INVITED REVIEW online ML Comm J Neurocrit Care 2010;3 Suppl 2:S108-S114 ISSN 중환자에서정맥영양지원 연세대학교의과대학중환자관리및외상외과, 외과학교실 이재길 Parenteral Nutrition

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1 INVITED REVIEW online ML Comm J Neurocrit Care 2010;3 Suppl 2:S108-S114 ISSN 중환자에서정맥영양지원 연세대학교의과대학중환자관리및외상외과, 외과학교실 이재길 Parenteral Nutritional Support in Critical Patients Jae Gil Lee, MD Division of Surgical Critical Care and Trauma, Department of Surgery, Yonsei University College of Medicine, Seoul, Korea Understanding of principles of nutritional support is very important to manage the critically ill patients. We consider and remind the importance of nutritional support. When we start nutritional support, enteral nutrition is considered primarily. However we have to know the indication and practice of parenteral nutrition. Hereby I review the current guideline for parenteral nutrition and practical points. J Neurocrit Care 2010;3 Suppl 2:S108-S114 KEY WORDS: Nutritional support Parenteral Critical ill. 서론 중환자는영양불량이흔히발생하며, 그예후와밀접한관련이있다. 영양불량이동반된환자는감염의위험성이증가하며, 상처의회복과인공호흡기간이늘어나며, 사망률과이환률이높은것으로알려져있다. 1,2 따라서중환자의회복을돕기위해서는영양지원이필수적이며, 이에대한명확한이해가필요하다. 본글에서는중환자의영양지원과정맥영양 (parenteral nutrition) 에대해알아보고자한다. 영양지원시고려해야할사항 영양지원을시행하기위해서는다음과같은사항을고려하여야한다. 1) 영양지원의필요성 ( 적응증 ) 2) 영양지원의경로 : 경장 (enteral) 또는정맥영양 3) 영양공급량의결정 : 에너지소비량의예측 4) 영양소의구성 : 탄수화물 ( 포도당 ), 단백질 ( 아미노산 ), 지방, 비타민, 미량원소등 5) 영양지원의합병증위의내용을중심으로정맥영양지원방법과현재까지발표되어있는권고안등을설명하고자한다. 영양지원의적응증중환자에서영양지원이필요한환자는경구또는경장투여를먼저고려해야한다. 영양지원이필요한환자는중환자실에서치료받는환자는거의모두해당된다고볼수있으며, 정리하면다음과같다. 1) 영양불량이동반된환자 2) 3~4일이상경구섭취가불가능하거나금식중인환자 3) 중증외상및화상환자 4) 중환자 : 인공호흡적용환자 5) 광범위한장절제를시행한환자 Address for correspondence: Jae Gil Lee, MD Division of Surgical Critical Care and Trauma, Department of Surgery, Yonsei University College of Medicine, 250 Seongsan-ro, Seodaemun-gu, Seoul , Korea Tel: , Fax: jakii@yuhs.ac 영양지원경로영양지원은장관을이용하거나 ( 경장영양 ) 과정맥을이용 ( 정맥영양 ) 하여시행한다. 경장영양은정맥영양에비해많은장점을가지고있으며, 정맥영양은감염의위험성을높이며, S108 Copyright 2010 The Korean Neurocritical Care Society

2 PN in Critical Patients JG Lee Need for nutritional support Possible oral intake? Yes Oral diet No Usable GI tract? Enteral nutrition Yes No Parenteral nutrition Adequte nutrition? (nutritional goal) Delivery of EN 60% No EN+PN Yes FIGURE 1. Algorithm of nutritional support for critically ill patients. EN: Enteral nutrition, PN : parenteral nutrition. Maintain EN After build up TABLE 1. Indications of parenteral nutrition 1. Contraindications of enteral nutrition 1) Hemodynamical instability (Shock) 2) Gastrointestinal failure: perforation, obstruction, ischemia 3) Extensive bowel resection (Short bowel syndrome) 4) High-output fistula or stoma 5) Severe peritonitis 2. Patients who not tolerate enteral nutrition (feeding) Severe nausea, vomiting, diarrhea, abdominal distension, abdominal pain 3. Critically ill patients who cannot start enteral nutrition within 24 hours 4. Patients who cannot reach full enteral nutrition after 3dayssupplementary parenteral nutrition 면역억제작용이있고, 고혈당및간내지방축적및담즙정체, 장점막의위축및면역체계를약화시키는등많은불이익이많은상황이다. 따라서영양지원을시작할때우선적으로경장영양을고려해야하며, 경장영양은다음과같은장점을가지고있다. 1) 저렴한가격 2) 장점막세포를유지시킴 3) 장점막의방어기능을유지시킴 4) 장점막을통한장내세균전위 (translocation) 의억제따라서위장관기능이유지되어있으며, 사용이가능하다면중환자실입실후 24~48 시간이내에경장영양을시행한 다. 3-8 경장영양을시작할수없거나, 경장영양으로충분한영양지원이되지않는경우에정맥영양을시행한다. 3-5,7,9,10 영양지원방법을선택하는알고리즘은다음과같다 (Fig. 1). 정맥영양은다음과같은상황에서선택한다 (Table 1). 그러나영양불량을동반하지않은환자에서정맥영양의시작시기는학회마다다르며, 일반적으로 5일이상경장영양이불가능한경우에정맥영양을시작한다. 7 영양지원의실제 에너지공급량의계산영양지원을시작할때환자에게필요한에너지소비량 (energy expenditure) 를구하는것이중요하다. 간접열량측정법 (indirect calorimetry) 이가장좋은측정법이지만이용상제한이많아, 임상적인제한이많은상태로국내에서는소수의기관에서만사용하고있다. 에너지소비량은구하기위해여러가지공식 (Table 2) 들이사용되고있지만, 4,5,9 각각의장단점이있어서, 일반적으로중환자의에너지소비량은약 25 kcal/kg 로계산하여공급한다. 영양소의구성영양소는탄수화물, 지방과단백질을적절히배합하여사용한다. 또한전해질과미량원소를적절하게공급해주어야 S109

3 J Neurocrit Care 2010;3 Suppl 2:S108-S114 TABLE 2. Methods for calculation of basal energy expenditure (BEE) Harris-Benedict Equations (HBE): Calculation of Basal Metabolic Rate (BMR) Men: BMR=66+(13.7 weight in kg)+(5 height in cm)-(6.76 age in years) Women: BMR=655+(9.6 weight in kg)+(1.8 height in cm)-(4.7 age in years) Consider stress factor Fever: BEE 1.1 (for each above the normal body temperature) Mild stress: BEE 1.2 Moderate stress: BEE 1.4 Severe stress: BEE 1.6 Miffin-St. Jeor Euqations Men: BMR=(10 weight in kg)+(6.25 height in cm)-(5 age in years)+5 Women: BMR=(10 weight in kg)+(6.25 height in cm)-(5 age in years)-161 Ireton-Jones Equation for ventilated patients Energy expenditure=1925-[(10 age in years)+(5 weight in kg)+(281 gender)+(292 trauma)+(851 burn)] Rule of thumb kcal/kg 한다. 탄수화물 (Carbohydrate) 액체형태의탄수화물은 1 g 당 3.4 kcal의에너지를만들어낸다. 탄수화물은비단백에너지 (non-protein energy) 의 60~70% 를공급하며, 최소 2 g/kg/day, 100~120 g/day 를투여하며, 최대 7 g/kg/day 를넘지않도록한다. 고농도의탄수화물공급은고혈당을유발할수있다. 고혈당은감염의위험성을높이고, 신기능장애, 신경병증등을유발하고, 인공호흡기간도늘리는것으로알려져있다. 따라서고농도의탄수화물공급시에혈당을자주체크하여야하며, 정상혈당으로 (80~140 mg/dl) 유지하기위해적극적인인슐린치료가필요하다. 11 지방 (Lipids) 지방제제는 1 g 당 9 kcal의에너지를공급할수있다. 그러나실제임상에서사용하는 10% 농도의지방제제는 1 g 당 11 kcal를공급하며, 20% 농도의제제는 1 g은 10 kcal의에너지를공급하게된다. 지방제제는대두유 (soybean oil), 중쇄중성지방 (Medium chain triglyceride: MCT), 올리브오일 (Olive oil), 어유 (Fish oil) 및혼합제제등이있다. 지방은적은용량으로높은에너지를공급하므로중요한에너지원으로활용되고있으며, 필수지방산과 eicosanoids 의전구체를공급하게된다. 정맥영양을시행할때지방은비단백에너지공급량의 30~ 40% 를공급하지만, 환자의상태, 기저질환등에따라공급량을조절한다. 지방은고혈당을유발하지않으면서높은에너지를공급할수있어서, 당뇨환자나포도당불내성이있는환자에서탄수화물의공급량을줄이기위해서도사용한다. TABLE 3. Daily Requirements for vitamins and trace elements Enteral dose Parenteral dose Vitamin Vitamin A 1,000 µg0. 3,300 IU000 Vitamin B µg 05 µg Vitamin C 0 60 mg 100 mg. Vitamin D 005 µg 200 IU0. Vitamin E 0 10 mg 10 IU0 Vitamin K 100 µg 10 mg Thiamine (B 1 ) 00 2 mg 0 3 mg Riboflavin (B 2 ) 00 2 mg 0 4 mg Pyridoxine (B 6 ) 00 2 mg 0 4 mg Pantothenic acid 00 6 mg 15 mg Biotin 150 µg 60 µg Folate 400 µg 400 µg0 Trace elements Chromium 200 µg 15 µg Copper 00 3 mg 1.5 mg Iodine 150 µg 150 µg0 Iron 0 10 mg 2.5 mg Manganese 00 5 mg 100 µg0 Selenium 200 µg 70 µg Zinc 0 15 mg 0 4 mg 단백질 (Protein) 중환자의체내에서는활발한단백질대사가일어나며, 급 성기단백질의합성과근육내단백질의분해가활발하게일 어나며질소평형이감소하게된다. 따라서질소평형을유지 하고, 단백질대사를원활하게만들기위해서는적절한양의 단백질은공급해주어야한다. 단백질은아마노산의형태로공급하며, 일반적으로 0.8~ 1.5 g/kg/day를공급해준다. 그러나공급된아미노산은 S110

4 PN in Critical Patients JG Lee TABLE 4. Summary of current guidelines for parenteral nutrition Canadian ESPEN ASPEN-SCCM Starting methods Enteral Enteral Enteral Start timing 24~48 hr 24~48 hr 24~48 hr Indications of PN Do not use PN in patients with intact gastrointestinal tract 1) Patients who do not have normal nutrition within 3 days 2) If EN is contraindicated 3) if patients cannot tolerate EN 1) Previously healthy: after the first 7 days of hospitalization, when EN is not available 2) Protein-calorie malnutrition: EN is not feasible, start PN as soon as possible 3) Use of PN 7 days Timing of PN Within 24~48 hr, if PN is indicated Above description Calorie requiremtn Indirect caloremetry 25 kcal/kg/day 25 kcal/kg/day (increasing to target over 2~3 days) Indirect caloremetry 25 kcal/kg/day (?) Components of nutrients Avoid lipid (soy-bean based lipid emulsion) (PN <10 days) CHO: >2g/kg/day (100~120 mg/day) (maximum 5 mg/kg/min) Lipid: 0.7~1.5 g/kg/day Amino acids: 1.3~1.5 g/kg/day IBW)* Permissive underfeeding: <80% of calculated calorie Avoid lipid (soy-bean based lipid emulsion) (PN <10 days)) Glycemic control 140 mg/dl (8 mmol/l) <180 mg/dl Immuno-nutrient Supply vitamin/trace elements Selenium (?) IV glutamine with PN Supply vitamin/trace elements Glutamine: 0.2~0.4 g/kg/day Fish oil (Ω-3 fattly acid): decrease length of stay Supply vitamin/trace elements IV glutamine with PN 혈중요질소 (BUN) 을증가시키고, 암모니아의생성을증가시킬수있어간기능장애가있거나신기능장애가있는환자에서는 0.6~1.0 g/kg/day 로낮추어공급한다. 아미노산이적절히공급되고있는지판단하기위해서질소평형을측정하며, 정상적인질소평형은 2~4 이며, 부족시에는아미노산을적절히공급해주어야한다. 질소평형 = 질소섭취량-질소배설량 =( 아미노산섭취량 /6.25)-(24 시간요질소 +4) 비타민 (Vitamine) 과미량원소비타민은생체대사에관여하는인자로, 대사가활발히일어나는중환자에서필요량이증가하게되므로, 적절히공급하지않으면비타민결핍증을유발할수있다. 미량원소도신체대사에중요한역할을하며, 정맥영양시충분히보충해주어야한다. 비타민과미량원소의일일요구량은다음과같다 (Table 3). 12 정맥영양의지침세계여러학회에서정맥영양의권고안을개발하여사용중에있으므로, 각자에맞는방법을선택하여정맥영양을시행한다. 각학회지침에대해다음표에요약하였다 (Table 4). 3,5,8 영양지원의합병증정맥영양지원시발생가능한합병증은다음과같다 (Table 5). 2,13-14 이중고혈당과재급식증후군 (Refeeding syndrome) 에대해간략히알아보고자한다. 고혈당 (Hyperglycemia) 중환자는기저질환이나활발한대사작용에의해간내포도당합성이증가되고, 말초조직에서인슐린에대한저항성이증가하며, 정맥영양으로공급되는다량의포도당에의해 TABLE 5. Potential Complications of Parenteral nutrition Catheter related Catheter malposition Pnemothorax Sepsis Thrombosis Metabolic complications Hepatic dysfunction Steatohepatitis Hyperbilirubinemia Hyperglycemia Hypertriglyceridemia Refeeding syndrome Gastrointestinal complications Mucosal atrophy Bacterial translocation Acalculous cholecystitis S111

5 J Neurocrit Care 2010;3 Suppl 2:S108-S114 고혈당이발생할수있다. 고혈당은내피세포와상피세포등에직접적으로독소작용을하고, 활성산소의생성을증가시키며, 염증반응을활성화시키면서, 면역억제등을유도하여중환자의감염성질환의이환율과사망률을높이는것으로알려져있다. 따라서중환자는적극적인혈당조절이필요하다. 그러나너무엄격한혈당조절은저혈당을유발할수있고, 저혈당이유발된환자의생존율이낮은것으로보고되어현재는혈당을 80~140 mg/dl 정도로유지하도록권고하고있다. 11,15-18 재급식증후군 (Refeeding syndrome) 13,19,20 재급식증후군은오랫동안금식하였거나, 영양상태가불량한상태에서영양지원을시작할때일어나는대사반응으로, 영양지원시작후수일내에발생한다. 주된증상은다량의설사또는오심, 구토등이유발될수있으며, 전해질및비타민불균형에의한다양한증상이나타날수있다. 저인산혈증 (hypophosphatemia) 가주된작용을하게되며대략적인발생기전은다음과같다 (Fig. 2). 20 심한경우혼수상태에빠질수있으며, 심부정맥등에의해사망까지이를수있다. 따라서영양지원을시작할때재급식증후군의위험성에대해인지하여야하며, 고위험환자에서는에너지공급량을처음부터 100% 로시작하지않고 25~70% 정도에서시작하 며, 4~7일에걸쳐서서히증량하여야한다. 또한영양지원을시작하기전에전해질불균형 ( 저인산혈증, 저칼륨혈증, 저마그네슘혈증 ) 을교정하여야하며, 부족한전해질을적절히보충해주어야한다. 면역영양 (Immuno-nutrition) 중환자및패혈증환자에서면역체계를활성화시켜, 회복을도와주고자하는노력들이활발히진행되고있다. 이와관련되어많은영양소 ( 아미노산과지방 ) 에대한연구가있었으며, 현재는글루타민과 Ω-3 지방산이어느정도효과가있는것으로알려져있다. 글루타민 (Glutamine) 영양지원시필수아미노산은반드시공급해주어야하나, 글루타민은필수지방산에포함되어있지는않지만중환자에서는체내사용이급증하여결핍증을일으키게된다. 글루타민은장점막세포의주된에너지원으로부족시장점막의위축을유발하여, 장내세균의전위를유발할수있으며이와더불어감염의위험성을높일수있다고알려져있다. 또한글루타민은면역세포와폐의내피세포, 심근세포의주된에너지원으로작용한다. 경장영양을시행하지못하는환자에서글루타민을투여하 Starvation/Malnutrition Refeeding syndrome Glycogenolysis, Gluconeogenesis Liver Hypokalemia Hypomagnesemia Hypophosphatemia Thiamine deficiency Water & salt retention Cardiac dysfuncion Hypotension Arrhythmia Decreased stroke volume Respiratory dyfunction Dyspnea Pulmonary edema Protein catabolism Insulin Respiratory failure Neurologic dysfuncion Weakness Confusion/Disorientation Seizure/Coma/Death Cell Protein production Glucose uptake Utilization of thiamine Uptake of K +, Mg 2+, PO 2-4 Hematologic dysfunction Gastrointestinal Nausea/Vomiting/Constipation Vitamin/Thiamine deficiency Encephalopathy Protein, fat, mineral electrolyte, vitamin depleion Lactic acidosis Insulin Nutritonal support (CHO: major source) FIGURE 2. Pathogenesis and clinical signs of refeeding syndrome. S112

6 PN in Critical Patients JG Lee 면감염의위험성과합병증, 인슐린요구량을감소시키며, 생존율또한높일수있다. 따라서정맥영양을지속적으로시행해야하는환자에서글루타민사용을고려해야한다. 3,5,7,21-23 ω-3 지방산지방산의세포막을형성하는데이용되며, 아라키돈산의전구체로작용한다. Cyclooxygenase(COX) 와 lipo-oxygenase(lox) 의효소작용에의해만들어지는프로스타글란딘 (prostaglandin: PG) 와 leukotriene(lt), 트롬복산 (thromboxane: TX) 는염증반응을매개하는물질로작용한다. ω-3 지방산에포함되어있는 docosahexaenoic acid(dha) 와 eicosapentaenoic acid(epa) 는항염증작용을가진 PG, LT와 TX를만들어내다 (Fig 3). 7,21,23,24 ω-3 지방산은트리글리세라이드의농도를조절하며, 합병증과재원기간을감소시키며, 급성폐부전환자에서는사망률을낮출수있는것으로보고되고있다. 따라서현재발표되어있는권고안들은정맥영양을시행하는중환자에서 ω-3 지방산을포함한지방제제를사용하도록권고하고있다. 3,5,7,8 결론 중환자에서영양지원은반드시필요한것으로경장영양을먼저고려해야하지만정맥영양을시행하는경우도흔히접 할수있다. 따라서정맥영양지원방법에대한이해와, 정맥지원시고려해야할사항에대한이해가필요하다. 중환자에서정맥영양을시작하기위한일련의과정을요약하며마무리하고자한다. 1) 영양지원이필요한가? 2) 영양지원방법은? 3) 에너지요구량은? 25 kcal/kg/day (15~20 kcal/kg/day 로시작하여서서히증량 ) Refeeding syndrome 주의 4) 필요한영양소는? CHO: 60~70% of Non-protein calorie Glycemic control: 80~140 mg/dl Lipid: 30~40% of Non-protein calorie Use of ω-3 fatty acid Amino acid: 0.8~1.5 g/kg/day Glutamine: Consider to use Normal liver & kidney function: 1.2~1.5 g/kg/day Liver failure/cholestasis: 0.6~1.0 g/kg/day Renal failure without renal replacement therapy: 0.6~1.0 g/kg/day Renal failure with renal replacement therapy: 1.2~ 2.0 g/kg/day DHA Arachidonic acid (membrance phospholipids) EPA NFkB Phospholipase A 2 Inflmmatory Free arachidonic acid (cytokines) 5-LOX COX-2 COX-2 5-LOX COX-2 D-series resolvins, etx 2-series PG & TX 4-series LT E-series recolvins 3-series PG & TX 5-series LT inflammatory Antiinflammatory Antiinflammatory Antiinflammatory Less Inflammatory than 2 /4-series FIGURE 3. Anti-inflammatory of ω-3 fatty acids. S113

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untitled SMN SURGICAL METABOLISM AND NUTRITION Vol. 1, No. 1, December 2010 REVIEW ARTICLE 면역지원영양소 이재길 연세대학교의과대학외과학교실 Immuno-supportive Elements Jae Gil Lee, M.D., Ph.D. Department of Surgery, Yonsei University