{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T01:11:35Z","timestamp":1792631495055,"version":"4.5.0"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T00:00:00Z","timestamp":1742256000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>The combination of remimazolam and esketamine effectively alleviates adverse hemodynamic effects, such as tachycardia and hypertension, during intubation. However, the dosage for achieving optimal intubation conditions when co-administered with remifentanil remains unestablished. Therefore, this study aimed to determine the effective doses of remimazolam and esketamine for endotracheal intubation without muscle relaxants in pediatric patients using Dixon\u2019s up-and-down method.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This prospective, non-controlled, non-randomized clinical trial sequentially allocated 41 children aged 3\u20136 into two phases. All patients underwent tracheal intubation under general anesthesia. Patients received a fixed dose of remifentanil at 2.5\u00a0\u03bcg\/kg via a pump over 90\u00a0s. In the first phase, the induction dose of remimazolam was set at 0.2\u00a0mg\/kg. The first patient received esketamine at a dose of 0.5\u00a0mg\/kg, administered with a dose gradient of 0.2\u00a0mg\/kg based on Dixon\u2019s up-and-down method. 50% effective dose (ED<jats:sub>50<\/jats:sub>) and 95% effective dose (ED<jats:sub>95<\/jats:sub>) for esketamine were then measured through probit regression analysis. Similarly, in the second phase, the ED<jats:sub>95<\/jats:sub> of esketamine was fixed. The first patient received remimazolam at a dose of 0.2\u00a0mg\/kg, administered at a dose gradient of 0.1\u00a0mg\/kg. ED<jats:sub>50<\/jats:sub> and ED<jats:sub>95<\/jats:sub> for remimazolam were then measured. Intubation conditions were assessed via the Copenhagen scale. Heart rate (HR) and mean arterial pressure (MAP) were recorded at the following time points: Just before intubation (T1) and 1\u00a0min after intubation (T2). Adverse events were also recorded during anesthesia induction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>At a fixed dose of remifentanil (2.5\u00a0\u03bcg\/kg), the ED<jats:sub>50<\/jats:sub> of esketamine was 0.74\u00a0mg\/kg (95% confidence interval [CI]: 0.61\u20130.89\u00a0mg\/kg), while the ED<jats:sub>95<\/jats:sub> was 0.97\u00a0mg\/kg (95% CI: 0.85\u20131.75\u00a0mg\/kg). The ED<jats:sub>50<\/jats:sub> of remimazolam was 0.39\u00a0mg\/kg (95% CI: 0.29\u20130.53\u00a0mg\/kg), while the ED<jats:sub>95<\/jats:sub> was 0.56\u00a0mg\/kg (95% CI: 0.46\u20131.47\u00a0mg\/kg). Hemodynamic stability was maintained during anesthesia induction, with no significant adverse events observed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The ED<jats:sub>50<\/jats:sub> and ED<jats:sub>95<\/jats:sub> values of remimazolam and esketamine in this study provide initial dosing references for pediatric endotracheal intubation without muscle relaxants. A fixed dose of 2.5\u00a0\u03bcg\/kg remifentanil combined with these agents is safe and effective in children aged 3\u20136\u00a0years, though further multicenter studies are recommended for validation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical trial registration<\/jats:title><jats:p><jats:ext-link>www.chictr.org.cn<\/jats:ext-link>, number: ChiCTR2200063847.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2025.1558966","type":"journal-article","created":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T07:02:51Z","timestamp":1742281371000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Effective doses of remimazolam and esketamine combined with remifentanil for endotracheal intubation without muscle relaxants in pediatric patients"],"prefix":"10.3389","volume":"16","author":[{"given":"Jinming","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Mai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolei","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongqi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,3,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1221","DOI":"10.2147\/dddt.S453440","article-title":"Clinical application and research progress of remimazolam for pediatric patients","volume":"18","author":"Bai","year":"2024","journal-title":"Drug Des. 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