谵妄是一种急性、波动性的大脑机能障碍的状态,其特征是意识改变,注意力集中、维持或转移能力降低,可导致认知或感知障碍,幻觉的出现以及睡眠-觉醒障碍,无法用预先存在、已发生或发展中的疾病更好地解释[1,2,3]。谵妄可能发生在各个年龄段,在遗传和生理角度认为,老年个体相较于年轻个体,更容易发生谵妄,婴幼儿期和儿童期个体相较于成年早、中期个体,对于谵妄的易感性更高[4]。 成人谵妄的研究已经相对成熟,危险因素明确[5,6,7,8],成人ICU意识模糊评估工具(the Confusion Assessment Method for the Intensive Care Unit,CAM-ICU)被广泛认可并用于临床[9,10,11,12],甚至针对癌症、ICU等亚科领域分别具有指导指南[13,14,15,16],然而儿科领域公认的指南较少。由于在精神障碍诊断与统计手册(Diagnostic and Statistical Manual of Mental disorders,DSM)和国际疾病分类标准(International Classification of Diseases,ICD)中谵妄的诊断标准并无不同年龄段的差别,同时随着儿科领域越来越多临床研究的报道,基于以上研究及证据,能够使我们对于儿童谵妄的防治有更进一步的了解。 1 儿童谵妄流行病学 儿童谵妄,尤其是PICU谵妄具有较高的发生率,从已发表的文献中可以得知,儿童谵妄的发生率波动在4%~57%[17,18,19,20,21,22,23,24]。这是因为不同研究中涉及的目标人群疾病类型、年龄段、诊断评估的工具和流程规范不尽相同。已报道的儿童谵妄发生率最高为57%[24],研究人群为儿童心脏重症监护室(pediatric cardiac intensive care unit,PCICU)内患儿。在一项25家多中心大样本的临床研究中,曾报道儿童谵妄发生率为25%[25],我国首个儿童谵妄临床研究结果显示发生率为24.4%[26]。目前认为儿童谵妄具有3种临床亚型,分别是躁动型谵妄、安静型谵妄以及混合型谵妄。躁动型谵妄多表现为躁动、烦躁、高度警惕和易激惹的状态,相反,安静型谵妄则表现为嗜睡、注意力不集中和反应迟缓。混合型表现则波动于两者之间[27]。其中安静型谵妄容易被误诊为镇静过度从而被忽视,有文献报道此型谵妄可能预示较差的临床结局[28]。然而在许多情况下,儿童谵妄的发生常被延迟发现甚至未被临床医护人员关注。 2 儿童谵妄危险因素 儿童谵妄的发生受多种因素影响,具体的发生机制尚不明确,但从成人研究的报道可以了解到,谵妄的发生可能与脑失衡导致多巴胺能相对过剩和胆碱能递质的缺乏有关,或是皮质醇异常、应激反应、炎症以及大脑氧化代谢的紊乱相关[29,30]。儿童谵妄已知危险因素包括儿童入院前基线水平:男童,年龄较小,存在认知功能障碍、原发疾病为急性、感染性疾病或者初步诊断为癫痫持续状态,术后;入院后水平:机械通气,器官损害的严重程度,约束的天数,抗胆碱能药物、苯二氮类药物(中高度剂量)的使用[3,24,31,32,33,34,35],其中有文献报道苯二氮卓类药物的使用随着剂量的增加,谵妄发生的机率和天数增加[33]。有研究报道指出急性肾损伤是成人ICU谵妄发生的危险因素,可能的机制与药物代谢障碍、神经毒素清除以及全身炎症有关[36]。儿童临床研究人群为心脏术后的患儿谵妄的发生率高于其他类型疾病[24],可能由于体外循环引起全身内皮激活以及炎症反应,无搏动性给氧,容易发生血栓,可能导致脑损伤和炎症的发生[37,38],这些临床暴露的因素,需要在未来儿童谵妄的研究中进一步讨论。 3 诊断与评估 儿童谵妄是由儿科精神科医生进行诊断,金标准即为精神障碍诊断与统计手册(DSM),目前更新至第五版[27]。PICU医生多通过咨询儿科精神科医生以及临床经验进行鉴别,因此极少医生会对谵妄进行诊断,儿童谵妄症状的多变以及临床沟通的障碍更容易使其被误诊和漏诊。随着儿科临床医生意识到成人ICU中谵妄带来的重大影响,改变谵妄识别的策略被提出,逐渐有儿童谵妄的床旁评估工具出现[39],由于儿童生长发育的特殊性,目前存在多种床旁评估工具[40,41,42,43,44,45]。 儿童麻醉苏醒期谵妄量表(the Pediatric Anesthesia Emergence Delirium Scale,PAED)最早是由Sikich和Lerman[40]于2004年提出,用于评价儿童麻醉后是否发生苏醒期谵妄研制的一种行为观察量表,共分为5个条目,每个条目分0~4分五个级别,得分一旦不小于8分,便可怀疑为儿童谵妄,适用于19个月至6岁间的术后苏醒期的儿童。儿科ICU谵妄诊断的意识状态评估法(the Pediatric-Confusion Assessment Method for the Intensive Care Unit,pCAM-ICU)最早由Smith等[41]于2011年提出使用,是由成人ICU谵妄评估量表CAM-ICU根据儿科患者特点改进而来,共分为4个条目,条目1和2再加上条目3或4显示为阳性结果,便可诊断儿童谵妄,要求评估人员接受一定的精神科专业知识的培训且仅适用于5岁以上儿童(不包括本身患有发育或精神方面疾病儿童),需要儿童的配合。康奈尔儿童谵妄评估量表(the Cornell Assessment of Pediatric Delirium scale,CAPD)是由Sliver等[42]于2012年在PAED的基础上进行一定程度的修改而制定的量表,增加了对患儿活动度和反应性评估条目,可以对谵妄的不同亚型进行辨别,每个条目仍为0~4分,五个级别,当得分为7~9分时就要注意潜在的谵妄并且进行复评;当得分不小于10分时,则可判定为发生谵妄。学龄前儿童ICU谵妄诊断的意识状态评估法(the PreSchool Confusion Assessment Method for the ICU,psCAM-ICU)是基于CAM-ICU和pCAM-ICU的基础上改进而来的[43],适用年龄≤5岁。索菲亚儿童戒断-谵妄观察量表(the Sophia Observation withdrawal Symptoms-Paediatric Delirium,SOS-PD)是由Ista等[44]及其团队于2016年在索菲亚儿童戒断症状观察表(the Sophia Observation withdrawal Symptoms,SOS)的基础上增加了对儿童谵妄观察条目,以便能早期筛查谵妄和(或)戒断症状,共有22个行为观察条目,17个条目与儿童谵妄症状有关,其中有10个条目与SOS量表相同,观察到发生即进行勾选,附加条目为是否父母主观认为患儿的认知和行为明显不同于患病前或入院前,当附加条目选项为'是'和(或)儿童谵妄观察条目得分≥4分或患儿出现幻觉即认定发生谵妄。 欧洲儿科和新生儿重症监护学会在2016年发布了共识指南,推荐使用CAPD量表作为儿科谵妄的评估工具[2],汉化版CAPD量表[26]具有较好的临床信效度,于2019年授权发表。 4 预防及治疗 目前没有任何干预措施或一组干预措施被大样本证明能够有效地预防和(或)治疗儿童谵妄[46,47]。现有方案多是基于专家共识,观察性研究和少量的临床对照试验。 4.1 药物预防及治疗 抗精神病药物在部分成人及儿童病例的回顾性文献中提及有效,能够缓解谵妄的症状[48,49,50],但该类药物说明中不包括用于儿童谵妄的治疗,不良反应可能延长QTc和增加锥体外系运动障碍的风险[51]。在成人ICU谵妄患者中,不具有治疗作用[52]。2018年JAMA杂志报道了预防性应用氟哌啶醇对重症患者死亡风险的影响,该随机对照的临床研究纳入了荷兰21家ICU的患者,将入住ICU≥24 h尚无谵妄的重症患者,分为3组(氟哌啶醇1 mg组、氟哌啶醇2 mg组以及安慰剂组)接受氟哌啶醇预防性治疗,每天3次,最终结果认为预防性应用氟哌啶醇无法改善谵妄高风险患者的生存时间、谵妄发生率以及次要结局指标,不具有临床优势[53]。 右美托咪啶对谵妄的治疗和预防,系统评价报道具有一定的效果[54,55,56]。Skrobik等[57]进行的一项成人随机双盲安慰剂对照试验,通过夜间给予静脉泵入0.2 mg/(kg·h)右美托咪定,结果显示ICU重症患者夜间小剂量应用右美托咪定能够预防患者谵妄的发生。 褪黑素是由松果体产生的,具有调节昼夜节律,以及作为抗氧化剂和抗炎剂的作用[58,59]。有一项成人研究直接评估了褪黑素激动剂对谵妄的影响,在这项研究中,谵妄的发生率明显降低[60]。Nishikimi等[61]进行的一项单中心随机三盲对照试验,结果显示雷美替胺(褪黑素)可以缩短住ICU的时间,同时减少重症患者谵妄发生率和缩短谵妄时间,与未接受干预或配备耳塞和眼罩的患者相比,给予褪黑素的受试者有更长的总睡眠时间,增加快速动眼期,更短的睡眠起始潜伏期,以及主观上更好的睡眠。 昂丹司琼(Ondansetron),一种止吐剂,在儿童谵妄研究中发现能够降低儿童谵妄的发生率[24],与成人术后患者中服用该药能够有效地减轻谵妄症状的效果一致[62,63]。 4.2 非药物预防及治疗 通过对可改变的危险因素以及非药物性干预的管理,能够降低谵妄的发生率[46,47]。推荐患儿入PICU后,以非药物预防为中心,旨在优化PICU环境,维持生理睡眠-觉醒周期,进行疼痛的管理,尽可能家庭人员参与其中。 在PICU内许多因素可能导致睡眠障碍[66],夜间明亮的灯光和较高的噪音水平,都可能导致ICU患儿出现睡眠紊乱,从而诱发或加剧谵妄的发生[67]。减少夜间的光线、噪音干扰,确保夜间关灯、白天亮灯(尽可能多的暴露在日光下),使用眼罩、耳塞[68,69]能够促进正常的昼夜节律;在病床放置患儿喜欢的毛绒玩具或毯子等,使其不感到陌生、恐惧等消极情绪[70],集中护理操作时间,尽可能减少身体约束。 早期舒适镇痛,最小化镇静[71],镇静先镇痛,最大限度地减少镇静药物的使用,允许患儿更好地表达疼痛,从而优化疼痛的控制,减少镇静相关的医源性谵妄的出现[72]。家庭成员的参与能够减少患儿和家长的焦虑,提高家属的满意度[73]。 成人ICU谵妄的临床实践模型中相对成熟的有早期镇痛,最小化镇静以及最大人文关怀以保证患者舒适度[74](early comfort using analgesia,minimal sedatives and maximal humanecare,eCASH)模式以及ABCDEF集束化策略[75](Assessing Pain,Both Spontaneous Awaken-ing and Breathing Trials,Choice of Drugs,Delirium Monitoring/Management,Early Exercise/Mobility,and Family Empowerment bundle)。ABCDEF集束化策略中每个元素都是基于单独应用时能够保证患者安全,以患者为中心,在成人研究领域,ABCDEF集束化策略在呼吸机天数、ICU住院时间、住院时间、非谵妄天数和住院病死率在内的几个领域都取得了较好的结果[76],随着时间的进展,谵妄的发生率也逐渐减少[77],但其实际应用率很低,在一项涉及47个国家的全球调查中,只有57%的人实施了ABCDEF集束化策略[78]。一项在梅奥医学儿科ICU网站上的报告显示,集束化策略用于儿科患者时,在减少机械通气时间、ICU住院日以及功能状态量表评分中均有改善[79]。一些指南确定了ICU中以家庭为中心的护理最佳实践的证据基础,但其中推荐意见证据不够充分[80]。 5 小结 谵妄的发生对于患儿自主神经系统、内分泌系统的稳定甚至原发疾病的恢复都是不利的,其他可能导致的不良事件包括非计划拔管、坠床的危险、住院时间延长、提高院内6个月病死率以及过多的医疗费用[3,24,35,51,81,82]。有研究报道谵妄可导致成人患者伴随长期的神经认知损害[35],这种危害在儿童中尤其令人担忧,对于儿童来讲,他们不仅需要康复,还需要成长和发育[83]。 儿童谵妄最佳的防治手段则是早发现,早预防,避免可改变的危险因素。儿科ICU患儿进行普遍筛查对于早期发现谵妄是可行且必要的,这种筛查能够针对性地识别高风险人群,从而进行非药物性干预,干预手段可以借鉴成人ABCDEF集束化临床策略,但干预措施的安全性需要在儿科人群中应用并得到验证。发病早、恢复快的儿童,极有可能与镇静药物诱导的谵妄有关,值得注意的是,有一部分(31%)儿童有持续性谵妄的存在,其中可能有45%的谵妄患儿在神志不清的状态下被转出儿童心胸外监护室[24],这一研究结果提示从ICU转出甚至出院回家的患儿需要进一步关注,以确定儿童谵妄的持续时间、解决时机以及长期影响。 儿科ICU医护人员对于儿童谵妄的有效识别是采取预防措施的基本前提,在儿科ICU安全有效能够减少谵妄发生的临床实践策略仍需进一步研究和探索,有必要进行进一步的研究以确定谵妄对儿童长期认知和心理的影响,进行干预性研究,从而建立儿童谵妄预防与治疗的最佳实践。 利益冲突 利益冲突 所有作者均声明不存在利益冲突 参考文献 [1] Van TuijlSG,Van CauterenYJ,PikhardT,et al.Management of pediatric delirium in critical illness:a practical update[J].Minerva Anestesiol,2015,81(3):333-341. [2] HarrisJ,RameletAS,van DijkM,et al.Clinical recommendations for pain,sedation,withdrawal and delirium assessment in critically ill infants and children:an ESPNIC position statement for healthcare professionals[J].Intensive Care Med,2016,42(6):972-986.DOI:10.1007/s00134-016-4344-1. [3] DervanLA,Di GennaroJL,FarrisRWD,et al.Delirium in a Tertiary PICU:Risk Factors and Outcomes[J].Pediatr Crit Care Med,2020,21(1):21-32.DOI:10.1097/PCC.0000000000002126. [4] JukićV,ArbanasG.Diagnostic and Statistical Manual of Mental Disorders:Fifth Edition(DSM-5)[J].Disabil Soc,2013,57(12):1546-1548. [5] van den BoogaardM,PickkersP,SlooterAJ,et al.Development and validation of PRE-DELIRIC(PREdiction of DELIRium in ICu patients) delirium prediction model for intensive care patients:observational multicentre study[J].BMJ,2012,344:e420.DOI:10.1136/bmj.e420. [6] WassenaarA,van den BoogaardM,van AchterbergT,et al.Multinational development and validation of an early prediction model for delirium in ICU patients[J].Intensive Care Med,2015,41(6):1048-1056.DOI:10.1007/s00134-015-3777-2. [7] 吴传芹,朱艳萍,李国宏.ICU患者谵妄的发生率及危险因素分析[J].第三军医大学学报,2018,40(11):1038-1043.DOI:10.16016/j.1000-5404.201801018. [8] WangJ,JiY,WangN,et al.Risk factors for the incidence of delirium in cerebrovascular patients in a Neurosurgery Intensive Care Unit:A prospective study[J].J Clin Nurs,2018,27(1-2):407-415.DOI:10.1111/jocn.13943. [9] ElyEW,InouyeSK,BernardGR,et al.Delirium in mechanically ventilated patients:validity and reliability of the confusion assessment method for the intensive care unit(CAM-ICU)[J].JAMA,2001,286(21):2703-2710.DOI:10.1001/jama.286.21.2703. [10] 王春立.ICU意识模糊评估法(CAM-ICU)评估ICU谵妄的评价研究[D].北京:首都医科大学,2010. [11] TobarE,RomeroC,GalleguillosT,et al.Confusion Assessment Method for diagnosing delirium in ICU patients(CAM-ICU):cultural adaptation and validation of the Spanish version[J].Med Intensiva,2010,34(1):4-13.DOI:10.1016/j.medin.2009.04.003. [12] ChanquesG,GarnierO,CarrJ,et al.The CAM-ICU has now a French 'official' version.The translation process of the 2014 updated Complete Training Manual of the Confusion Assessment Method for the Intensive Care Unit in French(CAM-ICU.fr)[J].Anaesth Crit Care Pain Med,2017,36(5):297-300.DOI:10.1016/j.accpm.2017.02.003. [13] BushSH,LawlorPG,RyanK,et al.Delirium in adult cancer patients:ESMO Clinical Practice Guidelines[J].Ann Oncol,2018,29(Suppl 4):iv143-165.DOI:10.1093/annonc/mdy147. [14] DevlinJW,SkrobikY,GélinasC,et al.Clinical Practice Guidelines for the Prevention and Management of Pain,Agitation/Sedation,Delirium,Immobility,and Sleep Disruption in Adult Patients in the ICU[J].Crit Care Med,2018,46(9):e825-873.DOI:10.1097/CCM.0000000000003299. [15] TsurutaR,FujitaM.Comparison of clinical practice guidelines for the management of pain,agitation,and delirium in critically ill adult patients[J].Acute Med Surg,2018,5(3):207-212.DOI:10.1002/ams2.337. [16] GroverS,AvasthiA.Clinical Practice Guidelines for Management of Delirium in Elderly[J].Indian J Psychiatry,2018,60(Suppl 3):S329-S340.DOI:10.4103/0019-5545.196977. [17] JanssenNJ,TanEY,StaalM,et al.On the utility of diagnostic instruments for pediatric delirium in critical illness:an evaluation of the Pediatric Anesthesia Emergence Delirium Scale,the Delirium Rating Scale 88,and the Delirium Rating Scale-Revised R-98[J].Intensive Care Med,2011,37(8):1331-1337.DOI:10.1007/s00134-011-2244-y. [18] PatelAK,BiagasKV,ClarkeEC,et al.Delirium in Children After Cardiac Bypass Surgery[J].Pediatr Crit Care Med,2017,18(2):165-171.DOI:10.1097/PCC.0000000000001032. [19] SmithHA,BoydJ,FuchsDC,et al.Diagnosing delirium in critically ill children:Validity and reliability of the Pediatric Confusion Assessment Method for the Intensive Care Unit[J].Crit Care Med,2011,39(1):150-157.DOI:10.1097/CCM.0b013e3181feb489. [20] DaoudA,DuffJP,JoffeAR.Diagnostic accuracy of delirium diagnosis in pediatric intensive care:a systematic review[J].Crit Care,2014,18(5):489.DOI:10.1186/s13054-014-0489-x. [21] TraubeC,SilverG,KearneyJ,et al.Cornell Assessment of Pediatric Delirium:a valid,rapid,observational tool for screening delirium in the PICU[J].Crit Care Med,2014,42(3):656-663.DOI:10.1097/CCM.0b013e3182a66b76. [22] LarsenGY,DonaldsonAE,ParkerHB,et al.Preventable harm occurring to critically ill children[J].Pediatr Crit Care Med,2007,8(4):331-336.DOI:10.1097/01.PCC.0000263042.73539.99. [23] SchieveldJN,LeroyPL,van OsJ,et al.Pediatric delirium in critical illness:phenomenology,clinical correlates and treatment response in 40 cases in the pediatric intensive care unit[J].Intensive Care Med,2007,33(6):1033-1040.DOI:10.1007/s00134-007-0637-8. [24] AlvarezRV,PalmerC,CzajaAS,et al.Delirium is a Common and Early Finding in Patients in the Pediatric Cardiac Intensive Care Unit[J].J Pediatr,2018,195:206-212.DOI:10.1016/j.jpeds.2017.11.064. [25] TraubeC,SilverG,ReederRW,et al.Delirium in Critically Ill Children:An International Point Prevalence Study[J].Crit Care Med,2017,45(4):584-590.DOI:10.1097/CCM.0000000000002250. [26] 何珊,王亚力,左泽兰.中文版康奈尔儿童谵妄量表的临床初步应用[J].中华儿科杂志,2019,57(5):344-349.DOI:10.3760/cma.j.issn.0578-1310.2019.05.006. [27] Diagnostic and statistical manual of mental disorders:DSM-V[M].5th edition.Washington,DC:American Psychiatric Association:Task Force on DSM-V,2013. [28] PeritogiannisV,BolosiM,LixouriotisC,et al.Recent Insights on Prevalence and Corelations of Hypoactive Delirium[J].Behav Neurol,2015,2015:416792.DOI:10.1155/2015/416792. [29] LawlorPG,BushSH.Delirium in patients with cancer:assessment,impact,mechanisms and management[J].Nat Rev Clin Oncol,2015,12(2):77-92.DOI:10.1038/nrclinonc.2014.147. [30] MaldonadoJR.Neuropathogenesis of delirium:review of current etiologic theories and common pathways[J].Am J Geriatr Psychiatry,2013,21(12):1190-1222.DOI:10.1016/j.jagp.2013.09.005. [31] TraubeC,AriagnoS,ThauF,et al.Delirium in Hospitalized Children with Cancer:Incidence and Associated Risk Factors[J].J Pediatr,2017,191:212-217.DOI:10.1016/j.jpeds.2017.08.038. [32] HollyC,PorterS,EchevarriaM,et al.CE:Original Research:Recognizing Delirium in Hospitalized Children:A Systematic Review of the Evidence on Risk Factors and Characteristics[J].Am J Nurs,2018,118(4):24-36.DOI:10.1097/01.NAJ.0000532069.55339.f9. [33] ModyK,KaurS,MauerEA,et al.Benzodiazepines and Development of Delirium in Critically Ill Children:Estimating the Causal Effect[J].Crit Care Med,2018,46(9):1486-1491.DOI:10.1097/CCM.0000000000003194. [34] TraubeC,SilverG,GerberLM,et al.Delirium and Mortality in Critically Ill Children:Epidemiology and Outcomes of Pediatric Delirium[J].Crit Care Med,2017,45(5):891-898.DOI:10.1097/CCM.0000000000002324. [35] SalluhJI,WangH,SchneiderEB.Outcome of delirium in critically ill patients:systematic review and meta-analysis[J].BMJ,2015,350:h2538.DOI:10.1136/bmj.h2538. [36] SiewED,FissellWH,TrippCM,et al.Acute Kidney Injury as a Risk Factor for Delirium and Coma during Critical Illness[J].Am J Respir Crit Care Med,2017,195(12):1597-1607.DOI:10.1164/rccm.201603-0476OC. [37] WhitingD,YukiK,DiNardoJA.Cardiopulmonary bypass in the pediatric population[J].Best Pract Res Clin Anaesthesiol,2015,29(2):241-256.DOI:10.1016/j.bpa.2015.03.006. [38] LeroyPL,SchieveldJN.Mind the Heart:Delirium in Children Following Cardiac Surgery for Congenital Heart Disease[J].Pediatr Crit Care Med,2017,18(2):196-198.DOI:10.1097/PCC.0000000000001038. [39] SchieveldJN,JanssenNJ.Delirium in the pediatric patient:On the growing awareness of its clinical interdisciplinary importance[J].JAMA Pediatr,2014,168(7):595-596.DOI:10.1001/jamapediatrics.2014.125. [40] SikichN,LermanJ.Development and psychometric evaluation of the pediatric anesthesia emergence delirium scale[J].Anesthesiology,2004,100(5):1138-1145.DOI:10.1097/00000542-200405000-00015. [41] SmithHA,BoydJ,FuchsDC,et al.Diagnosing delirium in critically ill children:Validity and reliability of the Pediatric Confusion Assessment Method for the Intensive Care Unit[J].Crit Care Med,2011,39(1):150-157.DOI:10.1097/CCM.0b013e3181feb489. [42] SilverG,TraubeC,KearneyJ,et al.Detecting pediatric delirium:development of a rapid observational assessment tool[J].Intensive Care Med,2012,38(6):1025-1031.DOI:10.1007/s00134-012-2518-z. [43] SmithHA,GangopadhyayM,GobenCM,et al.The Preschool Confusion Assessment Method for the ICU:Valid and Reliable Delirium Monitoring for Critically Ill Infants and Children[J].Crit Care Med,2016,44(3):592-600.DOI:10.1097/CCM.0000000000001428. [44] IstaE,TeBH,van RosmalenJ,et al.Sophia Observation withdrawal Symptoms-Paediatric Delirium scale:A tool for early screening of delirium in the PICU[J].Aust Crit Care,2018,31(5):266-273.DOI:10.1016/j.aucc.2017.07.006. [45] GangopadhyayM,SmithH,PaoM,et al.Development of the Vanderbilt Assessment for Delirium in Infants and Children to Standardize Pediatric Delirium Assessment By Psychiatrists[J].Psychosomatics,2017,58(4):355-363.DOI:10.1016/j.psym.2017.03.006. [46] HshiehTT,YueJ,OhE,et al.Effectiveness of multicomponent nonpharmacological delirium interventions:a meta-analysis[J].JAMA Intern Med,2015,175(4):512-520.DOI:10.1001/jamainternmed.2014.7779. [47] González-GilT.Interventions for preventing delirium in older people in institutional long-term care[J].Int J Nurs Stud,2016,55:133-134.DOI:10.1016/j.ijnurstu.2015.12.009. [48] SilverGH,KearneyJA,KutkoMC,et al.Infant delirium in pediatric critical care settings[J].Am J Psychiatry,2010,167(10):1172-1177.DOI:10.1176/appi.ajp.2010.09111606. [49] TurkelSB,HanftA.The pharmacologic management of delirium in children and adolescents[J].Paediatr Drugs,2014,16(4):267-274.DOI:10.1007/s40272-014-0078-0. [50] TurkelSB,JacobsonJ,MunzigE,et al.Atypical antipsychotic medications to control symptoms of delirium in children and adolescents[J].J Child Adolesc Psychopharmacol,2012,22(2):126-130.DOI:10.1089/cap.2011.0084. [51] TurkelSB,JacobsonJR,TavaréCJ.The diagnosis and management of delirium in infancy[J].J Child Adolesc Psychopharmacol,2013,23(5):352-356.DOI:10.1089/cap.2013.0001. [52] GirardTD,ExlineMC,CarsonSS,et al.Haloperidol and Ziprasidone for Treatment of Delirium in Critical Illness[J].N Engl J Med,2018,379(26):2506-2516.DOI:10.1056/NEJMoa1808217. [53] van den BoogaardM,SlooterAJC,BrüggemannRJM,et al.Effect of Haloperidol on Survival Among Critically Ill Adults With a High Risk of Delirium:The REDUCE Randomized Clinical Trial[J].JAMA,2018,319(7):680-690.DOI:10.1001/jama.2018.0160. [54] RikerRR,ShehabiY,BokeschPM,et al.Dexmedetomidine vs midazolam for sedation of critically ill patients:a randomized trial[J].JAMA,2009,301(5):489-499.DOI:10.1001/jama.2009.56. [55] FanH,ZhaoY,SunM,et al.Dexmedetomidine Based Sedation for Post-surgery Critically Ill Adults:A Meta-analysis of Randomized Controlled Trials[J].Iran J Public Health,2017,46(12):1611-1622. [56] KangX,TangX,YuY,et al.Intraoperative dexmedetomidine infusion is associated with reduced emergence agitation and improved recovery profiles after lung surgery:a retrospective cohort study[J].Drug Des Devel Ther,2019,13:871-879.DOI:10.2147/DDDT.S195221. [57] SkrobikY,DupreyMS,HillNS,et al.Low-Dose Nocturnal Dexmedetomidine Prevents ICU Delirium.A Randomized,Placebo-controlled Trial[J].Am J Respir Crit Care Med,2018,197(9):1147-1156.DOI:10.1164/rccm.201710-1995OC. [58] MarsegliaL,D′AngeloG,MantiS,et al.Analgesic,anxiolytic and anaesthetic effects of melatonin:new potential uses in pediatrics[J].Int J Mol Sci,2015,16(1):1209-1220.DOI:10.3390/ijms16011209. [59] MoY,ScheerCE,AbdallahGT.Emerging Role of Melatonin and Melatonin Receptor Agonists in Sleep and Delirium in Intensive Care Unit Patients[J].J Intensive Care Med,2016,31(7):451-455.DOI:10.1177/0885066615592348. [60] HattaK,KishiY,WadaK,et al.Preventive effects of ramelteon on delirium:a randomized placebo-controlled trial[J].JAMA Psychiatry,2014,71(4):397-403.DOI:10.1001/jamapsychiatry.2013.3320. [61] NishikimiM,NumaguchiA,TakahashiK,et al.Effect of Administration of Ramelteon,a Melatonin Receptor Agonist,on the Duration of Stay in the ICU:A Single-Center Randomized Placebo-Controlled Trial[J].Crit Care Med,2018,46(7):1099-1105.DOI:10.1097/CCM.0000000000003132. [62] PapadopoulosG,PouangareM,PapathanakosG,et al.The effect of ondansetron on postoperative delirium and cognitive function in aged orthopedic patients[J].Minerva Anestesiol,2014,80(4):444-451. [63] TagarakisGI,VoucharasC,TsolakiF,et al.Ondasetron versus haloperidol for the treatment of postcardiotomy delirium:a prospective,randomized,double-blinded study[J].J Cardiothorac Surg,2012,7:25.DOI:10.1186/1749-8090-7-25. [64] MuJL,LeeA,JoyntGM.Pharmacologic agents for the prevention and treatment of delirium in patients undergoing cardiac surgery:systematic review and metaanalysis[J].Crit Care Med,2015,43(1):194-204.DOI:10.1097/CCM.0000000000000673. [65] InouyeSK,WestendorpRG,SaczynskiJS.Delirium in elderly people[J].Lancet,2014,383(9920):911-922.DOI: 10.1016/S0140-6736(13)60688-1. [66] EngwallM,FridhI,JohanssonL,et al.Lighting,sleep and circadian rhythm:An intervention study in the intensive care unit[J].Intensive Crit Care Nurs,2015,31(6):325-335.DOI:10.1016/j.iccn.2015.07.001. [67] TrompeoAC,VidiY,LocaneMD,et al.Sleep disturbances in the critically ill patients:Role of delirium and sedative agents[J].Minerva Anestesiol,2011,77(6):604-612. [68] HuRF,JiangXY,ZengYM,et al.Effects of earplugs and eye masks on nocturnal sleep,melatonin and cortisol in a simulated intensive care unit environment[J].Crit Care,2010,14(2):R66.DOI:10.1186/cc8965. [69] AlwayA,HalmMA,ShilhanekM,et al.Do earplugs and eye masks affect sleep and delirium outcomes in the critically ill?[J].Am J Crit Care,2013,22(4):357-360.DOI:10.4037/ajcc2013545. [70] KudchadkarSR,YasterM,PunjabiNM.Sedation,sleep promotion,and delirium screening practices in the care of mechanically ventilated children:a wake-up call for the pediatric critical care community[J].Crit Care Med,2014,42(7):1592-1600.DOI:10.1097/CCM.0000000000000326. [71] 中华医学会儿科学分会急救学组,中华医学会急诊医学分会儿科学组,中国医师协会儿童重症医师分会.中国儿童重症监护病房镇痛和镇静治疗专家共识(2018版)[J].中华儿科杂志,2019,57(5):324-330.DOI:10.3760/cma.j.issn.0578-1310.2019.05.002. [72] BarnesSS,KudchadkarSR.Sedative choice and ventilator-associated patient outcomes:don′t sleep on delirium[J].Ann Transl Med,2016,4(2):34.DOI:10.3978/j.issn.2305-5839.2015.12.40. [73] SilverG,TraubeC.A systematic approach to family engagement:Feasibility pilot of a pediatric delirium management and prevention toolkit[J].Palliat Support Care,2019,17(1):42-45.DOI:10.1017/S1478951518000895. [74] VincentJL,ShehabiY,WalshTS,et al.Comfort and patient-centred care without excessive sedation:the eCASH concept[J].Intensive Care Med,2016,42(6):962-971.DOI:10.1007/s00134-016-4297-4. [75] DavidsonJE,WinkelmanC,GélinasC,et al.Pain,agitation,and delirium guidelines:nurses′ involvement in development and implementation[J].Crit Care Nurse,2015,35(3):17-31; quiz 32.DOI:10.4037/ccn2015824. [76] MorandiA,PivaS,ElyEW,et al.Worldwide Survey of the 'Assessing Pain,Both Spontaneous Awakening and Breathing Trials,Choice of Drugs,Delirium Monitoring/Management,Early Exercise/Mobility,and Family Empowerment' (ABCDEF) Bundle[J].Crit Care Med,2017,45(11):e1111-e1122.DOI:10.1097/CCM.0000000000002640. [77] SimoneS,EdwardsS,LardieriA,et al.Implementation of an ICU Bundle:An Interprofessional Quality Improvement Project to Enhance Delirium Management and Monitor Delirium Prevalence in a Single PICU[J].Pediatr Crit Care Med,2017,18(6):531-540.DOI:10.1097/PCC.0000000000001127. [78] Barnes-DalyMA,PhillipsG,ElyEW.Improving Hospital Survival and Reducing Brain Dysfunction at Seven California Community Hospitals:Implementing PAD Guidelines Via the ABCDEF Bundle in 6,064 Patients[J].Crit Care Med,2017,45(2):171-178.DOI:10.1097/CCM.0000000000002149. [79] ArteagaG,KawaiY,RowekampD,et al.1289:the pediatric ICU liberation project impact on patient outcomes the Mayo experience[J].Crit Care Med,2018,46(1):628. [80] DavidsonJE,AslaksonRA,LongAC,et al.Guidelines for Family-Centered Care in the Neonatal,Pediatric,and Adult ICU[J].Crit Care Med,2017,45(1):103-128.DOI:10.1097/CCM.0000000000002169. [81] SmeetsIA,TanEY,VossenHG,et al.Prolonged stay at the paediatric intensive care unit associated with paediatric delirium[J].Eur Child Adolesc Psychiatry,2010,19(4):389-393.DOI:10.1007/s00787-009-0063-2. [82] TraubeC,MauerEA,GerberLM,et al.Cost Associated With Pediatric Delirium in the ICU[J].Crit Care Med,2016,44(12):e1175-e1179.DOI:10.1097/CCM.0000000000002004. [83] SchieveldJN,van TuijlS,PikhardT.On nontraumatic brain injury in pediatric critical illness,neuropsychologic short-term outcome,delirium,and resilience[J].Crit Care Med,2013,41(4):1160-1161.DOI:10.1097/CCM.0b013e31827bf658. |
|