Objective:To investigate the effect of dexmedetomidine combined with parecoxib sodium on multimode analgesia during total knee arthroplasty (TKA) and its effect on cognitive function.Methods:One hundred and eighty-eight patients who underwent TKA from January 2017 to December 2019 in People′s Hospital of Xuyi County were divided into the multimode analgesia (MA) group and the postoperative patient-controlled intravenous analgesia (PCIA) group by the method of random number table, each group with 94 patients. Patients in the MA group were injected with parecoxib sodium and dexmedetomidine hydrochloride half an hour before anesthesia induction and PCIA after the operation, while PCIA was only given after the operation in the PCIA group. Visual analogue scale (VAS) and sedation Ramsay scores were performed at the time of entry into the operation room (T 0), 12 h (T 1), 24 h (T 2) and 48 h (T 3) postoperatively; simple mental state scale (MMSE) score, serum S-100β, and neuron-specific enolase (NSE) levels were measured at 24 h before the operation (T 01), T 2, and 72 h after the operation (T 4). The incidence of adverse reactions within 48 h after surgery and postoperatively cognitive dysfunction (POCD) in the two groups within 72 h after surgery were recorded and compared. Results:The VAS scores and sufentanil dosage at T 1, T 2 and T 3 in the MA group were significantly lower than those in the PCIA group ( P<0.05), and Ramsay scores were significantly higher than those in the PCIA group ( P<0.05). The total incidence of adverse reactions and POCD in the MA group were significantly lower than that in the PCIA group: 5.32% (5/94) vs. 20.21%(19/94), 8.51%(8/94) vs. 27.66%(26/94), there were significant differences ( P<0.05). At T 2 and T 4, the MMSE scores in the MA group were significantly higher than that in the PCIA group: (26.42 ± 1.68) scores vs. (25.30 ± 1.74) scores, (27.06 ± 1.93) scores vs. (26.49 ± 1.87) scores; the S-100β level in the MA group were significantly lower than that in the PCIA group: (1.35 ± 0.17) μg/L vs. (1.43 ± 0.19) μg/L, (1.26 ± 0.13) μg/L vs. (1.40 ± 0.16) μg/L; the NSE level in the MA group were significantly lower than that in the PCIA group: (0.88 ± 0.05) μg/L vs. (0.94 ± 0.06) μg/L, (0.83 ± 0.06) μg/L vs. (0.91 ± 0.04) μg/L, there were significant differences ( P<0.05). Conclusions:Dexmedetomidine combined with parecoxib sodium multimode analgesia has clear analgesia effect after TKA, can significantly reduce the occurrence of POCD and has high safety.