臺灣博碩士論文加值系統

一、研究背景及目的:
麻醉的目的是讓病人處於適度抑制、但正常生理狀態下，讓手術順利的進行。這包括了可恢復、可控制的神智喪失，我們可用腦波來偵測病人睡眠狀態。以肌肉鬆弛劑來暫時癱瘓病人的行動，同時以神經刺激器來偵測神經肌肉終端的阻斷程度。心跳、血壓、血氧飽和濃度、吐氣末二氧化碳濃度等循環、呼吸生理徵象也都要偵測，但這都受自主神經所控制、影響。所以探討麻醉藥物對自主神經的影響，就顯得非常重要。而自主神經的偵測，目前只有透過心率變異 (heart rate variability) 的分析來了解。本研究藉着對靜脈麻醉劑Propofol和吸入性麻醉劑 Desflurane對自主神經的影響，同時以聽力誘發電位 (Auditory evoked potential)作為睡眠狀態的偵測，來了解麻醉藥劑對自主神經系統的影響 (交感與副交感神經的平衡)，進而解釋此二藥劑在臨床上所產生血流動力學上的變化。
Propofol因為甦醒的快且副作用少,但是以Propofol誘導麻醉時,常會造成血壓及心跳下降，Propofol會引起動靜脈的擴張,減弱baroreflex機制,抑制心肌收縮力量,這都可解釋血壓下降。 雖然交感神經系統的抑制可部分解釋血液動力學的變化,但明確的作用機制尚不可知。如果Propofol降低心臟交感神經的活動性,它會造成心率下降。臨床麻醉誘導時,雖然周邊交感神經活動性及血壓大幅下降,但心率反而上升,並且預防性使用anticholingerics並不能防止Propofol在健康成人偶而造成的嚴重心率過慢 (profound bradycardia) 和心跳停止。
Desflurane是一種較新的吸入性麻醉氣，因為它有低的血氣溶解度 (blood gas solubility) 所以麻醉深度可迅速調整，並且病人可以很快地甦醒。在一個健康的、自願的人體實驗中，利用microneurography 來測定心臟血管的反應是否與交感神經有關，結果作者認為當desflurane 的濃度從1.0 到1.5 MAC時，會引起交感神經的興奮，高血壓、心跳加快。也有在狗的動物實驗中，desflurane 造成血壓的降低，全身血管阻力 (systemic vascular resistance) 以及心肌收縮力的下降，但都比isoflurane來得輕微，當使用藥物來阻斷交感神經時，這兩種藥物的差別便消失了， 這似乎看起來desflurane是個例外 (其他吸入性麻醉氣對交感神經似乎抑制大於活化)。Desflurane在濃度變化的瞬間，而不在穩定狀態 (steady-state)，會活化支配周邊血管的交感神經纖維。 但有的動物實驗抽驗desflurane和isoflurane麻醉下血中的norepinphine濃度來作比較， 結果並無不同，所以desflurane並非全面性交感神經系統的刺激物。也有動物實驗證實desflurane會放出 intramyocardial catecholamines，此物質會隨濃度的升高而使分離的心臟 (isolated heart) 心率越慢。也有動物實驗顯示給予乙型接受器 (β- receptor) 阻隔之後，並不會減少desflurane引起的心跳過快。但也有研究報告desflurane對低頻區的抑制大於高頻區，表示對交感神經的抑制作用大於副交感神經的抑制作用 (Widmark 1998)。

當我們觀察心電圖, 可發現每一次的心跳間格或者說瞬間心跳速率都不一樣, 這就是心率變異 (heart rate variability，HRV)。在正常人, 即使是在平靜、穩定的狀態下, 心跳也都會有相當程度的變化。傳統上這些變化都被忽視或利用平均速率來代瞬間心率, 一直到開始利用心率變化來測知胎兒在子宮內生存及活動情形, 心率變化才被重視。心率快慢為何如此變化,是不是有一控制頻率的內在機轉在管轄呢?為了解決這個問題, 人們開始嘗試使用一些頻譜分析法, 也就是依時間順序輸入的訊號, 利用數學工具加以轉換, 但是廣泛在人體應用的頻譜分析, 則是在快速傅利葉轉換 (Fast Fourier Transformation ,FFT) 出現後才有進展, 因為FFT可以在個人電腦上快速進行, 具有實用性。根據研究,有三個譜區可分離出來:超低頻區 (Very Low Frequency VLF: 0-0.04Hz) ,低頻區(Low frequency LF: 0.05-0.15Hz) ,高頻區 (High frequency HF: 015-0.4Hz)。各區的生理意義一直是大家企圖解釋的內容。超低頻區由於需要較長時間觀察及分析,手術期間較少利用。低頻區,由於實驗記錄時間可配合, 得到的結果也多,根據藥理與生理的實驗證明此區與交感、副交感神經的活躍度有關。至於高頻區, 許多實驗證實與呼吸頻率正好吻合, 由於呼吸對心跳的影響乃是藉副交感去控制, 所以此區被認為和副交感神經的活躍度有關, 有人利用低頻度區的高頻區的積分面積比, 代表兩種自主神經活躍度比。

因心率變異會受麻醉深度的影嚮，所以我們同時採用聽力誘發電位來作為麻醉深度的指標，一種新發展的指標ARX-derived Auditory evoked potential Index。此方法為從腦波中萃取 middle-latency auditory evoked potential (MLAEP)，同時以 autoregressive model 加以exogenous input (ARX) adaptive method 算出來的一個參數A-Line ARX Index (AAI)。而AAI即作為麻醉深度的指標。

本研究同時採用線性及非線性的兩種方法，探討麻醉的清醒度，同時測量心率變異在麻醉間的改變，可進一步探討麻醉中自主神經系統平衡的改變。本研究不但有助於對麻醉的基本原理的了解，同時也可減少麻醉藥物的用量，更增加病人的安全性。

二、研究方法:
本研究經人體試驗委員會同意及病人簽署同意書，我們將選取36位美國麻醉醫學會體位分級 (ASA classification) 第一級，接受常規手術的病患。排除有嚴重心肌梗塞，鬱血性心臟病，醣尿病 聽覺障礙以及其他影響自主神經系統的疾病，同時沒有服用影響心臟血管的藥物。每位病患需空腹八小時，到達手術室時，隨意分成兩組，給予標準生理偵器及AAI 偵測器A-Line，偵測器從腦中萃取 middle-latency auditory evoked potential (MLAEP)，而計算出一個參數 A-Line ARX Index (AAI)。 病人以平躺的姿勢，偵測心率並作心率變異的分析。誘導前每位病人給從靜脈給予１0 ml/kg 的生理食鹽水，吸入的氧氣、吐氣末二氧化碳以及desflurane的濃度，皆持續由氣體分析儀 (infrared gas analyzer)分析。病人分成兩組，在麻醉誘導前皆面罩式100%氧氣給予並持續 2-3分鐘。在propofol 那ㄧ組病人皆接受300ug/kg/min的propofol的持續靜脈注射，在desflurane那ㄧ組病人皆接受fentanyl I ug/kg的靜脈注射，並給予N2O,O2,以1L:1L中 3%-6%-9%-12% desflrane漸進方式來誘導.直到AAI數字降到25以下，持續偵測血氧飽合濃度和吐氣末二氧化碳，並以溫和間歇正壓呼吸 (IPPV) 從面罩式給予氧氣，以維持正常呼吸。

三、研究結果:
心率變異的分析顯示:在propofol麻醉下，高頻區 (HF) 的能量 (power) 有降低的趨勢，LH/FH反而上升，顯示propofol對自主神經有抑制作用，尤其是對副交感神經的抑制較強。desflurane降低低頻區 (LF)，但對高頻區 (HF) 有上升的趨勢,LH/FH下降，表示對交感神經的抑制較強。對於聽力誘發電位的偵測，則兩組都能達到麻醉狀態 (AAI=25±5) 。

四、結論
靜脈麻醉劑Propofol和吸入性麻醉劑 Desflurane對腦幹 (自主神經的活動性) 的影響是不一致的，但對大腦皮質 (神智的清醒) 的影響是一致的。

一、中文摘要•••••••••••••••••••5
二、緒論•••••••••••••••••••••8
三、研究方法與材料••••••••••••••••28
四、結果•••••••••••••••••••••30
五、討論•••••••••••••••••••••33
六、展望•••••••••••••••••••••44
七、論文英文簡述•••••••••••••••••45
八、參考文獻•••••••••••••••••••53
九、圖表•••••••••••••••••••••62

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