Prehospital Misdiagnosed Acute Coronary Syndrome-Incidence, Discriminating Features, and Differential Diagnoses.

Background: Acute coronary syndrome (ACS) is a major cause of morbidity and mortality in the western world. Classic angina pectoris (AP) is a common reason to request prehospital emergency medical services (EMS). Nevertheless, data on diagnostic accuracy and common misdiagnoses are scarce. Therefore, the aim of this study is to evaluate the amount and variety of misdiagnoses and assess discriminating features. Methods: For this retrospective cohort study, all patients requiring EMS for suspected ACS in the city of Bonn (Germany) during 2018 were investigated. Prehospital and hospital medical records were reviewed regarding medical history, presenting signs and symptoms, as well as final diagnosis. Results: Out of 740 analyzed patients with prehospital suspected ACS, 283 (38.2%) were ultimately diagnosed with ACS (ACS group). Common diagnoses in the cohort with non-confirmed ACS (nACS group) consisted of unspecific pain syndromes, arrhythmias, hypertensive crises, and heart failure. ST segment elevation (adjusted odds-ratios [adj. OR] 2.70), male sex (adj. OR 1.71), T wave changes (adj. OR 1.27), angina pectoris (adj. OR 1.15) as well as syncope (adj. OR 0.63) were identified among others as informative predictors in a multivariable analysis using the lasso technique for data-driven variable selection. Conclusions: Misdiagnosed ACS is as common as 61.8% in this cohort and analyses point to a complex of conditions and symptoms (i.e., male sex, electrocardiographic (ECG) changes, AP) for correct ACS diagnosis while neurological symptoms were observed significantly more often in the nACS group (e.g., Glasgow Coma Scale (GCS) < 15, p = 0.03). To ensure adequate and timely therapy for a potentially critical disease as ACS a profound prehospital examination and patient history is indispensable.

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.

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.

Occurrence of Postoperative Delirium and the Use of Different Assessment Tools.

(1) Background: Postoperative delirium (POD) poses a high risk of worsening outcomes for patients and is also a burden for hospitals. The leading guidelines recommend standardized POD assessment and prevention. The aim of this subgroup analysis of the PRe-Operative Prediction of Postoperative DElirium by Appropriate SCreening (PROPDESC) trial was to compare different delirium assessments and to analyse the frequency of POD on five postoperative days. (2) Methods: This prospective observational trial enrolled 1097 patients in a university hospital from 2018 until 2019. The following POD assessment tools were used for five consecutive days: Confusion Assessment Method for ICU (CAM-ICU) or Confusion Assessment Method for normal ward (CAM), 4 A's Test (4AT) and Delirium Observation Screening (DOS) scale. (3) Results: In a 5-day visit interval, most new POD developments occurred on the first and second postoperative day. A clear recommendation for a specific POD assessment tool based on our results cannot be given. (4) Conclusions: According to guidelines, a POD assessment should take place on the first five postoperative days, but of these, the first two are those of highest POD occurrence. The POD assessment tool used should at best include direct patient questioning and aspects of patient observation.

The Impact of Perioperative and Predisposing Risk Factors on the Development of Postoperative Delirium and a Possible Gender Difference.

(1) Background: Postoperative delirium (POD) is an undesirable event especially for older patients after surgery. Perioperative risks for POD development are multiple, but gender differences are still poorly considered. In this observational study, predisposing and precipitating risk factors of POD and the possible gender influence are distinguished. (2) Methods: This observational prospective trial enrolled 1097 patients in a tertiary hospital from September 2018 until October 2019. 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 Screening (DOS) scale was positive on one of five assessment days. (3) Results: POD incidence was 23.5% and the mean age of study population was 72.3 ± 7.3 years. The multiple logistic regression model showed a significant impact of age (Odds Ratio (OR) 1.74; 95% Confidence Interval (CI): 1.37-2.22), American Society of Anesthesiologists (ASA) (OR 1.67; 95% CI: 1.25-2.26), surgery risk (OR 2.10; 95% CI: 1.52-2.95) and surgery duration (OR 1.17; 95% CI: 1.07-1.28), ventilation time (OR 1.64; 95% CI: 1.27-2.24), as well as the male sex (OR 1.74; 95% CI: 1.37-2.22) on POD risk. (4) Conclusions: Perioperative and predisposing risk factors had an impact on the development of POD. The influence of male sex should be considered in future research.

The Impact of Drug Interactions in Patients with Community-Acquired Pneumonia on Hospital Length of Stay.

(1) Background: An aging society is frequently affected by multimorbidity and polypharmacy, which, in turn, leads to an increased risk for drug interaction. The aim of this study was to evaluate the influence of drug interactions on the length of stay (LOS) in hospitals. (2) Methods: This retrospective, single-centre study is based on patients treated for community-acquired pneumonia in the hospital. Negative binomial regression was used to analyse the association between drug interactions and the LOS in the hospital. (3) Results: The total cohort contained 503 patients, yet 46 inpatients (9%) that died were not included in the analyses. The mean age was 74 (±15.3) years, 35% of patients older than 65 years were found to have more than two drug interactions, and 55% had a moderate, severe, or contraindicated adverse drug reaction. The regression model revealed a significant association between the number of drug interactions (rate ratio (RR) 1.02; 95%-CI 1.01-1.04) and the severity of drug interactions (RR 1.22; 95%-CI 1.09-1.37) on the LOS for the overall cohort as well as for the subgroup of patients aged 80 years and older. (4) Conclusion: Drug interactions are an independent risk factor for prolonged hospitalisation. Standardised assessment tools to avoid drug interactions should be implemented in clinical routines.

Prehospital misdiagnosis of acute cerebral disease for acute coronary syndrome: a retrospective study.

OBJECTIVE: In cerebrovascular accidents symptoms, laboratory results and electrocardiogram (ECG) changes can mimic acute coronary syndrome (ACS) and is subsumed as neurogenic stunned myocardium. So far, data regarding the frequency of cerebrovascular accidents misdiagnosed for ACS in a prehospital setting are missing. This study aims to quantify misdiagnoses and discover discriminating features. METHODS: In a retrospective cohort study, prehospital and hospital medical records of all patients treated by physician-staffed emergency medical teams in the city of Bonn (Germany) with suspected ACS in 2018 were evaluated regarding medical history, prehospital symptoms and findings as well as hospital diagnoses. RESULTS: From 758 patients admitted for presumed ACS, 9 patients (1.2%, 95% CI: 0.5-2.2%) suffered from acute cerebral disease (ACD group). Mainly, diagnoses were cerebrovascular accidents and one case of neuroborreliosis. A history of intracranial haemorrhage was found more often in the ACD group compared to the remaining cohort (OR 19, p = 0.01), while a history of arterial hypertension was less frequent (OR 0.22, p = 0.03). Presentation with headaches (OR 10.1, p = 0.03) or neurological symptoms (OR 16.9, p = 0.01) occurred more frequent in the ACD group. ECG changes were similar between groups. CONCLUSION: Acute cerebral disease misdiagnosed for ACS seems more common than assumed. Out of 758 patients with presumed ACS, 9 patients (1.2%) suffered from ACD, which were cerebrovascular accidents mainly. This is highly relevant, since prehospital treatment with heparin and acetylsalicylic acid is indicated in ACS but contraindicated in cerebrovascular accidents without further diagnostics. Thus, discriminating these patients is crucial. An attentive patient history and examination may be the key to differentiating ACD. Due to small ACD group size, further studies are needed.

Effects of on-Table Extubation after Pediatric Cardiac Surgery.

Background: Enhanced recovery after surgery (ERAS) protocols are utilizing a multidisciplinary approach, reassessing physiology to improve clinical outcomes, reducing length of hospital stay (LOS) stay, resulting in cost reduction. Since its introduction in colorectal surgery. the concept has been utilized in various fields and benefits have been recognized also in adult cardiac surgery. However, ERAS concepts in pediatric cardiac surgery are not yet widely established. Therefore, the aim of the present study was to assess the effects of on-table extubation (OTE) after pediatric cardiac surgery compared to the standard approach of delayed extubation (DET) during intensive care treatment. Study Design and Methods: We performed a retrospective analysis of all pediatric cardiac surgery cases performed in children below the age of two years using cardiopulmonary bypass at our institution in 2021. Exclusion criteria were emergency and off pump surgeries as well as children already ventilated preoperatively. Results: OTE children were older (267.3 days vs. 126.7 days, p < 0.001), had a higher body weight (7.0 ± 1.6 kg vs. 4.9 ± 1.9 kg, p < 0.001), showed significantly reduced duration of ICU treatment (75.9 ± 56.8 h vs. 217.2 ± 211.4 h, p < 0.001) and LOS (11.1 ± 10.2 days vs. 20.1 ± 23.4 days; p = 0.001) compared to DET group. Furthermore, OTE children had significantly fewer catecholamine dependencies at 12-, 24-, 48-, and 72-h post-surgery, while DET children showed a significantly increased intrafluid shift relative to body weight (109.1 ± 82.0 mL/kg body weight vs. 63.0 ± 63.0 mL/kg body weight, p < 0.001). After propensity score matching considering age, weight, bypass duration, Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery Mortality (STATS)-Score, and the outcome variables, including duration of ICU treatment, catecholamine dependencies, and hospital LOS, findings significantly favored the OTE group. Conclusion: Our results suggest that on-table extubation after pediatric cardiac surgery is feasible and in our cohort was associated with a favorable postoperative course.

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.

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.