齐鲁医学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、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2021/9/291Part :Introduction of Dexmedetomidine2021/9/292Medetomidine動物鎮靜麻醉Ketamine (K他命）和 Midazolam 混合Medetomidine Medetomidine混合dextro-medetomidine levo-medetomidine2021/9/293DexmedetomidineAlpha-2 Agonist1999 美國FDA

2、 核准使用Drug2/1 selectivityDexmedetomidine1600Medetomidine1200Clonidine200Dyck, Shafer. Aneasth Pharm Review. 19932021/9/294Dexmedetomidine (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。2021/9/295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2021/9/296腎上腺素接受器Adrenergic receptorsa1b1平滑肌節前Pre-sy

3、naptic氣管平滑肌心臟a2b2擴張心跳心搏量收縮抑制新腎上腺素NE 分泌2021/9/297a2腎上腺素接受器負回饋Regulate release of neurotransmittersControl epinephrine, norepinephrine releaseModulate sympathetic response “negative feedback loop”2021/9/298Dexmedetomidine作用機轉2021/9/299Dexmedetomidine作用部位作用部位Brain (locus ceruleus)第4腦室底上角之色素隆凸Spinal cor

4、d 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 CordLOCUSCERULEUSFOURTHVENTRICLEPONSCEREBRUMCEREBELLUM2021/9/29102-Receptor Subtypes2C2A2Aa2A利尿止痛鎮靜心跳抑制顫抖血管2021/9/2911Mechanism for 2-induced sedation/ hypnosis in the rat locus coeruleus202

5、1/9/29122021/9/2913Dexmedetomidine: Side EffectsBradycardiaHypotensionTransient hypertensionDry mouthLimited amnestic effectExcessive sedationReduction in CBF/CMRO2 in animal model2021/9/2914Dexmedetomidine 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 va

6、soconstriction mediated by 2B-adrenoceptors will BPloading : 1 mcg/kg over 10 min maintenance : 0.2 to 0.7 mcg/kg/hrOnset: 5 -10 minReduced effect: 30 minDuration: 2 hour2021/9/2915Tournique induced hypertensionIncidence: 30%Tourniquet time 60 minAssociated with severe pain and augmented sympathetic

7、 outflowDifficult treatmentUnknown mechanism 2021/9/2916Previous study dataKetamine ( 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?2021/9/2917Exclu

8、sion and Inclusion CrietriaExclusion 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 2021/9/2918GroupingControl groupDexmedetomidine (continuous infusion) Loading

9、:(0.8 g/kg) Continuous infusion rate:(0.4 g/kg/h) Dexmedetomidine (single dose) 1ug/kg for over 10 minsDexmedetomidine (continuous infusion) Loading:(0.5 g/kg) Continuous infusion rate:(0.4 g/kg/h) 2021/9/2919Anesthetic standard procedure General AnesthesiaPre-op : IV 1.5-2 mg MidazolamInduction med

10、ication: 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.TOFRescue (BP) : Perdipine 1ml/ 5min Combined Spinal-Epidural AnesthesiaPre-op : IV 1.5-2 mg MidazolamSpinal bupivaccaine dosage: 12-15 mg Epidural dosage: 0.25% bupivacaine with continuous rate of 4-8 ml/h. Level 15 minRescue: fentanyl 1ml/15mn2021/9/2920Monitoring血液 NE & Epi 濃度(2 times x 10 ml)Post-induction (1 MAC) & tourniquet inflation 60 minFinom