Malnütrisyonu Olan ve Malnütrisyonu Olmayan 3-36 Ay Arası Akut İshalli Çocuklarda Glutamin Tedavisinin Etkinliği

Öz

Amaç: Beş yaş altı çocuklarda önemli bir morbidite nedeni olan ishalli hastalıklar önemini korumaya devam etmektedir. Uygun şekilde tedavi edilmeyen akut ishal olgularında malnütrisyon gelişebilmekte ve ishal-malnütrisyon arasındaki kısır döngü iyileşme sürecini uzatmaktadır. İshal tedavisinde beslenmenin devam edilmesi, dehidratasyonun önlenmesi ve çinko gibi fonksiyonel besinlerin kullanılması önerilmektedir. Son yıllarda ağır hastaların beslenmesinde glutamin, arjinin, omega-3 yağ asitleri gibi immün besinlerin kullanımı artmıştır. Çalışmamızda malnütrisyonu olan ve malnütrisyonu olmayan 3-36 ay arası akut ishalli çocuklarda glutamin verilmesinin ishal sıklığına, süresine ve kilo alımına etkisini değerlendirmeyi amaçladık. 
Materyal ve metod: Prospektif, randomize plasebo-kontrollü ve çift kör olarak yürütülen bu çalışmaya 21 Mayıs 2012- 24 Mart 2013 tarihleri arasında Tıp Fakültesi Hastanesi Çocuk Sağlığı ve Hastalıkları polikliniklerine başvuran yaşları 3-36 ay arasındaki, akut ishali olan 80 hasta dahil edildi.   Olgular malnütrisyonu olan ve olmayan olarak iki gruba ayrıldı. Her bir grubu glutamin ve plasebo alan 20’şer hasta oluşturdu. Çalışma grubuna 300 mg/kg/gün glutamin, kontrol grubuna ise plasebo yedi gün oral yolla verildi. Üç ay boyunca aylık olarak yapılan takiplerinde boy ve kilo değerleri ölçüldü. Geçirmiş oldukları enfeksiyon hastalıkları sorgulandı. 
Bulgular: Malnütrisyonu olan ve malnütrisyonu olmayan olguların demografik ö zellikleri a rasında i statistiksel o larak f ark yoktu. Gruplar arasında günlük ishal sayısı, başvuru sonrası ve toplam ishal süresi benzerdi, istatistiksel fark saptanmadı. Malnütrisyonu olan ve olmayan gruplarda bir yaş altındaki ve bir yaş üzerindeki olgularla; bir yaş altındaki ve bir yaş üzerindeki glutamin ve plasebo alanlar ve anne sütü alan ve almayan olguların (glutamin (n=40) ve plasebo(n=40)) başvuru sonrası ishal süreleri arasında da istatistiksel olarak fark yoktu. Takip döneminde kilo alımının da malnütrisyonu olan ve olmayan gruplarda benzer olduğu görüldü. Glutamin takviyesi olguların kilo alımını ve enfeksiyon sıklığını da etkilemedi.
Sonuç: Sonuç olarak hem malnütrisyonu olan ve olmayan akut ishalli olgularda hem de malnütrisyonu olup olmadığına bakılmadan yapılan değerlendirmede glutamin takviyesinin günlük ortalama ishal sayısını, başvuru sonrası ve toplam ishal süresi ile kilo alımını etkilemediği görüldü.

Anahtar Kelimeler

• Akut ishal
• Glutamin
• Malnütrisyon

Efficacy of Glutamine Therapy in Pediatric Acute Diarrhea Patients Aged 3-36 Months With and Without Malnutrition

Öz

Background: Diarrheal diseases, which remain a significant cause of morbidity globally, continue to be important in children under five y ears o f a ge. M alnutrition m ay d evelop i n c ases of acute diarrhea not treated appropriately, and the vicious cycle between diarrhea and malnutrition prolongs the recovery process. Continuation of nutrition, prevention of dehydration, and the use of functional nutrients such as zinc is recommended in the treatment of diarrhea. In recent years, the use of immune nutrients such as glutamine, arginine, and omega-3 fatty acids has increased in the nutrition of severely ill patients. In our study, we aimed to evaluate the effect o f g lutamine a dministration on diarrhea frequency, duration, and weight gain in 3-36 month old children with acute diarrhea, both with and without malnutrition. Materials and Methods: In this prospective, randomized, placebo-controlled, and double-blind study, 80 patients aged 3-36 months with acute diarrhea who were admitted to Faculty of Medicine Pediatrics outpatient clinics between 21 May 2012 and 24 March 2013 were included. The patients were divided into two groups based on the presence or absence of malnutrition. Each group consisted of 20 patients receiving glutamine and 20 receiving placebo. The study group received 300 mg/kg/day of glutamine, and the control group received a placebo orally for seven days. Height and weight values were measured at monthly follow-up visits for three months. Past infectious diseases were questioned.
Results: The demographic characteristics of the patients did not differ s tatistically b etween t hose w ith a nd w ithout malnutrition. The daily frequency of diarrhea, post-admission and total diarrhea duration were similar between the groups; no statistically significant difference was observed. In the groups with and without malnutrition, there was no statistically significant d ifference in the duration of diarrhea after admission in patients under and over one year of age, in patients under and over one year of age receiving glutamine and placebo, and in patients receiving breast milk and those not receiving breast milk (glutamine (n=40) and placebo (n=40)). Weight gain during the follow-up period was similar in the groups with and without malnutrition. Glutamine supplementation did not affect w eight g ain o r t he f requency of infection.
Conclusions: In conclusion, glutamine supplementation did not affect t he m ean d aily f requency o f d iarrhea, post-admission and total diarrhea duration, and weight gain, both in patients with acute diarrhea with and without malnutrition and in the evaluation performed regardless of malnutrition status.

Anahtar Kelimeler

• Acute diarrhea
• Glutamine
• Malnutrition

Kaynakça

1. 1. Bishop WP, Ulshen MH. Bacterial gastroenteritis. Pediatr Clin North Am. 1988;35(1):69-87.
2. 2. Özen M, Güleçol G. Çocukluk çağında akut gastroenteritler. Türkiye Klinikleri Pediatric Sciences-Special Topics. 2011;7(4):76-81.
3. 3. Bhutta ZA, Nelson EA, Lee WS, Tarr PI, Zablah R, Phua KB, et al. Recent advances and evidence gaps in persistent diarrhea. J Pediatr Gastroenterol Nutr. 2008;47(2):260-5.
4. 4. Evans MA, Shronts EP. Intestinal fuels: glutamine, short-chain fatty acids, and dietary fiber. J Am Diet Assoc. 1992;92(10):1239-49.
5. 5. Saito H, Furukawa S, Matsuda T. Glutamine as an immunoenhancing nutrient. JPEN J Parenter Enteral Nutr. 1999;23(5 Suppl):S59-61.
6. 6. Ziegler TR, Bazargan N, Leader LM, Martindale RG. Glutamine and the gastrointestinal tract. Curr Opin Clin Nutr Metab Care. 2000;3(5):355-62.
7. 7. Tannuri U, Carrazza FR, Iriya K. The effects of glutamine-supplemented diet on the intestinal mucosa of the malnourished growing rat. Rev Hosp Clin Fac Med Sao Paulo. 2000;55(3):87-92.
8. 8. Foitzik T, Kruschewski M, Kroesen AJ, Hotz HG, Eibl G, Buhr HJ. Does glutamine reduce bacterial translocation? A study in two animal models with impaired gut barrier. Int J Colorectal Dis. 1999;14(3):143-9.

9. 9. Reid CL, Campbell IT. Nutritional and metabolic support in trauma, sepsis and critical illness. Curr Anaesth Crit Care. 2004;15(4-5):336-49.
10. 10. Gutiérrez C, Villa S, Mota FR, Calva JJ. Does an L-glutamine-containing, glucose-free, oral rehydration solution reduce stool output and time to rehydrate in children with acute diarrhoea? A double-blind randomized clinical trial. J Health Popul Nutr. 2007;25(3):278-84.
11. 11. Yalçın SS, Yurdakök K, Tezcan I, Öner L. Effect of glutamine supplementation on diarrhea, interleukin-8 and secretory immunoglobulin A in children with acute diarrhea. J Pediatr Gastroenterol Nutr. 2004;38(5):494-501.
12. 12. Bergström J, Fürst P, Norée LO, Vinnars E. Intracellular free amino acid concentration in human muscle tissue. J Appl Physiol. 1974;36(6):693-7.
13. 13. Sacks GS. Glutamine supplementation in catabolic patients. Ann Pharmacother. 1999;33(3):348-54.
14. 14. Lacey JM, Wilmore DW. Is glutamine a conditionally essential amino acid? Nutr Rev. 1990;48(8):297-309.
15. 15. Panigrahi P, Gewolb IH, Bamford P, Horvath K. Role of glutamine in bacterial transcytosis and epithelial cell injury. JPEN J Parenter Enteral Nutr. 1997;21(2):75-80.
16. 16. Souba WW, Klimberg VS, Plumley DA, Salloum RM, Flynn TC, Bland KI, et al. The role of glutamine in maintaining a healthy gut and supporting the metabolic response to injury and infection. J Surg Res. 1990;48(4):383-91.
17. 17. O'Riordain MG, Fearon KC, Ross JA, Rogers P, Falconer JS, Bartolo DC, et al. Glutamine-supplemented total parenteral nutrition enhances T- lymphocyte response in surgical patients undergoing colorectal resection. Ann Surg. 1994;220(2):212-21.
18. 18. Stehle P, Zander J, Mertes N, Albers S, Puchstein C, Lawin P, et al. Effect of parenteral glutamine peptide supplements on muscle glutamine loss and nitrogen balance after major surgery. Lancet. 1989;1(8632):231-3.
19. 19. Griffiths RD, Jones C, Palmer TE. Six-month outcome of critically ill patients given glutamine-supplemented parenteral nutrition. Nutrition. 1997;13(4):295-302.
20. 20. van der Hulst RR, van Kreel BK, von Meyenfeldt MF, Brummer RJ, Arends JW, Deutz NE, et al. Glutamine and the preservation of gut integrity. Lancet. 1993;341(8857):1363-5.
21. 21. Lustosa AP, Rocha EM, Lima NL, Monte CM, Guerrant RL. Intestinal barrier function and weight gain in malnourished children taking glutamine supplemented enteral formula. J Pediatr Gastroenterol Nutr. 2005;40(1):28-35.
22. 22. Ribeiro Júnior H, Ribeiro T, Mattos A, Palmeira C, Fernandez D, Sant'Ana I, et al. Treatment of acute diarrhea with oral rehydration solutions containing glutamine. J Am Coll Nutr. 1994;13(3):251-5.
23. 23. Thompson SW, McClure BG, Tubman TR. A randomized, controlled trial of parenteral glutamine in ill, very low birth-weight neonates. J Pediatr Gastroenterol Nutr. 2003;37(5):550-3.
24. 24. Poindexter BB, Ehrenkranz RA, Stoll BJ, Wright LL, Poole WK, Oh W, et al. Parenteral glutamine supplementation does not reduce the risk of mortality or late-onset sepsis in extremely low birth weight infants. Pediatrics. 2004;113(5):1209-15.
25. 25. Vaughn P, Thomas P, Clark R, Neu J. Enteral glutamine supplementation and morbidity in low birth weight infants. J Pediatr. 2003;142(6):662-8.
26. 26. Parimi PS, Devapatla S, Gruca LL, Amini SB, Hanson RW, Kalhan SC. Effect of enteral glutamine or glycine on whole-body nitrogen kinetics in very-low-birth-weight infants. Am J Clin Nutr. 2004;79(3):402-9.
27. 27. Duggan C, Stark AR, Auestad N, Collier S, Fulhan J, Gura K, et al. Glutamine supplementation in infants with gastrointestinal disease: a randomized, placebo-controlled pilot trial. Nutrition. 2004;20(9):752-6.
28. 28. Albers MJ, Steyerberg EW, Hazebroek FW, Mourik M, Borsboom GJ, Rietveld T, et al. Glutamine supplementation of parenteral nutrition does not improve intestinal permeability, nitrogen balance, or outcome in newborns and infants undergoing digestive-tract surgery: results from a double-blind, randomized, controlled trial. Ann Surg. 2005;241(4):599-606.
29. 29. Özen H. İmmün beslenme. Türkiye Klinikleri Pediatric Sciences-Special Topics. 2007;3(6):99-104.
30. 30. Williams EA, Elia M, Lunn PG. A double-blind, placebo-controlled, glutamine-supplementation trial in growth-faltering Gambian infants. Am J Clin Nutr. 2007;86(2):421-7.
31. 31. Moore SR, Quinn LA, Maier EA, Guedes MM, Quetz JS, Perry M, et al. Intervention and Mechanisms of Alanyl-glutamine for Inflammation, Nutrition, and Enteropathy: A Randomized Controlled Trial. J Pediatr Gastroenterol Nutr. 2020;71(3):393-400.
32. 32. Neu J, Li N. Pathophysiology of glutamine and glutamate metabolism in premature infants. Curr Opin Clin Nutr Metab Care. 2007;10(1):75-9.
33. 33. Wischmeyer PE, Riehm J, Singleton KD, Ren H, Musch MW, Kahana M, et al. Glutamine attenuates tumor necrosis factor-alpha release and enhances heat shock protein 72 in human peripheral blood mononuclear cells. Nutrition. 2003;19(1):1-6.
34. 34. Huang Y, Li N, Liboni K, Neu J. Glutamine decreases lipopolysaccharide-induced IL-8 production in Caco-2 cells through a non-NF-kappaB p50 mechanism. Cytokine. 2003;22(3-4):77-83.
35. 35. Liboni KC, Li N, Scumpia PO, Neu J. Glutamine modulates LPS-induced IL-8 production through IkappaB/NF-kappaB in human fetal and adult intestinal epithelium. J Nutr. 2005;135(2):245-51.
36. 36. Ogden HB, Fallowfield JL, Child RB, Davison G, Fleming SC, Delves SK, et al. No protective benefits of low dose acute L-glutamine supplementation on small intestinal permeability, epithelial injury and bacterial translocation biomarkers in response to subclinical exertional-heat stress: A randomized cross-over trial. Temperature (Austin). 2022;9(2):196-210.
37. 37. Kamuchaki JM, Wobudeya E, Kiguli S, Bortolussi R. Efficacy of glutamine supplementation on the outcome of children admitted with persistent diarrhea in Uganda: A randomized controlled study. Paediatr Child Health. 2013;18(1):e1.