intravenous glutamine supplementation in critically ill patients receiving enteral feeding reporter:...

Intravenous Glutamine Supplementation in Critically Ill Patients Receiving Enteral

Feeding

Reporter: 黃孜立Instructor: 賴聖如營養師

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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

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What is Glutamine (GLN) ?3

Endogenous

Glutamine

Plasma Glutamine concentrations↑, improve:1.Antioxidant capacity2.Nitrogen balance ↑3.Immune function ↑4.Intestinal permeability ↑5.The incidence of hospital-acquired infection ↓

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Hypermetabolic response5

Metabolism under stress6

Stress hypermetabolismREE ↑↑Respiratory quotient 0.8-0.9Proteolysis ↑↑Hepatic protein synthesis

↑↑

Ureagenesis ↑↑Gluconeogenesis ↑↑Urinary nitrogen loss ↑↑

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Glutamine Therapy

Glutamine Therapy

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/ lIndication

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

Aim of the three papers9

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. ZieglerClinical Nutrition 27(2009),297–306

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Metabolic effects of enteral versus parenteral alanyl-glutamine dipeptide administration in critically ill patients receiving enteral feeding: a pilot study

Objective To 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

Design double-blind, pilot clinical trial

Setting surgical Intensive Care Unit (SICU)

Patients Critically ill patients (N=44) in the ICU with indication for PNExcluded:active uncontrolled infection, hepatic dysfunction, renal dysfunction, active GI bleeding or gastric outletobstruction, history of small intestinal or gastric resection

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Double-blindrandonmization

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)

11 33 66 99Study day

3-day N blance

Iso-N, iso-caloric tube feedsLab dataLab data Lab dataLab data

MethodMethod


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MethodMethod


Lab data:•Day1, 9:1.plasma Gln2.antioxidant indices3.lymphocyte subsets4.serum IGF-1 and IGF binding protein-35.intestinal permeability

•Days 6 to 8: Nitrogen balance study


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ConclusionConclusion

criteria Result (compared to control group)

antioxidant capacity X No significant differences

oxidative stress markers X No significant differences

α-tocopherol EN AG group↑

T-lymphocyte subset number X No significant differences

gut barrier function X No significant differences

whole-body protein metabolism

X No significant differences

Plasama glutamine ↑ IV AG group: Significant increase

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Plasama glutamine→ IV AG group: Significant increasePlasama glutamine→ IV AG group: Significant increase

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EN AG group : ↑

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IV AG group : ↑

The Effect Of Intravenous Alanyl-glutamine Supplementation On Plasma Glutathione Levels InIntensive Care Unit Trauma Patients Receiving Enteral Nutrition: The Results Of A Randomized Controlled Trial

Ahmet Eroglu, MDInternational Anesthesia Research Society 109(2009),502-505

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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

Design randomized, controlled study (double blind manner)

Setting Intensive Care Unit (ICU)

Patients 40 adult patients with severe trauma according to the Injury Severity Score(ISS) >20

Interventions 1. 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

Parameter Blood 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.

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Objective IV alanyl-glutamine dipeptide supplementation↔plasma glutathione

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ConclusionConclusion

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

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 LipmanAl Balushi RM, Paratz JD, Cohen J, et al. BMJ Open 1(2011),1-7

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Effect Of Intravenous Glutamine Supplementation IN Trauma Patients Receiving Enteral Nutrition Study Protocol (GLINT Study): A Prospective, Blinded, Randomised, Placebo Controlled Clinical Trial

• Objective

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IV alanyl-glutamine supplementation in multiple

trauma patients receiving enteral nutrition

preservation of lean body mass

infectious complications

infectious complications

organ failure

23Design Prospective, Blinded, Randomised, Placebo

Controlled Clinical Trial

Setting Intensive Care Unit (ICU)

Patients 88 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

Interventions 1. 0.5 g/kg/day IV alanyl-glutamine2. 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.

parameter 1. Total sequential organ failure assessment score on the last day of treatment

2. infectious complications during the ICU stay3. 60-day mortality4. length of stay in the intensive care unit 5. fat-free mass and fat percentage

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Strengths limitations

Longer study period

1. Mortality2. The long-term

outcomes 3. Trauma patients

with severe renal failure or hepatic impairment

Comparison251 2 3

Objective IV 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

Design double-blind,RCT

Setting ICU

Patients 44 40 88

Nutrition Regime

1. EN AG 2. IV AG 0.5 g /kg/d3. control

1. IV :0.5 g /kg/d2. control

1. IV :0.5 g/kg/day2. Control

管灌多元配方for 9 days for 7 days 最多 3 weeks

Conclusion IV:Plasama glutamine↑EN:α-tocopherol ↑

IV:7.10day total plasma glutathione levels ↑

Conclusion26

THANK YOU FOR YOUR ATTENTION

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