Article(id=1194617493185601725, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1194617490446721194, articleNumber=null, orderNo=null, doi=10.11855/j.issn.0577-7402.1632.2024.0711, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1702137600000, receivedDateStr=2023-12-10, revisedDate=null, revisedDateStr=null, acceptedDate=1704643200000, acceptedDateStr=2024-01-08, onlineDate=1762748605294, onlineDateStr=2025-11-10, pubDate=1740672000000, pubDateStr=2025-02-28, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1762748605294, onlineIssueDateStr=2025-11-10, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1762748605294, creator=13701087609, updateTime=1762748605294, updator=13701087609, issue=Issue{id=1194617490446721194, tenantId=1146029695717560320, journalId=1189873630562394117, year='2025', volume='50', issue='2', pageStart='123', pageEnd='244', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1762748604641, creator=13701087609, updateTime=1762749162199, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1194619829073191185, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1194617490446721194, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1194619829073191186, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1194617490446721194, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=141, endPage=145, ext={EN=ArticleExt(id=1194617493437259968, articleId=1194617493185601725, tenantId=1146029695717560320, journalId=1189873630562394117, language=EN, title=Determination of median effective dose of remimazolam for preoperative sedation in pediatric patients, columnId=1190310109000602400, journalTitle=Medical Journal of Chinese People’s Liberation Army, columnName=Clinical Research, runingTitle=null, highlight=null, articleAbstract=
Objective To determine the median effective dose (ED50) of remimazolam for preoperative sedation in pediatric patients aged 1-6 years using the modified Dixon sequential method. Methods This is a prospective clinical study. Pediatric patients scheduled for elective short surgery (surgery time ≤1 h) under general anesthesia from January to July 2023 were selected. Inclusion criteria were age 1-6 years, an ASA physical status Ⅰ-Ⅱ and the preoperative parent separation anxiety scale (PSAS) score ≥3 points. Remimazolam was administered intravenously preoperatively, and its sedative effect was assessed. The modified Dixon sequential method was used to determine the ED50 of remimazolam, with the initial dose set at 0.10 mg/kg and the dose increment set at 0.02 mg/kg. Sedation was considered successful (positive, included in positive group) if the child with sedation score ≥2 points, preoperative PSAS score <3 points,and the mask acceptance score of 4 points during anesthesia induction. If any criterion was not met, sedation was considered failure (negative, included in negative group), and the next patient's dosage was increased by 0.02 mg/kg based on the previous patient's dosage. The test was completed after 7 consecutive positive and negative turning points appeared alternately. Probabilistic unit regression analysis was used to determine the ED50, ED95 and the corresponding 95% confidence interval (CI) of remimazolam for preoperative sedation. Postoperative recovery time and adverse events such as airway spasm, respiratory depression, hypotension, nausea and vomiting during anesthesia were recorded. Results A total of 23 pediatric patients were included, with 13 in positive group and 10 in negative group. There were no statistically significant differences in mean arterial pressure, pulse oxygen saturation or heart rate before and after sedation (P>0.05). Compared with negative group, positive group showed a significant reduction in preoperative parent separation anxiety and an increase in mask acceptance during anesthesia (P<0.05). There was no significant difference in sedation score and anesthesia awakening time between two groups (P>0.05). The ED50 of remimazolam for preoperative sedation in pediatric patients aged 1-6 years was 0.051 mg/kg (95%CI 0.033-0.065 mg/kg), and the ED95 was 0.077 mg/kg (95%CI 0.064-0.161 mg/kg). No adverse events such as airway spasm, respiratory depression, hypotension, nausea and vomiting occurred during anesthesia in any of pediatric patients. Conclusion The ED50 of intravenous administration of remimazolam for preoperative sedation in pediatric patients aged 1-6 years is 0.051 mg/kg (95%CI 0.033-0.065 mg/kg).
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目的 采用改良Dixon序贯法确定瑞马唑仑用于1~6岁患儿术前镇静的半数有效剂量(ED50)。方法 本研究为前瞻性临床研究。纳入2023年1-7月在阜阳市人民医院择期行全身麻醉下短小手术(手术时间≤1 h)的小儿患者。纳入标准为:年龄1~6岁,美国麻醉医师协会(ASA)健康状况分级Ⅰ-Ⅱ级,术前父母分离焦虑量表(PSAS)评分≥3分。术前静脉注射瑞马唑仑并对镇静效果进行评估,采用改良Dixon序贯法确定其ED50,首例初始剂量设置为0.10 mg/kg,剂量梯度设置为0.02 mg/kg,当患儿镇静评分≥2分、术前PSAS评分<3分且麻醉诱导时面罩接受程度评分为4分时认定镇静成功(阳性,纳入阳性组),后一例患儿在前一例患儿用药量的基础上减少0.02 mg/kg,当任何一个指标评分达不到设定标准时则认定镇静失败(阴性,纳入阴性组),后一例患儿在前一例患儿用药量基础上增加0.02 mg/kg,当连续有7个阳性、阴性拐点交替显现后结束研究。采用概率单位回归分析(Probit)法确定瑞马唑仑术前镇静剂量的ED50、ED95及95%可信区间(CI)。记录患儿手术结束后的麻醉苏醒时间及麻醉期间气道痉挛、呼吸抑制、低血压、恶心呕吐等不良反应的发生情况。结果 共纳入患儿23例,其中阳性组13例,阴性组10例。所有患儿镇静前后平均动脉压、心率、血氧饱和度比较差异均无统计学意义(P>0.05)。与阴性组比较,阳性组患儿术前父母分离焦虑程度降低,麻醉诱导时面罩接受程度增高,差异有统计学意义(P<0.05);两组镇静评分及麻醉清醒时间比较差异均无统计学意义(P>0.05)。瑞马唑仑用于1~6岁患儿术前镇静的ED50为0.051 mg/kg(95%CI 0.033~0.065 mg/kg),ED95为0.077 mg/kg(95%CI 0.064~0.161 mg/kg)。所有患儿麻醉期间均未出现气道痉挛、呼吸抑制、低血压、恶心呕吐等不良反应。结论 瑞马唑仑静脉注射用于1~6岁患儿术前镇静的ED50为0.051 mg/kg(95%CI 0.033~0.065 mg/kg),且具有良好的可控性及安全性。
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吴美潮,硕士研究生,主治医师,主要从事小儿麻醉、骨科麻醉、区域阻滞麻醉等方面的临床研究
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115(2): 274-283., articleTitle=A placebo- and midazolam-controlled phase I single ascending-dose study evaluating the safety, pharmacokinetics, and pharmacodynamics of remimazolam (CNS 7056): Part I. Safety, efficacy, and basic pharmacokinetics, refAbstract=null)], funds=[Fund(id=1194650236590199359, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1194617493185601725, awardId=2022xkj087, language=EN, fundingSource=Anhui Medical University Funded Project(2022xkj087), fundOrder=null, country=null), Fund(id=1194650236644725312, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1194617493185601725, awardId=2022xkj087, language=CN, fundingSource=安徽医科大学校基金资助项目(2022xkj087), fundOrder=null, country=null)], companyList=[AuthorCompany(id=1194650232836297233, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1194617493185601725, xref=null, ext=[AuthorCompanyExt(id=1194650232844685842, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1194617493185601725, companyId=1194650232836297233, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=Department of Anesthesia, Fuyang People's Hospital, Fuyang, Anhui 236000, China), AuthorCompanyExt(id=1194650232857268755, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1194617493185601725, companyId=1194650232836297233, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=阜阳市人民医院麻醉科,安徽阜阳 236000)])], figs=[ArticleFig(id=1194650235944276535, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1194617493185601725, language=EN, label=Fig.1, caption=
Modified sequential diagram of remimazolam for preoperative sedation in pediatric patients, figureFileSmall=3vKlEZ0NSbOAJ6YGvIv+iA==, figureFileBig=GOn15npEJl5z6DiXSWa8Zw==, tableContent=null), ArticleFig(id=1194650236007191096, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1194617493185601725, language=CN, label=图1, caption=
瑞马唑仑用于患儿术前镇静的改良序贯图, figureFileSmall=3vKlEZ0NSbOAJ6YGvIv+iA==, figureFileBig=GOn15npEJl5z6DiXSWa8Zw==, tableContent=null), ArticleFig(id=1194650236086882873, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1194617493185601725, language=EN, label=Tab.1, caption=
Comparison of general indicators between two groups of pediatric patients with remimazolam for preoperative sedation
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| 指标 | 阳性组 (n=13) | 阴性组 (n=10) | t/χ2/Z | P |
|---|
| 性别[例(%)] | | | - | 1.000 |
| 男 | 11(84.6) | 8(80.0) | | |
| 女 | 2(15.4) | 2(20.0) | | |
| 年龄(岁, $\bar{x}±s$) | 3.3±1.5 | 3.5±1.0 | -0.353 | 0.728 |
| BMI(kg/m2, $\bar{x}±s$) | 19.25±2.96 | 18.75±3.10 | 0.390 | 0.700 |
| 手术时间(min, $\bar{x}±s$) | 29.23±14.41 | 25.50±9.27 | 0.711 | 0.485 |
| PSAS评分[例(%)] | | | -0.179 | 0.858 |
| 3分 | 7(53.8) | 5(50.0) | | |
| 4分 | 6(46.2) | 5(50.0) | | |
), ArticleFig(id=1194650236174963258, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1194617493185601725, language=CN, label=表1, caption=
两组瑞马唑仑术前镇静患儿基线指标比较
, figureFileSmall=null, figureFileBig=null, tableContent=
| 指标 | 阳性组 (n=13) | 阴性组 (n=10) | t/χ2/Z | P |
|---|
| 性别[例(%)] | | | - | 1.000 |
| 男 | 11(84.6) | 8(80.0) | | |
| 女 | 2(15.4) | 2(20.0) | | |
| 年龄(岁, $\bar{x}±s$) | 3.3±1.5 | 3.5±1.0 | -0.353 | 0.728 |
| BMI(kg/m2, $\bar{x}±s$) | 19.25±2.96 | 18.75±3.10 | 0.390 | 0.700 |
| 手术时间(min, $\bar{x}±s$) | 29.23±14.41 | 25.50±9.27 | 0.711 | 0.485 |
| PSAS评分[例(%)] | | | -0.179 | 0.858 |
| 3分 | 7(53.8) | 5(50.0) | | |
| 4分 | 6(46.2) | 5(50.0) | | |
), ArticleFig(id=1194650236254655035, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1194617493185601725, language=EN, label=Tab.2, caption=
Comparison of MAP, HR and SpO2 of pediatric patients before and after sedation with remimazolam ($\bar{x}±s$, n=23)
, figureFileSmall=null, figureFileBig=null, tableContent=
| 时间点 | MAP(mmHg) | HR(次/min) | SpO2(%) |
|---|
| 镇静前 | 69.48±7.03 | 107.30±10.68 | 98.00±0.91 |
| 镇静后 | 68.39±7.30 | 107.87±11.15 | 97.65±0.98 |
| t | 1.910 | -1.842 | 1.886 |
| P | 0.069 | 0.079 | 0.073 |
), ArticleFig(id=1194650236321763900, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1194617493185601725, language=CN, label=表2, caption=
患儿瑞马唑仑镇静前后MAP、HR、SpO2对比($\bar{x}±s$,n=23)
, figureFileSmall=null, figureFileBig=null, tableContent=
| 时间点 | MAP(mmHg) | HR(次/min) | SpO2(%) |
|---|
| 镇静前 | 69.48±7.03 | 107.30±10.68 | 98.00±0.91 |
| 镇静后 | 68.39±7.30 | 107.87±11.15 | 97.65±0.98 |
| t | 1.910 | -1.842 | 1.886 |
| P | 0.069 | 0.079 | 0.073 |
), ArticleFig(id=1194650236384678461, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1194617493185601725, language=EN, label=Tab.3, caption=
Comparison of sedation scores, PSAS scores, mask acceptance scores and anesthesia awakening time between two groups of patients with remimazolam for preoperative sedation
, figureFileSmall=null, figureFileBig=null, tableContent=
| 指标 | 阳性组 (n=13) | 阴性组 (n=10) | Z/t | P |
|---|
| 镇静评分[例(%)] | | | -1.888 | 0.059 |
| 2分 | 9(69.2) | 10(100.0) | | |
| 3分 | 4(30.8) | 0 | | |
| PSAS评分[例(%)] | | | -3.632 | <0.001 |
| 1分 | 8(61.5) | 4(40.0) | | |
| 2分 | 5(38.5) | 6(60.0) | | |
| 3分 | 0 | 0 | | |
| 面罩接受程度评分[例(%)] | | | -4.513 | <0.001 |
| 2分 | 0 | 4(40.0) | | |
| 3分 | 0 | 6(60.0) | | |
| 4分 | 13(100.0) | 0 | | |
| 麻醉清醒时间(min, $\bar{x}±s$) | 21.15±8.07 | 23.10±8.74 | -0.553 | 0.586 |
), ArticleFig(id=1194650236447593022, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1194617493185601725, language=CN, label=表3, caption=
两组瑞马唑仑术前镇静评分、PSAS评分、麻醉诱导时面罩接受程度评分、麻醉清醒时间比较
, figureFileSmall=null, figureFileBig=null, tableContent=
| 指标 | 阳性组 (n=13) | 阴性组 (n=10) | Z/t | P |
|---|
| 镇静评分[例(%)] | | | -1.888 | 0.059 |
| 2分 | 9(69.2) | 10(100.0) | | |
| 3分 | 4(30.8) | 0 | | |
| PSAS评分[例(%)] | | | -3.632 | <0.001 |
| 1分 | 8(61.5) | 4(40.0) | | |
| 2分 | 5(38.5) | 6(60.0) | | |
| 3分 | 0 | 0 | | |
| 面罩接受程度评分[例(%)] | | | -4.513 | <0.001 |
| 2分 | 0 | 4(40.0) | | |
| 3分 | 0 | 6(60.0) | | |
| 4分 | 13(100.0) | 0 | | |
| 麻醉清醒时间(min, $\bar{x}±s$) | 21.15±8.07 | 23.10±8.74 | -0.553 | 0.586 |
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