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

1、Part :Introduction of DexmedetomidineMedetomidine 動物鎮靜麻醉 Ketamine (K他命）和 Midazolam 混合 Medetomidine Medetomidine混合dextro-medetomidine levo-medetomidineDexmedetomidine Alpha-2 Agonist 1999 美國FDA 核准使用Drug2/1 selectivityDexmedetomidine1600Medetomidine1200Clonidine200Dyck, Shafer. Aneasth Pharm Review. 1

2、993Dexmedetomidine (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。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新腎上腺素NE 分泌a a2腎上腺素接受器負回饋 Regulate release of neurotransmitters Control epinephrine, norepinephrine release Modulat

3、e sympathetic response “negative feedback loop”Dexmedetomidine作用機轉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, HRDexmedetomidineSpinal CordLOCUSCERULEUSFOURTHVENTRICLEPONSCEREBRUMCEREB

4、ELLUMa a2-Receptor Subtypes2C2A2Aa2A利尿止痛鎮靜心跳抑制顫抖血管Mechanism for 2-induced sedation/ hypnosis in the rat locus coeruleusDexmedetomidine: Side Effects Bradycardia Hypotension Transient hypertension Dry mouth Limited amnestic effect Excessive sedation Reduction in CBF/CMRO2 in animal modelDexmedetomidi

5、ne 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 Duration: 2 hourTournique induced hypertensi

6、on Incidence: 30% Tourniquet time 60 min Associated with severe pain and augmented sympathetic outflow Difficult treatment Unknown mechanism Previous study data Ketamine ( Satsumae et al. A&A, 2001) Clonidine ( Zalunardo et al. A&A, 2002) Dextromethrophan ( Yamashita et al. A&A, 2004) St

7、ellate ganglion blockade ( Arai et al. Acta Anesthesiol Scand, 2004) Dexmedetomidine?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 criteria ASA I-II 20 至75 歲 預期接受骨科下肢常規手術

8、而會打止血帶超過60分鐘者 不論半身或全身麻醉 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) Continuous infusion rate:(0.4 g/kg/h) Anestheti

9、c 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) : Perdipine 1ml/ 5min Combined Spinal-Epidu

10、ral 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/15mnMonitoring 血液 NE & Epi 濃度(2 times x 10 ml)Post-induction (1 MAC) & tourniquet inflation 60 min Finomet

11、er and HRV recordingspreinduction, postinduction, inflation for 30 and 60 min, after deflation, and PORThank You!We are small, but we think big!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新腎上腺素NE 分泌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

12、之作用 Sedation 鎮靜 Anxiolysis 抗焦慮 Analgesia 止痛 交感神經之作用 Sympathetic activity BP, HRDexmedetomidineSpinal CordLOCUSCERULEUSFOURTHVENTRICLEPONSCEREBRUMCEREBELLUMa a2-Receptor Subtypes2C2A2Aa2A利尿止痛鎮靜心跳抑制顫抖血管Grouping Control group Dexmedetomidine (continuous infusion) Loading:(0.8 g/kg) Continuous infusion

13、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) 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) : Perdipine 1ml/ 5min Combined Spinal-Epidural Anesthesia P