中国临床试验注册中心 - 世界卫生组织国际临床试验注册平台一级注册机构

注册号： Registration number：	ChiCTR2400090337
最近更新日期： Date of Last Refreshed on：	2024-09-27 15:25:40
注册时间： Date of Registration：	2024-09-27 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	咪达唑仑口服溶液联合艾司氯胺酮用于小儿磁共振检查镇静的研究
Public title：	Study on midazolam oral solution combined with Esketamine for sedation in children undergoing magnetic resonance examination
注册题目简写：
English Acronym：
研究课题的正式科学名称：	咪达唑仑口服溶液联合艾司氯胺酮用于小儿磁共振检查镇静的研究
Scientific title：	Study on midazolam oral solution combined with Esketamine for sedation in children undergoing magnetic resonance examination
研究课题代号(代码)： Study subject ID：
在二级注册机构或其它机构的注册号： The registration number of the Partner Registry or other register：

申请注册联系人：	熊虹飞	研究负责人：	熊虹飞
Applicant：	Xiong Hongfei	Study leader：	Xiong Hongfei
申请注册联系人电话： Applicant telephone：	+86 185 0290 4320	研究负责人电话： Study leader's telephone：	+86 185 0290 4320
申请注册联系人传真： Applicant Fax：		研究负责人传真： Study leader's fax：
申请注册联系人电子邮件： Applicant E-mail：	bear_0320@163.com	研究负责人电子邮件： Study leader's E-mail：	bear_0320@163.com
申请单位网址(自愿提供)： Applicant website(voluntary supply)：		研究负责人网址(自愿提供)： Study leader's website(voluntary supply)：
申请注册联系人通讯地址：	陕西省西安市高新区西太路777号	研究负责人通讯地址：	陕西省西安市高新区西太路777号
Applicant address：	777 Xitai Road, High-tech Zone, Xi 'an, Shaanxi	Study leader's address：	777 Xitai Road, High-tech Zone, Xi 'an, Shaanxi
申请注册联系人邮政编码： Applicant postcode：		研究负责人邮政编码： Study leader's postcode：
申请人所在单位：	西安国际医学中心医院
Applicant's institution：	Xi'an International Medical Center Hospital
研究负责人所在单位：	西安国际医学中心医院
Affiliation of the Leader：	Xi'an International Medical Center Hospital

是否获伦理委员会批准：	是
Approved by ethic committee：	Yes
伦理委员会批件文号： Approved No. of ethic committee：	202465	伦理委员会批件附件： Approved file of Ethical Committee：	查看附件View
批准本研究的伦理委员会名称：	西安国际医学中心医院伦理委员会
Name of the ethic committee：	Ethics Committee of Xi'an International Medical Center Hospital
伦理委员会批准日期： Date of approved by ethic committee：	2024-08-13 00:00:00
伦理委员会联系人：	郭秀
Contact Name of the ethic committee：	Xiu Guo
伦理委员会联系地址：	陕西省西安市高新区西太路777号
Contact Address of the ethic committee：	777 Xitai Road, High-tech Zone, Xi 'an, Shaanxi
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 29 8981 1832	伦理委员会联系人邮箱： Contact email of the ethic committee：

研究实施负责（组长）单位：

西安国际医学中心医院

Primary sponsor：

Xi'an International Medical Center Hospital

研究实施负责（组长）单位地址：

陕西省西安市高新区西太路777号

Primary sponsor's address：

777 Xitai Road, Chang'an District, Xi'an, Shaanxi

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：	中国	省(直辖市)：	陕西	市(区县)：	西安
Country：	China	Province：	Shaanxi	City：	Xi'an
单位(医院)：	西安国际医学中心医院	具体地址：	高新区西太路777号
Institution hospital：	Xi'an International Medical Center Hospital	Address：	777 Xitai Road, Chang'an District

经费或物资来源：

陕西省科技厅

Source(s) of funding：

Shaanxi province science and technology department

研究疾病：

无

Target disease：

none

研究疾病代码：

Target disease code：

研究类型：

干预性研究

Study type：

Interventional study

研究所处阶段：

上市后药物

Study phase：

4

研究设计：

偏倚化抛硬币设计

Study design：

Biased Coin Design

研究目的：

1）探索咪达唑仑口服溶液联合艾司氯胺酮口服用于小儿磁共振检查镇静的ED95。 2）探索咪达唑仑口服溶液联合艾司氯胺酮滴鼻用于小儿磁共振检查镇静的ED95。 3）探索上述两种方法用于小儿磁共振检查镇静的优劣。

Objectives of Study：

1) To explore the combination of midazolam oral solution and escitalopram for sedation in children undergoing magnetic resonance examination. 2) To explore the application of midazolam oral solution combined with Esketamine nasal drops in children's magnetic resonance examination of sedation ED95. 3) Explore the advantages and disadvantages of the above two methods for sedation in children's magnetic resonance examination.

药物成份或治疗方案详述：

1.研究目的 1）探索咪达唑仑口服溶液联合艾司氯胺酮口服用于小儿磁共振检查镇静的ED95。 2）探索咪达唑仑口服溶液联合艾司氯胺酮滴鼻用于小儿磁共振检查镇静的ED95。 3）探索上述两种方法用于小儿磁共振检查镇静的优劣。 2.研究设计 2.1 偏性掷币随机（实验一与实验二）本研究采用偏性掷币设计的上下序贯法（Biased coin design up-and-down sequential method，BCD-UDM），每例患儿口服艾司氯胺酮的剂量取决于前一例患儿的反应，从低剂量开始，根据预实验和以往文献，艾司氯胺酮的起始口服剂量为2mg/kg。随后如果前一例患儿在分离时为阴性反应（服药后30分钟改良Ramsay镇静评分未能达到6c反或未能完成磁共振检查），下一例患者升高一个浓度单位（0.5mg/kg），直到出现第一例阳性反应（服药后30分钟内改良Ramsay镇静评分达到6c且完成磁共振检查）患儿。如果前一例患儿在分离时是阳性反应，则该患儿口服艾司氯胺酮的剂量根据偏性掷币随机原则来分配。根据以上规则对纳入研究的患儿进行序贯试验，直到样本量达到满足终止规则的数量。 2.2 随机对照研究（实验三）本研究采用单中心、随机、平行对照的试验设计。本研究分为A组（0.8254mg/kg咪达唑仑口服溶液+实验一中ED95艾司氯胺酮口服），B组（0.8254mg/kg咪达唑仑口服溶液+实验二中ED95艾司氯胺酮滴鼻）。 2.3 样本量实验一及实验二根据BCD序贯法，至少需要出现20-40个[19]阳性反应时方可终止研究并进行统计分析，因此，本研究的样本量即为45±2 例左右。实验三样本量计算利用在线软件（https://www.cnstat.org/samplesize/mean/）。根据预试验中两组组患者磁共振检查镇静成功率的均值估算样本量。采用1个对照组+1个试验组进行差异性检验（方差分析）的样本量计算。设定α为0.05（双侧），1-β=0.80，Sd=0.1。 3. 盲法实验一及实验二研究采用盲法设计，每一例患儿接受术前镇静的艾司氯胺酮剂量由专人配制好交给实施麻醉操作的麻醉医生，实施麻醉的麻醉医生、患儿及家属均不清楚药物实际剂量。服药后30分钟内改良Ramsay镇静评分达到6c且完成磁共振检查被定义为阳性反应，代表镇静成功；服药后30分钟改良Ramsay镇静评分未能达到6c反或未能完成磁共振检查则为阴性反应，代表镇静失败，由实施麻醉操作的麻醉医生判定并记录。 4. 主要研究结局和观察指标主要研究结局为：磁共振检查完成率。 5. 次要研究结局和观察观察指标次要研究结局为术后患儿对于给药方式的依从性、服药到开始检查的时间、检查时间、苏醒时间、不良反应的发生率以及家长满意度。次要观察指标包括： 给药时患儿的行为评分[20]； 检查开始时患儿改良Ramsay镇静评分[20]； 服药到开始检查的时间（T1）； 是否发生补救镇静； 检查时间（T2）； 家长对与患儿分离的满意度； 不良反应：①SpO2降至入室基线5%的次数；②EtCO2≥45mmHg的次数；③辅助呼吸的次数（SpO2≤90%，持续10s）；④HR下降超过基线值30%的次数；⑤苏醒期不良反应（恶心、呕吐及烦躁）； 苏醒时间（T3，检查结束到患儿自主睁眼的时间）。 6. 纳入和排除标准 6.1纳入标准患者必须满足以下所有入选标准才可入组本研究 行门诊磁共振检查的小儿（单部位）； 年龄 1-6 岁，性别不限； ASA 评级 I-Ⅱ级； 患儿法定监护人愿意参加本研究并签署知情同意书。 6.2排除标准具有以下任何一项的患儿不能入组本研究 营养不良或肥胖患儿 库兴综合征、垂体瘤、肾上腺肿瘤等内分泌系统疾病； 患有严重呼吸道病变（阻塞型睡眠呼吸暂停综合征、急性呼吸道感染、未受控制的哮喘、活动性大咯血、肺动脉高压等）； 任何先天性心脏病、急性心力衰竭、房室传导阻滞、严重心律失常； 感染性心脏疾病如心肌炎或心内膜炎；败血症；肺炎。 患有精神系统疾病（自闭症、多动症、精神分裂症）、大脑发育异常及认知功能障碍者； 贫血或者血小板减少：Hb<90g/L，PLT<80×109/L； 凝血功能异常：（PT>ULN+3s和/或APTT>ULN+10s）； 肝功能异常：AST和/或ALT≥2.5×ULN，TBIL≥1.5×ULN； 肾功能异常：尿素或尿素氮≥1.5×ULN，血肌酐大于正常值上限； 血糖未获满意控制的患者（筛选期随机血糖≥11.1mmol/L）； 对苯二氮䓬类药物、艾司氯胺酮等药物及其药物组分过敏或有禁忌者； 被判定为呼吸道管理有困难的患者（改良马氏评分为Ⅳ级）； 近3个月内作为受试者参加过任何临床药物试验且使用过该试验药物； 服用单胺氧化酶抑制剂2周内； 术前48小时内服用过镇静药物、镇吐药物、晕车药物、抗瘙痒药物； 其它可能干扰实验结果的因素。 6.3剔除标准： 患儿拒绝参加研究或者无法配合； 检查时间超过15分钟； 数据记录不完全患者； 研究者认为无法继续治疗的其它原因。 7.标准操作流程 7.1 镇静前准备术前对符合纳入标准的患儿及家属完成访视及宣教，充分告知本次研究目的，宣教麻醉的基本流程、风险，与患儿家属签署知情同意书。 7.2 镇静实施实验一及实验二：所有患儿术前禁食6小时、禁清饮2小时。在父母的陪伴下入预麻室后连接心电图及指脉氧饱和度，口服0.8254mg/kg咪达唑仑溶液及预设剂量的艾司氯胺酮，观察并记录患儿服药时的行为评分，服药后每 5 分钟评估并记录患儿的 Ramsay 镇静评分，待改良Ramsay镇静评分达到6c时进入磁共振检查室开始检查，若服药后30分钟镇静评分仍无法达到6c则视为镇静失败。记录服药后到开始检查时间、检查时间、苏醒时间及苏醒期不良反应（恶心、呕吐、烦躁）以及家长满意度，镇静期间SpO2降至入室基线5%的次数，EtCO2＞45mmHg的次数，辅助呼吸的次数（SpO2≤90%，持续≥10s），HR下降超过基线值30%的次数。实验三：所有患儿术前禁食6小时、禁清饮2小时。在父母的陪伴下入预麻室后连接心电图及指脉氧饱和度，A组口服0.8254mg/kg咪达唑仑溶液及给与实验一中ED95剂量的艾司氯胺酮口服，B组口服0.8254mg/kg咪达唑仑溶液及给与实验二中ED95剂量的艾司氯胺酮滴鼻，观察并记录患儿服药时的行为评分，服药后每 5 分钟评估并记录患儿的 Ramsay 镇静评分，待改良Ramsay镇静评分达到6c时进入磁共振检查室开始检查，若服药后30分钟镇静评分仍无法达到6c则视为镇静失败。若镇静失败则采用艾司氯胺酮3mg/kg肌注补救镇静。记录服药后到开始检查时间、检查时间、苏醒时间及苏醒期不良反应（恶心、呕吐、烦躁）以及家长满意度，镇静期间SpO2降至入室基线5%的次数，EtCO2＞45mmHg的次数，辅助呼吸的次数（SpO2≤90%，持续≥10s），HR下降超过基线值30%的次数。如果在此过程中发生呼吸抑制（SpO2≤90%，持续≥10s），我们将采用闭式面罩加压给氧，呼吸囊控制呼吸。 7.3 干预措施实验一0.8254mg/kg咪达唑仑口服溶液联合艾司氯胺酮口服，实验二0.8254mg/kg咪达唑仑口服溶液联合艾司氯胺酮口服艾司氯胺酮滴鼻，实验三A组0.8254mg/kg咪达唑仑口服溶液联合实验一中ED95剂量的艾司氯胺酮口服，B组0.8254mg/kg咪达唑仑口服溶液联合实验二中ED95剂量的艾司氯胺酮滴鼻。 7.4 剂量选择依据根据本课题组前期研究及既往研究。

Description for medicine or protocol of treatment in detail：

1. Research purpose 1) To explore the use of midazolam oral solution combined with esketamine for pediatric magnetic resonance examination sedation of ED95. 2) To explore the use of midazolam oral solution combined with esketamine nasal drops for pediatric magnetic resonance examination of sedation ED95. 3) To explore the advantages and disadvantages of the above two methods for pediatric magnetic resonance examination sedation. 2. Research design 2.1 Partial random coin toss (Experiment 1 and Experiment 2) In this study, Biased coin design up-and-down is adopted sequential method, BCD-UDM), the oral dose of esketamine for each child depends on the response of the previous child, starting at a low dose, based on the preliminary experiment and previous literature, the starting oral dose of esketamine is 2mg/kg. Subsequently, if the previous patient was negative at the time of separation (failed to reach 6c negative on the modified Ramsay sedation score at 30 minutes after administration or failed to complete the MRI), the next patient was increased by one concentration unit (0.5mg/kg). Until the first positive case (a modified Ramsay sedation score of 6c within 30 minutes of administration and completion of MRI). If the previous child was positive at the time of separation, the oral dose of esketamine for the child was allocated according to the partial random toss principle. The children included in the study were sequentially tested according to the above rules until the sample size was sufficient to meet the termination rules. 2.2 Randomized Controlled Study (Experiment 3) A single-center, randomized, parallel-controlled design was used in this study. This study was divided into group A (0.8254mg/kg midazolam oral solution + ED95 esketamine oral solution in experiment 1) and group B (0.8254mg/kg midazolam oral solution + ED95 Esketamine nasal drops in experiment 2). 2.3 Sample size In experiments 1 and 2, according to the BCD sequential method, at least 20-40 [19] positive reactions were required before the study could be terminated and statistical analysis could be carried out. Therefore, the sample size of this study was about 45±2 cases. The three sample size calculation using online software (https://www.cnstat.org/samplesize/mean/). The sample size was estimated based on the mean of the success rate of sedation by MRI in the two groups of patients in the pre-trial. The sample size of 1 control group +1 experimental group was calculated for variance test (ANOVA). Set alpha to 0.05 (both sides), 1-β=0.80, Sd=0.1. 3. Blind method In the first and second studies, the blind design was adopted. The dose of esketamine for each patient receiving pre-operative sedation was prepared by a special person and delivered to the anesthesiologist performing the anesthesia operation. The anesthesiologist performing the anesthesia, the child and his family members were not aware of the actual dose of the drug. A sedation score of 6c within 30 minutes of taking the modified Ramsay and completion of the MRI examination were defined as positive, indicating successful sedation. Failure of Ramsay to achieve a 6c negative sedation score 30 minutes after medication or failure to complete a magnetic resonance examination is a negative reaction, indicating a sedation failure, which is determined and recorded by the anesthesiologist performing the anesthesia procedure. 4. Main study outcomes and observational measures Primary outcome: MRI completion rate. 5. Secondary study outcomes and observational observational measures Secondary outcomes were postoperative compliance with dosing mode, time from medication to initial examination, time to examination, time to recovery, incidence of adverse reactions, and parental satisfaction. Secondary outcome measures included:  Behavioral scores of children at the time of administration [20];  Modified Ramsay sedation score at the beginning of examination [20];  Time from medication to start of examination (T1);  whether remedial sedation has occurred;  Inspection time (T2);  Parent satisfaction with separation from child;  Adverse reactions: ① Number of SpO2 drops to 5% of entry baseline; ② The number of EtCO2≥45mmHg; ③ The number of assisted breathing (SpO2≤90%, lasting 10s); ④ The number of times HR decreased by 30% above the baseline value; (5) Adverse reactions during recovery (nausea, vomiting and irritability);  time to wake up (T3, the time from the end of examination to voluntary eye opening). 6. Inclusion and exclusion criteria 6.1 Inclusion criteria Patients must meet all of the following inclusion criteria to be enrolled in this study  children undergoing outpatient magnetic resonance examination (single site);  Age 1-6 years old, gender unlimited; ASA Grade I-II;  The legal guardian of the child is willing to participate in this study and sign the informed consent. 6.2 Exclusion Criteria Children with any of the following conditions were excluded from the study  Malnourished or obese children  Cushing's syndrome, pituitary tumor, adrenal gland tumor and other endocrine system diseases;  severe respiratory disease (obstructive sleep apnea syndrome, acute respiratory infection, uncontrolled asthma, active massive hemoptysis, pulmonary hypertension, etc.);  any congenital heart disease, acute heart failure, atrioventricular block, severe arrhythmia;  Infectious heart disease such as myocarditis or endocarditis; Septicemia; pneumonia.  People with psychiatric disorders (autism, ADHD, schizophrenia), abnormal brain development and cognitive impairment;  anemia or thrombocytopenia: Hb<90g/L, PLT<80×109/L;  Abnormal coagulation: (PT>ULN+3s and/or APTT>ULN+10s);  Abnormal liver function: AST and/or ALT≥2.5×ULN, TBIL≥1.5×ULN;  Abnormal renal function: urea or urea nitrogen ≥1.5×ULN, serum creatinine greater than the upper limit of normal;  Patients with unsatisfactory blood glucose control (random blood glucose ≥11.1mmol/L during the screening period);  Allergic or contraindicated to benzodiazepines, esketamine and other drugs and their components;  patients diagnosed with respiratory management difficulties (modified Markov score Ⅳ);  Has participated in any clinical drug trial as a subject and used the investigational drug within the last 3 months;  Take a monoamine oxidase inhibitor for 2 weeks;  sedative drugs, antiemetic drugs, motion sickness drugs, anti-pruritus drugs taken within 48 hours before surgery;  Other factors that may interfere with the experimental results. 6.3 Exclusion criteria:  Children who refuse to participate in the study or are unable to cooperate;  The inspection time exceeds 15 minutes;  Patients with incomplete data recording;  Other reasons for which the investigators believe treatment cannot be continued. 7. Standard operating procedures 7.1 Preparation before sedation Children who met the inclusion criteria and their families were visited and educated before surgery, the purpose of this study was fully informed, the basic process and risks of anesthesia education were fully informed, and informed consent was signed with their families. 7.2 Sedation Implementation Experiment 1 and Experiment 2: All the children fasted for 6 hours and forbade clear drink for 2 hours before surgery. After entering the pre-anesthesia room accompanied by parents, ECG and pulse oxygen saturation were connected, 0.8254mg/kg midazolam solution and a preset dose of esketamine were taken orally, behavioral scores of the children were observed and recorded, and Ramsay sedation scores were assessed and recorded every 5 minutes after medication. When the improved Ramsay sedation score reaches 6c, he will enter the MRI examination room and start the examination. If the sedation score cannot reach 6c within 30 minutes after taking the medication, sedation failure will be considered. The time from medication to the start of examination, examination time, time to recovery and adverse reactions (nausea, vomiting, irritability) during recovery as well as parental satisfaction, the number of SpO2 drops to 5% of baseline entry during sedation, the number of EtCO2 > 45mmHg, and the number of assisted breathing (SpO2≤90%, lasting ≥10s) were recorded. The number of times HR drops 30% above the baseline value. Experiment 3: All the children fasted for 6 hours and forbade clear drink for 2 hours before surgery. After entering the pre-anesthesia room accompanied by parents, ECG and pulse oxygen saturation were connected. Group A was given 0.8254mg/kg midazolam solution and esketamine at ED95 dose in experiment 1; group B was given 0.8254mg/kg midazolam solution and Esketamine at ED95 dose in experiment 2. The behavioral score of the child during medication was observed and recorded, and Ramsay sedation score of the child was evaluated and recorded every 5 minutes after medication. When the Ramsay sedation score was improved and reached 6c, the child entered the MRI examination room for examination. If the sedation score was still unable to reach 6c 30 minutes after medication, sedation failure was considered. If sedation failed, esketamine 3mg/kg intramuscular injection was used for remedial sedation. The time from medication to the start of examination, examination time, time to recovery and adverse reactions (nausea, vomiting, irritability) during recovery as well as parental satisfaction, the number of SpO2 drops to 5% of baseline entry during sedation, the number of EtCO2 > 45mmHg, and the number of assisted breathing (SpO2≤90%, lasting ≥10s) were recorded. The number of times HR drops 30% above the baseline value. If respiratory depression occurs during this process (SpO2≤90%, lasting ≥10s), we will use a closed mask to pressurize oxygen and a respiratory sac to control breathing. 7.3 Intervention Measures Experiment 1:0.8254mg/kg midazolam oral solution combined with esketamine; experiment 2:0.8254mg/kg midazolam oral solution combined with Esketamine oral nasal drops; Experiment 3 Group A: 0.8254mg/kg midazolam oral solution combined with Esketamine at ED95 dose in experiment 1; Group B received 0.8254mg/kg oral midazolam solution combined with esketamine at ED95 dose in experiment 2. 7.4 Basis for dose selection According to the previous research and previous research of this research group.

纳入标准：

Inclusion criteria

排除标准：

1.营养不良或肥胖患儿； 2.库兴综合征、垂体瘤、肾上腺肿瘤等内分泌系统疾病； 3.患有严重呼吸道病变（阻塞型睡眠呼吸暂停综合征、急性呼吸道感染、未受控制的哮喘、活动性大咯血、肺动脉高压等）； 4.任何先天性心脏病、急性心力衰竭、房室传导阻滞、严重心律失常； 5.感染性心脏疾病如心肌炎或心内膜炎；败血症；肺炎； 6.患有精神系统疾病（自闭症、多动症、精神分裂症）、大脑发育异常及认知功能障碍者； 7.贫血或者血小板减少：Hb<90g/L，PLT<80×10^9/L； 8.凝血功能异常：（PT>ULN+3s和/或APTT>ULN+10s）； 9.肝功能异常：AST和/或ALT≥2.5×ULN，TBIL≥1.5×ULN； 10.肾功能异常：尿素或尿素氮≥1.5×ULN，血肌酐大于正常值上限； 11.血糖未获满意控制的患者（筛选期随机血糖≥11.1mmol/L）； 12.对苯二氮卓类药物、阿片类药物、依托咪酯、丙泊酚、氯胺酮等药物及其药物组分过敏或有禁忌者； 13.被判定为呼吸道管理有困难的患者（改良马氏评分为Ⅳ级）； 14.近3个月内作为受试者参加过任何临床药物试验且使用过该试验药物； 15.服用单胺氧化酶抑制剂2周内； 16.术前48小时内服用过镇静药物、镇吐药物、晕车药物、抗瘙痒药物； 17.其它可能干扰实验结果的因素。

Exclusion criteria：

1. Malnourished or obese children; 2. Cushing's syndrome, pituitary tumor, adrenal tumors such as endocrine system diseases; 3. Severe respiratory diseases (obstructive sleep apnea syndrome, acute respiratory tract infection, uncontrolled asthma, active massive hemoptysis, pulmonary hypertension, etc.); 4. Any congenital heart disease, acute heart failure, atrioventricular block, or severe arrhythmia; 5. Infectious heart disease such as myocarditis or endocarditis; Sepsis; Pneumonia; 6. Paients suffering from mental system diseases (autism, ADHD, schizophrenia), abnormal brain development and cognitive dysfunction; 7. Anemia or thrombocytopenia: Hb<90g/L, PLT<80x10^9/L; 8. Abnormal coagulation function: (PT>ULN+3s and/or APTT>ULN+10s); 9. Abnormal liver function: AST and/or ALT>=2.5xULN, TBIL>=1.5xULN; 10. Abnormal renal function: urea or urea nitrogen >=1.5xULN, blood creatinine greater than the upper limit of normal value; 11. Patients whose blood glucose was not satisfactorily controlled (random blood glucose >=11.1mmol/L during the screening period); 12. Allergic or contraindicated to benzodiazepines, opiates, etomidate, propofol, ketamine and other drugs and their components; 13. Patients judged to have difficulty managing the respiratory tract (modified Markov score level Ⅳ); 14. Participated in any clinical drug trial as a subject and used the test drug within the last 3 months; 15. Take monoamine oxidase inhibitors for 2 weeks; 16. Taking sedative drugs, antiemetic drugs, motion sickness drugs and anti-pruritus drugs within 48 hours before surgery; 17. Other factors that might interfere with the results of the experiment.

研究实施时间：

Study execute time：

从 From 2024-10-08 00:00:00至 To 2025-09-30 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2024-10-08 00:00:00 至 To 2025-09-30 00:00:00

干预措施：

Interventions：

组别：	咪达唑仑溶液联合艾司氯胺酮口服（实验一）	样本量：	50
Group：	Midazolam solution combined with S-ketamine oral(Experiment one)	Sample size：	50
干预措施：	口服咪达唑仑+艾司氯胺酮（实验一）	干预措施代码：
Intervention：	Oral midazolam+S-ketamine(Experiment one)	Intervention code：

组别：	咪达唑仑口服联合艾司氯胺酮滴鼻（实验二）	样本量：	50
Group：	Midazolam oral combined with S-ketamine nasal drops(Experiment two)	Sample size：	50
干预措施：	口服咪达唑仑+艾司氯胺酮滴鼻（实验二）	干预措施代码：
Intervention：	Oral midazolam+S-ketamine nasal drops(Experiment two)	Intervention code：

组别：	咪达唑仑溶液联合艾司氯胺酮口服（实验三）	样本量：	30
Group：	Midazolam solution combined with S-ketamine oral(Experiment three)	Sample size：	30
干预措施：	口服咪达唑仑+艾司氯胺酮（剂量为实验一结果，实验三）	干预措施代码：
Intervention：	Oral midazolam+S-ketamine(The dose is the result of experiment one, experiment three)	Intervention code：

组别：	咪达唑仑口服联合艾司氯胺酮滴鼻（实验三）	样本量：	30
Group：	Midazolam oral combined with S-ketamine nasal drops(Experiment three)	Sample size：	30
干预措施：	口服咪达唑仑+艾司氯胺酮滴鼻（剂量为实验二结果，实验三）	干预措施代码：
Intervention：	Oral midazolam+S-ketamine(The dose is the result of experiment two, experiment three)	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	陕西	市(区县)：	西安
Country：	China	Province：	Shaanxi	City：	Xi'an
单位(医院)：	西安国际医学中心医院	单位级别：	三级
Institution hospital：	Xi'an International Medical Center Hospital	Level of the institution：	Tertiary

测量指标：

Outcomes：

指标中文名：	磁共振检查成功率	指标类型：	主要指标
Outcome：	Success rate of magnetic resonance examination	Type：	Primary indicator
测量时间点：	磁共振检查完成时	测量方法：
Measure time point of outcome：	When the magnetic resonance examination is completed	Measure method：

指标中文名：	给药时患儿的行为评分	指标类型：	次要指标
Outcome：	Children's behavior scores at the time of drug administration	Type：	Secondary indicator
测量时间点：	给药时	测量方法：	评分表
Measure time point of outcome：	During Administration	Measure method：	Scoring Table

指标中文名：	检查开始时患儿改良Ramsay镇静评分	指标类型：	次要指标
Outcome：	Modified Ramsay sedation score at the beginning of examination	Type：	Secondary indicator
测量时间点：	检查开始时	测量方法：	评分表
Measure time point of outcome：	at the beginning of examination	Measure method：	Scoring Table

指标中文名：	服药到开始检查的时间（T1）	指标类型：	次要指标
Outcome：	Time from taking medicine to starting examination (T1)	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	是否发生补救镇静	指标类型：	次要指标
Outcome：	Whether remedial sedation has occurred	Type：	Secondary indicator
测量时间点：	分离时	测量方法：
Measure time point of outcome：	The Time Of Separation	Measure method：

指标中文名：	检查时间（T2）	指标类型：	次要指标
Outcome：	Inspection time (T2)	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	家长满意度	指标类型：	次要指标
Outcome：	Parent satisfaction	Type：	Secondary indicator
测量时间点：	检查完成后	测量方法：	评分表
Measure time point of outcome：	After the inspection is completed	Measure method：	Scoring Table

指标中文名：	镇静期及苏醒期不良反应	指标类型：	副作用指标
Outcome：	Adverse reactions during sedation and recovery	Type：	Adverse events
测量时间点：	镇静期及苏醒期	测量方法：
Measure time point of outcome：	Sedation and Recovery	Measure method：

指标中文名：	苏醒时间（T3，检查结束到患儿自主睁眼的时间）	指标类型：	次要指标
Outcome：	Awakening time (T3, the time from the end of the examination to the child's spontaneous opening of eyes)	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：	无	组织：
Sample Name：	none	Tissue：
人体标本去向	其它	说明
Fate of sample：	0thers	Note：

征募研究对象情况：

Recruiting status：

尚未开始

Not yet recruiting

年龄范围：

Participant age：

最小 Min age	1	岁 years
最大 Max age	6	岁 years

性别：

男女均可

Gender：

Both

随机方法（请说明由何人用什么方法产生随机序列）：

无

Randomization Procedure (please state who generates the random number sequence and by what method)：

None

是否公开试验完成后的统计结果:

Calculated Results after the Study Completed public access:

公开/Public

盲法：	每一例患儿接受术前镇静的药物由专人配制好交给实施麻醉操作的麻醉医生，实施麻醉的麻醉医生、患儿及家属均不清楚药物实际剂量。
Blinding：	The drugs for each child receiving preoperative sedation were prepared by a special person and handed over to the anesthesiologist who performed anesthesia. The anesthesiologist, the child and their families who performed anesthesia did not know the actual dosage of the drugs.
试验完成后的统计结果（上传文件）：	点击下载
Calculated Results after the Study Completed(upload file)：	download

是否共享原始数据： IPD sharing	是Yes
共享原始数据的方式（说明：请填入公开原始数据日期和方式，如采用网络平台，需填该网络平台名称和网址）：	resman
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	resman
数据采集和管理（说明：数据采集和管理由两部分组成，一为病例记录表(Case Record Form, CRF)，二为电子采集和管理系统(Electronic Data Capture, EDC)，如ResMan即为一种基于互联网的EDC：	resman
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	resman
数据与安全监察委员会： Data and Safety Monitoring Committee：	有/Yes
注册人： Name of Registration：	2024-09-27 15:25:35