臺灣博碩士論文加值系統

中央靜脈營養對長期或暫時性胃腸道失去功能的病人而言，是一項非常重要的治療。然而，中央靜脈營養的醫療費用亦是相當的昂貴。現行健保給付政策對中央靜脈營養輸液的給付，除藥品費用外尚有藥師特殊處方調劑費。但是後者並無法完全反映需特殊調配環境及設備進行之中央靜脈營養調配所需成本。因此，如何改善作業降低調配成本，是值得醫院藥局管理者深思的課題。在本研究中選擇市售之二合一中央靜脈營養輸液（NutriflexR70/240）使用於外科病人，並以習用之由成分原料調配的中央靜脈營養輸液作對照組，探討在不影響醫療品質的前提下，其在臨床使用情形及對中央靜脈營養醫療費用的影響。
本研究是一前瞻性、隨機、開放、有對照組的研究。於1998年11月到1999年4月間，以台大醫院外科病房預計使用中央靜脈營養7天或以上的成人病人進行研究。共收入53位病人，隨機分為實驗組（25人）和對照組（28人），再依病人體重分為實驗組A組（小於60公斤）、實驗組B組（大於等於60公斤）、對照組A組（小於60公斤）及對照組B組（大於等於60公斤）。實驗組給予二合一中央靜脈營養輸液，對照組則給予由一般調配自成分原料所得之習用成人中央靜脈營養輸液。所有病人於開始使用中央靜脈營養後連續7天作臨床觀察，每天記錄中央靜脈營養的使用情形，並定期抽血、追蹤血液生化檢驗值。
研究結果發現，在觀察albumin和prealbumin的檢驗值所反映之病人營養狀況變化上，並沒有顯著差異。在使用中央靜脈營養相關之併發症的分析上，可觀察到電解質不平衡在實驗組發生率為32.0%，小於對照組之64.3%（p值為0.028），兩組有顯著差異；其餘併發症的發生率在兩組間並沒有顯著差異。而造成電解質不平衡的各項變數中，又以低血磷的發生比率於兩組間的差異最為顯著（實驗組12.0%、對照組35.7%，p值為0.045）。探究其原因，可能是由於對照組所用之中央靜脈營養輸液內磷的濃度（4.2 mM）低於實驗組（14.7 mM）所致。因此臨床使用上，不論對病人的營養狀態或導致併發症的比率上，在兩組都是相當的。
由所收病人使用之中央靜脈營養配方計算每天平均中央靜脈營養藥品費用，可知實驗組A組之每天平均藥品費用較對照組A組減少約297元；而實驗組B組之每天平均藥品費用比對照組B組減少約300元。在每張中央靜脈營養處方之調配時間分析上，實驗組比對照組平均少約100秒，相當於節省約15.8%之對照組平均處方調配時間。因此，實驗組相較於對照組在中央靜脈營養藥品費用及調配時間上，皆有明顯降低。
由本研究可知，在不影響病人營養狀況的前提下，使用二合一中央靜脈營養產品調配中央靜脈營養輸液，對於降低中央靜脈營養的整體醫療費用是有幫助的，但是若考慮以NutriflexR70/240應用於不需限水的病人身上，則其輸液不足需額外添加輸液的情形，將會降低其應用價值。

The provision of total parenteral nutrition (TPN) to patients with gastroenteric dysfunction is very important. However, the therapy is expensive. The reimbursement of TPN from National Health Insurance includes the cost of drugs and dispensing fee of pharmacist. However, the later does not cover all the cost needed for compounding TPN, in which, an aseptic environment and special equipments are usually required. Consequently, reducing the cost of TPN by adequate adjustment in compounding procedure is an urgent topic for the administrator of hospital pharmacy. In this study a two-in-one TPN product was applied in surgical patients, and its clinical use and effects on medical-related expense was compared and discussed.
This was a prospective, randomized, open label, and controlled study. During November 1998 and April 1999, all patients of the age not less than 20 years old, admitted to National Taiwan University Hospital (NTUH) Surgery Wards and intended to use TPN above 7 days, were recruited for this study. There were 53 patients enrolled in this study. The patients were randomized to study group (n=25) and control group (n=28) to receive either 2-in-1 TPN products or common TPN preparations compounded from bottles. According to patients’ body weight (BW), the two groups were subdivided into study group A (BW < 60 kg), study group B (BW > 60 kg), control group A (BW < 60 kg), and control group B (BW > 60 kg). The patients were monitored for seven days started from the first day of using TPN.
By observing blood concentrations of albumin and prealbumin, no significant difference was found in nutrition status of patients during the study period for both groups. The complication ratios had no significant difference except the imbalance of electrolytes (study group vs control group; 32.0% vs 64.3%, p = 0.028). The major cause of significant difference in electrolytes imbalance came from the incidence of low serum phosphate (study group vs control group; 12.0% vs 35.7%, p = 0.045). It is most likely due to the difference in phosphate content of TPN solutions (14.7 mM in study group and 4.2 mM in control group). The overall benefit of clinical use of these two TPN preparations showed no significant difference.
The expense difference of TPN drugs between study group A and control group A was about 297 NT dollars per day, and that between study group B and control group B was about 300 NT dollars per day. Regarding to the compounding time per prescription, the study group was about 100 seconds less than the control group, which was about 15.8% of the total compounding time of the control group. It is suggested that TPN preparation in study group has the benefit of lowering the expense of TPN drugs and compounding time.
It is concluded that the two-in-one TPN products not only have adequate performance in clinical use, but also have benefit in lowering TPN medical-related expense.

目錄I
表目錄IV
圖目錄VI
中文摘要VII
英文摘要X
第一章 前言1
第二章 文獻探討
第一節 中央靜脈營養在醫療上的定位
一、中央靜脈營養之適應症3
二、給予中央靜脈營養導致之併發症6
第二節 病人營養需求的探討11
第三節 身體營養狀態的評估18
第三章 研究目的27
第四章 研究方法
第一節 研究對象
一、收入條件29
二、排除條件29
第二節 研究方法
一、中央靜脈營養輸液配方及分組設計31
二、病人分組31
三、觀察及紀錄之各項追蹤項目35
四、中央靜脈營養輸液醫療費用分析37
第三節 數據分析40
第五章 結果
第一節 病人基本資料42
第二節 中央靜脈營養的使用
一、病人各項臨床追蹤記錄之統計分析46
二、病人營養狀況分析49
三、相關併發症發生之統計分析52
第三節 中央靜脈營養醫療費用分析
一、中央靜脈營養藥品費用分析55
二、調配中央靜脈營養輸液所耗時間的分析57
第六章 討論
第一節 中央靜脈營養使用
一、中央靜脈營養使用分析59
二、營養狀態分析61
三、使用中央靜脈營養相關併發症63
第二節 中央靜脈營養費用及調配時間
一、中央靜脈營養輸液之藥品費用66
二、中央靜脈營養調配時間之比較67
第三節 研究期間使用NutriflexR70/240經驗70
第七章 結論與建議72
參考資料73
附錄一 79
附錄二 83
附錄三 84
附錄四 85
附錄五 88
表 目 錄
表一 中央靜脈營養之適應症5
表二 給予中央靜脈營養支持時的代謝併發症10
表三 估計成人總熱量需求時，在不同情況應考慮的壓力因子與
活動因子及其百分率13
表四 成人每日微量營養素需求建議值16
表五 不同情況之成人病人之中央靜脈營養各主要成分需求之建議
值17
表六 身體營養狀態主觀整體評估表(SGA, subjective global
assessment)19
表七 各種以觀察體重變化作營養狀態評估的方法21
表八 用於營養狀態評估的血清蛋白質的正常含量及其特性26
表九 本研究各組病人所用中央靜脈營養輸液之主要組成32
表十 實驗各組中央靜脈營養輸液之詳細成分含量表33
表十一 研究病人於研究期間之觀察追蹤項目36
表十二 台大醫院檢驗醫學部實驗室各項檢驗項目所列之正常值範
圍37
表十三 收入病人之基本資料分析44
表十四 收入病人開始使用中央靜脈營養時機及手術方式45
表十五 所收入病人於研究期間的臨床記錄之統計分析48
表十六 所收入的病人，試驗期間之血中albumin、prealbumin含量隨時間變化之分析比較50
表十七 所收入的病人於研究期間，發生與中央靜脈營養使用相關
之併發症的統計分析53
表十八 所收入病人於研究期間發生電解質不平衡的分析54
表十九 各組病人於研究期間（7天）使用中央靜脈營養輸液之每天平均中央靜脈營養藥品費用56
表二十 病人於研究期間使用albumin製劑之情況分析63
圖 目 錄
圖一 本研究之執行流程圖34
圖二 台大醫院藥劑部無菌調配組之中央靜脈營養輸液調配流程39
圖三 所收入病人於研究期間之血中albumin含量平均值隨時間變
化的情形50
圖四 所收入病人於研究期間之血中prealbumin含量平均值隨時間
變化的情形51

1. Holcombe BJ. Adult parenteral nutrition. In: Young LY, Koda-Kimble MA, editors. Applied therapeutics: the clinical use of drugs. 6th ed. WA: Applied therapeutics; 1995. p. 35-2-16.
2. Sand J, Luostarinen M, Matikanen M. Enteral or parenteral feeding after total gastrectomy: prospective randomized pilot study. Eur J Surg 1997;163:761-6.
3. The ASPEN Board of Directors. Guidelines for the use of parenteral and enteral nutrition in adults and pediatric patients. J Parenter Enter Nutr 1993;17(4 suppl):12SA-49SA.
4. Mattox TW. Parenteral nutrition. In: DiPiro JT, editors. Pharmacotherapy: a pathophysiologic approach. 3rd ed. Stamford: Appleton & Lange; 1997. p. 2735-58.
5. The A.S.P.E.N. Board of Directors. Guidelines of use of total parenteral nutrition in the hospitalized adult patient. J Parenter Enter Nutr 1986;10:441-5.
6. The Veterans Affairs Total Parenteral Nutrition Cooperative Study Group. Perioperative total parenteral nutrition in surgical patients. N Engl J Med 1991;325:525-32.
7. Bellatone R, Doglietto GB, Bossola M, Pacelli F, Negro F, Sofo L, et al. Preoperative parenteral nutrition in high risk surgical patients. J Parenter Enter Nutr 1988;12:195-7.
8. Muller JM, Brenner U, Dienst C, Pichlmaier H, et al. Preoperative parenteral feeding in patients with gastrointestinal carcinoma. Lancet 1982;1:68-71.
9. Sandstrom R, Drott C, Hyltander A, Arfvidsson B, Schersten T, Wickstrom I, et al. The effect of postoperative intravenous feeding (TPN) on outcome following ajor surgery evaluated in a randomized study. Ann Surg 1993;217:185-95.
10. Holter AR, Fischer JE. The effects of perioperative hyper-alimentation complications in patients with carcinoma and weight loss. J Surg Res 1977;23:31-4.
11. Heatley RV, Williams RH, Lewis MH. Pre-operative intravenous feeding: a controlled trial. Postgrad Med J 1979;55:541-5.
12. Brennan MF, Pisters Peter WT, Posner M, Quesada O, Shike M. A prospective randomized trial of total parenteral nutrition after major pancreatic resection for malgnancy. Ann Surg 1994;220:436-44.
13. Thompson BR, Julian TB, Stremple JF. Perioperative total parenteral nutrition in patients with gastrointestinal cancer. J Surg Res 1981;30:497-500.
14. Detsky AS, Baker JP, O’Rouke K, Goel V. Perioperative parenteral nutrition: a meta-analysis. Ann Intern Med 1987;107:195-203.
15. Meyenfeldt MF, Meyerink WJHJ, Soeters PB, Veen H, Buil-Maessen R. Perioperative nutritional support results in a reduction of major postoperative complications especially in high risk patients. Gastroenterology 1991;100:A553.
16. Bellatone R, Doglietto GB, Bossola M, Pacelli F, Negro F, Sofo L, et al. Preoperative parenteral nutrition of malnourished surgical patients. Acta Chir Scand 1988;154:249-251.
17. Souba WW. Nutritional support. In: Devita VT, Hellman S, Rosenberg SA editors. Cancer: principles & practice of oncology, 5th ed. PA: Lippincott-Raven; 1997. p. 2841-57.
18. Kudsk KA, Croce MA, Fabian TC, Minard G, Tolley EA, Poret HA, et al. Enteral vs parenteral feeding. Ann Surg 1992;215:503-11.
19. Grant JP. Nutrition in surgical patients. In: Sabiston DC, Lyerly HK editors. Sabiston essentials of surgery. 2nd ed. PA: WB. Sauders; 1994. p. 97-107.
20. Skipper A, Millikan KW. Parenteral nutrition implementation and management. In: The A.S.P.E.N. editors. The A.S.P.E.N. nutrition support practice manual. 1998. p. 9-1-9.
21. Sax HC. Complications of total parenteral nutrition and their prevention. In: Rombeau JL, editors. Clinical nutrition: parenteral nutrition. 2nd ed. Philadelphia: W.B. Saunders; 1993. p. 367-81.
22. Shronts EP, Fish JA, Pesce-Hammond K. Nutrition assessment. In: The A.S.P.E.N. editors. The A.S.P.E.N. nutrition support practice manual. 1998. p. 1-1-17.
23. Brooks MJ, Melnik G. The refeeding syndrome: an approach to understanding its complications and preventing its occurrence. Pharmacotherapy 1995;15:713-26.
24. Stephen JB. Nutritional therapy. In: Ewald GA, McKenzie CR, editors. Manual of medical therapeutics. 28th ed. Boston: Little, Brown and Company; 1995. p. 29-42.
25. Ioannides-Demos LL, Liolios L, Topliss DJ, Mclean AJ. A prospective audit of total parenteral nutrition at a major teaching hospital. Med J Aust 1995;163:233,235-7.
26. Bashir RM, Lipman TO. Hepatobiliary toxicity of total parenteral nutrition in adults. Gastroenterol Clin North Am 1995;24:1003-25.
27. ChrisAnderson D, Heimberger DC, Morgan SL, Geels WJ, Henry KL, Conner W, et al. Metabolic complications of total parenteral nutrition: effects of a nutrition support service. J Parenter Enter Nutr 1996;20:206-10.
28. Skoutakis VA, Martinez DR, Miller WA, Dobbie RP. Team approach to total parenteral ntrition. Am J Hosp Pharm 1975;32:693-7.
29. Nehme AE. Nutritional support of the hospitalized patient: The team concept. J Am Med Assn 1980;243:1906-8.
30. Reinhardt GF, Myscofski JW, Wilkens DB, Dobrin PB, Mangan JE, Stannard RT. Incidence and mortality of hypoalbuminemic patients in hospitalized veterans. J Parenter Enter Nutr 1980;4:357-9.
31. Donald PK, Laura F, Anita RT. Comparison of total parenteral nutrition and an oral, semielemental diet on body composition, physical function , and nutrition-related costs in patients with malabsorption due to acquired immunodeficiency syndrome. J Parenter Enter Nutr 1998;22:120-6.
32. Long CL, Schaffel N, Geiger JW, Schiller WR, Blakemore WS. Metabolic response to injury and illness: estimation of energy and protein needs from indirect calorimetry and nitrogen balance. J Parenter Enter Nutr 1979;3:452-6.
33. Muller JM, Keller HW, Brenner U, Walter M, Holzmuller W. Indications and effects of preoperative parenteral nutrition. World J Surg 1986;10:53-63.
34. Trujillo EB, Robinson MK, Jacobs DO. Critical illness. In: The A.S.P.E.N. editors. The A.S.P.E.N. nutrition support practice manual. 1998. p. 18-1-14.
35. Sax HC, Souba WW. Nutritional goals and macronutrient requirements. In: The A.S.P.E.N. editors. The A.S.P.E.N. nutrition support practice manual. 1998. p. 2-1-5.
36. Hiyama DT, Fischer JE. Nutritional support in hepatic failure. Nutr Clin Pract 1988;3:96-105.
37. Nespli A, Bevilacqua G, Staudacher C, Rossi N, Francesco D, Castelli MR. Pathogenesis of hepatic encephalopathy and hyperdynamic syndrome on cirrhosis: role of false neurotransmitters. Arch Surg 1981;116:1129-38.
38. Rossi-Fanelli F, Riggio O, Cangiano C, Cascino A, Conciliis DD, Merli M, et al. Branched-chain amino acids vs lactulose in the treatment of hepatic coma: a controlled study. Dig Dis Sci 1982;27:929-35.
39. Cerra FB, Cheung NK, Fischer JE, Kaplowitz N, Schiff ER, Dienstag JL, et al. Disease-specific amino acids infusion (F080) in hepatic encephalopathy: a prospective, randomized, double-blind, controlled trial. J Parenter Enter Nutr 1985;9:288-95.
40. Wahren JJ, Denis J, Desurmont P, Eridsson LS, Escoffier JM, Garthier AP, et al. Is intravenous administration of branched chain amino acids effective in the treatment of hepatic encephalopathy? A multicenter study. Hepatology 1983;3:475-80.
41. Detsky AS, McLaughlin JR, Baker JP, Johnston N, Whittaker S, Mendelson RA, et al. What is subjective global assessment of nutritional status. J Parenter Enter Nutr 1987;11:8-14.
42. Buzby GP, Knox LS, Crosby LO, Eisenberg JM, Haakenson CM, McNeal GE, et al. Study protocol: a randomized clinical trial of total parenteral nutrition in malnourished surgical patients. Am J Clin Nutr 1988;47 Suppl 2:366-81.
43. Teasley-Strausburg KM, Anderson JD. Assessment of nutrition status and nutrition requirements. In: DiPiro JT, editors. Pharmacotherapy: a pathophysiologic approach. 3ed ed. Stamford: Appleton & Lange Norwalk; 1997. p. 2679-97.
44. Osterkamp LK. Current perspective on assessment of human body proportions of relevance to amprtees. J Am Dien Assoc 1995;95:215-8.
45. Forbes GB. Bruining GJ. Urinary creatinine excretion and lean body mass. Am J Clin Nutr 1976;29:1359-66.
46. Seltzer MH, Slocum BA, Cataldi-Betcher EL, Fileti C, Gerson N. Instant nutritional assessment: absolute weight loss and surgical mortality. J Parenter Enter Nutr 1982;6:218-12.
47. Wolfe BM. Perioperative nutrition support. In: The A.S.P.E.N. editors. The A.S.P.E.N. nutrition support practice manual. 1998. p. 17-1-8.
48. Bistrian BR, Blackburn GL, Sherman M, Scrimshaw NS, Massachussetts B. Therapeutic index of nutritional depletion in hospitalized patients. Surg Gynecol Obstet 1975;141:512-6.
49. Zarowitz BJ, Pilla AM. Bioelectrical impedance in clinical practice. DICP 1989;23:548-55.
50. Chumlea WC, Guo S. Bioelectrical impedance and body composition: Present status and future directions. Nutr Rev 1994;52:123-31.
51. Teasley-Strausburg KM. Prevalence and significance of malnutrition. In: DiPiro JT, editors. Pharmacotherapy: a pathophysiologic approach. 3ed ed. Stamford: Appleton & Lange Norwalk; 1997. p. 2699-709.
52. Benjamin DR. Laboratory tests and nutritional assessment. Protein-energy status. Pediatr Clin N Am 1989;36:139-161.
53. Boosalis MG, Ott L, Levine AS, Slag MG, Morley JE, Young B, et al. Relationship of visceral proteins to nutritional status in chronic and acute stress. Crit Care Med 1989;17:741-7.
54. Church JM, Hill GL. Assessing the efficacy of intravenous nutrition in general surgical patients: dynamic nutritional assessment with plasma proteins. J Parenter Enter Nutr 1987;11:135-9.
55. Konstantinides FN, Kaproth PL, Cerra FB. Other aspects of metabolic monitoring in critically ill patients. Clin Chem 1990;36(8 Pt 2):1594-603.
56. Mullen JL, Gertner MH, Buzby GP, Goodhart GL, Rosato EF. Implications of malnutrition in the surgical patient. Arch Surg 1979;114:121-5.
57. Bienia R, Ratcliff S, Barbour GL, Kummer M. Malnutrition and hospital prognosis in the alcoholic patient. J Parenter Enter Nutr 1982;6:301-3.
58. Anderson CF, Wochos DN. The utility of serum albumin values in the nutritional assessment of hospitalized patients. Mayo Clinic Proceedings 1982;57:181-4.
59. Rudman D, Feller AG, Nagraj HS, Jackson DL, Rudman IW, Mattson DE. Relation of serum albumin concentration to death rate in nursing home men. J Parenter Enter Nutr 1987;11:360-3.
60. Bernstein LH, Leukhardt-Fairfield CJ, Pleban W, Rudolph R. Usefulness of data on albumin and prealbumin concentrations in determining effectiveness of nutritional support. Clin Chem 1989;35:271-4.
61. Spiekerman AM. Proteins used in nutritional assessment. Clinic in lab med 1993;13:353-69.
62. Ingenbleek Y, Van Den Schrieck HG, De Nayer P, De Visscher M. The role of retinol-binding protein in protein-calorie malnutrition. Metabolism: Clinical & Experimental 1975;24:633-41.
63. Winkler MF, Gerrior SA, Pomp A, Albina JE. Use of retinol-binding protein and prealbumin as indicators of the response to nutrition therapy. J Am Diet Assoc 1989;89:684-7.
64. Erstad BL, Campbell DJ, Rollins CJ, Rappaport ED. Albumin and prealbumin concentrations in patients receiving postoperative parenteral nutrition. Pharmacotherapy 1994;14:458-62.
65. Large S, Neal G, Glover J, Thanangkul O, Olson RE. The early changes in retinol-binding protein and prealbumin concentrations in plasma of protein-energy malnourished children after treatment with retinol and an improved diet. Br J Nutr 1980;43:393-402.
66. Kopple JD. Uses and limitations of the balance technique. J Parenter Enter Nutr 1987;11(5 suppl.):79S-85S.
67. TwomeyP. Ziegler D, Rombeau J. Utility of skin testing in nutritional assessment: a critical review. J Parenter Enter Nutr 1982;6:50-8.
68. Chandra RK. Interactions of nutrition, infection and immunity. Immunocompetence in nutritional deficiency, methodological considerations, and intervention strategies. Acta Paediatr Scand 1979;68:137-44.
69. Baker JP, Detsky AS, Wesson DE, Wolman SL, Stewart S, Whitewell J, et al. Nutritional assessment: a comparison of clinical judgment and objective measurements. N Engl J Med 1982;306:969-72.
70. Yves Ingenbleek, Vernon Young. Transthyretin (prealbumin) in health and disease: nutritional implications. Annu Res Nutr 1994;14:495-533.
71. Rosmarin DK, Wardlaw GM, Mirtallo J. Hyperglycemia associated with high, continuous infusion rates of total parenteral nutrition dextrose. Nutr Clin Prac 1996;11:151-6.
72. Frei A, Dinkel R, Kemen M, Senkal M, Zumtobel V. A new model for economic studies of therapies exemplified by postoperative parenteral nutrition. Zbl Chir 1997;122:358-65.
73. Durand ZI, Delaunay L, Langeron O, Belda E, Astier A, Brun-Brisson C. Infection risk and cost-effectiveness of commercial bags or glass bottles for total parenteral nutrition. Infect Control Hosp Epidemiol 1997;18:183-8.