Objective:To compare the preventive effects of different doses of esketamine on remifentanil-induced hyperalgesia(RIH)in the patients underwent thoracoscopic pnlmonary lobectomy,and to provide the basis for the multimodal analgesia and rapid postoperative recovery.Methods:The prospective,double-blind,parallel-designed randomized controlled trial(RCT)were conducted,and 107 patients who underwent visual-assisted thoracoscopic pulmonary lobectomy were included.The patients were randomly divided into normal control group,low dose of esketamine group,and high dose of esketamine group using random number methods.Except the patients who were eliminated and those who dropped out of the study,there were 31 patients in normal control group,33 patients in low dose of esketamine group,and 33 patients in high dose of esketamine group.The patients in low dose of esketamine group were given the intravenous injection of 0.25 mg·kg-1 esketamine(diluted to 5 mL)during anesthesia induction;the patients in high dose of esketamine group were given the intravenous injection of 0.50 mg·kg-1 esketamine(diluted to 5 mL),and the patients in normal control group were given 5 mL intravenous injection of saline.The mechanical pain thresholds of the non-dominant forearm skin and skin around the surgical incision at different time points,numeric rating scale(NRS)scores,Ramsay sedation scores,perioperative analgesic drug dosages,and the incidences of adverse reactions such as postoperative delirium,nausea,and vomiting of the patients in various groups were recorded.Results:Compared with normal control group,the mechanical pain thresholds around the surgical incision skin of the patients in low and high doses of esketamine groups were increased(P＜0.05);compared with low dose of esketamine group,the extubation time of the patients in high dose of esketamine group was increased(P＜0.05).Two minutes after anesthesia induction administration,compared with normal control group,the mean arterial pressure(MAP)and heart rate(HR)of the patients in low and high doses of esketamine groups were increased(P＜0.05),but there were no significant differences in the MAP and HR of the patients between low dose of esketamine and high dose of esketamine group(P＞0.05);compared with normal control group,the incidences of hallucinations and delirium among the patients in high dose of esketamine group were increased(P＜0.05),while there were no significant differences in the incidences of above adverse reactions in low dose of esketamine group(P＞0.05);compared with low dose of esketamine group,the incidences of hallucinations and delirium among the patients in high dose of esketamine group were increased(P＜0.05).Conclusion:Intravenous administration of esketamine with a dosage of 0.25 mg·kg-1 during anesthesia induction improves the postoperative mechanical pain threshold of the patients undergoing thoracoscopic pulmonary lobectomy,which exhibits effective prevention of RIH without an increase in incidences of adverse reactions during the perioperative period.