Surgery can induce cognitive decline, a risk that increases with advancing age. In rodents, postoperative cognitive decline (POCD) is associated with the inflammatory activation of hippocampal microglia. To examine the role of microglia in POCD, we inhibited the colony-stimulating factor 1 receptor (CSF1R) in adult mice, effectively depleting CNS microglia. Surgical trauma (tibial fracture) reduced the ability of mice to remember a conditioned response learned preoperatively, a deficit more pronounced and persistent in mice with diet-induced obesity (DIO). Whereas microglial depletion by itself did not affect learning or memory, perioperative microglial depletion remarkably protected mice, including those with DIO, from POCD. This protection was associated with reduced hippocampal levels of inflammatory mediators, abrogation of hippocampal recruitment of CCR2 ⁺ leukocytes, and higher levels of circulating inflammation-resolving factors. Targeting microglia may thus be a viable strategy to mitigate the development of POCD, particularly in those with increased vulnerability.

Postoperative delirium is prevalent in older patients and associated with worse outcomes. Recent data in animal studies demonstrate increases in inflammatory markers in plasma and cerebrospinal fluid (CSF) even after aseptic surgery, suggesting that inflammation of the central nervous system may be part of the pathogenesis of postoperative cognitive changes. We investigated the hypothesis that neuroinflammation was an important cause for postoperative delirium and cognitive dysfunction after major non-cardiac surgery. After Institutional Review Board approval and informed consent, we recruited patients undergoing major knee surgery who received spinal anesthesia and femoral nerve block with intravenous sedation. All patients had an indwelling spinal catheter placed at the time of spinal anesthesia that was left in place for up to 24 h. Plasma and CSF samples were collected preoperatively and at 3, 6, and 18 h postoperatively. Cytokine levels were measured using ELISA and Luminex. Postoperative delirium was determined using the confusion assessment method, and cognitive dysfunction was measured using validated cognitive tests (word list, verbal fluency test, digit symbol test). Ten patients with complete datasets were included. One patient developed postoperative delirium, and six patients developed postoperative cognitive dysfunction. Postoperatively, at different time points, statistically significant changes compared to baseline were present in IL-5, IL-6, I-8, IL-10, monocyte chemotactic protein (MCP)-1, macrophage inflammatory protein (MIP)-1α, IL-6/IL-10, and receptor for advanced glycation end products in plasma and in IFN-γ, IL-6, IL-8, IL-10, MCP-1, MIP-1α, MIP-1β, IL-8/IL-10, and TNF-α in CSF. Substantial pro- and anti-inflammatory activity in the central neural system after surgery was found. If confirmed by larger studies, persistent changes in cytokine levels may serve as biomarkers for novel clinical trials.

The escalation in the prevalence of obesity throughout the world has led to an upsurge in the number of obese surgical patients to whom perioperative care needs to be delivered. After determining the scope of the review, the authors used PubMed with select phrases encompassing the words in the scope. Both preclinical and clinical reports were considered. There were no controversies regarding preoperative management and the intraoperative care of the obese surgical patient. Is there a healthy obese state that gives rise to the obesity paradox regarding postoperative complications? This review considers how to prepare for and manage the obese surgical patient through the entire spectrum, from preoperative assessment to possible postoperative intensive care. What results in an obese patient developing ‘unhealthy’ obesity?

Background: Inflammation initiated by damage-associated molecular patterns has been implicated for the cognitive decline associated with surgical trauma and serious illness. We determined whether resolution of inflammation mediates dexmedetomidine-induced reduction of damage-associated molecular pattern–induced cognitive decline.Methods: Cognitive decline (assessed by trace fear conditioning) was induced with high molecular group box 1 protein, a damage-associated molecular pattern, in mice that also received blockers of neural (vagal) and humoral inflammation-resolving pathways. Systemic and neuroinflammation was assessed by proinflammatory cytokines.Results: Damage-associated molecular pattern–induced cognitive decline and inflammation (mean ± SD) was reversed by dexmedetomidine (trace fear conditioning: 58.77 ± 8.69%vs. 41.45 ± 7.64%,P< 0.0001; plasma interleukin [IL]-1β: 7.0 ± 2.2 pg/mlvs. 49.8 ± 6.0 pg/ml,P< 0.0001; plasma IL-6: 3.2 ± 1.6 pg/mlvs. 19.5 ± 1.7 pg/ml,P< 0.0001; hippocampal IL-1β: 4.1 ± 3.0 pg/mgvs. 41.6 ± 8.0 pg/mg,P< 0.0001; hippocampal IL-6: 3.4 ± 1.3 pg/mgvs. 16.2 ± 2.7 pg/mg,P< 0.0001). Reversal by dexmedetomidine was prevented by blockade of vagomimetic imidazoline and α₇nicotinic acetylcholine receptors but not by α₂adrenoceptor blockade. Netrin-1, the orchestrator of inflammation–resolution, was upregulated (fold-change) by dexmedetomidine (lung: 1.5 ± 0.1vs. 0.7 ± 0.1,P< 0.0001; spleen: 1.5 ± 0.2vs. 0.6 ± 0.2,P< 0.0001), resulting in upregulation of proresolving (lipoxin-A₄: 1.7 ± 0.2vs. 0.9 ± 0.2,P< 0.0001) and downregulation of proinflammatory (leukotriene-B₄: 1.0 ± 0.2vs. 3.0 ± 0.3,P< 0.0001) humoral mediators that was prevented by α₇nicotinic acetylcholine receptor blockade.Conclusions: Dexmedetomidine resolves inflammation through vagomimetic (neural) and humoral pathways, thereby preventing damage-associated molecular pattern–mediated cognitive decline.

Postoperative ileus is characterized by the inability to resume a normal diet, nausea and vomiting, abdominal distension, and constipation.¹ The incidence of postoperative ileus varies between 10% and 30%, depending on the type of abdominal surgery and anatomical site.² Moreover, the general decrease in gastrointestinal function among older patients increases their risk of developing postoperative ileus.^3,4 Postoperative ileus is associated with prolonged hospital stay,⁵ worse patient experience, increased 30-day readmission rate,⁶ and higher hospital costs.⁷