MEDLINE via PubMed). The search algorithm identified a total of 156 articles, 10 of which were taken into final review. These 10 selected articles included 3 were monocentric RCTs, five prospective cohort studies, one retrospective cohort study, and one manuscript that included a partial systematic review of the literature. Included trials were published between 2007 and 2015. Five of these studies used multiple intervention approaches while four trials used a single intervention approach. Among all studies, 1,278 patients were analysed (489 prospectively). There was a high heterogeneity among the studies in terms of applied intervention and outcome measures. The most frequent methodological limitations were a lack of precise definitions regarding the illuminance and the light spectrum utilised. The analyses indicate that further studies including clearly defined interventions with objective outcome measures, as these are currently lacking, would add significant knowledge to this new field of research.

From an elderly patient's perspective, acute and chronic cognitive disturbances are among the most harmful complications that can occur following surgery. For elderly patients, these complications often mean the end of an independent life. This article focuses on this serious aspect, which is increasingly prevalent in our aging society. Cognitive disturbances are associated with severe outcome impairments and increased mortality. This article aims to provide a current overview regarding the diagnosis, pathophysiology, prevention, and treatment of this severe social problem.The current knowledge of risk factors, diagnosis, prevention, and treatment of postoperative delirium and postoperative cognitive dysfunction should help to raise awareness and improve the outcome of delirious patients, particularly in the elderly population.Especially in elderly patients, postoperative delirium constitutes a common, severe complication. Early diagnosis and supportive treatment are essential to improve outcome. To date, no pharmacological treatment strategy was effective, so that further research about the underlying pathophysiology and the development of treatment strategies are urgently required.