Effects of immunonutrition on biomarkers in traumatic brain injury patients in Malaysia: a prospective randomized controlled trial

Vineya Rai Hakumat Rai, Lee Fern Phang, Sheau Fung Sia, Amirah Amir, Jeyaganesh S Veerakumaran, Mustafa Kassim Abdulazez Kassim, Rafidah Othman, Pei Chien Tah, Pui San Loh, Mohamad Irfan Othman Jailani, Gracie Ong, Vineya Rai Hakumat Rai, Lee Fern Phang, Sheau Fung Sia, Amirah Amir, Jeyaganesh S Veerakumaran, Mustafa Kassim Abdulazez Kassim, Rafidah Othman, Pei Chien Tah, Pui San Loh, Mohamad Irfan Othman Jailani, Gracie Ong

Abstract

Background: Head injury is one of the top three diagnosis leading to intensive care unit (ICU) admission in Malaysia. There has been growing interest in using immunonutrition as a mode of modulating the inflammatory response to injury or infection with the aim of improving clinical outcome. The aim of the present study was to evaluate the effect of an immunonutrition on biomarkers (IL-6, glutathione, CRP, total protein and albumin) in traumatic brain injury patients.

Methods: Thirty six patients with head injury admitted to neurosurgical ICU in University Malaya Medical Centre were recruited for this study, over a 6-month period from July 2014 to January 2015. Patients were randomized to receive either an immunonutrition (Group A) or a standard (Group B) enteral feed. Levels of biomarkers were measured at day 1, 5 and 7 of enteral feeding.

Results: Patients in Group A showed significant reduction of IL-6 at day 5 (p < 0.001) with concurrent rise in glutathione levels (p = 0.049). Patients in Group A also demonstrated a significant increase of total protein level at the end of the study (day 7).

Conclusion: These findings indicate the potential of immunonutrition reducing cytokines and increasing antioxidant indices in patients with TBI. However, further studies incorporating patient outcomes are needed to determine its overall clinical benefits.

Trial registration: National Medical Research Register (NMRR) ID: 14-1430-23,171. ClinicalTrials.gov identifier: NCT03166449 .

Keywords: Biomarkers; Cytokines; Enteral nutrition; Immunonutrition; Neomune; Traumatic brain injury.

References

    1. MOH: National trauma database January 2009 to December 2009 fourth report. 2011.
    1. Health Facts 2015 [].
    1. Hyder AA, Wunderlich CA, Puvanachandra P, Gururaj G, Kobusingye OC. The impact of traumatic brain injuries: a global perspective. NeuroRehabilitation. 2007;22(5):341–353.
    1. MOH: Malaysian registry of intensive care report for 2013. Malaysian Registry of Intensive Care, Clinical Research Centre, Ministry of Health Malaysia. 2013. .
    1. Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med. 2006;3(11):e442. doi: 10.1371/journal.pmed.0030442.
    1. Clifton GL, Robertson CS, Grossman RG, Hodge S, Foltz R, Garza C. The metabolic response to severe head injury. J Neurosurg. 1984;60(4):687–696. doi: 10.3171/jns.1984.60.4.0687.
    1. Clifton GL, Robertson CS, Choi SC. Assessment of nutritional requirements of head-injured patients. J Neurosurg. 1986;64(6):895–901. doi: 10.3171/jns.1986.64.6.0895.
    1. Young B, Ott L, Norton J, Tibbs P, Rapp R, McClain C, Dempsey R. Metabolic and nutritional sequelae in the non-steroid treated head injury patient. Neurosurgery. 1985;17(5):784–791. doi: 10.1227/00006123-198511000-00010.
    1. Alberda C, Gramlich L, Jones N, Jeejeebhoy K, Day AG, Dhaliwal R, Heyland DK. The relationship between nutritional intake and clinical outcomes in critically ill patients: results of an international multicenter observational study. Intensive Care Med. 2009;35(10):1728–1737. doi: 10.1007/s00134-009-1567-4.
    1. Wang X, Dong Y, Han X, Qi XQ, Huang CG, Hou LJ. Nutritional support for patients sustaining traumatic brain injury: a systematic review and meta-analysis of prospective studies. PLoS One. 2013;8(3):e58838. doi: 10.1371/journal.pone.0058838.
    1. Rosenfeld JV, Maas AI, Bragge P, Morganti-Kossmann MC, Manley GT, Gruen RL. Early management of severe traumatic brain injury. Lancet. 2012;380(9847):1088–1098. doi: 10.1016/S0140-6736(12)60864-2.
    1. Grimble R. Nutritional modulation of immune function. Proc Nutr Soc. 2001;60(03):389–397. doi: 10.1079/PNS2001102.
    1. Peterik A, Milbrandt EB, Darby JM. Immunonutrition in critical illness: still fishing for the truth. Crit Care. 2009;13(3):1–3. doi: 10.1186/cc7899.
    1. De Arruda ISF, de Aguilar-Nascimento JE. Benefits of early enteral nutrition with glutamine and probiotics in brain injury patients. Clin Sci. 2004;106(3):287–292. doi: 10.1042/CS20030251.
    1. Briassoulis G, Filippou O, Kanariou M, Papassotiriou I, Hatzis T. Temporal nutritional and inflammatory changes in children with severe head injury fed a regular or an immune-enhancing diet: a randomized, controlled trial. Pediatr Crit Care Med. 2006;7(1):56–62. doi: 10.1097/01.PCC.0000192339.44871.26.
    1. Khorana J, Rerkasem K, Apichartpiyakul C, Sakonwasun C, Watcharasalcslip W, Waniyapong T, Norasethtada T, Jittawatanarak K. Immunonutrition and cytokine response in patients with head injury. J Med Assoc Thail. 2009;92(2):188.
    1. Marik PE, Zaloga GP. Immunonutrition in critically ill patients: a systematic review and analysis of the literature. Intensive Care Med. 2008;34(11):1980–1990. doi: 10.1007/s00134-008-1213-6.
    1. Serhan CN, Chiang N, Van Dyke TE. Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators. Nat Rev Immunol. 2008;8(5):349–361. doi: 10.1038/nri2294.
    1. Calder PC. n-3 Polyunsaturated fatty acids, inflammation, and inflammatory diseases. Am J Clin Nutr. 2006;83:S1505–S1519.
    1. Hasadsri L, Wang BH, Lee JV, Erdman JW, Llano DA, Barbey AK, Wszalek T, Sharrock MF, Wang H. Omega-3 fatty acids as a putative treatment for traumatic brain injury. J Neurotrauma. 2013;30(11):897–906. doi: 10.1089/neu.2012.2672.
    1. Bullock MR, Povlishock JT. Guidelines for the management of severe traumatic brain injury. Editor’s Commentary. J Neurotrauma. 2007;24(Suppl 1):2.
    1. Harris JA, Benedict FG. A biometric study of human basal metabolism. Proc Natl Acad Sci. 1918;4(12):370–373. doi: 10.1073/pnas.4.12.370.
    1. Roza AM, Shizgal HM. The Harris Benedict equation reevaluated: resting energy requirements and the body cell mass. Am J Clin Nutr. 1984;40(1):168–182.
    1. Painter TJ, Rickerds J, Alban RF. Immune enhancing nutrition in traumatic brain injury–A preliminary study. Int J Surg. 2015;21:70–74. doi: 10.1016/j.ijsu.2015.07.008.
    1. McClave SA, Martindale RG, Vanek VW, McCarthy M, Roberts P, Taylor B, Ochoa JB, Napolitano L, Cresci G. 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 (ASPEN) J Parenter Enter Nutr. 2009;33(3):277–316. doi: 10.1177/0148607109335234.
    1. Wu GH, Zhang YW, Wu ZH. Modulation of postoperative immune and inflammatory response by immune-enhancing enteral diet in gastrointestinal cancer patients. World J Gastroenterol. 2001;7(3):357–362. doi: 10.3748/wjg.v7.i3.357.
    1. Uno H, Furukawa K, Suzuki D, Shimizu H, Ohtsuka M, Kato A, et al. Immunonutrition suppresses acute inflammatory responses through modulation of resolvin E1 in patients undergoing major hepatobiliary resection. Surgery. 2016;
    1. Frugier T, Morganti-Kossmann MC, O’Reilly D, McLean CA. In situ detection of inflammatory mediators in post mortem human brain tissue after traumatic injury. J Neurotrauma. 2010;27(3):497–507. doi: 10.1089/neu.2009.1120.
    1. Kossmann T, Hans VH, Imhof HG, Stocker R, Grob P, Trentz O, Morganti-Kossmann MC. Intrathecal and serum interleukin-6 and the acute-phase response in patients with severe traumatic brain injuries. Shock. 1995;4(5):311–317. doi: 10.1097/00024382-199511000-00001.
    1. Lenzlinger PM, Morganti-Kossmann M-C, Laurer HL, McIntosh TK. The duality of the inflammatory response to traumatic brain injury. Mol Neurobiol. 2001;24(1–3):169–181.
    1. Kalabalikis P, Papazoglou K, Gouriotis D, Papadopoulos N, Kardara M, Papageorgiou F, Papadatos J. Correlation between serum IL-6 and CRP levels and severity of head injury in children. Intensive Care Med. 1999;25(3):288–292. doi: 10.1007/s001340050837.
    1. Arand M, Melzner H, Kinzl L, Bruckner UB, Gebhard F. Early inflammatory mediator response following isolated traumatic brain injury and other major trauma in humans. Langenbeck's Arch Surg. 2001;386:241–248. doi: 10.1007/s004230100204.
    1. Woiciechowsky C, Schoning B, Cobanov J, Lanksch WR, Volk HD, Docke WD. Early IL-6 plasma concentrations correlate with severity of brain injury and pneumonia in brain-injured patients. J Trauma. 2002;5:339–45.
    1. Lloyd E, Somera-Molina K, Van Eldik LJ, Watterson DM, Wainwright MS. Suppression of acute proinflammatory cytokine and chemokine upregulation by post-injury administration of a novel small molecule improves long-term neurologic outcome in a mouse model of traumatic brain injury. J Neuroinflammation. 2008;5(1):28. doi: 10.1186/1742-2094-5-28.
    1. Bracken MB. CRASH (corticosteroid randomization after significant head injury trial): landmark and storm warning. Neurosurgery. 2005;57(6):1300–1302. doi: 10.1227/01.NEU.0000187320.71967.59.
    1. Ley EJ, Clond MA, Singer MB, Shouhed D, Salim A. IL6 deficiency affects function after traumatic brain injury. J Surg Res. 2011;170(2):253–256. doi: 10.1016/j.jss.2011.03.006.
    1. Yang SH, Gangidine M, Pritts TA, Goodman MD, Lentsch AB. Interleukin 6 mediates neuroinflammation and motor coordination deficits after mild traumatic brain injury and brief hypoxia in mice. Shock. 2013;40(6):471. doi: 10.1097/SHK.0000000000000037.
    1. Marik PE. Arginine: too much of a good thing may be bad! Crit Care Med. 2006;34(11):2844–2847. doi: 10.1097/01.CCM.0000242922.42660.91.
    1. Flaring UB, Rooyackers OE, Wernerman J, Hammarqvist F. Glutamine attenuates post-traumatic glutathione depletion in human muscle. Clin Sci (Lond) 2003;104(3):275–282. doi: 10.1042/cs1040275.
    1. Adesanya TA, Sullivan RC, Stawicki SP, Evans DC. Nutrition in Traumatic Brain Injury: Focus on the Immune Modulating Supplements. 2014.
    1. Petersen SR, Jeevanandam M, Holaday NJ, Lubhan CL. Arterial-jugular vein free amino acid levels in patients with head injuries: important role of glutamine in cerebral nitrogen metabolism. J Trauma. 1996;41(4):687–694. doi: 10.1097/00005373-199610000-00015.
    1. Platt SR. The role of glutamate in central nervous system health and disease--a review. Vet J. 2007;173(2):278–286. doi: 10.1016/j.tvjl.2005.11.007.
    1. van Landeghem FK, Weiss T, Oehmichen M, von Deimling A. Decreased expression of glutamate transporters in astrocytes after human traumatic brain injury. J Neurotrauma. 2006;23(10):1518–1528. doi: 10.1089/neu.2006.23.1518.
    1. Zlotnik A, Gurevich B, Tkachov S, Maoz I, Shapira Y, Teichberg VI. Brain neuroprotection by scavenging blood glutamate. Exp Neurol. 2007;203(1):213–220. doi: 10.1016/j.expneurol.2006.08.021.
    1. Cook AM, Peppard A, Magnuson B. Nutrition considerations in traumatic brain injury. Nutr Clin Pract. 2008;23(6):608–620. doi: 10.1177/0884533608326060.
    1. Fruin AH, Taylon C, Pettis MS. Caloric requirements in patients with severe head injuries. Surg Neurol. 1986;25(1):25–28. doi: 10.1016/0090-3019(86)90109-6.
    1. Li P-A, Liu G-J, He QP, Floyd RA, Siesjö BK. Production of hydroxyl free radical by brain tissues in hyperglycemic rats subjected to transient forebrain ischemia. Free Radic Biol Med. 1999;27(9):1033–1040. doi: 10.1016/S0891-5849(99)00152-5.
    1. Diaz-Parejo P, Ståhl N, Xu W, Reinstrup P, Ungerstedt U, Nordström C-H. Cerebral energy metabolism during transient hyperglycemia in patients with severe brain trauma. Intensive Care Med. 2003;29(4):544–550. doi: 10.1007/s00134-003-1669-3.
    1. O'Dwyer ST, Smith RJ, Hwang TL, Wilmore DW. Maintenance of small bowel mucosa with glutamine-enriched parenteral nutrition. J Parenter Enter Nutr. 1989;13(6):579–585. doi: 10.1177/0148607189013006579.
    1. Houdijk AP, Van Leeuwen PA, Boermeester MA, Van Lambalgen T, Teerlink T, Flinkerbusch EL, Sauerwein HP, Wesdorp RI. Glutamine-enriched enteral diet increases splanchnic blood flow in the rat. Am J Phys. 1994;267(6 Pt 1):G1035–G1040.
    1. Yang DL, Xu JF. Effect of dipeptide of glutamine and alanine on severe traumatic brain injury. Chin J Traumatol. 2007;10(3):145–149.
    1. Marik PE, Zaloga GP. Immunonutrition in High-Risk surgical patients a systematic review and analysis of the literature. J Parenter Enter Nutr. 2010;34(4):378–386. doi: 10.1177/0148607110362692.
    1. Forget P, Echeverria G, Giglioli S, Bertrand B, Nikis S, Lechat J-P, De Kock M. Biomarkers in immunonutrition programme, is there still a need for new ones? A brief review. Ecancermedicalscience. 2015;9:546.
    1. Aussel C, Cynober L. Is serum albumin a marker of nutritional status? Nutr Clin Metab. 2013;27(1):28–33. doi: 10.1016/j.nupar.2012.12.003.
    1. Heyland DK, Novak F, Drover JW, Jain M, Su X, Suchner U. Should immunonutrition become routine in critically ill patients? A systematic review of the evidence. JAMA. 2001;286(8):944–953. doi: 10.1001/jama.286.8.944.
    1. Roehl K. Immunonutrition in 2016: Benefit, Harm or Neither? Pract Gastroenterol. 2016;154:27.
    1. McCowen KC, Bistrian BR. Immunonutrition: problematic or problem solving? Am J Clin Nutr. 2003;77(4):764–770.
    1. Beale RJ, Bryg DJ, Bihari DJ. Immunonutrition in the critically ill: a systematic review of clinical outcome. Crit Care Med. 1999;27(12):2799–2805. doi: 10.1097/00003246-199912000-00032.
    1. Montejo JC, Zarazaga A, Lόpez-Martínez J, Urrútia G, Roqué M, Blesa AL, Celaya S, Conejero R, Galbán C, de Lorenzo AG, Grau T. Immunonutrition in the intensive care unit. A systematic review and consensus statement. Clin Nutr. 2003;22(3):221–233. doi: 10.1016/S0261-5614(03)00007-4.
    1. Chen QH, Yang Y, He HL, Xie JF, Cai SX, Liu AR, Wang HL, Qiu HB. The effect of glutamine therapy on outcomes in critically ill patients: a meta-analysis of randomized controlled trials. Crit Care. 2014;18(1):R8. doi: 10.1186/cc13185.
    1. Rathmacher JA, Nissen S, Panton L, Clark RH, May PE, Barber AE, D'Olimpio J, Abumrad NN. Supplementation with a combination of β-hydroxy-β-methylbutyrate(HMB), arginine, and glutamine is safe and could improve hematological parameters. J Parenter Enter Nutr. 2003;28:65–75. doi: 10.1177/014860710402800265.
    1. Heyland D, Dhaliwal R. Immunonutrition in the critically ill: from old approaches to new paradigms. Intensive Care Med. 2005;31:501–503. doi: 10.1007/s00134-005-2590-8.
    1. Jones NE, Heyland DK. Pharmaconutrition: a new emerging paradigm. Curr Opin Gastroenterol. 2008;24:215–222. doi: 10.1097/MOG.0b013e3282f4cdd8.
    1. Sparo M, Sanchez Bruni SF. Approach to optimise the treatment of bacterial infections: combined antimicrobial therapy with enhancers of innate immunity. Clin Exp Pharmacol. 2012;2:e106.
    1. Vincent JL. Search for effective immunomodulating strategies against sepsis. Lancet. 1998;351(9107):922–923. doi: 10.1016/S0140-6736(05)60595-8.
    1. Dellinger RP. Severe sepsis trials: why have they failed? Minerva Anestsesiol. 1999;65(6):340–345.
    1. Cohen J. Adjunctive therapy in sepsis: a critical analysis of the clinical trial programme. Br Med Bull. 1999;55(1):212–225. doi: 10.1258/0007142991902222.

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