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1、1,臨床試驗計劃:Dexmedetomidine對於止血帶所引起術中高血壓的療效及藥理機轉之探討,Presenter:勞萱之醫師 Correspondence: 黃俊仁主任,2,Part :Introduction of Dexmedetomidine,3,Medetomidine,動物鎮靜麻醉 Ketamine (K他命）和 Midazolam 混合 Medetomidine Medetomidine混合dextro-medetomidine levo-medetomidine,4,Dexmedetomidine,Alpha-2 Agonist 1999 美國FDA 核准使用,Dyck, S
2、hafer. Aneasth Pharm Review. 1993,5,Dexmedetomidine (Precedex),適應症： 適用於在加護病房中，插管且接受呼吸器治療的病患鎮靜用。Precedex應該以連續輸注的方式給予，連續輸注以24小時為限。,6,自主神經系統,副交感,交感,新腎上腺素,乙醯膽鹼,腎上腺素接受器,7,腎上腺素接受器Adrenergic receptors,a1,b1,平滑肌,節前Pre- synaptic,氣管平滑肌,心臟,a2,b2,擴張,心跳 心搏量,收縮,抑制 新腎上腺素NE 分泌,8,a2腎上腺素接受器,負回饋,Regulate release of ne
3、urotransmitters Control epinephrine, norepinephrine release Modulate sympathetic response “negative feedback loop”,9,Dexmedetomidine作用機轉,10,Dexmedetomidine作用部位,作用部位 Brain (locus ceruleus)第4腦室底上角之色素隆凸 Spinal cord 脊髓 交感神經 中樞神經之作用 Sedation 鎮靜 Anxiolysis 抗焦慮 Analgesia 止痛 交感神經之作用 Sympathetic activity BP,
4、 HR,Spinal Cord,LOCUSCERULEUS,FOURTHVENTRICLE,PONS,CEREBRUM,CEREBELLUM,11,12,Mechanism for 2-induced sedation/ hypnosis in the rat locus coeruleus,13,14,Dexmedetomidine: Side Effects,Bradycardia Hypotension Transient hypertension Dry mouth Limited amnestic effect Excessive sedation Reduction in CBF/
5、CMRO2 in animal model,15,Dexmedetomidine 的使用 (Adult),Heart block 心房心室傳導阻滯的病患，要小心使用 Administer loading dose slowly 第1個劑量要慢慢給 Transient vasoconstriction mediated by 2B-adrenoceptors will BP loading : 1 mcg/kg over 10 min maintenance : 0.2 to 0.7 mcg/kg/hr Onset: 5 -10 min Reduced effect: 30 min Durati
6、on: 2 hour,16,Tournique induced hypertension,Incidence: 30% Tourniquet time 60 min Associated with severe pain and augmented sympathetic outflow Difficult treatment Unknown mechanism,17,Previous study data,Ketamine ( Satsumae et al. A&A, 2001) Clonidine ( Zalunardo et al. A&A, 2002) Dextromethrophan
7、 ( Yamashita et al. A&A, 2004) Stellate ganglion blockade ( Arai et al. Acta Anesthesiol Scand, 2004) Dexmedetomidine?,18,Exclusion and Inclusion Crietria,Exclusion Criteria 貧血 (Hct 20) 肥胖 (BMI 40) 肝或腎功能異常者 心律不整,AV Block,或是心臟鬱血性衰竭 對dexmedetomidine或其他2 agonist過敏者 預期下肢止血帶使用會超過150分鐘或低於60分鐘,Inclusion cr
8、iteria ASA I-II 20 至75 歲 預期接受骨科下肢常規手術而會打止血帶超過60分鐘者 不論半身或全身麻醉,19,Grouping,Control group Dexmedetomidine (continuous infusion) Loading:(0.8 g/kg) Continuous infusion rate:(0.4 g/kg/h) Dexmedetomidine (single dose) 1ug/kg for over 10 mins Dexmedetomidine (continuous infusion) Loading:(0.5 g/kg) Continu
9、ous infusion rate:(0.4 g/kg/h),20,Anesthetic standard procedure,General Anesthesia Pre-op : IV 1.5-2 mg Midazolam Induction medication: fentanyl 2 ug/ml, propofol 2mg/kg, and recuronium 0.6 mg/kg. Maintenance medication: sevoflurane which concentration is adjusted to keep BIS 40-45. TOF Rescue (BP)
10、: Perdipine 1ml/ 5min,Combined Spinal-Epidural Anesthesia Pre-op : IV 1.5-2 mg Midazolam Spinal bupivaccaine dosage: 12-15 mg Epidural dosage: 0.25% bupivacaine with continuous rate of 4-8 ml/h. Level 15 min Rescue: fentanyl 1ml/15mn,21,Monitoring,血液 NE & Epi 濃度(2 times x 10 ml) Post-induction (1 MAC) & tourniquet inflation 60 min Finometer and HRV recordings preinduction, postinduction, inflation for 30 and 60 min, after deflation, and POR,22,Thank You!,We are small, but we think big!,23,
