Original Article J Clin Nutr 2015;7(3):75-80 pissn 2289-0203 ㆍ eissn 2383-7101 http://dx.doi.org/10.15747/jcn.2015.7.3.75 외과계중환자에서의초기정맥영양공급의현황분석과열량대단백비의임상적의의 허은정 1, 박가영 1, 전수정 1, 남궁형욱 1, 이은숙 1, 송인애 2 분당서울대학교병원 1 약제부, 2 마취통증의학과 Analysis of Current Use of Early Parenteral Nutrition and Clinical Significance of Non-protein Calorie: Nitrogen in Surgical Critically Ill Patients Eunjeong Heo 1, Kayoung Park 1, Sujeong Jeon 1, Hyungwook Namgung 1, Eunsook Lee 1, Inae Song 2 1 Department of Pharmacy, 2 Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, Seongnam, Korea Purpose: Surgical critically ill patients require adequate nutrition support and the American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) guidelines recommend low non-protein calorie:nitrogen ratio (NPC:N ratio, 70 100) for critically ill pateints. In this study, we assess the current use of early parenteral nutrition of surgical critically ill patients and analyze the clinical significance of NPC:N. Methods: This is a retrospective study of critically ill adult patients who remained in the intensive care unit (ICU) for over 3 days and could not receive enteral nutrition for the first 7 days. Data on parenteral intake of patients were collected from electronic medical records. Association of NPC:N scores with clinical outcome (length of ICU stay, length; of hospital stay, duration of ventilation, and mortality) were analyzed using Pearson correlation and multiple regression. Results: The study included 72 cases, average parenteral calorie intake was 14.6 kcal/kg/day and protein intake was 0.5 g/kg/day. We assessed the NPC:N scores to determine the patients NPC:N for the first 7 days in ICU close to the A.S.P.E.N guidelines. NPC:N scores showed weak negative correlation with length of hospital stay and duration of mechanical ventilation (r= 0.259, P=0.028; r= 0.495, P=0.001). Multiple regression adjusted with APACHE (Acute Physiology and Chronic Health Evaluation) II score, age, and body mass index showed correlation of higher NPC:N score with decreased length of hospital stay and shorter duration of ventilation (P=0.0001, P=0.035, respectively). However, length of ICU stay and mortality within 60 days showed no significant correlation with NPC:N scores. Conclusion: Parenteral calories and protein intakes of critically ill patients in ICU were lower in comparison to A.S.P.E.N. recommendation in this study. Low NPC:N scores might be related to shorter length of hospital stay, duration of mechanical ventilation. Consultation of a nutritional support team could have a positive effect in providing appropriate nutrition support. Key Words: Enteral nutrition, Parenteral nutrition, Protein-calorie malnutrition Received Aug 11, 2015; Revised Sep 28, 2015; Accepted Nov 8, 2015 Correspondence to Inae Song Department of Anesthesiology and Pain Medicine, 82 Gumi-ro 173beon-gil, Bundang-gu, Seongnam 13620, Korea Tel: +82-31-787-7499, Fax: +82-31-787-4063, E-mail: nodame1@naver.com Conflict of interest: None. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 서론 중환자의경우, 급성중환기의이화상태로인해열량고갈이빠르게일어나며근육량감소및세포고갈에기여하여기계환기이탈을어렵게하고, 중환자실재원기간을늘린다고알려져있다. 1,2 특히외과계중환자의대부분에서는복강내수술, 장마비, 감염, 위장내출혈, 흡인성폐렴, 창상및술후통증에의한활동제한에의한장활동감소등으로금식유지사유가발 2015, The Korean Society for Parenteral and Enteral Nutrition. All Rights Reserved.
Eunjeong Heo, et al. 생하여금식기간이장기화되는한편, 주요수술이후의과대사 (hypermetabolism) 가예상되므로외과계중환자에서적절한정맥영양공급의필요성이높다. 3 중환자에서는빠른경장영양이선호되며 24 48시간내에시작하는것이권고된다. 4-6 The American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) 가이드라인에서는 7일간경장영양단독을추천하며, the European Society of Clinical Nutirtion and Metabolism (E.S.P.E.N.) 가이드라인에서는입실 72시간이내에경장영양이불가능할것으로생각되는환자에서 24 48시간내에정맥영양을실시할것을권장하고있다. 5,6 그러나앞에언급한이유로인해많은경우, 외과계중환자에서경장영양시도는금기인경우가많으며이를대체할만한영양공급수단으로조기정맥영양공급을고려할수있다. A.S.P.E.N. 가이드라인에서는대부분의중환자에서열량요구량에비해단백요구량이증가되어있으므로일반환자보다낮은 70:1 100:1의열량대단백비 (non-protein calorie:nitrogen, NPC:N) 를권장하고있으며, E.S.P.E.N. 가이드라인에서는일반환자보다높은 1.3 1.5 g/kg/day의단백질공급을권장하고있다. 5,6 상기와같은적극적인단백질공급이중환자에서의체내단백질고갈을방지하기위해중요하다고알려져있다. 그러나실제임상에서는장기부전, 흡인성폐렴의위험, 정맥영양공급시작시점결정의어려움등의이유로충분한열량과단백량을공급하지못하고있다. 7 이에본연구에서는분당서울대학교병원외과계중환자실입실환자의금식시작첫일주일동안의평균열량공급량, 단백공급량을조사하여초기정맥영양공급현황을파악하고자하였다. 또한조기정맥영양시열량대단백비와중환자실재원기간, 총재원기간, 기계환기적용기간, 60일내사망률과의관련성에대해알아보고자하였다. 또한영양협진에따른외과계중환자들의영양상태개선에대해서도알아보았다. 대상및방법 1. 연구대상 2013년 1월부터 2014년 7월까지외과계중환자실에 3일이상재원하였던외과계중환자중, 만 18세이상환자들중중환자실입실일부터금식기간이 7일이상인환자를대상으로하였으며재입실의경우는제외하였다. 그외중증간기능부전환자, 신대체요법을실시하지않는중증의신부전환자, 급성쇼크환자또는심정지환자는대상군에서제외하였다. 상기기간동안외과계중환자실에 3일이상재원하였던성인환자들중금식기간이 7일이상인사례는총 249건이었으며, 이중입원중재입 실 67건, 중증간기능부전환자 56건, 신대체요법을실시하지않는중증의신부전환자 12건, 급성쇼크환자또는심정지환자 49건등을제외한대상사례수는 72건이었다. 본연구는분당서울대학교병원임상시험윤리위원회의승인하에시행되었으며환자의개인신상정보를포함하지않았으며동의서가면제되었다 (IRB No.B-1508-310-108). 2. 자료수집전자의무기록을후향적으로검토하여대상환자의 7일동안의정맥영양공급현황, 중환자실재원기간, 총재원기간, 기계환기적용기간, 사망여부를조사하였다. 7일동안의정맥영양공급량은의사처방과간호기록을기준으로일주일간정맥으로투여된영양수액, 약물희석수액등을모두포함하였으며, 투여된열량, 포도당, 단백질, 지질량을파악하여 g/kg/day ( 포도당, 단백질, 지질량 ), kcal/kg/day ( 열량 ) 를단위로평가하였다. 체중은대상환자의실제체중이이상체중보다적으면실제체중을사용하였으며, 이상체중보다초과되면조정체중을이용하였다. 조정체중계산법은다음과같다. 조정체중 ={( 실제체중 이상체중 ) 0.25}+ 이상체중 8 3. 열량대단백비의임상적의의분석열량대단백비는다음과같이계산되었다. 열량대단백비 (NPC:N)=( 포도당열량 [kcal]+지질열량 [kcal]):( 단백량 [g]/6.25) 열량대단백비율 (NPC/N)=( 포도당열량 [kcal]+지질열량 [kcal])/( 단백량 [g]/6.25) 열량대단백비율값을이용하여중환자실재원첫일주일간정맥으로공급된열량과단백질의비율이임상적으로갖는의미를분석하려하였으나, 단백질공급량이 0인경우, 무한대값으로책정되어통계적인분석이용이하지않았다. 이를보완하기위해본저자는열량대단백비점수 (NPC:N score) 를고안하였다. A.S.P.E.N. 가이드라인의 NPC:N 값의상한값인 100을기준으로이에가까울수록높은점수를매기고멀어질수록낮은점수를매겨, 중환자실입실첫 1주일간의점수의합을내어이값을 NPC:N score로명명하였다. NPC:N score는일별정맥영양공급의 NPC/N 100일때 4 점, 100<NPC/N 120일때 3점, 120<NPC/N 140일때 2 점, 140<NPC/N 160일때 1점, NPC/N>160일때 0점을부여한후, 7일간의점수를합계하여산출하였다. 예를들어환자의일주일간정맥영양공급이 Table 1과같았다고가정하면, 이와같은사례에서 NPC:N score는 day 1 7까지합산하여 19 로산출할수있다. 여기서입실일첫째날과둘째날의 NPC:N 76 Journal of Clinical Nutrition
Correlation NPC:N Score of PN with Clinical Outcome Table 1. Example of NPC:N scores calculation Parenteral intake Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7 Glucose(g) 96 96 80 175 100 121.5 105 Protein(g) 0 0 53 80 52 86 25 Lipid(g) 0 0 21 50 21.8 31.2 0 Calorie (kcal) 369.6 369.6 730.0 1,493.8 811.0 1,123.8 504.3 NPC/N a - - 61.1 91.7 72.5 56.7 101.1 NPC:N score b 0 0 4 4 4 4 3 NPC = non-protein calorie; N = nitrogen. a NPC/N=(glucose calorie[kcal]+lipid calorie[kcal])/(protein[g]/6.25). b A total sum of daily scores for first 7 days of admission to the intensive care unit according to a special scoring system. Daily NPC:N deserved score 4, when it was NPC:N 100; score 3, when it was 100<NPC/N 120; score 2, when it was 120<NPC/N 140; score 1, when it was 140<NPC/N 160; and score 0, when it was NPC/N>160. Table 2. Patient characteristics Baseline characteristic Case (n=72) Age (y) 68.0±14.8 Sex (male) 49 (68.0) BMI (kg/m 2 ) 21.7±3.7 APACHE II score 21.3±7.4 Diagnosis at admission to the ICU Gastrointestinal diseases 38 (53.8) Cardiovascular diseases 18 (25.0) Respiratory diseases 12 (16.7) Trauma 1 (1.4) Other 3 (4.2) Values are presented as mean±standard deviation or number (%). BMI = body mass index; APACHE = Acute Physiology and Chronic Health Evaluation; ICU = intensive care unit. Fig. 1. Parenteral total calorie, protein intake for first 7 days in intensive care unit. 값은무한대이므로 NPC:N score는 0점으로계산된다. NPC:N score가높을수록공급된열량중단백비율이 A.S.P.E.N. 가이드라인에가깝다고생각할수있다. 4. 통계분석 NPC:N score와재원기간, 중환자실재원기간, 기계환기적용기간, 사망률의비교시에는 Pearson correlation을사용하였다. 환자나이, body mass index (BMI), APACHE (Acute Physiology and Chronic Health Evaluation) II score와 NPC:N score가각각재원기간, 중환자실재원기간및기계환기적용기간에미치는영향을다중회귀분석을이용하여평가하였다. 영양집중지원팀의뢰유무로나누어 7일간의정맥영양공급현황을비교하면영양집중지원팀에의뢰가된군의공급열량과단백량을비교할때는 t-test로유의성검정을하였다. P-value 가 0.05 미만일때통계적으로유의한것으로판단하였다. 분석도구로는 IBM SPSS Statistics ver. 21.0 (IBM Co., Armonk, NY, USA) 을사용하였다. 결과 1. 환자특성총 72건의대상사례중남성 49건 (68%) 이었으며, 평균나이는 68.0±14.8세였다. 평균 BMI는 21.7±3.7 kg/m 2 였으며, 평균 APACHE II score는 21.3±7.4였다. 입원시진단명으로보면위장관계질환이 38건으로가장많았고, 심혈관계질환이 18 건, 호흡기계질환이 12건이었다 (Table 2). 2. 금식시작첫일주일동안의정맥영양공급현황전체대상사례의중환자실입실이후금식첫일주일동안의정맥영양공급을조사하였을때일평균열량공급량 14.6±5.7 g/kg/day, 일평균단백질공급량 0.5±0.3 g/kg/day 였다. A.S.P.E.N. 가이드라인의권장량과비교하였을때 7일간평균열량및단백공급량이권장량보다낮게나타났다. 또한무한대값을제외한일주일간의평균 NPC:N 값은 203.2±317.1:1과같아 A.S.P.E.N. 가이드라인의권장값인 70:1 100:1에비해높은것을알수있 Volume 7, Number 3, December 2015 77
Eunjeong Heo, et al. Table 3. Comparison of parenteral intake of two groups classified by NST consults Parenteral intake Consultation to NST (n=45) No consultation (n=27) P-value Calorie (kcal/kg/day) 14.5±4.8 11.5±5.6 0.001 Protein (g/kg/day) 0.6±0.3 0.36±0.3 0.001 NPC:N score a 10.8±4.6 7.3±6.1 0.013 Values are presented as mean±standard deviation. NST = nutrition support team; NPC:N = non-protein calorie: nitrogen. a A total sum of daily scores for first 7 days of admission to the intensive care unit according to a special scoring system. Daily NPC:N deserved score 4, when it was NPC:N 100; score 3, when it was 100<NPC/N 120; score 2, when it was 120<NPC/N 140; score 1, when it was 140<NPC/N 160; and score 0, when it was NPC/N>160. Table 4. Correlation of NPC:N score a with clinical outcome Clinical outcome Pearson correlation P-value Length of hospital stay 0.259 0.028 Length of ICU stay 0.053 0.661 Duration of MV 0.495 0.001 NPC:N = non-protein calorie:nitrogen; ICU = intensive care unit; MV = mechanical ventilation. a A total sum of daily scores for first 7 days of admission to the intensive care unit according to a special scoring system. Daily NPC:N deserved score 4, when it was NPC:N 100; score 3, when it was 100<NPC/N 120; score 2, when it was 120<NPC/N 140; score 1, when it was 140<NPC/N 160; and score 0, when it was NPC/N>160. 고 찰 다. 금식시작후 7일동안의일평균열량과일평균단백공급량을살펴보면입원일이경과할수록모두증가하는양상을보였다 (Fig. 1). 영양집중지원팀의뢰유무로나누어 7일간의정맥영양공급현황을비교하면영양집중지원팀에의뢰가된군의공급열량과단백량이 A.S.P.E.N. 가이드라인권장량을기준으로더적절한정맥영양공급이된것을볼수있으며공급열량, 단백량및 NPC:N score는두군간통계적으로유의하게차이가존재하였다 (Table 3). 3. NPC:N score와열량대단백비의임상적의의분석정맥으로공급된열량과단백질의비율이임상적결과와어떤관련이있는지분석하기위해고안한 NPC:N score와재원기간, 중환자실재원기간, 기계환기적용기간의상관관계를분석하였을때, 재원기간및기계환기적용기간과 NPC:N score는약한음의상관관계를보였다. 즉, 공급된단백비가증가할수록재원기간및기계환기적용기간은감소하는경향을보였다 (Table 4). 환자나이, BMI, APACHE II score와 NPC:N score를독립변수로각각재원기간, 중환자실재원기간, 기계환기적용기간에미치는영향을알아보기위한다중회귀분석결과, NPC:N score가재원기간 (P=0.035) 과기계환기적용기간 (P=0.0001) 과관련성을보였다. 반면 APACHE II score는중환자실재원기간과관련성을보였다 (P=0.002). 또한, 60일사망군 (n=7) 과비사망군 (n=65) 을나누어 NPC:N score를비교하였을때는통계적으로유의미한차이가없었다 (P>0.05). 본연구에서는외과계중환자들의금식시작첫일주일동안의평균열량공급량, 단백공급량을조사하여초기정맥영양공급현황을파악하고자하였으며, 열량대단백비를기준으로사례군을나누어임상적의의를평가해보고자하였다. 외과계중환자에서일주일간투여된정맥영양공급을분석하였을때일주일평균의공급량은물론이고, 6일동안의금식기간후인 7일째의정맥영양공급또한권장량보다적은부적절한영양공급이이루어지고있는것으로나타났다. 이와같은현황의이유로는금식초기정맥영양공급의이점에대해서아직논쟁이있는상황이기때문으로생각된다. 2011년발표된 EPaNIC trial 9 에서 early-initiation군에서는 20% 포도당용액을이용하여첫째날에포도당 100 g, 둘째날에포도당 180 g을공급하였으며, 셋째날부터 total nutrient admixtures (TNA) 제제를공급하였다. Late-initiation군에서는 5% 포도당용액을이용하여동일한용량의수액을공급하였으며 7일후에도요구량에도달하지못한사람들에게정맥영양을시작하였다. 그결과두군간의사망률에는차이가없었으나입실초기에정맥영양공급을시작했던군에서감염률및재원기간증가를보여경장식이가가능한환자에서는정맥영양이이점을보이지못했다고발표하였다. 반면, 2013년에발표된 Early PN Study 10 에서는식이가어려울것으로예상되는중환자군을대상으로연구하였으며, early PN군은입실 24시간이내에 TNA 제형으로정맥영양공급을시행하였고, standard care군에서는 protocol을따르지않고의사재량으로영양공급을하였다. 그결과 early PN군에서기계환기적용기간감소를보였으며, 통계적으로유의미하지않지만중환자실재원기간및병원재원기간감소를보여입실초기정맥영양공급의이점가능성에대해발표하였다. 2014년에발표된한연구 11 에서는 78 Journal of Clinical Nutrition
Correlation NPC:N Score of PN with Clinical Outcome 패혈성의중환자를대상으로입실초기의권장된열량과단백량에가까운경장영양의효과에대해발표하였는데, 입실초기일주일동안권장열량과단백량에가깝게경장영양을할수록환자의 60일사망률, 기계환기이탈기간이감소되는것으로나타났다. 그러나초기경장영양이아닌정맥영양에대한권장공급열량, 단백량에대한연구는아직없는실정이고, 위와같이금식초기의정맥영양공급시작시점, 어떻게시작해야하는지에대한연구가부족하며합의가이루어지지않은상황이기때문에금식이예상되는외과계중환자들의일주일간평균공급량은권장량보다적었을가능성이있다. 분당서울대학교병원에서는의사, 간호사, 약사, 영양사로이루어진영양집중지원팀활동이이루어지고있다. 담당주치의가영양집중지원팀에의뢰하면각분야에서환자의영양상태를파악하고회신을하며회신이후에도사후관리를통하여환자의영양상태를관리하고있다. 금식초기일주일간영양공급이영양집중지원팀회신유무에따라회신이있는군에서단백량, 열량이더적극적으로, 열량대단백비가더적절하게정맥영양공급이된것으로보이므로팀활동의영향을적절히평가하여활발한팀활동이필요할것으로생각된다. 12 정맥영양공급량의열량대단백비 (NPC:N) 는이론적으로정맥공급량의 protein-sparing capacity 를평가할수있다. 13 Protein-sparing capacity는열량및단백을공급하여체내단백이소실되는것을막는것을의미한다. 열량을공급하면열량고갈상태에서체내단백질이열량으로소모되는것을막을수있다고알려져있다. 또한, 제한된열량이외에아미노산을공급하여필수아미노산을공급하고고갈된단백을재충전할수있다. 본연구에서외과계중환자에서일주일간투여된정맥영양공급을분석하였을때 NPC:N score가증가할수록재원기간및기계환기적용기간이감소하는경향을보였다. 즉, 투여된단백의비율이증가할수록재원기간및기계환기적용기간이감소하는것으로볼수있다. 과거아미노산을충분히공급하여임상적효과를평가했던연구들을보면, 1995년연구에서수술후환자에서아미노산을중점적으로공급하는저칼로리정맥영양공급을시행하였을때환자의 nitrogen balance의개선을보였다. 14 또한 2013년의리뷰논문에서는환자에게정맥단백공급을충분히한연구들에서좋은임상적결과를얻었다고분석하고있으며, BMI 25 35 kg/m 2 의영양상태가좋은환자에서비단백열량공급감소와적절한단백공급 (1.2 2.0 g/kg/day) 이최적일수있다고제안하고있다. 15 본연구에서의 7일간의 NPC:N이 A.S.P.E.N. 가이드라인보 다높게분석되었고, 즉, 공급열량중단백량이적게공급되었다는것을의미한다. 서론에기술하였듯이중환자에서는단백요구량이증가되어있으나환자의임상상태악화 ( 예 : blood urea nitrogen [BUN] 상승, 중증의부종등 ), 치료과정중영양공급에대한우선순위제외등의이유로이상적인단백공급량이공급되지는못한것으로보인다. 본연구의한계점으로는첫째로임상상황에따라단백요구량및공급가능량이달라질수있다는점이다. Continuous renal replacement therapy (CRRT) 및 conventional hemodialysis (HD) 시행시단백의소실로단백요구량이증가하며, 신부전으로 BUN 수치가증가하게되면공급가능량이감소한다. 연구대상중 7개의사례에서정맥영양공급을하는기간에 CRRT를시행하였고, 2개의사례에서 HD를시행하였다. 환자의임상상황에따른단백요구량및공급가능량이달라짐에따라공급량이변동됨을고려하기어려웠으나이군의환자들을제외하여다시통계를처리해도전체적인결과는변하지않았다. 두번째로 NPC:N score는 NPC/N을구간별로나누어점수화한것으로, NPC/N이무한대가나와도통계처리가가능하도록하여중환자실체류첫일주일의공급정맥열량중단백질의비율이임상적지표에미치는영향의분석에도움이되고실제로도중환자실체류기간과기계환기적용기간에영향을주었지만후속연구에의한검증과보완이필요하겠다. 결론 결론적으로금식초기일주일간정맥영양공급량은권장량보다낮은것으로보이며, 영양집중지원팀에의뢰를하였을때좀더가이드라인에맞는정맥영양공급이되는것으로보이므로중환자에서적절한정맥영양공급을위해적극적인영양집중지원팀활동권장이필요하겠다. 또한금식을유지한중환자에서초기정맥영양공급의단백비가높을수록재원기간및기계환기적용기간이감소하는것으로보이므로중환자의초기정맥단백공급이중요한의미를가질수있음을추정할수있다. REFERENCES 1. Casaer MP, Van den Berghe G. Nutrition in the acute phase of critical illness. N Engl J Med 2014;370(13):1227-36. 2. Dempsey DT, Mullen JL, Buzby GP. The link between nutritional status and clinical outcome: can nutritional intervention modify it? Am J Clin Nutr 1988;47(2 Suppl):352-6. 3. Heyland DK, Montalvo M, MacDonald S, Keefe L, Su XY, Drover JW. Total parenteral nutrition in the surgical patient: a meta- Volume 7, Number 3, December 2015 79
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