Influence of a chronic beta-blocker therapy on perioperative opioid consumption - a post hoc secondary analysis.

BACKGROUND: Beta-blocker (BB) therapy plays a central role in the treatment of cardiovascular diseases. An increasing number of patients with cardiovascular diseases undergoe noncardiac surgery, where opioids are an integral part of the anesthesiological management. There is evidence to suggest that short-term intravenous BB therapy may influence perioperative opioid requirements due to an assumed cross-talk between G-protein coupled beta-adrenergic and opioid receptors. Whether chronic BB therapy could also have an influence on perioperative opioid requirements is unclear. METHODS: A post hoc analysis of prospectively collected data from a multicenter observational (BioCog) study was performed. Inclusion criteria consisted of elderly patients (≥ 65 years) undergoing elective noncardiac surgery as well as total intravenous general anesthesia without the use of regional anesthesia and duration of anesthesia ≥ 60 min. Two groups were defined: patients with and without BB in their regular preopreative medication. The administered opioids were converted to their respective morphine equivalent doses. Multiple regression analysis was performed using the morphine-index to identify independent predictors. RESULTS: A total of 747 patients were included in the BioCog study in the study center Berlin. 106 patients fulfilled the inclusion criteria. Of these, 37 were on chronic BB. The latter were preoperatively significantly more likely to have arterial hypertension (94.6%), chronic renal failure (27%) and hyperlipoproteinemia (51.4%) compared to patients without BB. Both groups did not differ in terms of cumulative perioperative morphine equivalent dose (230.9 (BB group) vs. 214.8 mg (Non-BB group)). Predictive factors for increased morphine-index were older age, male sex, longer duration of anesthesia and surgery of the trunk. In a model with logarithmised morphine index, only gender (female) and duration of anesthesia remained predictive factors. CONCLUSIONS: Chronic BB therapy was not associated with a reduced perioperative opioid consumption. TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov ( NCT02265263 ) on the 15.10.2014 with the principal investigator being Univ.-Prof. Dr. med. Claudia Spies.

Quality contract 'prevention of postoperative delirium in the care of elderly patients' study protocol: a non-randomised, pre-post, monocentric, prospective trial.

INTRODUCTION: Postoperative delirium (POD) is seen in approximately 15% of elderly patients and is related to poorer outcomes. In 2017, the Federal Joint Committee (Gemeinsamer Bundesausschuss) introduced a 'quality contract' (QC) as a new instrument to improve healthcare in Germany. One of the four areas for improvement of in-patient care is the 'Prevention of POD in the care of elderly patients' (QC-POD), as a means to reduce the risk of developing POD and its complications.The Institute for Quality Assurance and Transparency in Health Care identified gaps in the in-patient care of elderly patients related to the prevention, screening and treatment of POD, as required by consensus-based and evidence-based delirium guidelines. This paper introduces the QC-POD protocol, which aims to implement these guidelines into the clinical routine. There is an urgent need for well-structured, standardised and interdisciplinary pathways that enable the reliable screening and treatment of POD. Along with effective preventive measures, these concepts have a considerable potential to improve the care of elderly patients. METHODS AND ANALYSIS: The QC-POD study is a non-randomised, pre-post, monocentric, prospective trial with an interventional concept following a baseline control period. The QC-POD trial was initiated on 1 April 2020 between Charité-Universitätsmedizin Berlin and the German health insurance company BARMER and will end on 30 June 2023. INCLUSION CRITERIA: patients 70 years of age or older that are scheduled for a surgical procedure requiring anaesthesia and insurance with the QC partner (BARMER). Exclusion criteria included patients with a language barrier, moribund patients and those unwilling or unable to provide informed consent. The QC-POD protocol provides perioperative intervention at least two times per day, with delirium screening and non-pharmacological preventive measures. ETHICS AND DISSEMINATION: This protocol was approved by the ethics committee of the Charité-Universitätsmedizin, Berlin, Germany (EA1/054/20). The results will be published in a peer-reviewed scientific journal and presented at national and international conferences. TRIAL REGISTRATION NUMBER: NCT04355195.

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.

Neurocognitive disorders in the elderly: altered functional resting-state hyperconnectivities in postoperative delirium patients.

Postoperative delirium (POD) represents a confusional state during days/weeks after surgery and is particularly frequent in elderly patients. Hardly any fMRI studies were conducted to understand the underlying pathophysiology of POD patients. This prospective observational cohort study aims to examine changes of specific resting-state functional connectivity networks across different time points (pre- and 3-5 months postoperatively) in delirious patients compared to no-POD patients. Two-hundred eighty-three elderly surgical patients underwent preoperative resting-state fMRI (46 POD). One-hundred seventy-eight patients completed postoperative scans (19 POD). For functional connectivity analyses, three functional connectivity networks with seeds located in the orbitofrontal cortex (OFC), nucleus accumbens (NAcc), and hippocampus were investigated. The relationship of POD and connectivity changes between both time points (course connectivity) were examined (ANOVA). Preoperatively, delirious patients displayed hyperconnectivities across the examined functional connectivity networks. In POD patients, connectivities within NAcc and OFC networks demonstrated a decrease in course connectivity [max. F = 9.03, p = 0.003; F = 4.47, p = 0.036, resp.]. The preoperative hyperconnectivity in the three networks in the patients at risk for developing POD could possibly indicate existing compensation mechanisms for subtle brain dysfunction. The observed pathophysiology of network function in POD patients at least partially involves dopaminergic pathways.

C-reactive protein for risk prediction of post-operative delirium and post-operative neurocognitive disorder.

BACKGROUND: Post-operative delirium (POD) and post-operative neurocognitive disorder (NCD) are frequently seen in the elderly. Development of biomarkers for pre-operative risk prediction is of major relevance. As inflammation present before surgery might predispose to POD and post-operative NCD development, we aim to determine associations between pre-operative C-reactive protein (CRP) and the incidence of POD and post-operative NCD. METHODS: In this observational study, we analyzed 314 patients enrolled in the SuDoCo trial, who had a pre-operative CRP measurement the day before surgery. Primary outcomes were POD assessed according DSM-4 from day 1 until day 7 after surgery and post-operative NCD assessed 3 months after surgery. We conducted multivariable logistic regression analysis adjusted for age, sex, randomization, body mass index, MMSE, ASA status, infection/autoimmune disease/malignoma and types of surgery to determine associations between CRP with POD and post-operative NCD, respectively. RESULTS: Pre-operative CRP was independently associated with POD [OR 1.158 (95% CI 1.040, 1.291); P = .008]. Patients with CRP values ≥5 mg/dL had a 4.8-fold increased POD risk [OR 4.771 (95% CI 1.765, 12.899; P = .002)] compared to patients with lower CRP values. However, no association was seen between pre-operative CRP and post-operative NCD [OR 0.552 (95% CI 0.193, 1.581); P = .269]. CONCLUSIONS: Pre-operative CRP levels were independently associated with POD but not post-operative NCD after three months. Moreover, higher pre-operative CRP levels showed higher risk for POD. This strengthens the role of inflammation in the development of POD. Assessment of CRP before surgery might allow risk stratification of POD. TRIAL REGISTRATION: This study was registered with ISRCTN Register 36437985 on 02 March 2009.

Cerebral microbleeds are not associated with postoperative delirium and postoperative cognitive dysfunction in older individuals.

BACKGROUND: Cerebral microbleeds (CMB) occur in the context of cerebral small vessel disease. Other brain MRI markers of cerebral small vessel disease are associated with the occurrence of postoperative delirium (POD) and postoperative cognitive dysfunction (POCD), but for CMB this is unknown. We aimed to study the association between CMB and the occurrence of POD and POCD in older individuals. METHODS: The current study consists of 65 patients (72±5 years) from the BIOCOG study, which is a prospective, observational study of patients who underwent an elective surgery of at least 60 minutes. Patients in the current study received a preoperative cerebral MRI scan including a 3D susceptibility-weighted imaging sequence to detect CMB. The occurrence of POD was screened for twice a day until postoperative day 7 by using the DSM-5, NuDesc, CAM, and CAM-ICU. The occurrence of POCD was determined by the reliable change index model at 7 days after surgery or discharge, respectively, and 3 months after surgery. Statistical analyses consisted of logistic regression adjusted for age and gender. RESULTS: A total of 39 CMB were detected in 17 patients (26%) prior to surgery. POD occurred in 14 out of 65 patients (22%). POCD at 7 days after surgery occurred in 11 out of 54 patients (20%) and in 3 out of 40 patients at the 3 month follow-up (8%). Preoperative CMB were not associated with the occurrence of POD (OR (95%-CI): 0.28 (0.05, 1.57); p = 0.147) or POCD at 7 days after surgery (0.76 (0.16, 3.54); p = 0.727) or at 3 months follow-up (0.61 (0.03, 11.64); p = 0.740). CONCLUSION: We did not find an association between preoperative CMB and the occurrence of POD or POCD. TRIAL REGISTRATION: clinicaltrials.gov (NCT02265263) on 23 September 2014.

Associations of the metabolic syndrome and its components with cognitive impairment in older adults.

BACKGROUND: The metabolic syndrome (MetS) is an established cardiovascular risk factor. Here, we investigated its role in cognitive impairment. METHODS: Baseline data from 202 participants (aged 65 to 87 years) of the BioCog study were used. All were free of clinical dementia (MMSE≥24/30). Cognitive impairment was defined as the lowest tertile of a cognitive summary score. Multiple logistic regression analyses examined associations of body mass index (BMI), triglycerides (TG), high-density lipoprotein (HDL-C), glucose and glycated hemoglobin A1c (HbA1c) levels with the odds of cognitive impairment. MetS was defined as ≥3 of its 5 components obesity (BMI ≥ 30 kg/m2), elevated TG (TG ≥1.7 mmol/L), reduced HDL-C (males: < 1.0 mmol/L; females: < 1.3 mmol/L), elevated glucose (glucose ≥5.5 mmol/L and/or diagnosed diabetes) and elevated blood pressure (history of hypertension). Analyses controlled for age, sex and smoking history. RESULTS: Lower HDL-C was significantly associated with a higher odds of cognitive impairment (OR 2.70 per 1 mmol/L reduction; 95% CI 1.25, 5.56; p = 0.011), whereas BMI, TG, glucose and HbA1c were not (all p > 0.05). Results for HDL-C were similar when HDL-C, glucose, BMI and TG were entered into a single model (OR 2.56 per 1 mmol/L reduction, 95% CI 1.09, 5.88, p = 0.031) and when cerebrovascular disease and coronary heart disease were additionally controlled for (OR 2.56 per 1 mmol/L reduction, 95% CI 1.06, 6.25, p = 0.036). Among the 5 MetS components, participants with elevated TG were at 2-fold increased odds of impairment (OR 2.09, 95% CI 1.08, 4.05, p = 0.028) including when the remaining 4 MetS components were entered (OR 2.23, 95% CI 1.07, 4.65, p = 0.033), but the finding was no longer statistically significant when cerebrovascular disease and coronary heart disease were additionally controlled for (p = 0.11). Presence of MetS and of obesity, reduced HDL-C, elevated glucose or elevated blood pressure were not significantly associated with impairment (all p > 0.05). CONCLUSION: Our findings support low HDL-C as an independent risk marker of cognitive impairment in older age. The need for research into mediatory and confounding factors, and re-evaluation of traditional cut-off points is highlighted. TRIAL REGISTRATION: The study was registered on 15th October 2014 at clinicaltrials.gov ( NCT02265263 ).

Pre- and postoperative management of risk factors for postoperative delirium: who is in charge and what is its essence?

Postoperative delirium (POD) is an adverse clinical outcome characterized by cognitive, affective and behavioral symptoms with typically an acute onset and a fluctuating course. POD is attributed to certain patients' predisposing factors as well as to treatment-related precipitating factors. While there are several single-component interventions for the prevention of POD, evolving evidence suggests the importance of a system approach in the prevention of POD. This involves strategies by multidisciplinary teams with additional geriatric consultation services to identify risk factors for POD and to modify their impact on the perioperative course. Some patients may profit from postponing an elective surgery and undergoing a prehabilitation program to optimize his/her resilience for the surgical and anesthesiologic stressors.

Managing ICU delirium.

PURPOSE OF REVIEW: ICU delirium is a common and serious acute brain dysfunction with adverse outcome and high risk of mortality. The awareness of ICU delirium as a problem, which immediately requires therapeutic intervention, has been increased in the past years. This article aims to provide information in order to increasingly modify the management of this severe problem, that is, its detection, prevention, and treatment toward algorithm-based and protocol-driven procedures. RECENT FINDINGS: The bundle of target-controlled and protocol-driven management of sedation, analgesia, and delirium and its monitoring included in this work offer the opportunity to improve the outcome of ICU patients based on the best evidence available to date. Moreover, the knowledge about precipitating and predisposing factors to prevent ICU delirium is essential and is represented in this review. Unresolved seems the pharmacological therapy of delirium because of the contradictory results of research published so far, especially regarding neuroleptics and cholinesterase inhibitors. SUMMARY: The management of ICU delirium must be a key aspect to improve the outcome of critically ill patients. The development of pharmacological treatment strategies and deeper understanding of the underlying pathophysiology will require further research.

Analysis of Memory Formation during General Anesthesia (Propofol/Remifentanil) for Elective Surgery Using the Process-dissociation Procedure.

BACKGROUND: There have been reports of memory formation during general anesthesia. The process-dissociation procedure has been used to determine if these are controlled (explicit/conscious) or automatic (implicit/unconscious) memories. This study used the process-dissociation procedure with the original measurement model and one which corrected for guessing to determine if more accurate results were obtained in this setting. METHODS: A total of 160 patients scheduled for elective surgery were enrolled. Memory for words presented during propofol and remifentanil general anesthesia was tested postoperatively by using a word-stem completion task in a process-dissociation procedure. To assign possible memory effects to different levels of anesthetic depth, the authors measured depth of anesthesia using the BIS XP monitor (Aspect Medical Systems, Norwood, MA). RESULTS: Word-stem completion performance showed no evidence of memory for intraoperatively presented words. Nevertheless, an evaluation of these data using the original measurement model for process-dissociation data suggested an evidence of controlled (C = 0.05; 95% confidence interval [CI] 0.02-0.08) and automatic (A = 0.11; 95% CI 0.09-0.12) memory processes (P < 0.01). However, when the data were evaluated with an extended measurement model taking base rates into account adequately, no evidence for controlled (C = 0.00; 95% CI -0.04 to 0.04) or automatic (A = 0.00; 95% CI -0.02 to 0.02) memory processes was obtained. The authors report and discuss parallel findings for published data sets that were generated by using the process-dissociation procedure. CONCLUSION: Patients had no memories for auditory information presented during propofol/remifentanil anesthesia after midazolam premedication. The use of the process-dissociation procedure with the original measurement model erroneously detected memories, whereas the extended model, corrected for guessing, correctly revealed no memory.

Variability comparison of the composite auditory evoked potential index and the bispectral index during propofol-fentanyl anesthesia.

BACKGROUND: Monitors of hypnotic depth help anesthesiologists to guide the anesthetic. The performance of different monitors depends on several factors, index variability at a steady state of hypnotic depth being one. We compared the recently introduced AAI1.6 with the established bispectral index (BIS), regarding index variability during stable values of propofol effect-site concentration. METHODS: After ethics committee approval and written informed consent, anesthesia was performed in 40 patients with propofol as the target controlled infusion and fentanyl. Variability of BIS and AAI1.6 was calculated during periods of constant predicted propofol effect compartment concentration and constant levels of surgical stimulation as the median absolute deviation (MAD) from the median value. A variability index was calculated as 1.48*MAD/(threshold - median value), with threshold being the division line between awake and asleep. Threshold crossing time was used to evaluate the performance in predicting return of consciousness. RESULTS: Variability index, however, was significantly larger for the AAI1.6, despite similar absolute variability measured as MAD. Lightening of anesthesia before recovery could be noticed earlier using the BIS than the AAI1.6, although consciousness was detected with a significantly higher Pk-value by the AAI1.6. CONCLUSION: Variability in relation to the difference between the median index value during anesthesia and the threshold necessary to detect consciousness with high sensitivity is higher for the AAI1.6 than for the BIS. This, as well as the steeper concentration-response function found for AAI1.6, impairs the performance of the AAI1.6 in predicting imminent return of consciousness during decreasing propofol concentrations. However, it makes AAI1.6 well suited to detect consciousness when it has occurred.