吉林大学学报(医学版)  2018, Vol. 44 Issue (02): 388-393

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曹雪峰, 赵亮, 刘旭东, 李艳, 甄瑞鑫, 段凤梅, 刘玉伶
CAO Xuefeng, ZHAO Liang, LIU Xudong, LI Yan, ZHEN Ruixin, DUAN Fengmei, LIU Yuling
右美托咪定非静脉给药对下腹部及下肢手术患儿的镇静效果
Sedative effect of non-intravenous administration dexmedetomidine in pediatric patients underwent lower abdomen and limb surgery
吉林大学学报(医学版), 2018, 44(02): 388-393
Journal of Jilin University (Medicine Edition), 2018, 44(02): 388-393
10.13481/j.1671-587x.20180233

文章历史

收稿日期: 2017-08-03
右美托咪定非静脉给药对下腹部及下肢手术患儿的镇静效果
曹雪峰1 , 赵亮2 , 刘旭东3 , 李艳1 , 甄瑞鑫4 , 段凤梅1 , 刘玉伶1     
1. 承德医学院附属医院麻醉科, 河北 承德 067000;
2. 承德医学院药理教研室, 河北 承德 067000;
3. 河北省承德市中心医院麻醉科, 河北 承德 067000;
4. 承德医学院附属医院骨科, 河北 承德 067000
[摘要]: 目的: 探讨右美托咪定(DEX)非静脉给药在儿科下腹部及下肢手术中的应用,观察DEX在该类手术中的镇静效果。方法: 选择全身麻醉下行下腹部及下肢手术的患儿60例,随机分为罗骶组、DEX鼻组和DEX骶组,每组20例。DEX鼻组患儿于术前30min给予DEX 1μg·kg-1滴鼻,另2组患儿给予等容积生理盐水滴鼻。30min后不能顺利转入手术室及诱导时不能耐受面罩或七氟醚的患儿给予丙泊酚1mg·kg-1。罗骶组和DEX鼻组患儿行骶管阻滞注入0.25%罗哌卡因1mL·kg-1,DEX骶组患儿给予0.25%罗哌卡因1mL·kg-1+DEX 1μg·kg-1,药物总量20 mL。记录患儿的一般资料、离开父母时的镇静评分、诱导期面罩和七氟醚接受评分;记录患儿离开父母的满意度、面罩吸氧和七氟醚吸入的接受满意度;记录麻醉诱导时间、手术时间、拔喉罩时间和苏醒时间;记录苏醒期喉痉挛、苏醒延迟及苏醒躁动评分;记录麻醉恢复评分及丙泊酚的用量;记录术后4、8、12、16、20和24h时的镇静评分。结果: DEX鼻组患儿与父母分离时的镇静评分、面罩诱导和七氟醚接受评分、患儿家属分离满意度、面罩和七氟醚接受满意度均高于罗骶组和DEX骶组(P < 0.05),丙泊酚用量低于罗骶组和DEX骶组(P < 0.05)。3组患儿手术时间、拔喉罩时间和苏醒时间比较差异无统计学意义(P>0.05),DEX鼻组患儿诱导时间短于罗骶组和DEX骶组(P < 0.05)。3组患儿均无苏醒延迟发生,罗骶组患儿喉痉挛和躁动评分明显高于DEX鼻组和DEX骶组(P < 0.05)。3组患儿麻醉后意识、呼吸、活动评分和麻醉恢复评分比较差异无统计学意义(P>0.05)。3组患儿术后4 h时镇静评分均小于3分,DEX鼻组和DEX骶组8 h时的镇静评分明显低于罗骶组(P < 0.05),DEX骶组12、16和20h时的镇静评分明显低于罗骶组和DEX鼻组(P < 0.05),3组患儿术后24 h时镇静评分比较差异无统计学意义(P>0.05)。结论: DEX非静脉给药应用于儿科下腹部及下肢手术时患儿可以安静合作地进入手术室,快速平稳完成诱导过程,苏醒躁动发生概率明显降低,有早期术后镇静的作用。
关键词: 右美托咪定    滴鼻    骶管阻滞    镇静    
Sedative effect of non-intravenous administration dexmedetomidine in pediatric patients underwent lower abdomen and limb surgery
CAO Xuefeng1, ZHAO Liang2, LIU Xudong3, LI Yan1, ZHEN Ruixin4, DUAN Fengmei1, LIU Yuling1     
1. Department of Anesthesiology, Affiliated Hospital, Chengde Medical College, Chengde 067000, China;
2. Department of Pharmacology, Chengde Medical College, Chengde 067000, China;
3. Department of Anesthesiology, Central Hospital of Chengde, Hebei Province, Chengde 067000, China;
4. Department of Orthopaedics, Affiliated Hospital, Chengde Medical College, Chengde 067000, China
[Abstract]: Objective: To investigate the application of non-intravenous dexmedetomidine(DEX) in the pediatric patients underwent lower abdomen and limb surgery, and to observe the sedative effect of DEX in this procedure. Methods: Sixty patients undergoing the general anesthesia for lower abdomen and limb surgery were selected and randomly devided into ropivacaine sacral block (RS) group, intranasal DEX + ropivacaine sacral block (ID) group, ropivacaine + DEX sacral block (DS) group, 20 cases in each group. The children in ID group received intranasal DEX 1 μg·kg-1 30 min before operation and the children in RS and DS groups received physiological saline. 1 mL·kg-1 propofol was infused intravenously in the children who could not smoothly enter into the operating room as well as the intolerance to oxygen mask or sevoflurane inhalation while induction. The children in RS and ID groups received 0.25% ropivacaine 1 mL·kg-1, and the children in DS group received the same dose of ropivacaine mixed with 1 μg·kg-1 DEX, and the total volume of drugs was 20 mL. The general information of each child was recorded; the sedation status when separated from their parents and induction period mask and sevoflurane acceptance scores were assessed; the satisfaction of separation with parents, oxygen mask and sevoflurane inhalation were recorded; the time of operation, induction, extraction of laryngeal mask and anesthesia awake were recorded; delayed awakening, laryngismus and awakening period agitation score were recorded. The scores of anesthesia recovery and the dosage of propofol were recorded; the sedation scores 4, 8, 12, 16, 20, and 24 h after operation were recorded. Results: Compared with RS and DS groups, the sedation scores of the children when they were separated from their parents and mask induction and sevoflurane inhalation acceptance, the satisfaction degree of separation, mask and sevoflurane acceptance in ID group were increased(P < 0.05); the dosage of propofol in ID group were decreased(P < 0.05). The time of operation, extraction of laryngeal mask and anesthesia awake had no significant differences between three groups (P>0.05), the induction time of children in ID group was shorter than those in RS and DS groups(P < 0.05). There was no delayed awakening in three groups, and the laryngismus and the awakening period agitation score in RS group were higher than those in ID and DS groups (P < 0.05). There was no differences in the consciousness, respiration, activity scores and the scores of anethesia recovery between three groups(P>0.05). The sedation scores in the three groups were less than 3 points 4 h after operation. Compared with RS group, the sedation scores in ID and DS groups were decreased 8 h after operation (P < 0.05). Compared with RS and ID groups, the sedation scores in DS group 12, 16 and 20h after operation were decreased(P < 0.05). There were no significant differences in the sedation scores between three groups 24 h after operation (P>0.05). Conclusion: When non-intravenous DEX is used in the pediatric patients underwent lower abdomen and limb surgery, the children can quietly and co-operationly enter into the operating room and quickly and smoothly complete the induction process; the incidence of revival restlessness is significantly reduced, and it can play a role in the early postoperative sedation.
Key words: dexmedetomidine     intranasal     caudal block     sedation    

需要手术的患儿术前常伴有惊慌甚至哭闹,出现入室和静脉开放困难,一般均需要术前用药。目前常用的药物有丙泊酚、氯胺酮和咪达唑仑等。丙泊酚会引起呼吸抑制和较大的血流动力学波动,氯胺酮会引起苏醒期躁动,而咪达唑仑可出现嗜睡、苏醒延迟和头痛等症状[1-2]。右美托咪定(DEX)是一种强效、高选择性α2-肾上腺素受体激动剂,有镇痛、抗交感和镇静的作用,且对呼吸循环影响较小[3]。目前DEX在国内主要应用于成人全身麻醉手术的患者气管插管和机械通气时的镇静。国外关于DEX在儿科镇静方面的相关报道[4-6]较多。Choon等[7]发表了1篇在婴儿腹股沟疝修补术中应用DEX骶管麻醉镇静的初步研究。但在国内有关DEX在儿科麻醉中应用的研究较少,尤其在非静脉给药途径。本研究通过设计DEX滴鼻给药、DEX骶管阻滞以及第1次将2种给药途径联合比较,阐明DEX在儿科下腹部及下肢手术不同阶段中的镇静效果,以期为临床儿科麻醉提供更合理的术前用药、术后镇静药物及途径。

1 资料与方法 1.1 临床资料

本研究获得承德医学院附属医院伦理委员会批准,与患者家属签署麻醉知情同意书。入选标准:全身麻醉下行下腹部及下肢手术的患儿,年龄2~6岁,ASAⅠ级,心、肺、肝和肾功能未见明显异常,排除标准:近2周内发生呼吸道感染。采用随机数字表法将其分为罗骶(RS)组、DEX鼻(ID)组和DEX骶(DS)组。

1.2 麻醉方法

常规禁食禁饮,术前30min将患儿接入麻醉准备间,在父母的陪伴下实施滴鼻操作,DEX鼻组患儿给予1μg·kg-1DEX滴鼻,罗骶和DEX骶组患儿给予等容积生理盐水滴鼻,30min后转入手术室,入室后常规监测。麻醉诱导:建立外周静脉通路后,3组患儿面罩吸氧,氧流量2L·min-1,七氟醚6%~8%,静脉均给予阿托品0.01 mg·kg-1,利多卡因1 mg·kg-1,丙泊酚2 mg·kg-1,待睫毛反射消失置入喉罩后行机械通气。麻醉维持:七氟醚1%~2%,缝皮结束时停药。

1.3 监测指标

记录患儿姓名、性别、年龄、身高和体质量;记录手术时间、诱导时间、拔喉罩时间和苏醒时间(即手术结束到唤醒睁眼时间);记录患儿离开父母时的镇静情绪评分[8]:1分,哭闹,与父母分离时挣扎;2分,清醒,与父母分离时哭泣;3分,嗜睡,与父母分离时安静;4分,入睡。3和4分认为达到满意的镇静状态。记录诱导期面罩和七氟醚接受度:1分,恐惧、哭闹,具有攻击性;2分,中等恐惧,面罩或七氟醚不耐受;3分,安抚后可配合;4分,平静,配合或镇静;3和4分视为面罩/七氟醚接受满意[9]。记录丙泊酚用量。记录苏醒期躁动评分:1分为安静合作、无躁动;2分为焦虑、激动但可配合;3分为轻度躁动,需固定上肢;4分为严重躁动,需外力按压四肢。苏醒镇静评分:1分,对刺激较迟钝或无反应;2分,睡眠,对移动或刺激有反应;3分,清醒,可安慰;4分,无法安慰的哭闹;5分,行为激烈需要约束限制。记录麻醉后恢复评分,包括神志、呼吸和活动。神志:4分,完全清醒,睁眼交谈;3分,浅睡,有时睁眼;2分,呼吸时睁眼;1分,对夹耳有反应;0分,无反应。呼吸:3分,按指令张口,咳嗽;2分,无有意识咳嗽,能自己保持呼吸道通畅;1分,特定位置时可保持通畅;0分需用通气道。活动:2分,按指令抬上肢;1分,无意识活动;0分,无活动。记录术后4、8、12、16、20和24h的镇静评分。

1.4 统计学分析

采用SPSS 19.0统计软件进行统计学分析。各组患儿年龄、体质量指数(BMI)、镇静情绪评分、面罩和七氟醚接受度、手术时间、诱导时间、苏醒时间、拔喉罩时间、苏醒延迟、喉痉挛、躁动评分和镇静评分均符合正态分布,以x ± s表示,资料组间、组内比较采用重复测量设计的方差分析,各组患儿性别、与父母分离满意度、面罩和七氟醚接受满意度比较采用χ2检验。以P<0.05为差异有统计学意义。

2 结果 2.1 3组患儿一般情况

3组患儿性别、年龄和BMI比较差异无统计学意义(P>0.05)。见表 1

表 1 3组患儿一般情况 Table 1 General situation of patients in three groups
(n=20)
Group Gender (M/F) Age (year) BMI (kg·m-2)
RS 12/8 3.6±1.2 18.8±4.0
ID 11/9 3.5±1.3 19.0±4.7
DS 10/10 3.5±1.4 19.7±5.2
χ2 or F 0.404 0.030 0.217
P 0.820 0.970 0.810
2.2 全麻诱导前指标

DEX鼻组患儿与父母分离时镇静评分、面罩和七氟醚接受度、患儿家属分离满意度、面罩和七氟醚接受满意度均高于罗骶组和DEX骶组(P < 0.05)。DEX鼻组丙泊酚用量低于罗骶组和DEX骶组(P < 0.05)。见表 2

表 2 3组患儿全麻诱导前指标 Table 2 Indicators before general anesthesia induction of patients in three groups
(n=20, x ± s)
Group Separated satisfaction [n(%)] Mask acceptance satisfaction [n(%)] Sevoflurane acceptance satisfaction[n(%)] Dosage of propofol (m/mg) Sedation score Mask acceptance score Sevoflurane acceptance score
RS 0(0)* 7(35)* 7(35)* 33.3±5.7* 1.3±0.5* 2.2±0.6* 2.2±0.6*
ID 14(70) 20(100) 20(100) 11.1±3.8 3.1±0.8 3.2±0.5 3.3±0.5
DS 0(0)* 7(35)* 7(35)* 31.2±5.5* 1.4±0.5* 2.3±0.6* 2.3±0.6*
χ2 or F 22.941 36.522 36.522 11.529 47.841 7.579 7.579
P < 0.01 0.01 0.01 < 0.01 < 0.01 0.01 0.01
* P < 0.05 compared with ID group.
2.3 术中指标

3组患儿手术时间、拔喉罩时间和苏醒时间比较差异无统计学意义(P>0.05),DEX鼻组患儿诱导时间短于罗骶组和DEX骶组(P < 0.05)。见表 3

表 3 3组患儿术中指标 Table 3 Intraoperative indicators of patients in three groups
(n=20, x ± s)
Group Operation time (t/min) Induction time (t/min) Anesthesia awake time (t/min) Extraction of laryngeal mask time(t/min)
RS 64.8±4.0 2.8±0.5* 4.5±1.2 4.8±1.1
ID 65.5±2.7 1.3±0.4 5.0±1.4 5.3±1.4
DS 67.9±2.2 2.7±0.7* 4.9±1.2 5.0±0.9
F 0.171 45.257 0.704 0.854
P 0.70 < 0.01 0.40 0.10
* P < 0.05 compared with ID group.
2.4 3组患儿不良反应和躁动评分

3组患儿均无苏醒延迟的发生,罗骶组患儿喉痉挛的发生和躁动评分高于DEX鼻组和DEX骶组(P < 0.05)。见表 4

表 4 3组患儿不良反应和躁动评分 Table 4 Adverse reactions and sedation-agitation scores of patients in three groups
(n=20, x ± s)
Group Delayed awakening Laryngeal spasm Sedation-agitation score
RS 0 0.15±0.8 2.1±0.1
ID 0 0* 1.5±0.1*
DS 0 0* 1.1±0.1*
F 0 5.478 19.781
P - 0.03 0.02
* P < 0.05 compared with RS group. “-”:No data.
2.5 3组患儿麻醉恢复评分

3组患儿麻醉恢复评分比较差异无统计学意义(P>0.05),各组患儿意识、呼吸和活动评分比较差异无统计学意义(P>0.05)。见表 5

表 5 3组患儿麻醉恢复评分 Table 5 Scores of anesthesia recovery of patients in three groups
(n=20, x ± s)
Group Consciousnessscore Respiratory score Activity score Total score
RS 3.20±0.81 2.20±0.62 1.90±0.31 7.30±0.97
ID 3.10±0.79 2.10±0.64 1.90±0.37 7.10±1.37
DS 3.10±0.76 2.20±0.59 1.90±0.31 7.10±1.07
F 0.522 0.263 0.154 0.776
P 0.596 0.770 0.857 0.465
2.6 3组患儿各时间点镇静评分

3组患儿术后4 h镇静评分均小于3分,DEX鼻组和DEX骶组8 h镇静评分明显低于罗骶组(P < 0.05),DEX骶组12、16和20h镇静评分明显低于罗骶组和DEX鼻组(P < 0.05),术后24h 3组镇静评分比较差异无统计学意义(P>0.05)。见表 6

表 6 3组患儿各时间点镇静评分 Table 6 Sedation scores of patients in three groups at each time point
(n=20, x ± s)
Group Sedation score
(t/h) 4 8 12 16 20 24
RS 2.40±0.11 3.10±0.07 4.30±0.11 4.30±0.11 3.50±0.11 3.50±0.11
ID 2.00±0.00* 2.50±0.11* 4.30±0.14 4.20±0.18 3.70±0.13 3.70±0.12
DS 2.00±0.00* 2.20±0.09* 2.70±0.11 2.90±0.07 3.40±0.11 3.40±0.11
F 9.292 86.191 50.701 125.294 73.014 0.784
P 0.02 < 0.01 0.01 0.02 0.02 0.06
* P < 0.05 compared with RS group; P < 0.05 compared with DS group.
3 讨论

对陌生人、陌生环境的抵触、恐惧和哭闹是每一位患儿面临的问题,术前的禁食禁饮,会加重哭闹,这样患儿分泌物增多,增加喉痉挛发生的风险,增加了开通液路和入室的难度。术前使用丙泊酚和阿片类药,转运途中有呼吸抑制低氧血症发生的危险,因此如何使孩子安静、安全地转入手术室、平稳地诱导和苏醒及良好地术后镇静是一线医生非常关注的问题。

DEX通过激动α2肾上腺素能受体发挥作用,具有较强的镇静、镇痛和抗焦虑作用,且不抑制呼吸[8, 10]。由于DEX独特药理特点,临床应用日渐广泛,经静脉途径给药是目前常用方式,主要应用于手术麻醉和监护室镇静。近几年DEX非静脉给药渐渐出现,在儿科中复合骶管阻滞,以滴鼻的形式复合全麻应用于手术中,而且效果显著。DEX无色无味,无黏膜刺激,单位剂量内药物浓度高,更适合于滴鼻途径用药[11]。与静脉用药比较,非静脉途径用药起效缓慢但平稳,可安全应用于手术前。经鼻给药患儿易接受,滴入5~20 min起效,30 min可达到高峰,虽然慢于静脉注射,但镇静作用无明显减弱。Yuen等[12]研究发现:成人及2~12岁儿童中经鼻滴入DEX亦可产生明显镇静作用。本研究结果显示:术前30min DEX滴鼻使用,患儿易于接受,在转入手术室的过程中安静合作,镇静评分明显高于对照组,从而降低了呼吸抑制、低氧血症的发生风险,而且进入手术室后大部分患儿能耐受面罩吸氧和七氟醚的吸入,与对照组比较,患儿与父母分离满意度高,面罩吸氧、七氟醚吸入接受满意度均高于对照组,而且诱导迅速,缩短了诱导时间。全麻苏醒期躁动(EA)是麻醉苏醒期的行为异常,出现在麻醉后苏醒的早期阶段,主要表现为哭闹、兴奋、躁动和定向障碍。尤其在七氟烷吸入麻醉后发生率更高,虽然在镇静、镇痛药物的应用下这种兴奋性行为的发生有所减少,但仍无较好的预防及治疗方法。国外研究[13-16]显示:DEX由于其镇静、镇痛特点能够有效预防EA的发生。

儿科择期手术部位多集中在下腹部及下肢,恰恰是实施骶管麻醉的适应证,骶管阻滞相对安全,可以减少静脉和吸入全麻药的应用,降低术中对手术创伤的应激反应,有利于患儿平稳复苏,并且能提供早期的术后镇痛镇静。常用药物是左布比卡因和罗哌卡因,但单次骶管阻滞所提供的镇痛时间非常有限,即使使用长效局麻药,仍有超过60%的患儿需要进一步镇痛治疗[17],因此临床上常复合其他药物以延长镇痛时间。Kanazi等[18]研究发现:DEX在蛛网膜下腔混合局麻药使用中能明显延长阻滞和镇痛时间。而且该研究未发现DEX对脊髓神经有毒性作用。罗哌卡因属于长效酰胺类局麻药,其心血管和神经毒性更小,浓度适中时能产生运动神经与感觉神经阻滞的分离,罗哌卡因能够安全地用于区域阻滞麻醉和小儿椎管内镇痛镇静。所以本研究设计3组进行比较,目的是找到一种安全有效、既可以减轻患儿进入手术室的焦虑、减少苏醒期躁动的发生,又可以提供更好更持久的术后镇痛镇静的方法。

本研究中罗骶组患儿未给予DEX,与其他2组比较,喉痉挛的发生率明显增高,而DEX鼻组和DEX骶组以不同形式给予DEX降低了喉痉挛的发生,患儿苏醒特别平稳,苏醒期躁动评分明显降低,麻醉恢复评分与罗骶组比较,并无差异,且无苏醒延迟的发生,提示骶管和滴鼻给予DEX均能有效预防七氟烷麻醉后EA的发生,患儿术后较长一段时间均处于轻度睡眠的镇静状态,容易被唤醒。因患儿术后仍不能马上进食水,对于几乎无控制力的患儿而言睡眠状态远比苏醒状态舒适,而且便于术后生命体征的监测,同时减轻家长的心理负担。

骶管阻滞有明显的术后镇静作用,本研究中3组患儿均进行了骶管阻滞,而且均有术后镇静的作用,只是时间长短不一致。本研究结果显示:术后4 h内3组患儿镇静评分均小于3分,即镇静效果满意,无需追加镇静药物,即单纯的骶管阻滞术后4 h可以起到镇静作用,这与罗哌卡因作用于成人硬膜外的作用时间要明显延长,可能因为全麻药残余与罗哌卡因协同作用所致。DEX鼻组和DEX骶组8h的镇静评分明显低于罗骶组,说明术前30 min DEX滴鼻给药有延长骶管阻滞术后镇静的作用,这与国外Weldom等[19]的研究结果一致,即在小儿进行下腹部手术时将DEX 2 μg·kg-1混合0.25%布比卡因用于骶管麻醉及镇痛,发现DEX能明显延长镇痛镇静时间,且无心动过缓、低血压及呼吸抑制等不良反应。术后回访,8h内患儿处于睡眠状态,但是呼之能应,接近生理睡眠状态,而且无过度镇静的现象。DEX骶组患儿12、16和20 h的镇静评分明显低于罗骶组和DEX鼻组。术后24 h 3组患儿镇静评分差异无统计学意义,评分均比较低,可能术后24 h已经过了早期最疼痛的时期。由此可见,罗哌卡因复合1 μg·kg-1DEX进行骶管阻滞镇痛镇静时间最长,效果最满意的。这样不再需要追加其他镇痛镇静药物,也不担心呼吸抑制的发生,是一种安全舒适的镇静方式。

综上所述,DEX滴鼻给药能使患儿安全合作地转入手术室,与父母分离及诱导满意度高,而且诱导时间明显缩短,麻醉药丙泊酚的用量减少。DEX术前滴鼻或复合罗哌卡因骶管阻滞均能减轻术后EA的发生,麻醉恢复好,安全有效,明显延长了术后镇静效果,是一种理想的选择。

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