Determinants of Subjective Mental and Functional Health of Critical Illness Survivors: Comparing Pre-ICU and Post-ICU Status.

OBJECTIVES: To compare ICU survivors' subjective mental and functional health before ICU admission and after discharge and to assess determinants of subjective health decline or improvement. DESIGN: Secondary analysis of the multicenter cluster-randomized Enhanced Recovery after Intensive Care trial ( ClinicalTrials.gov : NCT03671447). SETTING: Ten ICU clusters in Germany. PATIENTS: Eight hundred fifty-five patients with 1478 follow-up assessments. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: At two patient follow-ups scheduled 3 and 6 months after ICU discharge, patients rated their subjective mental and functional/physical health on two separate visual analog scales from 0 (worst) to 10 (best) in the previous week and before ICU admission. We compared pre-ICU and post-ICU subjective health and used mixed-effects regression to assess determinants of a health decline or improvement. At the first follow-up, 20% ( n = 165/841) and 30% ( n = 256/849) of patients reported a decline in subjective mental and functional health of at least three points, respectively; 16% ( n = 133/841 and n = 137/849) outlined improvements of mental and functional health. For 65% ( n = 543/841) and 54% ( n = 456/849), mental and functional health did not change three points or more at the first follow-up. Multivariable mixed-effects logistic regressions revealed that the ICU length of stay was a predictor of mental (adjusted odds ratio [OR] per ICU day, 1.04; 95% CI, 1.00-1.09; p = 0.038) and functional health (adjusted OR per ICU day, 1.06; 95% CI, 1.01-1.12; p = 0.026) decline. The odds of a mental health decline decreased with age (adjusted OR per year, 0.98; 95% CI, 0.96-0.99; p = 0.003) and the odds of a functional health decline decreased with time after discharge (adjusted OR per month, 0.86; 95% CI, 0.79-0.94; p = 0.001). CONCLUSIONS: The majority of ICU survivors did not experience substantial changes in their subjective health status, but patients with long ICU stays were prone to subjective mental and functional health decline. Hence, post-ICU care in post-ICU clinics could focus on these patients.

Update of the European Society of Anaesthesiology and Intensive Care Medicine evidence-based and consensus-based guideline on postoperative delirium in adult patients.

Postoperative delirium (POD) remains a common, dangerous and resource-consuming adverse event but is often preventable. The whole peri-operative team can play a key role in its management. This update to the 2017 ESAIC Guideline on the prevention of POD is evidence-based and consensus-based and considers the literature between 01 April 2015, and 28 February 2022. The search terms of the broad literature search were identical to those used in the first version of the guideline published in 2017. POD was defined in accordance with the DSM-5 criteria. POD had to be measured with a validated POD screening tool, at least once per day for at least 3 days starting in the recovery room or postanaesthesia care unit on the day of surgery or, at latest, on postoperative day 1. Recent literature confirmed the pathogenic role of surgery-induced inflammation, and this concept reinforces the positive role of multicomponent strategies aimed to reduce the surgical stress response. Although some putative precipitating risk factors are not modifiable (length of surgery, surgical site), others (such as depth of anaesthesia, appropriate analgesia and haemodynamic stability) are under the control of the anaesthesiologists. Multicomponent preoperative, intra-operative and postoperative preventive measures showed potential to reduce the incidence and duration of POD, confirming the pivotal role of a comprehensive and team-based approach to improve patients' clinical and functional status.

Structural disconnectivity in postoperative delirium: A perioperative two-center cohort study in older patients.

BACKGROUND: Structural disconnectivity was found to precede dementia. Global white matter abnormalities might also be associated with postoperative delirium (POD). METHODS: We recruited older patients (≥65 years) without dementia that were scheduled for major surgery. Diffusion kurtosis imaging metrics were obtained preoperatively, after 3 and 12 months postoperatively. We calculated fractional anisotropy (FA), mean diffusivity (MD), mean kurtosis (MK), and free water (FW). A structured and validated delirium assessment was performed twice daily. RESULTS: Of 325 patients, 53 patients developed POD (16.3%). Preoperative global MD (standardized beta 0.27 [95% confidence interval [CI] 0.21-0.32] p < 0.001) was higher in patients with POD. Preoperative global MK (-0.07 [95% CI -0.11 to (-0.04)] p < 0.001) and FA (0.07 [95% CI -0.10 to (-0.04)] p < 0.001) were lower. When correcting for baseline diffusion, postoperative MD was lower after 3 months (0.05 [95% CI -0.08 to (-0.03)] p < 0.001; n = 183) and higher after 12 months (0.28 [95% CI 0.20-0.35] p < 0.001; n = 45) among patients with POD. DISCUSSION: Preoperative structural disconnectivity was associated with POD. POD might lead to white matter depletion 3 and 12 months after surgery.

Subjective Ratings of Mental and Physical Health Correlate With EQ-5D-5L Index Values in Survivors of Critical Illness: A Construct Validity Study.

OBJECTIVES: Survivors of critical illness commonly show impaired health-related quality of life (HrQoL). We investigated if HrQoL can be approximated by brief, easily applicable items to be used in primary care. DESIGN: Secondary analysis of data from the multicenter, cluster-randomized controlled Enhanced Recovery after Intensive Care trial ( ClinicalTrials.gov : NCT03671447) and construct validity study. SETTING: Ten participating clusters of ICUs in the metropolitan area of Berlin, Germany. PATIENTS: Eight hundred fifty ICU survivors enrolled in a mixed, medical or surgical ICU when they had an expected ICU length of stay of at least 24 hours, were at least 18 years old, and had statutory health insurance coverage. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients received follow-ups scheduled 3 and 6 months after ICU discharge. HrQoL was assessed with the EuroQol 5-Dimension 5-Level (EQ-5D-5L), and patients were asked to rate their current mental and physical health state from 0 (worst) to 10 (best). We fitted prediction models for the EQ-5D-5L index value using these two items and additional covariates, applying stepwise regression and adaptive lasso. Subjective mental health (Spearman: 0.59) and subjective physical health (Spearman: 0.68) correlated with EQ-5D-5L index values and were better predictors of EQ-5D-5L index values in the two-item regression (normalized root mean squared error [nRMSE] 0.164; normalized mean absolute error [nMAE] 0.118; R2adj 0.43) than the EQ-5D Visual Analog Scale (nRMSE 0.175; nMAE 0.124; R2adj 0.35). Stepwise regression with additional covariates further increased prediction performance (nRMSE 0.133; nMAE 0.1; R2adj 0.51). CONCLUSIONS: Asking patients to rate their subjective mental and physical health can be an easily applicable tool for a first impression of the HrQoL in primary care settings.

Functional brain network and trail making test changes following major surgery and postoperative delirium: a prospective, multicentre, observational cohort study.

BACKGROUND: Delirium is a frequent complication after surgery in older adults and is associated with an increased risk of long-term cognitive impairment and dementia. Disturbances in functional brain networks were previously reported during delirium. We hypothesised that alterations in functional brain networks persist after remission of postoperative delirium and that functional brain network alterations are associated with long-term cognitive impairment. METHODS: In this prospective, multicentre, observational cohort study, we included older patients who underwent clinical assessments (including the Trail Making Test B [TMT-B]) and resting-state functional MRI (rs-fMRI) before and 3 months after elective surgery. Delirium was assessed on the first seven postoperative days. RESULTS: Of the 554 enrolled patients, 246 remained after strict motion correction, of whom 38 (16%) developed postoperative delirium. The rs-fMRI functional connectivity strength increased 3 months after surgery in the total study population (ß=0.006; 95% confidence interval [CI]: 0.001-0.011; P=0.013), but it decreased after postoperative delirium (ß=-0.015; 95% CI: -0.028 to 0.002; P=0.023). No difference in TMT-B scores was found at follow-up between patients with and without postoperative delirium. Patients with decreased functional connectivity strength declined in TMT-B scores compared with those who did not (ß=11.04; 95% CI: 0.85-21.2; P=0.034). CONCLUSIONS: Postoperative delirium was associated with decreased brain functional connectivity strength after 3 months, suggesting that delirium has a long-lasting impact on brain networks. The decreased connectivity strength was associated with significant cognitive deterioration after major surgery. CLINICAL TRIAL REGISTRATION: NCT02265263.

Enhancing European Management of Analgesia, Sedation, and Delirium: A Multinational, Prospective, Interventional Before-After Trial.

BACKGROUND: The objective of this study was to analyze the impact of a structured educational intervention on the implementation of guideline-recommended pain, agitation, and delirium (PAD) assessment. METHODS: This was a prospective, multinational, interventional before-after trial conducted at 12 intensive care units from 10 centers in Germany, Austria, Switzerland, and the UK. Intensive care units underwent a 6-week structured educational program, comprising online lectures, instructional videos, educational handouts, and bedside teaching. Patient-level PAD assessment data were collected in three 1-day point-prevalence assessments before (T1), 6 weeks after (T2), and 1 year after (T3) the educational program. RESULTS: A total of 430 patients were included. The rate of patients who received all three PAD assessments changed from 55% (107/195) at T1 to 53% (68/129) at T2, but increased to 73% (77/106) at T3 (p = 0.003). The delirium screening rate increased from 64% (124/195) at T1 to 65% (84/129) at T2 and 77% (82/106) at T3 (p = 0.041). The pain assessment rate increased from 87% (170/195) at T1 to 92% (119/129) at T2 and 98% (104/106) at T3 (p = 0.005). The rate of sedation assessment showed no signficiant change. The proportion of patients who received nonpharmacological delirium prevention measures increased from 58% (114/195) at T1 to 80% (103/129) at T2 and 91% (96/106) at T3 (p < 0.001). Multivariable regression revealed that at T3, patients were more likely to receive a delirium assessment (odds ratio [OR] 2.138, 95% confidence interval [CI] 1.206-3.790; p = 0.009), sedation assessment (OR 4.131, 95% CI 1.372-12.438; p = 0.012), or all three PAD assessments (OR 2.295, 95% CI 1.349-3.903; p = 0.002) compared with T1. CONCLUSIONS: In routine care, many patients were not assessed for PAD. Assessment rates increased significantly 1 year after the intervention. Clinical trial registration ClinicalTrials.gov: NCT03553719.

Boosting for insight and/or boosting for agency? How to maximize accurate test interpretation with natural frequencies.

BACKGROUND: Many physicians do not know how to accurately interpret test results using Bayes' rule. As a remedy, two kinds of interventions have been shown effective: boosting insight and boosting agency with natural frequencies. To boost insight, test statistics are provided in natural frequencies (rather than conditional probabilities), without instructions on how to use them. To boost agency, a training is provided on how to translate probabilities into natural frequencies and apply them in Bayes' rule. What has not been shown is whether boosting agency is sufficient or if representing test statistics in natural frequencies may additionally boost insight to maximize accurate test interpretation. METHODS: We used a pre/posttest design to assess test interpretation accuracy of 577 medical students before and after a training on two Bayesian reasoning tasks, one providing conditional probabilities, the other natural frequencies. The pretest assessed baseline abilities versus the effect of natural frequencies to boost insight. After participants received a training on how to translate conditional probabilities into natural frequencies and how to apply them in Bayes' rule, test interpretation skills were assessed using the same tasks again, comparing the effects of training-induced agency with versus without additionally boosting insight (i.e., test statistics in natural frequencies versus conditional probabilities). RESULTS: Compared to the test question formatted in conditional probabilities (34% correct answers), natural frequencies facilitated Bayesian reasoning without training (68%), that is, they increased insight. The training on how to use natural frequencies improved performance for tasks formatted in conditional probabilities (64%). Performance was maximal after training and with test statistics formatted in natural frequencies, that is, with a combination of boosting insight and agency (89%). CONCLUSIONS: Natural frequencies should be used to boost insight and agency to maximize effective use of teaching resources. Thus, mandating that test statistics are provided in natural frequencies and adopting short trainings on how to translate conditional probabilities into natural frequencies and how to apply them in Bayes' rule will help to maximize accurate test interpretation. TRIAL REGISTRATION: The study was a registered with the German Clinical Trial Registry ( DRKS00008723 ; 06/03/2015).

Presurgical Thalamus Volume in Postoperative Delirium: A Longitudinal Observational Cohort Study in Older Patients.

BACKGROUND: Previous studies suggest a role of the thalamus in cognitive function, while others implicate it as a central effect site of anesthetics. Yet, its role in postoperative neurocognition in the aging brain remains uncertain. We used presurgical thalamic volume as a functional indicator and determined its association with postoperative delirium (POD). METHODS: For this study, 301 older adults (aged ≥65) without dementia and scheduled for surgery were enrolled. Before surgery, participants underwent magnetic resonance imaging (MRI). Thalamus volume was segmented using Freesurfer (Version 5.3.). Participants were screened for POD twice a day until discharge or for a maximum of 7 days. POD was defined as a positive screening on ≥1 of 4 validated instruments: Richmond Agitation Sedation Scale (RASS), Nursing Delirium Screening Scale (Nu-DESC), Confusion Assessment Method (CAM), and Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) score. A logistic regression associated thalamus volume with POD with adjustment for age, global brain atrophy, and physical status according to the American Society of Anesthesiologists (ASA) classification. RESULTS: In this cohort, 44 participants (14.6%) were diagnosed with POD. Independently of age, global brain atrophy, and physical status score, a higher preoperative thalamus volume was associated with a reduced odds of POD (odds ratio per 1-cm3 increment; 0.73 [95% confidence interval (CI), 0.58-0.92]; P = .008). CONCLUSIONS: A larger thalamus volume was associated with reduced odds of POD. Thus, the thalamus marks a region of interest in POD in the aging brain. These findings may help to understand the neuronal basis of POD.

Association of cholinesterase activities and POD in older adult abdominal surgical patients.

BACKGROUND: Postoperative delirium (POD) is a frequent complication after surgery. Older adult patients undergoing abdominal surgery are at higher risk for developing POD. Studies on the association of cholinesterase activities and POD are rare, but leading hypotheses implicate that the cholinergic pathway might play an important role in neuroinflammation and development of POD. The objective of this study was to figure out if there is an association between the development of POD and acetyl- and butyrylcholinesterase (AChE and BuChE) activities in older adult patients undergoing abdominal surgery. METHODS: The investigation was performed with a subpopulation of BioCog study patients. The BioCog project ( http://www.biocog.eu ) is a prospective multicenter observational study in older adult surgical patients. Patients ≥ 65 years undergoing elective surgery of at least 60 minutes who scored more than 23 points in the Mini-Mental-State-Examination were included. POD was assessed twice a day on seven consecutive days after the surgery, using the test instruments Nursing Delirium Screening Scale (Nu-Desc) and Confusion Assessment Method (CAM and CAM-ICU) and a patient chart review. Pre- and postoperative blood cholinesterase activities were measured with a photometric rapid-point-of-care-testing. The association between cholinesterase activities and POD was analyzed in a subpopulation of abdominal surgical patients using multivariable logistic regression analysis adjusting for confounders. RESULTS: One hundred twenty-seven patients were included for analysis (mean age 73 years, 59% female). Fifty-two patients (41%) fulfilled the criteria of POD. These patients were significantly older, had a longer time of surgery and anesthesia and achieved higher comorbidity scores compared to patients without POD. After adjusting for age, duration of surgery and charlson comorbity index, we found an association between pre- and postoperative AChE activity (U/gHb) and the development of POD (Odds ratio (OR), [95% confidence interval (CI)], preoperative 0.95 [0.89-1.00], postoperative 0.94 [0.89-1.00]). CONCLUSIONS: We found an association between POD and AChE activity and provided new information considering patients with abdominal surgery. Future analyses should examine course dynamics of postoperative cholinesterase activities in order to clarify interactions between the cholinergic system and pathophysiological mechanisms leading to POD. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02265263.

Influence of Patient-Specific Covariates on Test Validity of Two Delirium Screening Instruments in Neurocritical Care Patients (DEMON-ICU).

BACKGROUND: Delirium screening instruments (DSIs) should be used to detect delirium, but they only show moderate sensitivity in patients with neurocritical illness. We explored whether, for these patients, DSI validity is impacted by patient-specific covariates. METHODS: Data were prospectively collected in a single-center quality improvement project. Patients were screened for delirium once daily using the Intensive Care Delirium Screening Checklist (ICDSC) and the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Reference was the daily assessment using criteria from the Diagnostic and Statistical Manual, 4th Edition, Text Revision (DSM-IV-TR). In a two-step receiver operating characteristics regression analysis adjusting for repeated measurements, the impact of acute diagnosis of stroke or transient ischemic attack (TIA), neurosurgical intervention, Richmond Agitation Sedation Scale, and ventilation status on test validity was determined. RESULTS: Of 181 patients screened, 101 went into final analysis. Delirium incidence according to DSM-IV-TR was 29.7%. For the first complete assessment series (CAM-ICU, ICDSC, and DSM-IV-TR), sensitivity for the CAM-ICU and the ICDSC was 73.3% and 66.7%, and specificity was 91.8% and 94.1%, respectively. Consideration of daily repeated measurements increased sensitivity for the CAM-ICU and ICDSC to 75.7% and 73.4%, and specificity to 97.3% and 98.9%, respectively. Receiver operating characteristics regression revealed that lower Richmond Agitation Sedation Scale levels significantly impaired validity of the ICDSC (p = 0.029) and the CAM-ICU in its severity scale version (p = 0.004). Neither acute diagnosis of stroke or TIA nor neurosurgical intervention or mechanical ventilation significantly influenced DSI validity. CONCLUSIONS: The CAM-ICU and ICDSC perform well in patients requiring neurocritical care, regardless of the presence of acute stroke, TIA, or neurosurgical interventions. Yet, even very light or moderate sedation can significantly impair DSI performance.

A Decade of Post-Intensive Care Syndrome: A Bibliometric Network Analysis.

Background and Objectives: In 2012, the umbrella term post-intensive care syndrome (PICS) was introduced to capture functional long-term impairments of survivors of critical illness. We present a bibliometric network analysis of the PICS research field. Materials and Methods: The Web of Science core database was searched for articles published in 2012 or later using 'post-intensive care syndrome' and variant spellings. Using VOSviewer, we computed co-authorship networks of countries, institutions, and authors, as well as keyword co-occurrence networks. We determined each country's relative research effort and Category Normalized Citation Index over time and analyzed the 100 most-cited articles with respect to article type, country of origin, and publishing journal. Results: Our search yielded 379 articles, of which 373 were analyzed. Annual PICS research output increased from 11 (2012) to 95 articles (2020). Most PICS research originates from the US, followed by England, Australia, the Netherlands, and Germany. We found various collaborations between countries, institutions, and authors, with recent collaborative networks of English and Australian institutions. Article keywords cover aspects of cognitive, mental health, and physical impairments, and more recently, COVID-19. Only a few keywords and articles pertained to PICS prevention and treatment. Conclusions: Our analysis of Web of Science-indexed PICS articles highlights the stark increase in PICS research output in recent years, primarily originating from US- and Europe-based authors and institutions. Despite the research field's growth, knowledge gaps with respect to PICS prevention and treatment remain.

Methodology of measuring postoperative cognitive dysfunction: a systematic review.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is an adverse outcome that impacts patients' quality of life. Its diagnosis relies on formal cognitive testing performed before and after surgery. The substantial heterogeneity in methodology limits comparability and meta-analysis of studies. This systematic review critically appraises the methodology of studies on POCD published since the 1995 Consensus Statement and aims to provide guidance to future authors by providing recommendations that may improve comparability between future studies. METHODS: This systematic review of literature published between 1995 and 2019 included studies that used baseline cognitive testing and a structured cognitive test battery, and had a minimal follow-up of 1 month. For cohorts with multiple publications, data from the primary publication were supplemented with available data from later follow-up studies. RESULTS: A total of 274 unique studies were included in the analysis. In the included studies, 259 different cognitive tests were used. Studies varied considerably in timing of assessment, follow-up duration, definition of POCD, and use of control groups. Of the 274 included studies, 70 reported POCD as a dichotomous outcome at 1 to <3 months, with a pooled incidence of 2998/10 335 patients (29.0%). CONCLUSIONS: We found an overwhelming heterogeneity in methodology used to study POCD since the publication of the 1995 Consensus Statement. Future authors could improve study quality and comparability through optimal timing of assessment, the use of commonly used cognitive tests including the Consensus Statement 'core battery', application of appropriate cut-offs and diagnostic rules, and detailed reporting of the methods used. PROSPERO REGISTRY NUMBER: CRD42016039293.

Physostigmine for prevention of postoperative delirium and long-term cognitive dysfunction in liver surgery: A double-blinded randomised controlled trial.

BACKGROUND: Anecdotally, cholinergic stimulation has been used to treat delirium and reduce cognitive dysfunction. OBJECTIVE: The aim of this investigation was to evaluate whether physostigmine reduced the incidence of postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) in patients undergoing liver resection. DESIGN: This was a double-blind, randomised, placebo-controlled trial. Between 11 August 2009 and 3 March 2016, patients were recruited at the Charité - Universitätsmedizin Berlin in Germany. Follow-ups took place at 1 week (T1), 90 days (T2) and 365 days (T3) after surgery. SETTING: This single-centre study was conducted at an academic medical centre. PARTICIPANTS: In total, 261 participants aged at least 18 years scheduled for elective liver surgery were randomised. The protocol also included 45 non-surgical matched controls to provide normative data for POCD and neurocognitive deficit (NCD). INTERVENTION: Participants were allocated to receive either intravenous physostigmine, as a bolus of 0.02 mg kg-1 body weight followed by 0.01 mg kg-1 body weight per hour (n = 130), or placebo (n = 131), for 24 h after induction of anaesthesia. MAIN OUTCOMES AND MEASURES: Primary outcomes were POD, assessed using the Diagnostic and Statistical Manual of Mental Disorders (DSM-4-TR) twice daily up to day 7 after surgery, and POCD assessed via the CANTAB neuropsychological test battery, and two paper pencil tests on the day before surgery, and on postoperative days 7, 90 and 365. RESULTS: In total, 261 patients were randomised, 130 to the physostigmine and 131 to the placebo group. The incidence of POD did not differ significantly between the physostigmine and placebo groups (20 versus 15%; P = 0.334). Preoperative cognitive impairment and POCD frequencies did not differ significantly between the physostigmine and placebo groups at any time. Lower mortality rates were found in the physostigmine group compared with placebo at 3 months [2% (95% confidence interval (CI), 0 to 4) versus 11% (95% CI, 6 to 16), P = 0.002], and 6 months [7% (95% CI, 3 to 12) versus 16% (95% CI, 10 to 23), P = 0.012] after surgery. CONCLUSION: Physostigmine had no effect on POD and POCD when applied after induction of anaesthesia up to 24 h. TRIAL REGISTRATION: DOI 10.1186/ISRCTN18978802, EudraCT 2008-007237-47, Ethics approval ZS EK 11 618/08 (15 January 2009).

[Avoiding Long-term Impairment in Critical Care Using Telemedicine: The ERIC Example]. / Qualitätssteigerung in der Intensivmedizin durch Telemedizin: Beispiel ERIC.

There is a high demand for critical care, which is forecasted to further grow in the future. Increasing patient morbidity and complexity concurring with a shortage of trained intensivists imposes challenges on critical care clinicians. Weathering these challenges, telemedical programs can help utilize and allocate resources more efficiently as well as foster adherence to best practice, thereby directly impacting quality of care. Studies have predominantly shown reductions in mortality and length of stay. Successful telemedical programs employ experienced intensivists, have well-functioning equipment and high acceptance among on-site clinicians. The multicenter, pragmatic, stepped wedge cluster-randomized controlled quality improvement trial Enhanced Recovery after Intensive Care (ERIC) pilots a new form of critical care provision in Germany. With a target study sample size of n = 1431 patients, the study aims to utilize telemedicine to increase adherence to a set of evidence- and consensus-based quality indicators for acute critical care. In an intersectoral case-care management, patients are followed three and six months after discharge from the intensive care unit to be assessed for long-term impairments and post-intensive care syndrome.

[Blended Learning in Critical Care to Improve Quality of Care the ERIC-Training]. / Blended-Learning-Konzepte in der Intensivmedizin am Beispiel des ERIC-Trainings.

Communication and teamwork skills are, besides clinical knowledge, key components of high quality care in modern intensive care units. In light of high staff fluctuations among intensive care unit teams and disparities in clinical experience, an ongoing training is essential to ensure optimal performance in stressfull situations. Further, when implementing new procedures, an adequate concept for staff education is of utmost importance. Blended learning is a novel approach, combining autonomous web-based education and on-site workshops in order to improve the training process. Enhanced Recovery after Intensive Care (ERIC) is a newly developed telemedical intervention targeted at improving evidence-based practice in critical care, guided by quality indicators defined by the German Interdisciplinary Society of Emergency and Critical Care Medicine (DIVI). This telemedical intervention is supplemented with a blended-learning concept combining an e-learning website, simulator-based workshops and on-site training in order to expand the knowledge and practical skills regarding adherence to the quality indicators.

End-of-Life Decision-Making in Intensive Care Ten Years after a Law on Advance Directives in Germany.

Background and Objectives: Mortality on Intensive Care Units (ICUs) is high and death frequently occurs after decisions to limit life-sustaining therapies. An advance directive is a tool meant to preserve patient autonomy by guiding anticipated future treatment decisions once decision-making capacity is lost. Since September 2009, advance directives are legally binding for the caregiver team and the patients' surrogate decision-maker in Germany. The change in frequencies of end-of-life decisions (EOLDs) and completed advance directives among deceased ICU patients ten years after the enactment of a law on advance directives in Germany is unknown. Materials and Methods: Retrospective analysis on all deceased patients of surgical ICUs of a German university medical center from 08/2008 to 09/2009 and from 01/2019 to 09/2019. Frequency of EOLDs and advance directives and the process of EOLDs were compared between patients admitted before and after the change in legislation. (No. of ethical approval EA2/308/20) Results: Significantly more EOLDs occurred in the 2019 cohort compared to the 2009 cohort (85.8% vs. 70.7% of deceased patients, p = 0.006). The number of patients possessing an advance directive to express a living or therapeutic will was higher in the 2019 cohort compared to the 2009 cohort (26.4% vs. 8.9%; difference: 17.5%, p < 0.001). Participation of the patients' family in the EOLD process (74.7% vs. 60.9%; difference: 13.8%, p = 0.048) and the frequency of documentation of EOLD-relevant information (50.0% vs. 18.7%; difference: 31.3%, p < 0.001) increased from 2009 to 2019. Discussion: During a ten-year period from 2009 to 2019, the frequency of EOLDs and the completion rate of advance directives have increased considerably. In addition, EOLD-associated communication and documentation have further improved.

Sense of coherence, mental well-being and perceived preoperative hospital and surgery related stress in surgical patients with malignant, benign, and no neoplasms.

BACKGROUND: This prospective, cross-sectional, observational study examined associations between sense of coherence (SOC), mental well-being, and perceived preoperative hospital and surgery related stress of surgical patients with malignant, benign, and no neoplasms. The objective was to assess a putative association between SOC and preoperative stress, and to test for a statistical mediation by mental well-being. METHOD: The sample consisted of 4918 patients from diverse surgical fields, of which 945 had malignant neoplasms, 333 benign neoplasms, and 3640 no neoplasms. For each subsample, we conducted simple mediation analyses to test an indirect effect of SOC on preoperative stress mediated by mental well-being. The models were adjusted for age, gender, and essential medical factors. RESULTS: Patient groups did not differ significantly regarding degrees of SOC and mental well-being (SOC, M [SD]: 12.31 [2.59], 12.02 [2.62], 12.18 [2.57]; mental well-being M [SD]: 59.26 [24.05], 56.89 [22.67], 57.31 [22.87], in patients with malignant, benign, and without neoplasms, respectively). Patients without neoplasms reported significantly lower stress (4.19 [2.86], M [SD]) than those with benign (5.02 [3.03], M [SD]) and malignant neoplasms (4.99 [2.93], M [SD]). In all three mediation models, SOC had significant direct effects on stress, with higher SOC being associated with lower stress (- 0.3170 [0.0407], - 0.3484 [0.0752], - 0.2919 [0.0206]; c' [SE], p < 0.001 in patients with malignant, benign, and without neoplasms, respectively). In patients with malignant neoplasms and without neoplasms, SOC showed small indirect effects on stress that were statistically mediated by well-being. Higher SOC was related to higher well-being, which in turn was related to lower stress. In patients with benign neoplasms, however, no significant indirect effects of SOC were found. CONCLUSIONS: SOC was directly associated with lower perceived hospital and surgery related stress, over and above the direct and mediation effects of mental well-being. Because the data are cross-sectional, conclusions implying causality cannot be drawn. Nevertheless, they indicate important relationships that can inform treatment approaches to reduce elevated preoperative stress by specifically addressing low SOC. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01357694 . Registered 18 May 2011.

Routine management of postoperative delirium outside the ICU: Results of an international survey among anaesthesiologists.

BACKGROUND: Postoperative delirium (POD) is a severe brain dysfunction. Although data indicate a high relevance, no survey has investigated the routine practice to monitor delirium outside the ICU setting after surgery. Prior to publishing of the new European Society of Anaesthesiology (ESA) guidelines on POD, an international survey was conducted to assess current practice. METHODS: European Society of Anaesthesiology-endorsed online survey; Trial Registration: NCT-identifier: 02513537. RESULTS: In total, 566 respondents from 62 countries accessed, and 564 (99.6%) completed the survey (completion rate). Overall, 385 (68%) of the respondents reported that delirium is either "very relevant" or "relevant" for their daily clinical practice. In all, 38 (7%) of the respondents routinely monitor for delirium in >50% of all patients. Asked on the monitoring time point, more than half (n = 308, 55%) indicated to screen before or at recovery room discharge, 235 (42%) up to the first postoperative day, 143 (25%) up to 3 days, and 77 (14%) up to 5 postoperative days. Although there is a lack of long-term monitoring, nearly all respondents (n = 530, 94%) reported to treat delirium. Availability of EEG/EMG-based monitoring to assess the depth of anaesthesia was high in the study group (n = 547, 97%) and was used by more than one-third of the respondents to reduce risk of burst suppression (n = 189, 34%). CONCLUSION: Although delirium is perceived as a relevant condition among anaesthesiologists, there is a high demand for implementing monitoring strategies after publishing of the POD Guideline. The survey shows that tools necessary for POD Guideline implementation are available in the centres represented by the respondents.

Influence of Sedation Level and Ventilation Status on the Diagnostic Validity of Delirium Screening Tools in the ICU-An International, Prospective, Bi-Center Observational Study (IDeAS).

Background and objectives: The use of delirium screening instruments (DSIs) is recommended in critical care practice for a timely detection of delirium. We hypothesize that the patient-related factors "level of sedation" and "mechanical ventilation" impact test validity of DSIs. Materials and Methods: This is a prospective, bi-center observational study (clinicaltrials.gov: NCT01720914). Critically ill patients were screened for delirium daily for up to seven days after enrollment using the Nursing Delirium Screening Scale (Nu-DESC), Intensive Care Delirium Screening Checklist (ICDSC), and Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Reference standard for delirium diagnosis was the neuropsychiatric examination using the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR). Immediately before delirium assessment, ventilation status and sedation levels were documented. Results: 160 patients were enrolled and 151 patients went into final analysis. Delirium incidence was 23.2%. Nu-DESC showed a sensitivity and specificity of 88.5%, a positive predictive value (PPV) of 71.9%, and a negative predictive value (NPV) of 95.8%. ICDSC had a sensitivity of 62.5%, a specificity of 92.4%, a PPV of 71.4%, and a NPV of 89.0%. CAM-ICU showed a sensitivity of 75.0%, a specificity of 94.7%, a PPV of 85.7%, and a NPV of 90.0%. For Nu-DESC and ICDSC, test validity was significantly better for non-sedated patients (Richmond Agitation Sedation Scale (RASS) 0/-1), whereas test validity for CAM-ICU in a severity scale version showed no significant differences for different sedation levels. No DSI showed a significant difference in test validity between noninvasively and invasively ventilated patients. Conclusions: Test validities of DSIs were comparable to previous studies. The observational scores ICDSC and Nu-DESC showed a significantly better performance in awake and drowsy patients (RASS 0/-1) when compared with other sedation levels. Physicians should refrain from sedation whenever possible to avoid suboptimal performance of DSIs.

Lung Purinoceptor Activation Triggers Ventilator-Induced Brain Injury.

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 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.