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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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
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What is Glutamine (GLN) ?
Endogenous
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Glutamine
Plasma Glutamine concentrations↑, improve:
1.Antioxidant capacity
2.Nitrogen balance ↑
3.Immune function ↑
4.Intestinal permeability ↑
5.The incidence of hospital-acquired infection ↓
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Hypermetabolic response
Major
surgery
Sepsis
Fractures
Trauma
Hypermetabolic
response
Burns
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Metabolism under stress
REE
Respiratory quotient
Proteolysis
Stress hypermetabolism
↑↑
0.8-0.9
↑↑
Hepatic protein
synthesis
Ureagenesis
↑↑
Gluconeogenesis
↑↑
Urinary nitrogen loss
↑↑
↑↑
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Glutamine
Therapy
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Dipeptiven雙胜胺
 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
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Aim of the three papers
Intravenous
glutamine
1.Antioxidant capacity
2.Nitrogen balance
3.Immune function
4.Intestinal permeability
Control
5.The incidence of hospitalacquired infection
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Metabolic Effects Of Enteral Versus Parenteral Alanylglutamine 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
Metabolic effects of enteral versus parenteral alanyl-glutamine
dipeptide administration in critically ill patients receiving enteral
feeding: a pilot study
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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 PN
Excluded:
active uncontrolled infection, hepatic dysfunction, renal
dysfunction, active GI bleeding or gastric outlet
obstruction, history of small intestinal or gastric resection
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Metabolic effects of enteral versus parenteral alanyl-glutamine
dipeptide administration in critically ill patients receiving enteral
feeding: a pilot study
Method
Control:IV Gln-free amino acid (0.5g/kg/d) (n=15)
Double-blind
randonmization
IV AG: IV Gln (0.5g/kg/d) (n=14)
EN AG: IV placebo + EN Gln (0.5g/kg/d) (n=15)
3-day N blance
Study day
1
Lab data
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6
9
Iso-N, iso-caloric tube feeds
Lab data
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Metabolic effects of enteral versus parenteral alanyl-glutamine
dipeptide administration in critically ill patients receiving enteral
feeding: a pilot study
Method
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
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Metabolic effects of enteral versus parenteral alanyl-glutamine
dipeptide administration in critically ill patients receiving enteral
feeding: a pilot study
Conclusion
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 increase
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EN AG group : ↑
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IV AG group : ↑
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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
Ahmet Eroglu, MD
International Anesthesia Research Society 109(2009),502-505
The Effect of Intravenous Alanyl-Glutamine Supplementation on 19
Plasma Glutathione Levels in Intensive Care Unit Trauma Patients
Receiving Enteral Nutrition: The Results of a Randomized Controlled
Trial
Objective
IV alanyl-glutamine dipeptide supplementation↔plasma glutathione
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 alanylglutamine
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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Conclusion
IV alanyl-glutamine supplementation for 7 days
→ total plasma glutathione levels ↑
•No differences in : CRP, prealbumin, glucose
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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
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
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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
preservation of
lean body mass
IV alanyl-glutamine
supplementation in multiple
trauma patients receiving
enteral nutrition
infectious
complications
organ failure
Design
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.
2.
parameter
1.
0.5 g/kg/day IV alanyl-glutamine
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.
2.
3.
4.
5.
Total sequential organ failure assessment
score on the last day of treatment
infectious complications during the ICU stay
60-day mortality
length of stay in the intensive care unit
fat-free mass and fat percentage
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Strengths
limitations
Longer study
period
1. Mortality
2. The long-term
outcomes
3. Trauma patients
with severe renal
failure or hepatic
impairment
Objective
1
2
3
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
Comparison
Design
double-blind,RCT
Setting
ICU
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Patients
44
40
88
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 days
Conclusion
for 7 days
IV:Plasama glutamine↑ IV:7.10day total plasma
glutathione levels ↑
EN:α-tocopherol ↑
最多3 weeks
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Conclusion
Parental
glutamine
Control
1.Antioxidant capacity
2.Nitrogen balance
IV
3.Immune function
1.Plasma
glutamine ↑
4.Intestinal permeability
2.Plasma
glutathione ↑
5.The incidence of hospitalacquired infection
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