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To explore the effect of acute hypervolemic hemodilution (AHH) with bicarbonated Ringer's solution (BRS) on perioperative serum S100β protein (S100β) and neuron-specific enolase (NSE) in elderly patients undergoing spine surgery. Ninety patients with lumbar spondylolisthesis and fracture surgery admitted to our hospital from January 2022 to August 2022 were selected as the study subjects, and they were randomly and equally divided into group H1 (AHH with BRS), group H2 (AHH with lactated Ringer's solution) and group C (no hemodilution). The serum contents of S100β and NSE of the three groups at different times were evaluated. There were significant differences in the incidence of postoperative cognitive dysfunction (POCD) among the three groups at T1 and T2 (P < 0.05). There were obvious differences in the contents of S100β and NSE among the three groups at T1 and T2 (P < 0.001), with no overt difference in the incidence of perioperative complications among the three groups (P > 0.05). The use of AHH with BRS can effectively reduce the effect on cognitive function in the elderly with spine surgery, which greatly reduces the nervous system injury, and has certain application value in clinic. [ABSTRACT FROM AUTHOR]