- 學位論文
麻醉與神經學監測-動物模型與臨床應用
Anesthesia and Intraoperative Neuromonitoring - Animal Model and Clinical Applications
摘要
目的: 手術中神經學監測，近年來逐漸被接受應用於確認肉眼神經之辨識，降低神經傷害的機率，然而這項技術可能因為麻醉影響，導致訊息的誤判而會增加神經受傷的風險。本研究目的為建立標準化麻醉模式運用於術中神經監測，包括確認喉部電極置放、最佳化的使用非去極化肌肉鬆弛劑對神經監測的影響。進一步建立一套前瞻性豬隻實驗模型來探討: 去極化與非去極化肌肉鬆弛劑之肌電圖訊號恢復曲線、肌肉鬆弛劑拮抗劑可以快速恢復肌電圖訊號。研究成果有助於使術中神經監測成為可信的工具，預防手術中神經受損。 方法: 動物實驗部分共使用27隻雄性國產豬，所有豬隻均接受氣管插管全身麻醉與神經監測系統。紀錄6隻豬給予去極化肌肉鬆弛劑前後，不同肌肉群的肌電圖變化與恢復。使用9隻豬，比較去極化與非去極化肌肉鬆弛劑對喉部肌肉群神經監測訊號之恢復情況。以12隻豬接受肌肉鬆弛劑rocuronium後，觀察使用肌肉鬆弛劑之拮抗劑與自然恢復組，喉部肌電圖之恢復情況。 臨床試驗部分，共納入350位接受甲狀腺手術並使用神經監測系統之病患，以四聯刺激(TOF)作為神經肌肉傳導的量化監控工具。第一階段:探討220位病患，肌電圖氣管內管深度與位移。第二階段:比較常用之非去極化肌肉鬆弛劑對術中神經監測系統的影響；並納入80位病患，找出肌肉鬆弛劑的最佳劑量。第三階段:納入50位病患，建立神經肌肉阻斷快速恢復之麻醉流程，麻醉誘導使用肌肉鬆弛劑rocuronium，手術開始時給予拮抗劑sugammadex。 結果: 動物實驗部分首先建立一套探討肌肉鬆弛劑對術中神經監測影響的動物模式，並發現對去極化肌肉鬆弛劑以喉部肌肉最敏感，依序是肱三頭肌、斜方肌，最後是橫膈肌。其次發現使用去極化肌肉鬆弛劑與低劑量非去極化肌肉鬆弛劑，喉部肌肉肌電圖訊號恢復良好。最後喉部肌電圖之恢復時間，在自然恢復、接受低與高劑量肌肉鬆弛劑之拮抗劑後，分別為: 49±15、13.2±5.6與 4.2±1.5分鐘。 臨床試驗部分，第一階段發現: 肌電圖氣管內管深度平均深度為男性20.6 ± 0.97公分、女性19.6 ± 1.0公分；而頸部擺位後氣管內管位移則由變深16公厘至變淺5公厘。第二階段發現:使用單次插管劑量之非去極化肌肉鬆弛劑，手術中仍神經監測系統仍可使用但是肌電圖訊號則會減弱；投與肌肉鬆弛劑rocuronium0.3或0.6毫克/公斤30分鐘後，則發現可測得肌電圖訊號的比例分別為100%與53%。第三階段發現: 給予拮抗劑(sugammadex) 5分鐘內，四聯刺激(TOF)即可由0恢復至0.9；所有病患皆可於手術初期測得高品質之肌電圖訊號。 結論: 本試驗建立有用可靠的動物模式來探討肌肉鬆弛劑對術中神經監測影響；此模式顯示神經監測時，可以用低劑量肌肉鬆弛劑rocuronium取代去極化肌肉鬆弛劑做為麻醉誘導。臨床設立甲狀腺手術術中神經監測系統時，氣管內管深度平均深度適用於一般群眾，是實用的參考值；然而頸部擺位可能導致氣管內管嚴重位移。單次插管劑量之非去極化肌肉鬆弛劑可用於神經監測；使用肌肉鬆弛劑rocuronium 0.3毫克/公斤是最佳用法，可以在手術初期即有良好肌電圖訊號以及在絕大部分病患達到足夠的插管條件。動物模型與臨床試驗均顯示拮抗劑(sugammadex 2毫克/公斤)可快速回復被抑制的神經肌肉傳導而且確保最佳的神經監測條件。
並列摘要
Objectives: The application of intraoperative neuromonitoring (IONM) in thyroid, parotid and spine surgery has gained wide acceptance as an adjunct to prevent nerve injury. It can be applied to aid in nerve localization during surgery and to prevent irreversible neurological damage. However, the anesthetic factors might interfere with the interpretation of EMG signal and put the nerve at risk of injury. The porcine model was setup to investigate the effect of following anesthetic factors on IONM: 1. To investigate differential sensitivity of different muscles to succinylcholine. 2. To compare the neuromuscular transmission recovery profiles between succinylcholine and rocuronium. 3. To confirm the feasibility of reversal of rocuronium-induced neuromuscular block with sugammadex. The aims in clinical application were: firstly, to setup up standardized anesthesia and IONM protocol; secondly, to explore the optimal usage of non-depolarizing neuromuscular blocking agent (NMBA); and finally, to investigate the feasibility of rapid neuromuscular blockade reversal to improve neuromonitoring signal. Methods: The prospective porcine model recruited 27 male Duroc-Landrace male piglets that underwent general anesthesia and nerve integrity monitor (NIM) system for IONM. Firstly, 6 piglets were enrolled to setup a feasible animal model for IONM and to investigate electromyography (EMG) differential sensitivity of different muscles to succinylcholine. Secondly, 9 piglets were enrolled to compare between succinylcholine and rocuronium on the recovery profile of the laryngeal muscles during IONM of the recurrent laryngeal nerve. Finally, 12 piglets were injected with rocuronium and randomly allocated to receive normal saline, sugammadex 2 mg/kg, or sugammadex 4 mg/kg to compare the recovery of laryngeal EMG. In the clinical application research, 350 patients undergoing IONM during thyroid surgery were enrolled. Firstly, optimal endotracheal tube depth and displacement was investigated (n=220). Second, comparison of commonly used NMBAs (atracurium and rocuronium) and optimal NMBA dosage were investigated (n=80). The train-of-four (TOF) ratio was used for continuous quantitative monitoring of neuromuscular transmission. Finally, an enhanced neuromuscular recovery protocol- rocuronium at anesthesia induction and sugammadex at the operation start was investigated (n=50). Results: In porcine research, firstly, we found that the vocalis muscle was the most sensitive to succinylcholine. Second, both succinylcholine (1 mg/kg) and low-dose rocuronium (0.3 mg/kg) had favorable EMG recovery profiles on the laryngeal muscle. Finally, it took 49±15, 13.2±5.6, and 4.2±1.5 minutes for the 80% recovery of laryngeal EMG after injection of saline, sugammadex 2 mg/kg, and sugammadex 4 mg/kg respectively. In clinical application, firstly, the optimal tube depth was 20.6 ± 0.97 cm in men and 19.6 ± 1.0 cm in women (p<0.01). The tube displacement after neck extension ranged from 16 mm upward to 5 mm downward. Secondly, EMG signal was detectable but reduced during IONM after single dose of atracurium or rocuronium. At 30 minutes after administration of rocuronium 0.3 and 0.6 mg/kg, the rate of positive EMG response was 100% and 53% respectively. Finally, the TOF ratio recovered from 0 to >0.9 within 5 minutes after administration of sugammadex 2 mg/kg at the operation start. All patients had positive and high EMG amplitude at the early stage of the operation. Conclusions: The porcine model was demonstrated to be useful and reliable to investigate the effects of NMBA on IONM. In this model, low-dose rocuronium may replace succinylcholine for anesthesia induction during IONM. For setup of IONM, the mean depth of the NIM EMG tube would be a useful reference value for the general population undergoing IONM during thyroid surgery. However, the EMG tube position can be severely displaced after the patient has been fully positioned. With respect to NMBA for IONM during thyroid surgery, a single dose of either rocuronium or atracurium was feasible. Moreover, 0.3 mg/kg of rocuronium might be an optimal dosage that provided good EMG signals at the early stage of the operation and satisfactory intubating conditions in most patients. Both porcine model and human application showed that sugammadex 2 mg/kg allows effective restoration of neuromuscular function suppressed by rocuronium and assures optimal IONM condition.