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1 [ 특집 ] 경장영양 : 우리의현실과나아갈길 경장영양의장점 연세대학교의과대학외과학교실및세브란스병원영양집중지원팀 김성훈, 김경식 Abstract Malnutrition has been known to affect negatively to patients prognosis. Especially, it causes considerable side effects when the nutrition supply discontinues for a long period. It can be assumed that artificial nutrition is beneficial when the patient is in undernourished condition or malnutrition is anticipated. Enteral nutrition is widely known as reducing infectious complication by protecting intestinal mucosa. Historically, enteral nutrition existed from ancient period of Egypt, but introduced in 1910 by attempting postpyloric tube insertion, and was widely spread in 1970 s when many kinds of enteral feeding formulas were developed. However, the proving efficacy of enteral nutrition is essential due to the possibility of risks as a medical intervention and cost issues. Therefore, the principal indications of enteral nutrition should be looked into and verify its efficacy through literature review. Key Words: Malnutrition, Enteral feeding, Systematic review, Evidence 중심단어 : 영양불량, 경장영양, 체계적문헌고찰, 근거 서 론 영양불량 (malnutrition) 은환자의경과에나쁜영향을미치는것으로알려져왔다. 1 특히장기간영양공급이중단되는경우에는적지않은부작용을야기한다는점에서영양상태가불량하거나영양불량이예상되는경우에인공영양 (artificial nutrition) 이이로울것이라고가정할수있다. 2 인공영양중경장영양요법은장점막을유지하여감염성합병증을줄이는것으로알려져있다. 경장영양은역사적으로볼때이집트시대부터있었지만 1910년 postpyloric tube 삽입이시도되면서도입되었고, 1970년대부터는많은경구용제제가개발되면서활기를띠게되었다. 3 하지만경장영양역시의학적인처치 (medical intervention) 로서위험과비용이라는문제 책임저자 : 김경식, 서울시서대문구성산로 250 번지 , 연세대학교의과대학외과학교실 Tel: , 2100, Fax: kskim88@yuhs.ac 3

2 4 한국정맥경장영양학회지제 3 권제 1 호 2010 가생길수있어이에대한효능을검증할필요가있다. 2 그러므로본문에서경장영양요법의주요적응증에대해살펴보고각경우에있어서문헌고찰을통하여경장영양요법의효능을검증하고자한다. 본 론 1. Meta-analysis 를통한경장영양의효능검증 경장영양 (entral nutrition, EN) 은일반적으로비용이저렴하고혈관통로 (vascular access) 를포함한정맥내경로 (intravenous route) 와연관된합병증이적다는점에서경정맥영양 (parenteral nutrition, PN) 보다선호된다. 하지만각질환에있어경장영양의효능을입증하기란그리쉽지만은않다. 그러므로보다객관적인자료인경장영양에대한무작위배정연구를중심으로효능을살펴보았다. 1) 수술전후경장영양요법수술전경장영양요법을시행한군과시행하지않은군을비교해보면경장영양요법은사망률 (mortality), 총합병증발생률, 대부분의수술후합병증 ( 창상감염, 폐렴, 오심및구토, 수술후장마비 ), 입원기간에대해유의한차이를보이지않았다. 2 하지만연구마다약간의차이는있으나감염합병증에관해서는매우의미있는효과가보고되었다 (Table 1). 예를들어감염의경우에는절대위험감소 (absolute risk reduction) 가 11% 로이는 9명의환자에서경장영양요법을시행할경우 1명에서감염을방지하는것을의미한다. Table 1. Meta-analyses of perioperative trials between enteral nutrition and no nutrition treatment 2 Outcome Absolute risk difference 95% CI Number of (patients) studies Tests of heterogeneity P value I 2 Mortality 2% 5% to +1% 13 (1,032) % Total complications 10% 22% to +2% 12 (941) < % Infectious complications 11% 20% to 1% 10 (911) % Major complications 5% 13% to +3% 11 (911) % Wound complications 5% 11% to +1% 12 (1,053) % Intra-abdominal/thoracic complications 5% 9% to 0% 11 (871) % Postoperative pneumonia 4% 9% to +1% 9 (854) % Nausea/Vomiting 4% 20% to +12% 4 (483) % Diarrhea +4% 3% to +11% 4 (441) % Postoperative ileus 0% 5% to +6% 3 (445) % Duration of hospitalization days 1.93 days to days 8 (459) % 자료가제한되어의미있는결론을내리기에는한계가있지만면역영양제 (immunonutrients ( 오메가-3 fatty acids, arginine, ribonucleic acid, and/or glutamine) 을투여한경우전형적인 EN에비해감염을낮추는것으로알려져있다. 4-6 경구섭취가가능한환자들을대상으로의지적영양 (volitional feeding) 을시행한경우수술후및영양불량환자에서유의적으로입원기간이감소되었으나수술후합병증및사망률에는차이가없었다 (Table 2). 2) 중증질환환자중환자에있어서경장영양을공급한경우와경장영양을공급하지않은군과의비교를한무작위연구들은매우드물어경장영양공급이우월하다는강력한증거가제시된바는없다. 즉사망률, 호흡기장착시간, 중

3 김성훈ㆍ김경식 : 경장영양의장점 5 Table 2. Trials of early postoperative volitional feeding 7 Study No. of patients Vomiting, % Postoperative complications, % Mortality, % Duration of Hospitalization, day Weinstein 60/58 3.3/3.2 Binderow 32/32 44/25 6.7/8.0 Reissman 80/81 21/14 8/6 6.2/6.8 Oritz 95/95 More in early fed group 18/19 0/0 Hartsell 29/29 48/33 3/3 0/3 7.2/8.1 Schilder 49/47 More in early fed group 0/0 3.1/4.0 Stewart 40/40 35/35 25/28 9/11 Pearl 92/103 44/24 78/102 1/1 4.6/5.8 Cutillo 61/61 28/38 16/13 5/6 Behrns 27/17 7/18 19/29 4.4/6.1 Han-Guerts 56/49 20/27 11/11 Steed 47/49 No difference 9/13 5/0 4/6 Feo 50/50 32/14 13/12 7/7 Lucha 26/25 4/4 6.3/6.6 Zhou 161/155 14/45 8.4/9.5 Han-Guerts 61/67 5/3 9/8 환자실및병실재원기간에있어서차이를발견하지못하였다. 하지만경장영양공급을한경우감염률은낮아졌다. 8,9 그러나대조군의 30% 에서 5일까지먹지못하여경정맥영양공급을시행하게되었으므로감염의잠재적인위험요소들로인하여연구결과의해석에유의해야한다. 투여시기에관한연구에서는입원후 1 2일안에인위적인영양공급을시작하는것이통계학적으로의미있는차이를보이지는못했지만생존에서더우수하다고보고하였다. 10 입원하자마자경장영양요법을시작한화상환자에서는패혈증의빈도가낮았다. 수술동안에 EN을지속적으로공급한환자들은창상감염이적었다. 그러나이역시무작위배정과정에오류가있어분석에유의해야한다. 기계환기를하는환자에서경장영양요법이스트레스성출혈을예방하는지에대한단기간 (72시간) 의연구에서는대조군에서혈액이보이는비위관흡입물이흔하게나타났지만의미있는출혈이있던환자는없었다. 11 인위적인영양공급이중요하다고믿는많은중환자관리의사들이여러가지다른치료방법에대한비교연구를시행해왔다. 이런연구들은치료를하지않은대조군이부족하기때문에경장혹은경정맥영양공급을결정하는데있어서한계가있다. 중환자에관한연구결과를정리하면 Table 3과같다. Table 3. Meta-analysis of trials comparing EN with PN in critically Ill patients 2 Outcome Absolute risk difference 95% CI Number of (patients) studies Tests of heterogeneity P value I 2 Mortality 0% 9% to +8% 9 (427) % Infectious complication rate 9% 22% to +5% 7 (374) % Metabolic complications 30% 57% to 3% 3 (170) % Diarrhea 4% 26% to +18% 4 (252) % Duration of hospitalization 0.40 days 4.10 to (236) % 3) 간질환및간이식환자경장영양공급및의지적영양공급에있어서효과가우월하다는보고가없다. 12 즉의지적영양공급 (VNS)

4 6 한국정맥경장영양학회지제 3 권제 1 호 2010 은생존에있어서어떤효과도가지고있지않다. 의지적영양공급보충제로서경장영양이함께제공된경우와동화기에주어진경우에도역시생존에영향을미치지못했다. 의지적영양공급이감염합병증과간성혼수의발생에의미있는효과를보이지못했다. 자료를통합할수는없지만입원기간에도영향을주지못했다. 또한간암혹은위장관출혈의발생에도영향이없었다. 하지만두개의연구에서의지적영양공급이총합병증을줄이고복수의발생을줄인다는보고가있다. 경장영양공급은간질환에관련된유병률혹은재원기간에영향이없는것처럼보인다. 경장영양공급의생존률과경정맥영양공급과의생존률사이에차이가없다. Branched-chain amino acids는간성혼수의치료에있어서별로크지않은효과를가지고있지만연구설계가잘되어있는연구에서보면효과가없는것으로보인다. 13 간이식환자에서의미있는차이는보이지않는다. 14 4) 급성췌장염급성췌장염에서의경장영양공급과경정맥영양공급에대해무작위연구결과를보면경정맥영양공급보다경장영양공급이더안전하고효과적이다 (Table 4). 15,16 Table 4. Meta-analyses of trials comparing EN with PN in acute pancreatitis 2 Outcome Absolute risk difference 95% CI Number of (patients) studies Tests of heterogeneity P value I 2 Mortality 1% 12% to +10% 4 (151) % Total complication rate 16% 35% to +10% 3 (119) % Infectious complication rate 15% 26% to 4% 4 (187) % Pseudocysts.abscesses/phlegmons 12% 24% to 0% 3 (170) % Metabolic complications 21% 36% to 6% 3 (123) % 최근의연구결과는중증의급성췌장염환자에서조기에경장영양공급을시행할것을권유하고있다. 15 췌장염합병증으로수술을한환자를대상으로경장영양공급과금식을비교한경우사망률과합병증이감소하는경향을보였는데스트레스의반응은줄고질병의과정이조절되는것으로보고되었다. 5) 염증성장질환궤양성장염혹은크론병에대한경장영양공급의이용에대한직접적인연구는없지만경장영양공급과경정맥영양공급을비교한 4개의무작위연구가있다. 활성크론병에있어서경감률의차이가없었고의지적영양공급과경정맥영양공급과의비교역시차이가없었다. 17 염증성장질환을치료하는데있어서는 steroid 치료가가장중요하기때문에영양공급으로서염증성장질환을치료하는데있어서는한계가있다. 전소화 (predigested) 이유식이항원성 (antigenecity) 이낮다면크론병에서유익할수있지만소화가되지않은단백질을함유한이유식과의비교에서는차이가없었다. 18 6) 만성폐쇄성폐질환의지적영양공급을시도한 10개의연구에서는폐질환, 주로만성폐쇄성폐질환을가진환자를대상으로평가하였다. 1개의무작위연구에서일일생활점수 (daily living score) 를향상시키는것을보고하였고다른연구에서는호흡근육의강도의측면에서장점을설명하였다. 또다른연구에서는운동능력, handgrip strength, 폐기능, 호흡근육강도혹은삶의질에서의차이를보이지못했다. 모든연구결과중에서 1개만이사망이있었고, 총합병증에관한자료를보이는 2개의시도에서는차이가없었다. 다른체계적인분석에서도인위적인영양공급이만성폐쇄성폐질환에도움을주는지를밝히지못했다. 19

5 김성훈ㆍ김경식 : 경장영양의장점 7 7) 신부전만성혈액투석환자에서경장영양공급은혈청알부민수치를의미있게증가시키는것으로알려져있으나전향적연구가필요하다. 20 8) 그밖의질환들많은질환에서경장영양공급에대한무작위연구가되어있지않다. 현재까지알려진효과를정리하면 Table 5와같다. Disease state Acquired immunodeficiency syndrome Table 5. Evidence grades regarding utility of EN or VNS in specific disease 2 Route of artificial nutrition Grade Comments EN C No RCTs available. VNS C Two RCTs (165 patients) failed to demonstrate a benefit but the presence of a type II error could not be excluded. VNS was comparable with PN, but PN was no better than no artificial nutrition. Low birth weight Infants EN B Trophic feeding may be of benefit, but the trial quality is low. Other pediatric conditions EN C No RCTs available. VNS C No RCTs available. Malnourished geriatric patients EN C One RCT (129 patients) failed to find any benefit from EN with regard to mortality or the prevention of pressure ulcers in elderly patients with hip fractures. VNS B One RCT (129 patients) failed to find any benefit from EN with regard to mortality or the prevention of pressure ulcers in elderly patients with hip fractures. Nourished geriatric patients EN C No RCTs available. VNS C No RCTs available. Hip fractures EN D Three RCTs failed to find any benefit. VNS D Six RCTs failed to demonstrate any benefit. Stroke patients EN E High-quality evidence exists indicating that early (at the time of admission versus waiting at least 1 wk) EN in dysphagic stroke patients is not of any benefit.if dysphagia persists for weeks (or is permanent), some type of gastric infusion of nutrients will be necessary. VNS E High-quality evidence exists indicating that long-term VNS in nondysphagic patients is of no benefit. Other neurologic conditions EN C No RCTs have assessed EN (specifically through gastrostomies) in patients with end-stage dementia. VNS C No RCTs available. Allergic disorders VNS C No RCTs available. Arthritis VNS C No RCTs available. Cardiac disease VNS C No RCTs available. Pregnancy VNS C No RCTs available. Bowel preparation VNS C One RCT (26 patients) in surgical patients failed to find any difference between low-residue diets and commercial liquid diets. 결 론 경장영양요법은장점막을유지하여감염성합병증을줄이는것으로알려져있다. 하지만아직무작위연구가부족하여확실한근거를입증하기에는많은어려움이있다. 그러므로경장영양공급역시의학적인처치

6 8 한국정맥경장영양학회지제 3 권제 1 호 2010 (medical intervention) 의한분야로서위험과비용이라는문제가생길수있으므로향후국내환자를대상으로한효능검증을위한대단위연구가필요할것으로사료된다. 참고문헌 1. The Veterans Affairs Total Parenteral Nutrition Cooperative Study Group. Perioperative total parenteral nutrition in surgical patients. N Engl J Med 1991;325(8): Koretz RL, Avenell A, Lipman TO, Braunschweig CL, Milne AC. Does enteral nutrition affect clinical outcome? A systematic review of the randomized trials. Am J Gastroenterol 2007;102(2): Harkness L. The history of enteral nutrition therapy: from raw eggs and nasal tubes to purified amino acids and early postoperative jejunal delivery. J Am Diet Assoc 2002;102(3): Gianotti L, Braga M, Nespoli L, Radaelli G, Beneduce A, Di Carlo V. A randomized controlled trial of preoperative oral supplementation with a specialized diet in patients with gastrointestinal cancer. Gastroenterology 2002;122(7): Heslin MJ, Latkany L, Leung D, Brooks AD, Hochwald SN, Pisters PW, et al. A prospective, randomized trial of early enteral feeding after resection of upper gastrointestinal malignancy. Ann Surg 1997;226(4): Heyland DK, Novak F, Drover JW, Jain M, Su X, Suchner U. Should immunonutrition become routine in critically ill patients? A systematic review of the evidence. JAMA 2001;286(8): Koretz R. Enteral nutrition: a hard look at some soft evidence. Nutr Clin Pract 2009;24(3): Moore EE, Jones TN. Benefits of immediate jejunostomy feeding after major abdominal trauma-a prospective, randomized study. J Trauma 1986;26(10): Dvorak MF, Noonan VK, Belanger L, Bruun B, Wing PC, Boyd MC, et al. Early versus late enteral feeding in patients with acute cervical spinal cord injury: a pilot study. Spine (Phila Pa 1976) 2004;29(9):E Heyland DK, Dhaliwal R, Drover JW, Gramlich L, Dodek P. Canadian clinical practice guidelines for nutrition support in mechanically ventilated, critically ill adult patients. JPEN J Parenter Enteral Nutr 2003;27(5): MacLaren R, Jarvis CL, Fish DN. Use of enteral nutrition for stress ulcer prophylaxis. Ann Pharmacother 2001;35(12): Poon RT, Yu WC, Fan ST, Wong J. Long-term oral branched chain amino acids in patients undergoing chemoembolization for hepatocellular carcinoma: a randomized trial. Aliment Pharmacol Ther 2004;19(7): Als-Nielsen B, Koretz RL, Kjaergard LL, Gluud C. Branched-chain amino acids for hepatic encephalopathy. Cochrane Database Syst Rev 2003;(2):CD Le Cornu KA, McKiernan FJ, Kapadia SA, Neuberger JM. A prospective randomized study of preoperative nutritional supplementation in patients awaiting elective orthotopic liver transplantation. Transplantation 2000;69(7): Petrov MS, Whelan K. Comparison of complications attributable to enteral and parenteral nutrition in predicted severe acute pancreatitis: a systematic review and meta-analysis. Br J Nutr 2010;103(9): Louie BE, Noseworthy T, Hailey D, Gramlich LM, Jacobs P, Warnock GL MacLean-Mueller prize enteral or parenteral nutrition for severe pancreatitis: a randomized controlled trial and health technology assessment. Can J Surg 2005;48(4): Wright RA, Adler EC. Peripheral parenteral nutrition is no better than enteral nutrition in acute exacerbation of Crohn's disease: a prospective trial. J Clin Gastroenterol 1990;12(4): Griffiths AM, Ohlsson A, Sherman PM, Sutherland LR. Meta-analysis of enteral nutrition as a primary treatment of active Crohn's disease. Gastroenterology 1995;108(4): Ferreira IM, Brooks D, Lacasse Y, Goldstein RS, White J. Nutritional supplementation for stable chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2005;(2):CD Sharma M, Rao M, Jacob S, Jacob CK. A controlled trial of intermittent enteral nutrient supplementation in maintenance hemodialysis patients. J Ren Nutr 2002;12(4):

황지웅

황지웅 Comparison of Laparoscopy and Exploration in the Distal Pancreatectomy BACKGROUND: To determine the benefits of laparoscopic surgery compared with exploration, the clinical outcomes of open and laparoscopic