Nutritional Support for Abdominal Sepsis

  • Martin D. Rosenthal
  • Cameron M. Rosenthal
  • Amir Y. Kamel
  • Frederick A. Moore
Part of the Hot Topics in Acute Care Surgery and Trauma book series (HTACST)


Intra-abdominal sepsis can be a challenging pathophysiologic state. There are a lot of misconceptions surrounding nutrition supplementation in patients with intra-abdominal sepsis. Persistent inflammation immunosuppression catabolism syndrome (PICS) is a new phenotype of multiple organ failure associated with a severe stress such as intra-abdominal sepsis. Nutritional support of these patients is paramount to their recovery and should still largely follow the ASPEN guidelines. Certain nutritional adjuncts could ultimately prove to provide benefit in treating patients with intra-abdominal sepsis and PICS.


Enteral nutrition Gut integrity Ischemia Microbiome Mucosal defense PICS (persistent inflammation immunosuppression catabolism syndrome) 



Supported by P50 GM-111152 (F.A. Moore) and awarded by the National Institute of General Medical Sciences (NIGMS). P50GM111152 (NIH/NIGMS) “PICS: A New Horizon for Surgical Critical Care”.


  1. 1.
    Gentile LF, Cuenca AG, Efron PA, Ang D, Bihorac A, McKinley BA, Moldawer LL, Moore FA. Persistent inflammation and immunosuppression: a common syndrome and new horizon for surgical intensive care. J Trauma Acute Care Surg. 2012;72(6):1491–501.PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Fearon K, Strasser F, Anker SD, Bosaeus I, Bruera E, Fainsinger RL, Jatoi A, Loprinzi C, MacDonald N, Mantovani G, Davis M, Muscaritoli M, Ottery F, Radbruch L, Ravasco P, Walsh D, Wilcock A, Kaasa S, Baracos VE. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol. 2011;12(5):489–95.PubMedCrossRefGoogle Scholar
  3. 3.
    Friedrich O, Reid MB, Van den Berghe G, Vanhorebeek I, Hermans G, Rich MM, Larsson L. The sick and the weak: neuropathies/myopathies in the critically ill. Physiol Rev. 2015;95(3):1025–109.PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Elliott D, Davidson JE, Harvey MA, Bemis-Dougherty A, Hopkins RO, Iwashyna TJ, Wagner J, Weinert C, Wunsch H, Bienvenu OJ, Black G, Brady S, Brodsky MB, Deutschman C, Doepp D, Flatley C, Fosnight S, Gittler M, Gomez BT, Hyzy R, Louis D, Mandel R, Maxwell C, Muldoon SR, Perme CS, Reilly C, Robinson MR, Rubin E, Schmidt DM, Schuller J, Scruth E, Siegal E, Spill GR, Sprenger S, Straumanis JP, Sutton P, Swoboda SM, Twaddle ML, Needham DM. Exploring the scope of post-intensive care syndrome therapy and care: engagement of non-critical care providers and survivors in a second stakeholders meeting. Crit Care Med. 2014;42(12):2518–26.PubMedCrossRefGoogle Scholar
  5. 5.
    Cuenca AG, Delano MJ, Kelly-Scumpia KM, Moreno C, Scumpia PO, Laface DM, Heyworth PG, Efron PA, Moldawer LL. A paradoxical role for myeloid-derived suppressor cells in sepsis and trauma. Mol Med. 2011;17(3–4):281–92.Google Scholar
  6. 6.
    Delano MJ, Moldawer LL. The origins of cachexia in acute and chronic inflammatory diseases. Nutr Clin Pract. 2006;21(1):68–81.PubMedCrossRefGoogle Scholar
  7. 7.
    Mathias B, Delmas AL, Ozrazgat-Baslanti T, Vanzant EL, Szpila BE, Mohr AM, Moore FA, Brakenridge SC, Brumback BA, Moldawer LL, Efron PA, and C.I.R.C.I. and the Sepsis. Human myeloid-derived suppressor cells are associated with chronic immune suppression after severe sepsis/septic shock. Ann Surg. 2017;265(4):827–34.PubMedCrossRefGoogle Scholar
  8. 8.
    Vanzant EL, Lopez CM, Ozrazgat-Baslanti T, Ungaro R, Davis R, Cuenca AG, Gentile LF, Nacionales DC, Cuenca AL, Bihorac A, Leeuwenburgh C, Lanz J, Baker HV, McKinley B, Moldawer LL, Moore FA, Efron PA. Persistent inflammation, immunosuppression, and catabolism syndrome after severe blunt trauma. J Trauma Acute Care Surg. 2014;76(1):21–9. discussion 29–30PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Gabrilovich DI, Nagaraj S. Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol. 2009;9(3):162–74.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Yamanouchi S, Kudo D, Yamada M, Miyagawa N, Furukawa H, Kushimoto S. Plasma mitochondrial DNA levels in patients with trauma and severe sepsis: time course and the association with clinical status. J Crit Care. 2013;28(6):1027–31.PubMedCrossRefGoogle Scholar
  11. 11.
    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):50–6.PubMedCrossRefGoogle Scholar
  12. 12.
    Janu PG, Kudsk KA, Li J, Renegar KB. Effect of bombesin on impairment of upper respiratory tract immunity induced by total parenteral nutrition. Arch Surg. 1997;132(1):89–93.PubMedCrossRefGoogle Scholar
  13. 13.
    Li J, Kudsk KA, Janu P, Renegar KB. Effect of glutamine-enriched total parenteral nutrition on small intestinal gut-associated lymphoid tissue and upper respiratory tract immunity. Surgery. 1997;121(5):542–9.PubMedCrossRefGoogle Scholar
  14. 14.
    Kudsk KA. Beneficial effect of enteral feeding. Gastrointest Endosc Clin N Am. 2007;17(4):647–62.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Kudsk KA, Carpenter G, Petersen S, Sheldon GF. Effect of enteral and parenteral feeding in malnourished rats with E. coli-hemoglobin adjuvant peritonitis. J Surg Res. 1981;31(2):105–10.PubMedCrossRefGoogle Scholar
  16. 16.
    Kudsk KA. Effect of route and type of nutrition on intestine-derived inflammatory responses. Am J Surg. 2003;185(1):16–21.PubMedCrossRefGoogle Scholar
  17. 17.
    Kudsk KA, Gomez FE, Kang W, Ueno C. Enteral feeding of a chemically defined diet preserves pulmonary immunity but not intestinal immunity: the role of lymphotoxin beta receptor. JPEN J Parenter Enteral Nutr. 2007;31(6):477–81.PubMedCrossRefGoogle Scholar
  18. 18.
    Alverdy J, Zaborina O, Wu L. The impact of stress and nutrition on bacterial-host interactions at the intestinal epithelial surface. Curr Opin Clin Nutr Metab Care. 2005;8(2):205–9.PubMedCrossRefGoogle Scholar
  19. 19.
    Alverdy JC. During critical illness the gut does not pass the acid test. Crit Care. 2012;16(5):150.PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Alverdy JC, Laughlin RS, Wu L. Influence of the critically ill state on host-pathogen interactions within the intestine: gut-derived sepsis redefined. Crit Care Med. 2003;31(2):598–607.PubMedCrossRefGoogle Scholar
  21. 21.
    Long J, Zaborina O, Holbrook C, Zaborin A, Alverdy J. Depletion of intestinal phosphate after operative injury activates the virulence of P. aeruginosa causing lethal gut-derived sepsis. Surgery. 2008;144(2):189–97.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Zaborina O, Zaborin A, Romanowski K, Babrowski T, Alverdy J. Host stress and virulence expression in intestinal pathogens: development of therapeutic strategies using mice and C. elegans. Curr Pharm Des. 2011;17(13):1254–60.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Yan F, Cao H, Cover TL, Whitehead R, Washington MK, Polk DB. Soluble proteins produced by probiotic bacteria regulate intestinal epithelial cell survival and growth. Gastroenterology. 2007;132(2):562–75.PubMedCrossRefGoogle Scholar
  24. 24.
    Bengmark S. Bioecologic control of inflammation and infection in critical illness. Anesthesiol Clin. 2006;24(2):299–323. viPubMedCrossRefGoogle Scholar
  25. 25.
    Swidsinski A, Loening-Baucke V, Theissig F, Engelhardt H, Bengmark S, Koch S, Lochs H, Dorffel Y. Comparative study of the intestinal mucus barrier in normal and inflamed colon. Gut. 2007;56(3):343–50.PubMedCrossRefGoogle Scholar
  26. 26.
    Hickson M, D'Souza AL, Muthu N, Rogers TR, Want S, Rajkumar C, Bulpitt CJ. Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics: randomised double blind placebo controlled trial. BMJ. 2007;335(7610):80.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Johnston BC, Ma SS, Goldenberg JZ, Thorlund K, Vandvik PO, Loeb M, Guyatt GH. Probiotics for the prevention of Clostridium difficile-associated diarrhea: a systematic review and meta-analysis. Ann Intern Med. 2012;157(12):878–88.PubMedCrossRefGoogle Scholar
  28. 28.
    Morowitz MJ, Babrowski T, Carlisle EM, Olivas A, Romanowski KS, Seal JB, Liu DC, Alverdy JC. The human microbiome and surgical disease. Ann Surg. 2011;253(6):1094–101.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Hempel S, Newberry SJ, Maher AR, Wang Z, Miles JN, Shanman R, Johnsen B, Shekelle PG. Probiotics for the prevention and treatment of antibiotic-associated diarrhea: a systematic review and meta-analysis. JAMA. 2012;307(18):1959–69.PubMedCrossRefGoogle Scholar
  30. 30.
    Spindler-Vesel A, Bengmark S, Vovk I, Cerovic O, Kompan L. Synbiotics, prebiotics, glutamine, or peptide in early enteral nutrition: a randomized study in trauma patients. JPEN J Parenter Enteral Nutr. 2007;31(2):119–26.PubMedCrossRefGoogle Scholar
  31. 31.
    Morrow LE, Gogineni V, Malesker MA. Probiotics in the intensive care unit. Nutr Clin Pract. 2012;27(2):235–41.PubMedCrossRefGoogle Scholar
  32. 32.
    Watkinson PJ, Barber VS, Dark P, Young JD. The use of pre- pro- and synbiotics in adult intensive care unit patients: systematic review. Clin Nutr. 2007;26(2):182–92.PubMedCrossRefGoogle Scholar
  33. 33.
    Smith AJ, Nissan A, Lanouette NM, Shi W, Guillem JG, Wong WD, Thaler H, Cohen AM. Prokinetic effect of erythromycin after colorectal surgery: randomized, placebo-controlled, double-blind study. Dis Colon Rectum. 2000;43(3):333–7.PubMedCrossRefGoogle Scholar
  34. 34.
    Trudel L, Tomasetto C, Rio MC, Bouin M, Plourde V, Eberling P, Poitras P. Ghrelin/motilin-related peptide is a potent prokinetic to reverse gastric postoperative ileus in rat. Am J Physiol Gastrointest Liver Physiol. 2002;282(6):G948–52.PubMedCrossRefGoogle Scholar
  35. 35.
    Heyland DK, Murch L, Cahill N, McCall M, Muscedere J, Stelfox HT, Bray T, Tanguay T, Jiang X, Day AG. Enhanced protein-energy provision via the enteral route feeding protocol in critically ill patients: results of a cluster randomized trial. Crit Care Med. 2013;41(12):2743–53.PubMedCrossRefGoogle Scholar
  36. 36.
    Weijs PJ, Sauerwein HP, Kondrup J. Protein recommendations in the ICU: g protein/kg body weight – which body weight for underweight and obese patients? Clin Nutr. 2012;31(5):774–5.PubMedCrossRefGoogle Scholar
  37. 37.
    Allingstrup MJ, Esmailzadeh N, Wilkens Knudsen A, Espersen K, Hartvig Jensen T, Wiis J, Perner A, Kondrup J. Provision of protein and energy in relation to measured requirements in intensive care patients. Clin Nutr. 2012;31(4):462–8.PubMedCrossRefGoogle Scholar
  38. 38.
    Rosenthal MD, Vanzant EL, Martindale RG, Moore FA. Evolving paradigms in the nutritional support of critically ill surgical patients. Curr Probl Surg. 2015;52(4):147–82.PubMedCrossRefGoogle Scholar
  39. 39.
    McClave SA, Taylor BE, Martindale RG, Warren MM, Johnson DR, Braunschweig C, McCarthy MS, Davanos E, Rice TW, Cresci GA, Gervasio JM, Sacks GS, Roberts PR, Compher C, M. Society of Critical Care, P. American Society for, and N. Enteral. 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):159–211.PubMedCrossRefGoogle Scholar
  40. 40.
    Engelen MP, van der Meij BS, Deutz NE. Protein anabolic resistance in cancer: does it really exist? Curr Opin Clin Nutr Metab Care. 2016;19(1):39–47.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Arends J, Bodoky G, Bozzetti F, Fearon K, Muscaritoli M, Selga G, van Bokhorst-de van der Schueren MA, von Meyenfeldt M, DGEM, Zurcher G, Fietkau R, Aulbert E, Frick B, Holm M, Kneba M, Mestrom HJ, Zander A, and ESPEN. ESPEN guidelines on enteral nutrition: non-surgical oncology. Clin Nutr. 2006;25(2):245–59.Google Scholar
  42. 42.
    Morley JE, Argiles JM, Evans WJ, Bhasin S, Cella D, Deutz NE, Doehner W, Fearon KC, Ferrucci L, Hellerstein MK, Kalantar-Zadeh K, Lochs H, MacDonald N, Mulligan K, Muscaritoli M, Ponikowski P, Posthauer ME, Rossi Fanelli F, Schambelan M, Schols AM, Schuster MW, Anker SD, Society for Sarcopenia C, Wasting D. Nutritional recommendations for the management of sarcopenia. J Am Med Dir Assoc. 2010;11(6):391–6.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Hart DW, Wolf SE, Chinkes DL, Gore DC, Mlcak RP, Beauford RB, Obeng MK, Lal S, Gold WF, Wolfe RR, Herndon DN. Determinants of skeletal muscle catabolism after severe burn. Ann Surg. 2000;232(4):455–65.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Alexander JW, MacMillan BG, Stinnett JD, Ogle CK, Bozian RC, Fischer JE, Oakes JB, Morris MJ, Krummel R. Beneficial effects of aggressive protein feeding in severely burned children. Ann Surg. 1980;192(4):505–17.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Herndon DN, Tompkins RG. Support of the metabolic response to burn injury. Lancet. 2004;363(9424):1895–902.PubMedCrossRefGoogle Scholar
  46. 46.
    Gibran NS, Committee on Organization and Delivery of Burn Care, American Burn Association. Practice Guidelines for burn care, 2006. J Burn Care Res. 2006;27(4):437–8.PubMedCrossRefGoogle Scholar
  47. 47.
    Rousseau AF, Losser MR, Ichai C, Berger MM. ESPEN endorsed recommendations: nutritional therapy in major burns. Clin Nutr. 2013;32(4):497–502.PubMedCrossRefGoogle Scholar
  48. 48.
    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.e1PubMedCrossRefGoogle Scholar
  49. 49.
    Suchner U, Heyland DK, Peter K. Immune-modulatory actions of arginine in the critically ill. Br J Nutr. 2002;87(Suppl 1):S121–32.PubMedCrossRefGoogle Scholar
  50. 50.
    Moore FA. Effects of immune-enhancing diets on infectious morbidity and multiple organ failure. JPEN J Parenter Enteral Nutr. 2001;25(2 Suppl):S36–42. discussion S42–3PubMedCrossRefGoogle Scholar
  51. 51.
    Bansal V, Ochoa JB. Arginine availability, arginase, and the immune response. Curr Opin Clin Nutr Metab Care. 2003;6(2):223–8.PubMedCrossRefGoogle Scholar
  52. 52.
    Zhu X, Pribis JP, Rodriguez PC, Morris SM Jr, Vodovotz Y, Billiar TR, Ochoa JB. The central role of arginine catabolism in T-cell dysfunction and increased susceptibility to infection after physical injury. Ann Surg. 2014;259(1):171–8.PubMedCrossRefGoogle Scholar
  53. 53.
    Daly JM, Reynolds J, Thom A, Kinsley L, Dietrick-Gallagher M, Shou J, Ruggieri B. Immune and metabolic effects of arginine in the surgical patient. Ann Surg. 1988;208(4):512–23.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Barbul A, Sisto DA, Wasserkrug HL, Efron G. Arginine stimulates lymphocyte immune response in healthy human beings. Surgery. 1981;90(2):244–51.PubMedGoogle Scholar
  55. 55.
    Morris SM Jr. Arginine: master and commander in innate immune responses. Sci Signal. 2010;3(135):pe27.PubMedCrossRefGoogle Scholar
  56. 56.
    Barbul A, Rettura G, Levenson SM, Seifter E. Arginine: a thymotropic and wound-healing promoting agent. Surg Forum. 1977;28:101–3.PubMedGoogle Scholar
  57. 57.
    Barbul A, Wasserkrug HL, Sisto DA, Seifter E, Rettura G, Levenson SM, Efron G. Thymic stimulatory actions of arginine. JPEN J Parenter Enteral Nutr. 1980;4(5):446–9.PubMedCrossRefGoogle Scholar
  58. 58.
    Taheri F, Ochoa JB, Faghiri Z, Culotta K, Park HJ, Lan MS, Zea AH, Ochoa AC. l-Arginine regulates the expression of the T-cell receptor zeta chain (CD3zeta) in Jurkat cells. Clin Cancer Res. 2001;7(3 Suppl):958s–65s.PubMedGoogle Scholar
  59. 59.
    Rodriguez PC, Zea AH, Culotta KS, Zabaleta J, Ochoa JB, Ochoa AC. Regulation of T cell receptor CD3zeta chain expression by l-arginine. J Biol Chem. 2002;277(24):21123–9.PubMedCrossRefGoogle Scholar
  60. 60.
    Rodriguez PC, Zea AH, DeSalvo J, Culotta KS, Zabaleta J, Quiceno DG, Ochoa JB, Ochoa AC. l-Arginine consumption by macrophages modulates the expression of CD3 zeta chain in T lymphocytes. J Immunol. 2003;171(3):1232–9.PubMedCrossRefGoogle Scholar
  61. 61.
    Zea AH, Rodriguez PC, Culotta KS, Hernandez CP, DeSalvo J, Ochoa JB, Park HJ, Zabaleta J, Ochoa AC. l-Arginine modulates CD3zeta expression and T cell function in activated human T lymphocytes. Cell Immunol. 2004;232(1–2):21–31.PubMedCrossRefGoogle Scholar
  62. 62.
    Makarenkova VP, Bansal V, Matta BM, Perez LA, Ochoa JB. CD11b+/Gr-1+ myeloid suppressor cells cause T cell dysfunction after traumatic stress. J Immunol. 2006;176(4):2085–94.PubMedCrossRefGoogle Scholar
  63. 63.
    Scumpia PO, Delano MJ, Kelly-Scumpia KM, Weinstein JS, Wynn JL, Winfield RD, Xia C, Chung CS, Ayala A, Atkinson MA, Reeves WH, Clare-Salzler MJ, Moldawer LL. Treatment with GITR agonistic antibody corrects adaptive immune dysfunction in sepsis. Blood. 2007;110(10):3673–81.PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Popovic PJ, Zeh HJ 3rd, Ochoa JB. Arginine and immunity. J Nutr. 2007;137(6 Suppl 2):1681S–6S.PubMedCrossRefGoogle Scholar
  65. 65.
    Rosenthal MD, Moore FA. Persistent inflammatory, immunosuppressed, catabolic syndrome (PICS): a new phenotype of multiple organ failure. J Adv Nutr Hum Metab. 2015;1(1):e784.PubMedPubMedCentralGoogle Scholar
  66. 66.
    Rosenthal M, Gabrielli A, Moore F. The evolution of nutritional support in long term ICU patients: from multisystem organ failure to persistent inflammation immunosuppression catabolism syndrome. Minerva Anestesiol. 2016;82(1):84–96.PubMedGoogle Scholar
  67. 67.
    Cuenca AG, Moldawer LL. Myeloid-derived suppressor cells in sepsis: friend or foe? Intensive Care Med. 2012;38(6):928–30.PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Ochoa JB. Arginine deficiency caused by myeloid cells: importance, identification and treatment. Nestle Nutr Inst Workshop Ser. 2013;77:29–45.PubMedCrossRefGoogle Scholar
  69. 69.
    Rodriguez PC, Ochoa AC. Arginine regulation by myeloid derived suppressor cells and tolerance in cancer: mechanisms and therapeutic perspectives. Immunol Rev. 2008;222:180–91.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Fletcher M, Ramirez ME, Sierra RA, Raber P, Thevenot P, Al-Khami AA, Sanchez-Pino D, Hernandez C, Wyczechowska DD, Ochoa AC, Rodriguez PC. l-Arginine depletion blunts antitumor T-cell responses by inducing myeloid-derived suppressor cells. Cancer Res. 2015;75(2):275–83.PubMedCrossRefGoogle Scholar
  71. 71.
    Cuenca AG, Cuenca AL, Winfield RD, Joiner DN, Gentile L, Delano MJ, Kelly-Scumpia KM, Scumpia PO, Matheny MK, Scarpace PJ, Vila L, Efron PA, LaFace DM, Moldawer LL. Novel role for tumor-induced expansion of myeloid-derived cells in cancer cachexia. J Immunol. 2014;192(12):6111–9.PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Delano MJ, Thayer T, Gabrilovich S, Kelly-Scumpia KM, Winfield RD, Scumpia PO, Cuenca AG, Warner E, Wallet SM, Wallet MA, O'Malley KA, Ramphal R, Clare-Salzer M, Efron PA, Mathews CE, Moldawer LL. Sepsis induces early alterations in innate immunity that impact mortality to secondary infection. J Immunol. 2011;186(1):195–202.PubMedCrossRefGoogle Scholar
  73. 73.
    Pribis JP, Zhu X, Vodovotz Y, Ochoa JB. Systemic arginine depletion after a murine model of surgery or trauma. JPEN J Parenter Enteral Nutr. 2012;36(1):53–9.PubMedCrossRefGoogle Scholar
  74. 74.
    Zhu X, Herrera G, Ochoa JB. Immunosuppression and infection after major surgery: a nutritional deficiency. Crit Care Clin. 2010;26(3):491–500. ixPubMedCrossRefGoogle Scholar
  75. 75.
    de Jonge WJ, Hallemeesch MM, Kwikkers KL, Ruijter JM, de Gier-de Vries C, van Roon MA, Meijer AJ, Marescau B, de Deyn PP, Deutz NE, Lamers WH. Overexpression of arginase I in enterocytes of transgenic mice elicits a selective arginine deficiency and affects skin, muscle, and lymphoid development. Am J Clin Nutr. 2002;76(1):128–40.PubMedCrossRefGoogle Scholar
  76. 76.
    Ochoa JB, Bernard AC, O'Brien WE, Griffen MM, Maley ME, Rockich AK, Tsuei BJ, Boulanger BR, Kearney PA, Morris SM Jr. Arginase I expression and activity in human mononuclear cells after injury. Ann Surg. 2001;233(3):393–9.PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Luiking YC, Poeze M, Dejong CH, Ramsay G, Deutz NE. Sepsis: an arginine deficiency state? Crit Care Med. 2004;32(10):2135–45.PubMedCrossRefGoogle Scholar
  78. 78.
    Osland E, Hossain MB, Khan S, Memon MA. Effect of timing of pharmaconutrition (immunonutrition) administration on outcomes of elective surgery for gastrointestinal malignancies: a systematic review and meta-analysis. JPEN J Parenter Enteral Nutr. 2014;38(1):53–69.PubMedCrossRefGoogle Scholar
  79. 79.
    Laufenberg LJ, Pruznak AM, Navaratnarajah M, Lang CH. Sepsis-induced changes in amino acid transporters and leucine signaling via mTOR in skeletal muscle. Amino Acids. 2014;46(12):2787–98.PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Kazi AA, Pruznak AM, Frost RA, Lang CH. Sepsis-induced alterations in protein-protein interactions within mTOR complex 1 and the modulating effect of leucine on muscle protein synthesis. Shock. 2011;35(2):117–25.PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Vary TC, Lynch CJ. Nutrient signaling components controlling protein synthesis in striated muscle. J Nutr. 2007;137(8):1835–43.PubMedCrossRefGoogle Scholar
  82. 82.
    Vary TC. Acute oral leucine administration stimulates protein synthesis during chronic sepsis through enhanced association of eukaryotic initiation factor 4G with eukaryotic initiation factor 4E in rats. J Nutr. 2007;137(9):2074–9.PubMedCrossRefGoogle Scholar
  83. 83.
    Beugnet A, Wang X, Proud CG. Target of rapamycin (TOR)-signaling and RAIP motifs play distinct roles in the mammalian TOR-dependent phosphorylation of initiation factor 4E-binding protein 1. J Biol Chem. 2003;278(42):40717–22.PubMedCrossRefGoogle Scholar
  84. 84.
    Beugnet A, Tee AR, Taylor PM, Proud CG. Regulation of targets of mTOR (mammalian target of rapamycin) signalling by intracellular amino acid availability. Biochem J. 2003;372(Pt 2):555–66.PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Smith IJ, Lecker SH, Hasselgren PO. Calpain activity and muscle wasting in sepsis. Am J Physiol Endocrinol Metab. 2008;295(4):E762–71.PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Al-Majid S, Waters H. The biological mechanisms of cancer-related skeletal muscle wasting: the role of progressive resistance exercise. Biol Res Nurs. 2008;10(1):7–20.PubMedCrossRefGoogle Scholar
  87. 87.
    Callahan LA, Supinski GS. Sepsis-induced myopathy. Crit Care Med. 2009;37(10 Suppl):S354–67.PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Elijah IE, Branski LK, Finnerty CC, Herndon DN. The GH/IGF-1 system in critical illness. Best Pract Res Clin Endocrinol Metab. 2011;25(5):759–67.PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Puthucheary ZA, Rawal J, McPhail M, Connolly B, Ratnayake G, Chan P, Hopkinson NS, Phadke R, Dew T, Sidhu PS, Velloso C, Seymour J, Agley CC, Selby A, Limb M, Edwards LM, Smith K, Rowlerson A, Rennie MJ, Moxham J, Harridge SD, Hart N, Montgomery HE. Acute skeletal muscle wasting in critical illness. JAMA. 2013;310(15):1591–600.PubMedCrossRefGoogle Scholar
  90. 90.
    Marik PE, Zaloga GP. Early enteral nutrition in acutely ill patients: a systematic review. Crit Care Med. 2001;29(12):2264–70.PubMedCrossRefGoogle Scholar
  91. 91.
    Marik PE, Zaloga GP. Gastric versus post-pyloric feeding: a systematic review. Crit Care. 2003;7(3):R46–51.PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Marik PE, Pinsky M. Death by parenteral nutrition. Intensive Care Med. 2003;29(6):867–9.PubMedCrossRefGoogle Scholar
  93. 93.
    Singer P, Berger MM, Van den Berghe G, Biolo G, Calder P, Forbes A, Griffiths R, Kreyman G, Leverve X, Pichard C, ESPEN. ESPEN guidelines on parenteral nutrition: intensive care. Clin Nutr. 2009;28(4):387–400.PubMedCrossRefGoogle Scholar
  94. 94.
    Casaer MP, Mesotten D, Hermans G, Wouters PJ, Schetz M, Meyfroidt G, Van Cromphaut S, Ingels C, Meersseman P, Muller J, Vlasselaers D, Debaveye Y, Desmet L, Dubois J, Van Assche A, Vanderheyden S, Wilmer A, Van den Berghe G. Early versus late parenteral nutrition in critically ill adults. N Engl J Med. 2011;365(6):506–17.PubMedCrossRefGoogle Scholar
  95. 95.
    Casaer MP, Hermans G, Wilmer A, Van den Berghe G. Impact of early parenteral nutrition completing enteral nutrition in adult critically ill patients (EPaNIC trial): a study protocol and statistical analysis plan for a randomized controlled trial. Trials. 2011;12:21.PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    McClave SA, Martindale RG, Vanek VW, McCarthy M, Roberts P, Taylor B, Ochoa JB, Napolitano L, Cresci G, A.S.P.E.N. Board of Directors; American College of Critical Care Medicine; Society of Critical Care Medicine. 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. 2009;33(3):277–316.PubMedCrossRefGoogle Scholar
  97. 97.
    Heyland DK, Dhaliwal R, Drover JW, Gramlich L, Dodek P, Canadian Critical Care Clinical Practice Guidelines Committee. Canadian clinical practice guidelines for nutrition support in mechanically ventilated, critically ill adult patients. JPEN J Parenter Enteral Nutr. 2003;27(5):355–73.PubMedCrossRefGoogle Scholar
  98. 98.
    Wanten GJ, Calder PC. Immune modulation by parenteral lipid emulsions. Am J Clin Nutr. 2007;85(5):1171–84.PubMedCrossRefGoogle Scholar
  99. 99.
    Hart DW, Herndon DN, Klein G, Lee SB, Celis M, Mohan S, Chinkes DL, Wolf SE. Attenuation of posttraumatic muscle catabolism and osteopenia by long-term growth hormone therapy. Ann Surg. 2001;233(6):827–34.PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Herndon DN, Hart DW, Wolf SE, Chinkes DL, Wolfe RR. Reversal of catabolism by beta-blockade after severe burns. N Engl J Med. 2001;345(17):1223–9.PubMedCrossRefGoogle Scholar
  101. 101.
    Jeschke MG, Kulp GA, Kraft R, Finnerty CC, Mlcak R, Lee JO, Herndon DN. Intensive insulin therapy in severely burned pediatric patients: a prospective randomized trial. Am J Respir Crit Care Med. 2010;182(3):351–9.PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Jeschke MG, Chinkes DL, Finnerty CC, Kulp G, Suman OE, Norbury WB, Branski LK, Gauglitz GG, Mlcak RP, Herndon DN. Pathophysiologic response to severe burn injury. Ann Surg. 2008;248(3):387–401.PubMedPubMedCentralGoogle Scholar
  103. 103.
    Porro LJ, Herndon DN, Rodriguez NA, Jennings K, Klein GL, Mlcak RP, Meyer WJ, Lee JO, Suman OE, Finnerty CC. Five-year outcomes after oxandrolone administration in severely burned children: a randomized clinical trial of safety and efficacy. J Am Coll Surg. 2012;214(4):489–502. discussion 502–4PubMedPubMedCentralCrossRefGoogle Scholar
  104. 104.
    Serhan CN, Krishnamoorthy S, Recchiuti A, Chiang N. Novel anti-inflammatory—pro-resolving mediators and their receptors. Curr Top Med Chem. 2011;11(6):629–47.PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Serhan CN. Pro-resolving lipid mediators are leads for resolution physiology. Nature. 2014;510(7503):92–101.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Martin D. Rosenthal
    • 1
  • Cameron M. Rosenthal
    • 2
  • Amir Y. Kamel
    • 3
  • Frederick A. Moore
    • 1
  1. 1.Department of Surgery, College of MedicineUniversity of FloridaGainesvilleUSA
  2. 2.Department of PediatricsUniversity of FloridaGainesvilleUSA
  3. 3.Department of Pharmaceutical ServicesUniversity of FloridaGainesvilleUSA

Personalised recommendations