General and Specialized Parenteral Amino Acid

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• ??? ??

2000/04/26
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??????? ??????

• Aminosyn 10 (Abbott)
• Aminoplasmal 10 (B. Braun)
• Amiparen 10 (Otsuka)
• Moriamin SN 10 (??)
• FreAmin II 8.5 (McGaw)
• TeruAmino 12X (Terumo)
• Amino 12X (??)

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General Parenteral Amino Acids

• 1st generation 1940-1970
• Goat muscle, casein, lactalbumin, bovine serum
  proteins, fibrin, and serum albumin
• 2nd generation 1960-1970
• Hydrochloride salt and Glycine
• Acidosis and hyperammonemia
• 3rd generation 1970s
• Focus on EAA/NEAA ratio
• Superceded by alkalosis due to over replace of
  HCl with acetate
• Additional glutamic acid, aspartic acid, taurine,
  cysteine, tyrosine
• High glycine decrease
• 4th generation tailor-made solutions
• Liver and kidney failure, sepsis or immature or
  abnormal metabolic pathways

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??????? ?????? FAO/WHO High Biologic Value ??
?E/T?(?????/???)3.21 (hens egg 3.21,
human breast milk 3.11) ?E/N?(?????/??????)1 ?In
crease Arginine ?Decreased Glycine ?????
(Lysine in added as the acetate) ?Molar Ratio
BCAAs to AAAs3.0-3.51 ?BCAAs 23-25
Hospital pharmacy Jan. 1981 p29-33
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(No Transcript)
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Amino Acid formulas impact acid-base balance
Anionic AA Glutamic acid, Aspartic
acid Sulfur-containing AA Methionine,
Cysteine As HCl from lysine HCl
Hospital pharmacy Jan. 1988 p78-82
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Amino Acid formulas impact acid-base balance

• Hyperchloremic acidosis
• Lysine Cl- 7O2 CH4ON2 (urea) 5CO2 5H2O
  H Cl-
• C2H3O2- (acetate) 2O2 CO2 H2O HCO3-
• Methionine or cysteine O2 CO2 H2O CH4ON2
  (urea) SO4-2 2H
• Aminosyn profile
• Lysine acetate, lower methionine
• Tendency for blood ammonia levels to rise
• Clinical insignificant, but chemical measurable
  alkalosis
• In present a potent chloruretic such as
  furosemide will produce significant clinical
  alkalosis

Hospital pharmacy Jan. 1988 p78-82
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Amino acid?????
Richard J Wood Am. J. Clin Nutr 40 101-106 1983
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????????TPN???????
Serum Ca and P level (mg/dl)
Plt0.025
Plt0.001
Plt0.001
10
?
?
5
Plt0.025
Plt0.001
Plt0.005
0
Period A (?)
Period B (?)
Period C (? ?)
Saburo JPEN 10 513-516, 1986
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??????? ??????

• HepatAmine 8 (McGaw)
• Aminoleban 8 (Otsuka)
• TalAmin-Hepa 8 (??)
• Aminosteril N-Hepa 8 (Fresenius)
• Aminopoly-H 7 (??)

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???????Stage of Hepatic Encephalopathy
Modified Parsons-Smith Rating Scale
J. Y. Pang
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Pathogenesis of Hepatic Encephalopathy Theories

• Ammonia
• Amino acid imbalances
• BCAA/AAA False neurotransmitters
• Methionine
• Tryptophan
• Unified theory - BCAA/AAA NH3
• Mercaptans
• Short Chain Fatty Acids (SCFA)
• Increased cerebral sensitivity

J. Y. Pang
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?????????????
400
Glu
350
Meth
Asp
Phe
300
250
Tyr
of Normal
200
Try
150
Gly
100
Orn
Thr
Ser
Lys
Tau
His
Val
50
Leu
Arg
Pro
Ala
Ileu
??????
?????
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??????? ?????? HepatAmine/Aminoleban 8 inj.

• ?????? High BCAA (36)
• ??????? Low Aromatics
• BCAAAAA 371
• Low Methionine
• IsoLeuVal ratio 111
• ??????? (for liver disease)

• 48???????
• ????????
• ??????????
• ??????

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Hapatic failure - Hypercatabolism ???
0.6-1.1g/kg/day ,?? 30-35kcal/kg/day
BCAA Enriched Solution

• ??????? ?
• ???125 g BCAA-enriched solutions
• ????????
• ????????????
• fulminant hepatitis - massive hyperaminoacidemia,
  reflecting a dying liver

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Resection of hepatocellular carcinoma
N124?
7 days preoperation and 7 days postoperation
nutrition
Fan S-T et al , N Engl J Med 3311547, 1994
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??????? ??????

• Essential Amino Acids Formula
• NephAmine 5.4 (McGaw)
• Amiyu 7.4 (??)
• Aminosyn-RF (Abbott)
• Essential/Non-Essential (60/40) Formula
• Nephrosteril 7 (Fresenius)
• TalAmin-Nephro 7 (??)

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Guildlines for protein administration in acute
and chronic renal failure

• Patients not regularly dialyzed
• Dialysis undesirable or contraindicated 14-28
  gm EAA /day
• Dialysis not contraindicated
• GFR?70ml/min without progression no protein
  restriction
• GFR?70ml/min with progression
  0.55-0.70gm/kg/day
• GFR 5-70ml/min 0.55-0.60gm/kg/day
• Supplement for each hemodialysis or peritoneal
  dialysis 40-42gm
• Patient regularly dialysis
• Hemodialysis 1.2-1.4gm/kg/day
• Peritoneal dialysis (CAPD) 1.2-1.5gm/kg/day

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??????????
EXTENT OF CATABOLISM MILD
MODERATE SEVERE
Excess urea appearance(above N intake)
lt5 g 6-12 g
gt12 g
Clinical setting Drug toxicity
Elective surgery Severe
injury or
/-
infection sespsis
Mortality
20 60
gt80
Dialysis frequency rare
As needed
Frequent
Route of nutrient
Oral Enteral and/or
Enteral and/or
administration
parenteral
parenteral
Energy recommendations 25 glucose
25-35 glucose fat 35-45
glucose fat (Kcal/kg/day)
Protein (g/kg/day)
0.6-0.8 EAA 0..8-1.2 EAA NEAA
1.0-1.5 EAA NEAA
Nutritions used Food, enteral
formulas, Enteral Formulas, Glucose,
Enteral Formulas,
EAA solution
50-70 fat emulsion 10-20 Glucose, 50-70

EAA NEAA
Solution fat emulsion, 10-20


EAA
NEAA Solution
Nutrition management of ARF 3rd 1993,Chapter15
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Giordano - Giovannetti Theory Glucose Analine
Cycle

• ??????
• ????????

• ??????
• ???

Ammonia ?-ketoglutarate ? glutamate Glutamate
pyruvate ? ?-ketoglutarate alanine
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????????NephrAmine 5.4 Amiyu 7.4
?????????BUN ????????? ?????????????? ????????????
?? ???ARF?????? ???ARF???
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New concept of NEAA in renal failure

• Arginine
• Intermediate in the urea cycle
• improved and more rapid achievement of positive
  nitrogen balance
• improved immunoglobulins

J.Y. Pang
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New concept of NEAA in renal failure

• Histidine
• Hemoglobin decrease progressively
• Glycine and analine
• As cytoprotective effect to proximal tubule
  cells
• tyrosine
• precursor of catecholamines and thyroid hormones
• Negative nitrogen balance
• Theoretically, it may be beneficial to include
  NEAAs to maintain N balance and optimize protein
  synthesis

Parenteral Nutrition 2nd, 1993, p567-673
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The Nutrition Management with ARF

• . The "essential" AAs, more ammonia-genic.
• increased serum ammonia levels
• Small quantity EAA (0.4 to 0.5g/kg/day) may be
  utilized more efficiently than EAA/NEAA
• Large EAA alone may be very hazardous to the
• patients at least some NEAA should be added

Kopple JPEN 203-12, 1996
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??????? ??????45 High Branched Chain Amino
Acids Formula

• ??
• ???
• ???10???/?
• ??????
• ?????
• ??
• ????
• ??????
• ?????

• FreAmine HBC 6.9 (McGaw)
• TalAmin HBC (??)
• Aminosyn HBC (Abbott)

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Metabolic Stress???
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Metabolic needs relative to stress level
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THE STRESS SYNDROME

•  
• Sepsis / Injury
• ?
• ?? steroid (Cortisol, Catecholamine, Glucagon,
  GH)??
• ?
• ????????
• ? 1.   
  ???????
• 2.       ?? BCAA
  ?????
• ?
• ??????
• ?
• ?? BCAA ??
• ?
• ?? BCAA ???????
• ?
• Multiple System Organ Failure
• ?
• Death

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BCAA in sepsis
Standard BCAA
Supranormal BCAA
??
??
??
??
???
???
???
???
???
???
GLUCOSE POOL
GLUCOSE POOL
BCAA
BCAA
AA
AA
BCAA
BCAA
AA
AA
ATP
ATP
Protein
Protein
SKELETAL MUSCLE
SKELETAL MUSCLE
MARKED INCREASE
INCREASE
NO CHANGE
Murry F JPEN vol. 10,No.5, 1986
DECREASE
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Nitrogen Balance in Traumatized PatientsBCAA
Enriched AA Vs. Standard AA
Cerra FB Pocket Manual of Surgical Nutrition.
1984, p70
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Summary TalAmin-HBC vs. HepatAmine
Base on Recommended Daily Treatment
TalAmin-HBC 5 HepatAmine 4
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??????? ????????

• 1st generation (without taurine)
• Aminoplasma ped 6 (B. Braun)
• Aminovenos N-pad 6 10 (Fresenius)
• 2nd generation (with taurine and tyrosine)
• Aminosteril Infant 6 10 (Fresenius Kabi)
• TrophAmine 6 10 (McGaw)
• TalAmin-Troph 6 10 (??)
• Cysteine HCl injection USP 0.5g/10mL (50mg/mL)

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Immature Metabolic Pathways in the Infants
Methionine ? Homocysteine ? ?
Cystathionine Synthase Cystathionine ? ?
Cysthathionase Cysteine ? ? Cysteine
sulfinic acid decarboxylase Taurine Tr
anssulfuration Pathway

• Phenylalanine
• ? ? Phenylalanine
• hydroxylase
• Tyrosine
• Phenylalanine Pathway

The activity enzymes in the liver and brain of
fetus, preterm and term newborn infants is ¼ to
1/3 that in mature humans
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The important of Taurine Cysteine
Cysteine
Taurine

• Impared growth and nitrogen retention
• Depress level of cysteine and tyrosine
• Cysteine cause sloution precipitate

• Retinal dysfunction
• Cardiac Function
• Membrane stabilizing
• Antiarrhythmogenic action
• Neurotransmitter-neuromodulator effects
• Central Nerve System
• Integrated nerve function eg. Control of
  temperature and muscle tone
• Bile acid Conjugation
• cholestasis

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??? ??? ?????TrophAmine 10/TalAmin Troph 6

• ?????????????????

Tyrosine

• High concentration Glutamic and Aspartic acids
• ?? phenylalanineine
• methionine, glycine

• Impared growth and nitrogen retention
• Depress level of cysteine and tyrosine
• Soluble N-acetyl-L-tyrosine (NAT) as precusor
  (???tyrosine)

Add cysteine HCl after final parenteral Solution
for increase cysteine and increase P and Ca
conc.
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