基于IPAD2013指南的药物及非药物应用-於江泉

基于IPAD（2013）指南的药物及非药物应用,重症医学科 於江泉,镇静镇痛抗谵妄的必要性！,Hey! I Think he just moved! Add one more!,ICU患者回顾性调查,噪音 医护操作,(翻身、胸部物理治疗、吸痰、穿刺或置管、内窥镜检查、大换药等),没有哪个地方比ICU更恐怖了！再也不想到ICU了！,镇痛镇静抗谵妄,镇痛不足,1,381 patients 44 ICUs in FranceAnalgesic and sedative usePain and sedation assessment on days 2,4 and 6 of the ICU stay,Anesthesiology, 2007，106,近一半患者镇静过深,多数患者镇痛不足,尤其是操作时,指南推荐的镇痛不足药物,Critical Care Medicine，2013 ， 41,建议考虑使用非阿片类镇痛药，以减少阿片类药物用量（或避免使用IV阿片类药物）以及药物相关副作用(+2C)。,Critical Care Medicine，2013 ， 41,阿片类药物最大的问题：成瘾性,Critical Care Medicine，2013 ， 41,Patients 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 and IV meperidine for 24 hours. BPS and VAS is used until extubation.,J Crit Care 2010; 25:458462,Safety of Multiple-Dose IntravenousAcetaminophen,213 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 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) 25:458462,However, their safety profile and effectiveness as sole agents for pain management have not been adequately studied in critically ill patients. Pharmacologic treatment principles extrapolated from non-ICU studies may not be applicable to critically ill patients.然而，作为危重患者疼痛管理的唯一替代药品它们的安全系数和有效性还没有充分研究过。从非ICU患者研究得出的药理学结论可能并不适用于危重症患者。,Critical Care Medicine，2013 ， 41,治疗神经病性疼痛时，除阿片类药物外，推荐经肠道给予加巴喷丁(gabapentin)或卡马西平(carbamazepine) (+1A)。,Critical Care Medicine，2013 ， 41,36 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 rating .Sedation was recorded with a Ramsay sedation scale .,Anesth Analg 2005;101:2205,成年ICU患者接受其他有创或可能引起疼痛的操作前，建议进行预先镇痛和（或）非药物性干预以减轻疼痛(+2C)。成年ICU患者拔除胸腔引流管前，推荐进行预先镇痛和（或）非药物性干预（如放松）(+1C)。,Critical Care Medicine，2013 ， 41,40 adults CABG patientsA 10-cm 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 removal.,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 epidural analgesia be considered for patients with traumatic rib fractures (+2B).,Critical Care Medicine，2013 ， 41,镇 静,对于成年ICU患者维持轻度镇静可以改善临床预后（如缩短机械通气时间及ICU住院日）(B)。 对于接受机械通气的成年ICU患者，建议使用非苯二氮卓类（异丙酚或右美托咪定）而不是咪达唑仑或劳拉西泮，以改善临床预后(+1A)。,Critical Care Medicine，2013 ， 41,理想的ICU镇静药物,起效决,镇静作用强镇静程度易控制对呼吸循环功能影响小 与其他药物无明显的相互干扰作用 消除方式不依赖于肝、肾具有多种体内代谢途径消除半衰期短、不蓄积 价格低廉最小的不良反应、后遗效应小兼有镇痛、抗谵妄的效应,目前尚无药物能符合以上所有要求！,与广泛分布于中枢与周围神经系统及其他器官组织2AR 结合脑内2AR最密集的区域在脑干的蓝斑蓝斑是大脑内负责调解觉醒与睡眠的关键部位右美托咪啶作用于脑干蓝斑核内的2AR,而产生镇静-催眠，引发并维持自然非动眼睡眠,生理作用,与拟 GABA 药物的差别,Dexmedetomidine作用于脑干（蓝斑）自然非动眼睡眠唤醒系统功能依然存在拟GABA药物作用于下丘脑非自然睡眠,Dexmedetomidine vs Midazolam,Prospective, 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 for dexmedetomidine 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 trials 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 European countries and 2 centers in Russia,JAMA, 2012, 307( 11),Dexmedetomidine vs Midazolam/ Propofol,Dexmedetomidine vs Midazolam/ Propofol,右美托咪定对呼吸的影响,10名健康男性 (2027 yr) 持续静脉输注右美托咪定使血浆浓度达0.5, 0.8, 1.2, 2.0, 3.2, 5.0, and 8.0ng/ml（正常血药浓度5-10倍）并维持40min,Anesthesiology, 2000 ，93（ 2）：382-94,右美托咪定对循环的影响,出现两相反应第一相：血压增高，心率减慢机制：激动突触前 2B和突触后 1受体第二相：典型的突触前 2受体激动,血压下降 心率减慢,Fig 1 Alfentanil requirements for patients receiving dexmedetomidine and propofol whilst mechanically ventilated in the ICU. Median, IQR and extremes are shown.,J. Anaesth. 2001;87:684-690,Dexmedetomidine 减少镇痛药物用量,20个成年患者术后随机分成右美托咪定组或丙泊酚组同时使用Ramsay和 bispectral index (BIS)进行镇静效果评价,Psychosomatics,2009,50:3,Dexmedetomidine 可能减少谵妄发生率,苯二氮唑类也非一无是处,Despite the apparent advantages in using either propofol or dexme-detomidine over benzodiazepines for ICU sedation,benzodiazepines 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 Care Medicine，2013 ， 41,谵 妄,成年ICU患者的谵妄伴随病死率升高(A)。 成年ICU患者的谵妄伴随ICU住院日及总住院日延长(A)。,Critical Care Medicine，2013 ， 41,Patients 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 ventilation.,Crit Care Med 2010 Vol. 38,Crit Care Med 2010 Vol. 38,谵妄常见因素,Intensive Care Med ,2007, 33:6673,Intensive Care Med ,2007, 33:6673,多因素回归分析，昏迷是独立危险因素，包括镇静诱导的昏迷,谵 妄,昏迷是ICU患者发生谵妄的独立危险因素(B)。 使用苯二氮卓类药物可能是成年ICU患者发生谵妄的危险因素(B)。对于有发生谵妄危险的接受机械通气治疗的成年ICU患者，与输注苯二氮卓类药物相比，输注右美托咪定可能减少谵妄的罹患率(B)。,Critical Care Medicine，2013 ， 41,谵 妄,非典型的抗精神病药物可能缩短成年ICU患者的谵妄持续时间(C)。如果患者具有发生尖端扭转性室速的危险（即基础QTc间期延长，服用可延长QTc间期的药物，或有心律失常病史），反对使用抗精神病药物(-2C