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.

Implementation of a software-based decision support tool for guideline-appropriate preoperative evaluation: a prospective agreement study.

BACKGROUND: Guideline adherence in the medical field leaves room for improvement. Digitalised decision support helps improve compliance. However, the complex nature of the guidelines makes implementation in clinical practice difficult. METHODS: This single-centre prospective study included 204 adult ASA physical status 3-4 patients undergoing elective noncardiac surgery at a German university hospital. Agreement of clearance for surgery between a guideline expert and a digital guideline support tool was investigated. The decision made by the on-duty anaesthetists (standard approach) was assessed for agreement with the expert in a cross-over design. The main outcome was the level of agreement between digital guideline support and the expert. RESULTS: The digital guideline support approach cleared 18.1% of the patients for surgery, the standard approach cleared 74.0%, and the expert approach cleared 47.5%. Agreement of the expert decision with digital guideline support (66.7%) and the standard approach (67.6%) was fair (Cohen's kappa 0.37 [interquartile range 0.26-0.48] vs 0.31 [0.21-0.42], P=0.6). Taking the expert decision as a benchmark, correct clearance using digital guideline support was 50.5%, and correct clearance using the standard approach was 44.6%. Digital guideline support incorrectly asked for additional examinations in 31.4% of the patients, whereas the standard approach did not consider conditions that would have justified additional examinations before surgery in 29.4%. CONCLUSIONS: Strict guideline adherence for clearance for surgery through digitalised decision support inadequately considered patients, clinical context. Vague formulations, weak recommendations, and low-quality evidence complicate guideline translation into explicit rules. CLINICAL TRIAL REGISTRATION: NCT04058769.

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.

Does the gender of emergency physicians have an impact on the prehospital care of psychiatric emergencies? a retrospective cohort analysis.

BACKGROUND: Psychiatric emergencies pose a special challenge for emergency physicians. It is known from other areas of medicine that the influence of a doctor's gender can have an impact on the type of treatment and quality of patient care. However, this has not yet been investigated in the context of prehospital care in psychiatric emergencies. OBJECTIVES: To identify whether the gender of the prehospital emergency physicians has an influence on the "on-scene" time, treatment strategy and on the potential escalation of interventions for patients with a psychiatric diagnosis. METHODS: A retrospective cohort analysis of emergency missions with a psychiatric diagnosis was performed between January 1, 2015 and December 31, 2021 at the Department of Emergency Medicine, Department of Anesthesiology and Intensive Care Medicine, University Hospital Ulm, Germany. RESULTS: 2882 emergency missions with a psychiatric indication/prehospital psychiatric diagnosis were studied and divided into: intoxication (n = 1343, 46.6%), suicidal behavior (n = 488, 16.9%), exceptional mental situation (n = 282, 9.8%), agitation (n = 262, 9.1%), anxiety and panic disorders (n = 262, 9.1%) and "psychiatric miscellaneous" (n = 245, 8.5%). Inpatient hospitalization occurred in 67.9% (n = 1958) of emergency missions. Of these, 20.3% (n = 392) were admitted directly to a psychiatric hospital. Male emergency physicians had a slightly longer "on-scene" time for psychiatric emergencies than female emergency physicians (p = 0.024). However, the variance in "on-scene" time for all interventions was significantly greater for female emergency physicians than for male emergency physicians (p = 0.025). Male emergency physicians were significantly more likely than their female counterparts to administer intravenous hypnotics in prehospital psychiatric emergencies (p = 0.001). For psychiatric patients who refused medically indicated inpatient psychiatric admission ("involuntary psychiatric admission"), male and female emergency physicians were equally likely to take the required action (p = 0.522). However, male emergency physicians were significantly more likely to administer an intravenous hypnotic to enforce involuntary admission (p = 0.009). CONCLUSIONS: Similar to other medical specialties where the influence of physician gender on patient care is certainly relevant, the gender of prehospital emergency physicians also appears to influence their prehospital management strategy in psychiatric emergencies. The influence of gender is sometimes subtle and limited to specific aspects, such as the administration of hypnotics. Prospective study designs are needed to thoroughly investigate the influence of the gender of the prehospital emergency physician on the quality of care in psychiatric emergencies. TRIAL REGISTRATION: The study was approved by the ethics committee of the University Ulm, Trial-Code No. 110/22 and was prospectively registered in the German Clinical Trials Register (DRKS-ID: DRKS00031237). Patient information was not required for retrospective data analysis.

Intraoperative haemodynamic monitoring and management of adults having non-cardiac surgery: Guidelines of the German Society of Anaesthesiology and Intensive Care Medicine in collaboration with the German Association of the Scientific Medical Societies.

Haemodynamic monitoring and management are cornerstones of perioperative care. The goal of haemodynamic management is to maintain organ function by ensuring adequate perfusion pressure, blood flow, and oxygen delivery. We here present guidelines on "Intraoperative haemodynamic monitoring and management of adults having non-cardiac surgery" that were prepared by 18 experts on behalf of the German Society of Anaesthesiology and Intensive Care Medicine (Deutsche Gesellschaft für Anästhesiologie und lntensivmedizin; DGAI).

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.

Medical experience as an influencing parameter in emergency medical care for psychiatric emergencies: retrospective analysis of a multicenter survey.

BACKGROUND: Prehospital care of psychiatric patients often relies on the medical experience of prehospital emergency physicians (PHEPs). The psychiatrists (PSs) involved in the further treatment of psychiatric patients also often rely on their experience. Furthermore, the interaction between PHEPs and PSs is characterized by interaction problems and different approaches in the prehospital care of the psychiatric emergency. OBJECTIVES: To analyze the phenomenon of "medical experience" as a cause of possible interaction-related problems and assess its impact on the prehospital decision-making process between prehospital emergency physicians and psychiatrists. METHODS: The retrospective data analysis was conducted between November 2022 and March 2023. Medical experience was defined as follows, based on the demographic information collected in the questionnaires: For PHEPs, the period since obtaining the additional qualification in emergency medicine was defined as a surrogate marker of medical experience: (i) inexperienced: < 1 year, (ii) experienced: 1-5 years, (iii) very experienced: > 5 years. For PSs, age in years was used as a surrogate parameter of medical experience: (i) inexperienced: 25-35 years, (ii) experienced: 35-45 years, (iii) very experienced: > 45 years. RESULTS: Inexperienced PSs most frequently expressed anxiety about the psychiatric emergency referred by a PHEP (27.9%). Experienced PHEPs most frequently reported a lack of qualifications in handling the care of psychiatric emergencies (p = 0.002). Very experienced PHEPs were significantly more likely to have a referral refused by the acute psychiatric hospital if an inexperienced PS was on duty (p = 0.01). Experienced PHEPs apply an intravenous hypnotic significantly more often (almost 15%) than PSs of all experience levels (p = 0.001). In addition, very experienced PHEPs sought prehospital phone contact with acute psychiatry significantly more often (p = 0.01). CONCLUSION: PHEPs should be aware that the PS on duty may be inexperienced and that treating emergency patients may cause him/her anxiety. On the other hand, PHEPs should be receptive to feedback from PS who have identified a qualification deficiency in them. Jointly developed, individualized emergency plans could lead to better prehospital care for psychiatric emergency patients. Further training in the prehospital management of psychiatric disorders is needed to minimize the existing skills gap among PHEPs in the management of psychiatric disorders.

Emergency medical care of patients with psychiatric disorders - challenges and opportunities: Results of a multicenter survey.

BACKGROUND: Pre-clinical psychiatric emergencies are generally treated by emergency medical staff. The subsequent clinical treatment is often conditioned by interaction problems between emergency medical staff and psychiatric clinical staff. OBJECTIVES: To identify problems affecting interaction between emergency medical and psychiatric care of mentally ill patients and pinpoint aspects of optimized emergency care. METHODS: To shed light on the interaction problems an anonymous, questionnaire-based, nonrepresentative survey of 98 emergency physicians (EM) and 104 psychiatrists (PS) practicing in acute psychiatry was conducted between March 1, 2021 and October 1, 2021. RESULTS: The chi-square test for multiple response sets revealed consistently significant differences (p < 0.001) between EM and PS with respect to the questions analyzed. Approximately 36% of EM reported not to be adequately qualified to handle psychiatric emergencies (p = 0.0001), while around 50% of respondents were neutral in their assessment in how to deal with psychiatric emergencies. 80% of EM reported a negative interaction (rejection of patients) with PS when referring a psychiatric emergency patient to the acute psychiatric unit. The most common reasons for refusal were intoxication (EM: 78.8%, PS: 88.2%), emergency physician therapy (EM: 53.8%, PS: 63.5%), and not resident in the catchment area of the hospital (EM 68.8%, PS: 48.2%). In the casuistry presented, most respondents would choose "talk down" for de-escalation (EM: 92.1%, PS: 91.3%). With respect to drug therapy, benzodiazepine is the drug of choice (EM: 70.4%, PS: 78.8%). More EM would choose an intravenously (i.v.) or a Mucosal Atomization Device (MAD) administration as an alternative to oral medication (i.v.: EM: 38.8%, PS: 3.8%, p = 0.001, MAD: EM: 36.7%, PS: 10.6%, p = 0.006). Significantly more EM would seek phone contact with the acute psychiatric hospital (EM: 84.7%, PS: 52.9%, p = 0.0107). A psychiatric emergency plan was considered useful in this context by more than 90% of respondents. The need for further training for EM with regard to treating psychiatric clinical syndromes was considered important by all respondents. In particular, the topics of "psychogenic seizure," "intoxication," and "legal aspects of psychiatric emergencies" were considered important (Mann-Whitney U test, p < 0.001). CONCLUSION: The interaction-related problems identified in the emergency medical care of pre-clinical psychiatric patients relate to non-modifiable, structural problems, such as insufficient admission capacity and non-existent or inadequate monitoring capabilities in acute psychiatric hospitals. However, factors such as the education and training of EM and communication between EM and PS can be improved. Developing personalized emergency care plans for psychiatric patients could help to optimize their care.

Block of Voltage-Gated Sodium Channels by Aripiprazole in a State-Dependent Manner.

Aripiprazole is an atypical antipsychotic drug, which is prescribed for many psychiatric diseases such as schizophrenia and mania in bipolar disorder. It primarily acts as an agonist of dopaminergic and other G-protein coupled receptors. So far, an interaction with ligand- or voltage-gated ion channels has been classified as weak. Meanwhile, we identified aripiprazole in a preliminary test as a potent blocker of voltage-gated sodium channels. Here, we present a detailed analysis about the interaction of aripiprazole with the dominant voltage-gated sodium channel of heart muscle (hNav1.5). Electrophysiological experiments were performed by means of the patch clamp technique at human heart muscle sodium channels (hNav1.5), heterologously expressed in human TsA cells. Aripiprazole inhibits the hNav1.5 channel in a state- but not use-dependent manner. The affinity for the resting state is weak with an extrapolated Kr of about 55 µM. By contrast, the interaction with the inactivated state is strong. The affinities for the fast and slow inactivated state are in the low micromolar range (0.5-1 µM). Kinetic studies indicate that block development for the inactivated state must be described with a fast (ms) and a slow (s) time constant. Even though the time constants differ by a factor of about 50, the resulting affinity constants were nearly identical (in the range of 0.5 µM). Besides this, aripirazole also interacts with the open state of the channel. Using an inactivation deficit mutant, an affinity of about 1 µM was estimated. In summary, aripiprazole inhibits voltage-gated sodium channels at low micromolar concentrations. This property might add to its possible anticancer and neuroprotective properties.

Concentrations of estradiol, progesterone and testosterone in sefrum and cerebrospinal fluid of patients with aneurysmal subarachnoid hemorrhage correlate weakly with transcranial Doppler flow velocities.

BACKGROUND: The implication of the steroids estradiol, progesterone and testosterone in cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH) has not been comprehensively assessed. In rodents, studies suggested beneficial effects of steroids on cerebral vasospasm after experimental SAH. Studies in humans are warranted, however, a general dilemma of human studies on neuroactive substances is that the brain is not directly accessible and that concentrations in the periphery may not adequately parallel concentrations in the central compartments. In the present study, concentrations of estradiol, progesterone and testosterone in serum and cerebrospinal fluid (CSF) of patients with aSAH were determined. Blood flow velocities in cerebral arteries were measured by transcranial Doppler sonography (TCD). The aim of this study was to evaluate the correlations between the cerebral blood flow velocities and levels of estradiol, progesterone and testosterone in CSF and serum. RESULTS: Samples of serum and CSF of 42 patients with aSAH were collected concomitantly daily or every other day via the arterial line and the external ventricular drainage for two weeks after the hemorrhage. Blood flow velocities in the cerebral arteries were determined by TCD. Total estradiol, progesterone and testosterone concentrations were measured by electro-chemiluminescence immunoassay. The strength of correlation was assessed by Spearman's rank correlation coefficient. The correlation analysis revealed very weak correlations between cerebral blood flow velocities and concentrations of estradiol, progesterone and testosterone levels in both compartments with correlation coefficients below 0.2. CONCLUSIONS: In humans with aSAH, merely very weak correlations between flow velocities in cerebral arteries and concentrations of estradiol, progesterone and testosterone in serum and CSF were demonstrated. These results suggest a limited influence of the respective steroids on cerebral vascular tone although vasodilatory effects were described in rodent studies. Thus, the implication of steroids in processes of neurological deterioration warrants further clarification.

Machine learning identifies ICU outcome predictors in a multicenter COVID-19 cohort.

BACKGROUND: Intensive Care Resources are heavily utilized during the COVID-19 pandemic. However, risk stratification and prediction of SARS-CoV-2 patient clinical outcomes upon ICU admission remain inadequate. This study aimed to develop a machine learning model, based on retrospective & prospective clinical data, to stratify patient risk and predict ICU survival and outcomes. METHODS: A Germany-wide electronic registry was established to pseudonymously collect admission, therapeutic and discharge information of SARS-CoV-2 ICU patients retrospectively and prospectively. Machine learning approaches were evaluated for the accuracy and interpretability of predictions. The Explainable Boosting Machine approach was selected as the most suitable method. Individual, non-linear shape functions for predictive parameters and parameter interactions are reported. RESULTS: 1039 patients were included in the Explainable Boosting Machine model, 596 patients retrospectively collected, and 443 patients prospectively collected. The model for prediction of general ICU outcome was shown to be more reliable to predict "survival". Age, inflammatory and thrombotic activity, and severity of ARDS at ICU admission were shown to be predictive of ICU survival. Patients' age, pulmonary dysfunction and transfer from an external institution were predictors for ECMO therapy. The interaction of patient age with D-dimer levels on admission and creatinine levels with SOFA score without GCS were predictors for renal replacement therapy. CONCLUSIONS: Using Explainable Boosting Machine analysis, we confirmed and weighed previously reported and identified novel predictors for outcome in critically ill COVID-19 patients. Using this strategy, predictive modeling of COVID-19 ICU patient outcomes can be performed overcoming the limitations of linear regression models. Trial registration "ClinicalTrials" (clinicaltrials.gov) under NCT04455451.

Surgical tracheostomy in a cohort of COVID-19 patients.

BACKGROUND: One of the main symptoms of severe infection with the new coronavirus­2 (SARS-CoV-2) is hypoxemic respiratory failure because of viral pneumonia with the need for mechanical ventilation. Prolonged mechanical ventilation may require a tracheostomy, but the increased risk for contamination is a matter of considerable debate. OBJECTIVE: Evaluation of safety and effects of surgical tracheostomy on ventilation parameters and outcome in patients with COVID-19. STUDY DESIGN: Retrospective observational study between March 27 and May 18, 2020, in a single-center coronavirus disease-designated ICU at a tertiary care German hospital. PATIENTS: Patients with COVID-19 were treated with open surgical tracheostomy due to severe hypoxemic respiratory failure requiring mechanical ventilation. MEASUREMENTS: Clinical and ventilation data were obtained from medical records in a retrospective manner. RESULTS: A total of 18 patients with confirmed SARS-CoV­2 infection and surgical tracheostomy were analyzed. The age range was 42-87 years. All patients received open tracheostomy between 2-16 days after admission. Ventilation after tracheostomy was less invasive (reduction in PEAK and positive end-expiratory pressure [PEEP]) and lung compliance increased over time after tracheostomy. Also, sedative drugs could be reduced, and patients had a reduced need of norepinephrine to maintain hemodynamic stability. Six of 18 patients died. All surgical staff were equipped with N99-masks and facial shields or with powered air-purifying respirators (PAPR). CONCLUSION: Our data suggest that open surgical tracheostomy can be performed without severe complications in patients with COVID-19. Tracheostomy may reduce invasiveness of mechanical ventilation and the need for sedative drugs and norepinehprine. Recommendations for personal protective equipment (PPE) for surgical staff should be followed when PPE is available to avoid contamination of the personnel.

Impact of Goal-Directed Therapy on Delayed Ischemia After Aneurysmal Subarachnoid Hemorrhage: Randomized Controlled Trial.

BACKGROUND AND PURPOSE: Delayed cerebral ischemia (DCI) is the most important cause for a poor clinical outcome after a subarachnoid hemorrhage. The aim of this study was to assess whether goal-directed hemodynamic therapy (GDHT), as compared to standard clinical care, reduces the rate of DCI after subarachnoid hemorrhage. METHODS: We conducted a prospective randomized controlled trial. Patients >18 years of age with an aneurysmal subarachnoid hemorrhage were enrolled and randomly assigned to standard therapy or GDHT. Advanced hemodynamic monitoring and predefined GDHT algorithms were applied in the GDHT group. The primary end point was the occurrence of DCI. Functional outcome was assessed using the Glasgow Outcome Scale (GOS) 3 months after discharge. RESULTS: In total, 108 patients were randomized to the control (n=54) or GDHT group (n=54). The primary outcome (DCI) occurred in 13% of the GDHT group and in 32% of the control group patients (odds ratio, 0.324 [95% CI, 0.11-0.86]; P=0.021). Even after adjustment for confounding parameters, GDHT was found to be superior to standard therapy (hazard ratio, 2.84 [95% CI, 1.18-6.86]; P=0.02). The GOS was assessed 3 months after discharge in 107 patients; it showed more patients with a low disability (GOS 5, minor or no deficits) than patients with higher deficits (GOS 1-4) in the GDHT group compared with the control group (GOS 5, 66% versus 44%; GOS 1-4, 34% versus 56%; P=0.025). There was no significant difference in mortality between the groups. CONCLUSIONS: GDHT reduced the rate of DCI after subarachnoid hemorrhage with a better functional outcome (GOS=5) 3 months after discharge. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01832389.

Weak correlations between serum and cerebrospinal fluid levels of estradiol, progesterone and testosterone in males.

BACKGROUND: Neuroactive steroids seem to be implicated in a variety of neurophysiological and behavioral processes, such as sleep, learning, memory, stress, feeding and aging. Numerous studies have also addressed this implication in various cerebral disorders and diseases. Yet, the correlation and association between steroids in the periphery, e.g. blood, and the central compartments, e.g. cerebrospinal fluid (CSF), have not yet been comprehensively assessed. As the brain is not directly accessible, and the collection of human CSF usually requires invasive procedures, easier accessible compartments, such as blood, have always attracted attention. However, studies in humans are scarce. In the present study we determined estradiol, progesterone and testosterone levels in CSF and serum of 22 males without cerebral disorders or diseases. RESULTS: Samples were taken under conditions corresponding closest to basal conditions with patients expecting only spinal anesthesia and minor surgery. All samples per patient were collected concomitantly. Total estradiol, progesterone and testosterone concentrations were measured by electro-chemiluminescence immunoassay. The strength of correlation was assessed by Spearman's rank correlation coefficient. Correlation analysis revealed merely weak to very weak correlations for estradiol, progesterone and testosterone respectively between the CSF and serum compartments. CONCLUSIONS: Total steroid levels of estradiol, progesterone and testosterone in CSF and serum of males without neurological disorders were determined. Weak to very weak correlations between CSF and serum were found thus suggesting that concentrations in the periphery do not parallel concentrations in the central compartments. Further research is needed to clarify to what extent and under which conditions serum levels of estradiol, progesterone and testosterone may possibly serve as a biomarker reflecting the respective concentrations in the CSF or in the brain.

Perioperative multi-system optimization protocol in elderly hip fracture patients: a randomized-controlled trial.

PURPOSE: Hip fractures in elderly patients are associated with increased postoperative morbidity and mortality. We evaluated whether a perioperative multi-system optimization protocol can reduce postoperative complications in these patients. METHODS: Immediately after diagnosis of hip fracture, patients ≥ 60 yr were randomized to an intervention or control group. Patients in the intervention group were admitted to our postanesthesia care unit where they were treated with goal-directed hemodynamic management, optimized pain therapy, oxygen therapy, and optimized nutrition. Patients in the control group were managed according to our usual standard of care on a regular ward. Postoperative complications during hospital stay included pre-determined cardiovascular, respiratory, neurologic, renal, or surgical events. RESULTS: The incidence of at least one postoperative complication (primary outcome) was seen in 32 of 65 (49%) controls compared with 24 of 62 (39%) in the intervention group (relative risk [RR], 0.79; 95% confidence interval [CI], 0.53 to 1.17; P = 0.23). The secondary unadjusted outcomes showed that patients in the intervention group received more Ringer's acetate compared with controls (median difference, 1.3 L; 95% CI, 0.6 to 2.1 L; P < 0.001), had more frequently a mean arterial pressure > 70 mmHg (57% control vs 75% intervention; median percentage difference, 16%; 95% CI, 7 to 25%; P = 0.001), better pain control (numeric rating scale < 4 at all postoperative measurements; 25% control vs 81% intervention; RR, 0.26; 95% CI, 0.15 to 0.43; P < 0.001), and possibly a lower incidence of acute renal failure (RR, 0.37; 95% CI, 0.14 to 0.98; P = 0.04). CONCLUSIONS: The implementation of a perioperative multi-system optimization protocol algorithm did not significantly reduce the risk of postoperative complications. Nevertheless, we likely over-estimated the potential treatment effect in our study design and thus were under-powered to show an effect. TRIAL REGISTRATION: Clinicaltrials.gov (NCT01673776). Registered 23 August, 2012.

Algorithm-guided goal-directed haemodynamic therapy does not improve renal function after major abdominal surgery compared to good standard clinical care: a prospective randomised trial.

BACKGROUND: Acute kidney injury is a common complication after major surgery. In this study, we investigated whether an algorithm-guided goal-directed haemodynamic therapy (GDT) can improve renal outcome compared to good standard clinical care. METHODS: A total of 180 patients undergoing major abdominal surgery were prospectively and randomly assigned to one of two groups: in the GDT group, patients were treated with a GDT algorithm using transpulmonary thermodilution while standard care was applied to the control patients. Change in creatinine was studied as the primary end point, postoperative complications as well as 1-year mortality as secondary outcomes. Haemodynamics in GDT and control patients were compared calculating goal-achievement rates. RESULTS: Postoperative change in creatinine (18 ± 39 µmol/l (control) vs. 16 ± 42 µmol/l (GDT); mean difference (95 % confidence interval) 1.6 µmol/l (-10 to 13 µmol/l)) was comparable between the GDT and the control group. Postoperative complications and mortality during hospital stay and after 1 year were not influenced by the use of a GDT algorithm. Achievement rates of haemodynamic goals were not higher in the GDT group compared to the already high (>80 %) rates in the control group. Multivariate regression analysis revealed intraoperative hypotension (MAP < 70 mmHg) and postoperative hypovolaemia (GEDI < 640 ml/m(2)) as risk factors for postoperative renal impairment. CONCLUSIONS: In this study, GDT was not superior to standard clinical care in order to avoid renal failure after major abdominal surgery. The reason for this finding is most likely the high achievement rate of haemodynamic goals in the control group, which cannot be improved by the GDT algorithm. TRIAL REGISTRATION: Clinicaltrials.gov; NCT01035541; registered 17 December 2009.

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.

Case Report: Traumatic cardiac arrest due to pericardial tamponade: successful pericardiocentesis with a Shaldon catheter.

In this report, we describe the successful resuscitation of a 4-year-old child who suffered a traumatic cardiac arrest during a routine procedure in the operating room. The diagnosis of a sanguineous pericardial tamponade was made by emergency ultrasonography. Consecutive subxiphoid pericardiocentesis with an adult Shaldon catheter led to return of spontaneous circulation. Subsequent thoracotomy and surgical suturing definitively stopped the bleeding from the right ventricle. The combined expertise of all perioperative disciplines was decisive for the patient's survival.