基于IPAD(2013)指南的藥物及非藥物應(yīng)用-於江泉課件

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)沒有哪個地方比ICU更恐怖了！再也不想到ICU了！鎮(zhèn)痛不足1,381 patients 44 ICUs in FranceAnalgesic and sedative usePain and sedation assessment on days 2,4 and 6 of the ICU stayAnesthesiology, 2

2、007，106近一半患者鎮(zhèn)靜過深,多數(shù)患者鎮(zhèn)痛不足,尤其是操作時指南推薦的鎮(zhèn)痛不足藥物Critical Care Medicine，2013 ， 41建議考慮使用非阿片類鎮(zhèn)痛藥，以減少阿片類藥物用量（或避免使用IV阿片類藥物）以及藥物相關(guān)副作用(+2C)。 Critical Care Medicine，2013 ， 41Patients were randomized into 2 groups in ICU. Patients received either serum saline IV q 6 h and IV meperidine or IV paracetamol 1 g q 6 h

3、 and IV meperidine for 24 hours. BPS and VAS is used until extubation.J Crit Care 2010; 25:458462Safety of Multiple-Dose IntravenousAcetaminophen213 adult 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

4、of adverse events (AEs) and clinically meaningful changes from baseline laboratory parameters.Given as repeated doses for up to 5 days.Journal of Critical Care, (2010) 25:458462However, their safety profile and effectiveness as sole agents for pain management have not been adequately studied in crit

5、ically 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)和有效性還沒有充分研究過。從非ICU患者研究得出的藥理學(xué)結(jié)論可能并不適用于危重癥患者。Critical Care Medicine，2013 ， 41治療神經(jīng)病性疼痛時，除阿片類藥物外，推薦經(jīng)腸道給予加巴噴丁(gabapentin)或卡馬西平(carbamazepin

6、e) (+1A)。Critical Care Medicine，2013 ， 4136 Guillain-Barre syndrome patients.Patients were randomly assigned to 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 rati

7、ng .Sedation was recorded with a Ramsay sedation scale .Anesth Analg 2005;101:2205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鎮(zhèn) 靜對于成年ICU患者維持輕度鎮(zhèn)靜可以改善臨床預(yù)后（如縮短機(jī)械通氣時間及ICU住院日）(B)。 對于接受機(jī)械通氣的成年ICU患者，建議使用非苯二氮卓類（異丙酚或右美托咪定

8、）而不是咪達(dá)唑侖或勞拉西泮，以改善臨床預(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)靜程度易控制對呼吸循環(huán)功能影響小 與其他藥物無明顯的相互干擾作用 消除方式不依賴于肝、腎具有多種體內(nèi)代謝途徑消除半衰期短、不蓄積 價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)目前尚無藥物能符合以上所有要求！與廣泛分布于中樞與周圍神經(jīng)系統(tǒng)及其他器官組織2AR 結(jié)合腦內(nèi)2AR最密集的區(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2AR,而產(chǎn)生鎮(zhèn)靜-催眠，引發(fā)并維持自然非動眼睡眠生理作用與擬

9、 GABA 藥物的差別Dexmedetomidine作用于腦干（藍(lán)斑）自然非動眼睡眠喚醒系統(tǒng)功能依然存在擬GABA藥物作用于下丘腦非自然睡眠Dexmedetomidine vs MidazolamProspective, double-blind, randomized 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 g/kg/h

10、 for dexmedetomidine 0.06 mg/kg/h for midazolamopen-label midazolam bolus doses of 0.01 to 0.05mg/kg at 10- to 15-minuteJAMA, 2009，301（ 5）Dexmedetomidine vs Midazolam/ PropofolDexmedetomidine vs Midazolam/ Propofol 右美托咪定對呼吸的影響10名健康男性 (2027 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 8.0ng

11、/ml（正常血藥濃度5-10倍）并維持40minAnesthesiology, 2000 ，93（ 2）：382-94右美托咪定對循環(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 血壓下降 心率減慢Fig 1 Alfentanil requirements for patients receiving dexmedetomidine and propofol whilst mechanically ventilated in the ICU. Median, IQR and extremes are shown. J. An

12、aesth. 2001;87:684-690Dexmedetomidine 減少鎮(zhèn)痛藥物用量20個成年患者術(shù)后隨機(jī)分成右美托咪定組或丙泊酚組同時使用Ramsay和 bispectral index (BIS)進(jìn)行鎮(zhèn)靜效果評價Psychosomatics,2009,50:3Dexmedetomidine 可能減少譫妄發(fā)生率苯二氮唑類也非一無是處Despite the apparent advantages in using either propofol or dexme-detomidine over benzodiazepines for ICU sedation,benzodiazepin

13、es remain important for managing 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 use of other sedative agents is required.Critical Car

14、e 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(A)。 Critical Care Medicine，2013 ， 41Patients from 68 ICUs in five countries.354 patients enrolled in the SEDCOM (Safety and Efficacy of Dexmedetomidine Compared with Midazolam) Delirium assessments up to 30 days of mechanical ven

15、tilation.Crit Care Med 2010 Vol. 38,Crit Care Med 2010 Vol. 38,譫妄常見因素睡眠障礙其他如高齡等麻醉藥物昏迷腦血管意外、癲癇感染中毒或戒斷代謝障礙譫妄睡眠障礙代謝障礙Intensive Care Med ,2007, 33:6673Intensive Care Med ,2007, 33:6673多因素回歸分析，昏迷是獨(dú)立危險因素，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)立危險因素(B)。 使用苯二氮卓類藥物可能是成年ICU患者發(fā)生譫妄的危險因素(B)。對于有發(fā)生譫妄危險的接受機(jī)械通氣治療的成年ICU患者，與輸注苯二氮卓

16、類藥物相比，輸注右美托咪定可能減少譫妄的罹患率(B)。 Critical 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)時間(C)。如果患者具有發(fā)生尖端扭轉(zhuǎn)性室速的危險（即基礎(chǔ)QTc間期延長，服用可延長QTc間期的藥物，或有心律失常病史），反對使用抗精神病藥物(-2C)。Critical Care Medicine，2013 ， 4136 patients with delirium Interventions: Patients 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 Med ,2010 , 38預(yù)防譫妄反對成年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