1、臨床試驗計劃臨床試驗計劃:DexmedetomidineDexmedetomidine對於止血帶所引起術中高對於止血帶所引起術中高血壓的療效及藥理機轉之探討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Dexmedetomidine对於止血带所引起术中高血压的疗效及药理机转之探讨1Part:Introduction of DexmedetomidineDexmedetomidine对於止血带所引起术中高血压的疗效及药理机转之探讨2Medetomidine 動物鎮靜麻醉 Ketamine(K他命）和 Midazolam 混合 Medetomid
2、ine Medetomidine混合dextro-medetomidine levo-medetomidineDexmedetomidine对於止血带所引起术中高血压的疗效及药理机转之探讨3Dexmedetomidine Alpha-2 Agonist 1999 美國FDA 核准使用Drug2/1 selectivityDexmedetomidine1600Medetomidine1200Clonidine200Dyck,Shafer.Aneasth Pharm Review.1993Dexmedetomidine对於止血带所引起术中高血压的疗效及药理机转之探讨4Dexmedetomidine
3、(Precedex)適應症：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。Dexmedetomidine对於止血带所引起术中高血压的疗效及药理机转之探讨5自主神經系統副交感交感新腎上腺素新腎上腺素乙醯膽鹼腎上腺素接受器腎上腺素接受器Dexmedetomidine对於止血带所引起术中高血压的疗效及药理机转之探讨6腎上腺素接受器腎上腺素接受器Adrenergic receptors平滑肌節前Pre-synaptic氣管平滑肌心臟擴張心跳心搏量收縮抑制抑制新腎上腺素新腎上腺素NE 分泌分泌Dexmedetomidine
4、对於止血带所引起术中高血压的疗效及药理机转之探讨7a a2腎上腺素接受器腎上腺素接受器負回饋 Regulate release of neurotransmitters Control epinephrine,norepinephrine release Modulate sympathetic response“negative feedback loop”Dexmedetomidine对於止血带所引起术中高血压的疗效及药理机转之探讨8Dexmedetomidine作用機轉Dexmedetomidine对於止血带所引起术中高血压的疗效及药理机转之探讨9Dexmedetomidine作用部位
5、作用部位 Brain(locus ceruleus)第第4腦室底上角之色素隆凸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,HRDexmedetomidineSpinal CordLOCUSCERULEUSFOURTHVENTRICLEPONSCEREBRUMCEREBELLUMDexmedetomidine对於止血带所引起术中高血压的疗效及药理机转之探讨10a a2-Receptor Subtypes2C2A2Aa2A利尿
6、止痛鎮靜心跳抑制顫抖血管Dexmedetomidine对於止血带所引起术中高血压的疗效及药理机转之探讨11Mechanism for 2-induced sedation/hypnosis in the rat locus coeruleusDexmedetomidine对於止血带所引起术中高血压的疗效及药理机转之探讨12Dexmedetomidine对於止血带所引起术中高血压的疗效及药理机转之探讨13Dexmedetomidine:Side Effects Bradycardia Hypotension Transient hypertension Dry mouth Limited amn
7、estic effect Excessive sedation Reduction in CBF/CMRO2 in animal modelDexmedetomidine对於止血带所引起术中高血压的疗效及药理机转之探讨14Dexmedetomidine 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
8、 maintenance:0.2 to 0.7 mcg/kg/hr Onset:5-10 min Reduced effect:30 min Duration:2 hourDexmedetomidine对於止血带所引起术中高血压的疗效及药理机转之探讨15Tournique induced hypertension Incidence:30%Tourniquet time 60 min Associated with severe pain and augmented sympathetic outflow Difficult treatment Unknown mechanism Dexmed
9、etomidine对於止血带所引起术中高血压的疗效及药理机转之探讨16Previous study data Ketamine(Satsumae et al.A&A,2001)Clonidine(Zalunardo et al.A&A,2002)Dextromethrophan(Yamashita et al.A&A,2004)Stellate ganglion blockade(Arai et al.Acta Anesthesiol Scand,2004)Dexmedetomidine?Dexmedetomidine对於止血带所引起术中高血压的疗效及药理机转之探讨17Exclusion an
10、d 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 criteriaASA I-II20 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 Dexmedetomidine对於止血带所引起术中高血压的疗效及药理机转之探讨18Grouping Control group Dexmedetomidine(conti
11、nuous 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)Continuous infusion rate:(0.4 g/kg/h)Dexmedetomidine对於止血带所引起术中高血压的疗效及药理机转之探讨19Anesthetic standard procedure General Anesthes
12、ia 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):Perdipine 1ml/5min Combined Spinal-Epidural Anesthesia Pre-op:IV 1.5-2 mg Midazolam Spina
13、l bupivaccaine dosage:12-15 mg Epidural dosage:0.25%bupivacaine with continuous rate of 4-8 ml/h.Level 15 min Rescue:fentanyl 1ml/15mnDexmedetomidine对於止血带所引起术中高血压的疗效及药理机转之探讨20Monitoring 血液 NE&Epi 濃度(2 times x 10 ml)Post-induction(1 MAC)&tourniquet inflation 60 min Finometer and HRV recordingspreinduction,postinduction,inflation for 30 and 60 min,after deflation,and PORDexmedetomidine对於止血带所引起术中高血压的疗效及药理机转之探讨21Thank You!We are small,but we think big!Dexmedetomidine对於止血带所引起术中高血压的疗效及药理机转之探讨22
