Predictiveness of preoperative laboratory values for postoperative delirium.

Background: Postoperative delirium (POD) is a common postoperative complication, especially in patients over 60 years, with an incidence ranging from 15% to 50%. In most cases, POD manifests in the first 5 days after surgery. Multiple contributing risk factors for POD have been detected. Besides the predisposing factors such as higher age, cognitive impairment, high blood pressure, atrial fibrillation, and past stroke, pathophysiological mechanisms like neuroinflammation are also considered as contributing factors. Methods: In a subanalysis of the "PRe- Operative  Prediction of postoperative  DElirium by appropriate  SCreening" (PROPDESC) study, the preoperative laboratory values of sodium, potassium, total protein, hemoglobin concentration (Hgb), and white blood cells as well as the biomarkers creatinine, HbA1c, NT-pro-BNP, high sensitive Troponin T (hsTnT), and C-reactive protein (CRP) were assessed to investigate a possible relationship to the occurrence of POD. Results: After correction for age, physical status classification, surgery risk after Johns Hopkins, and operative discipline (cardiac surgery vs. noncardiac surgery), male patients with a Hgb <13 g/dL had significantly higher odds for POD (p = 0.025). Furthermore, patients with CRP ≥ 10 mg/L, HbA1c value ≥ 8.5% as well as patients with hypernatraemia (>145 mmol/L) presented significantly higher odds to develop POD (p = 0.011, p < 0.001, and p = 0.021, respectively). A raised (>14-52 ng/L) or high (>52 ng/L) hsTnT value was also associated with a significantly higher chance for POD compared to the patient group with hsTnT <14 ng/L (p < 0.001 and p = 0.016, respectively). Conclusions: Preoperative Hgb, CRP, HbA1c, sodium, and hsTnT could be used to complement and refine the preoperative screening for patients at risk for POD. Further studies should track these correlations to investigate the potential of targeted POD protection and enabling hospital staff to initiate POD-preventing measures in time.

Functional intervention following cardiac surgery to prevent postoperative delirium in older patients (FEEL WELL study).

BACKGROUND: Postoperative delirium is a common complication in patients after cardiac surgery, especially in older patients, and can manifest as a disturbance of attention and consciousness. It can lead to increased postoperative morbidity, prolonged need for care, and mortality. The presented study investigates whether the occurrence of postoperative delirium after cardiac surgery can be prevented by a multisensory stimulation. It was conducted as a prospective, randomized, controlled, non-pharmacological intervention study in the years 2021 and 2022 at the University Hospital Bonn in Germany. A total of 186 patients over 65 years with elective cardiac surgery were enrolled. Patients were randomized either to the intervention or control group. In both groups, postoperative delirium was assessed with the 3-min diagnostic interview for confusion assessment method on the first 5 days after surgery and pain was assessed using the Numeric Rating Scale. Multisensory stimulation was performed 20 min a day for the first three postoperative days in the intervention group. RESULTS: The incidence of postoperative delirium was 22.6% in the intervention group and 49.5% in the control group (p < 0.001). Duration of postoperative delirium was significantly shorter in the intervention group (p < 0.001). Stay in the intensive care unit was significantly longer in the control group (p = 0.006). In the regression model non-intervention, high pain scores, advanced age, and prolonged mechanical ventilation were associated with postoperative delirium (p = 0.007; p = 0.032; p = 0.006; p = 0.006, respectively). CONCLUSIONS: Results of the study imply that a multisensory stimulation done on the first 3 days after planned cardiac surgery can reduce the incidence and duration of postoperative delirium in older patients. Influence of the treatment on the incidence of delirium in other patient groups, the length of stay in the intensive care unit, and patients´ postoperative pain should be confirmed in further clinical studies. TRIAL REGISTRATION: DRKS, DRKS00026909. Registered 28 October 2021, Retrospectively registered, https://drks.de/search/de/trial/DRKS00026909 .

Postoperative delirium is an independent factor influencing the length of stay of elderly patients in the intensive care unit and in hospital.

PURPOSE: Postoperative delirium (POD) is an often unrecognized adverse event in older people after surgery. The aim of this subgroup analysis of the PRe-Operative Prediction of postoperative DElirium by appropriate SCreening (PROPDESC) trial in patients aged 70 years and older was to identify preoperative risk factors and the impact of POD on length of stay (LOS) in intensive care unit (ICU) and hospital. METHODS: Of the total 1097 patients recruited at a German university hospital (from September 2018 to October 2019) in the PROPDESC prospective observational study, 588 patients aged 70 years and older (mean age 77.2 ± 4.7 years) were included for subgroup analysis. The primary endpoint POD was considered positive if one of the following tests were positive on any of the five postoperative visit days: Confusion Assessment Method for ICU (CAM-ICU), Confusion Assessment Method (CAM), 4'A's (4AT) and Delirium Observation Scale (DOS). Trained doctoral students carried out these visitations and additionally the nursing staff were interviewed for completion of the DOS. To evaluate the independent effect of POD on LOS in ICU and in hospital, a multi-variable linear regression analysis was performed. RESULTS: The POD incidence was 25.9%. The results of our model showed POD as an independent predictor for a prolonged LOS in ICU (36%; 95% CI 4-78%; < 0.001) and in hospital (22%; 95% CI 4-43%; < 0.001). CONCLUSION: POD has an independent impact on LOS in ICU and in hospital. Based on the effect of POD for the elderly, a standardized risk screening is required. TRAIL REGISTRATION: German Registry for Clinical Studies: DRKS00015715.

PRe-Operative Prediction of postoperative DElirium by appropriate SCreening (PROPDESC) development and validation of a pragmatic POD risk screening score based on routine preoperative data.

STUDY OBJECTIVE: To develop and validate a pragmatic risk screening score for postoperative delirium (POD) based on routine preoperative data. DESIGN: Prospective observational monocentric trial. SETTING: Preoperative data and POD assessment were collected from cardiac and non-cardiac surgical patients at a German university hospital. Data-driven modelling approaches (step-wise vs. component-wise gradient boosting on complete and restricted predictor set) were compared to predictor selection by experts (investigators vs. external Delphi survey). PATIENTS: Inpatients (≥60 years) scheduled for elective surgery lasting more than 60 min. MEASUREMENTS: POD was assessed daily during first five postoperative or post-sedation days with confusion assessment method for intensive and standard care unit (CAM-ICU/CAM), 4 'A's test (4AT) and Delirium Observation Screening (DOS) scale. MAIN RESULTS: From 1023 enrolled patients, 978 completed observations were separated in development (n = 600; POD incidence 22.2%) and validation (n = 378; POD incidence 25.7%) cohorts. Data-driven approaches generated models containing laboratory values, surgical discipline and several items on cognitive and quality of life assessment, which are time consuming to collect. Boosting on complete predictor set yielded the highest bootstrapped prediction accuracy (AUC 0.767) by selecting 12 predictors, with substantial dependence on cardiac surgery. Investigators selected via univariate comparison age, ASA and NYHA classification, surgical risk as well as ´serial subtraction´ and ´sentence repetition´ of the Montreal Cognitive Assessment (MoCA) to enable rapid collection of their risk score for preoperative screening. This investigator model provided slightly lower bootstrapped prediction accuracy (AUC 0.746) but proved to have robust results on validation cohort (AUC 0.725) irrespective of surgical discipline. Simplification of the investigator model by scaling and rounding of regression coefficients into the PROPDESC score achieved a comparable precision on the validation cohort (AUC 0.729). CONCLUSIONS: The PROPDESC score showed promising performance on a separate validation cohort in predicting POD based on routine preoperative data. Suitability for universal screening needs to be shown in a large external validation.

Perioperative Vascular Biomarker Profiling in Elective Surgery Patients Developing Postoperative Delirium: A Prospective Cohort Study.

BACKGROUND: Postoperative delirium (POD) ranks among the most common complications in surgical patients. Blood-based biomarkers might help identify the patient at risk. This study aimed to assess how serum biomarkers with specificity for vascular and endothelial function and for inflammation are altered, prior to or following surgery in patients who subsequently develop POD. METHODS: This was a study on a subcohort of consecutively recruited elective non-cardiac as well as cardiac surgery patients (age > 60 years) of the single-center PROPDESC trial at a German tertiary care hospital. Serum was sampled prior to and following surgery, and the samples were subjected to bead-based multiplex analysis of 17 serum proteins (IL-3, IL-8, IL-10, Cripto, CCL2, RAGE, Resistin, ANGPT2, TIE2, Thrombomodulin, Syndecan-1, E-Selectin, VCAM-1, ICAM-1, CXCL5, NSE, and uPAR). Development of POD was assessed during the first five days after surgery, using the Confusion Assessment Method for ICU (CAM-ICU), the CAM, the 4-'A's test (4AT), and the Delirium Observation Scale (DOS). Patients were considered positive if POD was detected at least once during the visitation period by any of the applied methods. Non-parametric testing, as well as propensity score matching were used for statistical analysis. RESULTS: A total of 118 patients were included in the final analysis; 69% underwent non-cardiac surgery, median overall patient age was 71 years, and 59% of patients were male. In the whole cohort, incidence of POD was 28%. The male gender was significantly associated with the development of POD (p = 0.0004), as well as a higher ASA status III (p = 0.04). Incidence of POD was furthermore significantly increased in cardiac surgery patients (p = 0.002). Surgery induced highly significant changes in serum levels of almost all biomarkers except uPAR. In preoperative serum samples, none of the analyzed parameters was significantly altered in subsequent POD patients. In postoperative samples, CCL2 was significantly increased by a factor of 1.75 in POD patients (p = 0.03), as compared to the no-POD cohort. Following propensity score matching, CCL2 remained the only biomarker that showed significant differences in postoperative values (p = 0.01). In cardiac surgery patients, postoperative CCL2 serum levels were more than 3.5 times higher than those following non-cardiac surgery (p < 0.0001). Moreover, after cardiac surgery, Syndecan-1 serum levels were significantly increased in POD patients, as compared to no-POD cardiac surgery patients (p = 0.04). CONCLUSIONS: In a mixed cohort of elective non-cardiac as well as cardiac surgery patients, preoperative serum biomarker profiling with specificity for vascular dysfunction and for systemic inflammation was not indicative of subsequent POD development. Surgery-induced systemic inflammation-as evidenced by the significant increase in CCL2 release-was associated with POD, particularly following cardiac surgery. In those patients, postoperative glycocalyx injury might furthermore contribute to POD development.

Postoperative delirium after cardiac surgery of elderly patients as an independent risk factor for prolonged length of stay in intensive care unit and in hospital.

BACKGROUND: Postoperative delirium (POD) is a relevant and underdiagnosed complication after cardiac surgery that is associated with increased intensive care unit (ICU) and hospital length of stay (LOS). The aim of this subgroup study was to compare the frequency of tested POD versus the coded International Statistical Classification of Diseases and Related Health Problems (ICD) diagnosis of POD and to evaluate the influence of POD on LOS in ICU and hospital. METHODS: 254 elective cardiac surgery patients (mean age, 70.5 ± 6.4 years) at the University Hospital Bonn between September 2018 and October 2019 were evaluated. The endpoint tested POD was considered positive, if one of the tests Confusion Assessment Method for ICU (CAM-ICU) or Confusion Assessment Method (CAM), 4 'A's Test (4AT) or Delirium Observation Scale (DOS) was positive on one day. RESULTS: POD occurred in 127 patients (50.0%). LOS in ICU and hospital were significantly different based on presence (ICU 165.0 ± 362.7 h; Hospital 26.5 ± 26.1 days) or absence (ICU 64.5 ± 79.4 h; Hospital 14.6 ± 6.7 days) of POD (p < 0.001). The multiple linear regression showed POD as an independent predictor for a prolonged LOS in ICU (48%; 95%CI 31-67%) and in hospital (64%; 95%CI 27-110%) (p < 0.001). The frequency of POD in the study participants that was coded with the ICD F05.0 and F05.8 by hospital staff was considerably lower than tests revealed by the study personnel. CONCLUSION: Approximately 50% of elderly patients who underwent cardiac surgery developed POD, which is associated with an increased ICU and hospital LOS. Furthermore, POD is highly underdiagnosed in clinical routine.

Estimating patients' risk for postoperative delirium from preoperative routine data - Trial design of the PRe-Operative prediction of postoperative DElirium by appropriate SCreening (PROPDESC) study - A monocentre prospective observational trial.

BACKGROUND: Postoperative Delirium (POD) is the most common complication of elderly patients after surgery associated with increased postoperative morbidity, persistent care dependency and even mortality. Prevention of POD requires detection of patients at high risk prior to surgery. PROPDESC intends to provide an instrument for preoperative routine screening of patients' risk for POD. METHODS: PROPDESC is a monocentric prospective observatory trial including 1000 patients older than 60 years from various disciplines of a university hospital planned for surgery of at least 60 min. To develop a score predicting the risk for POD, anesthesiological stratifications, laboratory values, medication and known risk factors as well as quality of life and cognitive performance are taken into account. POD assessment is performed daily on the first five days after the operation respectively the end of sedation in the intensive care units and normal wards. The score is evaluated from 600 data sets and subsequently validated internally. The most appropriate predictors are determined by a component-wise gradient boosting approach. DISCUSSION: Based on retrospective investigations, etiology of POD is considered multifactorial. By a prospective analysis of various factors, PROPDESC intends to provide an applicable tool to predict the risk for POD from preoperative routine data and assessment of cognitive function. Objective is to establish an automatically generating score in preoperative routine to screen patients for increased risk of POD as starting point for POD reduction and management. Model compilation requires a high significance and enhancement within compound as well as regular availability of the selected predictors. TRIAL REGISTRATION: DRKS, DRKS00015715. Registered 13 December 2018 - Retrospectively registered, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00015715.

Association of DNA polymorphisms in the synaptic vesicular amine transporter gene (SLC18A2) with alcohol and nicotine dependence.

The brain synaptic vesicular amine transporter SLCA18A2 is a key component for the uptake of monoamines like dopamine or serotonin into vesicles. We have analyzed seven DNA polymorphisms located in the genomic region of SLC18A2 for association with alcohol- and nicotine dependence, using a family-based design. Our sample comprised 131 families with alcohol-dependent offspring and 96 families with at least one nicotine-dependent offspring. For the alcohol-dependent sample, we found statistical significant association for two single markers (rs363387, P=0.03; rs363333, P=0.0066) as well as for several haplotypes (minimal P=0.0038). When the sample with alcohol dependence was stratified according to gender, we observed increased association for the male subgroup (rs363387, P=0.0011). None of the markers showed association in the sample of families with nicotine dependence. However, analysis of a combined sample of alcohol and nicotine-dependent families resulted in single markers as well as several haplotypes showing statistical significant association with substance dependence (minimal P=0.0044). We conclude that DNA polymorphisms located in SLC18A2 might contribute to the development of substance dependence.