Optimizing Protein in the Diets of Critically Ill Children: Time for Re-Evaluation

Abstract

See related article, p 27The role of nutrition in improving the outcomes of children with critical illness has not been extensively studied in terms of rigorous clinical trials designed to define the optimal doses of macronutrients (carbohydrates, protein, and fat). As a result, solid evidence-based recommendations for critically ill children regarding the mode of nutrient delivery and specific intake of macronutrients are not available. Recent clinical practice guidelines for nutrition support in critically ill children published by the American Society of Parenteral and Enteral Nutrition are based on limited data and the experience of experts in the field.1Mehta N.M. Compher C. ASPEN clinical guidelines: nutrition support of the critically ill child.J Parenter Enteral Nutr. 2009; 33: 260-276Crossref PubMed Scopus (323) Google Scholar Despite advances in the medical management of critically ill children, the prevalence of malnutrition in hospitalized children, especially those with critical illness, continues to be high.1Mehta N.M. Compher C. ASPEN clinical guidelines: nutrition support of the critically ill child.J Parenter Enteral Nutr. 2009; 33: 260-276Crossref PubMed Scopus (323) Google Scholar, 2Joosten K.F. Hulst J.M. Malnutrition in pediatric hospital patients: current issues.Nutrition. 2011; 27: 133-137Abstract Full Text Full Text PDF PubMed Scopus (100) Google Scholar, 3Botran M. Lopez-Herce J. Mencia S. Urbano J. Solana M.J. Garcia A. Enteral nutrition in the critically ill child: comparison of standard and protein-enriched diets.J Pediatr. 2011; 159: 27-32Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar This is due to several factors, including the difficulty in identifying malnutrition, a need for fluid restriction in certain patients, prescription of inappropriate nutrition, and absence of a dedicated nutrition support team in some centers.2Joosten K.F. Hulst J.M. Malnutrition in pediatric hospital patients: current issues.Nutrition. 2011; 27: 133-137Abstract Full Text Full Text PDF PubMed Scopus (100) Google Scholar, 4Rogers E.J. Gilbertson H.R. Heine R.G. Henning R. Barriers to adequate nutrition in critically ill children.Nutrition. 2003; 19: 865-868Abstract Full Text Full Text PDF PubMed Scopus (137) Google ScholarThere is growing evidence indicating the need to directly monitor the energy expenditure of critically ill children and the inadequacy of using generalized equations to estimate these children’s caloric needs.5White M.S. Shepherd R.W. McEniery J.A. Energy expenditure in 100 ventilated, critically ill children: improving the accuracy of predictive equations.Crit Care Med. 2000; 28: 2307-2312Crossref PubMed Scopus (106) Google Scholar, 6Framson C.M. LeLeiko N.S. Dallal G.E. Roubenoff R. Snelling L.K. Dwyer J.T. Energy expenditure in critically ill children.Pediatr Crit Care Med. 2007; 8: 264-267Crossref PubMed Scopus (98) Google Scholar Energy needs and energy expenditure must be assessed throughout the course of illness. This involves modifying energy calculations based on the patient’s metabolic state, phase of illness, and organ systems affected. The use of indirect calorimetry to assess energy expenditure and basal energy needs in patients who meet certain criteria is sometimes desirable7Mehta N.M. Bechard L.J. Dolan M. Ariagno K. Jiang H. Duggan C. Energy imbalance and the risk of overfeeding in critically ill children.Pediatr Crit Care Med. 2010; ([epub ahead of press])Google Scholar; however, conventional indirect calorimetry does not provide specific guidance regarding optimal protein/amino acid administration. Care should be taken in interpreting respiratory quotient values for estimating carbohydrate or fat administration. Increasing caloric intake inappropriately by providing excessive carbohydrates without focusing on the distribution of nutrients may lead to increased protein breakdown, amino acid oxidation, and lower protein balance, which not only worsens protein malnutrition, but also increases carbon dioxide production.8Shew S.B. Keshen T.H. Jahoor F. Jaksic T. The determinants of protein catabolism in neonates on extracorporeal membrane oxygenation.J Pediatr Surg. 1999; 34: 1086-1090Abstract Full Text PDF PubMed Scopus (41) Google ScholarIn this issue of The Journal, Botran et al3Botran M. Lopez-Herce J. Mencia S. Urbano J. Solana M.J. Garcia A. Enteral nutrition in the critically ill child: comparison of standard and protein-enriched diets.J Pediatr. 2011; 159: 27-32Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar provide much-needed evidence regarding the delivery of protein to critically ill children in the context of a well-designed prospective, randomized pilot study. This adds an important dimension to understanding the role of supplementing protein in the management of critically ill children, given that most currently available data are derived from nonrandomized cohorts with historical controls, case series, uncontrolled studies, and/or expert opinions. As a result, the available data are insufficient to allow solid evidence-based recommendations.1Mehta N.M. Compher C. ASPEN clinical guidelines: nutrition support of the critically ill child.J Parenter Enteral Nutr. 2009; 33: 260-276Crossref PubMed Scopus (323) Google Scholar Botran et al’s preliminary data will inform larger studies to evaluate the clinical impact of different protein intake doses in a variety of conditions present in critically ill children. Further evaluation of the appropriate delivery of nutrients to critically ill children is needed.Botran et al compared the use of a standard diet and a protein-enriched diet (standard diet supplemented with an additional 1.1 g of nonhydrolyzed cow’s milk–based protein/100 mL of formula). The majority of the patients (88%) were studied after cardiac surgery (73%) or airway surgery (15%).3Botran M. Lopez-Herce J. Mencia S. Urbano J. Solana M.J. Garcia A. Enteral nutrition in the critically ill child: comparison of standard and protein-enriched diets.J Pediatr. 2011; 159: 27-32Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar Recovery from trauma or surgery is typically characterized by increased protein catabolism but not necessarily with increased energy needs.1Mehta N.M. Compher C. ASPEN clinical guidelines: nutrition support of the critically ill child.J Parenter Enteral Nutr. 2009; 33: 260-276Crossref PubMed Scopus (323) Google Scholar, 9Chwals W.J. The metabolic response to surgery in neonates.Curr Opin Pediatr. 1994; 6: 334-340Crossref PubMed Scopus (17) Google Scholar As Botran et al show, energy needs tend to decrease during certain phases of recovery in the sedated and intubated patients, accompanied by increased protein turnover, presumably to make amino acids available for tissue repair, wound healing, and acute-phase inflammatory responses.3Botran M. Lopez-Herce J. Mencia S. Urbano J. Solana M.J. Garcia A. Enteral nutrition in the critically ill child: comparison of standard and protein-enriched diets.J Pediatr. 2011; 159: 27-32Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar The response of improved nitrogen balance observed in the protein-supplemented group likely reflects a net decrease in total protein loss after surgery.10Keshen T.H. Miller R.G. Jahoor F. Jaksic T. Stable isotopic quantitation of protein metabolism and energy expenditure in neonates on and post-extracorporeal life support.J Pediatr Surg. 1997; 32: 958-962Abstract Full Text PDF PubMed Scopus (76) Google Scholar This anabolic response is similar to that previously reported in infants with bronchiolitis and lung failure who received a higher-calorie/higher-protein diet compared with controls who received standard prescribed nutrition.11van Waardenburg D.A. de Betue C.T. Goudoever J.B. Zimmermann L.J. Joosten K.F. Critically ill infants benefit from early administration of protein and energy-enriched formula: a randomized controlled trial.Clin Nutr. 2009; 28: 249-255Abstract Full Text Full Text PDF PubMed Scopus (48) Google ScholarAs illustrated by Botran et al, nitrogen balance measurements can provide significant insight into nutritional status.1Mehta N.M. Compher C. ASPEN clinical guidelines: nutrition support of the critically ill child.J Parenter Enteral Nutr. 2009; 33: 260-276Crossref PubMed Scopus (323) Google Scholar, 3Botran M. Lopez-Herce J. Mencia S. Urbano J. Solana M.J. Garcia A. Enteral nutrition in the critically ill child: comparison of standard and protein-enriched diets.J Pediatr. 2011; 159: 27-32Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar Nitrogen balance studies are difficult to perform in clinical settings; however, when performed accurately, they provide a relatively proficient assessment of protein status and are more sensitive to acute changes than albumin and prealbumin (transthyretin) levels. Albumin and prealbumin concentrations in plasma are not reliable markers of protein status in critical illness because they can be affected by multiple factors, including fluid status changes, infusions (eg, albumin, packed red blood cells, immunoglobulins, parenteral nutrition), trauma, and liver and renal disease. They are also markedly decreased in the setting of infection or inflammation due to increased clearance and/or decreased production.12Ziegler T.R. Parenteral nutrition in the critically ill patient.N Engl J Med. 2009; 361: 1088-1097Crossref PubMed Scopus (198) Google ScholarThis relatively small, yet promising study does not support the routine use of increased protein delivery in all categories of critically ill children. Nonetheless, the study can serve to generate hypotheses as to the subgroups of critically ill children who may benefit from increased protein delivery in the postoperative setting. Excessive protein administration may be detrimental in such conditions as renal and hepatic dysfunction or failure. Stable isotope techniques can be used for further pediatric research in intensive care settings to evaluate rates of protein synthesis and degradation in response to different protein/amino acid loads.1Mehta N.M. Compher C. ASPEN clinical guidelines: nutrition support of the critically ill child.J Parenter Enteral Nutr. 2009; 33: 260-276Crossref PubMed Scopus (323) Google Scholar, 8Shew S.B. Keshen T.H. Jahoor F. Jaksic T. The determinants of protein catabolism in neonates on extracorporeal membrane oxygenation.J Pediatr Surg. 1999; 34: 1086-1090Abstract Full Text PDF PubMed Scopus (41) Google ScholarUntil more evidence is provided from well-controlled, randomized clinical trials and comparative effectiveness research, uncertainty will persist regarding protein and macronutrient needs in subgroups of critically ill children. New data, such as provided in this study, are needed to provide evidence-based information specific to children of different age groups under different catabolic conditions.3Botran M. Lopez-Herce J. Mencia S. Urbano J. Solana M.J. Garcia A. Enteral nutrition in the critically ill child: comparison of standard and protein-enriched diets.J Pediatr. 2011; 159: 27-32Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar When precise protein needs are anticipated and safely delivered to the critically ill child, then safe caloric provisions using carbohydrate and fat sources will have similar effects on net protein synthesis and overall positive protein balance.1Mehta N.M. Compher C. ASPEN clinical guidelines: nutrition support of the critically ill child.J Parenter Enteral Nutr. 2009; 33: 260-276Crossref PubMed Scopus (323) Google Scholar See related article, p 27The role of nutrition in improving the outcomes of children with critical illness has not been extensively studied in terms of rigorous clinical trials designed to define the optimal doses of macronutrients (carbohydrates, protein, and fat). As a result, solid evidence-based recommendations for critically ill children regarding the mode of nutrient delivery and specific intake of macronutrients are not available. Recent clinical practice guidelines for nutrition support in critically ill children published by the American Society of Parenteral and Enteral Nutrition are based on limited data and the experience of experts in the field.1Mehta N.M. Compher C. ASPEN clinical guidelines: nutrition support of the critically ill child.J Parenter Enteral Nutr. 2009; 33: 260-276Crossref PubMed Scopus (323) Google Scholar Despite advances in the medical management of critically ill children, the prevalence of malnutrition in hospitalized children, especially those with critical illness, continues to be high.1Mehta N.M. Compher C. ASPEN clinical guidelines: nutrition support of the critically ill child.J Parenter Enteral Nutr. 2009; 33: 260-276Crossref PubMed Scopus (323) Google Scholar, 2Joosten K.F. Hulst J.M. Malnutrition in pediatric hospital patients: current issues.Nutrition. 2011; 27: 133-137Abstract Full Text Full Text PDF PubMed Scopus (100) Google Scholar, 3Botran M. Lopez-Herce J. Mencia S. Urbano J. Solana M.J. Garcia A. Enteral nutrition in the critically ill child: comparison of standard and protein-enriched diets.J Pediatr. 2011; 159: 27-32Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar This is due to several factors, including the difficulty in identifying malnutrition, a need for fluid restriction in certain patients, prescription of inappropriate nutrition, and absence of a dedicated nutrition support team in some centers.2Joosten K.F. Hulst J.M. Malnutrition in pediatric hospital patients: current issues.Nutrition. 2011; 27: 133-137Abstract Full Text Full Text PDF PubMed Scopus (100) Google Scholar, 4Rogers E.J. Gilbertson H.R. Heine R.G. Henning R. Barriers to adequate nutrition in critically ill children.Nutrition. 2003; 19: 865-868Abstract Full Text Full Text PDF PubMed Scopus (137) Google Scholar See related article, p 27 See related article, p 27 There is growing evidence indicating the need to directly monitor the energy expenditure of critically ill children and the inadequacy of using generalized equations to estimate these children’s caloric needs.5White M.S. Shepherd R.W. McEniery J.A. Energy expenditure in 100 ventilated, critically ill children: improving the accuracy of predictive equations.Crit Care Med. 2000; 28: 2307-2312Crossref PubMed Scopus (106) Google Scholar, 6Framson C.M. LeLeiko N.S. Dallal G.E. Roubenoff R. Snelling L.K. Dwyer J.T. Energy expenditure in critically ill children.Pediatr Crit Care Med. 2007; 8: 264-267Crossref PubMed Scopus (98) Google Scholar Energy needs and energy expenditure must be assessed throughout the course of illness. This involves modifying energy calculations based on the patient’s metabolic state, phase of illness, and organ systems affected. The use of indirect calorimetry to assess energy expenditure and basal energy needs in patients who meet certain criteria is sometimes desirable7Mehta N.M. Bechard L.J. Dolan M. Ariagno K. Jiang H. Duggan C. Energy imbalance and the risk of overfeeding in critically ill children.Pediatr Crit Care Med. 2010; ([epub ahead of press])Google Scholar; however, conventional indirect calorimetry does not provide specific guidance regarding optimal protein/amino acid administration. Care should be taken in interpreting respiratory quotient values for estimating carbohydrate or fat administration. Increasing caloric intake inappropriately by providing excessive carbohydrates without focusing on the distribution of nutrients may lead to increased protein breakdown, amino acid oxidation, and lower protein balance, which not only worsens protein malnutrition, but also increases carbon dioxide production.8Shew S.B. Keshen T.H. Jahoor F. Jaksic T. The determinants of protein catabolism in neonates on extracorporeal membrane oxygenation.J Pediatr Surg. 1999; 34: 1086-1090Abstract Full Text PDF PubMed Scopus (41) Google Scholar In this issue of The Journal, Botran et al3Botran M. Lopez-Herce J. Mencia S. Urbano J. Solana M.J. Garcia A. Enteral nutrition in the critically ill child: comparison of standard and protein-enriched diets.J Pediatr. 2011; 159: 27-32Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar provide much-needed evidence regarding the delivery of protein to critically ill children in the context of a well-designed prospective, randomized pilot study. This adds an important dimension to understanding the role of supplementing protein in the management of critically ill children, given that most currently available data are derived from nonrandomized cohorts with historical controls, case series, uncontrolled studies, and/or expert opinions. As a result, the available data are insufficient to allow solid evidence-based recommendations.1Mehta N.M. Compher C. ASPEN clinical guidelines: nutrition support of the critically ill child.J Parenter Enteral Nutr. 2009; 33: 260-276Crossref PubMed Scopus (323) Google Scholar Botran et al’s preliminary data will inform larger studies to evaluate the clinical impact of different protein intake doses in a variety of conditions present in critically ill children. Further evaluation of the appropriate delivery of nutrients to critically ill children is needed. Botran et al compared the use of a standard diet and a protein-enriched diet (standard diet supplemented with an additional 1.1 g of nonhydrolyzed cow’s milk–based protein/100 mL of formula). The majority of the patients (88%) were studied after cardiac surgery (73%) or airway surgery (15%).3Botran M. Lopez-Herce J. Mencia S. Urbano J. Solana M.J. Garcia A. Enteral nutrition in the critically ill child: comparison of standard and protein-enriched diets.J Pediatr. 2011; 159: 27-32Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar Recovery from trauma or surgery is typically characterized by increased protein catabolism but not necessarily with increased energy needs.1Mehta N.M. Compher C. ASPEN clinical guidelines: nutrition support of the critically ill child.J Parenter Enteral Nutr. 2009; 33: 260-276Crossref PubMed Scopus (323) Google Scholar, 9Chwals W.J. The metabolic response to surgery in neonates.Curr Opin Pediatr. 1994; 6: 334-340Crossref PubMed Scopus (17) Google Scholar As Botran et al show, energy needs tend to decrease during certain phases of recovery in the sedated and intubated patients, accompanied by increased protein turnover, presumably to make amino acids available for tissue repair, wound healing, and acute-phase inflammatory responses.3Botran M. Lopez-Herce J. Mencia S. Urbano J. Solana M.J. Garcia A. Enteral nutrition in the critically ill child: comparison of standard and protein-enriched diets.J Pediatr. 2011; 159: 27-32Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar The response of improved nitrogen balance observed in the protein-supplemented group likely reflects a net decrease in total protein loss after surgery.10Keshen T.H. Miller R.G. Jahoor F. Jaksic T. Stable isotopic quantitation of protein metabolism and energy expenditure in neonates on and post-extracorporeal life support.J Pediatr Surg. 1997; 32: 958-962Abstract Full Text PDF PubMed Scopus (76) Google Scholar This anabolic response is similar to that previously reported in infants with bronchiolitis and lung failure who received a higher-calorie/higher-protein diet compared with controls who received standard prescribed nutrition.11van Waardenburg D.A. de Betue C.T. Goudoever J.B. Zimmermann L.J. Joosten K.F. Critically ill infants benefit from early administration of protein and energy-enriched formula: a randomized controlled trial.Clin Nutr. 2009; 28: 249-255Abstract Full Text Full Text PDF PubMed Scopus (48) Google Scholar As illustrated by Botran et al, nitrogen balance measurements can provide significant insight into nutritional status.1Mehta N.M. Compher C. ASPEN clinical guidelines: nutrition support of the critically ill child.J Parenter Enteral Nutr. 2009; 33: 260-276Crossref PubMed Scopus (323) Google Scholar, 3Botran M. Lopez-Herce J. Mencia S. Urbano J. Solana M.J. Garcia A. Enteral nutrition in the critically ill child: comparison of standard and protein-enriched diets.J Pediatr. 2011; 159: 27-32Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar Nitrogen balance studies are difficult to perform in clinical settings; however, when performed accurately, they provide a relatively proficient assessment of protein status and are more sensitive to acute changes than albumin and prealbumin (transthyretin) levels. Albumin and prealbumin concentrations in plasma are not reliable markers of protein status in critical illness because they can be affected by multiple factors, including fluid status changes, infusions (eg, albumin, packed red blood cells, immunoglobulins, parenteral nutrition), trauma, and liver and renal disease. They are also markedly decreased in the setting of infection or inflammation due to increased clearance and/or decreased production.12Ziegler T.R. Parenteral nutrition in the critically ill patient.N Engl J Med. 2009; 361: 1088-1097Crossref PubMed Scopus (198) Google Scholar This relatively small, yet promising study does not support the routine use of increased protein delivery in all categories of critically ill children. Nonetheless, the study can serve to generate hypotheses as to the subgroups of critically ill children who may benefit from increased protein delivery in the postoperative setting. Excessive protein administration may be detrimental in such conditions as renal and hepatic dysfunction or failure. Stable isotope techniques can be used for further pediatric research in intensive care settings to evaluate rates of protein synthesis and degradation in response to different protein/amino acid loads.1Mehta N.M. Compher C. ASPEN clinical guidelines: nutrition support of the critically ill child.J Parenter Enteral Nutr. 2009; 33: 260-276Crossref PubMed Scopus (323) Google Scholar, 8Shew S.B. Keshen T.H. Jahoor F. Jaksic T. The determinants of protein catabolism in neonates on extracorporeal membrane oxygenation.J Pediatr Surg. 1999; 34: 1086-1090Abstract Full Text PDF PubMed Scopus (41) Google Scholar Until more evidence is provided from well-controlled, randomized clinical trials and comparative effectiveness research, uncertainty will persist regarding protein and macronutrient needs in subgroups of critically ill children. New data, such as provided in this study, are needed to provide evidence-based information specific to children of different age groups under different catabolic conditions.3Botran M. Lopez-Herce J. Mencia S. Urbano J. Solana M.J. Garcia A. Enteral nutrition in the critically ill child: comparison of standard and protein-enriched diets.J Pediatr. 2011; 159: 27-32Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar When precise protein needs are anticipated and safely delivered to the critically ill child, then safe caloric provisions using carbohydrate and fat sources will have similar effects on net protein synthesis and overall positive protein balance.1Mehta N.M. Compher C. ASPEN clinical guidelines: nutrition support of the critically ill child.J Parenter Enteral Nutr. 2009; 33: 260-276Crossref PubMed Scopus (323) Google Scholar Enteral Nutrition in the Critically Ill Child: Comparison of Standard and Protein-Enriched DietsThe Journal of PediatricsVol. 159Issue 1PreviewTo compare a standard diet and a protein-enriched diet in critically ill children. Full-Text PDF