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1、目标化镇静和体温管理与脑保护,关于地震和海啸的联想,原发损伤,继发损伤,灌注障碍,利用障碍,让时间凝固，将整个城市催眠,Pharmacology&Therapeutics 105(2005)2356,脑损伤的原发和继发机制,Primary Injury&Neurosurgery,脑复苏Cerebral resuscitation,CHINA International Neuroscience Institute ICU,治疗原发疾病：包括中枢神经系统血管病；创伤和肿瘤等。Situations where primary brain insult occurs.防治继发脑损伤：实质上是防治减少
2、细胞灌注的各种因素，包括：低氧血症；低血压，脑水肿，细胞内改变，代谢，还有保护脑血管自动调节功能，血脑屏障等。Management directed towards prevention of secondary brain insult multiple insults all end up in reduced cellular perfusion：hypoxia，hypotension，cerebral oedema，intracellular changes，metabolic,如何防治继发脑损伤?,继发脑损伤形成的机制仅仅是“缺血缺氧性脑病”吗？,CHINA Internationa
3、l Neuroscience Institute ICU,原发损伤：物理损伤：外伤，血肿，脑疝，手术创伤等。继发损伤：缺乏足够的血供：动脉低血压，血管梗阻，高CVP或ICP或组织压，微循环障碍等。血供质量差：低氧血症（充血），高血糖，低血糖，内环境紊乱，不良代谢产物等。脑组织充血和再灌注损伤：过高的脑灌注压（不仅仅是高血压脑病），尤其是脑血管自动调节功能受损时。代谢需求过高（相对于血供）：高热，癫痫，兴奋性神经递质增加等。,继发脑损伤形成的过程 就是不同程度的脑灌注与脑代谢失衡的过程,继发脑损伤防治的过程 就是不断寻找脑灌注与脑代谢平衡点的过程。,继发脑损伤的防治,CHINA Internat
4、ional Neuroscience Institute ICU,如何寻找脑灌注与代谢的平衡点？如何达到脑灌注与代谢的平衡点？如何维持脑灌注和代谢的平衡？,继发脑损伤的防治,CHINA International Neuroscience Institute ICU,如何寻找脑灌注与代谢的平衡点？如何达到脑灌注与代谢的平衡点？如何维持脑灌注和代谢的平衡？,CHINA International Neuroscience Institute ICU,脑 自身如何实现灌注与代谢匹配？,脑血管自动调节功能（CA）:脑自我保护功能血脑屏障(BBB)：脑自我保护功能脑血流量：占心输出量（CO）的15-2
5、0%；供能；散热。脑代谢：体重的2%，消耗 20%氧；60%ATP；循环停止10秒就出现意识障碍，5-6分钟神经损伤不可逆。基本无储备。,大脑是需求最苛刻的器官吗？,CHINA International Neuroscience Institute ICU,脑的自我保护功能：脑血管自主调节功能（CA）本质是：脑根据代谢需求调节脑血管舒缩调节脑血流量。,脑血管自主调节功能的各个机制是相互独立的。CA对于保证颅腔内容积稳定至关重要。,理解CA：CA 与 Bp,注意CA是肌源性的。通过调节血管直径改变脑血管阻力。,寻找适当的脑灌注：滴定治疗,脑血管自主调节功能受损或丧失的情况下，CPP与CBF，C
6、BV和ICP呈正比。此种状况下，适当的脑灌注压选择变得异常重要；不适当的灌注压会造成不适当的脑灌注，意味着脑缺血或充血。灌注压过高或过低对患者都会造成损害。7,7.J.H.van Blankenstein,et al.Effect of arterial blood pressure and ventilation gases on cardiac depression induced by coronary air embolism.J Appl Physiol,1994;77:1896-1902.,CHINA International Neuroscience Institute ICU
7、,脑的自我保护功能：血脑屏障（BBB）,本质是为了保持中枢神经系统内环境的稳定。,继发脑损伤的防治,CHINA International Neuroscience Institute ICU,如何寻找脑灌注与代谢的平衡点？找不到的！要保护脑，先保护血管！保护和恢复脑血管自动调节功能保护和恢复血脑屏障功能保持内环境良好且稳定动态连续评估脑代谢状况和底物供应状况,继发脑损伤的防治,CHINA International Neuroscience Institute ICU,如何寻找脑灌注与代谢的平衡点？如何达到脑灌注与代谢的平衡点？如何维持脑灌注和代谢的平衡？,脑保护和脑复苏,先保护、再复苏：保
8、护脑血管自动调节功能保护血脑屏障功能保护脑组织增加灌注并且降低代谢,脑保护和脑复苏,先保护、再复苏：保护脑血管自动调节功能保护血脑屏障功能保护脑组织增加灌注并且降低代谢,脑保护和脑复苏,脑保护策略：避免损害脑血管自动调节功能的因素：稳定血压，降低灌注压力、稳定内环境（PCO2等）避免损伤血脑屏障的因素：如甘露醇保护脑组织，降低脑水肿还有吗？,低温与脑保护：降低脑代谢，降低氧耗稳定细胞膜保护血脑屏障减少细胞内酸中毒减少脑充血、减少脑水肿,脑保护和脑复苏,先保护、再复苏：保护脑血管自动调节功能保护血脑屏障功能保护脑组织增加灌注并且降低代谢,脑保护和脑复苏,增加灌注：控制颅内高压提高灌注压,颅内压增
9、高的根本原因是什么？：颅腔内容物增多颅内压增高的本质风险是什么？：原发损伤：脑组织移位，脑疝造成脑组织直接损伤：继发损伤：最终导致脑灌注下降甚至停止，缺血缺养性脑病。包括早期充血再灌注导致细胞水肿和微循环障碍。所以，防治早期充血也应包括在治疗方案内。,关于颅内压增高的几个问题Think Different,Think Different！,颅内高压?Yes!CBF？,颅内压增高意味着脑代偿的到达极限，继发脑损伤将随之到来！,CHINA International Neuroscience Institute ICU,缺血还是充血？,TCD告诉你!,脑脊液引流,CPP,PEEP,过度通气；体位；
10、颈位；静脉窦支架LUND therapy,渗透压治疗,镇静，低温,外科手术减压,颅内高压的形成和针对性治疗方案,隆德概念（Lund concept）,基本概念：脑血管自动调节功能（CA）血脑屏障(BBB)脑代谢重点关注：减少颅腔内容体积，哪怕5ml也好！不用甘露醇控制颅内压！,Midazolam 5-20 mg/h+Low-dose thiopental 0.5-3 mgkg-1h-1+Fentanyl 2-5 gkg-1h-1+1-antagonist metoprolol 0.2-0.3 mgkg-124h-1 iv.+2-agonist clonidine 0.4-0.8 gkg-1h-
11、1 4-6 iv.+维持正常血容量，适度液体负平衡：速尿1-3mg/hr+维持胶体渗透压和携氧能力：ALB40g/L;Hb 12.5 g%,隆德概念的 BUNDLE,镇静,控制应激反应,脑灌注的质和量的管理,镇痛,输血加镇静：提高灌注质量+减低代谢,脑代谢的指标：Microdialysis,颅内压增高的控制思路Think Different,脑脊液引流,CPP,PEEP,过度通气；体位；颈位；静脉窦支架LUND therapy,渗透压治疗,镇静，低温。,外科手术减压,脑水肿治疗：扬汤止沸还是釜底抽薪？,ICP异常增高！为什么？,看上去很安静？,强化镇静试试？5mg 咪唑安定静推！,寒战、镇静与
12、ICP控制,降低脑代谢的手段：镇静和麻醉依赖或不依赖于脑血流变化,Think DifferentDHCA脑保护带来的启示,体温与脑血流量和脑氧代谢率的关系,镇静低温就是循环支持,脑保护和脑复苏,先保护、再复苏：保护脑血管自动调节功能保护血脑屏障功能保护脑组织增加灌注并且降低代谢,调整策略，主动出击、釜底抽薪：降低脑代谢-镇静和低温,仅仅关于镇静的问题:拿什么指标作镇静的尺子？用什么药物镇静？用什么药物镇痛？多早？多深？多久？蓄积？如何减药？停药？,目标化镇静管理的目标制定,仅仅关于镇静的问题:拿什么指标作镇静的尺子？用什么药物镇静？用什么药物镇痛？多早？多深？多久？蓄积？如何减药？停药？,目标
13、化镇静管理的目标制定,目标化镇静的质控：Bis和EEG,NCSE,仅仅关于镇静的问题:拿什么指标作镇静的尺子？用什么药物镇静？用什么药物镇痛？多早？多深？多久？蓄积？如何减药？停药？,目标化镇静管理的目标制定,关于中长期镇静药物的问题:冬眠合剂：氯丙嗪50mg、异丙嗪50mg、哌替定100mg，iv 持续泵入，每日2-3 个全量。咪达唑仑：5-20mg/h iv 持续泵入辅助：异丙酚、右美托嘧啶。不使用肌松剂！不间断唤醒！,目标化镇静管理的目标制定,仅仅关于镇静的问题:拿什么指标作镇静的尺子？用什么药物镇静？用什么药物镇痛？多早？多深？多久？蓄积？如何减药？停药？,目标化镇静管理的目标制定,关
14、于镇静药物减药、蓄积和停药的问题:长期应用存在蓄积可能，需要注意。但长程“冷静”治疗后更多见耐药！根据脑代谢灌注平衡情况及病理生理过程逐渐减药停药。,目标化镇静管理的目标制定,仅仅关于镇静的问题:拿什么指标作镇静的尺子？用什么药物镇静？用什么药物镇痛？多早？多深？多久？蓄积？如何减药？停药？同温度控制策略,目标化镇静管理的目标制定,Fever Management in SAH V.Scaravilli G.Tinchero G.Citerio The Participants in the International Multi-disciplinary ConsensusConferenc
15、e on the Critical Care Management of Subarachnoid Hemorrhage.2011,仅仅关于温度的问题:拿什么温度作尺子？多早？多低？多久？用什么控温？复温？,目标化体温管理的目标制定,Fever Management in SAH V.Scaravilli G.Tinchero G.Citerio The Participants in the International Multi-disciplinary ConsensusConference on the Critical Care Management of Subarachnoid
16、Hemorrhage.2011,仅仅关于温度的问题:拿什么温度作尺子？多早？多低？多久？用什么控温？复温？,目标化体温管理的目标制定,Fever Management in SAH V.Scaravilli G.Tinchero G.Citerio The Participants in the International Multi-disciplinary ConsensusConference on the Critical Care Management of Subarachnoid Hemorrhage.2011,仅仅关于温度的问题:拿什么温度作指标：皮肤温度？腋温？鼻咽温？肛温？
17、膀胱温？血温？脑温？,目标化体温管理的目标制定,Pediatric Anesthesia 21(2011)347358 2011 Blackwell Publishing Ltd,SummaryNeurological insults are a leading cause of morbidity and mortality,both in adults and especially in children.Among possible therapeutic strategies to limit clinical cerebral damage and improve outcomes,
18、hypothermia remains a promising and benecial approach.However,its advantages are still debated after decades of use.Studies in adults have generated conicting results,whereas in children recent data even suggest that hypothermia may be detrimental.Is it because brain temperature physiology is not we
19、ll understood and/or not applied properly,that hypothermia fails to convince clinicians of its potential benets?Or is it because hypothermia is not,as believed,the optimal strategy to improve outcome in patients affected with an acute neurological insult?This review article should help to explain th
20、e fundamental physiological principles of brain heat production,distribution and elimination under normal conditions and discuss why hypothermia cannot yet be recommended routinely in the management of children affected with various neurological insults.低温治疗：拿什么作尺子？体温？核心温度？脑温！脑温与脑代谢程度和局部血流灌注情况密切相关；不
21、同部位，不同病理生理状态下均有不同。,膀胱温与脑温的差异：T即可作为脑损伤严重程度和微循环障碍的评估，也可作为治疗的目标点,Fever Management in SAH V.Scaravilli G.Tinchero G.Citerio The Participants in the International Multi-disciplinary ConsensusConference on the Critical Care Management of Subarachnoid Hemorrhage.2011,仅仅关于温度的问题:拿什么温度作尺子？：脑温！多早？多低？多久？用什么控温？复
22、温？,目标化体温管理的目标制定,Fever Management in SAH V.Scaravilli G.Tinchero G.Citerio The Participants in the International Multi-disciplinary ConsensusConference on the Critical Care Management of Subarachnoid Hemorrhage.2011,仅仅关于温度的问题:拿什么温度作尺子？：脑温！多早？多低？多久？用什么控温？温度的质控！复温？,目标化体温管理的目标制定,低温方法的选择决定了目标化体温管理的质控从一个病
23、理生理状态到另一个,最适合你的方法就是最好的方法：无创，智能，精确，高效，稳定，方便，便宜,CHINA International Neuroscience Institute ICU,Fever Management in SAH V.Scaravilli G.Tinchero G.Citerio The Participants in the International Multi-disciplinary ConsensusConference on the Critical Care Management of Subarachnoid Hemorrhage.2011,仅仅关于镇静和温
24、度的问题:拿什么温度作尺子？脑温！多早？多低？多久？用什么控温？温度的质控！复温？,目标化镇静和体温管理的目标制定,Time is Brain,For every minutes delay,the brain loses:1.9 million neurons;190万神经元14 billion synapses;140亿突触7.5 miles of myelinated fibers.7.5英里有髓鞘的神经纤维If a stroke runs its full course an estimated 10 hours on average the brain loses:1.2 billi
25、on neurons;12亿神经元8.3 trillion synapses;830万兆突触4,470 miles of myelinated fibers.4470英里神经纤维,Stroke 2006;37:263-266,在永久性损伤发生前锁定问题！确保适当的脑灌注！,Think Different,Discussion We found no signicant dierence in outcome in patients treated with hypothermia compared with those treated with normothermia;however,pat
26、ients in the hypothermia group did have a signicantly higher number of episodes of increased intracranial pressure than those in the normothermia group.,Lancet Neurol 2011;10:13139,Methods The National Acute Brain Injury Study:Hypothermia II(NABIS:H II)was a randomised,multicentre clinical trial of
27、patients with severe brain injury who were enrolled within 25 h of injury at six sites in the USA and Canada.Patients with non-penetrating brain injury who were 1645 years old and were not responsive to instructions were randomly assigned(1:1)by a random number generator to hypothermia or normotherm
28、ia.Patients randomly assigned to hypothermia were cooled to 35C until their trauma assessment was completed.Patients who had none of a second set of exclusion criteria were either cooled to 33C for 48 h and then gradually rewarmed or treated at normothermia,depending upon their initial treatment ass
29、ignment.Investigators who assessed the outcome measures were masked to treatment allocation.The primary outcome was the Glasgow outcome scale score at 6 months.Analysis was by modied intention to treat.This trial is registered with ClinicalTrials.gov,NCT00178711.,Lancet Neurol 2011;10:13139,Think Di
30、fferent,Lancet Neurol 2011;10:13139,Think Different,Fever Management in SAH V.Scaravilli G.Tinchero G.Citerio The Participants in the International Multi-disciplinary ConsensusConference on the Critical Care Management of Subarachnoid Hemorrhage.2011,仅仅关于镇静和温度的问题:拿什么温度作尺子？脑温！多早？尽早！尽快！多低？多久？用什么控温？温度的
31、质控！复温？,目标化镇静和体温管理的目标制定,long-term hypothermia therapy,Clinical Articles Effect of long-term mild hypothermia therapy in patients with severe traumatic brain injury:1-year follow-up review of 87 casesObject.The goal of this study was to investigate the protective effects of long-term(314 days)mild hyp
32、othermia therapy(3335C)on outcome in 87 patients with severe traumatic brain injury(TBI)(Glasgow Coma Scale score 8).Methods.In 43 patients assigned to a mild hypothermia group,body temperatures were cooled to 33 to 35C a mean of 15 hours after injury and kept at 33 to 35C for 3 to 14 days.Rewarming
33、 commenced when the individual patients intracranial pressure(ICP)returned to the normal level.Body temperatures in 44 patients assigned to a normothermia group were maintained at 37 to 38C.Each patients outcome was evaluated 1 year later by using the Glasgow Outcome Scale.One year after TBI,the mor
34、tality rate was 25.58%(11 of 43 patients)and the rate of favorable outcome(good recovery or moderate disability)was 46.51%(20 of 43 patients)in the mild hypothermia group.In the normothermia group,the mortality rate was 45.45%(20 of 44 patients)and the rate of favorable outcome was 27.27%(12 of 44 p
35、atients)(p 0.05).Induced mild hypothermia also markedly reduced ICP(p 0.01)and inhibited hyperglycemia(p 0.05).The rates of complication were not significantly different between the two groups.Conclusions.The data produced by this study demonstrate that long-term mild hypothermia therapy significant
36、ly improves outcomes in patients with severe TBI.Journal of Neurosurgery October 2000/Vol.93/No.4/Pages 546-549 Ji-Yao Jiang,M.D.,Ph.D.,Ming-Kun Yu,M.D.,Ph.D.,and Cheng Zhu,M.D,Think Different，Make Difference,Fever Management in SAH V.Scaravilli G.Tinchero G.Citerio The Participants in the Internati
37、onal Multi-disciplinary ConsensusConference on the Critical Care Management of Subarachnoid Hemorrhage.2011,仅仅关于镇静和温度的问题:拿什么温度作尺子？脑温！多早？尽早！何时都有意义！多低？多久？病理生理过程；ICP？用什么控温？温度的质控！复温？,目标化镇静和体温管理的目标制定,临床决策多样性：Think Different,CHINA International Neuroscience Institute ICU,h,不同的疾病不同的病理生理过程和阶段不同的代谢状态,不同的个体不同
38、的器官不同的角度不同的反应性,理解病理生理过程需要“过程”！,没那么简单！Think Different!,理解病理生理过程需要“过程”：不同的疾病的自然病程脑血管自动调节功能状态的动态评估TCD？ICP?脑电生理？脑代谢指标？血生化：CK?,TCD动态评估：脑灌注和脑血管自动调节功能评估治疗反应和病理生理状态和阶段,Fever Management in SAH V.Scaravilli G.Tinchero G.Citerio The Participants in the International Multi-disciplinary ConsensusConference on th
39、e Critical Care Management of Subarachnoid Hemorrhage.2011,仅仅关于镇静和温度的问题:拿什么温度作尺子？：脑温！多点！多早？尽早！何时都有意义！温度多低？镇静多深？多久？病理生理过程；ICP？用什么控温？温度的质控！复温？,目标化镇静和体温管理的目标制定,降低脑代谢的手段：镇静和麻醉,Fever Management in SAH V.Scaravilli G.Tinchero G.Citerio The Participants in the International Multi-disciplinary ConsensusConf
40、erence on the Critical Care Management of Subarachnoid Hemorrhage.2011,仅仅关于镇静和温度的问题:拿什么温度作尺子？：脑温！多点！多早？尽早！何时都有意义！镇静多深？以代谢状态以及脑代谢灌注失衡程度定，Bis 30-40？多久？病理生理过程；ICP？用什么控温？温度的质控！复温？,目标化镇静和体温管理的目标制定,Fever Management in SAH V.Scaravilli G.Tinchero G.Citerio The Participants in the International Multi-discip
41、linary ConsensusConference on the Critical Care Management of Subarachnoid Hemorrhage.2011,仅仅关于镇静和温度的问题:拿什么温度作尺子？：脑温！多点！多早？尽早！何时都有意义！温度多低？多久？病理生理过程；ICP？用什么控温？温度的质控！复温？,目标化镇静和体温管理的目标制定,低温治疗的利与弊评估、权衡和妥协,神经重症体温升高是影响预后和LOS的独立危险因素,Diringer MN,Reaven NL,Funk SE,Uman GC.Elevated body temperature independen
42、tly contributes to increased length of stay in neurologic intensive care unit patients.Crit Care Med.2004;32:148995.,Think Different：我们是否曾经片面强调追求灌注而忽略了体温的控制？！,Fever Management in SAH V.Scaravilli G.Tinchero G.Citerio The Participants in the International Multi-disciplinary ConsensusConference on the
43、 Critical Care Management of Subarachnoid Hemorrhage.2011,NORMOTHERMIA:蛛网膜下腔出血的发热控制1、发热（体温38.3，72%SAH患者）与SAH后的不良预后及住院日延长相关，是独立于血管痉挛的有害因素。但发热如何影响预后仍不明确，发热可能促进继发性神经损伤，也可能发热本身即是某些不良事件的标志。2、独立于出血严重程度和感染，发热可能与症状性脑血管痉挛有关，两者中均有炎症激活。3、发热发生发展的危险因素：疾病严重程度、蛛网膜下腔出血量及脑室内出血；加重缺血性损伤及脑水肿，升高颅内压，影响意识状态。SAH后即使是一过性发热，与
44、预后不良有关，在级别较低的SAH患者中亦然。4、非感染性发热通常比感染性发热早，多发生在SAH后3天内；感染性发热也不少见，需要立即应用抗生素治疗。累计性发热负荷（SAH后13天体温38的累计）与患者预后不良及延迟康复有关。5、发热的控制包括应用退热剂、体表降温及血管内降温。降温的益处可能由寒战带来的不良反应抵消。寒战的防治包括应用丁螺环酮、纠正低血镁、使用杜冷丁，及镇静。,发热负荷管理和目标化体温管理,Fever Management in SAH V.Scaravilli G.Tinchero G.Citerio The Participants in the International
45、Multi-disciplinary ConsensusConference on the Critical Care Management of Subarachnoid Hemorrhage.2011,关于NORMOTHERMIA的问题:Fever Burden 发热负荷的监测和管理有所谓的正常体温吗？正常人有，那病人呢？,发热负荷管理和目标化体温管理,体温也是个相对概念：脑灌注和代谢的平衡！,脑灌注代谢平衡匹配的评估Think Different,ICP 18CPP70BIS 50Tb 38,ICP16CPP90BIS 40Tb37,ICP 14CPP100BIS 35Tb 33,ICP
46、22CPP100BIS 30Tb 32,CHINA International Neuroscience Institute ICU,脑代谢的指标：Microdialysis,输血加镇静,脑代谢的指标：Microdialysis,CHINA International Neuroscience Institute ICU,Think Different：没有所谓金指标不同的方法、不同的参数、不同的角度,不同的结果、能相互替代吗？,平衡、匹配和妥协,继发脑损伤的防治,CHINA International Neuroscience Institute ICU,如何寻找脑灌注与代谢的平衡点？如何达
47、到脑灌注与代谢的平衡点？如何维持脑灌注和代谢的平衡？,Targeted Sedation and Temperature Management Protocol For a SAH,Monitoring:CA,TCD,ICP,MAP,VS,生化：PAB,CRP、CKICP 150 mmHg（FiO2 50%）；PCO2：30-35mmHgPH 7.40T brain 30-35（匹配）BIS 30-50 EEG？NCSE?CI:3-5;视 CBF 定EVLW:10G/L;HCT 30-35%I/O:避免大出大入器官保护：早期放置鼻肠管，低流量EN，必要时加PN，低热卡护理：引流：呼吸道，消化道
48、，脑脊液。目标治疗和综合治理并举,总结：目标化镇静和体温管理,主动的镇静和体温控制避免充血，减少组织水肿，控制颅内压，经常可以不甘露醇有利于维护血脑屏障完整有利于保护和修复脑血管自动调节功能有利于减少体循环压力，保护心肺有利于全程、全面地实现脑保护，帮助受损的脑组织度过病理生理过程,“冷静”面对脑保护,Think different：从一个病理状态到另一个，我们还了解的太少！,低温治疗的并发症从一个病理状态到另一个！,如何实现脑保护？,需要保持“冷和静”！,CHINA International Neuroscience Institute ICU,谢谢!,Keep Thinking in Neurocritical Care,Think Different，Make Difference.,
