1187CHAPTER 99 Nutrition of the Critically Ill Child Central venous access is required for delivery of hyperosmo lar PN solutions into a large bore vein with high volume blood flow to prevent thrombos[.]
CHAPTER 99 Nutrition of the Critically Ill Child Central venous access is required for delivery of hyperosmolar PN solutions into a large-bore vein with high-volume blood flow to prevent thrombosis and phlebitis The incidences of infective and life-threatening complications related to indwelling central lines have necessitated extreme caution with central PN use.114,115 A central line for PN use should be placed by experienced operators The optimal line tip position should be discussed with the nutrition team and confirmed by radiography before the line is used for PN delivery It is recommended that central line tips be positioned in large vessels but outside the cardiac chambers at all times Central lines are recommended for delivery of infusions with osmolarity greater than 900 mOsm/L (10% dextrose, 2% amino acids with standard additives) Obese Critically Ill Children Overweight/obesity continues to increase in children and adolescents Annual obesity-related hospital costs in 6- to 17-year-olds have reached $127 million per year Obesity may be a risk factor for higher mortality in children with critical illness, particularly those with oncologic diseases or undergoing organ transplantation.116 The severity of obesity is classified based on BMI into the following three categories: (1) overweight BMI 25 to 30 kg/ m2, (2) obesity BMI 30 to 40 kg/m2, and (3) morbid obesity BMI more than 40 kg/m2 Overweight children and adolescents are increasingly being diagnosed with impaired glucose tolerance and type diabetes, and they show early signs of insulin resistance syndrome and cardiovascular risk Centralized distribution of body fat is associated with the risk of metabolic syndrome Metabolic syndrome is observed in obese children and is characterized by visceral obesity, insulin resistance, and dyslipidemia There is a high risk for type diabetes and cardiovascular complications in patients with metabolic syndrome Grossly overweight patients are prone to sleep apnea syndrome, restrictive lung disease, venous thrombosis, musculoskeletal degenerative disorders, hepatic steatosis, and metabolic disorders associated with bariatric surgery The metabolic response to stress in obese critically ill patients is complex, given that it occurs in a population with preexisting major metabolic and endocrine alterations In critically ill obese patients, the pattern of substrate oxidation is mainly protein and glucose, with decreased fat oxidation.117 The extent of protein breakdown is greater than in nonobese critically ill adults No data on metabolic abnormalities of obese children are available In the adult critically ill population, hypocaloric nutrition estimated for ideal weight has been recommended.118 The limited adult literature suggests that protein requirements are higher in critically ill adult obese patients It is recommended that fat be administrated sparingly, mainly to prevent essential fatty acid deficiency.119 Evidence for the best nutritional support strategy for critically ill obese children is not currently available Routine equations tend to overestimate energy expenditure in obese patients.120 Energy requirements in this group should be guided by IC measurement of REE, where available When REE is estimated, there is no consensus on the use of ideal body weight versus adjusted body weight As the incidence of obesity in children admitted to the PICU is rising, future research aimed at addressing some of these knowledge gaps is desirable 1187 Revised Guidelines for Pediatric Critical Care Nutrition Published in 2017, the Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Pediatric Critically Ill Child replaced the former 2009 guidelines.54 This statement was developed as a collaboration between ASPEN and SCCM Given the advances in published nutrition research, the current document triaged over 2000 citations from 1995 to 2016 The guideline provided quality of evidence and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) recommendations for eight clinical questions, shown in eTable 99.5.54 Providing early EN (within 24–48 hours) with minimal interruptions in delivery remains the preferred route of nutrition in appropriate patients Patients are recommended to have a detailed nutritional assessment on admission, including weight, height/length, and BMI IC remains the gold standard to energy expenditure measurement, but Schofield or Food Agriculture Organization/World Health Organization/United Nations University equations may be used (without addition of stress factors) to estimate energy expenditure A goal of achieving, in a stepwise algorithmic approach, at least two-thirds of the prescribed daily energy requirement is recommended With regard to PN, no expert consensus has been achieved on the exact timing of initiating PN In general, for children who are not at risk of severe malnutrition and are slowly advancing on EN, it is likely safe to delay PN initiation in the first week of critical illness Conclusions Accurate assessment of nutritional needs and the provision of individually tailored optimal nutrition support to the critically ill child are important goals of pediatric critical care Malnutrition and obesity are prevalent in the PICU and have significant influence on the outcome of critical illness Furthermore, the hypermetabolic stress response places demand on the critically ill child that must be met with evidence-based nutrient supplementation Intensivists must remain alert to the possibility of both underfeeding and overfeeding in order to prevent unintended cumulative energy imbalances in critically ill children The significant relationship between inadequate protein intake and poor outcomes from critical illness has spurred studies exploring the optimal protein dosage and route A multidisciplinary effort to overcome common barriers to enteral nutrient delivery with the help of stepwise algorithms will help achieve nutrition goals in the PICU The timing and threshold for PN as a supplement to insufficient EN may need to be individualized and a universal aggressive approach with early PN should be discouraged Patients will benefit from individually tailored nutritional regimens suited to the type and stage of their illness, comorbidities, and nutritional history and status There are a number of knowledge gaps in the field of critical care nutrition that need to be addressed by collaborative research Until then, increased awareness of nutritional issues, effort to prioritize nutritional assessment support, and collaborative research to describe the nutrition-outcome relationship will help guide bedside nutrition therapies in the PICU 1187.e1 eTABLE Nutritional Support Clinical Guideline Recommendations for the Critically Ill Child54 99.5 Questions and Recommendations Evidence/GRADE Q1A: What is the impact of nutrition status on outcomes in critically ill children? R1A: Based on observational studies, malnutrition, including obesity, is associated with adverse clinical outcomes, including longer periods of mechanical ventilation, higher risk of hospital-acquired infection, longer PICU and hospital stay, and increased mortality We recommend that patients in the PICU undergo detailed nutrition assessment within 48 hours of admission Furthermore, as patients are at risk of nutrition deterioration during hospitalization, which can adversely affect clinical outcomes, we suggest that the nutrition status of patients be reevaluated at least weekly throughout hospitalization Quality of evidence: very low GRADE recommendation: strong Q1B: What are the best practices to screen and identify patients with malnutrition or those at risk of nutrition deterioration in the PICU? R1B: On the basis of observational studies and expert consensus, we recommend that weight and height/length be measured on admission to the PICU and that z-scores for body mass index for age (weight for length ,2 years) or weight for age (if accurate height is not available) be used to screen for patients at extremes of these values In children ,36 months, head circumference must be documented Validated screening methods for the PICU population to identify patients at risk of malnutrition must be developed Screening methods might allow limited resources to be directed to high-risk patients who are most likely to benefit from early nutrition assessment and interventions Quality of evidence: very low GRADE recommendation: strong Q2A: What is the recommended energy requirement for critically ill children? R2A: On the basis of observational cohort studies, we suggest that measured energy expenditure by IC be used to determine energy requirements and guide prescription of the daily energy goal Quality of evidence: low GRADE recommendation: weak Q2B: How should energy requirement be determined in the absence of IC? R2B: If IC measurement of resting energy expenditure is not feasible, we suggest that the Schofield or Food Agriculture Organization/World Health Organization/United Nations University equations be used without the addition of stress factors to estimate energy expenditure Multiple cohort studies have demonstrated that most published predictive equations are inaccurate and lead to unintended overfeeding or underfeeding The Harris-Benedict equations and the RDAs, which are suggested by the dietary reference intakes, should not be used to determine energy requirements in critically ill children Quality of evidence: very low GRADE recommendation: weak Q2C: What is the target energy intake in critically ill children? R2C: On the basis of observational cohort studies, we suggest achieving delivery of at least two-thirds of the prescribed daily energy requirement by the end of the first week in the PICU Cumulative energy deficits during the first week of critical illness may be associated with poor clinical and nutrition outcomes On the basis of expert consensus, we suggest attentiveness to individualized energy requirements, timeline initiation and attainment of energy targets, and energy balance to prevent unintended cumulative caloric deficit or excesses Quality of evidence: low GRADE recommendation: weak Q3A: What is the minimum recommended protein requirement for critically ill children? R3A: On the basis of evidence from RCTs and as supported by observational cohort studies, we recommend a minimum protein intake of 1.5 g/kg/d Protein intake higher than this threshold has been shown to prevent cumulative negative protein balance in RCTs In critically ill infants and young children, the optimal protein intake required to attain a positive protein balance may be much higher than this minimum threshold Negative protein balance may result in loss of lean muscle mass, which has been associated with poor outcomes in critically ill patients Based on a large observational study, higher protein intake may be associated with lower 60-day mortality in mechanically ventilated children Quality of evidence: moderate GRADE recommendation: strong Q3B: What is the optimal protein delivery strategy in the PICU? R3B: On the basis of results of randomized trials, we suggest the provision of protein early in the course of critical illness to attain protein delivery goals and promote positive nitrogen balance Delivery of a higher proportion of the protein goal has been associated with positive clinical outcomes in observational studies Quality of evidence: moderate GRADE recommendation: weak Q3C: How should protein delivery goals be determined in critically ill children? R3C: The optimal protein dose associated with improved outcomes is not known We not recommend the use of RDA values to guide protein prescription in critically ill children These values were developed for healthy children and often underestimate the protein needs during critical illness Quality of evidence: moderate GRADE recommendation: strong Q4A: Is EN feasible in critically ill children? R4A: On the basis of observational studies, we recommend EN as the preferred mode of nutrient delivery to the critically ill child Observational studies support the feasibility of EN, which can be safely delivered to critically ill children with medical and surgical diagnoses and to those receiving vasoactive medications Common barriers to EN in the PICU include delayed initiation, interruptions due to perceived intolerance, and prolonged fasting around procedures On the basis of observational studies, we suggest that interruptions to EN be minimized in an effort to achieve nutrient delivery goals by the enteral route Quality of evidence: low GRADE recommendation: strong Continued 1187.e2 eTABLE Nutritional Support Clinical Guideline Recommendations for the Critically Ill Child—cont'd 99.5 Questions and Recommendations Evidence/GRADE Q4B: What is the benefit of EN in this group? R4B: Although the optimal dose of macronutrients is unclear, some amount of nutrient delivered as EN has been beneficial for gastrointestinal mucosal integrity and motility Based on large cohort studies, early initiation of EN (within 24–48 hours of PICU admission) and achievement of up to two-thirds of the nutrient goal in the first week of critical illness have been associated with improved clinical outcomes Quality of evidence: low GRADE recommendation: weak Q5A: What is the optimum method of advancing EN in the PICU population? R5A: On the basis of observational studies, we suggest the use of a stepwise algorithmic approach to advance EN in children admitted to the PICU The stepwise algorithm must include bedside support to guide the detection and management of EN intolerance and optimal rate of increase in EN delivery Quality of evidence: low GRADE recommendation: weak Q5B: What is the role of a nutrition support team or dedicated dietitian in optimizing nutrition therapy? R5B: On the basis of observational studies, we suggest a nutrition support team, including a dedicated dietitian, be available on the PICU team to facilitate timely nutrition assessment, and optimal nutrient delivery and adjustment to other patients Quality of evidence: low GRADE recommendation: weak Q6A: What is the best site for EN delivery: gastric or small bowel? R6A: Existing data are insufficient to make universal recommendations regarding the optimal site to deliver EN in critically ill children On the basis of observational studies, we suggest the gastric route be the preferred site for EN in patients in the PICU The postpyloric or small intestinal site for EN may be used in patients unable to tolerate gastric feeding or those at high risk for aspiration Existing data are insufficient to make recommendations regarding the use of continuous vs intermittent gastric feeding Quality of evidence: low GRADE recommendation: weak Q6B: When should EN be initiated? R6B: On the basis of expert opinion, we suggest the EN be initiated in all critically ill children, unless it is contraindicated Given observational studies, we suggest early initiation of EN, within the first 24–48 hours of admission to the PICU, in eligible patients We suggest the use of institutional EN guidelines and stepwise algorithms that include criteria for eligibility of EN, timing of initiation, and rate of increase, as well as a guide to detecting and managing EN intolerance Quality of evidence: low GRADE recommendation: weak Q7A: What is the indication for and optimal timing of PN in critically ill children? R7A: On the basis of a single RCT, we not recommend the initiation of PN within 24 hours of PICU admission Quality of evidence: moderate GRADE recommendation: strong Q7B: What is the role of PN as a supplement to inadequate EN? R7B: For children tolerating EN, we suggest stepwise advancement of nutrient delivery via the enteral route and delaying commencement of PN Based on current evidence, the role of supplemental PN to reach a specific goal for energy delivery is not known The time when PN should be initiated to supplement insufficient EN is also unknown The threshold for and timing of PN initiation should be individualized Based on a single RCT, supplemental PN should be delayed until week after PICU admission for patients with normal baseline nutrition state and low risk of nutrition deterioration On the basis of expert consensus, we suggest PN supplementation for children who are unable to receive any EN during the first week in the PICU For patients who are severely malnourished or at risk of nutrition deterioration, PN may be supplemented in the first week if they are unable to advance to past low volumes of EN Quality of evidence: low GRADE recommendation: weak Q8: What is the role of immunonutrition in critically ill children? R8: On the basis of available evidence, we not recommend the use of immunonutrition in critically ill children Quality of evidence: moderate GRADE recommendation: strong EN, Enteral nutrition; GRADE, Grading of Recommendations, Assessment, Development, and Evaluation; IC, indirect calorimetry; PICU, pediatric intensive care unit; PN, parenteral nutrition; Q, question; R, recommendation; RCT, randomized controlled trial; RDA, recommended daily allowance From Mehta NM, Skillman HE, Irving SY, et al Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Pediatric Critically Ill Patient: Society of Critical Care Medicine and American Society for Parenteral and Enteral Nutrition Pediatr Crit Care Med 2017;18(7):675–715 1188 S E C T I O N X Pediatric Critical Care: Gastroenterology and Nutrition Key References Anez-Bustillos L, Dao DT, Baker MA, Fell GL, Puder M, Gura KM intravenous fat emulsion formulations for the adult and pediatric patient: understanding the differences Nutr Clin Pract 2016;31(5): 596-609 Coss-Bu JA, Klish WJ, Walding D, Stein F, Smith EO, Jefferson LS Energy metabolism, nitrogen balance, and substrate utilization in critically ill children Am J Clin Nutr 2001;74(5):664-669 Fivez T, Kerklaan D, Mesotten D, et al Early versus late parenteral nutrition in critically ill children N Engl J Med 2016;374(12):1111-1122 Hamilton S, McAleer DM, Ariagno K, et al A stepwise enteral nutrition algorithm for critically ill children helps achieve nutrient delivery goals Pediatr Crit Care Med 2014;15(7):583-589 Hardy CM, Dwyer J, Snelling LK, Dallal GE, Adelson JW Pitfalls in predicting resting energy requirements in critically ill children: a comparison of predictive methods to indirect calorimetry Nutr Clin Pract 2002;17(3):182-189 Jotterand Chaparro C, Laure Depeyre J, Longchamp D, Perez MH, Taffe P, Cotting J How much protein and energy are needed to equilibrate nitrogen and energy balances in ventilated critically ill children? Clin Nutr 2016;35(2):460-467 Meert KL, Daphtary KM, Metheny NA Gastric vs small-bowel feeding in critically ill children receiving mechanical ventilation: a randomized controlled trial Chest 2004;126(3):872-878 Mehta NM, Bechard LJ, Cahill N, et al Nutritional practices and their relationship to clinical outcomes in critically ill children—an international multicenter cohort study Crit Care Med 2012;40(7):22042211 Mehta NM, Bechard LJ, Zurakowski D, Duggan CP, Heyland DK Adequate enteral protein intake is inversely associated with 60-d mortality in critically ill children: a multicenter, prospective, cohort study Am J Clin Nutr 2015;102(1):199-206 Mehta NM, McAleer D, Hamilton S, et al Challenges to optimal enteral nutrition in a multidisciplinary pediatric intensive care unit JPEN J Parenter Enteral Nutr 2010;34(1):38-45 Mehta NM, Skillman HE, Irving SY, et al Guidelines for the provision and assessment of nutrition support therapy in the pediatric critically ill patient: Society of Critical Care Medicine and American Society for Parenteral and Enteral Nutrition Pediatr Crit Care Med 2017;18(7):675-715 Mikhailov TA, Kuhn EM, Manzi J, et al Early enteral nutrition is associated with lower mortality in critically ill children JPEN J Parenter Enteral Nutr 2014;38(4):459-466 The full reference list for this chapter is available at ExpertConsult.com e1 References Hulst J, Joosten K, Zimmermann L, et al Malnutrition in critically ill children: from admission to months after discharge Clin Nutr 2004;23(2):223-232 Pollack MM, Wiley JS, Kanter R, Holbrook PR Malnutrition in critically ill infants and children JPEN J Parenter Enteral Nutr 1982;6(1):20-24 Mehta NM, Bechard LJ, Leavitt K, Duggan C Cumulative energy imbalance in the pediatric intensive care unit: role of targeted indirect calorimetry JPEN J Parenter Enteral Nutr 2009;33(3):336-344 Pollack MM, Ruttimann UE, Wiley JS Nutritional depletions in critically ill children: associations with physiologic instability and increased quantity of care JPEN J Parenter Enteral Nutr 1985;9(3):309-313 McWhirter JP, Pennington CR Incidence and recognition of malnutrition in hospital BMJ 1994;308(6934):945-948 Jensen GL, Mirtallo J, Compher C, et al Adult starvation and disease-related malnutrition: a proposal for etiology-based diagnosis in the clinical practice setting from the International Consensus Guideline Committee Clin Nutr 2010;29(2):151-153 Mehta NM, Corkins MR, Lyman B, et al Defining pediatric malnutrition: a paradigm shift toward etiology-related definitions JPEN J Parenter Enteral Nutr 2013;37(4):460-481 Mehta NM, Bechard LJ, Leavitt K, Duggan C Severe weight loss and hypermetabolic paroxysmal dysautonomia following hypoxic ischemic brain injury: the role of indirect calorimetry in the intensive care unit JPEN J Parenter Enteral Nutr 2008;32(3):281-284 Becker PJ, Nieman Carney L, Corkins MR, et al Consensus statement of the Academy of Nutrition and Dietetics/American Society for Parenteral and Enteral Nutrition: indicators recommended for the identification and documentation of pediatric malnutrition (undernutrition) J Acad Nutr Diet 2014;114(12):1988-2000 10 Sood M, Adams JE, Mughal MZ Lean body mass in children with cystic fibrosis Arch Dis Child 2003;88(9):836 11 Brambilla P, Rolland-Cachera MF, Testolin C, et al Lean mass of children in various nutritional states Comparison between dualenergy X-ray absorptiometry and anthropometry Ann N Y Acad Sci 2000;904:433-436 12 Elberg J, McDuffie JR, Sebring NG, et al Comparison of methods to assess change in children’s body composition Am J Clin Nutr 2004;80(1):64-69 13 Levine A, Maayan A, Shamir R, Dinari G, Sulkes J, Sirotta L Parenteral nutrition-associated cholestasis in preterm neonates: evaluation of ursodeoxycholic acid treatment J Pediatr Endocrinol Metab 1999;12(4):549-553 14 Eisenmann JC, Heelan KA, Welk GJ Assessing body composition among 3- to 8-year-old children: anthropometry, BIA, and DXA Obes Res 2004;12(10):1633-1640 15 Mehta NM, Raphael B, Guteirrez IM, et al Comparison of body composition assessment methods in pediatric intestinal failure J Pediatr Gastroenterol Nutr 2014;59(1):99-105 16 Zamberlan P, Feferbaum RAPoP, Doria Filho U, Brunow de Carvalho WFPoP, Figueiredo Delgado AAPoP Bioelectrical impedance phase angle and morbidity and mortality in critically ill children Nutr Clin Pract 2019;34(1):163-171 17 Robinson MK, Trujillo EB, Mogensen KM, Rounds J, McManus K, Jacobs DO Improving nutritional screening of hospitalized patients: the role of prealbumin JPEN J Parenter Enteral Nutr 2003;27(6): 389-395; quiz 439 18 Measurement of visceral protein status in assessing protein and energy malnutrition: standard of care Prealbumin in Nutritional Care Consensus Group Nutrition 1995;11(2):169-171 19 Dickson PW, Bannister D, Schreiber G Minor burns lead to major changes in synthesis rates of plasma proteins in the liver J Trauma 1987;27(3):283-286 20 Letton RW, Chwals WJ, Jamie A, Charles B Early postoperative alterations in infant energy use increase the risk of overfeeding J Pediatr Surg 1995;30(7):988-992; discussion 992-983 21 Martinez EE, Smallwood CD, Bechard LJ, Graham RJ, Mehta NM Metabolic assessment and individualized nutrition in children dependent on mechanical ventilation at home J Pediatr 2015;166(2): 350-357 22 de Groof F, Joosten KF, Janssen JA, et al Acute stress response in children with meningococcal sepsis: important differences in the growth hormone/insulin-like growth factor I axis between nonsurvivors and survivors J Clin Endocrinol Metab 2002;87(7):3118-3124 23 Fullerton BS, Sparks EA, Khan FA, et al Whole body protein turnover and net protein balance after pediatric thoracic surgery: a noninvasive single-dose (15) N glycine stable isotope protocol with end-product enrichment JPEN J Parenter Enteral Nutr 2018;42(2):361-370 24 Long CL, Kinney JM, Geiger JW Nonsuppressability of gluconeogenesis by glucose in septic patients Metabolism 1976;25(2):193201 25 Coss-Bu JA, Klish WJ, Walding D, Stein F, Smith EO, Jefferson LS Energy metabolism, nitrogen balance, and substrate utilization in critically ill children Am J Clin Nutr 2001;74(5):664-669 26 Friedman Z, Danon A, Stahlman MT, Oates JA Rapid onset of essential fatty acid deficiency in the newborn Pediatrics 1976;58(5):640-649 27 Paulsrud JR, Pensler L, Whitten CF, Stewart S, Holman RT Essential fatty acid deficiency in infants induced by fat-free intravenous feeding Am J Clin Nutr 1972;25(9):897-904 28 Giovannini M, Riva E, Agostoni C Fatty acids in pediatric nutrition Pediatr Clin North Am 1995;42(4):861-877 29 Askanazi J, Rosenbaum SH, Hyman AI, Silverberg PA, Milic-Emili J, Kinney JM Respiratory changes induced by the large glucose loads of total parenteral nutrition JAMA 1980;243(14):1444-1447 30 Framson CM, LeLeiko NS, Dallal GE, Roubenoff R, Snelling LK, Dwyer JT Energy expenditure in critically ill children Pediatr Crit Care Med 2007;8(3):264-267 31 Hardy CM, Dwyer J, Snelling LK, Dallal GE, Adelson JW Pitfalls in predicting resting energy requirements in critically ill children: a comparison of predictive methods to indirect calorimetry Nutr Clin Pract 2002;17(3):182-189 32 Hunter DC, Jaksic T, Lewis D, Benotti PN, Blackburn GL, Bistrian BR Resting energy expenditure in the critically ill: estimations versus measurement Br J Surg 1988;75(9):875-878 33 Mehta NM, McAleer D, Hamilton S, et al Challenges to optimal enteral nutrition in a multidisciplinary pediatric intensive care unit JPEN J Parenter Enteral Nutr 2010;34(1):38-45 34 Rogers EJ, Gilbertson HR, Heine RG, Henning R Barriers to adequate nutrition in critically ill children Nutrition 2003;19(10):865-868 35 Heyland DK, Schroter-Noppe D, Drover JW, et al Nutrition support in the critical care setting: current practice in Canadian ICUs— opportunities for improvement? JPEN J Parenter Enteral Nutr 2003;27(1):74-83 36 Mehta NM, Bechard LJ, Cahill N, et al Nutritional practices and their relationship to clinical outcomes in critically ill children—an international multicenter cohort study* Crit Care Med 2012;40(7): 2204-2211 37 Taylor RM, Cheeseman P, Preedy V, Baker AJ, Grimble G Can energy expenditure be predicted in critically ill children? Pediatr Crit Care Med 2003;4(2):176-180 38 Briassoulis G, Venkataraman S, Thompson AE Energy expenditure in critically ill children Crit Care Med 2000;28(4):1166-1172 39 White MS, Shepherd RW, McEniery JA Energy expenditure in 100 ventilated, critically ill children: improving the accuracy of predictive equations Crit Care Med 2000;28(7):2307-2312 40 Jaksic T, Shew SB, Keshen TH, Dzakovic A, Jahoor F Do critically ill surgical neonates have increased energy expenditure? J Pediatr Surg 2001;36(1):63-67 41 Jones MO, Pierro A, Hammond P, Lloyd DA The metabolic response to operative stress in infants J Pediatr Surg 1993;28(10):12581262; discussion 1262-1253 42 Shew SB, Keshen TH, Jahoor F, Jaksic T The determinants of protein catabolism in neonates on extracorporeal membrane oxygenation J Pediatr Surg 1999;34(7):1086-1090 ... motility Based on large cohort studies, early initiation of EN (within 24–48 hours of PICU admission) and achievement of up to two-thirds of the nutrient goal in the first week of critical illness... R2C: On the basis of observational cohort studies, we suggest achieving delivery of at least two-thirds of the prescribed daily energy requirement by the end of the first week in the PICU Cumulative... cohort studies, we recommend a minimum protein intake of 1.5 g/kg/d Protein intake higher than this threshold has been shown to prevent cumulative negative protein balance in RCTs In critically