Objective  To explore the interaction and compatibility optimization of esketamine combined with oxycodone in postoperative analgesia after cesarean section.

Methods  A total of 138 postpartum women who received cesarean section in Zhejiang  Provincial Hospital of Chinese Medicine from April 2021 to October 2022 were selected as the study subjects. The initial compatibility concentration of target-controll infusion of esketamine and oxycodone was selected, and the pain disappearance time (T_LOP) of patients after anesthesia, who visual analogue scale (VAS) scores≤3 was observed. The target-controlled infusion concentrations of esketamine and oxycodone were adjusted according to bispectral index (BIS), mean arterial pressure (MAP) and heart rate (HR) during operation, and BIS 42-65, MAP≥60 mmHg and HR>50 times/min were maintained. The pain recovery time (T_ROP) from esketamine and oxycodone infusion to VAS score≥3 was recorded. The median effective dose (ED50) of each group of drugs at BIS50 was calculated by point-slope method. The pharmacodynamic interaction of esketamine and oxycodone in postoperative analgesia after cesarean section was analyzed by response surface model, and the optimal compatible concentration range was calculated.

Results  When the BIS value was 50, ED50 of esketamine combined with oxycodone deviated from the addition line without statistical significance (P>0.05). The compound drug effect (compound point SP) fell to the left of the addition line, indicating that the analgesic effect of the two drugs was synergistic. The response surface model showed that esketamine and oxycodone had a significant synergistic effect on the body motor response and circulation response during postoperative analgesia in patients undergoing cesarean section. The optimal compatible concentration range was as follows: when the concentration of oxycodone was 2 mg/ mL, 0.38-0.80 mg/kg esketamine was used; when the concentration of oxycodone was 3 mg/ mL, 0.30-0.70 mg/kg esketamine was used; when the concentration of oxycodone was 4 mg/ mL, 0.23-0.46 mg/kg esketamine was used; when the concentration of oxycodone was 5 mg/ mL, 0.18-0.37 mg/kg esketamine was used; when the concentration of oxycodone was 6 mg/mL, 0.20 mg/kg esketamine was used.

Conclusion  The target-controlled infusion of esketamine and oxycodone target controlled infusion has a synergistic effect in postoperative analgesia after cesarean section. The combination of different pharmacodynamic responses creates the optimal dosage range of esketamine and oxycodone, which can provide patients with good analgesia effect and fewer adverse reactions within the optimal concentration range.

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