Objective:To evaluate the efficacy of combination of intranasal dexmedetomidine and esketamine for preoperative sedation in pediatric patients with congenital heart disease.Methods:Fifty American Society of Anesthesiologists physical status Ⅱ or Ⅲ pediatric patients, aged 1-3 yr, undergoing elective cardiac surgery for left-to-right shunt type congenital heart diseases, were divided into dexmedetomidine group (group D, n=25) or dexmedetomidine combined with esketamine group (group DK, n=25) using a random number table method.Dexmedetomidine 3.9 μg/kg was intranasally delivered in group D. Dexmedetomidine 3.3 μg/kg combined with esketamine 2 mg/kg was intranasally administered in group DK.The Children′s Hospital of Wisconsin Sedation Scale score, SpO 2, HR, and pulmonary artery systolic pressure (PAP) were recorded before and at 30 min after administration, and the rate of decrease in SpO 2, HR and PAP after administration was calculated.The onset time of sedation and occurrence of adverse effects such as nausea and vomiting, bradycardia and respiratory depression during sedation were recorded. Results:Inadequate sedation and over-sedation were not observed in either group.Compared with group D, Children′s Hospital of Wisconsin Sedation Scale scores were significantly decreased at 30 min after administration, the onset time of sedation was shortened, and the decrease rate of HR was decreased in group DK ( P<0.05), and there were no significant changes in HR, SpO 2 and PAP before and after administration ( P>0.05). In group DK, nausea and vomiting occurred in 2 cases, but the symptoms were mild and no medication intervention was needed.No other adverse effects such as bradycardia and respiratory depression were found in either group. Conclusion:Combination of intranasal dexmedetomidine and esketamine can optimize the efficacy of preoperative sedation in pediatric patients with congenital heart disease, esketamine may induce nausea and vomiting, and the fasting time should be strictly controlled during sedation.