Evaluating Mechanisms of Postoperative Delirium and Cognitive Dysfunction Following Elective Spine Surgery in Elderly Patients (CONFESS): Protocol for a Prospective Observational Trial

Abstract

Background Elderly people are at particular high risk for postoperative delirium (POD) following spine surgery, which is associated with longer hospital stays, higher costs, risk for delayed complications, long-term care dependency, and cognitive dysfunction (POCD). It is insufficiently understood which mechanisms and risk factors contribute to the development of POD and POCD following these major but plannable surgeries. Objective This study aims to identify modifiable risk factors in spine surgery. A better understanding thereof would help adapt medical management and surgical strategies to individual risk profiles. Methods This is a single-center observational study jointly conducted by the departments of neurosurgery, neurology, and anesthesiology at a tertiary care hospital in Germany. All patients aged 60 years and older presenting to the neurosurgery outpatient clinic or ward for elective spine surgery are screened for eligibility. Exclusion criteria include presence of neurodegenerative or history of psychiatric disease and medication with significant central nervous system activity (eg, antidepressants, antipsychotics, sedatives). Surgical and anesthetic procedures including duration of surgery as primary end point of this study are thoroughly documented. All patients are furthermore evaluated for their preoperative cognitive abilities by a number of tests, including the Consortium to Establish a Registry for Alzheimer's Disease Plus test battery. Physical, mental, and social health and well-being are assessed using the Patient-Reported Outcome Measurement Information System Profile 29 and Hospital Anxiety and Depression Scale. Patients additionally receive preoperative cerebrovascular ultrasound and structural and functional brain imaging. The immediate postoperative period includes screening for POD using the Nursing Delirium Screening Scale and validation through Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, criteria. We furthermore investigate markers of (neuro)inflammation (eg, interleukins, C-reactive protein, tumor necrosis factor alpha). Preoperative examinations are repeated 3 months postoperatively to investigate the presence of POCD and its mechanisms. Statistical analyses will compare delirious and nondelirious patients for predictors of immediate (POD) and delayed (POCD) cognitive dysfunction. Results This is the first study to prospectively evaluate risk factors for POD and POCD in spine surgery. Recruitment is ongoing, and data collection is estimated to be finished with the inclusion of 200 patients by mid-2020. Conclusions The identification of mechanisms, possibly common, underlying POD and POCD would be a major step toward defining effective interventional strategies early in or even before the postoperative period, including the adaptation of surgical strategies to individual risk profiles. Trial Registration ClinicalTrials.gov NCT03486288; https://clinicaltrials.gov/ct2/show/NCT03486288

Prevalence and Factors Affecting Postoperative Delirium in a Neurosurgical Intensive Care Unit

“…It disrupts the cognitive functions of neurosurgical patients during their NSICU stay 7,18. This situation may lead to difficulties in patient follow-up and has negative effects on the treatment process during the NSICU stay 10,22,24. We found that the prevalence of POD among neurosurgical patients was 18.9%.…”

“…Identifying the prevalence of POD and populations at risk is crucial for early diagnosis and intervention 3. Postoperative delirium is an expected and complex postoperative complication 3,24. It disrupts the cognitive functions of neurosurgical patients during their NSICU stay 7,18.…”

Up-regulation of miR-20a ameliorates sevoflurane anesthesia-induced cognitive impairment in rats by targeting EphA4

“…Anesthetic agents affect the central nervous system, and preoperative agents have been associated with postoperative psychiatric disorders [16]. Even though some studies have shown that, after SEV sevoflurane administration, patients have a lower degree of cognitive decline and a faster recovery time, understanding how SEV causes cognitive impairment is still worth further study [17]. In this study, a SEV anesthesia rat model of POCD was developed to simulate cognitive impairment, and our results demonstrate that miR-20a upregulation ameliorates SEV-induced cognitive impairment.…”

Dexmedetomidine in Prevention of Postoperative Delirium: A Systematic Review

“…With this, the DEX administration might not only decrease postoperative delirium condition but also other benefits that have a positive impact on the nervous system in a postsurgical condition and the stress that the body is exposed to. These mechanisms contribute to the decrease in the neuronal inflammation, neurotransmitter imbalance, and endocrine stress response suggested for developing postoperative delirium [ 4 ], which is better illustrated in Figure 3 .…”

“…As the human organism advances in age, physiologic changes occur, such as greater sensitivity to anesthetic drugs, higher drug concentrations at central nervous system receptors (SNC), and an increased risk of postoperative cognitive dysfunction and postoperative delirium (POD) [ 3 ]. The full mechanism behind POD remains unknown, but it’s suggested that it is a multifactorial condition influenced by neurotransmitter imbalance, neuroinflammation, brain network dysfunction, and endocrine stress response [ 4 ]. Delirium affects around 37% to 46% of the general surgical population.…”