1. Intravenous Glutamine Supplementation in Critically Ill Patients Receiving Enteral Feeding Reporter: 黃孜立 Instructor: 賴聖如 營養師 1

2. Abstract Glutamine and Dipeptiven Metabolism under stress Paper – Metabolic Effects Of Enteral Versus Parenteral Alanyl-glutamine Dipeptide Administration In Critically Ill Patients Receiving Enteral Feeding: A Pilot Study – The Effect Of Intravenous Alanyl-glutamine Supplementation On Plasma Glutathione Levels In Intensive Care Unit Trauma Patients Receiving Enteral Nutrition: The Results Of A Randomized Controlled Trial – Effect Of Intravenous Glutamine Supplementation IN Trauma Patients Receiving Enteral Nutrition Study Protocol (GLINT Study): A Prospective, Blinded, Randomised, Placebo Controlled Clinical Trial Conclusion 2

3. What is Glutamine (GLN) ? 3 Endogenous

4. Glutamine Plasma Glutamine concentrations↑, improve: 1.Antioxidant capacity 2.Nitrogen balance ↑ 3.Immune function ↑ 4.Intestinal permeability ↑ 5.The incidence of hospital-acquired infection ↓ 4

5. Hypermetabolic response Fractures Sepsis Major surgery Trauma Burns 5

6. Metabolism under stress 6 Stress hypermetabolism REE↑↑ Respiratory quotient0.8-0.9 Proteolysis↑↑ Hepatic protein synthesis ↑↑ Ureagenesis↑↑ Gluconeogenesis↑↑ Urinary nitrogen loss↑↑

7. 7 Glutamine Therapy

8. Dipeptiven 雙胜胺 8  Concentrated GLN solution containing the dipeptide alanyl-glutamine (Ala-Gln)  100 ml contains: 20 g N(2)-L-alanyl-L-glutamine =>13.46 g L-glutamine, 8.20 g L-alanine(= 3.87 g N) -Water for injection -Theoretical osmolarity: 921 mosmol/ l Indication  In patients in catabolic and/ or hypermetabolic states Prescribing information  Dosage per day:0.4 g Ala-Gln / kg BW (= 2.0 ml Dipeptiven ® / kg BW) Administration: For central venous infusion, as part of a PN regime

9. Aim of the three papers 1.Antioxidant capacity 2.Nitrogen balance 3.Immune function 4.Intestinal permeability 5.The incidence of hospital- acquired infection Intravenous glutamine Control 9

10. Metabolic Effects Of Enteral Versus Parenteral Alanyl- glutamine Dipeptide Administration In Critically Ill Patients Receiving Enteral Feeding: A Pilot Study Menghua Luo, Niloofar Bazargan, Daniel P. Griffith, Concepción Fernández-Estívariz, Lorraine M. Leader, Kirk A. Easley, Nicole M. Daignault, Li Hao, Jon B. Meddings, John R. Galloway, Jeffrey B. Blumberg, Dean P. Jones, and Thomas R. Ziegler Clinical Nutrition 27(2009),297–306 10

11. Metabolic effects of enteral versus parenteral alanyl-glutamine dipeptide administration in critically ill patients receiving enteral feeding: a pilot study ObjectiveTo find the metabolic effects of intravenous (IV) alanyl-Gln dipeptide (AG) supplementation and enteral (EN) AG supplementation in adult critically ill patients requiring tube feeding Designdouble-blind, pilot clinical trial Settingsurgical Intensive Care Unit (SICU) PatientsCritically ill patients (N=44) in the ICU with indication for PN Excluded: active uncontrolled infection, hepatic dysfunction, renal dysfunction, active GI bleeding or gastric outlet obstruction, history of small intestinal or gastric resection 11

12. 12 Double-blind randonmization Control:IV Gln-free amino acid (0.5g/kg/d) (n=15) IV AG: IV Gln (0.5g/kg/d) (n=14) EN AG: IV placebo + EN Gln (0.5g/kg/d) (n=15) 1 1 3 3 6 6 9 9 Study day 3-day N blance Iso-N, iso-caloric tube feeds Lab data Method Metabolic effects of enteral versus parenteral alanyl-glutamine dipeptide administration in critically ill patients receiving enteral feeding: a pilot study

13. 13 Method Metabolic effects of enteral versus parenteral alanyl-glutamine dipeptide administration in critically ill patients receiving enteral feeding: a pilot study Lab data: Day1, 9: 1.plasma Gln 2.antioxidant indices 3.lymphocyte subsets 4.serum IGF-1 and IGF binding protein-3 5.intestinal permeability Days 6 to 8: Nitrogen balance study

14. Metabolic effects of enteral versus parenteral alanyl-glutamine dipeptide administration in critically ill patients receiving enteral feeding: a pilot study 14 Conclusion criteriaResult (compared to control group) antioxidant capacityX No significant differences oxidative stress markersX No significant differences α- tocopherol EN AG group↑ T-lymphocyte subset numberX No significant differences gut barrier functionX No significant differences whole-body protein metabolism X No significant differences Plasama glutamine↑ IV AG group: Significant increase

15. 15 Plasama glutamine→ IV AG group: Significant increase

16. 16 EN AG group : ↑

17. 17 IV AG group : ↑

18. The Effect Of Intravenous Alanyl-glutamine Supplementation On Plasma Glutathione Levels In Intensive Care Unit Trauma Patients Receiving Enteral Nutrition: The Results Of A Randomized Controlled Trial Ahmet Eroglu, MD International Anesthesia Research Society 109(2009),502-505 18

19. The Effect of Intravenous Alanyl-Glutamine Supplementation on Plasma Glutathione Levels in Intensive Care Unit Trauma Patients Receiving Enteral Nutrition: The Results of a Randomized Controlled Trial Designrandomized, controlled study (double blind manner) SettingIntensive Care Unit (ICU) Patients40 adult patients with severe trauma according to the Injury Severity Score(ISS) >20 Interventions1.Group G received 0.5 g /kg/d of IV alanyl-glutamine dipeptide supplementation 2.Group C received a control solution without alanyl- glutamine for 7 days ParameterBlood samples: total glutathione, C reactive protein (CRP), prealbumin, and glucose before the initiation of supplementation and on the 3rd, 7th, and 10th days of feeding. 19 Objective IV alanyl-glutamine dipeptide supplementation↔plasma glutathione

20. 20 Conclusion IV alanyl-glutamine supplementation for 7 days → total plasma glutathione levels ↑ IV alanyl-glutamine supplementation for 7 days → total plasma glutathione levels ↑ No differences in : CRP, prealbumin, glucose

21. Effect Of Intravenous Glutamine Supplementation IN Trauma Patients Receiving Enteral Nutrition Study Protocol (GLINT Study): A Prospective, Blinded, Randomised, Placebo Controlled Clinical Trial Ruqaiya M Al Balushi,1 Jennifer D Paratz,1,2 Jeremy Cohen,1,2 Merrilyn Banks,3 Joel Dulhunty,1,2 Jason A Roberts,1,2 Jeffrey Lipman Al Balushi RM, Paratz JD, Cohen J, et al. BMJ Open 1(2011),1-7 21

22. Effect Of Intravenous Glutamine Supplementation IN Trauma Patients Receiving Enteral Nutrition Study Protocol (GLINT Study): A Prospective, Blinded, Randomised, Placebo Controlled Clinical Trial Objective 22 IV alanyl-glutamine supplementation in multiple trauma patients receiving enteral nutrition preservation of lean body mass infectious complications organ failure

23. 23 DesignProspective, Blinded, Randomised, Placebo Controlled Clinical Trial SettingIntensive Care Unit (ICU) Patients88 critically ill patients with a diagnosis of multiple trauma requiring mechanical ventilation, patients requiring enteral feeding for >48 h, expected length of stay in the ICU >48 h Interventions1.0.5 g/kg/day IV alanyl-glutamine 2.IV placebo continuous infusion (24 h/day) & the same standard enteral nutrition protocol until discharge from the intensive care unit, death or a maximum duration of 3 weeks. parameter1.Total sequential organ failure assessment score on the last day of treatment 2.infectious complications during the ICU stay 3.60-day mortality 4.length of stay in the intensive care unit 5.fat-free mass and fat percentage

24. 24 Strengthslimitations Longer study period 1.Mortality 2.The long-term outcomes 3.Trauma patients with severe renal failure or hepatic impairment

25. Comparison 25 123 ObjectiveIV EN ↔ 1. 血糖 2. 抗氧化力 3. 免疫能力 4. 腸道保護 5. 住院天數、死亡率、 併發症 IV ↔ 1. 抗氧化力 (plasma glutathione) 2. 血糖 3. 住院天數、死亡率、 併發症 IV ↔ 1. 保留 LBM 能力 2. 住院天數、死亡 率、併發症 3.ICU 常規檢測數值 Designdouble-blind,RCT SettingICU Patients444088 Nutrition Regime 1.EN AG 2.IV AG 0.5 g /kg/d 3.control 1.IV :0.5 g /kg/d 2.control 1.IV :0.5 g/kg/day 2.Control 管灌多元配方 for 9 daysfor 7 days 最多 3 weeks ConclusionIV:Plasama glutamine↑ EN: α -tocopherol ↑ IV:7.10day total plasma glutathione levels ↑

26. Conclusion 26 1.Antioxidant capacity 2.Nitrogen balance 3.Immune function 4.Intestinal permeability 5.The incidence of hospital- acquired infection Parental glutamine Control IV 1.Plasma glutamine ↑ 2.Plasma glutathione ↑

27. THANK YOU FOR YOUR ATTENTION 27