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研究生:蔣馨儀
研究生(外文):Sin-Yi Jiang
論文名稱:Diazepam-Ketamine和Midazolam-Ketamine於斑龜 之麻醉作用和Flumazenil之翻轉效果
論文名稱(外文):Anesthesia with Diazepam-Ketamine and Midazolam-Ketamine and its Reversal with Flumazenil in the Chinese Stripe-Necked Turtle (Ocadia sinensis)
指導教授:楊志寰
指導教授(外文):Chih-Huan Yang
口試委員:董光中吳應寧
口試委員(外文):Kwong-Chung Tung
口試日期:2007-06-12
學位類別:碩士
校院名稱:國立中興大學
系所名稱:獸醫學系所
學門:獸醫學門
學類:獸醫學類
論文種類:學術論文
論文出版年:2007
畢業學年度:95
語文別:中文
論文頁數:65
中文關鍵詞:斑龜麻醉
外文關鍵詞:ketaminediazepammidazolamflumazenilOcadia sinensis
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龜類通常需要麻醉或鎮靜以施行臨床上之處理程序。由於其解剖與生理學和哺乳類有所差異,因此龜類對於藥物之反應亦可能有所不同。本研究的目的在評估各種diazepam-ketamine(DIZ-KET)和midazolam-ketamine(MID-KET)劑量組對斑龜(Chinese stripe- necked turtle, Ocadia sinensis)之麻醉作用,並觀察特異性拮抗劑flumazenil(FMZ)對DIZ-KET和MID-KET麻醉作用之影響。同時亦欲瞭解定量劑量組是否對不同體重斑龜之麻醉作用具有差異性。本實驗使用之劑量組包括DIZ-KET(2-60、4-60、2-90 mg/kg,n = 6)和MID-KET(2-60、4-60、2-90 mg/kg,n = 6)。實驗龜在藥物注射後,根據保護性反射(眼瞼、角膜、顎張力、頭頸部張力、四肢對夾捏或碰觸之回縮性反射)之反應,判定其麻醉深度,並記錄麻醉各分期時間(導入期、麻醉期、外科麻醉期與回復期)和麻醉深度各分級時間。本研究使用之DIZ-KET與MID-KET劑量組皆可使斑龜達到麻醉期。於定量DIZ(2 mg/kg)和MID(2 mg/kg),KET由60 mg/kg增加至90 mg/kg,可分別縮短導入期角膜反射減弱(由5.3 ± 0.8分鐘減至2.2 ± 0.3分鐘)與眼瞼反射減弱(由3.0 ± 0.4分鐘減至1.3 ± 0.2分鐘)時間,且能顯著延長麻醉時間(分別由97.2 ± 18.0分鐘增至187.8 ± 28.8分鐘和由103.3 ± 9.4分鐘增至181.8 ± 19.5分鐘),但並未延長回復期。於體重差異性實驗,相同劑量DIZ-KET(2-90 mg/kg)引起之麻醉現象,重體重組龜(平均:2.66 ± 0.07 kg;範圍:2.48-3.00 kg)之外科麻醉期(83.4 ± 16.1分鐘)明顯較輕體重組(平均:1.03 ± 0.04 kg;範圍:0.91-1.13 kg)(12.5 ± 6.2分鐘)長(p<0.05),但於導入期、麻醉期或回復期,彼此無顯著性差異。FMZ(0.05 mg/kg,IM)可在給藥後1-2分鐘內能有效翻轉DIZ-KET(2-90 mg/kg)和MID-KET(2-90 mg/kg)之麻醉作用和顯著性縮短麻醉期和所有反射完全回復之時間,亦顯著縮短MID-KET(2-90 mg/kg)之回復期。於本實驗使用之劑量組,增加DIZ、MID或KET劑量均會增強心搏速率和呼吸速率之抑制作用。不過,拮抗劑之使用並未顯著影響心搏速率和呼吸速率。本實驗使用之DIZ-KET與MID-KET劑量組雖然皆可使斑龜達到麻醉,但以2-90 mg/kg劑量最能產生一致的穩定麻醉狀態。而且flumazenil可以翻轉斑龜DIZ-KET和MID-KET之麻醉作用,應可應用於臨床上以縮短麻醉時間。
Chelonians frequently require anesthesia or sedation to perform clinical procedures. Many of the commonly used anesthetic agents were designed for use in mammalian species. Given the differences in respiratory anatomy and physiology, the response in chelonians to these agents often differs from the response in mammalian species. The aim of the study was to determine the anesthetic effect of diazepam–ketamine (DIZ-KET) and midazolam-ketamine (MID-KET) in the chinese stripe-necked turtle (Ocadia sinensis), and to observed the ability of specific antagonist flumazenil (FMZ) to antagonize the effect of DIZ-KET (2-90 mg/kg) and MID-KET (2-90 mg/kg), respectively. The experiments also aimed to evaluate whether weight was a factor in the anesthetic effect on the turtles. The dosage groups in the study included DIZ-KET (2-60, 4-60 and 2-90 mg/kg, n=6) and MID-KET (2-60, 4-60 and 2-90 mg/kg, n=6). Anesthetic depth was based on testing protective reflexes (palpebral reflex, corneal reflex, jaw tone, head withdrawal reflex, and limbs withdrawal reflexes/ by touching or pinching). The induction time, duration of anesthesia, duration of surgical anesthesia and recovery time were recorded. The duration of each anesthesia level were also recorded. All dosages of DIZ-KET and MID-KET could achieve levels of anesthesia. Both dosages of DIZ (2 mg/kg) and MID (2 mg/kg) with an increased KET dosage (from 60 to 90 mg/kg) shortened the time of diminished corneal reflex (from 5.3 ± 0.8 to 2.2 ± 0.3 min) and palpebral reflex (from 3.0 ± 0.4 to 1.3 ± 0.2 min) and significantly prolonged the duration of anesthesia (from 97.2 ± 18.0 to 187.8 ± 28.8 min vs. from 103.3 ± 9.4 to 181.8 ± 19.5 min), but did not reduce the recovery time. In the experiments factoring in weight, the same dosage of DIZ-KET (2-90 mg/kg) in heavier turtles (mean: 2.66 ± 0.07 kg ; range: 2.48-3.00 kg) had much longer periods of surgical anesthesia (83 ± 15 min) than in the lighter turtles (mean: 1.03 ± 0.04 kg ; range: 0.91-1.13 kg) (13 ± 5 min), but there were no significant differences between these two groups in induction time, duration of anesthesia, or recovery time. Flumazenil was effective on reversing the anesthetic effects of DIZ-KET and MID-KET within 1-2 minutes and significantly shortened the duration of anesthesia, the recovery time for all the reflexes, and the complete recovery time of MID-KET (2-90 mg/kg) regimen. The dosage groups revealed that DIZ-KET and MID-KET could increase the heart rate and the respiratory rate. However, the use of antagonist did not affect the heart rate or the respiratory rate significantly. Although all dosages of DIZ-KET and MID-KET regimens induced anesthesia, the results indicated that DIZ-KET and MID-KET at 2-90 mg/kg induced the most stable surgical anesthesia. The anesthetic effects were effectively and safely antagonized by 0.05 mg/kg flumazenil, which could be applied clinically to reduce the duration of anesthesia.
中文摘要……………………………………………i
英文摘要…………………………………………...ii
目次………………………………………………..iii
表次………………………………………………..vi
圖次………………………………………………viii
第一章 緒言…………………….………………...1
第二章 文獻探討……………….………………...3
第一節 台灣原生龜類─斑龜之介紹……….…....3
一、 外型特徵……………………………….……...3
二、 性別之判定……………………….…………...3
三、 年齡之判定………………………….………...4
四、 野外斑龜之族群結構......................................5
五、 生殖特性……………….……………………...5
六、 食性……………………….…………………...5
第二節 龜之解剖與生物學………………….…...5
一、 殼……….……………………………………...5
二、 四肢…………………….……………………...6
三、 心血管系統…………………….……………...6
四、 心電圖…………………………………….…...9
五、 呼吸系統………………….……………….….11
六、 腎門系統……………………..……………….13
第三節 Benzodiazepines類藥物…………..….....13
一、 Benzodiazepines類藥物之簡介……......…….13
二、 作用機制………………......……………...…..14
三、 Midazolam……………………………..……...15
(一) 歷史與簡介……………………………..….15
(二) 物理與化學性狀…………………………….15
(三) 藥理作用…………………………………….16
(四) 獸醫學之應用……………………………….17
四、 Diazepam……………………………………….18
(一) 歷史與簡介………………………………….18
(二) 物理與化學性狀…………………………….19
(三) 藥理作用…………………………………….20
(四) 獸醫學之應用……………………………….20
五、 Midazolam與Diazepam之比較………………21
第四節 Flumazenil………………………………....22
一、 Benzodiazepines類受體拮抗劑歷史與簡介…..22
二、 物理與化學性狀……………….……………….22
三、 作用機制…………………………….………….22
四、 藥理作用…………………………….………….22
五、 人類醫學之應用…………………….………….23
六、 獸醫學之應用………………..……………...….23
第五節 龜類注射式給藥方式之介紹……...….......24
一、 肌肉內注射…………………………….....…….24
二、 皮下注射…………………………………….….25
三、 靜脈內注射………………………………….….26
四、 體腔內注射……………………………………..27
五、 骨內注射………………………………………..28
第六節 疼痛管理…………………………….…….29
一、 使用於爬蟲類之止痛劑…………………….….29
(一) 類鴉片類…………….……………………….29
(二) 非類固醇性抗炎症藥物……………….….…30
二、 急性與慢性疼痛的管理………………….….….30
(一) 急性疼痛的管理……….……………….…….30
(二) 慢性疼痛的管理………….…………………..31
第三章 材料與方法………….……………….…….32
一、 實驗動物…………………….……………….….32
二、 飼養管理……………………….…………….….32
三、 使用之藥物…………………….…………….….32
四、 麻醉用藥物之注射方式………………….….….32
五、 預備實驗……………………….…………….….33
六、 正式實驗……………………….…………….….33
七、 統計分析…………………….………………......36
第四章 結果…………….…………………….…….37
第一節 預備實驗………………………….….…….37
第二節 正式實驗………………………….…….….38
一、 實驗一………………………………….….…….38
二、 實驗二…………………………….………….….43
三、 實驗三……………………….…………….…….47
四、 實驗四…………………………….……….…….50
五、 實驗五……………………….…………….…….54
第五章 討論…………………….……………….….57
參考文獻………………………….…………………..61
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