immunonutrients in surgical patients benny philippi
TRANSCRIPT
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Immunonutrients in Surgical Patients
Benny Philippi
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Introduction
1. Increased complexity of managing nutritional support in surgical patients (trauma, sepsis, critically ill)
2. Malnutrition is a common practice in these patients
3. Understanding normal nutrition & metabolic changes is essential for surgeon
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MALNUTRITION: PARAMETERS RSUPN – C.M.
DIGESTIVE SURGERY DIVISION
BODY MASS INDEX (BMI):FEMALE : BMI 18,5 – 23,5 (NORMAL VALUE)MALE : BMI 22,5 – 25 (NORMAL VALUE)
ALBUMIN: 3 g%TOTAL LYMPHOCYTE COUNT SCORING: PROGNOSTIC NUTRITION INDEX
(PNI)
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Malnutrition: Digestive Operative Cases 2003 (Overview: BMI Value)Patients
Colorectal 14 (46,4%)
Hepatobiliary 9 (30%)
Esofago Gastric 3 (10%)
Others 4 (13,4%)
30 Cases
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• BMI– Female: 18
• Malnutrition 6 (20%)
– Male: 12• Malnutrition 11 (36%)
• Albumin: Hypoalbuminemia– Preoperative : 13%– Post Operative Day 1 : 70%
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Fat Cell
Keton
Free fatty acid
Growth hormon cortisol
Thyroid hormon
NE/E
GlucoseGlucose
Glucagon
NE/N
Insulin
Thyroid hormon
cortisolcortisol
ADHNE / EACTHTSH
GH
Amino acid
METABOLIC RESPONSE TO OVERNIGHT FASTING
HepaticGluconeogenesis
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Fat Cell
METABOLIC RESPONSE TO TRAUMA / ELECTIVE SURGERY
Keton
Free fatty acid
Growth hormon cortisol
Thyroid hormon
NE/E
GlucoseGlucose
Glucagon
NE/N
Insulin
Thyroid hormon
cortisolcortisol
ADH (post hypophisis)NE / E (symp n / adrenal med)ACTH TSH ant hypophisisGH
Amino acid
NeuroendocrineActivation
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Fat Cell
METABOLIC RESPONSE TO SEPSIS
Keton
Free fatty acid
Growth hormon cortisol
Thyroid hormon
NE/E
GlucoseGlucose
Glucagon
NE/N
Insulin
Thyroid hormon
cortisol
cortisol
ADHNE / EACTHTSHGH
Amino acid
Cytokines
“Cytokine driven”
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METABOLIC RESPONSE TO SEVERE INJURYINJURY / SURGERYY
Afferent neural activity Tissue hypoperfusion Neutrophils Macrophages
CENTRAL NERVOUS SYSTEM
Cytokiens Oxygen free radicals
Arachidonic acid matabolites
Hormonal activity Anorexia Immobility
Pyrexia
Afferent neural activity Direct tissue effects
Changes in cellular hydration and cellular energetics Protein catabolism
Capillary leak Organ dysfunction
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THE GOAL IN SURGERY IS TO THE GOAL IN SURGERY IS TO KEEP CYTOKINES OUT OF THE KEEP CYTOKINES OUT OF THE
CIRCULATIONCIRCULATION
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METABOLICMETABOLIC
CHANGESCHANGES
REEREE
INCREASESINCREASES
URINARYURINARY
NITROGENNITROGEN
EXCRETIONEXCRETION
Uncomplicated
Surgery
10% < 15 g/day
Severe Trauma 25 – 30%
(median survival 15 days)
15 – 20 g/day
( lean tissue lost 750 g/day)
Severe Burns 100 – 200%
(median survival
7 – 10 days)
30 -40 g/day
( lean tissue lost 1500 g/day)
Sepsis 50 – 80%
(median survival 10 days)
20 – 30 g/day
Cancer with PCM 20 – 30%
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GENERAL GOAL AND PRINCIPLES
Macronutrients:
1. Total Calories: 25 kcal/kg BW, in general 1 ml of water/kcal (matching energy input with expenditure remains controversial)
2. Glucose: 30 – 70% of total calories/day (2 – 5 g glucose/kg BW/day)
3. Fat: 15 – 30% of total calories/day
4. Protein: 15 – 20% of the total calories/day (estimated 1.2 – 1.5 g/kg BW/day)
Micronutrients:
Potassium, Magnesium, Zinc, and Phosphate.
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Route of Administration
Enteral route:
Preferred for NS, preserve gut integrity, barrier, immune functions, and reduce infection.
Early enteral nutrition (as soon as possible after resuscitation) is preferred.
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ENTERAL NUTRITION
1. In the early years EN focused predominantly on delivering adequate calories and protein
2. As more was learned from altered metabolism (renal, hepatic, diabetic, organ dysfunction ) : New formulas emerged
Specialized formulation
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IMMUNE ENHANCE FORMULA / IMMUNO-NUTRIENT
1. Contain spesific substrates aimed at cellular target
2. Intended to enhance immune cellularity and function minimized inflammation
3. Potential to alter outcomes : infections (morbidity)
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HOW TO PRACTICE :1. Which specific patients subgroups will
benefit from “ These formula “ compared with standard formula
2. Therapeutic dose for that benefit ?
3. When should the intervention be initiated for that benefit and for how long ?
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NUTRITION IN CLINICAL PRACTICE : EVIDENCE BASE
1. Critically ill patient / sepsis : These patients were extremely heterogenous “ Varied in results “
2. Elective surgical gastrointestinal cancer patients were more homogenous
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Immunonutrients
• Greater effects– Glutamine– Arginine -3 Fatty Acids
• Lesser effects– Nucleotides– Vitamins A, C, E– Zinc– Taurine
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Arginine:
• Conditionally essential AA (growth, illness, metabolic stress)
• Exogenous source of arginine appears necessary for optimal immune system functioning (T lymphocyte)
• Improve N – balance• “Modulate vascular flow patterns
via nitric oxide”
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Glutamine:
• Conditionally essential AA:– stress conditions– fuel for rapidly replicating cells: immune
cells, GI mucosa cells
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Product Neomune Impact Immun-Aid Oxepa
Manufacturer Otsuka Novartis B Braun Ross
Protein Source Caseinates, L-arginine; L-glutamine
Caseinates, L-arginine
Lactalbumin, L-arginine; L-
glutamine, L-valine, L-isoleucine
Caseinates
Fat Source MCT, fish oil, corn oil Palm kernel oil (MCT), fish oil, sunflower oil
MCT, Canola oil Canola oil, MCT, fish oil, Borage oil,
Lecithin
Carbohydrate Source Maltodextrin, fructose Hydrolized cornstarch
Maltodextrin, corn starch
Sucrose, Maltodextrin
% Protein (g/L)
% CHO (g/L)
% Fat (g/L)
25 (62.5)
50 (125)
25 (28)
22 (56)
53 (130)
25 (28)
32 (80)
48 (120)
20 (22)
16.7 (62.5)
28.1 (105.5)
55.2 (93.7)
Cal/mL 1.0 1.0 1.0 1.5
Free arginine (g/L) 12.5 12.5 14 0
Dietary Nucleotides (g/L)
0 1.2 1.0 0
-3 : -6 ratio
MCT : LCT ratio
1 : 2.52
50 : 50
1 : 1.47
27 : 63
1 : 2.18
50 : 50
1 : 2
25 : 75
Free Glutamine (g/L)
6.25 0 9 0
Beta Carotene
Carnitine & Taurine
Yes
Yes
Yes
No
Yes
No
Yes
Yes
Osmolality (mOsm/kg Water)
400 375 460 493
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Meta-analysis of Immunonutrition Enteral Feeds in GI Surgical Patients
Heys, et al: Ann Surg 1999; 229: 467.
Immunonutrition Control
Mortality 6/246 (2%) 4/251 (2%)
Infection rate 32/243 (13%) * 61/244 (25%)
Length of stay - 2,4 days *
6 trials: 497 patients * significant
Infections: pneumonia, intra abdominal abcess, wound infection, bactremia
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Effects of Perioperative Effects of Perioperative Imunonutrition inImunonutrition in
Malnourished Surgical PatientsMalnourished Surgical Patients
Postop-StandardDiet
(n=50)
Preop-IMNPostop-Standard diet
(n=50)
Preop-Postop IMN
(n=50)
Patients with majorcomplications
Patients with infectiouscomplications
Patients withcomplications, total No.
Mean LOS (days)
12
12
21
15.3
9
8
14
13.2**
6
5
9*
12.0#
*P=.02 VS the control group.**P=.01 VS the control group.
#P=.04 VS the preoperative group and P=.001 VS the control group.Weight loss>10%
Braga M et al: Arch Surg 2002;137:174
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Effects of Preoperative Oral Effects of Preoperative Oral ImmunonutritionImmunonutrition
in Non-malnourished Patientsin Non-malnourished Patients
Patients with infectiouscomplications
Length of hospital stay(days)
1 1 2
31 14* 16*
36 30 28
49 36 34
14 12* 12*Body weight loss<10% Preop 5days oral impact 1 L/d* p<0.03
Gianotti L et al:Gastroenterol 2002;122:1763
Preop-IMN
(n=102)
Preop-Postop IMN
(n=101)
Conventional
(n=102)
Death
Patients with noninfectiouscomplications
Patients with anycomplication
Gastroesophageal, pancreatic and colorectal resections
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When to Begin
Pre operative Peri operative Post operative
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The Use of Immune-Enhancing Enteral Formula with L-arginine, L-glutamine, Omega-3 Fatty Acids for Post
Operative Digestive Cancer Patients: Report of 20 Cases
Benny Philippi
Daldiyono
Lanny C. Salim
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Table 1. Inclusion and Exclusion Criteria
Inclusion Criteria:Weight loss 10% (from recent usual BW)post operative digestive malignancy patients, 18-65 years old, appropriate candidates to receive enteral nutrition for at least 7 days post operatively.
Exclusion Criteria:preoperative evidence of infection, hepatic and renal dysfunction,history of insulin-dependent diabetes mellitus, body weight > 130% of IBW, patients receiving immunosupressive agents or corticosteroids within 6 months
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Objective
• To evaluate the nutritional and immunology effects and clinical outcome of immune-enhancing formula compared with standard hospital formula in post operative digestive cancer patients.
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Patient’s Distribution
• Number of patients recruited: 27• Number of patients drop out: 7• Number of patients completed the trial: 20• Comparison: Male & Female = 9 (45%) : 11 (55%)• Age interval: 27 – 65 years (mean: 43.46 years)
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Table 2. Diagnosis and procedures
Variable No Procedures
Ca Gaster 6 Gastric resection (2)
Total Gastrectomy (4) *
Hepatobilier 1 Biliodigestive
Ca Caecum 2 Hemicolectomy Dex
Ca Sigmoid 8 Sigmoid resection
Ca Rectum 3 LAR
Total 20
* One case wound infection
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Table 3. Blood Analysis
Male Female
Pre - Op Post - Op Pre – Op Post - Op
Albumin (g/DL) 2,99 3,73 2,92 3,56
Pre albumin
(mg/dL)
13,06 21,98 15,53 22,87
Transferin
(mg/dL)
200,78 229 231 246,40
TLC 1031,11 2300 1272 1832
CD 4 474 847 297,11 568,33
CD 8 441,44 535,56 209.89 264,22
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Understanding CD4 and CD8 cells
• CD4 cells and CD8 cells are types of immune system white blood cells:– CD4 cells (also called helper T-cells)
coordinate immune activity and direct other immune cells
– CD8 killer T cells attack cancerous cells and cells infected with viruses
– (CD8 suppressor T cells inhibit immune activity once an invader is conquered)
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Table 4. Average Neomune® Intake
Mean Kcal/day 1041,36
Mean Protein g/day 64,96
Mean Days to start Neomune®
0.93
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500
1.000
1.500
2.000
2.500
pre 1.388,3 977,9
post 2.100,0 1721,4
ca gastric ca colon
* =p<0.05 ; Normal Value > 1000 cells/μL
*
*
Immunologic Status: TLC
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250,0
500,0
750,0
1.000,0
pre 643,0 271,9
post 848,3 597,6
ca gastric ca colon
* =p<0.05
*
*
Immunologic Status: cd 4
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200
300
400
500
600
700
pre 636,0 212,6
post 553,0 311,4
ca gastric ca colon
ns=p>0.05
Immunologic Status: cd 8
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10
15
20
25
pre 14,28 12,65
post 22,53 18,38
ca gastric ca colon
* = p<0.05; Normal Value: 16 – 40 mg/dL
*
Catabolic Status: Pre albumin
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150
200
250
300
pre 221,3 184,9
post 255,2 192,1
ca gastric ca colon
* = p<0.05; Normal Value: 200 – 360 mg/dL
*
Catabolic Status: Transferrin
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2,5
3,0
3,5
4,0
pre 3,22 2,84
post 3,82 3,53
ca gastric ca colon
* = p<0.05; Normal value: 3.5 – 5 g/dL
**
Albumin
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1,000
1,200
1,400
1,600
1,800
2,000
pre 1,158
post 1,812
tlc
*=p<0.05
*
Immunologic Status: TLC
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300.0
400.0
500.0
600.0
700.0
800.0
pre 385.6
post 707.7
cd4
*=p<0.05
*
Immunologic Status: cd 4
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100.0
200.0
300.0
400.0
pre 325.7
post 399.9
cd8
ns=p>0.05
Immunologic Status: cd 8
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10.00
15.00
20.00
25.00
pre 14.36
post 22.45
prealbumin
*
*=p<0.05
Catabolic Status: Pre Albumin
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200.0
210.0
220.0
230.0
240.0
pre 216.7
post 238.2
transferin
ns=p>0.05
Catabolic Status: Transferrin
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2.5
3.0
3.5
4.0
pre 2.95
post 3.64
albumin
*=p<0.05
*Albumin
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Recommendations US Summit on Immune-enhancing enteral therapy 2001; benefits from
immunonutrition include:
1. Patients undergoing major elective gastrointestinal (GI) surgery, especially malnourished patients
2. Patients with blunt and penetrating torso trauma
3. Malnourished patients undergoing surgery for head and neck cancer
4. Patients with severe head injury5. Burn patients6. Ventilator – dependent non septic patients at
risk for infection
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Practical Strategies
• Adequate IEF Nutrition content (glutamine, arginine, ω-3 Fatty Acid) and volume (arginine > 12 g/L)
• Duration of giving IEF > 3 days ( 5 – 10 days)
• Nasogastric feeding (every 4 – 6 hours,gastric residual 150 – 200 ml)
• Feeding goals: 25 kcal/kg BW, 800 ml.day
• NEO-MUNE Formula: 5 – 8 sachet/day
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Thank You