臺灣博碩士論文加值系統

　　慢性腹膜透析患者和血液透析患者類似，常因長期透析而導致肉質素失調(dialysis related carnitine disorder, DCD)，血漿中游離型左旋肉質素(free L-carnitine)下降，醯化肉質素(acyl-carnitine)/游離型肉質素的比值上升，而長期透析導致肉質素失調通常會伴隨尿毒症肌肉病變(uremic myopathy)，尿毒症肌肉病變會限制透析患者運動耐力及持久力(endurance)，其臨床表現為肌肉痙攣/疼痛或肌肉無力/疲勞，已有報告顯示，血液透析患者每天口服補充低劑量左旋肉質素(500mg)，可降低肌肉症狀，且降低醯化肉質素/游離型肉質素比值。
　　我們進行六個月前瞻性開放式平行試驗，評估腹膜透析患者每天口服600mg左旋肉質素其肌肉症狀之變化，在進入研究前及第三、六個月，以標準無刻度100 mm視覺類比評量尺(visual analog scale, VAS)讓病患作肌肉症狀自覺評估，評估項目包括：肌肉痙攣/疼痛、肌肉無力/疲勞以及非肌肉痙攣引起之肌肉酸痛，另外，評估病患生活品質之變化，於研究前後使用36項生活品質評估表(36-item short-form health survey, SF-36)進行評估，並監測病患紅血球生成素(epoietin, rhuEPO)之治療反應、心臟射出分率（EF值）和心衰竭之症狀。
　　本研究中，一共有45位尿毒症肌肉病變之腹膜透析患者，分為實驗組(n=22)和對照組(n=23)，先以100mm的視覺類比評量尺評估肌肉痙攣/疼痛症狀，在基準期兩組間並無差異，經過六個月治療後，實驗組較對照組有改善症狀之趨勢(overall P = 0.05)；肌肉無力/疲勞症狀方面，在基準值兩組間無差異，經六個月實驗組較對照組呈現明顯改善(overall P = 0.02)；兩者症狀的改善與完整型副甲狀腺素、鐵質狀態、全身肌肉量並無相關。使用SF-36進行生活品質評估，經過六個月，實驗組較對照組在身體功能、身體角色、一般健康、和情緒角色四個面項有明顯改善(P < 0.05)，對於紅血球生成素之治療反應、心臟射出分率和心衰竭之症狀，服用左旋肉質素並無觀察到明顯反應。
　　因此由本實驗發現慢性腹膜透析患者口服補充左旋肉質素，耐受性不錯，未出現嚴重副作用，且服用六個月後可明顯改善肌肉症狀和增加生活品質。

　　Uremic patients receiving chronic peritoneal dialysis (PD), similar to hemodialysis patients, were associated with a reduction in plasma and tissue free carnitine concentration and high ratio of acyl-carnitine to free carnitine (AC/FC). The disturbed L-carnitine concentrations were referred to as dialysis–related carnitine deficiency which was associated with symptoms of uremic myopathy. Uremic myopathy frequently manifested with muscle weakness/fatigue, cramps/pain, and limited exercise tolerance and endurance. Oral low-dose supplement with L-carnitine had been shown benefits in alleviating skeletal muscle symptoms and increased physical activity by reducing AC/FC ratio in hemodialysis patients.
　　We performed a prospective open-label parallel controlled study to evaluate the effects of oral L-carnitine (600 mg/day) supplementation for six months on muscle symptoms and quality of life. Three components of muscle symptoms (muscle weakness/fatigue, muscle cramps/pain, and aching excluding pain during cramps) of PD patients were assessed via three standard un-graded 100-mm visual analog scales (VAS) separately at baseline, the 3rd month and the 6th month.The quality of life was measured by 36-item short-form health survey (SF-36) at baseline and the 6th month. Recombinant human erythropoietin (epoietin, rhuEPO) responsiveness, cardiac function and symptoms of heart failure were also monitored.
　　Forty-five patients with uremic myopathy were recruited into carnitine group (n=22) and control group (n=23). The 100mm VAS of muscle weakness/fatigue did not differ at entry. The carnitine group demonstrated an improvement as comparison to the control group (repeated measures ANOVA, overall P = 0.05). The 100-mm VAS of muscle cramps/pain of both was similar at baseline. After six months supplementation, carnitine group had lesser muscle cramps/pain than control group (overall P = 0.02). L-carnitine therapy also had positive effects on physical functioning, physical role, general health and emotional role concepts of SF-36 (P < 0.05). The epoietin responsiveness, ejection fraction of left ventricle and symptoms of heart failure did not have significant changes. No severe adverse effect was reported.
　　The oral low-dose supplementation of L-carnitine is well tolerated.L-carnitine therapy demonstrates significant alleviation of skeletal muscle symptoms and improves quality of life in chronic PD patients.

中文摘要 I
Abstract III
誌謝 V
目錄 VI
圖目錄 IX
表目錄 X

第一篇 慢性腹膜透析患者口服補充左旋肉質素之臨床效應 1

第一章 研究背景 1

第二章 文獻回顧 2
第一節 L-carnitine介紹 2
1.1 結構 2
1.2 體內平衡狀態 2
1.3 Carnitine之生理功能 3
1.4 體內L-carnitine含量和正常值 6
1.5 Carnitine的缺乏型態(Carnitine deficiency type) 7
1.6 Carnitine缺乏之治療 10
1.7 L-carnitine的藥物動力學 11
1.7.1 注射劑型L-carnitine 11
1.7.2 口服劑型L-carnitine 12
1.8 L-carnitine副作用 13
1.9 美國食品藥物管理局(Food and Drug Administration, FDA)適應症 14
1.10 台灣衛生署(Department of Health, DOH)適應症 14
第二節 長期透析患者的carnitine缺乏 15
2.1 血液透析患者體內carnitine狀態 15
2.2 腹膜透析患者體內carnitine狀態 17
第三節 透析病患補充L-carnitine的臨床效果評估 20
3.1 透析引起的carnitine失調(Dialysis-related carnitine disorder, DCD) 20
3.2 貧血(Anemia hyporesponsive to rhuEPO) 20
3.3 透析期間低血壓(Intrdialytic hypotension, IDH) 22
3.4 心肌病變(Cardiomyopathy) 23
3.5 生活品質(Quality of life) 31
3.6 腹膜透析患者補充L-carnitine 臨床效果評估 31
第四節 結論 32

第三章 研究目的 34

第四章 研究材料、方法 35
第一節 研究材料 35
1.1 研究藥品 35
第二節 研究設計 35
2.1 研究類型 35
2.2 研究時間及對象 36
2.3 研究流程 37
2.4 評估指標 37
2.5 評估方式 38
2.6 指標評估方式 40
2.7 安全性評估 44
第三節 統計分析 45
3.1 統計模式設定 45
3.2 資料分析方法 45
3.3 統計軟體 46

第五章 研究結果 47
第一節 研究對象 47
第二節 治療結果 50
2.1 肌肉症狀 50
2.2 生活品質 53
2.3 貧血和rhuEPO治療反應 56
2.4 心衰竭症狀 58
2.5 安全性評估 59

第六章 討論 60
第一節 研究對象 60
第二節 臨床治療反應 61
2.1 肌肉症狀 61
2.2 生活品質 67
2.3 貧血及rhuEPO治療反應 71
2.4 心衰竭症狀 73
第三節 安全性評估 75
第四節 研究限制 76
第五節 未來研究方向 77

第七章 結語 78

附錄一：同意書 79
附錄二：病患資料記錄表 81
附錄三：肌肉症狀量表 82
附錄四: SF-36生活品質評估表 83
附錄五: 心衰竭自覺症狀量表 87
附錄六: 客觀營養評估 88

參考文獻： 89

第二篇 臨床藥事服務（Clinical service） 94
一、目的： 94
二、方法： 94
三、記錄方式： 94
四、結果： 95
第一節.藥事服務個案 95
1.1 不良反應評估個案 99
第二節.藥物諮詢 103
2.1 藥物治療監測 (Therapeutic Drug Monitoring , TDM) 104
2.2 抗生素與肝素於抗生素鎖住療法(Lock therapy)之相容性 106
2.3 易造成血小板低下之頭孢菌素(Cephalosporins) 109
2.4 腎功能不全和腎衰竭患者抗結核藥物之使用 111
2.5 Vancomycin 與 teicoplanin腎毒性之比較 114
2.6 Allopurinol在腎功能不全患者之使用 119
2.7 透析患者抗生素建議給藥方式 122

參考文獻: 128

第一篇 慢性腹膜透析患者口服補充左旋肉質素之臨床效應
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