Background: Preoperative anxiety is a prevalent concern among preschool pediatric patients. Esketamine, an S-enantiomer of ketamine, has emerged as a potential option for pediatric premedication. This study aimed to determine the 95% effective dose (ED95) of oral or intranasal esketamine for alleviating preoperative anxiety in this age group. Methods: Children patients aged between 1 to 6 years old who were undergoing elective surgery under general anesthesia were recruited in the study. The initial patient received a single dose of esketamine orally (2.5 mg/kg) or intranasally (1 mg/kg), which was adjusted for subsequent patients using the Dixon up-and-down method, where the dose of esketamine administered orally or intranasally to each patient depended on the sedation success of the previous patient. Doses were increased or decreased by increments of 0.5 mg/kg (oral) or 0.05 mg/kg (intranasal). An effective response was defined as having a modified Ramsay sedation score ≥3a, separation anxiety score ≤2, and mask acceptance score ≤2 during inhalational anesthesia induction. Results: A total of 62 children in the oral group and 66 children in the intranasal group were included in the final analysis. The ED95 for a single dose of oral or intranasal esketamine to alleviate preoperative separation anxiety in children was 8.2125 mg/kg (95% confidence interval [CI]: 7.4250–8.4597) and 2.1770 mg/kg (95% CI: 2.0952–2.1958), respectively. After surgery, the median of consciousness recovery time in esketamine oral and intranasal group was 30.00 (13.00–41.25) and 31.00 (20.00–45.00) min, respectively. Nausea, vomiting, increased secretions, and emergence delirium were the major adverse events that occurred following esketamine administration. Conclusion: This study demonstrates the efficacy of single-dose esketamine regimens, administered orally (ED95: 8.2125 mg/kg; 95% CI: 7.4250–8.4597 mg/kg) and intranasally (ED95: 2.1770 mg/kg; 95% CI: 2.0952–2.1958 mg/kg), in mitigating preoperative anxiety within a pediatric population. These findings highlight the safety and efficacy of esketamine for this patient group.

To evaluate the efficacy and safety of combinations of oral midazolam and esketamine for pediatric preoperative sedation. Children aged 1‒6-years undergoing elective surgery were assigned to Group A (0.62 mg/kg midazolam and 2.05 mg/kg esketamine), Group B (0.41 mg/kg midazolam and 4.1 mg/kg esketamine), and Group C (0.21 mg/kg midazolam and 6.16 mg/kg esketamine). The combination was administered orally before anesthesia induction. Primary outcome was sedation success, defined as a modified Ramsay sedation score ≥3a, low parent-child separation anxiety, and acceptance of the face mask for inhalation induction. Secondary outcomes included parental satisfaction, occurrence of Adverse Events (AE), and recovery times. The sedation success rate in Group B was 71.8%, which was significantly higher than Group A (53.5%, p < 0.05) but not Group C (68.2%, p > 0.05). There was no difference in the sedation success rate between Group A and Group C (p > 0.05). The overall incidence rate of AE in Group C was 25.90%, which was significantly higher than that in Group A (2.30%) and Group B (4.70%) (p < 0.05). No significant differences in sedation success rates were observed between genders within each group (p > 0.05). The combination of 0.41 mg/kg midazolam and 4.1 mg/kg esketamine provided the most effective sedation with the fewest adverse events in pediatric patients. This regimen may reduce rescue sedation needs and improve perioperative flow. http://www.chictr.org.cn (ChiCTR2400080633; date of first registration: February 4th, 2024).