重症脑损伤患者的镇痛镇静

BeijingTiantanHospital,CMU重症脑损伤患者的镇痛镇静首都医科大学附属北京天坛医院周建新Dept.ofCriticalCareMedicine,BeijingTiantanHospital,CMU镇痛镇静是脑损伤治疗的重要组成WunschH,etal.Criticalcaremedicine2009.北美ICU机械通气调查：169ICU、97,000例患者Dept.ofCriticalCareMedicine,BeijingTiantanHospital,CMU镇痛镇静是脑损伤治疗的重要组成北美和欧洲15国、2177例重度TBI患者的流行病学调查，90%以上患者应用镇静治疗ChantaletalJNeurosurg2002.Dept.ofCriticalCareMedicine,BeijingTiantanHospital,CMU脑损伤患者镇痛镇静的目的控制疼痛和躁动为主要目的（轻度脑损伤GCS9~15）缓解疼痛、焦虑和躁动，降低应激反应减少并发症提高人工气道和机械通气的耐受性利于医疗和护理操作CNS保护为目的（重度脑损伤GCS=8）降低脑代谢、控制ICP辅助低温治疗癫痫持续状态Dept.ofCriticalCareMedicine,BeijingTiantanHospital,CMUDept.ofCriticalCareMedicine,BeijingTiantanHospital,CMUCooperletalNEJM2011.Dept.ofCriticalCareMedicine,BeijingTiantanHospital,CMU新近研究提示的几点问题低温中的镇痛镇静冬眠合剂DISDept.ofCriticalCareMedicine,BeijingTiantanHospital,CMU关于低温治疗中的镇静咪达唑仑57.4%：5mg/kg0.3mg/kg/h异丙酚19.1%：6mg/kg/h芬太尼48.5%：0.510ug/kg/h吗啡5.9%肌松剂79.4%（泮库溴铵、顺式阿曲库铵）Dept.ofCriticalCareMedicine,BeijingTiantanHospital,CMU关于冬眠合剂曾经是低温治疗的标准辅助药物优点在于降低体温调定阈值主要缺点在于对循环的影响Dept.ofCriticalCareMedicine,BeijingTiantanHospital,CMU关于DISCCM2012NCC2013CC2012Dept.ofCriticalCareMedicine,BeijingTiantanHospital,CMU脑损伤患者镇痛镇静的目的控制疼痛和躁动为主要目的（轻度脑损伤GCS9~15）缓解疼痛、焦虑和躁动，降低应激反应减少并发症提高人工气道和机械通气的耐受性利于医疗和护理操作CNS保护为目的（重度脑损伤GCS=8）降低脑代谢、控制ICP辅助低温治疗癫痫持续状态Dept.ofCriticalCareMedicine,BeijingTiantanHospital,CMU中重度疼痛将近70%应用PCA后中重度疼痛将近50%Dept.ofCriticalCareMedicine,BeijingTiantanHospital,CMU术后第1天躁动发生率达30%Dept.ofCriticalCareMedicine,BeijingTiantanHospital,CMUDept.ofCriticalCareMedicine,BeijingTiantanHospital,CMU神经专科对镇痛镇静持谨慎态度主要担心意识评估，不能及时发现脑损伤病情变化传统上，Neuro-ICU仅在下列情况时应用镇静躁动给患者带来危险躁动影响诊断、治疗和护理操作的实施Albin’sTextbook(1998)Dept.ofCriticalCareMedicine,BeijingTiantanHospital,CMU对躁动原因的鉴别非常重要全身低氧低灌注的表现疼痛颅内压升高的早期表现颅内积气脑水肿颅内血肿麻醉药的残余作用额部损伤Dept.ofCriticalCareMedicine,BeijingTiantanHospital,CMU轻度脑损伤患者控制疼痛和躁动为主要目的：重点是评估RASS、SAS（信度和效度最佳）VAS、NRSBPS、CPOT（信度和效度最佳）GCS生理指标EEGDept.ofCriticalCareMedicine,BeijingTiantanHospital,CMUYu.CCM2013Dept.ofCriticalCareMedicine,BeijingTiantanHospital,CMU神经系统体检应列为常规监测应包括：意识、认知、脑干功能、运动功能镇静的实施应尽可能减少对神经系统体检的影响（除非减浅镇静深度会导致颅内压升高）神经系统体检是实施其他进一步监测的依据神经系统体检对部分患者群体的预后评估具有帮助（CA、TBI）IntensiveCareMed2014aheadofprintDept.ofCriticalCareMedicine,BeijingTiantanHospital,CMUDept.ofCriticalCareMedicine,BeijingTiantanHospital,CMU停用镇静剂后的神经系统体检项目意识、认知、脑干功能、运动功能影像学生化脑脊液药物筛查EEG局灶体征✔coma✔✔✔✔谵妄✔✔✔✔✔癫痫✔✔✔✔✔Dept.ofCriticalCareMedicine,BeijingTiantanHospital,CMU镇痛镇静剂选择原则对CNS无附加损害快速苏醒Dept.ofCriticalCareMedicine,BeijingTiantanHospital,CMUJCritCare2014Dept.ofCriticalCareMedicine,BeijingTiantanHospital,CMUDept.ofCriticalCareMedicine,BeijingTiantanHospital,CMU入室患者DEX(0.4)(0.6)ug/kg/hNS相同速度常规监测治疗排除患者转归评价纳入：开颅术后保留气管插管的成年患者年龄18岁孕产妇急诊或24小时内二次手术延髓手术术前意识障碍或癫痫肝肾功能不全入室GCS-M=14入室BPs90mmHg、HR50bpm、或需血管活性药物维持入室表现房室传导阻滞、急性心肌梗死随机、双盲、安慰剂对照SAS》5：(Mida)(Prop)bolusorbump疼痛主诉：Fent0.05mgIV理想镇静百分比给药期间躁动频次，镇静剂量给药期间疼痛主诉频次，镇痛剂量次要转归和并发症ProphylacticAnalgesiaandSedationTrial(PASTrialI&II)Dept.ofCriticalCareMedicine,BeijingTiantanHospital,CMUDept.ofCriticalCareMedicine,BeijingTiantanHospital,CMUPAD指南ICU患者镇痛治疗一线药物：阿片类药物拔除胸腔引流管前预先镇痛，可推广到其他创伤性操作Dept.ofCriticalCareMedicine,BeijingTiantanHospital,CMUICU常用阿片类药物T1/2β(h)Cl(ml/kg/min)费用代谢主要副作用吗啡1.5-514$脱甲基HR/BP、支气管痉挛芬太尼1.3-313$脱甲基呼吸抑制、肌肉僵硬舒芬1314$脱甲基HR、肌肉僵硬瑞芬0.0550$$非特异酯酶HR/BP、肌肉僵硬Dept.ofCriticalCareMedicine,BeijingTiantanHospital,CMUContext-sensitivehalftimeJohnK.CurrOpinAnaesthesiol1999;12:443-8.Dept.ofCriticalCareMedicine,BeijingTiantanHospital,CMU舒芬太尼（sufentanil）芬太尼的衍生物脂溶性高，极易透过血脑屏障，并能迅速在脑内达到有效浓度。但由于与阿片受体的亲和力较芬太尼强，故镇痛强度大，效价约为芬太尼的5～10倍，作用持续时间也更长有较宽的安全阈范围。大鼠研究的治疗指数为25211，高于芬太尼(277)和吗啡(69.5)尤其适用于脑损伤患者呼吸抑制发生率低，且残留呼吸抑制作用较少对颅内血流动力学影响小Dept.ofCriticalCareMedicine,BeijingTiantanHospital,CMU国内开展的多中心研究结论：与芬太尼比较，舒芬太尼的镇痛效能强、生理干扰轻、不良反应低Dept.ofCriticalCareMedicine,BeijingTiantanHospital,CMU瑞芬太尼（remifentanil）肝脏外代谢：非特异性酯酶时量相关半衰期短，撤药后迅速清除呼吸抑制作用呈剂量依赖性对颅内血流动力学影响小Dept.ofCriticalCareMedicine,BeijingTiantanHospital,CMUDept.ofCriticalCareMedicine,BeijingTiantanHospital,CMUDept.ofCriticalCareMedicine,BeijingTiantanHospital,CMUExcluded(n=141)·Agelessthan18yrormorethan65yr(n=35)·Emergencyoperation(n=10)·Beyond72hafteroperation(n=22)·NotbeabletocopewiththeassessmentofVAS(n=32)·Operationrelatingtomedullaoblongataregion(n=12)·Pregnantorlactatingwomen(n=1)·Enrolledinanothertrial(n=19)·Refusedtoenrollmentbyphysicianincharge(n=10)Randomized(n=160)AllocatedtoRemifentanilgroup(n=80)·Receivedallocatedintervention(n=80)·Emergencytermination(n=0)·Discontinuedintervention(n=2)Assessedforeligibility(n=301)AllocatedtoNSgroup(n=80)·Receivedallocatedintervention(n=80)·Emergencytermination(n=0)·Discontinuedintervention(n=2)EnrollmentLosttofollow-up(n=0)AllocatedtoNSgroup(n=0)Analysed(n=80)·Excludedfromanalysis,partially(n=2)Analysed(n=80)·Excludedfromanalysis(n=0)AllocationFollow-upAnalysisDept.ofCriticalCareMedicine,BeijingTiantanHospital,CMUDept.ofCriticalCareMedicine,BeijingTiantanHospital,CMUDept.ofCriticalCareMedicine,BeijingTiantanHospital,CMU脑损伤患者镇痛方案短期应用(术后患者)：瑞芬有助于拔管24h：舒芬瑞芬有助于快速消除24h：芬太尼，疗效+经济学考虑De