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1 Review Article J Clin Nutr 2017;9(2):38-47 pissn ㆍ eissn 중환자의영양집중치료에대한임상지침최근동향 : 2016 년 Society of Critical Care Medicine/American Society for Parenteral and Enteral Nutrition 임상지침을중심으로 최유진, 이재명 고려대학교의과대학고려대학교안암병원외과 Yoo Jin Choi, Jae-Myeong Lee Department of Surgery, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea Critically ill and injured patients admitted in the intensive care unit have a range of diseases with various severities. Their conditions should be assessed and the patients should receive specialized nutrition therapy depending on their condition. Like general intensive care, nutrition therapy is upgraded every few years with revised information to provide more idealized nutrition support. The main guidelines in this review are from the Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (ASPEN). Their previous 2009 guidelines were revised and published in This review summarizes the 2016 SCCM/ASPEN guidelines focusing on the changes from the previous 2009 guidelines. Key Words: Nutrition support, Guidelines, Critically illness 서 론 중환자에게적용되는영양지원은이제중환자치료의중요한일환으로인정되고있다. 중환자실에입원하여관리받는환자들은다양한기저질환및중증도를갖고있으며, 환자별로상태가매우다양하고치료가어렵다. 이때문에일반적인중환자치료임상지침내용도수년마다바뀌는경우가더러있는데, 중환자의영양치료역시최근제시된여러임상지침들에서새롭게 Received Aug 18, 2017; Revised Nov 8, 2017; Accepted Nov 18, 2017 Correspondence to Jae-Myeong Lee Department of Surgery, Korea University Anam Hospital, Korea University College of Medicine, 73 Inchon-ro, Seongbuk-gu, Seoul 02841, Korea Tel: , Fax: , ljm3225@hanmail.net Conflict of interest: None. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 정리된부분들이있다. 1-5 특히 2016년에개정된 Society of Critical Care Medicine (SCCM, 미국중환자의학회 )/American Society for Parenteral and Enteral Nutrition (ASPEN, 미국정맥경장영양학회 ) 의성인중환자영양치료지침 ( 앞으로 2016 SCCM/ASPEN 중환자영양지침으로명시 ) 은 2009년성인중환자영양치료지침이처음으로제시된이후 7년만에개정된내용으로, 2013년 12월 31일까지의문헌조사내용을반영하여광범위한내용을제시하고있다. 1,6 이종설에서는이임상지침을중심으로최근에새롭게제시되거나변경된중환자영양치료에대한내용을정리함으로써, 실제임상에서쉽게적용할수있도록돕고자하였다. 중환자의영양치료지침내용자체가매우방대한양이므로, 기존임상지침의모든내용을다담기보다는, 새로운내용또는논란이있다가최근들어정립되고있는임상지침에대한내용만을중점적으로다루고자한다. c 2017, The Korean Society for Parenteral and Enteral Nutrition. All Rights Reserved.

2 본론 SCCM/ASPEN 중환자영양지침의묶음지침 (Bundle statements) 2009년임상지침대비 2016년도임상지침에서달라진내용중대표적인것은, 6개의주요지침을 Bundle statements로제시하였다. 1 중환자실에입실을하면곧바로영양평가가이루어져야한다는것을강조하였고, 필요열량과단백질량을계산하여야하며, 첫경장영양은입원후 24 48시간안에이루어지는것이이상적이라고권고하고있다. 영양치료시작후에는일주일안에그목표량에도달해야하고, 환자의경장영양허용여부나흡인가능성여부를지속적으로평가해야한다. 흡인을줄이기위해서는위장운동촉진제, 지속적경장영양액주입, 하루 2 회클로르헥시딘구강가글, 침상머리 30도반좌위 (Semi- Fowler 자세 ), 위장관섭취우회로이용등을할수있다. 경장영양이불가능하다고판단된다면정맥영양을일찍시작하는것이좋다. 위내용은일반적인중환자영양지침에해당되는핵심내용이라고하겠다. 2. 중환자의영양평가및영양요구량산정 2009 SCCN/ASPEN 중환자영양지침에서는영양평가에대한내용이없었으나, 2016 SCCM/ASPEN 중환자영양지침에서는첫번째세부항목으로중환자의영양평가내용을새로삽입한것을볼수있다. 6,7 중환자영양치료의시작이기도한중요한부분인데, 2009년임상지침에서는누락되었다가, 저자들이언급한대로 2014년캐나다임상지침을보고새롭게추가한부분으로생각된다. 7 모든입원환자들에게있어입원후 48시간안에영양평가가이루어져야한다거나, 특히중환자실입원환자들에게는더정확하고충분한영양평가가필요하다는내용에이견이있는사람은없을것이다. 8 다양한영양평가도구들중에서, 9-12 어떠한영양평가도구가가장중환자에게적합할것인가에대해서고민해보자면, 결국다양한중환자의특성중질병의심각성에대한평가와영양상태에대한평가가함께이루어지는것이바람직할것이다. 이에 2016 SCCN/ASPEN 중환자영양지침에서는 Nutritional Risk Screening 2002 (NRS 2002) 나 Nutrition Risk in the Critically Ill (NUTRIC) score를사용할것을권유하고있다 (Table 1 3) 영양치료의목표를설정하고이를달성하기위해서환자별필요열량과단백량에대해평가해야한다. 에너지는간접열량 측정기 (indirect calorimetry, IC) 로평가하는것이가장바람직하다고하였으나, 14 현재대부분의병원에서 IC의실물을구경조차해보지못했거나, 실제측정해본경험이없는의료진및영양사가대부분인것이국내의실정이다. 게다가 IC의임상적용을위해서는검사인력및많은시간이소요되므로현실성이낮다. 따라서체중에따른계산공식, 열량 kcal/kg/d, 단백량 g/kg/d를사용하면되겠다. 1 중환자를위한적절한단백질의공급은지속적으로강조되고있는부분으로, 환자의침상옆에서항상충분한양의단백질을공급하고있는지에대해질문을던져야할것으로생각된다 설정한영양요구량대비얼마만큼의양을전달할것인가에대해서는최근까지도계속해서논란이되고있다 Full feeding 은요구량의 80% 이상을전달하는것이고, trophic feeding 은 ml/h 또는 kcal/h로해서일일최대 500 kcal만을전달하는것, 그리고 permissive underfeeding 은요구량의 50% 80% 를전달하는것으로개념이정리되어있다. 22 Trophic feeding 을주장하는사람들은, 일일 500 ml 정도의경장영양만으로도장내점막구조와기능을유지하는데충분하다고주장하며, 급성폐손상환자들에서 full feeding 환자와비교하였을때인공호흡기제거일, 중환자실재원일, 사망률등에서비슷한성적을보인반면, 변비나구토등의경장영양관련문제의발생은적었다고보고하고있다. 20,21,23 어느정도의양을전달할것인가에대해서는앞으로도계속논란이될것으로생각되며, 더많은연구결과가모아져야할것으로생각된다 SCCM/ASEPN 중환자영양지침에서달라진내용 1) 경장영양과정맥영양의시작시점 NRS 2002와 NUTRIC score에서영양불량고위험군으로분류된환자군은입원후 24 48시간안에가능하면경장영양의형태로영양집중치료를시작하고, 저위험군환자들은입원후일주일동안은 specialized nutrition support를피할것을제시하였다. 2009, 2016 SCCN/ASPEN 중환자영양지침모두영양불량위험도가낮으면, 경장영양이불가능하더라도첫 7일이내굳이정맥영양치료를하지말라고권고하였다. 1,6 그러나이번 2016년새지침에서는영양평가결과에따라저위험영양불량환자에서는 7일이후에정맥영양을시작하지만, NRS 2002 또는 NUTRIC score 5점이상의고위험영양불량환자들에게는경장영양이불가능할경우, 단독정맥영양을되도록일찍시작하는것을추천하는것으로내용이변경되었다. 1 하지만고위험군에속하고경장영양이불가능하더라도패혈증환자들은영양상태와무관하게정맥영양을일찍시작하지말것을권고하 Volume 9, Number 2, December

3 Yoo Jin Choi and Jae-Myeong Lee 고있고, 1,24,25 혈역학적으로불안정한환자들도혈압이안정되거나승압제를저용량으로줄일수있을때까지경장영양을보류할것을권유하고있다. 1 Table 1. NUTRIC scoring system NUTRIC Score variables Age (y) < < APACHE II < < SOFA <6 0 6 < Number of Co-morbidities Days from hospital to ICU 0 <1 0 admission 1 1 IL-6 (pg/ml) 0 < Modified from the article of Heyland et al. Crit Care 2011;15(6): R NUTRIC = Nutrition Risk in the Critically Ill; APACHE II = Acute Physiology and Chronic Health Evaluation II; SOFA = Sequential Organ Failure Assessment; ICU = intensive care unit; IL = interleukin. 2) 경장영양제제와경장영양보조요법 2016 SCCN/ASPEN 중환자영양지침경장영양부분에서제제와보조요법에대해서도바뀐내용들이있다 (Table 4). 경장영양의제제는표준제제와특수제제로나뉘는데, 특수제제는질환별, 장기별, 소화효소에의해서가수분해된펩타이드 (semi-elemantal), 소화효소에의해서가수분해된유리아미노산 (elemental), 면역조절제제등이있다 지침에서는주요정규수술환자, 외상, 화상, 두경부암, 기계호흡중인환자, 중증패혈증환자에서는면역조절제제 (arginine with eicosapentaenoic acid [EPA], docosahexaenoic acid [DHA], glutamine, nucleic acid) 를투여하라고하였으나, 지침에는내과계중환자에게는특수제제를처음부터일상적으로사용하지말고, 외과계중환자중에서도외상, 외상성뇌손상, 수술전후로중환자실로입실하는환자들에게만사용하기를권고한다. 1 경장영양의보조요법에는글루타민, 프로바이오틱스, 섬유질, 항산화제, 미량원소등이포함된다 지침에서는경장글루타민의첨가가외상, 화상환자들에게추천되었었으나, 다섯개의무작위대조군연구들을통해경장글루타민제제가환자의사망률, 감염, 입원기간면에서도움이되지않는다고밝혀져, 2016년지침에서는추가하지말라는권고로바뀌었다. 1 프로바이오틱스는보통중환자실환자들에게안전하나사망률이나설사발생률에영향이없었기때문에, 사용여부에대해서는아직지침을만들정도가아니라고하였다. 26 그러나외상, 간이식, 췌장절제환자들에게유익성이있었다는보고들이있었으므로, 이런환자들에게서사용될수있겠다는정도로가능 Table 2. NUTRIC scoring system: if IL-6 available Sum of points Category Explanation 6 10 High score Associated with worse clinical outcomes (mortality, ventilation). These patients are the most likely to benefit from aggressive nutrition therapy 0 5 Low score These patients havea low malnutrition risk. Reproduced from the article of Heyland et al. Crit Care 2011;15(6):R NUTRIC = Nutrition Risk in the Critically Ill; IL = interleukin. Table 3. NUTRIC scoring system: if no IL-6 available a Sum of points Category Explanation 5 9 High score Associated with worse clinical outcomes (mortality, ventilation). These patients are the most likely to benefit from aggressive nutrition therapy 0 5 Low score These patients have a low malnutrition risk. Reproduced from the article of Heyland et al. Crit Care 2011;15(6):R NUTRIC = Nutrition Risk in the Critically Ill; IL = interleukin. a It is acceptable to not include IL-6 data when it is not routinely available; it was shown to contribute very little to the overall prediction of the NUTRIC score. 40 Journal of Clinical Nutrition

4 Table 4. Comparison between 2009 and 2016 SCCM/ASPEN nutrition guidelines for critically ill patients Subjects Enteral formulation Adjunctive therapy Parenteral nutrition Immune-modulating enteral formulations (arginine with other agents, including EPA, DHA, glutamine, and nucleic acid) Supplemental enteral glutamine Anti-inflammatory lipid profile (i.e., -3 fish oils, borage oil) and antioxidants in ARDS/ALI Major elective surgery, trauma, burns, head and neck cancer, critically ill patients on mechanical ventilation with caution in patients with severe sepsis. Should be considered in burn, trauma, and mixed ICU patients. (B) Should be placed. (A) No routine use in the MICU. TBI, perioperative patients in the SICU. Not be added to an EN regimen routinely in critically ill patients. (Moderate) Cannot make a recommendation at this time. (Low to Very Low) Probiotics No recommendation can be currently made. Cannot make a recommendation. Consider in LT, trauma, pancreatectomy. Soluble fiber (FOSs, inulin) Maybe beneficial. (C) Routine use for hemodynamically stable patients, g/d of fermentable soluble fiber. Target blood glucose 100~150 mg/dl (E) 140 or mg/dl (Moderate) Parenteral glutamine Consideration should be given. (C) Not be used routinely. (Moderate) supplementation Lipids In the first week, should be given a parenteral formulation without soy-based lipids. (D) Alternative IVFEs (SMOF [soybean oil, MCT, olive oil, and fish oil emulsion], MCT, olive oil, and fish oil) may provide outcome benefit over soy-based IVFEs. The level of evidence are adopted from that of 2009 and 2016 guidelines. SCCM = Society of Critical Care Medicine; ASPEN = American Society for Parenteral and Enteral Nutrition; EPA = eicosapentaenoic acid; DHA = docosahexaenoic acid; MICU = medical intensive care unit; TBI = traumatic brain injury; SICU = surgical intensive care unit; ICU = intensive care unit; EN = enteral nutrition; LT = liver transplantation; FOSs =fructo-oligossaccharides; IVFE = intravenous fat emulsion; MCT = medium chain triglyceride. 성만열어두고있다 섬유질에대해서는 2009 지침에서는유익성이있을것이라고추측만했으나, 2016 지침에서는혈역학적으로안정된모든환자들에게발효불용성섬유질 (fermentable soluble fiber, ex. fructo-oligossacharides, inulin) 을일상적으로공급하기를권고하고있으며, 섬유질양도구체적으로 24시간동안 g 정도를추천하고있다. 1 수용성섬유질과불용성섬유질을다포함하고있는상용화제제를일상적으로사용하는것은추천되지않으며, 장허혈증이나심한장운동장애의가능성이있는환자들에게는섬유질을공급하지말아야한다. 국내에서는섬유질이약품이아닌식품으로생산되고있고한끼식사금액은한정되어있으므로, 일상적인섬유질사용과동반된경제적인문제역시고민이될수있다. 그밖에항산화비타민제 ( 비타민 C, E) 와미량원소 ( 셀레늄, 아연, 구리 ) 는중환자들에게안전하게사용될수있으며, 특히화상, 외상환자나기계호흡을필요로하는환자들의치료성적을향상시킨다. 1,31,32 3) 정맥영양과정맥영양보조요법정맥영양부분에서도몇가지바뀐내용들이있다. 일단, 기본 Volume 9, Number 2, December 2017 적으로저위험군 (NRS or NUTRIC score 5) 환자들은먹지못하거나이른경장영양이불가능하더라도중환자실입원후 7일까지는정맥영양을보류해야한다. 하지만영양적고위험군 (NUTRI score 5 or NRS ) 이고경장영양이불가능한환자들에서는중환자실입원후되도록빨리정맥영양을시작하며, 저열량정맥영양 ( 20 kcal/kg/d 또는예상열량의 80%) 과적절할단백질량 ( 1.2 g/kg/d) 을투여하기를권고하고있다. 또한경장영양을하고있으나 7 10일후에도필요에너지와단백질량의 60% 이상에도달하지못하면정맥영양을추가한다 지침에서는일주일안에대두유가아닌지방제제를공급해야한다고하였으나, 2016 지침에서는정맥영양시작후일주일안에지방제제를전달하는것은보류하라고하고있다. 만약필수지방산결핍이있다면 100 g/ 주 ( 대개주 2회로나누어서공급 ) 로제한하여사용하라고하고있다. 1 그러나다른연구들에서중쇄지방산 (medium chain triglyceride, MCT), 올리브유 (olive oil), 생선유 (fish oil), SMOF (soybean oil, MCT, olive oil, and fish oil) 가유익한결과를제공할수도있다는보고들이있다. 33,34 미국에는아직 SMOF 제제가보급이안되어사용할수가없었기때문에이에대한경험이없어지침에서는 41

5 Yoo Jin Choi and Jae-Myeong Lee 사용권고를조심스러워하나, 국내에서는사용이가능하므로지방제제가필요하다면대두유사용보다는위에언급된지방제제를사용하는것이좋겠다. 정맥글루타민제제는경장영양과마찬가지로 2016 지침에서는일상적인사용을하지말기를권고하고있다. 1 4) 중환자의혈당관리중환자들의경우스트레스로인한고혈당증이매우흔하게나타난다. 과거에는엄격하게혈당을조절하여혈당을 mg/dl에맞추라고하였으나, 엄격한혈당조절은오히려저혈당발생률을높였고, 이는높은사망률로이어지는결과를보였다. 35 이후대규모연구인 NICE-SUGAR 연구에서혈당목표를 mg/dl로맞추어도합병증과사망률에큰차이가없다는것을보고한것을기반으로, 36 현재에는일반적인중환자실환자들의목표혈당을 140 또는 mg/dl 사이로맞추기를권유하고있다. 4,37,38 4. 중환자에서흔한질환별또는환자상태별영양치료지침요약 1) 호흡부전과거호흡부전환자들에게고지방 / 저탄수화물경장영양이기계환기의기간을줄인다는이유로추천되어왔다. 39 그러나이연구는 20명정도의환자만을대상으로얻어진연구결과였으며, 39 이후시행한무작위대조실험에서는같은결과를얻을수없었다. 40 게다가우리가과영양공급을할때에만고지방 / 저탄수화물영양이혈중이산화탄소분율을낮추는것으로보고되어, 41 더이상호흡부전환자에게고지방 / 저탄수화물경장영양은추천되지않는다. 1 폐질환환자들은폐수분저류, 폐부종, 신부전등이흔하게발생하므로, 수액제한고농도영양제제 (1.5 2 kcal/ml) 가추천된다. 42 인 (phosphate) 은 adenosine triphosphate (ATP) 같은에너지생산에필수요소이며, 이들이횡경막수축과폐기능에결정적인요소가될수있기때문에, 중환자에서는인의혈중농도를측정하고부족분을보충해주는것이좋다. 43,44 2) 신부전급성신부전환자라도일반환자처럼열량 kcal/kg/d, 단백량 g/kg/d를제공한다. 45 지속적투석이나잦은투석치료를받는환자들에게는단백질이절대로제한되어서는안되며, 오히려최대 2.5 g/kg/d까지투여해야한다. 46,47 3) 간부전장시간정맥영양은간부전환자들에게합병증을유발할수있기때문에경장영양공급이중요하다. 48 최근연구들에서간부전으로인한뇌증이있는환자들에게가지사슬아미노산 (branched-chain amino acid) 제제의사용은더이상유익성이없다고보고하여, 49 그냥표준경장영양을실시하는것을추천한다. 4) 급성췌장염급성췌장염환자들은병의중증도에따라영양치료를해야한다. 50 경미한급성췌장염환자는특별한영양치료없이식이진행을하면서경과관찰을하는것이좋다. 51,52 중증의급성췌장염환자들에게는수분제한이끝나면, 입원한지 24 48시간안에표준경장영양제제를이용하여경관영양을시작하는것을추천하고있다 이때프로바이오틱스를같이투여하는것이좋다. 56 하지만경관영양이불가능할경우췌장염이있은지일주일후부터는정맥영양을고려해보아야한다. 53,57 5) 외상혈역학적으로안정된환자들은외상이발생한지 24 48시간안에경관영양과고단백질식이를시작하고, 58,59 중증외상에서는아르기닌과생선유가첨가된면역조절제제를투여하는것을추천한다. 60 6) 외상성뇌손상보통외상환자들과비슷하게일찍경관영양을시작하고, 61,62 아르기닌과 EPA/DHA가첨가된면역조절제제를추천한다. 61 7) 개방성복부손상장손상이없는한외상당한지 24 48시간안에경관영양을투여할것이권고되며, 63 하루필요한열량총량은일반중환자와같이 kcal/kg/d이고, 단백질은복부손상에서흘러나온삼출물 1 L당 g을추가로투여해준다. 64,65 8) 화상매주 IC로환자의에너지필요량을체크하고단백질은 g/kg/d를보충한다. 66,67 가장중요한것은화상입은지 4 6 시간안에매우빠르게경관영양을시작해야한다는점이다. 68 9) 패혈증패혈증환자들에서혈역학적으로안정되면 시간안에경관영양을빨리시작하는것이좋다는것은여러연구에서밝 42 Journal of Clinical Nutrition

6 혀졌다 경관영양을시작한환자들에게서보조적인정맥영양의추가는권장되지않는다. 25,73,74 또한셀레늄, 아연, 산화방지보조제는여러연구의모순된결과로아직정확한기준이없다 면역조절제제, 대사조절경장영양제제 ( 아르기닌, EPA, DHA, 글루타민, 핵산 ) 를일상적으로사용하는것역시권장되지않는다. 77 급성기에는저열량으로 kcal/h 또는하루 500 kcal 정도만투여하고, 24 48시간후부터일주일동안에목표열량에도달해야한다고권고하고있다 ) 수술후환자중환자실에입실하게되는주요수술후환자들의영양위험도를평가할때, 혈중 albumin, prealbumin, transferrin 등의사용은더이상추천되지않는다. 79,80 24시간안에경장영양을시작하고, 81 경장영양의종류로아르기닌이나생선유를사용시감염률과입원기간을줄인다는메타분석이있고, 82 수술전후이제제를사용했을경우유익한점들이많아추천하고있다. 83 그리고고형식이가가능하면유동식단계를밟지않고곧바로고형식식이로진행한다. 84,85 결론 이종설은최근에소개된중환자를위한영양지침중, 가장포괄적으로정리가잘되었다고평가되는 2016년에개정된 SCCM/ASPEN 중환자영양지침의내용을중심으로, 중환자영양치료의최신지침경향에대해정리하였다. 중환자에게는질병과동반질환등의특성이반영된영양평가도구를사용하는것이중요하고, 환자개개인의임상및영양상태에따라영양집중치료를시행하는것이중요하다. 질병이나환자의특성별로환자에게도움이되거나필요한영양요법들이다르기때문에, 이에대해서잘알고최대한반영하는것이중요하겠다. 최근중환자를위한영양집중치료에대해많은연구가진행되고있다. 영양집중치료역시중환자의치료결과에영향을미칠수있는주요요인중하나이기때문에, 우리는최대한증거를중심으로한최신지견에따라치료하려고노력해야할것이다. 또하나, 지침을최대한반영하되, 환자의옆에서환자개개인의특성에맞는치료를시행하려고노력하는것이중요하겠다. REFERENCES 11) 만성중증환자지속적장기부전으로중환자실입원기간이 21일이상되는사람들을말하며, 86 이들에게는고단백경장영양과단백손실예방을위한재활치료가중요하다 ) 비만중환자중증비만환자는심혈관계질병과이로인한사망가능성이높으므로, 비만과관련된지방과다증 (central adiposity), 대사증후군, 근감소증, 체질량지수 40 kg/m 2 초과, 전신염증성반응, 다른동반질환등을포함하여영양평가를시행하여야한다. 88 비만환자들을위한열량필요량은 IC로측정한목표열량의 65% 70% 를목표로하며, IC를사용할수없는경우에는몸무게기반계산식사용을권유한다. 체질량지수가 kg/m 2 인환자는 kcal/actual body weight/d, 체질량지수 50 kg/m 2 이상인환자는 kcal/actual body weight/d 로계산한다. 89 단백질필수량은, 체질량지수 kg/m 2 인환자는 2.0g/ideal body weight/d, 40 kg/m 2 이상인환자는 2.5 g/ 이상체중 /d를제공한다. 90,91 비만환자들은특히고혈당, 고지혈증, 고이산화탄소혈증, 수분저류, 간지방축척등을유심히관찰해야한다 McClave SA, Taylor BE, Martindale RG, Warren MM, Johnson DR, Braunschweig C, et al. Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient: society of critical care medicine (SCCM) and American society for parenteral and enteral nutrition (A.S.P.E.N.). JPEN J Parenter Enteral Nutr 2016;40(2): Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, et al. Surviving sepsis campaign guidelines for management of severe sepsis and septic shock. Crit Care Med 2004;32(3): Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: Crit Care Med 2008;36(1): Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: Crit Care Med 2013;41(2): Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: Intensive Care Med 2017;43(3): McClave SA, Martindale RG, Vanek VW, McCarthy M, Roberts P, Taylor B, et al. Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient: society of critical care medicine (SCCM) and American society for parenteral and enteral nutrition (A.S.P.E.N.). JPEN J Parenter Volume 9, Number 2, December

7 Yoo Jin Choi and Jae-Myeong Lee Enteral Nutr 2009;33(3): Dhaliwal R, Cahill N, Lemieux M, Heyland DK. The Canadian critical care nutrition guidelines in 2013: an update on current recommendations and implementation strategies. Nutr Clin Pract 2014;29(1): Kondrup J. Nutritional-risk scoring systems in the intensive care unit. Curr Opin Clin Nutr Metab Care 2014;17(2): Anthony PS. Nutrition screening tools for hospitalized patients. Nutr Clin Pract 2008;23(4): Kondrup J, Allison SP, Elia M, Vellas B, Plauth M. ESPEN guidelines for nutrition screening Clin Nutr 2003;22(4): Kondrup J, Rasmussen HH, Hamberg O, Stanga Z. Nutritional risk screening (NRS 2002): a new method based on an analysis of controlled clinical trials. Clin Nutr 2003;22(3): Rahman A, Hasan RM, Agarwala R, Martin C, Day AG, Heyland DK. Identifying critically-ill patients who will benefit most from nutritional therapy: further validation of the "modified NUTRIC" nutritional risk assessment tool. Clin Nutr 2016; 35(1): Heyland DK, Dhaliwal R, Jiang X, Day AG. Identifying critically ill patients who benefit the most from nutrition therapy: the development and initial validation of a novel risk assessment tool. Crit Care 2011;15(6):R Schlein KM, Coulter SP. Best practices for determining resting energy expenditure in critically ill adults. Nutr Clin Pract 2014;29(1): Hoffer LJ. Protein requirement in critical illness. Appl Physiol Nutr Metab 2016;41(5): Weijs PJ, Looijaard WG, Beishuizen A, Girbes AR, Oudemansvan Straaten HM. Early high protein intake is associated with low mortality and energy overfeeding with high mortality in non-septic mechanically ventilated critically ill patients. Crit Care 2014;18(6): Nicolo M, Heyland DK, Chittams J, Sammarco T, Compher C. Clinical outcomes related to protein delivery in a critically ill population: a multicenter, multinational observation study. JPEN J Parenter Enteral Nutr 2016;40(1): Arabi YM, Aldawood AS, Haddad SH, Al-Dorzi HM, Tamim HM, Jones G, et al. Permissive underfeeding or standard enteral feeding in critically ill adults. N Engl J Med 2015;372(25): Arabi YM, Tamim HM, Dhar GS, Al-Dawood A, Al-Sultan M, Sakkijha MH, et al. Permissive underfeeding and intensive insulin therapy in critically ill patients: a randomized controlled trial. Am J Clin Nutr 2011;93(3): Rice TW, Mogan S, Hays MA, Bernard GR, Jensen GL, Wheeler AP. Randomized trial of initial trophic versus full-energy enteral nutrition in mechanically ventilated patients with acute respiratory failure. Crit Care Med 2011;39(5): National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network, Rice TW, Wheeler AP, Thompson BT, Steingrub J, Hite RD, et al. Initial trophic vs full enteral feeding in patients with acute lung injury: the EDEN randomized trial. JAMA 2012;307(8): Mulherin DW, Cogle SV. Updates in nutrition support for critically ill adult patients. Hosp Pharm 2017;52(1): Braunschweig CA, Sheean PM, Peterson SJ, Gomez Perez S, Freels S, Lateef O, et al. Intensive nutrition in acute lung injury: a clinical trial (INTACT). JPEN J Parenter Enteral Nutr 2015; 39(1): Casaer MP, Mesotten D, Hermans G, Wouters PJ, Schetz M, Meyfroidt G, et al. Early versus late parenteral nutrition in critically ill adults. N Engl J Med 2011;365(6): Elke G, Kuhnt E, Ragaller M, Schädler D, Frerichs I, Brunkhorst FM, et al. Enteral nutrition is associated with improved outcome in patients with severe sepsis. A secondary analysis of the VISEP trial. Med Klin Intensivmed Notfmed 2013;108(3): Bo L, Li J, Tao T, Bai Y, Ye X, Hotchkiss RS, et al. Probiotics for preventing ventilator-associated pneumonia. Cochrane Database Syst Rev 2014;(10):CD Rayes N, Seehofer D, Müller AR, Hansen S, Bengmark S, Neuhaus P. 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Am J Clin Nutr 1998;68(2): Nathens AB, Neff MJ, Jurkovich GJ, Klotz P, Farver K, Ruzinski JT, et al. Randomized, prospective trial of antioxidant supplementation in critically ill surgical patients. Ann Surg 2002; 236(6): Manzanares W, Dhaliwal R, Jurewitsch B, Stapleton RD, Jeejeebhoy KN, Heyland DK. Alternative lipid emulsions in the critically ill: a systematic review of the evidence. Intensive Care Med 2013;39(10): Palmer AJ, Ho CK, Ajibola O, Avenell A. The role of -3 fatty acid supplemented parenteral nutrition in critical illness in adults: a systematic review and meta-analysis. Crit Care Med 2013;41(1): Journal of Clinical Nutrition

8 35. Lee JM. The importance of glycemic control in critically ill surgical patients. Surg Metab Nutr 2013;4(1): NICE-SUGAR Study Investigators, Finfer S, Chittock DR, Su SY, Blair D, Foster D, et al. Intensive versus conventional glucose control in critically ill patients. N Engl J Med 2009;360(13): Shetty S, Inzucchi SE, Goldberg PA, Cooper D, Siegel MD, Honiden S. Adapting to the new consensus guidelines for managing hyperglycemia during critical illness: the updated Yale insulin infusion protocol. Endocr Pract 2012;18(3): Whitcomb BW, Pradhan EK, Pittas AG, Roghmann MC, Perencevich EN. Impact of admission hyperglycemia on hospital mortality in various intensive care unit populations. Crit Care Med 2005;33(12): al-saady NM, Blackmore CM, Bennett ED. High fat, low carbohydrate, enteral feeding lowers PaCO2 and reduces the period of ventilation in artificially ventilated patients. Intensive Care Med 1989;15(5): Mesejo A, Acosta JA, Ortega C, Vila J, Fernández M, Ferreres J, et al. Comparison of a high-protein disease-specific enteral formula with a high-protein enteral formula in hyperglycemic critically ill patients. Clin Nutr 2003;22(3): Radrizzani D, Iapichino G. Nutrition and lung function in the critically ill patient. Clin Nutr 1998;17(1): Barale F, Verdy S, Boillot A, Balvay P, Cordier A, Taberlet C, et al. Calorimetric study of enteral low-carbohydrate diet in patients with respiratory insufficiency and decompensation. Agressologie 1990;31(1): Aubier M, Murciano D, Lecocguic Y, Viires N, Jacquens Y, Squara P, et al. Effect of hypophosphatemia on diaphragmatic contractility in patients with acute respiratory failure. N Engl J Med 1985;313(7): Alsumrain MH, Jawad SA, Imran NB, Riar S, DeBari VA, Adelman M. Association of hypophosphatemia with failure-towean from mechanical ventilation. Ann Clin Lab Sci 2010; 40(2): Fiaccadori E, Regolisti G, Maggiore U. Specialized nutritional support interventions in critically ill patients on renal replacement therapy. Curr Opin Clin Nutr Metab Care 2013;16(2): Wooley JA, Btaiche IF, Good KL. Metabolic and nutritional aspects of acute renal failure in critically ill patients requiring continuous renal replacement therapy. Nutr Clin Pract 2005; 20(2): Bellomo R, Tan HK, Bhonagiri S, Gopal I, Seacombe J, Daskalakis M, et al. High protein intake during continuous hemodiafiltration: impact on amino acids and nitrogen balance. Int J Artif Organs 2002;25(4): Xu ZW, Li YS. Pathogenesis and treatment of parenteral nutrition-associated liver disease. Hepatobiliary Pancreat Dis Int 2012;11(6): Holecek M. Branched-chain amino acids and ammonia metabolism in liver disease: therapeutic implications. Nutrition 2013;29(10): Tenner S, Baillie J, DeWitt J, Vege SS. American college of gastroenterology guideline: management of acute pancreatitis. Am J Gastroenterol 2013;108(9): ; Rajkumar N, Karthikeyan VS, Ali SM, Sistla SC, Kate V. Clear liquid diet vs soft diet as the initial meal in patients with mild acute pancreatitis: a randomized interventional trial. Nutr Clin Pract 2013;28(3): Sathiaraj E, Murthy S, Mansard MJ, Rao GV, Mahukar S, Reddy DN. Clinical trial: oral feeding with a soft diet compared with clear liquid diet as initial meal in mild acute pancreatitis. Aliment Pharmacol Ther 2008;28(6): McClave SA, Chang WK, Dhaliwal R, Heyland DK. Nutrition support in acute pancreatitis: a systematic review of the literature. JPEN J Parenter Enteral Nutr 2006;30(2): Sun JK, Li WQ, Ke L, Tong ZH, Ni HB, Li G, et al. Early enteral nutrition prevents intra-abdominal hypertension and reduces the severity of severe acute pancreatitis compared with delayed enteral nutrition: a prospective pilot study. World J Surg 2013;37(9): Wereszczynska-Siemiatkowska U, Swidnicka-Siergiejko A, Siemiatkowski A, Dabrowski A. Early enteral nutrition is superior to delayed enteral nutrition for the prevention of infected necrosis and mortality in acute pancreatitis. Pancreas 2013;42(4): Zhang MM, Cheng JQ, Lu YR, Yi ZH, Yang P, Wu XT. Use of pre-, pro- and synbiotics in patients with acute pancreatitis: a meta-analysis. World J Gastroenterol 2010;16(31): Yang SQ, Xu JG. Effect of glutamine on serum interleukin-8 and tumor necrosis factor-alpha levels in patients with severe pancreatitis. Nan Fang Yi Ke Da Xue Xue Bao 2008;28(1): Doig GS, Heighes PT, Simpson F, Sweetman EA. Early enteral nutrition reduces mortality in trauma patients requiring intensive care: a meta-analysis of randomised controlled trials. Injury 2011;42(1): O'Keefe GE, Shelton M, Cuschieri J, Moore EE, Lowry SF, Harbrecht BG, et al. Inflammation and the host response to injury, a large-scale collaborative project: patient-oriented research core--standard operating procedures for clinical care VIII--Nutritional support of the trauma patient. J Trauma 2008;65(6): Marik PE, Zaloga GP. Immunonutrition in critically ill patients: a systematic review and analysis of the literature. Intensive Care Med 2008;34(11): Hasadsri L, Wang BH, Lee JV, Erdman JW, Llano DA, Barbey AK, et al. Omega-3 fatty acids as a putative treatment for traumatic brain injury. J Neurotrauma 2013;30(11): Perel P, Yanagawa T, Bunn F, Roberts I, Wentz R, Pierro A. Volume 9, Number 2, December

9 Yoo Jin Choi and Jae-Myeong Lee Nutritional support for head-injured patients. Cochrane Database Syst Rev 2006;(4):CD Dissanaike S, Pham T, Shalhub S, Warner K, Hennessy L, Moore EE, et al. Effect of immediate enteral feeding on trauma patients with an open abdomen: protection from nosocomial infections. J Am Coll Surg 2008;207(5): Diaz JJ Jr, Cullinane DC, Dutton WD, Jerome R, Bagdonas R, Bilaniuk JW, et al. The management of the open abdomen in trauma and emergency general surgery: part 1-damage control. J Trauma 2010;68(6): Hourigan LA, Linfoot JA, Chung KK, Dubick MA, Rivera RL, Jones JA, et al. Loss of protein, immunoglobulins, and electrolytes in exudates from negative pressure wound therapy. Nutr Clin Pract 2010;25(5): Rousseau AF, Losser MR, Ichai C, Berger MM. ESPEN endorsed recommendations: nutritional therapy in major burns. Clin Nutr 2013;32(4): Gibran NS. Practice Guidelines for burn care, J Burn Care Res 2006;27(4): Vicic VK, Radman M, Kovacic V. Early initiation of enteral nutrition improves outcomes in burn disease. Asia Pac J Clin Nutr 2013;22(4): Ortiz Leyba C, Montejo González JC, Vaquerizo Alonso C. Guidelines for specialized nutritional and metabolic support in the critically-ill patient. Update. Consensus of the Spanish Society of Intensive Care Medicine and Coronary Units-Spanish Society of Parenteral and Enteral Nutrition (SEMICYUC- SENPE): patient with sepsis. Med Intensiva 2011;35 Suppl 1: Simpson F, Doig GS. Parenteral vs. enteral nutrition in the critically ill patient: a meta-analysis of trials using the intention to treat principle. Intensive Care Med 2005;31(1): Gramlich L, Kichian K, Pinilla J, Rodych NJ, Dhaliwal R, Heyland DK. Does enteral nutrition compared to parenteral nutrition result in better outcomes in critically ill adult patients? A systematic review of the literature. Nutrition 2004;20(10): Peter JV, Moran JL, Phillips-Hughes J. A metaanalysis of treatment outcomes of early enteral versus early parenteral nutrition in hospitalized patients. Crit Care Med 2005;33(1): ; discussion Elke G, Schädler D, Engel C, Bogatsch H, Frerichs I, Ragaller M, et al. Current practice in nutritional support and its association with mortality in septic patients--results from a national, prospective, multicenter study. Crit Care Med 2008;36(6): Berger MM, Shenkin A. Trace element requirements in critically ill burned patients. J Trace Elem Med Biol 2007;21 Suppl 1: Berger MM, Shenkin A. Selenium in intensive care: probably not a magic bullet but an important adjuvant therapy. Crit Care Med 2007;35(1): Besecker BY, Exline MC, Hollyfield J, Phillips G, Disilvestro RA, Wewers MD, et al. A comparison of zinc metabolism, inflammation, and disease severity in critically ill infected and noninfected adults early after intensive care unit admission. Am J Clin Nutr 2011;93(6): Pontes-Arruda A, Martins LF, de Lima SM, Isola AM, Toledo D, Rezende E, et al. Enteral nutrition with eicosapentaenoic acid, -linolenic acid and antioxidants in the early treatment of sepsis: results from a multicenter, prospective, randomized, double-blinded, controlled study: the INTERSEPT study. Crit Care 2011;15(3):R Levy MM, Artigas A, Phillips GS, Rhodes A, Beale R, Osborn T, et al. Outcomes of the surviving sepsis campaign in intensive care units in the USA and Europe: a prospective cohort study. Lancet Infect Dis 2012;12(12): Davis CJ, Sowa D, Keim KS, Kinnare K, Peterson S. The use of prealbumin and C-reactive protein for monitoring nutrition support in adult patients receiving enteral nutrition in an urban medical center. JPEN J Parenter Enteral Nutr 2012;36(2): Raguso CA, Dupertuis YM, Pichard C. The role of visceral proteins in the nutritional assessment of intensive care unit patients. Curr Opin Clin Nutr Metab Care 2003;6(2): Osland E, Yunus RM, Khan S, Memon MA. Early versus traditional postoperative feeding in patients undergoing resectional gastrointestinal surgery: a meta-analysis. JPEN J Parenter Enteral Nutr 2011;35(4): Drover JW, Dhaliwal R, Weitzel L, Wischmeyer PE, Ochoa JB, Heyland DK. Perioperative use of arginine-supplemented diets: a systematic review of the evidence. J Am Coll Surg 2011; 212(3):385-99, 399.e 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): Pearl ML, Frandina M, Mahler L, Valea FA, DiSilvestro PA, Chalas E. A randomized controlled trial of a regular diet as the first meal in gynecologic oncology patients undergoing intraabdominal surgery. Obstet Gynecol 2002;100(2): Lassen K, Kjaeve J, Fetveit T, Tranø G, Sigurdsson HK, Horn A, et al. Allowing normal food at will after major upper gastrointestinal surgery does not increase morbidity: a randomized multicenter trial. Ann Surg 2008;247(5): MacIntyre NR, Epstein SK, Carson S, Scheinhorn D, Christopher K, Muldoon S. Management of patients requiring prolonged mechanical ventilation: report of a NAMDRC consensus conference. Chest 2005;128(6): Boonen E, Langouche L, Janssens T, Meersseman P, Vervenne H, De Samblanx E, et al. Impact of duration of critical illness on the adrenal glands of human intensive care patients. J Clin Endocrinol Metab 2014;99(11): Journal of Clinical Nutrition

10 88. McClave SA, Kushner R, Van Way CW 3rd, Cave M, DeLegge M, Dibaise J, et al. Nutrition therapy of the severely obese, critically ill patient: summation of conclusions and recommendations. JPEN J Parenter Enteral Nutr 2011;35(5 Suppl):88S-96S. 89. Robinson MK, Mogensen KM, Casey JD, McKane CK, Moromizato T, Rawn JD, et al. The relationship among obesity, nutritional status, and mortality in the critically ill. Crit Care Med 2015;43(1): Dickerson RN, Boschert KJ, Kudsk KA, Brown RO. Hypocaloric enteral tube feeding in critically ill obese patients. Nutrition 2002;18(3): Dickerson RN, Medling TL, Smith AC, Maish GO 3rd, Croce MA, Minard G, et al. Hypocaloric, high-protein nutrition therapy in older vs younger critically ill patients with obesity. JPEN J Parenter Enteral Nutr 2013;37(3): Dickerson RN, Drover JW. Monitoring nutrition therapy in the critically ill patient with obesity. JPEN J Parenter Enteral Nutr 2011;35(5 Suppl):44S-51S. Volume 9, Number 2, December