Transcript Nutrition in the septic Patient

Nutrition Support in Critically Ill
Later Nutritional Needs and Metabolic
Aberrations in Ventilated Patients
John P. Grant, MD, CNSP
Director Nutrition Support Service
Professor of Surgery
Duke University Medical Center
Durham, NC
Optimal Metabolic Care of the
Critically Ill Patient
Provide Optimal Metabolic Milieu
Maintain oxygenation
Adjust pH
Ensure perfusion
Control waste (dialysis - vol,lytes,prot)
Optimal Metabolic Care of the
Critically Ill Patient
Minimize Metabolic Stress Response
Control pain
Debridement of necrotic/infected tissue
Drain abscesses
Dress or cover wounds
Optimal Metabolic Care of the
Critically Ill Patient
Optimize milieu for cell metabolism
Minimize stress response
Provide adequate and appropriate
nutritional support
Importance of Adequate Nutrition
in the Critically Ill Patient
Nutrient balance and mortality in ICU patients
4/15 with positive nitrogen balance died (27%)
11/28 with 0 to -10,000 Kcal balance died (39%)
12/14 with > -10,000 Kcal balance died (86%)
Bartlett et al., Surgery 92:771, 1982
Caloric Balance and Outcome in ICU
A = positive caloric
balance
B = 0 to -10,000
kcal balance
C = > -10,000 kcal
balance
Caloric Balance vs % Mortality
86
90
80
70
60
50
40
30
20
10
0
39
27
A
B
Bartlett et al., Surgery 92:771, 1982
C
Days of Survival Without Nutrition
Days = { [(UBW X 2430) x K] - [(UBW - BW) x 2430]}
AEE - Ei
Where:
UBW = usual body weight in kg
BW = current body weight in kg
K = 0.35 with stress; 0.4 with simple starvation
AEE = actual energy expenditure (kcal/d)
Ei = energy intake (kcal/d)
Importance of Adequate Nutrition
in Respirator Dependent Patients
Arora and Rochester evaluated the effects of malnutrition on
diaphragmatic muscle dimensions at necropsy and in vivo
function in patients after prolonged illness (75% UBW) as
compared with well nourished patients.
Diaphragmatic muscle mass
Max Inspiratory Vacuum
43% less
35% normal
Max Expiratory Pressure
Max Ventilatory Volume
59% normal
41% normal
Arora, N.S., and Rochester, D.F.: Am. Rev. Respir. Dis., 126:5-8, 1982.
Adequate Nutritional Support of
Respirator Dependent Patients
Excessive calories, especially excess glucose calories, can
result in excessive CO2 production and increased ventilatory
demand in the already compromised patient. May delay
weaning.
In ventilatory dependent patients, a high caloric load (2 X
REE) has been shown to result in significantly higher O2
consumption and CO2 production than a moderate load
(1.5 X REE) in patients otherwise receiving an identical diet.
Van den Berg, B., and Stam, H.: Intensive Care Medicine, 14:206-211, 1988.
Adequate Nutritional Support of
Respirator Dependent Patients
Formulas for estimating caloric needs:
Ireton-Jones formula was designed specifically
for patients with burns or trauma who simultaneously had
pulmonary failure. The Ireton-Jones formula is:
BEE = 1925 - 10(A) + 5(W) + 281(S) 292(T) + 851(B)
where A = age in years, W = weight in kilograms,
S = sex (male = 1, female = 0),
and T = trauma and B = burn (present = 1, absent = 0)
Adequate Nutritional Support of
Respirator Dependent Patients
Formulas for estimating caloric needs: Cal Long
AEE (men) = (66.47 + 13.75 W + 5.0 H - 6.76 A) x (activity
factor) x (injury factor)
AEE (women) = (655.10 + 9.56 W + 1.85 H - 4.68 A) x (activity
factor) x (injury factor)
Activity Factor
Use
Injury Factor
Use
Confined to bed
1.2
Minor OR
1.2
Out of Bed
1.3
Skeletal Trauma
1.3
Major Sepsis
1.6
Severe Burn
2.1
Caloric Support of the ICU Patient
Organ Specific Substrate Support
Carbohydrate
Long-chain fatty acids
Medium-chain fatty acids
(Structured Lipids)
Branched-chain amino acids
Glutamine
Organ Specific Substrate Support
Glucose
Glucose is required by the brain, renal
medulla, red blood cells, and
fibroblasts
Recommended daily consumption:
Minimum of 200 and up to 700
grams/day (700 to 2400 kcal/day)
As increasing amounts of
glucose are infused, a
maximal rate of glucose
oxidation and whole body
protein synthesis is
obtained at 5.0 to 6.0
mg/kg/min (~630 g/d for
80 kg patient)
Burke et al., Ann Surg, 190:274, 1979
Use of Insulin to Stimulate
Glucose Utilization
Does lower blood sugar in most cases
Drives glucose mainly into muscle
No documented increase in glucose
oxidation or nitrogen sparing
Vary et al., JPEN 10:351, 1986
Use of Insulin in Glucose
Utilization
Anaerobic Glycolysis
Pyruvate
Pyruvate Dehydrogenase
Insulin
Krebs cycle

Fat Synthesis
Organ Specific Substrate
Support
Long-Chain Fatty Acids
Used as a fuel by many organs in the body
Must provide essential fatty acids (Linoleic,
Arachidonic, Linolenic) = 15 grams/day
Organ Specific Substrate Support
Long-Chain Fatty Acids
Increased fat clearance from
bloodstream during stress
Yet only about 8% is oxidized
immediately
Goodenough et al., JPEN 8:357, 1984
Organ Specific Substrate Support
Long-Chain Fatty Acids
In severe stress, fat clearance is minimal
Cerra et al., Surgery 86:409, 1979
Lundholm et al., Crit Care Med 10:740, 1982
May depress RES (>1 kcal/kg/h)
Hamaway et al., JPEN 9:559, 1985
Organ Specific Substrate Support
Long-Chain Fatty Acids
Substituted glucose isocalorically with fat
in an experimental animal burn model
Demonstrated a linear decrease in
nitrogen balance as glucose was reduced
N loss = 17.44 - 1.997 log e (glucose intake
Kcal/sq m/d) + 0.0752 RME (kcal/sq m/d)
Long et al., Ann Surg 185:417, 1977
Long-Chain Fatty
Acids
Require carnitine for
transport through the
inner mitochondrial
membrane for beta
oxidation
Organ Specific Substrate
Support
Long-Chain Fatty Acids
Average recommended dose = 40 - 60
grams/day (360 to 540 kcal/day)
Adequate Nutritional Support of
Respirator Dependent Patients
Lipid Support - Intravenous lipid emulsions can be harmful
There is a nonlinier relationship between triglyceride
concentration and rate of lipoprotein lipase-mediated
triglyceride hydrolysis. When infusion of triglyceride exceeds
hydrolysis, serum triglyceride concentrations rise. If triglyceride
concentrations exceed a certain level, triglyceride-rich
lipoproteins can be removed via nonenzymatic pathways,
particularly by the reticuloendothelial system and the lung.
Adequate Nutritional Support of
Respirator Dependent Patients
Lipid Support - Intravenous lipid emulsions can be harmful
Higher infection rate, prolonged pulmonary failure, and
delayed recovery was observed in a group of trauma patients
given TPN with lipid infusions compared to a second group
given TPN without lipids.
Battistella, F.D., et al.: J. Trauma, 43:52-58, 1997.
Adequate Nutritional Support of
Respirator Dependent Patients
Lipid Support –
A minimum of 1 to 2 percent of total caloric intake
should be in the form of essential fatty acids to
meet nutritional requirements
Give a mixture of glucose and long-chain fatty acids
in a ratio of 60 to 80 percent glucose to 20 to 40
percent fat
Organ Specific Substrate Support
Structured Lipids
Contain both long-chain (40-50%)
and medium-chain (50-60%) fatty
acids (MCFA)
MCFA are used as a fuel by most
tissues
Organ Specific Substrate Support
Structured Lipids
MCFA do not require carnitine for
entry into mitochondria
Provide adequate essential fatty acids
Organ Specific Substrate Support
Structured Lipids
Improved N2 balance in burned rats
Maiz et al., Metabolism 33:901, 1984
Improved N2 balance in stressed
patients
Dennison et al., JPEN 12:15, 1988
Less interference with the RES
Hamaway et al., JPEN 9:559, 1985
Adequate Nutritional Support of
Respirator Dependent Patients
Protein Support – adjusted for positive nitrogen balance,
reduced for renal and hepatic dysfunction
No stress
Mild Stress
Moderate Stress
Severe Stress
0.7 to 0.8 g/kg/day
0.8 to 1.0 g/kg/day
1.0 to 1.5 g/kg/day
1.5 to 2.0 g/kg/day
Organ Specific Substrate Support
Branched-Chain Amino Acids
Alanine
Leucine
Isoleucine
Organ Specific Substrate Support
Branched-Chain Amino Acids
Main energy source for skeletal muscle
during stress and sepsis
Not metabolized by the liver: safe to give
during liver failure
Give 30 - 40 grams/day: 100 -160
kcal/day (45% BCAA Solution)
Protein
BCAA can
enhance nitrogen
balance during
periods of
maximal stress
Cerra et al., Crit Care Med, 11:775, 1983
Organ Specific Substrate Support
Glutamine
Necessary precursor for protein and
nucleotide synthesis
Regulates acid-base balance
through production of urinary
ammonia
Major transporter of nitrogen (along
with alanine)
Importance of Glutamine
in Cell Nutrition
Enterocytes
Lymphocytes
Fibroblasts
Bone Marrow
Pancreas
Lung
Tumor Cells
Renal Tubular Cells
Vascular Epithelial
Cells
Glutamine Metabolism
Metabolized similarly whether it enters
enterocyte across the brush border from
intestinal lumen or across the basolateral
cell membrane from the arterial blood
Oxidation via Krebs cycle yields 30 mole
ATP per mole glutamine (glucose = 36)
Glutamine Metabolism
Gut normally extracts 20 to 30% of
glutamine from blood
During stress, muscle releases amino
acids with glutamine and alanine
making up 60% of total
Muscle glutamine concentration
decreases by up to 50% with
prolonged stress
Glutamine Metabolism
Uptake of glutamine by the gut is
greatly increased in stress,
exceeding muscle release
Serum glutamine concentrations fall
leading to a relative deficiency state
Provide 6 - 50 grams/day (24 - 200
kcal)
Appropriate Nutritional Support of
Respirator Dependent Patients
Enteral vs Parenteral Support
Postburn Hypermetabolism and
Early Enteral Feeding
30% BSA burn in
guinea pigs
Enteral feeding via
g-tube at 2 or 72
hours following burn
Mucosal weight and
thickness were similar
RME % Initial
160
175 Kcal - 72 h
150
140
200 Kcal - 72 h
130
120
175 Kcal - 2 h
110
100
0
2
4
6
8
10 12
Postburn day
Alexander, Ann Surg 200:297, 1984
Denham, Gastroenterology, 113:1741, 1997
Suppression of Cytokines
Antagonizing IL-1 and/or TNF
activity or blocking receptors –
antibody and receptor antagonists
Dramatic improvement in severity and
mortality of experimental acute
pancreatitis
Norman, Ann Surg, 221;625, 1995
Tanaka, Crit Care Med, 23:901,
1995
Suppression of Cytokines
Preventing IL-1 and/or TNF production
Generic macrophage pacification
IL-10 regulation of IL-1 and TNF
Inhibiting post-transcriptional modification
of pro-IL-1
Norman, J. Interfer Cytokine Res, 17:113, 1997
VanLaethem, Gastroenterology, 108:1917, 1995
Suppression of Cytokines
Gene therapy to inhibit systemic
hyperinflammatory response of
pancreatitis
Denham, J Gastrointest Surg, 2:95, 1998
Norman, Gastroenterology, 112:A467, 1997
GALT System
Gut-associated
lymphoid tissue
Intraepithelial
lymphocytes
Lamina propria
lymphoid tissue
Peyer’s patches
Mesenteric lymph
nodes
GALT System
Intraepithelial lymphocytes
First to recognize foreign antigens
Lamina propria lymphoid tissue
Source of IgA
Peyer’s patches
Process antigens from intestinal
lumen
GALT System
Responsible for reacting to harmful
foreign antigens (e.g. bacterial or
viral pathogens)
Must not react to non-threatening
antigens to avoid chronic
inflammatory condition
GALT System
Intravenous feeding with bowel rest and
starvation result in significant suppression
of the mass and function of GALT, with
reduction in IgA secretion and increased
gut permeability.
Oral and enteral feedings preserve GALT
mass and function
Li, J Trauma, 39:44, 1995
GALT System
Bowel rest (or an elemental diet)
reduces intraluminal nutrients that
bacteria need
Induces an adaptive response of
bacteria to increase their adherence to
the intestinal wall as a source of
nutrients.
Bacterial adherence causes cellular
injury, or even bacterial penetration
Optimal Metabolic Care of the
Critically Ill Patient
If 2% L-glutamine is added to TPN in
experimental animal models
Mass and function of GALT is better preserved
Reduces mortality in experimental sepsis model
Not as effective as enteral nutrition
Onset
of Pain
Or
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nD
ysf
un
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on
ER Pres
entation
Relative Incidence
Interventional Window
Hours
Caloric Support of the Critically
Ill Patient
Kcal/kg/day for stress = 25 (mild), 30
(moderate), 35 (severe)
Long modification of Harris-Benedict
Formula
Indirect calorimetry
Nutrition Support in Critically Ill
Patients
Conclusions
Optimize milieu for cell metabolism
Minimize stress response
± Early dialysis (volume, protein, lytes)
Nutrition Support in Critically Ill
Patients
Conclusions
Begin nutrition support early (24-48
hrs)
If the gut works, use it….
If the gut doesn’t work, make it work
Use insulin sparingly