Genotype- and sex-specific changes in vital parameters during isoflurane anesthesia in a mouse model of Alzheimer's disease.

Background: The prevalence of neurodegenerative diseases is increasing as is life expectancy with Alzheimer's disease accounting for two-thirds of dementia cases globally. Whether general anesthesia and surgery worsen cognitive decline is still a matter of debate and most likely depending on the interplay of various influencing factors. In order to account for this complexity, Alzheimer's disease animal models have been developed. The Tg2576 model of Alzheimer's disease is a well-established mouse model exhibiting amyloidopathy and age-dependent sex-specific differences in Alzheimer's disease symptomology. Yet, data on anesthesia in this mouse model is scarce and a systematic comparison of vital parameters during anesthesia with wild-type animals is missing. In order to investigate the safety of general anesthesia and changes in vital parameters during general anesthesia in Tg2576 mice, we did a secondary analysis of vital parameters collected during general anesthesia in aged Tg2576 mice. Methods: After governmental approval (General Administration of the Free State of Bavaria, file number: 55.2-1-54-2532-149-11) 60 mice at 10-12 months of age were exposed to isoflurane (1.6 Vol%) for 120 min, data of 58 mice was analyzed. During general anesthesia, heart rate, respiratory rate, temperature, isoflurane concentration and fraction of inspired oxygen were monitored and collected. Data were analyzed using univariate and multivariate linear mixed regression models. Results: During general anesthesia, heart rate decreased in a sex-specific manner. Respiratory rate decreased and body temperature increased dependent on genotype. However, the changes were limited and all vital parameters stayed within physiological limits. Conclusion: Isoflurane anesthesia in the Tg2576 mouse model is safe and does not seem to influence experimental results by interacting with vital parameters. The present study provides information on appropriate anesthesia in order to advance research on anesthesia and AD and could contribute to improving laboratory animal welfare.

Susceptibility of AutoML mortality prediction algorithms to model drift caused by the COVID pandemic.

BACKGROUND: Concept drift and covariate shift lead to a degradation of machine learning (ML) models. The objective of our study was to characterize sudden data drift as caused by the COVID pandemic. Furthermore, we investigated the suitability of certain methods in model training to prevent model degradation caused by data drift. METHODS: We trained different ML models with the H2O AutoML method on a dataset comprising 102,666 cases of surgical patients collected in the years 2014-2019 to predict postoperative mortality using preoperatively available data. Models applied were Generalized Linear Model with regularization, Default Random Forest, Gradient Boosting Machine, eXtreme Gradient Boosting, Deep Learning and Stacked Ensembles comprising all base models. Further, we modified the original models by applying three different methods when training on the original pre-pandemic dataset: (Rahmani K, et al, Int J Med Inform 173:104930, 2023) we weighted older data weaker, (Morger A, et al, Sci Rep 12:7244, 2022) used only the most recent data for model training and (Dilmegani C, 2023) performed a z-transformation of the numerical input parameters. Afterwards, we tested model performance on a pre-pandemic and an in-pandemic data set not used in the training process, and analysed common features. RESULTS: The models produced showed excellent areas under receiver-operating characteristic and acceptable precision-recall curves when tested on a dataset from January-March 2020, but significant degradation when tested on a dataset collected in the first wave of the COVID pandemic from April-May 2020. When comparing the probability distributions of the input parameters, significant differences between pre-pandemic and in-pandemic data were found. The endpoint of our models, in-hospital mortality after surgery, did not differ significantly between pre- and in-pandemic data and was about 1% in each case. However, the models varied considerably in the composition of their input parameters. None of our applied modifications prevented a loss of performance, although very different models emerged from it, using a large variety of parameters. CONCLUSIONS: Our results show that none of our tested easy-to-implement measures in model training can prevent deterioration in the case of sudden external events. Therefore, we conclude that, in the presence of concept drift and covariate shift, close monitoring and critical review of model predictions are necessary.

Goal-directed Perioperative Albumin Substitution Versus Standard of Care to Reduce Postoperative Complications: A Randomized Clinical Trial (SuperAdd Trial).

OBJECTIVE: To investigate whether goal-directed albumin substitution during surgery and postanesthesia care to maintain a serum albumin concentration >30 g/L can reduce postoperative complications. BACKGROUND: Hypoalbuminemia is associated with numerous postoperative complications. Since albumin has important physiological functions, substitution of patients with hypoalbuminemia is worth considering. METHODS: We conducted a single-center, randomized, controlled, outcome assessor-blinded clinical trial in adult patients, American Society of Anesthesiologists physical status classification 3 to 4 or undergoing high-risk surgery. Patients, whose serum albumin concentration dropped <30 g/L were randomly assigned to goal-directed albumin substitution maintaining serum concentration >30 g/L or to standard care until discharge from the postanesthesia intermediate care unit. Standard of care allowed albumin substitution in hemodynamic instable patients with serum concentration <20 g/L, only. Primary outcome was the incidence of postoperative complications ≥2 according to the Clavien-Dindo Classification in at least 1 of 9 domains (pulmonary, infectious, cardiovascular, neurological, renal, gastrointestinal, wound, pain, and hematological) until postoperative day 15. RESULTS: Of 2509 included patients, 600 (23.9%) developed serum albumin concentrations <30 g/L. Human albumin 60 g (40-80 g) was substituted to 299 (99.7%) patients in the intervention group and to 54 (18.0%) in the standard care group. At least 1 postoperative complication classified as Clavien-Dindo Classification ≥2 occurred in 254 of 300 patients (84.7%) in the intervention group and in 262 of 300 (87.3%) in the standard treatment group (risk difference -2.7%, 95% CI, -8.3% to 2.9%). CONCLUSION: Maintaining serum albumin concentration of >30 g/L perioperatively cannot generally be recommended in high-risk noncardiac surgery patients.

Under-dosing and over-dosing of neuromuscular blocking drugs and reversal agents: beware of the risks.

The phenomena of residual curarisation and recurarisation after the use of long-acting non-depolarising neuromuscular blocking drugs such as tubocurarine and pancuronium were well recognised 60 years ago. But the incidence seemed to decline with the introduction of atracurium and vecuronium. However, recently there have been an increasing number of reports of residual and recurrent neuromuscular block. Some of these reports are a result of inappropriate doses of rocuronium, sugammadex or both, together with inadequate neuromuscular monitoring. We urge clinicians to review their practice to ensure the highest standards of clinical care when using neuromuscular blocking drugs and reversal agents. This includes the use of quantitative neuromuscular monitoring whenever neuromuscular blocking drugs are administered.

The optimal dose of mobilisation therapy in the ICU: a prospective cohort study.

BACKGROUND: This study aimed to assess the impact of duration of early mobilisation on survivors of critical illness. The hypothesis was that interventions lasting over 40 min, as per the German guideline, positively affect the functional status at ICU discharge. METHODS: Prospective single-centre cohort study conducted in two ICUs in Germany. In 684 critically ill patients surviving an ICU stay > 24 h, out-of-bed mobilisation of more than 40 min was evaluated. RESULTS: Daily mobilisation ≥ 40 min was identified as an independent predictor of an improved functional status upon ICU discharge. This effect on the primary outcome measure, change of Mobility-Barthel until ICU discharge, was observed in three different models for baseline patient characteristics (average treatment effect (ATE), all three models p < 0.001). When mobilisation parameters like level of mobilisation, were included in the analysis, the average treatment effect disappeared [ATE 1.0 (95% CI - 0.4 to 2.4), p = 0.16]. CONCLUSIONS: A mobilisation duration of more than 40 min positively impacts functional outcomes at ICU discharge. However, the maximum level achieved during ICU stay was the most crucial factor regarding adequate dosage, as higher duration did not show an additional benefit in patients with already high mobilisation levels. TRIAL REGISTRATION: Prospective Registry of Mobilization-, Routine- and Outcome Data of Intensive Care Patients (MOBDB), NCT03666286. Registered 11 September 2018-retrospectively registered, https://classic. CLINICALTRIALS: gov/ct2/show/NCT03666286 .

Wearable in-ear pulse oximetry validly measures oxygen saturation between 70% and 100%: A prospective agreement study.

Objectives: Postoperative monitoring outside intensive and post-anaesthesia care units is seldom, partly due to lack of suitable and approved systems. We therefore aim to validate the oxygen saturation (SpO2) and pulse rate measurement of the in-ear sensor c-med° alpha with a reference pulse oximeter. Methods: This prospective agreement study was conducted in 12 healthy (ASA 1) adult (18-50 years) volunteers according to the EN ISO 80601-2-61. The sitting volunteers were equipped with the finger pulse oximeter Rad-5 and two c-med° alpha sensors in each ear. The inspiratory oxygen content was reduced via a tight-fitting breathing mask to achieve five defined plateaus with stable SpO2 between 99% and 70%. The deviation of the SpO2 and pulse rate measurements of the c-med° alpha from those of the Rad-5 was calculated using the mean square error (Arms). Bias and limits of agreement between both devices were calculated using the Bland-Altman technique. The precision was compared based on the repeatability coefficients. Results: The c-med° alpha measured SpO2 had an Arms = 1.9% relative to the Rad-5, a non-significant bias (-0.1% (-0.2% to 0.0%)), levels of agreement from -4.0% to 3.8%, and the same repeatability coefficient (0.8% vs. 0.8%). The c-med° alpha measured pulse rate did not deviate from the one measured with the certified finger pulse oximeter (bias: 0.1 min-1 (0 to 0.1 min-1), level of agreement: -3.6 to 3.7 min-1, Arms: 1.8 min-1). Conclusions: The c-med° alpha fulfils the EN ISO 80601-2-61 standard and is sufficiently accurate for measuring SpO2 and pulse rate in healthy adults at rest. Trial registration: EUDAMED No. CIV-21-03-036033.

Effects of mobility dose on discharge disposition in critically ill stroke patients.

BACKGROUND: Mobilization in the intensive care unit (ICU) has the potential to improve patient outcomes following acute stroke. The optimal duration and intensity of mobilization for patients with hemorrhagic or ischemic stroke in the ICU remain unclear. OBJECTIVE: To assess the effect of mobilization dose in the ICU on adverse discharge disposition in patients after stroke. DESIGN: This is an international, prospective, observational cohort study of critically ill stroke patients (November 2017-September 2019). Duration and intensity of mobilization was quantified daily by the mobilization quantification score (MQS). SETTING: Patients requiring ICU-level care were enrolled within 48 hours of admission at four separate academic medical centers (two in Europe, two in the United States). PARTICIPANTS: Participants included individuals (>18 years old) admitted to an ICU within 48 hours of ischemic or hemorrhagic stroke onset who were functionally independent at baseline. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: The primary outcome was adverse discharge disposition. RESULTS: Of the patients screened, 163 were eligible for inclusion in the study. One patient was subsequently excluded due to insufficient data collection (n = 162). The dose of mobilization varied greatly between centers and patients, which could not be explained by patients' comorbidities or disease severity. High dose of mobilization (mean MQS > 7.3) was associated with a lower likelihood of adverse discharge (adjusted odds ratio, [aOR]: 0.14; 95% confidence interval [CI]: 0.06-0.31; p < .01). CONCLUSION: The increased use of mobilization acutely in the ICU setting may improve patient outcomes.

Corrigendum: The functional trajectory in frail compared with non-frail critically ill patients during the hospital stay.

[This corrects the article DOI: 10.3389/fmed.2021.748812.].

Enabling personalized perioperative risk prediction by using a machine-learning model based on preoperative data.

Preoperative risk assessment is essential for shared decision-making and adequate perioperative care. Common scores provide limited predictive quality and lack personalized information. The aim of this study was to create an interpretable machine-learning-based model to assess the patient's individual risk of postoperative mortality based on preoperative data to allow analysis of personal risk factors. After ethical approval, a model for prediction of postoperative in-hospital mortality based on preoperative data of 66,846 patients undergoing elective non-cardiac surgery between June 2014 and March 2020 was created with extreme gradient boosting. Model performance and the most relevant parameters were shown using receiver operating characteristic (ROC-) and precision-recall (PR-) curves and importance plots. Individual risks of index patients were presented in waterfall diagrams. The model included 201 features and showed good predictive abilities with an area under receiver operating characteristic (AUROC) curve of 0.95 and an area under precision-recall curve (AUPRC) of 0.109. The feature with the highest information gain was the preoperative order for red packed cell concentrates followed by age and c-reactive protein. Individual risk factors could be identified on patient level. We created a highly accurate and interpretable machine learning model to preoperatively predict the risk of postoperative in-hospital mortality. The algorithm can be used to identify factors susceptible to preoperative optimization measures and to identify risk factors influencing individual patient risk.

Successful treatment of out-of-hospital cardiac arrest is still based on quick activation of the chain of survival.

Background and goal of study: Cardiopulmonary resuscitation (CPR) in prehospital care is a major reason for emergency medical service (EMS) dispatches. CPR outcome depends on various factors, such as bystander CPR and initial heart rhythm. Our aim was to investigate whether short-term outcomes such as the return of spontaneous circulation (ROSC) and hospital admission with spontaneous circulation differ depending on the location of the out-of-hospital cardiac arrest (OHCA). In addition, we assessed further aspects of CPR performance. Materials and methods: In this monocentric retrospective study, protocols of a prehospital physician-staffed EMS located in Munich, Germany, were evaluated using the Mann-Whitney U-test, chi-square test, and a multifactor logistic regression model. Results and discussion: Of the 12,073 cases between 1 January 2014 and 31 December 2017, 723 EMS responses with OHCA were analyzed. In 393 of these cases, CPR was performed. The incidence of ROSC did not differ between public and non-public spaces (p = 0.4), but patients with OHCA in public spaces were more often admitted to the hospital with spontaneous circulation (p = 0.011). Shockable initial rhythm was not different between locations (p = 0.2), but defibrillation was performed significantly more often in public places (p < 0.001). Multivariate analyses showed that hospital admission with spontaneous circulation was more likely in patients with shockable initial heart rhythm (p < 0.001) and if CPR was started by an emergency physician (p = 0.006). Conclusion: The location of OHCA did not seem to affect the incidence of ROSC, although patients in public spaces had a higher chance to be admitted to the hospital with spontaneous circulation. Shockable initial heart rhythm, defibrillation, and the start of resuscitative efforts by an emergency physician were associated with higher chances of hospital admission with spontaneous circulation. Bystander CPR and bystander use of automated external defibrillators were low overall, emphasizing the importance of bystander education and training in order to enhance the chain of survival.

Insulin signaling in skeletal muscle during inflammation and/or immobilisation.

BACKGROUND: The decline in the downstream signal transduction pathway of anabolic hormone, insulin, could play a key role in the muscle atrophy and insulin resistance observed in patients with intensive care unit acquired weakness (ICUAW). This study investigated the impact of immobilisation via surgical knee and ankle fixation and inflammation via Corynebacterium parvum injection, alone and in combination, as risk factors for altering insulin transduction and, therefore, their role in ICUAW. RESULTS: Muscle weight was significantly decreased due to immobilisation [estimated effect size (95% CI) - 0.10 g (- 0.12 to - 0.08); p < 0.001] or inflammation [estimated effect size (95% CI) - 0.11 g (- 0.13 to - 0.09); p < 0.001] with an additive effect of both combined (p = 0.024). pAkt was only detectable after insulin stimulation [estimated effect size (95% CI) 85.1-fold (76.2 to 94.0); p < 0.001] irrespective of the group and phosphorylation was not impaired by the different perturbations. Nevertheless, the phosphorylation of GSK3 observed in the control group after insulin stimulation was decreased in the immobilisation [estimated effect size (95% CI) - 40.2 (- 45.6 to - 34.8)] and inflammation [estimated effect size (95% CI) - 55.0 (- 60.4 to - 49.5)] groups. The expression of phosphorylated GS (pGS) was decreased after insulin stimulation in the control group and significantly increased in the immobilisation [estimated effect size (95% CI) 70.6-fold (58.8 to 82.4)] and inflammation [estimated effect size (95% CI) 96.7 (85.0 to 108.5)] groups. CONCLUSIONS: Both immobilisation and inflammation significantly induce insulin resistance, i.e., impair the insulin signaling pathway downstream of Akt causing insufficient GSK phosphorylation and, therefore, its activation which caused increased glycogen synthase phosphorylation, which could contribute to muscle atrophy of immobilisation and inflammation.

Association of immature platelets with perioperative complications in neurosurgery.

Immature platelets are newly formed platelets with an increased prothrombotic potential. This study evaluates whether immature platelets are associated with relevant complications in neurosurgical patients. Data were obtained in the frame of a prospectively conducted observational study exploring the association between immature platelets and major cardiovascular events after surgery. Immature platelet fraction (IPF) and H-IPF (highly fluorescent immature platelet fraction) were measured preoperatively and postoperatively at the neurosurgical ward (24-72 hours after surgery). Therapy-relevant complications after surgery were stratified using the Clavien-Dindo Grade (CDG >2) as primary outcome. Data were analyzed in 391 neurosurgical patients. While preoperatively there were no differences in IPF or H-IPF, patients with higher therapy-complication grades had higher values post-op compared to patients with lower grade complications (≤2 CDG). Cut-off values identified by receiver operating characteristic curve analysis revealed that there were significantly more patients with H-IPF ≥0.95% in the group with serious complications (CDG >2) [odds ratio OR (95% confidence interval CI) = 2.06 (1.09-3.9), p = .025], whereas this association was not present for the IPF cutoff value. In a multivariate model, H-IPF≥0.95% was independently associated with serious complications after surgery [OR (95% CI) = 1.97 (1.03-3.78), p = .041]. These findings suggest that H-IPF is associated with surgical complications and may improve risk stratification of neurosurgical patients (clinicaltrials.gov: NCT02097602, registration date: 27/03/2014).

What is the context?Immature platelets are newly formed platelets with a higher thrombotic potential and play an important role in atherothrombotic events.Higher levels of immature platelets were observed in patients with acute coronary syndrome or stroke.Lately, the focus in immature platelet research shifted from observation to outcomes. Immature platelets were identified as independent predictors of major cardiovascular events in cardiologic patients with coronary artery disease. Besides, an association between immature platelets and major cardiovascular events was described in surgical patients after non-cardiac surgery.What is new?This study builds on these findings and extends the focus to perioperative complications after neurosurgery.The data were obtained prospectively in the frame of an observational clinical trial exploring the association of immature platelets and major cardiovascular events in general. Data measured in the neurosurgical cohort of that study (391 neurosurgical patients) were analyzed in the present work.Within the limitations of our study, our analyses suggest that the postoperative IPF (immature platelet fraction) and H-IPF (highly fluorescent immature platelet fraction) values, which were measured at the neurosurgical ward after surgery are both associated with higher therapy-relevant complication grades (>2 according to Clavien-Dindo Grade), whereas preoperatively obtained values were not.What is the impact?This is the first study showing a relationship between immature platelets and therapy-relevant perioperative complications in neurosurgical patients. It could be a pilot trial for varied scientific questions including risk stratification of neurosurgical patients.

Clustering of critically ill patients using an individualized learning approach enables dose optimization of mobilization in the ICU.

BACKGROUND: While early mobilization is commonly implemented in intensive care unit treatment guidelines to improve functional outcome, the characterization of the optimal individual dosage (frequency, level or duration) remains unclear. The aim of this study was to demonstrate that artificial intelligence-based clustering of a large ICU cohort can provide individualized mobilization recommendations that have a positive impact on the likelihood of being discharged home. METHODS: This study is an analysis of a prospective observational database of two interdisciplinary intensive care units in Munich, Germany. Dosage of mobilization is determined by sessions per day, mean duration, early mobilization as well as average and maximum level achieved. A k-means cluster analysis was conducted including collected parameters at ICU admission to generate clinically definable clusters. RESULTS: Between April 2017 and May 2019, 948 patients were included. Four different clusters were identified, comprising "Young Trauma," "Severely ill & Frail," "Old non-frail" and "Middle-aged" patients. Early mobilization (< 72 h) was the most important factor to be discharged home in "Young Trauma" patients (ORadj 10.0 [2.8 to 44.0], p < 0.001). In the cluster of "Middle-aged" patients, the likelihood to be discharged home increased with each mobilization level, to a maximum 24-fold increased likelihood for ambulating (ORadj 24.0 [7.4 to 86.1], p < 0.001). The likelihood increased significantly when standing or ambulating was achieved in the older, non-frail cluster (ORadj 4.7 [1.2 to 23.2], p = 0.035 and ORadj 8.1 [1.8 to 45.8], p = 0.010). CONCLUSIONS: An artificial intelligence-based learning approach was able to divide a heterogeneous critical care cohort into four clusters, which differed significantly in their clinical characteristics and in their mobilization parameters. Depending on the cluster, different mobilization strategies supported the likelihood of being discharged home enabling an individualized and resource-optimized mobilization approach. TRIAL REGISTRATION: Clinical Trials NCT03666286, retrospectively registered 04 September 2018.

The rate and assessment of muscle wasting during critical illness: a systematic review and meta-analysis.

BACKGROUND: Patients with critical illness can lose more than 15% of muscle mass in one week, and this can have long-term detrimental effects. However, there is currently no synthesis of the data of intensive care unit (ICU) muscle wasting studies, so the true mean rate of muscle loss across all studies is unknown. The aim of this project was therefore to systematically synthetise data on the rate of muscle loss and to identify the methods used to measure muscle size and to synthetise data on the prevalence of ICU-acquired weakness in critically ill patients. METHODS: We conducted a systematic literature search of MEDLINE, PubMed, AMED, BNI, CINAHL, and EMCARE until January 2022 (International Prospective Register of Systematic Reviews [PROSPERO] registration: CRD420222989540. We included studies with at least 20 adult critically ill patients where the investigators measured a muscle mass-related variable at two time points during the ICU stay. We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and assessed the study quality using the Newcastle-Ottawa Scale. RESULTS: Fifty-two studies that included 3251 patients fulfilled the selection criteria. These studies investigated the rate of muscle wasting in 1773 (55%) patients and assessed ICU-acquired muscle weakness in 1478 (45%) patients. The methods used to assess muscle mass were ultrasound in 85% (n = 28/33) of the studies and computed tomography in the rest 15% (n = 5/33). During the first week of critical illness, patients lost every day -1.75% (95% CI -2.05, -1.45) of their rectus femoris thickness or -2.10% (95% CI -3.17, -1.02) of rectus femoris cross-sectional area. The overall prevalence of ICU-acquired weakness was 48% (95% CI 39%, 56%). CONCLUSION: On average, critically ill patients lose nearly 2% of skeletal muscle per day during the first week of ICU admission.

Comparison of Different Ultrasound Methods to Assess Changes in Muscle Mass in Critically ill Patients.

BACKGROUND: Muscle ultrasound represents a promising approach to aid diagnoses of neuromuscular diseases in critically ill patients. Unfortunately, standardization of ultrasound measurements in clinical research is lacking, making direct comparisons between studies difficult. Protocols are required to assess qualitative muscle changes during an ICU stay in patients at high risk for the development of neuromuscular acquired weakness (ICUAW). METHODS: We conducted a retrospective, observational analysis comprised of three prospective observational studies with the aim of diagnosing muscle changes by ultrasound measurement of the quadriceps muscle. Different protocols were used in each of the three studies. In total, 62 surgical, neurocritical care and trauma intensive care patients were serially assessed by different ultrasound protocols during the first week of critical illness. The relative change in ultrasound measurements was calculated for all possible locations, methods and sides. Comparison was obtained using mixed effect models with the location, the height and the side as influencing variables and patients as fixed effect. The relationship between variables and outcomes was assessed by multivariable regression analysis. RESULTS: Ultrasound methods and measurement sites of the quadriceps muscles from all protocols were equally effective in detecting muscle changes. During the first week of an ICU stay, two groups were identified: patients with decreased muscle mass on ultrasound (n = 42) and a cohort with enlargement (n = 23). Hospital mortality was significantly increased in the cohort with muscle swelling (8 (19%) versus 12 (52%), p = .013). CONCLUSIONS: Different approaches of ultrasound measurement during critical-illness are equally able to detect muscle changes. While some patients have a decrease in muscle mass, others show swelling, which may result in a reduced probability of surviving the hospital stay. Causative reasons for these results still remain unclear.

How robust are the STRONGER and STIL-STRONGER studies?

In 2020, the Sugammadex vs Neostigmine for Reversal of Neuromuscular Blockade and Postoperative Pulmonary Complications (STRONGER) study provided evidence for the first time that use of sugammadex is associated with fewer postoperative pulmonary complications than use of neostigmine. In a recent publication in the British Journal of Anaesthesia, a secondary analysis of the same data, the Association Between Neuromuscular Blockade Reversal Agent Choice and Postoperative Pulmonary Complications (STIL-STRONGER) study, has produced similar evidence of the advantages of sugammadex over neostigmine in high-risk and older patients undergoing prolonged, elective surgery. Here we consider the implications of the detailed statistical analysis used in these two studies and how its limitations could possibly have enhanced the statistical differences between the two drugs with respect to postoperative pulmonary complications.

Isoflurane has no effect on cognitive or behavioral performance in a mouse model of early-stage Alzheimer's disease.

Background: Patients with Alzheimer's disease show a sex-dependent decline of cognitive and behavioral performance. It is controversially discussed whether general anesthesia itself can aggravate or even cause this neurocognitive decline. Therefore, we investigated the effect of general anesthesia on neurocognitive and behavioral function and amyloidopathy in a mouse model of early-stage Alzheimer's disease with respect to sex. Methods: After governmental approval 10 months old Tg2576 mice and wild type (total 85 mice) either underwent general anesthesia with 1.0 minimal alveolar concentration of isoflurane for 2 h or were not exposed to isoflurane (controls). Following cognitive and behavioral testing using the modified hole board test (mHBT), brains were investigated regarding amyloidopathy, inflammation, and apoptosis. Data were analyzed using repeated measure analysis of variance (ANOVA) and univariate analysis of variance (UNIANOVA). Results: Tg2576 mice showed a decline in memory function (p < 0.001), less anxiety (p = 0.022 and p = 0.024), increased locomotor activity (p = 0.025), and impaired fine motor skills (p < 0.001). Amyloid precursor protein (p < 0.001), soluble amyloid-beta (p < 0.001) and insoluble amyloid deposits (p < 0.001) were increased in Tg2576 animals. Neither sex nor exposure to isoflurane had an effect on cognitive or behavioral testing or expression of amyloid-related biomarkers. Discussion and conclusion: We found that 10 months old Tg2576 showed typical signs of early-stage Alzheimer's disease and corresponding histopathological alterations. Relevant sex-specific differences or an effect of isoflurane anesthesia could not be detected at this early stage of the disease.

Perioperative Hemodynamic Optimization in Patients at Risk for Delirium - A Randomized-Controlled Trial.

Background: Post-operative delirium is common in elderly patients and associated with increased morbidity and mortality. We evaluated in this pilot study whether a perioperative goal-directed hemodynamic optimization algorithm improves cerebral oxygenation and can reduce the incidence of delirium. Materials and Methods: Patients older than 70 years with high risk for post-operative delirium undergoing elective non-cardiac surgery were randomized to an intervention or control group. Patients in the intervention group received a perioperative hemodynamic optimization protocol based on uncalibrated pulse-contour analysis. Patients in the control group were managed according to usual standard of care. Incidence of delirium until day seven was assessed with confusion assessment method (CAM) and chart review. Cerebral oxygenation was measured with near-infrared spectroscopy. Results: Delirium was present in 13 of 85 (15%) patients in the intervention group and 18 of 87 (21%) in the control group [risk difference -5.4%; 95% confidence interval, -16.8 to 6.1%; P = 0.47]. Intervention did not influence length of stay in hospital or in-hospital mortality. Amounts of fluids and vasopressors applied, mean arterial pressure, cardiac index, and near-infrared spectroscopy values were comparable between groups. Conclusion: The hemodynamic algorithm applied in high-risk non-cardiac surgery patients did not change hemodynamic interventions, did not improve patient hemodynamics, and failed to increase cerebral oxygenation. An effect on the incidence of post-operative delirium could not be observed. Clinical Trial Registration: [Clinicaltrials.gov], identifier [NCT01827501].