Effect of parecoxib sodium pretreatment combined with dexmedetomidine on postoperative cognitive dysfunction and expression of indoleamine 2, 3 dioxygenase mRNA in the elderly patients

Objective To investigate the effect of parecoxib sodium pretreatment combined with dexmedetomidine on postoperative cognitive dysfunction and expression of indoleamine 2, 3 dioxygenase (IDO) mRNA in the elderly patients. Methods Sixty USA society of Anesthesiologists score standard (ASA) Ⅱ or Ⅲ patients, aged 65-80 yr, weighing 50-76 kg, undergoing elective operation on the intertrochanteric femoral fracture and hip joint, were randomly divided into 4 groups (n=32 each)using a random number table: control group (group C), parecoxib sodium pretreatment group (group P), dexmedetomidine group (group D), parecoxib sodium pretreatment combined with dexmedetomidine group (group PD). In group PD, At 15 min before induction of anaesthesia, Pareeoxib sodium 40 mg in 5 ml normal saline was injected iv, and at the same time a loading dose of dexmedetomidine 0.5 μg/kg was infused iv over 15 min, and then was infused at a rate of 0.5 μg/(kg·h) until the end of operation. In group P and D, pareeoxib sodium and dexmedetomidine were injected iv respectively, then received the equal volume of normal saline. Group C received the equal volume of normal saline. Venous blood samples were taken at 15 min before induction of anesthesia (T1), the end of surgery (T2), 6 h after operation (T3)and 24 h after operation (T4) for determination of plasma concentrations of interleukin (IL)-1β, IL-6 and expression of IDO mRNA and plasma concentrations of TRP and KYN, ratio activity of IDO was calculated. Early postoperative cognitive function was assessed by Montreal Cognitive Assessment. Results The plasma concentrations of IL-1β [(10.5±2.1), (12.9±2.8), (9.7±1.8) pg/ml] and IL-6 [(44.7±5.6), (61.1±6.8), (34.9±5.2) pg/ml] in group P, IL-1β [(11.5±2.3), (14.6±3.2), (10.4±2.2) pg/ml] and IL-6 [(46.2±6.3), (60.8±7.3), (36.3±4.8) pg/ml] in group D, IL-1β [(8.1±1.4), (9.5±2.1), (7.2±1.6) pg/ml] and IL-6 [(32.5±5.4), (42.4±6.5), (25.7±5.2) pg/ml] in group PD were significantly lower at T2-4 than the plasma concentrations of IL-1β [(16.4±3.7), (20.2±4.8), (15.6±3.5) pg/ml] and IL-6 [(63.2±7.8), (81.5±8.2), (50.4±6.5) pg/ml] in group C (P=0.000); expression of IDO mRNA [(2.011±0.612)×103] and ratio activity of IDO [(82.75±9.32) μmol/mmol] in group P, expression of IDO mRNA [(1.982±0.568)×103] and ratio activity of IDO [(84.75±8.91) μmol/mmol] in group D, expression of IDO mRNA [(0.893±0.339)×103] and ratio activity of IDO [(40.54±5.58) μmol/mmol] in group PD were significantly lower at T4 than expression of IDO mRNA [(3.426±0.581)×103] and ratio activity of IDO [(201.41±33.74) μmol/mmol] in group C (P=0.000); Compared with group P and D, all the changes were decreased in group PD (P=0.000); Incidence of early postoperative cognitive dysfunction in group C, P, D, PD respectively was 59%, 34%, 31% and 9%. Compared with group C, incidence of early postoperative cognitive dysfunction was lower in group P, D and PD. Compared with group P and D, incidence of early postoperative cognitive dysfunction was lower in group PD (P=0.000). There were no significant difference between group P and D. Conclusion Parecoxib sodium pretreatment combined with dexmedetomidine can reduce the incidence of early postoperative cognitive dysfunction in the elderly patients, the mechanism may be related to inhibiting the inflammatory reaction and expression of IDO mRNA and ratio activity of IDO. Key words: Cyclooxygenase-2 inhibitors; Dexmedetomidine; Inflammation; Indoleamine 2, 3 dioxygenase; Cognition disorders; Aged