Effective doses of remimazolam and esketamine combined with remifentanil for endotracheal intubation without muscle relaxants in pediatric patients.
Jinming Chen, Ying Mai, Xiaolei Cheng, Hao Sun, Zhihong Chen, Zhongqi Zhang
Frontiers in Pharmacology 2025 DOI: 10.3389/fphar.2025.1558966 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Prospective, non-controlled, non-randomized clinical trial Peer reviewed |
|---|---|
| Sample size | 41 |
| Population | Children aged 3-6 years undergoing tracheal intubation under general anesthesia |
| Interventions | Remimazolam Esketamine Remifentanil |
| Dose | remifentanil 2.5 μg/kg; esketamine 0.5 mg/kg initial with 0.2 mg/kg gradient; remimazolam 0.2 mg/kg initial with 0.1 mg/kg gradient |
| Topics | Esketamine |
| Keywords | Dixon’s up-and-down method Effective dose Remimazolam Without muscle relaxants Pediatric anesthesia Intubation techniques Drug combinations Anesthetic dosing Clinical research methods |
| Citations | 5 |
| Key findings | With a fixed 2.5 μg/kg remifentanil dose, the ED50 of esketamine was 0.74 mg/kg and ED95 was 0.97 mg/kg; the ED50 of remimazolam was 0.39 mg/kg and ED95 was 0.56 mg/kg for pediatric intubation without muscle relaxants. |
Abstract
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's up-and-down method. This prospective, non-controlled, non-randomized clinical trial sequentially allocated 41 children aged 3-6 into two phases. All patients underwent tracheal intubation under general anesthesia. Patients received a fixed dose of remifentanil at 2.5 μg/kg via a pump over 90 s. In the first phase, the induction dose of remimazolam was set at 0.2 mg/kg. The first patient received esketamine at a dose of 0.5 mg/kg, administered with a dose gradient of 0.2 mg/kg based on Dixon's up-and-down method. 50% effective dose (ED50) and 95% effective dose (ED95) for esketamine were then measured through probit regression analysis. Similarly, in the second phase, the ED95 of esketamine was fixed. The first patient received remimazolam at a dose of 0.2 mg/kg, administered at a dose gradient of 0.1 mg/kg. ED50 and ED95 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 min after intubation (T2). Adverse events were also recorded during anesthesia induction. At a fixed dose of remifentanil (2.5 μg/kg), the ED50 of esketamine was 0.74 mg/kg (95% confidence interval [CI]: 0.61-0.89 mg/kg), while the ED95 was 0.97 mg/kg (95% CI: 0.85-1.75 mg/kg). The ED50 of remimazolam was 0.39 mg/kg (95% CI: 0.29-0.53 mg/kg), while the ED95 was 0.56 mg/kg (95% CI: 0.46-1.47 mg/kg). Hemodynamic stability was maintained during anesthesia induction, with no significant adverse events observed. The ED50 and ED95 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 μg/kg remifentanil combined with these agents is safe and effective in children aged 3-6 years, though further multicenter studies are recommended for validation. www.chictr.org.cn, number: ChiCTR2200063847.
Comparable studies
Other non-randomized and open-label trials on esketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Esketamine Nasal Spray Plus Oral Antidepressant in Patients With Treatment-Resistant Depression Adults (≥ 18 years) with treatment-resistant depression | 2020 | Phase 3, open-label, multicenter, long-term study | n = 802 |
| Long-Term Safety and Maintenance of Response With Esketamine Nasal Spray in Participants With Treatment-Resistant Depression: Interim Results of the SUSTAIN-3 Study Adults with treatment-resistant depression | 2023 | Open-label, long-term extension study | n = 1,148 |
| Safety and efficacy with esketamine in treatment-resistant depression: long-term extension study. Adults with treatment-resistant depression who participated in ≥1 of 6 phase 3 parent... | 2025 | Open-label, single-arm long-term extension study | n = 1,148 |
| Efficacy and Safety of Intranasal Esketamine in Patients With Treatment-Resistant Depression and Comorbid Chronic Post-traumatic Stress Disorder: Open-Label Single-Arm Pilot Study Patients with treatment-resistant major depressive disorder and comorbid post-traumatic... | 2022 | Open-label, single-arm, retrospective pilot study | n = 11 |
| Managing Esketamine Treatment Frequency Toward Successful Outcomes: Analysis of Phase 3 Data Patients with treatment-resistant depression | 2020 | Post-hoc analysis of an open-label, long-term study | n = 778 |
Citations in the library
Cites 3
- Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms Pharmacological Reviews June 26, 2018
- Use of esketamine for tracheoscopic drug injection: a randomized controlled trial. Frontiers in Medicine 2024
- Ketamine—50 years in use: from anesthesia to rapid antidepressant effects and neurobiological mechanisms Pharmacological Reports February 20, 2021