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Effect of Preoperative Administration of Oral Arginine and Glutamine in Patients with Enterocutaneous Fistula Submitted to Definitive Surgery: a Prospective Randomized Trial

  • Original Article
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Journal of Gastrointestinal Surgery Aims and scope

Abstract

Background

The use of glutamine and arginine has shown several advantages in postoperative outcomes in patients after gastrointestinal surgery. We determined the effects of its use in patients with enterocutaneous fistula after operative treatment.

Patients and Methods

Forty patients with enterocutaneous fistula were randomly assigned to one of two groups. The control group received the standard medical care while the patients of the experimental group were supplemented with enteral administration of 4.5 g of arginine and 10 g of glutamine per day for 7 days prior to the surgery. The primary outcome variable was the recurrence of the fistula and the secondary outcomes were preoperative and postoperative serum concentrations of interleukin 6 and C-reactive protein and postoperative infectious complications.

Results

Twenty patients were assigned to each group. The fistula recurred in two patients (10%) of the experimental group and in nine patients (45%) of the control group (P < 0.001). We found a total of 13 infectious complications in six patients of the control group (all with fistula recurrence) and none in the experimental group. Mean preoperative serum concentrations of interleukin 6 and C-reactive protein were lower in patients from the experimental group. In addition, these levels were lower in patients who had recurrence if compared to patients that did not recur.

Conclusion

Preoperative administration of oral arginine and glutamine could be valuable in the postoperative recovery of patients with enterocutaneous fistulas submitted to definitive surgery.

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References

  1. Schecter WP, Hirshberg A, Chang DS, Harris HW, Napolitano LM, Wexner SD, et al. Enteric fistulas: principles of management. J Am Coll Surg 2009;209(4):484–91.

    PubMed  Google Scholar 

  2. Dudrick SJ, Maharaj AR, McKelvey AA. Artificial nutritional support in patients with gastrointestinal fistulas. World J Surg 1999;23(6):570–6.

    CAS  PubMed  Google Scholar 

  3. Soeters PB, Ebeid AM, Fischer JE. Review of 404 patients with gastrointestinal fistulas. Impact of parenteral nutrition. Ann Surg 1979;190(2):189–202.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Campos AC, Andrade DF, Campos GM, Matias JE, Coelho JC. A multivariate model to determine prognostic factors in gastrointestinal fistulas. J Am Coll Surg 1999;188(5):483–90.

    CAS  PubMed  Google Scholar 

  5. Owen RM, Love TP, Perez SD, Srinivasan JK, Sharma J, Pollock JD, et al. Definitive surgical treatment of enterocutaneous fistula: outcomes of a 23-year experience. JAMA Surg 2013;148(2):118–26.

    PubMed  Google Scholar 

  6. Teixeira PGR, Inaba K, Dubose J, Salim A, Brown C, Rhee P, et al. Enterocutaneous fistula complicating trauma laparotomy: a major resource burden. Am Surg 2009;75(1):30–2.

    PubMed  Google Scholar 

  7. Martinez JL, Luque-de-Leon E, Mier J, Blanco-Benavides R, Robledo F. Systematic management of postoperative enterocutaneous fistulas: factors related to outcomes. World J Surg 2008;32(3):436–43; discussion 444.

    PubMed  Google Scholar 

  8. Marinis A, Gkiokas G, Anastasopoulos G, Fragulidis G, Theodosopoulos T, Kotsis T, et al. Surgical techniques for the management of enteroatmospheric fistulae. Surg Infect (Larchmt) 2009;10(1):47–52.

    Google Scholar 

  9. Berry SM, Fischer JE. Classification and pathophysiology of enterocutaneous fistulas. Surg Clin North Am 1996;76(5):1009–18.

    CAS  PubMed  Google Scholar 

  10. Jones NE, Heyland DK. Pharmaconutrition: a new emerging paradigm. Curr Opin Gastroenterol 2008;24(2):215–22.

    CAS  PubMed  Google Scholar 

  11. 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.

    PubMed  Google Scholar 

  12. 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.e1.

    PubMed  Google Scholar 

  13. Braga M, Gianotti L, Vignali A, Carlo VD. Preoperative oral arginine and n-3 fatty acid supplementation improves the immunometabolic host response and outcome after colorectal resection for cancer. Surgery 2002;132(5):805–14.

    PubMed  Google Scholar 

  14. Cerantola Y, Hübner M, Grass F, Demartines N, Schäfer M. Immunonutrition in gastrointestinal surgery. Br J Surg 2011;98(1):37–48.

    CAS  PubMed  Google Scholar 

  15. Probst P, Ohmann S, Klaiber U, Hüttner FJ, Billeter AT, Ulrich A, et al. Meta-analysis of immunonutrition in major abdominal surgery. Br J Surg 2017;104(12):1594–608.

    CAS  PubMed  Google Scholar 

  16. Wong CS, Aly EH. The effects of enteral immunonutrition in upper gastrointestinal surgery: A systematic review and meta-analysis. Int J Surg 2016;29:137–50.

    PubMed  Google Scholar 

  17. de Aguilar-Nascimento JE, Caporossi C, Dock-Nascimento DB, de Arruda IS, Moreno K, Moreno W. Oral glutamine in addition to parenteral nutrition improves mortality and the healing of high-output intestinal fistulas. Nutr Hosp 2007;22(6):672–6.

    PubMed  Google Scholar 

  18. Parli SE, Pfeifer C, Oyler DR, Magnuson B, Procter LD. Redefining «bowel regimen»: Pharmacologic strategies and nutritional considerations in the management of small bowel fistulas. Am J Surg 2018;216(2):351–8.

    PubMed  Google Scholar 

  19. Martinez JL, Luque-de-León E, Ballinas-Oseguera G, Mendez JD, Juárez-Oropeza MA, Román-Ramos R. Factors predictive of recurrence and mortality after surgical repair of enterocutaneous fistula. J Gastrointest Surg 2012;16(1):156–63; discussion 163-164.

    PubMed  Google Scholar 

  20. Lynch AC, Delaney CP, Senagore AJ, Connor JT, Remzi FH, Fazio VW. Clinical outcome and factors predictive of recurrence after enterocutaneous fistula surgery. Ann Surg 2004;240(5):825–31.

    PubMed  PubMed Central  Google Scholar 

  21. Brenner M, Clayton JL, Tillou A, Hiatt JR, Cryer HG. Risk factors for recurrence after repair of enterocutaneous fistula. Arch Surg 2009;144(6):500–5.

    PubMed  Google Scholar 

  22. Senkal M. Outcome and Cost-effectiveness of Perioperative Enteral Immunonutrition in Patients Undergoing Elective Upper Gastrointestinal Tract Surgery: A Prospective Randomized Study. Archives of Surgery 1999;134(12):1309.

    CAS  PubMed  Google Scholar 

  23. Braga M. Perioperative Immunonutrition in Patients Undergoing Cancer Surgery: Results of a Randomized Double-blind Phase 3 Trial. Archives of Surgery 1999;134(4):428.

    CAS  PubMed  Google Scholar 

  24. Marano L, Porfidia R, Pezzella M, Grassia M, Petrillo M, Esposito G, et al. Clinical and immunological impact of early postoperative enteral immunonutrition after total gastrectomy in gastric cancer patients: a prospective randomized study. Ann Surg Oncol 2013;20(12):3912–8.

    PubMed  Google Scholar 

  25. Davis JS, Anstey NM. Is plasma arginine concentration decreased in patients with sepsis? A systematic review and meta-analysis. Crit Care Med 2011;39(2):380–5.

    CAS  PubMed  Google Scholar 

  26. Souba WW, Herskowitz K, Klimberg VS, Salloum RM, Plumley DA, Flynn TC, et al. The effects of sepsis and endotoxemia on gut glutamine metabolism. Ann Surg 1990;211(5):543–9; discussion 549-551.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Donmez R, Oren D, Ozturk G, Kisaoglu A, Ozogul B, Atamanalp SS. The combined effects of glutamine and growth hormone on intestinal anastomosis in the rat intra-abdominal sepsis model. J Surg Res 2013;182(1):142–5.

    CAS  PubMed  Google Scholar 

  28. Kusabbi R, Kismet K, Kuru S, Barlas AM, Duymus ME, Hasanoglu A, et al. Effects of the Oral Nutritional Supplement Containing Arginine, Glutamine, and Hydroxymethylbutyrate (Abound®) on Healing of Colonic Anastomoses in Rats. Indian J Surg 2015;77(Suppl 3):1242–7.

    PubMed  PubMed Central  Google Scholar 

  29. Sapidis N, Tziouvaras C, Ioannidis O, Kalaitsidou I, Botsios D. The effect of glutamine and synbiotics on the healing of colonic anastomosis. Rev Esp Enferm Dig 2014;106(4):255–62.

    CAS  PubMed  Google Scholar 

  30. Vermeulen MAR, van de Poll MCG, Ligthart-Melis GC, Dejong CHC, van den Tol MP, Boelens PG, et al. Specific amino acids in the critically ill patient--exogenous glutamine/arginine: a common denominator? Crit Care Med 2007;35(9 Suppl):S568–576.

    CAS  PubMed  Google Scholar 

  31. Chow O, Barbul A. Immunonutrition: Role in Wound Healing and Tissue Regeneration. Adv Wound Care (New Rochelle) 2014;3(1):46–53.

    Google Scholar 

  32. Akbarshahi H, Andersson B, Nordén M, Andersson R. Perioperative nutrition in elective gastrointestinal surgery--potential for improvement? Dig Surg 2008;25(3):165–74.

    CAS  PubMed  Google Scholar 

  33. Déchelotte P, Darmaun D, Rongier M, Hecketsweiler B, Rigal O, Desjeux JF. Absorption and metabolic effects of enterally administered glutamine in humans. Am J Physiol 1991;260(5 Pt 1):G677–682.

    PubMed  Google Scholar 

  34. Tangphao O, Grossmann M, Chalon S, Hoffman BB, Blaschke TF. Pharmacokinetics of intravenous and oral L-arginine in normal volunteers. Br J Clin Pharmacol 1999;47(3):261–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Evenson AR, Fischer JE. Current management of enterocutaneous fistula. J Gastrointest Surg 2006;10(3):455–64.

    PubMed  Google Scholar 

  36. Jawa RS, Anillo S, Huntoon K, Baumann H, Kulaylat M. Interleukin-6 in surgery, trauma, and critical care part II: clinical implications. J Intensive Care Med 2011;26(2):73–87.

    PubMed  PubMed Central  Google Scholar 

  37. Bozza FA, Salluh JI, Japiassu AM, Soares M, Assis EF, Gomes RN, et al. Cytokine profiles as markers of disease severity in sepsis: a multiplex analysis. Crit Care 2007;11(2):R49.

    PubMed  PubMed Central  Google Scholar 

  38. Singh B, Haffejee AA, Allopi L, Moodley J. Surgery for high-output small bowel enterocutaneous fistula: a 30-year experience. Int Surg 2009;94(3):262–8.

    CAS  PubMed  Google Scholar 

  39. Woeste G, Müller C, Bechstein WO, Wullstein C. Increased serum levels of C-reactive protein precede anastomotic leakage in colorectal surgery. World J Surg 2010;34(1):140–6.

    PubMed  Google Scholar 

  40. Lagoutte N, Facy O, Ravoire A, Chalumeau C, Jonval L, Rat P, et al. C-reactive protein and procalcitonin for the early detection of anastomotic leakage after elective colorectal surgery: pilot study in 100 patients. J Visc Surg 2012;149(5):e345–349.

    CAS  PubMed  Google Scholar 

  41. Warschkow R, Beutner U, Steffen T, Müller SA, Schmied BM, Güller U, et al. Safe and early discharge after colorectal surgery due to C-reactive protein: a diagnostic meta-analysis of 1832 patients. Ann Surg 2012;256(2):245–50.

    PubMed  Google Scholar 

  42. Martinez JL, Luque-de-León E, Ferat-Osorio E, Estrada-Castellanos A. Predictive value of preoperative serum C-reactive protein for recurrence after definitive surgical repair of enterocutaneous fistula. Am J Surg 2017;213(1):105–11.

    PubMed  Google Scholar 

  43. Wernerman J. Clinical use of glutamine supplementation. J Nutr 2008;138(10):2040S–2044S.

    CAS  PubMed  Google Scholar 

  44. Weitzel L-RB, Wischmeyer PE. Glutamine in critical illness: the time has come, the time is now. Crit Care Clin 2010;26(3):515–25, ix-x.

    CAS  PubMed  Google Scholar 

  45. Jayarajan S, Daly JM. The relationships of nutrients, routes of delivery, and immunocompetence. Surg Clin North Am 2011;91(4):737–53, vii.

    PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of General and Gastrointestinal Surgery, UMAE Hospital de Especialidades – Centro Médico Nacional Siglo XXI (Instituto Mexicano del Seguro Social, IMSS), Mexico City, Mexico

    Jose L. Martinez, Luis Manuel Souza-Gallardo & Eduardo Ferat-Osorio

  2. Programa de Doctorado en Ciencias Biológicas, Universidad Autónoma Metropolitana-Iztapalapa, Mexico City, Mexico

    Jose L. Martinez

  3. Unidad de Investigación Médica en Inmunoquímica, UMAE Hospital de Especialidades – Centro Médico Nacional Siglo XXI (Instituto Mexicano del Seguro Social, IMSS), Av.Cuauhtémoc 330, 3er piso, Colonia Doctores, Delegación Cuauhtémoc, 06720, Mexico City, Mexico

    Ilka Bosco-Garate & Eduardo Ferat-Osorio

  4. Unidad de Investigación Médica en Enfermedades Metabólicas, UMAE Hospital de Especialidades, Centro Médico Nacional Siglo XXI (Instituto Mexicano del Seguro Social, IMSS), Mexico City, Mexico

    José D. Méndez

  5. Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico

    Marco A. Juárez-Oropeza

  6. División Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana-Iztapalapa, Mexico City, Mexico

    Ruben Román-Ramos

Authors
  1. Jose L. Martinez
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  2. Ilka Bosco-Garate
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  4. José D. Méndez
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  5. Marco A. Juárez-Oropeza
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  7. Eduardo Ferat-Osorio
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Contributions

Study conception and design: Martinez, Mendez, Roman, Juarez, Ferat

Acquisition of data: Martinez, Bosco, Souza, Ferat

Analysis and interpretation of data: Martinez, Bosco, Souza, Mendez, Roman, Juarez, Ferat

Drafting of manuscript: Martinez, Souza, Ferat

Critical revision: Martinez, Bosco, Souza, Mendez, Juarez, Roman, Ferat

Final approval: Martinez, Bosco, Souza, Mendez, Juarez, Roman, Ferat

All authors (Martinez, Bosco, Souza, Mendez, Juarez, Roman, Ferat) agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved

Corresponding author

Correspondence to Eduardo Ferat-Osorio.

Ethics declarations

The study was reviewed and approved by the Hospital de Especialidades de Centro Medico Nacional SXXI Institutional Review Board (R-2010-3601-98).

Conflict of Interest

The authors declare that they have no conflict of interest.

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Martinez, J.L., Bosco-Garate, I., Souza-Gallardo, L.M. et al. Effect of Preoperative Administration of Oral Arginine and Glutamine in Patients with Enterocutaneous Fistula Submitted to Definitive Surgery: a Prospective Randomized Trial. J Gastrointest Surg 24, 426–434 (2020). https://doi.org/10.1007/s11605-018-04099-4

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