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ESPEN GUIDELINES
ENERGY
Provide energy to cover 1.3 x REE (C)
Give glucose to cover 50 % - 60 % of non-protein energy
requirements. (C )
Reduce glucose infusion rate to 23 g kg/day in case of hyperglycemia
and use consider the use of i.v. insulin. (C)
Use lipid emulsions with a content of n-6 unsaturated fatty acids
lower than in traditional pure soybean oil emulsions
AMINO ACIDS
Provide amino acids at 1.21.5 g kg1 d1. C
In encephalopathy III or IV, consider the use of solutions rich in BCAA
and low in AAA, methionine and tryptophane. A
Plauth M et al. ESPEN Guidelines on Parenteral Nutrition: Hepatology Clinical Nutrition 28 (2009) 436444
Riazi et al. The Total Branched-Chain Amino Acid Requirement in Young Healthy
Adult Men Determined by Indicator Amino Acid Oxidation by Use
of L-[1-13C]Phenylalanine. J. Nutr. 133: 13831389, 2003
Hyperammonemia is linked to
impairment of normal brain function
and the onset of the neurological
condition, hepatic encephalopathy
BCAA increases removal rate of
Ammonia from muscle
Daniel J. Wilkinson *, Nicholas J. Smeeton, Peter W. Watt G. Dam, O.L. Munk, P. Ott, S. Keiding, M. Srensen Ammonia
metabolism, the brain and fatigue; revisiting the link. Progress in Neurobiology 91 (2010) 200219
EFFECT OF BRANCHED-CHAIN AMINO ACIDS ON AMMONIA
METABOLISM IN SKELETAL MUSCLE IN PATIENTS WITH LIVER CIRRHOSIS AND HEALTHY CONTROLS MEASURED BY
13N-AMMONIA PET. Journal of Hepatology 2010 vol. 52 | S59S182
MULTIFACTORIAL MECHANISM OF EH
NH3
Tryptophan
NH3
Arousal
(serotonin)
Direct
neural toxin
False
neurotransmitters
Motor/cognitive
(dopamine)
Excitatory
glutamate
Inhibitory
GABA
ENCEPHALOPATHY
Endogen
eous
BZ
Liver
Pactreatic duct
Gall bladder
Cystic duct
Portal vein
Normal
Liver
Stomach
Esophagus
liver
Stomach varix
Stomach
Peritoneal
vein
Navel
Spleen
Superior
rectal vein
Rectum
Spleen
Esophageal varix
Paraumbilical vein
Superior
mesenteric
Superior rectal vein
vein
Paraumbilical vein
Navel
Shunt
Esophagus
Splenomegaly
Rectal varix
Rectum
Supervised by Akiharu Watanabe, Kawasaki University of Medical Welfare
Affection lability
Night awakening
and daytime
sleepiness
Sensitive to stimulation
Loss of
attention
In severe case
Coma
Restlessness
Severity of hepatic encephalopathy (consciousness disturbed) varies from very slight (degree I) to coma (degree IV or
V). Initial symptoms in particular may not be noticed even by family members without careful watching.
Psychiatric symptoms
Reference notes
Only retrospective
judgment is possible in
many cases
II
Absence of excitement
Absence of
urinary/fecal
incontinence
Presence of flapping
tremor
III
Presence of flapping
tremor (if cooperation of
a patient is obtained)
Severe disorientation
IV
Reactions such as
shaking off and frowning
are observed.
Deep coma
No response even to pain stimulus
12th Inuyama Symposium: Hepatitis A and fulminant hepatitis, Chugai Igakusha, 1982: pp.116-125
Supervised by Akiharu Watanabe, Kawasaki University of Medical Welfare
Excessive
consumption of
dietetic proteins
Constipation
Gastrointestinal
hemorrhage
Diuretics
Medication
(sedatives,
analgesics),
infections
Akiharu Watanabe: Clinical pathology of hepatic failure, Nagai Shoten, 1994: pp.255-257
Supervised by Akiharu Watanabe, Kawasaki University of Medical Welfare
Processing of ammonia and amino acid metabolism in patients with liver cirrhosis
(decompensated)
Normal liver
Collateral circulation
Urea
Hepatic vein
Glutamine
Amino acids
Urea
cycle
Ammonia
Ammonia+
NH 4
Amino acids
Urea
cycle
Ammonia
Glutamic acid
BCAA
Portal vein
Ammonia
Energy
Muscle
Ammonia
Urea
(intestine)
Supervised by Akiharu Watanabe, Kawasaki University of Medical Welfare
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Orn. Lys. His. Arg. Thr. Ser. Glu. Pro. Gly. Ala. Met. Val. Ile.
Leu.
Aromatic amino acids (AAA) such as Tyr and Phe increase whereas branched-chain amino acids (BCAA) such as Val,
Ile and Leu decrease showing a decreased BCAA/AAA ratio.
The concentration of each amino acid in the plasmas of 13 healthy subjects was
defined as 1 and its multiple number was plotted along the horizontal axis.
Yasutoshi Muto, et al.: The Saishin Igaku 1980;35(8): 1573-1582
Metabolisme Protein
.
BCAA
BCAA
AAA
BCAA
CH3
CH3
CH-CH2-CH-COOH
NH2
CH3
CH-CH-COOH
Valine
(Val)
CH3
CH3
Phenylalanine
(Phe)
NH2
CH-CH-COOH
NH2
NH2
Molecular weight: 181.19
Isoleucine
CH3-CH2
(Ile)
-CH2-CH-COOH
-CH2-CH-COOH
NH2
Molecular weight: 165.19
Tryptophan
(Trp)
- CH2 -CH
CH -COOH
COOH
N
NH2
H
Molecular weight: 204.23
Reimbursement
point1)
1300
(molar ratio)
Normal range2)
2.43 - 4.40
= Phenylalanine + Tyrosine
BTR
Reimbursement
point1)
300
=
=
(molar ratio)
Normal range2)
4.84 - 10.00 (male)
3.65 - 9.97 (female)
BTR in patients with liver cirrhosis4)
Compensated
3.490.89
Decompensated 2.56 0.72
1): Japanese Medical Journal 2008; 4374: p84, 2): Ed. Kanai, M.: Kanais Manual of Chemical Laboratory Medicine, Kanahara Shppan 2005: p510-513,
3): Fujisawa R.: KAN-TAN-SUI 1983; 6(6): 867-8724): Hiyama, Y.: Frontiers in Gastroenterology 4(4), 1999 409-419
Competitive inhibition
Brain-blood barrier
Brain
L-DOPA
Dopamine
Norepinephrine
Tyr
Phe
Tyramine
Octopamine
(*)
Trp
Phenyl tyramine
5HTP
Phenyl
ethanolamine (*)
Serotonin
5HIAA
Abnormality in brain
neurotransmitters
(*)
false neurotransmitter
: Tyrosine hydrogenase
Hepatic
encephalopathy
4.20 g
5.50 g
4.50 g
2.25 g
0.35 g
0.50 g
0.50 g
3.80 g
3.04 g
L-Alanine
L-Arginine hydrochloride
(as L-arginine)
L-Histidine hydrochloride
(as L-histidine)
L-Proline
L-Serine
L-Cysteine hydrochloride
hydrate (as L-cysteine)
Glycine
Amino acid
content
Total
nitrogen
Content of branched-chain
amino acida)
7.99 w/v%
6.11 g
35.5 w/w%
Fischer ratiob)
37.05
E/N
Na+
Cl-
pHc)
1.09
About 7 mEq
About 47 mEq
5.5-6.5
3.75 g
3.65 g
3.02 g
1.60 g
1.18 g
4.00 g
2.50 g
0.20 g
0.14 g
4.50 g
Specific
gravity (20C)
1.025
Osmotic pressured)
About 3
Disease (n)
Efficacy rate
73.3%
62.2%
Others* (8)
62.5%
Total (368)
70.4%
The efficacy of Aminoleban intravenous drip infusion was examined in patients with
chronic hepatic failure complicated by hepatic encephalopathy (76 facilities in total, 368
patients). The product was judged effective when decreased consciousness level was
resolved or improved definitely or the degree of coma (Davidsons classification) was
improved by one degree.
*: Metastatic hepatocellular carcinoma: 2, hepatic fibrosis: 3, bile duct cancer: 1, hepatic amyloidosis: 1, Eck
fistula syndrome: 1
Cited from Revised Package Insert, June 2008
Any EBM?
Indication
Improvement of encephalopathy in chronic liver disorder
Lung function:
Maintain oxygen saturation> 90%
Protect airway
Maintain PaCO2 > 30 mmHg
LOLA
Nutrition:
BCAA
AAA
Fat emulsion
Carbohydrate
Lactulose,
Neomisin/
Rifamycin
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