Dexmedetomidine對(duì)於止血帶所引起術(shù)中高血壓的療效及藥理機(jī)轉(zhuǎn)之探討

1、Part :Introduction of DexmedetomidineMedetomidine 動(dòng)物鎮(zhèn)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 核準(zhǔn)使用Drug2/1 selectivityDexmedetomidine1600Medetomidine1200Clonidine200Dyck, Shafer. Aneasth Pharm Review. 1

2、993Dexmedetomidine (Precedex)適應(yīng)癥：適應(yīng)癥：適用於在加護(hù)病房中，插管且接受呼吸器治療的病患鎮(zhèn)靜用。Precedex應(yīng)該以連續(xù)輸注的方式給予，連續(xù)輸注以24小時(shí)為限。自主神經(jīng)系統(tǒng)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(jié)前Pre-synaptic氣管平滑肌心臟擴(kuò)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(fù)回饋 Regulate release of neurotransmitters Control epinephrine, norepinephrine release Modulat

3、e sympathetic response “negative feedback loop”Dexmedetomidine作用機(jī)轉(zhuǎn)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(jīng) 中樞神經(jīng)之作用 Sedation 鎮(zhèn)靜 Anxiolysis 抗焦慮 Analgesia 止痛 交感神經(jīng)之作用 Sympathetic activity BP, HRDexmedetomidineSpinal CordLOCUSCERULEUSFOURTHVENTRICLEPONSCEREBRUMCEREB

4、ELLUMa a2-Receptor Subtypes2C2A2Aa2A利尿止痛鎮(zhèn)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(dǎo)阻滯的病患，要小心使用 Administer loading dose slowly 第1個(gè)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(duì)dexmedetomidine或其他2 agonist過敏者 預(yù)期下肢止血帶使用會(huì)超過150分鐘或低於60分鐘 Inclusion criteria ASA I-II 20 至75 歲 預(yù)期接受骨科下肢常規(guī)手術(shù)

8、而會(huì)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(jié)前Pre-synaptic氣管平滑肌心臟擴(kuò)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(jīng) 中樞神經(jīng)

12、之作用 Sedation 鎮(zhèn)靜 Anxiolysis 抗焦慮 Analgesia 止痛 交感神經(jīng)之作用 Sympathetic activity BP, HRDexmedetomidineSpinal CordLOCUSCERULEUSFOURTHVENTRICLEPONSCEREBRUMCEREBELLUMa a2-Receptor Subtypes2C2A2Aa2A利尿止痛鎮(zhèn)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