/pdf/dexmedetomidine-in-neurosurgical-anesthesia-4e1qr43l5x.pdf

Dexmedetomidine in neurosurgical anesthesia

https://escholarship.mcgill.ca/downloads/gf06g674n

microRNA dysregulation in neurodegenerative diseases: A systematic review

Summary Postoperative delirium is a relatively common and serious complication. It increases hospital stay by 2–3 days and is associated with a 30-day mortality of 7–10%. It is most prevalent in older patients, those with existing neurocognitive disorders, and those undergoing complex or emergency procedures. Preclinical and clinical research in recent years has uncovered more about the pathophysiology of postoperative delirium and may yield more potential therapeutic options. Using the enhanced recovery pathway framework of risk stratification, risk reduction, and rescue treatment, we have reviewed the current clinical evidence on the validity of delirium prediction scores for the surgical population, the effectiveness of perioperative delirium risk reduction interventions, and management options for established delirium. Effective perioperative interventions include depth of anaesthesia monitoring, intraoperative dexmedetomidine infusion, and multimodal analgesia. Choice of general anaesthetic agent may not be associated with significant difference in delirium risk. Several other factors, such as preoperative fasting, temperature control, and blood pressure management have some association with the risk of postoperative delirium; these will require further studies. Because of the limited treatment options available for established delirium, we propose that risk assessment and perioperative risk reduction may be the most effective approaches in managing postoperative delirium.

Postoperative delirium: perioperative assessment, risk reduction, and management

Background Dexmedetomidine (DEX) is a highly selective alpha2 adrenoceptor agonist with broad pharmacological effects, including sedation, analgesia, anxiolysis, and sympathetic tone inhibition. Here we report a systematic review and meta-analysis of its effects on stress, inflammation, and immunity in surgical patients during the perioperative period. Methods We searched MEDLINE, METSTR, Embase, and Web of Science for clinical studies or trials to analyse the effects of DEX on perioperative stress, inflammation, and immune function. Results Sixty-seven studies (including randomised controlled trials and eight cohort studies) with 4842 patients were assessed, of which 2454 patients were in DEX groups and 2388 patients were in control (without DEX) groups. DEX infusion during the perioperative period inhibited release of epinephrine, norepinephrine, and cortisol; decreased blood glucose, interleukin (IL)-6, tumour necrosis factor-α, and C-reactive protein; and increased interleukin-10 in surgical patients. In addition, the numbers of natural killer cells, B cells, and CD4+ T cells, and the ratios of CD4+:CD8+ and Th1:Th2 were significantly increased; CD8+ T-cells were decreased in the DEX group when compared with the control group. Conclusions DEX, an anaesthesia adjuvant, can attenuate perioperative stress and inflammation, and protect the immune function of surgical patients, all of which may contribute to decreased postoperative complications and improved clinical outcomes.

Effects of dexmedetomidine on perioperative stress, inflammation, and immune function: systematic review and meta-analysis

Background
The aim of this study was to summarize and discuss the similarities and differences in inflammatory biomarkers in postoperative delirium (POD) and cognitive dysfunction (POCD).

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Inflammatory markers in postoperative delirium (POD) and cognitive dysfunction (POCD): A meta-analysis of observational studies.

ObjectiveTo explore the risk factors associated with postoperative delirium (PD) in elderly patients following total hip arthroplasty (THA) for hip fracture.MethodsThis prospective study enrolled elderly patients (≥ 65 years) with hip fractures who underwent THA under general anaesthesia, and who had a complete set of postoperative observations. Detailed medical history and perioperative characteristics were recorded. During the postoperative period, patients were assessed twice daily for PD using the Confusion Assessment Method.ResultsA total of 572 patients were eligible for inclusion in the study. Of these, 120 patients (21.0%) were diagnosed with PD and 452 patients (79.0%) did not experience PD. Multivariate stepwise logistic regression analyses showed that older age, a history of stroke, lower albumin, higher blood glucose, higher total bilirubin, higher C-reactive protein, longer surgery duration and higher volume of red blood cell transfusions were independent risk factors for PD.ConclusionsCorrec...

https://imr.sagepub.com/content/44/2/317.full.pdf

Prevalence and risk factors of postoperative delirium in elderly hip fracture patients

Impact of multicomponent, nonpharmacologic interventions on perioperative cortisol and melatonin levels and postoperative delirium in elderly oral cancer patients.

Alzheimer's disease (AD) is a neurodegenerative disease prevalent in aged people, clinically characterized by progressive memory loss, behavioral and learning dysfunction, and cognitive deficits. The pathogenesis of AD is hallmarked by formation of amyloid-β peptide aggregates (Aβ) and intraneuronal neurofibrillary tangles (NFTs), which are induced by hyperphosphorylation of amyloid-β protein precursor and tau protein, respectively. The hyperphosphorylation is controlled by cyclin-dependent kinase-5 (CDK5), the aberrant activation of which is mediated by calpain (CAPN)-induced cleavage of p35 into p25. However, the regulation of CAPN in AD remains largely unknown. Here, we studied the post-transcriptional control of CAPN1 by microRNAs (miRNAs) in the setting of AD. We found that miR-124-3p, previously reported as a miRNA that was downregulated in AD, was a CAPN1-targeting miRNA that functionally inhibited the protein translation of CAPN1 in a human neural cell line, HCN-2. In vitro, transfection with miR-124-3p reduced the levels of CAPN1 protein, the cleavage of p35 into p25, and cell apoptosis dose-dependently in HCN-2 cells. Moreover, a significant inverse correlation was detected between the levels of miR-124-3p and CAPN1 in AD specimens. Furthermore, intracranial injection of adeno-associated virus expressing miR-124-3p into APP/PS1-AD mice significantly reduced Aβ deposition and significantly improved the AD-mouse behavior in the social recognition test and plus-maze discriminative avoidance task. Together, our data suggest that post-transcriptional control of calpain by miR-124-3p plays an essential role in the development of AD.

Role of Post-Transcriptional Control of Calpain by miR-124-3p in the Development of Alzheimer's Disease

Aim Pathophysiological disorders after surgery might be related to postoperative delirium (POD) This study was designed to elucidate the pathogenesis of POD in elderly oral cancer patients by determining the perioperative kinetics of inflammatory cytokines, cortisol, and amyloid β1-40 (Aβ1-40) Methods A total of 257 elderly oral cancer patients who underwent tumor resection surgery were selected Venous blood was collected prior to surgery (T0), at the end of surgery (T1), and at 12 hours after surgery (T2) During the first three postoperative days, patients were examined using the confusion assessment method twice a day (8 am and 8 pm) Mini-Mental State Examination scores were recorded at T0 and on postoperative days 1, 3, and 7 Ultimately, 56 patients suffering from POD made up the POD group, and 56 patients randomly selected from a cohort of patients without POD were allocated to the no POD (NPOD) group Subsequently, interleukin-6, C-reactive protein, procalcitonin, cortisol, and Aβ1-40 in plasma from the two groups were measured Results The two groups displayed comparable basic characteristics There were no differences in all tested biomarkers between the two groups at T0 However, after surgery, the biomarker levels displayed distinct patterns between the two groups The peak levels of all biomarkers were higher in the POD group than in the NPOD group Conversely, the Mini-Mental State Examination scores after surgery were lower in the POD group than in the no POD group Conclusion The boost of inflammatory cytokines, cortisol, and Aβ1-40 after surgery might be involved in POD onset among elderly oral cancer patients POD was accompanied by progressive cognitive deficiency

Yong Guo

Papers

Prevalence and risk factors of postoperative delirium in elderly hip fracture patients

Impact of multicomponent, nonpharmacologic interventions on perioperative cortisol and melatonin levels and postoperative delirium in elderly oral cancer patients.

Role of Post-Transcriptional Control of Calpain by miR-124-3p in the Development of Alzheimer's Disease

Production of inflammatory cytokines, cortisol, and Aβ1-40 in elderly oral cancer patients with postoperative delirium

Ang-(1-7) treatment attenuates lipopolysaccharide-induced early pulmonary fibrosis.