臺灣博碩士論文加值系統

重症病患主要以腸道及靜脈兩途徑給予營養支持。許多研究探討不同的灌食途徑對於病患營養狀況的影響，以及重症病患在進入加護病房48小時內給予早期餵食(early feeding)，是否可以降低腸胃道耐受不良的機率，改善臨床結果；然而上述研究，很少有以疾病嚴重度為基準來探討腸胃道灌食及早期餵食對重症病患臨床結果的影響。支鏈胺基酸可提升免疫功能，被部分醫師用於腸胃道癌症術後恢復期的營養支持，但是否真正有利病情亦存有爭議。故本研究以重症病患為對象，探討在疾病嚴重度的影響下，不同的灌食途徑及灌食開始時間的早晚，與病患的營養狀況及臨床結果之相關性；同時也以大腸直腸癌的病患為對象，探討富含支鏈胺基酸的周邊靜脈營養對於術後臨床結果的影響。整體研究之目的為提昇重症病患的醫療品質，改善其營養狀況，以避免併發症的發生，節省醫療資源。
實驗ㄧ是探討疾病嚴重度是否影響灌食途徑對重症病患臨床結果的功效並決定適宜重症病人的灌食途徑。101位內科加護病房的重症病患隨機分配到鼻胃（n = 51）或鼻-十二指腸（n = 50）灌食途徑，病情的嚴重度以『急性生理和慢性健康評估Ⅱ』（APACHE II）為評估標準，分為“較不嚴重（APACHE II〈20）”和“極重病（APACHE II〉=20）”兩組。在21天的研究期間，收集每日熱量和蛋白質攝取量、灌食併發症、加護病房住院天數、死亡率、氮平衡、血清白蛋白和血清前白蛋白等數據。研究結果顯示，在較不嚴重組的病患中，鼻胃灌食及鼻-十二指腸灌食兩組在每日熱量和蛋白質攝取量、灌食併發症、加護病房住院天數及氮平衡都無顯著性差異。在極重病組的病患中，鼻胃灌食比鼻-十二指腸灌食顯示較低的熱量和蛋白質攝取量，較多的灌食併發症，較長的加護病房住院天數，及較差的氮平衡。故為讓營養支持更為適當，且考慮到醫療資源的有效運用，建議病情較不嚴重的患者使用鼻胃灌食，極重病組的患者使用鼻腸灌食。
實驗二是釐清疾病嚴重度與灌食開始時間之相關性。108位內科加護病房的重症病患進入加護病房48小時內開始灌食者屬於“早期灌食”（n = 40），超過 48小時則屬“晚期灌食”（n = 68）。病情的嚴重度以APACHE II 20分為區分標準，分為“較不嚴重 （APACHE II〈20）”和“極重病（APACHE II〉=20）”兩組，於研究21天期間，收集病患每日熱量及蛋白質攝取量、血清白蛋白及前白蛋白、24小時尿素氮、灌食併發症、住加護病房天數、住院天數、呼吸器相關性肺炎發生率、死亡率等數據。研究結果顯示，極重病組的患者，早期灌食比晚期顯示較佳白蛋白及前白蛋白、較差氮平衡、較多灌食併發症、較長加護病房住院天數。早期灌食可以改善極重病者之營養狀況，而灌食併發症及住加護病房天數雖劣於晚期灌食，但灌食併發症可被控制而不影響營養攝取量，而最終之住院天數及死亡率無顯著差異。故早期灌食相較於晚期對於極重病者仍是較佳之營養治療方式。
實驗三是探討富含支鏈胺基酸的周邊靜脈營養對於癌症術後病患恢復之臨床效益。這個觀察研究是將61位入院接受大腸直腸癌手術的病患，依照術後使用靜脈營養的支鏈胺基酸含量多寡，分為控制組“葡萄糖液”，低劑量組“葡萄糖液加低量支鏈胺基酸及脂肪滴劑”，高劑量組“葡萄糖液加高量支鏈胺基酸及脂肪滴劑”等三組，收集手術前ㄧ天至術後第7天的各項臨床數據。這些病患術前營養狀況正常，整個7天觀察期間，控制組的身體質量指數比低劑量及高劑量兩組，有明顯減少的現象；且控制組比高劑量組有較少的尿素氮流失及較低的氮平衡下降現象，而其他的臨床結果如免疫力、生化檢驗值、靜脈炎、住院天數及死亡率，控制組與其他兩組比較，均無顯著差異。因此，不建議術前無營養不良的大腸直腸癌患者，術後恢復期間給予富含支鏈胺基酸的周邊靜脈營養支持。
綜合以上結果，疾病嚴重度影響灌食途徑的有效性，並與灌食開始時間的早晚有密切相關；且富含支鏈胺基酸的周邊靜脈營養，無助於術前無營養不良的大腸直腸癌患者的術後臨床結果，此資訊可助醫療團隊改善重症病患的營養支持。

Patients with critical illness require either enteral or parenteral nutrition support. Many studies have investigated what the effects of using different feeding routes are on nutritional outcomes as well as whether the effect of early feeding can reduce the incidence of gastrointestinal intolerance and improve clinical outcomes in critically ill patients. However, effects of feeding on clinical and nutritional outcomes in patients with differences in illness severity have not been fully examined. Branched-chain amino acids are essential for lymphocyte responsiveness and support immune cell functions. Some physicians prescribe short-term peripheral parenteral nutrition with enriched branched-chain amino acids as nutritional support during the postoperative recovery in patients with gastrointestinal cancer. Whether this intervention provides better clinical benefit than routine management is still under debate. This study investigated the possible association between severity of illness and efficacy of enteral feeding route and the effect of commencement of enteral feeding on nutritional and clinical outcomes in patients with critical illnesses in a medical intensive unit and the effects of peripheral parenteral nutrition with high dosage of branched-chain amino acids on clinical outcomes in postoperative colorectal patients. The overall purpose of the study is to enhance the quality of medical care, improve nutritional status, avoid the occurrence of complications, and save medical resources in critically ill patients.

Experiment I-Different feeding routes
Experiment I was conducted to test whether severity of illness influenced the efficacy of enteral feeding route on clinical outcomes in patients with critical illnesses and determine the optimal enteral feeding route for different levels of severity.
One hundred and one patients in medical intensive care unit were randomly assigned to receive feeding through one of two routes, nasogastric (n = 51) or nasoduodenal (n = 50). These critically ill patients were dichotomized into “less severe” and “more severe” subgroups using a Acute Physiology and Chronic Health Evaluation (APACHE) II score of 20 as a cutoff. Daily energy and protein intake, feeding complications (gastric retention, vomiting, diarrhea, gastrointestinal bleeding), length of intensive care unit stay, hospital mortality, nitrogen balance, albumin, and prealbumin were collected over 21 days. In the less severely ill patients, there was no difference between the nasogastric and nasoduodenal groups in daily energy and protein intake, feeding complications, length of intensive care unit stay, and nitrogen balance. In the more severely ill patients, the nasogastric group had lower energy and protein intake, more tube feeding complications, longer intensive care unit stay, and poorer nitrogen balance than the nasoduodenal group.
These results suggest that gastric feeding route be used for less severely ill patients and postpyloric feeding route for more severely ill patients to optimize nutritional support and conserve medical resources.

Experiment II-timing of enteral feeding initiation
Experiment II was conducted to investigate the possible association between illness severity and commencement of enteral nutrition.
One hundred and eight medical intensive care unit patients receiving enteral feeding within 48 h of intensive care unit admission were assigned to an early feeding group (n = 40) and those receiving eternal feeding beyond 48 h of admission were assigned to a late feeding group (n = 68). Patients were further dichotomized into a less severe group (APACHE II 〈20) and more severe group (APACHE II 〉=20). Daily energy and protein intake, feeding complications (gastric retention, vomiting, diarrhea, gastrointestinal bleeding), length of intensive care unit stay, length of hospital stay, ventilator-associated pneumonia, hospital mortality, serum albumin, serum prealbumin, nitrogen balance, and 24-h urinary urea nitrogen were collected over 21 days. There were no differences in measured outcomes between early and late feedings for less severely ill patients. In the more severely ill patients, however, the early feeding group were found to have improved serum albumin and prealbumin but worsened nitrogen balance, more feeding complications, and prolonged intensive care unit stays than their late feeding counterparts.
These results demonstrated a relationship between illness severity and enteral feeding commencement time and the influence of this relationship on clinical outcomes. In more severely ill patients, early feeding was associated with improved nutritional outcome and late feeding with reduced feeding complications and shorter intensive care unit stays. The feeding complications of more severely ill patients started early on feeding can be handled without significantly affecting nutritional intake, and thus early feeding may be a more beneficial nutritional intervention than late feeding in patients with more severe illnesses.

Experiment III-Hypocaloric peripheral parenteral nutrition enriched with BCAA
Experiment III was conducted to examine whether the infusion of hypocaloric peripheral parenteral nutrition with high dose branched-chain amino acids provides better clinical benefits than routine fluid management in postoperative gastrointestinal cancer patients.
In this retrospective observational study, 61 colorectal cancer patients receiving postoperative hypocaloric peripheral parenteral nutrition were assigned to one of three feeding groups based on what nutrients they received: control group received dextrose infusion only, the low dose group received dextrose plus branched-chain amino acids and fat infusion and high dose group received dextrose plus high dose branched-chain amino acids and fat infusion. Outcome data were collected on the day before and seven days after surgery. Patients were non-malnourished. Over the observation period, the dextrose only control group had a significantly higher reduction in body mass index than the lower dose and the higher dose branched-chain amino acids groups. Compared to the high dose branched-chain amino acids group, the control group also had a lower urinary nitrogen loss and less reduction in nitrogen balance. There were no differences between the control and low dose/high dose groups in immunity, biochemical measures, phlebitis, hospital stay and hospital mortality. We found no clinical advantage to the postoperative administration of hypocaloric peripheral parenteral nutrition with branched-chain-enriched amino acids to non-malnourished colorectal cancer patients.
In conclusion, these three experiments showed that severity of illness influenced the effect of different enteral feeding routes and feeding commencement on nutritional and clinical outcomes. Postoperative hypocaloric peripheral parenteral nutrition with branched-chain-enriched amino acids provides no obvious benefits in non-malnourished colorectal cancer patients. These findings can be used by interdisciplinary health care teams to improve nutrition interventions for patients with critical illnesses.

CONTENTS

Chinese Abstract I
English Abstract IV
Acknowledgements VIII
Contents IX
List of Tables XII
List of Figures XIII
Abbreviations XIV
Chapter 1 Introduction 1
Chapter 2 Literature Review 5
Nutrition support in critical illness 5
Energy and protein supply 5
Severity of illness 6
Enteral versus Parenteral nutrition 7
Enteral nutrition 7
Feeding complications 8
Parenteral nutrition 9
Supplemental parenteral nutrition 10
Feeding tube sites 10
Aspiration pneumonia 11
Energy target 11
Early versus Late feeding 12
Postoperative hypocaloric peripheral parenteral nutrition 13
Branched-chain amino acids 13
Hypocaloric versus Hypercaloric Parenteral Nutrition 14
Chapter 3 Experiments: Part I to III
I. Severity of illness influences the efficacy of enteral feeding route on clinical outcomes in critically ill patients
Abstract 16
Introduction 18
Materials and Methods 19
Results 24
Discussion 27
II. Association between illness severity and timing of initial enteral feeding in critically ill patients: A retrospective observational study
Abstract 37
Introduction 39
Materials and Methods 40
Results 43
Discussion 47
III. Hypocaloric peripheral parenteral nutrition with branched-chain-enriched amino acids provides no clinical advantage in well-nourished postoperative colorectal cancer patients
Abstract 56
Introduction 57
Materials and Methods 58
Results 62
Discussion 65
Chapter 4 Summary and Conclusions 74
Chapter 5 References 76
Appendixes 95
Publication List 98


List of Tables
Table 1-1. Comparison of demographic and clinical characteristics between nasogastric (NG) and nasoduodenal (ND) tube feeding groups and break down, by severity of illness 32
Table 1-2. Differences of measured outcomes between nasogastric (NG) and nasoduodenal (ND) feeding groups and break down, by severity of illness 33
Table 1-3. Effects of enteral feeding routes (nasogastric vs nasoduodenal) on measured outcomes after adjusting for gender, age and severity of illness in Acute Physiology and Chronic Health Evaluation II (APACHE II) 20 and APACHE II 20 group 34
Table 1-4. Incidence of tube feeding complications between nasogastric (NG) and nasoduodenal (ND) feeding groups in Acute Physiology and Chronic Health Evaluation II (APACHE II)  20 patients 35
Table 2-1. Demographic and clinical characteristics of the patients categorized by timing of feeding initiation and break down by illness severity 51
Table 2-2. Differences in measured outcomes between early and late feeding groups and break down by illness severity 52
Table 2-3. Differences in feeding complications between early and latefeeding groups categorized by illness severity 53
Table 2-4. Effects of the timing of enteral feeding initiation (early feeding) on different clinical and nutritional outcomes 54
Table 3-1. Composition of the PPN formula per group 70
Table 3-2. Comparison of patients’ characteristics between the control and experimental groups 71
Table 3-3. Differences in measured outcomes between the control and experimental groups 72
Table 3-4. Effects of HPPN with branched-chain enriched amino acids (high dose group) on different measured outcomes after adjusting BMI and NB on pre-operation in all cases 73

List of Figures
Figure 1-1. Differences between groups in mean NB during the feeding period 36
Figure 2-1. Differences between groups in mean serum albumin and serum prealbumin during the feeding period 55

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