Transcript Immunonutrients in Surgical Patients

Immunonutrients in Surgical
Patients
Benny Philippi
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
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)
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
• BMI
– Female: 18
• Malnutrition 6 (20%)
– Male: 12
• Malnutrition 11 (36%)
• Albumin: Hypoalbuminemia
– Preoperative
– Post Operative Day 1
: 13%
: 70%
METABOLIC RESPONSE TO OVERNIGHT FASTING
ADH
NE / E
ACTH
TSH
GH
Glucose
Keton
NE/E
Glucagon
Insulin
Fat Cell
cortisol
Hepatic
Gluconeogenesis 
NE/N
cortisol
Free fatty acid
Growth hormon
cortisol
Thyroid hormon
Thyroid hormon
Amino acid
METABOLIC RESPONSE TO TRAUMA / ELECTIVE SURGERY
ADH (post hypophisis)
NE / E (symp n / adrenal med)
ACTH
TSH
ant hypophisis
GH
Glucose
Keton
NE/E
Glucagon
Insulin
Fat Cell
cortisol
Neuroendocrine
Activation 
NE/N
cortisol
Free fatty acid
Growth hormon
cortisol
Thyroid hormon
Thyroid hormon
Amino acid
METABOLIC RESPONSE TO SEPSIS
ADH
NE / E
ACTH
TSH
GH
Glucose
Keton
NE/E
Cytokines
Glucagon
Insulin
cortisol
Fat Cell
NE/N
cortisol
Free fatty acid
“Cytokine driven”
Growth hormon
cortisol
Thyroid hormon
Thyroid hormon
Amino acid
METABOLIC RESPONSE TO SEVERE INJURY
INJURY / SURGERYY
Afferent neural activity
Tissue hypoperfusion
CENTRAL NERVOUS
SYSTEM
Hormonal activity
Anorexia
Immobility
Pyrexia
Afferent neural activity
Changes in cellular hydration and cellular energetics
Protein catabolism
Capillary leak
Organ dysfunction
Neutrophils
Macrophages
Cytokiens
Oxygen free radicals
Arachidonic acid matabolites
Direct tissue effects
THE GOAL IN SURGERY IS TO
KEEP CYTOKINES OUT OF THE
CIRCULATION
METABOLIC
CHANGES
REE
INCREASES
URINARY
NITROGEN
EXCRETION
Uncomplicated
Surgery
10%
< 15 g/day
Severe Trauma
25 – 30%
(median survival 15
days)
15 – 20 g/day
( lean tissue lost 750
g/day)
100 – 200%
(median survival
7 – 10 days)
30 -40 g/day
( lean tissue lost 1500
g/day)
50 – 80%
(median survival 10
days)
20 – 30 g/day
Severe Burns
Sepsis
Cancer with PCM
20 – 30%
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.
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.
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
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)
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 ?
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
Immunonutrients
• Greater effects
– Glutamine
– Arginine
– -3 Fatty Acids
• Lesser effects
– Nucleotides
– Vitamins A, C, E
– Zinc
– Taurine
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”
Glutamine:
• Conditionally essential AA:
– stress conditions
– fuel for rapidly replicating cells: immune cells, GI
mucosa cells
Product
Neomune
Impact
Immun-Aid
Oxepa
Otsuka
Novartis
B Braun
Ross
Protein Source
Caseinates, Larginine; L-glutamine
Caseinates, Larginine
Lactalbumin, Larginine; 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
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
Manufacturer
% Protein (g/L)
% CHO (g/L)
% Fat (g/L)
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
Effects of Perioperative Imunonutrition in
Malnourished Surgical Patients
Braga M et al: Arch Surg 2002;137:174
Postop-Standard
Preop-IMN
Preop-Postop IMN
Diet
Postop-Standard diet
(n=50)
(n=50)
(n=50)
Patients with major
complications
12
9
6
Patients with infectious
complications
12
8
5
Patients with
complications, total No.
21
14
9*
Mean LOS (days)
Weight loss>10%
15.3
13.2**
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.
Effects of Preoperative Oral Immunonutrition
in Non-malnourished Patients
Conventional Preop-IMN
(n=102)
(n=102)
Preop-Postop
IMN
(n=101)
1
1
2
Patients with infectious
complications
31
14*
16*
Patients with noninfectious
complications
36
30
28
Patients with any
complication
49
36
34
Length of hospital stay(days)
14
12*
12*
Death
Body weight loss<10%
Gastroesophageal, pancreatic and colorectal resections
Preop 5days oral impact 1 L/d * p<0.03
Gianotti L et al:Gastroenterol 2002;122:1763
When to Begin
 Pre operative
 Peri operative
 Post operative
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
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
Objective
• To evaluate the nutritional and immunology
effects and clinical outcome of immuneenhancing formula compared with standard
hospital formula in post operative digestive
cancer patients.
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)
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
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
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)
Table 4. Average Neomune® Intake
Mean Kcal/day
1041,36
Mean Protein g/day
64,96
Mean Days to start
Neomune®
0.93
Immunologic Status: TLC
2.500
*
*
2.000
1.500
1.000
500
pre
post
ca gastric
ca colon
1.388,3
2.100,0
977,9
1721,4
* =p<0.05 ; Normal Value > 1000 cells/μL
Immunologic Status: cd 4
1.000,0
*
*
750,0
500,0
250,0
pre
post
ca gastric
ca colon
643,0
848,3
271,9
597,6
* =p<0.05
Immunologic Status: cd 8
700
600
500
400
300
200
pre
post
ca gastric
ca colon
636,0
553,0
212,6
311,4
ns=p>0.05
Catabolic Status: Pre albumin
*
25
20
15
10
pre
post
ca gastric
ca colon
14,28
22,53
12,65
18,38
* = p<0.05; Normal Value: 16 – 40 mg/dL
Catabolic Status: Transferrin
300
*
250
200
150
pre
post
ca gastric
ca colon
221,3
255,2
184,9
192,1
* = p<0.05; Normal Value: 200 – 360 mg/dL
Albumin
*
4,0
*
3,5
3,0
2,5
pre
post
ca gastric
ca colon
3,22
3,82
2,84
3,53
* = p<0.05; Normal value: 3.5 – 5 g/dL
Immunologic Status: TLC
*
2,000
1,800
1,600
1,400
1,200
1,000
tlc
pre
1,158
post
1,812
*=p<0.05
Immunologic Status: cd 4
*
800.0
700.0
600.0
500.0
400.0
300.0
cd4
pre
385.6
post
707.7
*=p<0.05
Immunologic Status: cd 8
400.0
300.0
200.0
100.0
cd8
pre
325.7
post
399.9
ns=p>0.05
Catabolic Status: Pre Albumin
*
25.00
20.00
15.00
10.00
prealbumin
pre
14.36
post
22.45
*=p<0.05
Catabolic Status: Transferrin
240.0
230.0
220.0
210.0
200.0
transferin
pre
216.7
post
238.2
ns=p>0.05
4.0
Albumin
*
3.5
3.0
2.5
albumin
pre
2.95
post
3.64
*=p<0.05
Recommendations US Summit on Immuneenhancing 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 injury
5. Burn patients
6. Ventilator – dependent non septic patients at
risk for infection
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
Thank You