Objective Long‐term cognitive decline is an adverse outcome after major surgery associated with increased risk for mortality and morbidity. We studied the cerebrospinal fluid (CSF) and serum biochemical inflammatory response to a standardized orthopedic surgical procedure and the possible association with long‐term changes in cognitive function. We hypothesized that the CSF inflammatory response pattern after surgery would differ in patients having long‐term cognitive decline defined as a composite cognitive z score of ≥1.0 compared to patients without long‐term cognitive decline at 3 months postsurgery. Methods Serum and CSF biomarkers of inflammation and blood–brain barrier (BBB) integrity were measured preoperatively and up to 48 hours postoperatively, and cognitive function was assessed preoperatively and at 2 to 5 days and 3 months postoperatively. Results Surgery was associated with a pronounced increase in inflammatory biomarkers in both CSF and blood throughout the 48‐hour study period. A principal component (PC) analysis was performed on 52 inflammatory biomarkers. The 2 first PC (PC1 and PC2) construct outcome variables on CSF biomarkers were significantly associated with long‐term cognitive decline at 3 months, but none of the PC construct serum variables showed a significant association with long‐term cognitive decline at 3 months. Patients both with and patients without long‐term cognitive decline showed early transient increases of the astroglial biomarkers S‐100B and glial fibrillary acidic protein in CSF, and in BBB permeability (CSF/serum albumin ratio). Interpretation Surgery rapidly triggers a temporal neuroinflammatory response closely associated with long‐term cognitive outcome postsurgery. The findings of this explorative study require validation in a larger surgical patient cohort. Ann Neurol 2020;87:370–382

Background: Postoperative neurocognitive decline is a frequent complication in adult patients undergoing major surgery with increased risk for morbidity and mortality. The mechanisms behind cognitive decline after anaesthesia and surgery are not known. We studied the association between CSF and blood biomarkers of neuronal injury or brain amyloidosis and long-term changes in neurocognitive function. Methods: In patients undergoing major orthopaedic surgery (knee or hip replacement), blood and CSF samples were obtained before surgery and then at 4, 8, 24, 32, and 48 h after skin incision through an indwelling spinal catheter. CSF and blood concentrations of total tau (T-tau), neurofilament light, neurone-specific enolase and amyloid b (Ab1-42) were measured. Neurocognitive function was assessed using the International Study of Postoperative Cognitive Dysfunction (ISPOCD) test battery 1e2 weeks before surgery, at discharge from the hospital (2e5 days after surgery), and at 3 months after surgery. Results: CSF and blood concentrations of T-tau, neurone-specific enolase, and Ab1-42 increased after surgery. A similar increase in serum neurofilament light was seen with no overall changes in CSF concentrations. There were no differences between patients having a poor or good late postoperative neurocognitive outcome with respect to these biomarkers of neuronal injury and Ab1-42. Conclusions: The findings of the present explorative study showed that major orthopaedic surgery causes a release of CSF markers of neural injury and brain amyloidosis, suggesting neuronal damage or stress. We were unable to detect an association between the magnitude of biomarker changes and long-term postoperative neurocognitive dysfunction.

Learning and memory are cognitive functions commonly impaired after surgery, especially in elderly patients. Our aim was to evaluate the effect of sevoflurane anaesthesia on episodic-like memory in young and aged wild-type mice and mice with altered nicotinic cholinergic neurotransmission (beta2KO). Mice learned objects before randomization to control, anaesthesia or sham groups. Anaesthesia was maintained at 2.6% sevoflurane for 2 h, starting immediately after training. Object memory testing was performed after 24 h, when one familiar object was replaced by a nonfamiliar object. While nonanaesthetized mice showed memory retention of the familiar object, anaesthetized wild-type and beta2KO mice showed impaired memory. Sevoflurane anaesthesia thus causes memory impairment in mice regardless of beta2 receptor-mediated nicotinic cholinergic neurotransmission.

The wet fluorescent microsphere aerosol was as reliable as Technegas for high-resolution measurements of regional ventilation. The markedly different effects of 10 PEEP in supine and prone sheep may have important implications for gas exchange both in noninjured and injured lungs.