Lasting effects of general anesthetics on the brain in the young and elderly: “mixed picture” of neurotoxicity, neuroprotection and cognitive impairment (2019 Review)
Lingzhi
As an example:Exposure to anesthesia to the aged brain can be a risk of the long-lasting impairments of cognitive function. However, the neuroprotective property of general anesthetics in brain injury is also increasingly recognized. That is to say, one should bear in mind the “Ying and Yang” balance of general anesthetics in daily clinical practice. Once this is implemented well, patients will be benefit from “precision” anesthesia. In addition, one should also consider the detrimental effects of trauma induced by surgery on vital organs; in particular, systemic inflammatory responses following surgery can cause various organ injury/dysfunction including cognitive impairment [134]. Therefore, how the perioperative team including anesthetists, surgeons and intensivists should work together in an optimal manner is important for the best benefits of our patients. [Emphasis added]
The paper includes a rather long and detailed section headed 'Elderly and Cognition' with a subsection addressing 'Alzheimer's Disease' that I don't have time to look at. It concludes:In the search of prophylaxis and therapy against POD, the anesthetic adjuvant dexmedetomidine has been shortlisted as a promising candidate. As an alpha2-adrenergic receptor agonist, it is hypothesized that dexmedetomidine interacts with different physiological and biochemical pathways within the CNS to achieve multitude anti-delirium neuroprotection. Dexmedetomidine binds to a2 adrenoceptors in locus ceruleus (LC) to inhibit neuronal activity within LC, which subsequently leads to release of inhibitory neurotransmitters GABA and galanin into the cortex to promote natural sleep-like sedation [98, 99]. Moreover, dexmedetomidine also reduces the requirement of benzodiazepines and opioids throughout the perioperative period, and this could thus reduce delirium occurrence due to benzodiazepine/opioid use. Using animal models of surgical trauma and/or anesthesia exposure, it has been demonstrated that Dex has anti-apoptosis [100] and anti-inflammatory [101] properties that is associated with improved neurocognitive outcome. We proceeded to test the delirium-attenuating potential of dexmedetomidine in a prospective randomized trial, which enrolled 700 elderly patients to receive low-dose dexmedetomidine or saline for overnight hours in ICU after non-cardiac surgery. The trial demonstrated that low-dose, prophylactic dexmedetomidine in patients > 65 years of age significantly reduced the incidence of postoperative delirium in the first week after surgery [102]. In the 3-year follow-up study of the trial, we further demonstrated that dexmedetomidine recipients showed significantly improved quality of life, cognitive function and long-term survival [103]. In a parallel, in a separate randomized trial study, we demonstrated that prophylactic dexmedetomidine in non-cardiac surgery patients increased non-rapid eye movement sleep and improved overall sleep quality, which likely contribute to the lowered incidence of delirium [104]. In an independent study, as opposed to prolonged infusion, Deiner et al. showed that dexmedetomidine administration at a relative high dose during the intraoperative period and 2 subsequent hours in non-cardiac surgery patients did not significantly reduce the occurrence of delirium in the first perioperative week and cognitive dysfunction at 3–6 months after surgery [105]. The collective findings highlight the short-acting nature of dexmedetomidine, and the need for continuous infusion and specific timing when using dexmedetomidine for delirium and POCD prevention and may be also patient population specific.
Clearly a ton of research still needs to be done, including breaking out results by genotype and other variables, but just seeing that some anesthetics may be neuroprotective and that researchers are thinking in terms of 'precision anethesia' is encouraging.Current clinical evidences on this subject are far from conclusive. A meta-analysis on 15 case–control studies reported that GA exposure, single or cumulative, is not associated with higher risk of AD [130] compared to no- surgery/anesthesia control or regional anesthesia; a prospective cohort study similarly concluded that GA does not significantly increase dementia/AD incidence during a 7-year follow-up [131]. In contrast, a nationwide case–control study reported that subjects receiving surgery and general anesthesia are at higher risk of developing dementia, in particular with multiple surgery/anesthesia challenge, when compared to no-surgery/anesthesia controls [132]. Consistent with such, a cohort study concluded that surgery plus anesthesia is associated with increased incidence of dementia and reduced time interval to dementia diagnosis, regardless of the mode of anesthesia received (general or regional) [133]
