Neomune Pelni
-
Upload
sutiyono-tyo -
Category
Documents
-
view
119 -
download
9
Transcript of Neomune Pelni
1
Iyan DarmawanMedical Department PT Otsuka Indonesiaemail: [email protected]
Iyan DarmawanMedical Department PT Otsuka Indonesiaemail: [email protected]
2
Malnutrisi Trauma
ImunSistem
Operasi Antibiotik
Nutrisi
Obat Rawat Intensif
Dukungan Imunologis pada Operasi dan Sakit Kritis
Dukungan Imunologis pada Operasi dan Sakit Kritis
3
• Intestinal Mucosal barrier
• Fuel for Immune cells
• Modulasi respon radang
Mekanisme ImunonutrisiMekanisme Imunonutrisi
4
• Intestinal Mucosal barrier
Mekanisme ImunonutrisiMekanisme Imunonutrisi
5
• Intestinal Mucosal barrier
• Fuel for Immune cells
• Modulasi respon radang
Mekanisme ImunonutrisiMekanisme Imunonutrisi
9
InflammatoryResponses
+
-
Severe Systemic Inflammatory Response
Severe Systemic Immunosuppression
TraumaSepsisBedah mayor
Well-regulated Responseby Immunonutrition
Early MOF
InfectionLate MOF
Modulasi Respon Radang oleh Immunonutrisi
Modulasi Respon Radang oleh Immunonutrisi
10
-3 fatty acidsArginine
Taurine
NucleotidesVitamins A, C, E
Greater effects
Lesser effects
Zinc
Glutamine
Immunonutrients
11
Dengan dosis serendah 800-1200 kcalsudah terlihat efek immune-enhancing
kcal
Immune-enhancingproperty:
demam (-) atauLeukositosis (-)/
NEOMUNE Standard
12
Dengan dosis serendah 800-1200 kcalsudah terlihat efek immune-enhancing
kcal
Immune-enhancingproperty:
demam (-) atauLeukositosis (-)/
NEOMUNE Standard
Neomune+
Standard
13
GLUTAMINE
14
GlutamineGlutamine
15
Bahan bakar untuk enterosit dan sel imun
Precursor untuk nucleotide & glutathione
Substrat untuk gluconeogenesis & ureagenesis
Asam amino bebas terbanyak dalam plasma,
Pada kondisi normal tidak esensial
Conditionally essential selama catabolic state
Sintesis utama di otot rangka
otot rangka, dan seluruh tubuh
GlutamineGlutamine
16
Pemecahanotot
Glutamine
Alanine Glucose
Acute phase proteinUrea
Glutamine dibutuhkan lebih pada stress
Glutamine dibutuhkan lebih pada stress
17
Gln UptakeAla Uptake
Protein Synthesis
Release
Protein SynthesisGln Uptake
Integrity
Gln UptakeAla UptakeGluconeogenesisProtein Synthesis
Protein Synthesis
Whole BodyProtein Turnover
Protein Breakdown
Gln
Immune function
LactatePyruvate
Efek Suplementasi GlutamineEfek Suplementasi Glutamine
18
Glutamine
PMNs MacrophagesLymphocytes
Efek terhadap sel-sel imunologi
19
TNF, IL-1, IL-2, IL-10, Interferon
Host Defense Organ Injury
Stress
PMNs MacrophagesLymphocytes
Glutamine
Immune Cells
Stress and Cytokines
20
Control diet Gln diet
Pasien
Pneumonia
Bactremia
Sepsis
31 29
14 513 28 1
ISS>20 First 15 days morbidity
Houdijk APJ et al:Lancet 352:772, 1998
* p< 0.02=
(45%)(42%)(26%)
(17%)
(7%)
(3%)
*
*
*
Penurunan komplikasi infeksi dengan nutrisi enteral yg diperkaya glutamine
pada pasien multitrauma
Penurunan komplikasi infeksi dengan nutrisi enteral yg diperkaya glutamine
pada pasien multitrauma
21
ARGININEARGININE
22
1. Memacu sekresi hormonPituitary-GH, Prolactin
Pancreas-Insulin, Glucagon, Somatostatin
2. Sintesis protein inti sel
3. Zat antara siklus urea
4. Prekursor Glutamine
5. Prekursor Nitric Oxide
1. Protein Breakdown
2. Fungsi imun
3. Penyembuhan luka
4. Pertumbuhan tumor
Nitrogen Retention
Efek-efek ArginineEfek-efek Arginine
23
Arginine
PMNs MacrophagesLymphocytes
Efek Arginine terhadap fungsi sel imunEfek Arginine terhadap fungsi sel imun
24
Arginine
Ornithine
Glutamine Proline PolyamineImmuno-enhancing Wound healing
ProteinEnergy metabolism
arginase
Trauma diikuti oleh penurunan kadar arginine plasma
Penjelasan:Laju destruksi oleh arginase dalam sel-selimun meningkat 10-kali lipat
Trauma dan ArginineTrauma dan Arginine
25
NO ONOO OH
L-Arginine O 2-
- .(Nitric Oxide) (Peroxynitrite)
Nitric Oxide synthase
Vasodilatation Tissue Injury Bactericidalactivity
Arginine dan NO
26
Growth Hormone
Liver
IGF-1
Tissues
Anabolic Effect
Immune System
Immunostimulatory Effect
Prolactin
Arginine
Arginine memacu imunitas via sekresi hormon hipofisisArginine memacu imunitas via sekresi hormon hipofisis
27
Brittenden J et al:Surgery 115:205,1994
Patients with breast cancer (n=24)
Arginine 30g/day for 3 days orally
Lymphocyte mitogenesis
Natural killer cell cytotoxity
Lymphokine-activated killer cell cytotoxity
L-arginine merangsang pertahanan hospes pada pasien kanker payudaraL-arginine merangsang pertahanan
hospes pada pasien kanker payudara
280 95 190 380 760 1250 3040
0
0.5
1.0
1.5
2.0
Supplemental Arginine (mol)
Labeled Staph.aureus Normal human PMNs
Flow cytometry
Repeated measures ANOVA
p<0.001
Moffat FL Jr et al: J Cell Physiol 168:26,1996
Ph
ago
cyto
sis
(to
tal
flu
ore
sce
nce
)Efek terhadap fagositosis bakteri
oleh sel PMNEfek terhadap fagositosis bakteri
oleh sel PMN
31
FISH OIL
32
Fish oilFish oil
33
Omega-3-fatty acidsOmega-3-fatty acids• fish oilfish oil
• immune function, booster neutrophil immune function, booster neutrophil activity,activity,
• distribution of lymphocyte throughout the distribution of lymphocyte throughout the bodybody
• reducing the body’s inflammatory reducing the body’s inflammatory response to trauma [ level of CRP, IL-6, response to trauma [ level of CRP, IL-6, leukotriene B4, PAF]leukotriene B4, PAF]
34
Linoleic acid (18:2 w6) -Linolenic acid (13:3 W3)
Arachidonic acid(20:4 w6)
PG2 Series
LT4 Series
PG3 Series
LT5 Series
PG1 Series
-6 Fatty Acid -3 Fatty Acids
dihomo-γ-linoleic acid (20:3 w6) Eicosapentaenoic acid (20:5 w3)(EPA)
Docosahexaenoic acid (22:6 w3)(DHA)
Eicosapentaenoic acid (20:5 w3)(EPA)
Eicosanoid Synthesis from Polyunsaturated Fatty Acids
Eicosanoid Synthesis from Polyunsaturated Fatty Acids
35
Anti-inflamatorik ~ immunosupresif
-3 Fatty Acids
MISUNDERSTANDINGMISUNDERSTANDING
36
Alexander JW, Saito H et al:Ann Surg204:1986
Metabolic Rate
Cell-mediated Immunity
Serum Opsonic Activity
-3 Fatty Acids (Fish Oil) in a Burn Model
37
Optimum dietary ratio for -6:-3 fattyacids in critically ill patients?
In western countries, the ratio > 10
Ratio < 5 ( around 2 ) would be desirable.
In Japan, the ratio 12:3 = 4:1
Ratio of -6 to -3 PUFAsRatio of -6 to -3 PUFAs
38
Glutamine 10-15
Arginine 12-15
-3 fatty acids 1.5-2.0
Standard DietsDiets
Immune
3-6
1.5-2.5
0-0.1
(g/1000 cal)
(g/1000 cal)
(g/1000 cal)
Kandungan nutrientKandungan nutrient
39
Mortality
Treatment Effect
(Treat/Ctrl)1.05 NS
Infection rate 0.60 0.005
Length of stay
(Treat/Ctrl)
-2.9 days (Treat-Ctrl) 0.0002
ICU stay -1.4 days (Treat-Ctrl) NS
Ventilators days -2.6 days (Treat-Ctrl) 0.04
12 trials:Impact 10, Immune-Aid 2 1,482 patientsBeale RJ et al:Crit Care Med 1999;27:2799
Summary of Meta-analysis ofImmunonutritive Enteral DietsSummary of Meta-analysis ofImmunonutritive Enteral Diets
40
Effect of Immunonutrition on Infectious Complications
Daly et al 1992Daly et al 1995
Braga et al 1996Schilling et al 1996Gianotti et al 1997
Senkal et al 1997Braga et al 1999
Senkal et al 1999Snydemanl et al 1999
Critically III PatientsBrown et al 1994Moone et al 1994
Kudsk et al 1996Bower et al 1995
Ross Products Division
Engel et al 1997of Abbott Laboratories, 1996
Mendez et al 1997Rodrigo and Garcia 1997
Galban et al 2000
Pooled Risk Ratio
0.005 0.01 0.05 0.1 0.5 1 5 10 50 100
Risk Ratio (95% Confidence Interval)
18 trials
Heyland DK et al:JAMA 286:944, 2001
Immunonutrition
Favors
Elective Surgical PatientsStandard DietFavors
Impact
41
Effect of Immunonutrition on Length of Hospital Stay
Daly et al 1992Daly et al 1995
Braga et al 1996Schilling et al 1996Gianotti et al 1997
Senkal et al 1997Braga et al 1999
Senkal et al 1999Snydemanl et al 1999
Cerra et al 1990Moone et al 1994
Kudsk et al 1996Bower et al 1995
Ross Products Divisionof Abbott Laboratories, 1996
Mendez et al 1997
Atkinson et al 1998Weimann et al 1998
-4 -3 -2 -1 0 1 2 3Effect Size (95% Confidence Interval)
Heyland DK et al:JAMA 286:944, 2001
Critically III Patients
Pooled Risk Ratio
17 trialsImmunonutrition
Favors
Elective Surgical PatientsStandars Diet
FavorsImpact
42
Questions for Immunonutrition Therapy in Surgical Stress
What types of surgical stress ?
What types of nutritional status ?
When to begin ?
What is optimal dosing ?
What is optimal length of treatment ?
What is expected outcome ?
43
Indications of Immunonutrition
GI Surgery
Trauma
Burns
Critically Ill ?
Sepsis ?
44
Control IMN P
Mortality 32%Mortality (APACHEII=10-15)
Bactremia
>1 nosocomial infection
Length of stay (days)
Ventilator days
28%
22%
20%
17
12
19%
4 %
8 %
6 %
18
12
.05
.02
.01
.01
.41
.90181 patients Infection source: mainly pneumoniaAPACHE II >10
Calban C et al Crit Care Med 2000; 28:643
Effects of IMN in SepticICU Patients
Effects of IMN in SepticICU Patients
45
Immune-enhancing enteral nutrition resulted in asignificant reduction in the mortality rate andinfection rate in septic patients admitted to the ICU.
These reductions were greater for patients withless severe illness.
Calban C et al Crit Care Med 2000; 28:643
It is recommended that trials of immunonutrition bestratified by high-risk and low-risk patients toprospectively determine the benefits ofimmunonutrition for ICU patients, as a function ofillness severity.
Effects of IMN in Septic ICU PatientsEffects of IMN in Septic ICU Patients
46
Timing of Administration
47
TIMINGTIMING
EARLYEARLY( ( < 24 HOURS of ADMISSION, post-op.day 1< 24 HOURS of ADMISSION, post-op.day 1))
Napolitano.L.M, Bochiccio.G, Enteral feeding of critically ill.; Current Opinion in Critical Care 2000;6:136-142
Lower incidence of infections (RR:0.45 ; 95%CI,0.30-0.66 p=.00006), Lower incidence of infections (RR:0.45 ; 95%CI,0.30-0.66 p=.00006), Reduced LOS(hospital) (mean red.of 2.2 days,95%CI 0.81-3.63days Reduced LOS(hospital) (mean red.of 2.2 days,95%CI 0.81-3.63days p=.004), no significant diff.in mortality.p=.004), no significant diff.in mortality.Marik.P.E, Zaloga.P.G; Early enteral nutrition in acutely ill patients: A systematic review; Critical Care Medicine 2001;29:2264-2270
IMN, is associated with a significant reduction in the risk of IMN, is associated with a significant reduction in the risk of developing infectious complications and reduces the overall hospital developing infectious complications and reduces the overall hospital staystay
Suplementation of enteral diet with arginine,RNA, and omega-3-FA in Suplementation of enteral diet with arginine,RNA, and omega-3-FA in the early post.op. time period improves post.op. immunologic the early post.op. time period improves post.op. immunologic responses and helps to overcome more rapidly the immunologic responses and helps to overcome more rapidly the immunologic depression after surgical traumadepression after surgical trauma..
Kemen.M Senkel.M, Critical Care Medicine;1995;23:652-659Kemen.M Senkel.M, Critical Care Medicine;1995;23:652-659
48
50
40
30
20
10
0
1 4 8
* p<0.05
**
% P
hago
cyto
sis
Control
60
50
40
30
-8 -1
** IEF
% P
hago
cyto
sis
1 4 8
* p<0.01
OP
Braga M et al: Arch Surg 1996;131:1257Braga M et al:Eur J Surg 1996;162:105
Postop dayPre-op
Monocyte Phagocytosis
Enteral feeding
OP
Enteral feeding
Pre-op Postop day
Orally 1 L/d
Neutrophil Phagocytosis
Immune Effects of Early Enteral NutritionImmune Effects of Early Enteral Nutrition
49
Optimal Dose Given
50
DOSINGDOSING
??Glutamine 0.1-0.3 g/kg/oral(enteral)Glutamine 0.1-0.3 g/kg/oral(enteral)
Arginine Arginine up to 30 g/day up to 30 g/day
51
Dose-Response Effect of ImmunonutrientsIn GI Surgery
Post-Op IntakeEffects
Heslin MJ et al () 30% of goal
60% of goal
Ann Surg 1997;226:567
Daly JM et alAnn Surg 1995;221:327
(+)
Schlling J et al (+) 70% of goal Nutrition 1996;12:423
95% of goal Gianotti L et alArch Surg 1997;132:1222
(+)
52
Mean IntakeEffects
17 ml/kg/day**
Atkinson et alCrit care Med 1998;26:1164
(+)
Galban et al (+) Crit Care Med 2000;28:643
Diagnostic Category
Critically ill
19 ml/kg/daySepsis
**>2.5 L within 72 hrs of ICU admission
Bower et al (+) Crit Care Med 1995;23:43618 ml/kg/day*Sepsis
* 821 mL/day at least 7 days
Dose-Response Effect of ImmunonutrientsIn Critically Ill and Sepsis
Dose-Response Effect of ImmunonutrientsIn Critically Ill and Sepsis
53NPC 200 kcal/sachet; Protein 12,5 g/sachet
NeomuneNeomune
1 sachet 5 sachetArginine 2,5 g 12,5 gGlutamine 1,25 g 6,25 gFish oil 1,11 g 5,55 gCasein 12,5 g 62,5 gCarbohydrate 47,5 g 237,5 gVitamins Minerals
54
Impact Immun-Aid
Protein (% Calories)
Free Glutamine(g/l)
Free Arginine (g/l)
Fat (% Calories)
-3 fatty acids (g/l)
22 32
0 9.0
14.0 15.4
BCAA (g/l) 9.6 29.0
25 20
1.68 1.1
Neo-Mune
14.1
10.6
1.8
25
26
8.75
Nucleotides (g/l) 1.25 01.0
Immunonutrient FormulationImmunonutrient Formulation
55
Goal: 8 –10 sachets/day Full dose
5 Sachets/ day ( ~ 60% of goal) as supplement is sufficient given orally
Recommended DosageRecommended Dosage
56
NPC : 1500-1800 Kcal Protein 60-90 g
Neomune 5 sachet 1000 62,5
+ diet oral atau
1L KAENMG3 + 400 1L PanAmin G 200 27
Pasien kgPasien kg
57