Clinical Research Directory

PROSEVO Trial (Propofol-Sevoflurane Delirium Target Trial Emulation)

The results of this study have significant implications for clinical practice and guideline development. The current European guideline on postoperative Delirium prevention (ESAIC 2024) explicitly identifies a lack of large, adequately powered studies comparing different anesthetic techniques and is therefore currently unable to provide clear recommendations on the selection of an optimal technique. This study will close this knowledge gap and thus support future guideline recommendations. The results could show that a particular anesthetic technique (e.g., propofol) is associated with a significantly lower risk of postoperative delirium; if so, this would have immediate implications for modifying standard anesthesia protocols in hospitals. Furthermore, Delirium is a significant public health challenge in aging societies. With demographic aging, the number of older patients undergoing surgery is continuously increasing. The societal costs of Delirium are estimated at several billion euros per year in major industrialized nations. A reduction in the incidence of postoperative Delirium by just 10% through optimization of the anesthetic procedure would therefore have major health economic implications.

Opioid-free Anesthesia and Postoperative Delirium

Postoperative delirium (POD) is a common acute and transient form of brain dysfunction in elderly patients following surgery that can lead to serious adverse clinical outcomes and even death. Although existing studies have preliminarily investigated the effects of opioid-free anaesthesia (OFA) on POD, high-quality evidence on these effects for elderly patients undergoing gastrointestinal surgery remains limited. This study aims to investigate the effects of OFA on the development of POD in elderly patients following gastrointestinal surgery. This single-centre, prospective, randomized controlled trial will be conducted at the First Affiliated Hospital of Shandong First Medical University, China. A total of 654 patients aged 65 years or older who are scheduled for elective gastrointestinal surgery will be randomly allocated to receive either opioid-free anaesthesia (OFA; dexmedetomidine, esmolol, and esketamine) or conventional opioid-based anaesthesia (OBA). The primary outcome is the incidence of POD 7 days after surgery. The secondary outcomes are all-cause mortality within 30 days after surgery, intraoperative haemodynamic changes, the 15-item quality of recovery (QoR-15) scores at 24 h, 48 h, and 72 h after surgery, complications during postoperative hospitalization, pain numerical rating scale (NRS) score at 72 h after surgery, incidence of nausea and vomiting at 72 h after surgery, morphine milligram equivalent for analgesics at 72 h after surgery, duration of anaesthesia (from induction to discontinuation), duration of surgery (from skin incision to the last suture), duration of post-anaesthesia care unit (PACU) stay, and length of hospital stay. The results of this study may shed light on the effects of OFA on POD in elderly patients undergoing gastrointestinal surgery. The study is designed on the basis of the following key hypothesis: the use of opioid drugs for anaesthesia may increase the risk of POD through mechanisms such as blood-brain barrier destruction, neuroinflammatory responses, and central nervous system depression. Through the single-centre and prospective design of this randomized controlled trial, this study will directly analyse differences in the effects of OFA and conventional OBA on the incidence of POD, haemodynamic stability and long-term cognitive function in elderly patients.

Naples Prognostic Score for Predicting Postoperative Delirium

Naples Prognostic Score (NPS) originally developed to predict outcomes in inflammatory and malignant conditions; we asked if it can effectively predict postoperative delirium (POD) in elderly patients undergoing hip surgery? NPS integrate markers such as albumin, neutrophil-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio-all of which have been linked to adverse postoperative outcomes including POD.

Digital Sleep Optimization for Brain Health Outcomes in Older Surgical Patients

The Sleep Optimization for Brain Health Outcomes in Older Surgical Patients (SLEEP-BOOST) is a pilot randomized, controlled, singled-blinded (participant) trial in major orthopedic joint surgery patients that will build on a previously clinically tested cognitive behavioral therapy for insomnia (CBT-I) mobile application paired with a wearable device (wrist actigraphy).

The Effect of Omega 3 Supplementation on Postoperative Delirium in Elderly Patients Undergoing Major Cardiac Surgery

The purpose of this study is to determine whether giving omega-3 fatty acids prior to and after cardiac bypass surgeries decreases the incidence of postoperative delirium in patients aged 65 and over.

Conscious Sedation for Transcatheter Aortic Valve Implantation

Aortic valve stenosis is the heart valve disease with the highest prevalence among the elderly, and may lead to heart failure. Until recently, the only definitive treatment was surgical replacement (SAVR). However, the increased risk associated with the surgical procedure excluded patients with multiple co-morbidities. As the population is aging and more and more patients may present with aortic stenosis, the need of a less invasive approach has emerged. Transcatheter Aortic Valve Replacement (TAVR) offered an alternative therapy for these high risk patients. This new method has seen worldwide acceptance, has been proven very beneficial for these patients, and therefore its indications have been expanded to intermediate risk patients, as well. Until recently, general anesthesia was the primary anesthetic technique for TAVR, but conscious sedation or monitored anesthesia care (MAC) is gaining more and more popularity lately. Our knowledge regarding the comparison between general anesthesia and MAC in TAVR procedures is derived mainly from observational studies and few randomized trials. MAC seems to be associated with less inotropic drug usage, shorter procedural times, shorter intensive care unit (ICU) and hospital length of stay. However, according to published data, there were no differences in 30-day mortality and complications between these two techniques. Even less are known about the most suitable anesthetic agent for MAC during TAVR. Many drugs have been used, with propofol and dexmedetomidine being the most popular. However, there are only few comparative studies and their results are not conclusive. This study compares MAC under propofol and MAC under dexmedetomidine for TAVR in order to examine which method of conscious sedation comes with more beneficial postoperative outcomes for the patients.

Digitalized Clinical Decision Support for the Prevention of Postoperative Delirium (POD)

The project aims to improve patient safety, reduce barriers to the implementation of current guideline recommendations, reduce workload in clinics, increase efficiency in work processes and close gaps in care. Subprojects regarding delirium are implementes as well.

Incidence of Postoperative Delirium in Elderly Patients Undergoing Non-cardiac Surgery

Postoperative delirium (POD) is the most common adverse neurologic complication that can occur in patients of any age. Its incidence varies across age groups and is substantially influenced by patient-related risk factors. POD occurs in 17%-61% of major surgical procedures. Several risk factors which contribute to the development of POD include age more than 60 years, pre-existing cognitive dysfunction, presence of comorbidities, sensorial deficits, malnutrition, polypharmacy, impaired physical mobility and frailty. Postoperative delirium has several wide ranging and adverse outcomes that are consistently associated with delirium such as mortality, increased length of hospital stay, and increased hospital costs. A recently devised tool for rapid assessment of delirium is the 4 A's test. It has now been validated for identifying delirium in the surgical population. The proposed prospective observational study will be conducted on 150 patients belonging to ASA Physical Status I-III of either sex, scheduled to undergo non-cardiac surgery under general anaesthesia (GA), requiring at least 24 hours of postoperative inpatient care. This prospective, observational study aims to evaluate the incidence, risk factors and outcomes of postoperative delirium in elderly patients more than 65 years of age undergoing non-cardiac surgery.

Building a Platform for Precision Anesthesia in the Geriatric Surgical Patient

The research team is creating a foundational infrastructure in order to develop a precision medicine approach for geriatric patients who require surgery with anesthesia. The team plans to build the first of its kind comprehensive database of demographic and risk factor questionnaire responses, biobanked blood specimens, intraoperative electroencephalography (EEG), and inclusive cognitive testing throughout patient interaction starting at the preop appointment until a year later. This will be used to create a predictive model of periooperative neurocognitive disorders.

The Caffeine, Postoperative Delirium, and Change in Outcomes After Surgery (CAPACHINOS-2) Study

The objective of this study is to test the effects of caffeine on neurocognitive and clinical recovery after major surgery. Specifically, this trial tests the primary hypothesis that caffeine will reduce the incidence of postoperative delirium.

Creatine and Perioperative Brain Health

The goal of this study is to understand the effects of oral creatine supplementation in the perioperative period. Creatine is commonly used to enhance athletic performance, but it can also have positive effects on the brain. Since surgery can lead to alterations in thinking, memory, and attention patterns in some patients, we will assess whether creatine can be protective against these changes in older adults undergoing surgery.

Impact of Esketamine on Delayed Neurocognitive Recovery in Older Patients

Esketamine is frequently used during the perioperative period for supplemental analgesia. Small sample size trials showed that subanesthetic dose esketamine may decrease postoperative neurocognitive complications. However, conflicting results exist and optimal dose of esketamine remains to be determined. This dose-exploring pilot trial is designed to evaluate the safety and efficacy of three different perioperative esketamine dosing regimens in older patients undergoing major non-cardiac surgery. The primary purpose is to explore the optimal dosing strategy that produce maximal neurocognitive benefits with minimal adverse neuropsychiatric symptoms.

Correlation Between Preoperative Sleep and Postoperative Brain and Renal Dysfunction

To explore the correlation between preoperative sleep parameter clustering and postoperative brain and renal dysfunction.

Preoperative Distress and Postoperative Delirium in Elderly Patients Undergoing Major Orthopedic Surgery

Postoperative delirium is a common and serious complication in elderly patients undergoing major orthopedic surgery and is associated with increased morbidity, prolonged hospital stay, and higher healthcare costs. Preoperative psychological distress has been suggested as a potential risk factor influencing postoperative outcomes; however, its relationship with delirium and other clinical outcomes remains insufficiently explored. This prospective observational study aims to investigate the association between preoperative distress levels and postoperative delirium, pain intensity, and length of hospital stay in elderly patients undergoing major orthopedic surgery. Preoperative distress will be assessed using validated tools, and postoperative outcomes including delirium incidence, pain scores, and hospital stay duration will be recorded and analyzed. The findings of this study are expected to contribute to improved perioperative risk stratification and may support the development of targeted interventions to reduce postoperative complications in this vulnerable patient population.

Verification of a New Predictive Delirium Score in Adults With Elective Cardiac Valve or Bypass Surgery With Perioperative Use of a Heart-lung Machine; a Monocentric Pilot Observational Study

Basics (state of scientific knowledge): Delirium is an acute disturbance of consciousness and attention that develops over a short period of time and fluctuates in severity. It is accompanied by a deterioration in cognitive performance, such as memory deficits, disorientation, and speech and thinking disorders, which significantly exceed the degree of any pre-existing limitations . Surgery and intensive medical treatment are considered to be two of the triggers. In cardiac surgery, the incidence is reported to be between 10 and 50%, depending on the patient population. Delirium occurs approximately 3-4 days after surgery and lasts for several days. Relevant factors in the cardiac surgery population include age, duration of aortic clamping time or surgical technique, pre-existing conditions such as the extent of heart failure (EuroScore), diabetes mellitus, mental and cognitive impairments, or carotid stenosis. Both current studies and current recommendations emphasize prevention and the lack of successful treatment options. Preventive measures are primarily investigated in packages of measures. The study presented here aims to define risk populations and test the sensitivity and specificity of the MO-FA2-(TB) score for the development of delirium. Objectives of the study: Verification of the predictive score "MO-FA2-(TB)" for the development of postoperative delirium Recording of delirium and associated influencing factors and endpoints Categories examined in the score: Memory using a list of words that must be memorized and repeated after a few minutes Orientation by asking about the year, month, date, day of the week, city, and location Frailty using the ASA score Use of heart-lung machine Incision-suture time Study duration (for individual subjects): postoperative intensive care stay up to and including day 10 Study population Patients who have to undergo cardiac surgery with CPB Inclusion criteria: Elective cardiac surgery Heart valve surgery, bypass surgery with CPB Length of stay in ICU \> 48 hours Age ≥18 years Fluent German language skills Exclusion criteria: Age \<18 years Lack of capacity to give consent Emergency Readmission to intensive care unit OPCAB surgery, microsurgical procedure Recruitment: Information provided the day before surgery based on the surgical schedule If consent is given, score is recorded If ICU stay \>48 hours, treatment data is recorded, otherwise exclusion Data collection up to and including d10 Treatment data collected: Preoperative data, including ejection fraction, aids, abuse, scores collected ("4AT test" for rapid assessment of delirium and cognitive impairment, "MO-FA2-(TB)", "geriatric check" for identifying a geriatric patient) Intraoperative data, including duration of surgery, duration of heart-lung machine, acidosis Postoperative data in ICU, including delirium scores (ICDSC, CAM-ICU), days on ventilation, days of treatment, fluid intake, medication related to delirium, organ replacement therapy such as dialysis Number of cases: Approx. 100 patients Methodology Monocentric, observation

Orthopedic Procedures and Postoperative Delirium in Older Adults in the Czech Republic

This multicenter, prospective, non-interventional observational study (ORTOPODCZ) investigates the association between preoperative cognitive impairment and postoperative delirium (POD) in older adults undergoing elective total hip arthroplasty in the Czech Republic. Postoperative delirium is a frequent and serious neurocognitive complication in senior surgical patients and is associated with increased morbidity, mortality, prolonged hospitalization, and impaired functional and cognitive outcomes. Despite international recommendations, routine preoperative cognitive screening remains insufficiently implemented. The study evaluates the predictive value of the ALBA test, a brief cognitive screening tool, performed during the pre-anesthetic assessment. Postoperative delirium will be assessed using the validated CAM-ICU instrument for up to 72 hours after surgery. Secondary objectives include assessing the relationship between POD and frailty, polypharmacy, comorbidities, type of anesthesia, intraoperative hemodynamics, blood loss, vasoactive support, and postoperative complications. Approximately 300-400 participants aged ≥65 years will be enrolled across seven centers. No additional procedures, biological sampling, or deviations from standard clinical care are required. Data will be collected in REDCap and analyzed according to a predefined statistical analysis plan. The study aims to provide robust evidence supporting the integration of cognitive screening into routine preoperative evaluation and to describe feasibility and implementation requirements for the ALBA test in clinical practice.

Inflammatory Biomarkers and Postoperative Delirium in Pediatric Circumcision

Postoperative delirium may occur in children after general anesthesia, even following short procedures such as circumcision. Preoperative systemic inflammation has been associated with postoperative delirium in adults, but data in pediatric patients are limited. This prospective observational study aims to evaluate the association between preoperative inflammatory biomarkers and postoperative delirium in children aged 2-12 years undergoing elective circumcision under general anesthesia. Inflammatory biomarkers derived from routine complete blood count parameters, including NLR, PLR, MLR, SII, and SIRI, will be analyzed. Postoperative delirium will be assessed using the Pediatric Anesthesia Emergence Delirium (PAED) scale in the post-anesthesia care unit. The relationship between inflammatory biomarkers and delirium development and severity will be evaluated. This study seeks to identify simple preoperative markers that may help predict postoperative delirium risk in pediatric patients.

Increasing Preoperative Cognitive Reserve to Prevent Postoperative Cognitive Dysfunction in Cardiac Surgical Patients

Postoperative delirium (POD) and postoperative cognitive decline (POCD) can be observed after cardiosurgical interventions. Taken together, these postoperative neurocognitive dysfunctions contribute to increased morbidity and mortality and higher economic costs. Preoperative risk factors of postoperative neurocognitive dysfunctions, such as decreased neuropsychometric performance or decreased cognitive daily activities, can be interpreted as reduced cognitive reserve. The aim of this study is to build up cognitive reserves to protect against the development of POD and POCD through preoperative, home-based, cognitive training.

Decreasing Preoperative Stress to Prevent Postoperative Delirium and Postoperative Cognitive Decline in Cardiac Surgical Patients.

Patients undergoing cardiac surgery often complain of anxiety before a major operation and the resulting stress. This circumstance is a risk factor for mental problems that may occur after the operation (e.g., delirium or memory deficits). This study aims to prevent these discomforts by a preoperative relaxation intervention.

Dexmedetomidine vs Midazolam in Coronary Artery By-pass Surgery

The aim is to compare the incidence of postoperative delirium following coronary artery bypass grafting (CABG) between patients receiving dexmedetomidine and those receiving midazolam infusions.

Effect of Perioperative IV Ibuprofen on Cerebral Oxygenation and Postoperative Cognition During One-Lung Ventilation

This study compares the effects of ibuprofen administered during surgery and within the first 24 hours after surgery, versus no ibuprofen, on cerebral oxygenation, postoperative changes in consciousness (postoperative delirium and cognitive dysfunction), length of stay in the intensive care unit, and the incidence of postoperative pain, nausea, vomiting, and pruritus in patients undergoing lung lobectomy or segmentectomy using a closed (video-assisted) method (VATS - video-assisted thoracoscopic surgery), in whom one-lung ventilation is applied. The aim of this study is to evaluate the effects of ibuprofen on cerebral oxygenation, postoperative cognitive changes, and delirium in patients undergoing one-lung ventilation.

Impact of Personalised Cardiac Anaesthesia and Cerebral Autoregulation on Neurological Outcomes in Patients Undergoing Cardiac Surgery

This international, multicentre prospective cohort study will assess whether perioperative duration and magnitude of mean arterial pressure (MAP) outside of an individual's cerebral autoregulation (CA) limits using near-infrared spectroscopy (NIRS) and transcranial Doppler (TCD) are associated with adverse neurological events. It is to investigate whether patients with a higher burden of cerebral haemodynamic insults have an increased incidence or poorer neurological outcomes. Associations between neurologic outcomes, neurobiomarkers and genetic tests will be explored.

Association of Preoperative Hippocampal Glucose Metabolism With Postoperative Delirium in Older Diabetic Patients

Objective: To investigate the association between preoperative hippocampal glucose metabolism levels and the risk of postoperative delirium (POD) in elderly patients with type 2 diabetes (T2DM), and to provide a prospective neuroimaging biomarker for identifying high-risk populations. Methods: This prospective cohort study plans to enroll 154 elderly T2DM patients scheduled for liver tumor resection at the First Medical Center of Chinese PLA General Hospital. Baseline cognitive function will be assessed using the Mini-Mental State Examination (MMSE) one day before surgery. Hippocampal glucose metabolism will be quantitatively evaluated by measuring the mean standardized uptake value (SUVmean) of bilateral hippocampi using ¹⁸F-FDG PET/CT. POD will be assessed twice daily from postoperative days 1 to 7 using the 3-Minute Diagnostic Interview for CAM (3D-CAM). The correlation between preoperative hippocampal SUVmean and POD incidence will be analyzed using univariate and multivariate logistic regression models. The predictive performance will be evaluated by constructing receiver operating characteristic (ROC) curves. Furthermore, the relationship between a peripheral insulin resistance marker (the triglyceride-glucose index, TyG index) and hippocampal metabolism levels will be analyzed. Significance: This study aims to determine whether impaired preoperative hippocampal metabolism serves as an independent risk factor for POD. The findings are expected to provide a prospective functional neuroimaging biomarker for the early warning of POD and offer a theoretical basis for developing precise prevention strategies targeting cerebral metabolic abnormalities. This will facilitate the application of neuroimaging techniques in the field of perioperative brain dysfunction monitoring.

Remimazolam for Reducing Postoperative Delirium in Elderly Patients Undergoing Laparoscopic Gastrectomy

This prospective, randomized controlled clinical trial aims to evaluate whether remimazolam can reduce the incidence of postoperative delirium (POD) in elderly patients undergoing laparoscopic radical gastrectomy for gastric cancer. A total of 170 patients aged 65 years or older will be enrolled and randomized in a 1:1 ratio to receive either remimazolam or a propofol-midazolam regimen for anesthesia induction and maintenance. Standard perioperative monitoring, BIS-guided anesthesia depth control, and postoperative pain management will be applied in both groups. The primary outcome is the incidence of postoperative delirium within 5 days after surgery, assessed twice daily using the 3D-CAM. Secondary outcomes include emergence agitation, extubation time, postoperative pain scores, cognitive function at discharge, intraoperative hemodynamic stability, unplanned ICU admission, postoperative complications, and length of ICU stay. This study aims to determine whether remimazolam provides a safer and more effective anesthetic option for improving postoperative neurological outcomes and recovery in elderly patients undergoing laparoscopic radical gastrectomy.