ED50/ED95 is a common sensitive index in clinical study of drug dose-effect relationship [8]. Sequential method [6, 7] is a classical method for calculating the ED50/ED95 of drugs with fewer cases and less experimental period, and it is used normally in the anaesthetic drugs study. In our study, we measured the ED50/ED95 and 95% CI of esketamine by using the sequential method, and the main criterion was whether the body movement was inhibited during hysteroscopy.
Esketamine is a sedative and analgesic anesthetic. It is a dextral structure of ketamine and acts through antagonizing NMDA receptors. When combined with propofol, esketamine could produce a good clinical anesthetic effect [9–12]. Eberl et al [9]. reported that the synergistic effect of ketamine and propofol could improve the safety and satisfaction of patients and reduce the using dose of drugs during ERCP,. Zhang Zhongqi et al [10]. repoerted that esketamine at 0.3 mg/kg when combined with propofol in gastroscopy not only reduced the risk of cardiovascular and respiratory adverse events, but also provided sedation and analgesia. Zhan Yongtong et al [11]. also reported that esketamine at 0.2 mg/kg when combined with propofol in gastroscopy had shorter anesthesia induction time, lower incidence of cough and body movement, and less consumption of propofol per minute than propofol alone, and there was no effect on recovery time, hemodynamic stability, postoperative cognitive function, and incidence of adverse events. Chen Jiejuan et al [12]. reported that the anesthesia effect of intravenous esketamine at 0.25mg/kg combined with propofol for painless abortion was better than that of fentanyl combined with propofol.
In this study, we also found that the combination of esketamine and propofol also produced a good clinical anesthetic effect during hysteroscopy. None of the patients developed hypotension, bradycardia and respiratory inhibition, which was explained by the sympathomimetic activity of esketamine to antagonize the inhibitory effect of propofol on the respiratory and to counteract the vagal reflex effect during surgery [13, 14]. The mean arterial pressure (MAP) of patients during cervical dilatation (T3 ) was significantly higher than that of other four monitoring points (T1, T2, T4, T5), which indicated that cervical dilatation was a great stimulus in patients, but all MAP fluctuated within 20% range of preoperative blood pressure. The BIS value of intraoperative anesthetic depth was maintained between 65 and 75.
2 patients showed postoperative nausea and vomiting, and 3 patients experienced postoperative dizziness, which all of them relieved about 2 hours after operation. All patients did not experience psychiatric adverse effects such as nightmares and cognitive impairment, which correlated with the reduced use of esketamine and possibly also related with the reduced incidence of adverse effects by propofol through activating GABA receptors. The median VAS pain score (10 min, after awakening) of the patients was 1 (0, 2), which indicated that esketamine had a good analgesic effect. Its related mechanism may be through inhibiting NMDA receptor which linked nociceptive stimulus conduction at the central and peripheral system, and may also through activating the pain inhibitory system.
In this study, target-controlled infusion of propofol using a plasma concentration of 3 µg/mL was applied to maintain the whole procedure from anesthesia induction, anesthesia maintenance to awakening as a continuous procedure with less impact on the respiratory and circulatory system of patients, less medication consumption, and easier regulation of intraoperative anesthetic depth.
This study was limited to patients with no history of vaginal delivery. which had greater stimulation intensity during cervical dilatation than in those with a history of vaginal delivery. Therefore, patients with a history of vaginal delivery to undergo hysteroscopy may require a smaller dose of esketamine. The specific effective dose of esketamine requires further study.
In conclusion, combined with target-controlled infusion of propofol (3 µg/mL in plasma concentration) during hysteroscopy, the ED50 and ED95 of esketamine were 0.391 mg/kg and 0.476 mg/kg, respectively, without significant adverse effects.