基于ipad2013指南的藥物及非藥物應(yīng)用-於江泉

1、基于IPAD（2013）指南的藥物及非藥物應(yīng)用,重癥醫(yī)學(xué)科 於江泉,鎮(zhèn)靜鎮(zhèn)痛抗譫妄的必要性！,Hey! I Think he just moved! Add one more!,ICU患者回顧性調(diào)查,噪音 醫(yī)護(hù)操作,(翻身、胸部物理治療、吸痰、穿刺或置管、內(nèi)窺鏡檢查、大換藥等),沒(méi)有哪個(gè)地方比ICU更恐怖了！再也不想到ICU了！,鎮(zhèn)痛鎮(zhèn)靜抗譫妄,鎮(zhèn)痛不足,1,381

2、 patients 44 ICUs in FranceAnalgesic and sedative usePain and sedation assessment on days 2,4 and 6 of the ICU stay,Anesthesiology, 2007，106,近一半患者鎮(zhèn)靜過(guò)深,多數(shù)患者鎮(zhèn)痛不足,尤其是操作時(shí),指南推薦的鎮(zhèn)痛不足藥物,Critical Care Medicine，2013 ， 41,建議

3、考慮使用非阿片類(lèi)鎮(zhèn)痛藥，以減少阿片類(lèi)藥物用量（或避免使用IV阿片類(lèi)藥物）以及藥物相關(guān)副作用(+2C)。,Critical Care Medicine，2013 ， 41,阿片類(lèi)藥物最大的問(wèn)題：成癮性,Critical Care Medicine，2013 ， 41,Patients were randomized into 2 groups in ICU. Patients received either serum saline

4、 IV q 6 h and IV meperidine or IV paracetamol 1 g q 6 h and IV meperidine for 24 hours. BPS and VAS is used until extubation.,J Crit Care 2010; 25:458–462,Safety of Multiple-Dose IntravenousAcetaminophen,213 adult

5、 inpatients were randomized (3:3:1) to receive IV acetaminophen (1,000 mg q6h or 650 mg q4h).Safety was assessed according to spontaneous reports of adverse events (AEs) and clinically meaningful changes from baseline l

6、aboratory parameters.Given as repeated doses for up to 5 days.,Journal of Critical Care, (2010) 25:458–462,However, their safety profile and effectiveness as sole agents for pain management have not been adequately

7、studied in critically ill patients. Pharmacologic treatment principles extrapolated from non-ICU studies may not be applicable to critically ill patients.然而，作為危重患者疼痛管理的唯一替代藥品它們的安全系數(shù)和有效性還沒(méi)有充分研究過(guò)。從非ICU患者研究得出的藥理學(xué)結(jié)論可能并不適用于

8、危重癥患者。,Critical Care Medicine，2013 ， 41,治療神經(jīng)病性疼痛時(shí)，除阿片類(lèi)藥物外，推薦經(jīng)腸道給予加巴噴丁(gabapentin)或卡馬西平(carbamazepine) (+1A)。,Critical Care Medicine，2013 ， 41,36 Guillain-Barre´ syndrome patients.Patients were randomly assigned to

9、receive gabapentin 300 mg, carbamazepine 100 mg, or matching placebo q8h for 7 days. Fentanyl was used as a supplementary analgesic.The pain score was recorded by using a numeric pain rating .Sedation was recorded with

10、 a Ramsay sedation scale .,Anesth Analg 2005;101:220–5,成年ICU患者接受其他有創(chuàng)或可能引起疼痛的操作前，建議進(jìn)行預(yù)先鎮(zhèn)痛和（或）非藥物性干預(yù)以減輕疼痛(+2C)。成年ICU患者拔除胸腔引流管前，推薦進(jìn)行預(yù)先鎮(zhèn)痛和（或）非藥物性干預(yù)（如放松）(+1C)。,Critical Care Medicine，2013 ， 41,40 adults CABG patientsA 10-c

11、m vertical VAS was used to measure pain at three points: before CTR,immediately after CTR, and 15 minutes after CTR. The experimental group received slow breathing relaxation exercises in addition 5 minutes before remo

12、val.,Heart Lung, 2006;35:269 –276,We recommend that thoracic epidural anesthesia/analgesia be considered for postoperative analgesia in patients undergoing abdominal aortic surgery (+1B). We suggest that thoracic epid

13、ural analgesia be considered for patients with traumatic rib fractures (+2B).,Critical Care Medicine，2013 ， 41,鎮(zhèn) 靜,對(duì)于成年ICU患者維持輕度鎮(zhèn)靜可以改善臨床預(yù)后（如縮短機(jī)械通氣時(shí)間及ICU住院日）(B)。 對(duì)于接受機(jī)械通氣的成年ICU患者，建議使用非苯二氮卓類(lèi)（異丙酚或右美托咪定）而不是咪達(dá)唑侖或勞拉西泮，以改善臨床

14、預(yù)后(+1A)。,Critical Care Medicine，2013 ， 41,理想的ICU鎮(zhèn)靜藥物,起效決,鎮(zhèn)靜作用強(qiáng)鎮(zhèn)靜程度易控制對(duì)呼吸循環(huán)功能影響小 與其他藥物無(wú)明顯的相互干擾作用 消除方式不依賴(lài)于肝、腎具有多種體內(nèi)代謝途徑消除半衰期短、不蓄積 價(jià)格低廉最小的不良反應(yīng)、后遺效應(yīng)小兼有鎮(zhèn)痛、抗譫妄的效應(yīng),目前尚無(wú)藥物能符合以上所有要求！,與廣泛分布于中樞與周?chē)窠?jīng)系統(tǒng)及其他器官組織α2AR 結(jié)合腦內(nèi)α2AR最

15、密集的區(qū)域在腦干的藍(lán)斑藍(lán)斑是大腦內(nèi)負(fù)責(zé)調(diào)解覺(jué)醒與睡眠的關(guān)鍵部位右美托咪啶作用于腦干藍(lán)斑核內(nèi)的α2AR,而產(chǎn)生鎮(zhèn)靜-催眠，引發(fā)并維持自然非動(dòng)眼睡眠,生理作用,與擬 GABA 藥物的差別,Dexmedetomidine作用于腦干（藍(lán)斑）自然非動(dòng)眼睡眠喚醒系統(tǒng)功能依然存在擬GABA藥物作用于下丘腦非自然睡眠,Dexmedetomidine vs Midazolam,Prospective, double-blind, ra

16、ndomized trial 68 centers in 5 countriesbetween March 2005 and August 2007375 ICU patients with mechanical ventilation more than 24 hsAssessed using RASS (?2 to 1) 0.8 µg/kg/h for dexmedetomidine

17、0.06 mg/kg/h for midazolamopen-label midazolam bolus doses of 0.01 to 0.05mg/kg at 10- to 15-minute,JAMA, 2009，301（ 5）,,,,Dexmedetomidine vs Midazolam/ Propofol,Design, Setting, and Patients randomized, doubleblind tr

18、ials carried out from 2007 to 2010The MIDEX trial compared midazolam with dexmedetomidine in ICUs of 44 centers in 9 European countriesthe PRODEX trial compared propofol with dexmedetomidine in 31 centers in 6 Europea

19、n countries and 2 centers in Russia,JAMA, 2012, 307( 11),Dexmedetomidine vs Midazolam/ Propofol,Dexmedetomidine vs Midazolam/ Propofol,右美托咪定對(duì)呼吸的影響,10名健康男性 (20–27 yr) 持續(xù)靜脈輸注右美托咪定使血漿濃度達(dá)0.5, 0.8, 1.2, 2.0, 3.2, 5.0, and 8

20、.0ng/ml（正常血藥濃度5-10倍）并維持40min,Anesthesiology, 2000 ，93（ 2）：382-94,右美托咪定對(duì)循環(huán)的影響,出現(xiàn)兩相反應(yīng)第一相：血壓增高，心率減慢機(jī)制：激動(dòng)突觸前 ?2B和突觸后 ?1受體第二相：典型的突觸前 ?2受體激動(dòng),血壓下降 心率減慢,Fig 1 Alfentanil requirements for patients receiving dexmedetomidine

21、and propofol whilst mechanically ventilated in the ICU. Median, IQR and extremes are shown.,J. Anaesth. 2001;87:684-690,Dexmedetomidine 減少鎮(zhèn)痛藥物用量,20個(gè)成年患者術(shù)后隨機(jī)分成右美托咪定組或丙泊酚組同時(shí)使用Ramsay和 bispectral index (BIS)進(jìn)行鎮(zhèn)靜效果評(píng)價(jià),Psych

22、osomatics,2009,50:3,Dexmedetomidine 可能減少譫妄發(fā)生率,,,苯二氮唑類(lèi)也非一無(wú)是處,Despite the apparent advantages in using either propofol or dexme-detomidine over benzodiazepines for ICU sedation,benzodiazepines remain important for man

23、aging agitation in ICU patients, especially for treating anxiety, seizures, and alcohol or benzodiazepine with-drawal. Benzodiazepines are also important when deep sedation, amnesia, or combination therapy to reduce the

24、use of other sedative agents is required.,Critical Care Medicine，2013 ， 41,譫 妄,成年ICU患者的譫妄伴隨病死率升高(A)。 成年ICU患者的譫妄伴隨ICU住院日及總住院日延長(zhǎng)(A)。,Critical Care Medicine，2013 ， 41,Patients from 68 ICUs in five countries.354 patients

25、enrolled in the SEDCOM (Safety and Efficacy of Dexmedetomidine Compared with Midazolam) Delirium assessments up to 30 days of mechanical ventilation.,Crit Care Med 2010 Vol. 38,,Crit Care Med 2010 Vol. 38,,譫妄常見(jiàn)因素,Intens

26、ive Care Med ,2007, 33:66–73,Intensive Care Med ,2007, 33:66–73,多因素回歸分析，昏迷是獨(dú)立危險(xiǎn)因素，包括鎮(zhèn)靜誘導(dǎo)的昏迷,譫 妄,昏迷是ICU患者發(fā)生譫妄的獨(dú)立危險(xiǎn)因素(B)。 使用苯二氮卓類(lèi)藥物可能是成年ICU患者發(fā)生譫妄的危險(xiǎn)因素(B)。對(duì)于有發(fā)生譫妄危險(xiǎn)的接受機(jī)械通氣治療的成年ICU患者，與輸注苯二氮卓類(lèi)藥物相比，輸注右美托咪定可能減少譫妄的罹患率(B)。,C

27、ritical Care Medicine，2013 ， 41,譫 妄,非典型的抗精神病藥物可能縮短成年ICU患者的譫妄持續(xù)時(shí)間(C)。如果患者具有發(fā)生尖端扭轉(zhuǎn)性室速的危險(xiǎn)（即基礎(chǔ)QTc間期延長(zhǎng)，服用可延長(zhǎng)QTc間期的藥物，或有心律失常病史），反對(duì)使用抗精神病藥物(-2C)。,Critical Care Medicine，2013 ， 41,36 patients with delirium Interventions: Pat

28、ients were randomized to receive quetiapine 50 mg every 12 hrs or placebo. Quetiapine was increased every 24 hrs (50 to 100 to 150 to 200 mg every 12 hrs) therapy >10 days, or intensive care unit discharge.,Crit Care

29、 Med ,2010 , 38,,預(yù)防譫妄,反對(duì)成年ICU患者使用氟哌啶醇(haloperidol)或非典型的抗精神病藥物預(yù)防譫妄(-2C)。 推薦采用多種方法促進(jìn)成年ICU患者的睡眠，包括優(yōu)化環(huán)境、控制光線和噪音、集中進(jìn)行醫(yī)療護(hù)理工作和減少夜間刺激以保護(hù)患者的睡眠周期(+1C)。對(duì)于成年ICU患者，如有可能，推薦早期活動(dòng)以減少譫妄發(fā)生，縮短譫妄持續(xù)時(shí)間(+1B)。,Critical Care Medicine，2013 ，