Surgery, neuroinflammation and cognitive impairment.

The impact of general anesthesia on cognitive impairment is controversial and complex. A large body of evidence supports the association between exposure to surgery under general anesthesia and development of delayed neurocognitive recovery in a subset of patients. Existing literature continues to debate whether these short-term effects on cognition can be attributed to anesthetic agents themselves, or whether other variables are causative of the observed changes in cognition. Furthermore, there is conflicting data on the relationship between anesthesia exposure and the development of long-term neurocognitive disorders, or development of incident dementia in the patient population with normal preoperative cognitive function. Patients with pre-existing cognitive impairment present a unique set of anesthetic considerations, including potential medication interactions, challenges with cooperation during assessment and non-general anesthesia techniques, and the possibility that pre-existing cognitive impairment may impart a susceptibility to further cognitive dysfunction. This review highlights landmark and recent studies in the field, and explores potential mechanisms involved in perioperative cognitive disorders (also known as postoperative cognitive dysfunction, POCD). Specifically, we will review clinical and preclinical evidence which implicates alterations to tau protein, inflammation, calcium dysregulation, and mitochondrial dysfunction. As our population ages and the prevalence of Alzheimer’s disease and other forms of dementia continues to increase, we require a greater understanding of potential modifiable factors that impact perioperative cognitive impairment. Future research should aim to further characterize the associated risk factors and determine whether certain anesthetic approaches or other interventions may lower the potential risk which may be conferred by anesthesia and/or surgery in susceptible individuals.

/pdf/anesthesiology-and-cognitive-impairment-a-narrative-review-4u47i927y7.pdf

Anesthesiology and cognitive impairment: a narrative review of current clinical literature.

The involvement of NLRP3 inflammasome in the treatment of Alzheimer's disease.

Postoperative shivering is a common complication of anaesthesia. Shivering is believed to increase oxygen consumption, increase the risk of hypoxemia, induce lactic acidosis, and catecholamine release. Therefore, it might increase the postoperative complications especially in high-risk patients. Moreover, shivering is one of the leading causes of discomfort for postsurgical patients. Shivering is usually triggered by hypothermia. However, it occurs even in normothermic patients during the perioperative period. The aetiology of shivering has been understood insufficiently. Another potential mechanism is pain and acute opioid withdrawal (especially with the use of short-acting narcotics). Besides that shivering is poorly understood, the gold standard for the treatment and prevention has not been defined yet. Perioperative hypothermia prevention is the first method to avoid shivering. Many therapeutic strategies for treating shivering exist and most are empiric. Unfortunately, the overall quality of the antishivering guidelines is low. Two main strategies are available: pharmacological and non-pharmacological antishivering methods. The combination of forced-air warming devices and intravenous meperidine is the most validated method. We also analysed different medications but final conclusion about the optimal antishivering medication is difficult to be drawn due to the lack of high-quality evidence. Nevertheless, control of PS is possible and clinically effective with simple pharmacological interventions combined with non pharmacological methods. However, to be consistent with the most up-to-date, evidence-based practice, future antishivering treatment protocols should optimize methodological rigor and transparency.

/pdf/postanaesthetic-shivering-from-pathophysiology-to-prevention-4z5obegmws.pdf

Postanaesthetic shivering - from pathophysiology to prevention.

Postoperative cognitive dysfunction (POCD) is a common neurological complication following surgery and general anesthesia, especially in elderly patients. Severe cases delay patient discharge, affect the patient’s quality of life after surgery, and are heavy burdens to society. In addition, as the population ages, surgery is increasingly used for older patients and those with higher prevalences of complications. This trend presents a huge challenge to the current healthcare system. Although studies on POCD are ongoing, the underlying pathogenesis is still unclear due to conflicting results and lack of evidence. According to existing studies, the occurrence and development of POCD are related to multiple factors. Among them, the pathogenesis of neuroinflammation in POCD has become a focus of research in recent years, and many clinical and preclinical studies have confirmed the correlation between neuroinflammation and POCD. In this article, we reviewed how central nervous system inflammation occurred, and how it could lead to POCD with changes in peripheral circulation and the pathological pathways between peripheral circulation and the central nervous system (CNS). Furthermore, we proposed some potential therapeutic targets, diagnosis and treatment strategies at the cellular and molecular levels, and clinical applications. The goal of this article was to provide a better perspective for understanding the occurrence of POCD, its development, and preventive strategies to help manage these vulnerable geriatric patients.

/pdf/neuroinflammation-as-the-underlying-mechanism-of-21ts1hb4.pdf

Neuroinflammation as the Underlying Mechanism of Postoperative Cognitive Dysfunction and Therapeutic Strategies

Objective We undertook a meta-analysis to investigate the effect of dexmedetomidine on postoperative cognitive dysfunction (POCD). Methods We searched PubMed, EMBASE, the Cochrane Library, CNKI and Google Scholar to find randomized controlled trials (RCTs) of the influence of dexmedetomidine on POCD in elderly adults who had undergone general anaesthesia. Two researchers independently screened the literature, extracted data, and evaluated methodologic quality against inclusion and exclusion criteria. We used RevMan 5.2 to undertake our meta-analysis. Results Thirteen RCTs were included. Compared with controls, dexmedetomidine: 1) significantly reduced the incidence of POCD (relative risk = 0.59, 95% confidence interval [CI] 0.45-2.95) and improved Mini-Mental State Examination (MMSE) score (mean difference, MD = 1.74, 95% CI 0.43-3.05) on the first postoperative day; and 2) reduced the incidence of POCD after the first postoperative day (MD = 2.73, 95% CI 1.33-4.12). Conclusion Dexmedetomidine reduces the incidence of POCD and improves postoperative MMSE score.

https://journals.sagepub.com/doi/pdf/10.1177/0300060516671623

Effect of dexmedetomidine on postoperative cognitive dysfunction in elderly patients after general anaesthesia: A meta-analysis

ObjectiveWe evaluated the efficacy of 5-HT3 receptor antagonists for the prevention of postoperative shivering.MethodsWe searched PubMed, the Cochrane Library, EMBASE and Web of Knowledge to find r...

https://journals.sagepub.com/doi/pdf/10.1177/0300060516668776

5-HT3 receptor antagonists for the prevention of postoperative shivering: a meta-analysis

Background. 5HT3 antagonist, an antiemetic alternative to dexamethasone, is an effective drug for the prevention of postoperative nausea and vomiting (PONV). Methods. PubMed and The Cochrane Library (from inception to June 2016) were searched for relevant RCTs (randomized controlled trials). Results. Seven trials, totaling 682 patients, were included in this meta-analysis. This meta-analysis demonstrated that 5HT3 antagonist was as effective as dexamethasone in preventing PONV (RR, 1.12; 95% CI, [0.86, 1.45]; ) within 24 hours of laparoscopic cholecystectomy, and no significant heterogeneity was observed among the studies ( ; ). During the early postoperative period (0–6 h), 5HT3 antagonists were superior to dexamethasone in reducing POV (RR, 0.31; 95% CI, [0.11, 0.93]; ), while, in other postoperative stages (6–12 h, 12–24 h, and 0–24 h), it was not more effective in the prevention of POV than dexamethasone. And no significant difference was found in the prevention of PON between 5HT3 antagonists and dexamethasone at different postoperative periods (0–6 h, 6–12 h, 12–24 h, and 0–24 h). Conclusions. As a result, it is advisable to encourage 5HT3 antagonists as an alternative to dexamethasone for the prevention of PONV in patients undergoing laparoscopic cholecystectomy.

https://downloads.hindawi.com/journals/bmri/2016/8603409.pdf

5HT3 Antagonists versus Dexamethasone in the Prevention of PONV in Patients Undergoing Laparoscopic Cholecystectomy: A Meta-Analysis of RCTs

The aim of this meta-analysis was to evaluate the effect of dexmedetomidine on intraocular pressure (IOP) and hemodynamict. Methods: There were 12 randomized clinical trials in the meta-analysis. The Primary outcomes were the Weighted Mean Difference (WMD) and the 95% Confidence Intervals (CI) of changing IOP compared dexmedetomidine with placebo. And the second outcomes were the Standardized Mean difference (SMD) 、the Risk Ratio (RR) and the 95% Confidence Intervals (CI). Results: Twelve trials totaling 702 patients were analyzed. In the two key point time of the anesthesia administration, the pooled estimates favored lowering effect of dexmedetomidine on IOP when compared with placebo (WMD = -4.47 mmHg, 95% CI (-6.97,-1.96), P<0.00001; and WMD = -2.13 mmHg, 95% CI (-3.51,-0.75), P=0.003, respectively) . Dexmedetomidine also hastened the block onset time (WMD = -0.61 minute, 95% CI (-0.90,-0.33), P<0.0001). And there was no significant difference of hypotension between dexmedetomidine and placebo (RR = 1.12, 95% CI (0.47,2.64), P=0.80). However, for the point of the incidence of bradycardia, the use of dexmedetomidine could increase it when compared with placebo (RR = 7.50, 95% CI (1.76,31.80), P=0.006).

/pdf/dexmedetomidine-as-an-anesthetic-adjuvant-to-control-2jm6xewugj.pdf

Dexmedetomidine as an anesthetic adjuvant to control intraocular pressure: a meta-analysis

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Effect of dexmedetomidine on postoperative cognitive dysfunction in elderly patients after general anaesthesia: A meta-analysis

5-HT3 receptor antagonists for the prevention of postoperative shivering: a meta-analysis

5HT3 Antagonists versus Dexamethasone in the Prevention of PONV in Patients Undergoing Laparoscopic Cholecystectomy: A Meta-Analysis of RCTs

Dexmedetomidine as an anesthetic adjuvant to control intraocular pressure: a meta-analysis