Nutrition Support in Critically Ill Later Nutritional Needs and Metabolic Aberrations in Ventilated Patients John P. Grant, MD, CNSP Director Nutrition

Nutrition Support in Critically Ill

Later Nutritional Needs and Metabolic Aberrations in Ventilated

PatientsJohn P. Grant, MD, CNSPDirector Nutrition Support Service

Professor of SurgeryDuke 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)


Minimize Metabolic Stress Response Control pain

Debridement of necrotic/infected tissue Drain abscesses Dress or cover wounds


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

2739

86

0102030405060708090

A B C

Caloric Balance vs % Mortality

Bartlett et al., Surgery 92:771, 1982

Days = { [(UBW X 2430) x K] - [(UBW - BW) x 2430]}

AEE - Ei

Where:

Days of Survival Without Nutrition

UBW = usual body weight in kgBW = 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

43% less

Max Inspiratory Vacuum 35% normal

Max Expiratory Pressure 59% normal

Max Ventilatory Volume 41% normalArora, 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 specificallyfor 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)


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 PatientOrgan Specific Substrate Support

Carbohydrate Long-chain fatty acids Medium-chain fatty acids (Structured Lipids) Branched-chain amino acids Glutamine

Organ Specific Substrate SupportGlucose

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

UtilizationDoes lower blood sugar in most cases

Drives glucose mainly into muscle

No documented increase in glucose oxidation or nitrogen sparingVary 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



Increased fat clearance from bloodstream during stress

Yet only about 8% is oxidized immediately

Goodenough et al., JPEN 8:357, 1984



In severe stress, fat clearance is minimalCerra et al., Surgery 86:409, 1979Lundholm et al., Crit Care Med 10:740, 1982

May depress RES (>1 kcal/kg/h)Hamaway et al., JPEN 9:559, 1985


Long-Chain Fatty AcidsSubstituted glucose isocalorically with fat in an experimental animal burn modelDemonstrated 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


Require carnitine for transport through the inner mitochondrial membrane for beta oxidation



Average recommended dose = 40 - 60 grams/day (360 to 540 kcal/day)


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.


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.


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


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


Structured Lipids

MCFA do not require carnitine for entry into mitochondria

Provide adequate essential fatty acids


Structured Lipids

Improved N2 balance in burned ratsMaiz et al., Metabolism 33:901, 1984

Improved N2 balance in stressed patients Dennison et al., JPEN 12:15, 1988

Less interference with the RESHamaway et al., JPEN 9:559, 1985


Protein Support – adjusted for positive nitrogen balance, reduced for renal and hepatic dysfunction

No stress 0.7 to 0.8 g/kg/day

Mild Stress 0.8 to 1.0 g/kg/day

Moderate Stress 1.0 to 1.5 g/kg/day

Severe Stress 1.5 to 2.0 g/kg/day


Branched-Chain Amino Acids

Alanine

Leucine

Isoleucine


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

EnterocytesLymphocytesFibroblastsBone Marrow

PancreasLungTumor CellsRenal Tubular CellsVascular 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 MetabolismGut 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

PatientsEnteral vs Parenteral Support

Postburn Hypermetabolism and Early Enteral Feeding

30% BSA burn in guinea pigsEnteral feeding via g-tube at 2 or 72 hours following burnMucosal weight and thickness were similar

100

120

140

150

160

0 2 4 6 8 10 12

RME % Initial

Postburn day

175 Kcal - 72 h

200 Kcal - 72 h

175 Kcal - 2 h

Alexander, Ann Surg 200:297, 1984

130

110

Denham, Gastroenterology, 113:1741, 1997

Suppression of CytokinesAntagonizing 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, 1995Tanaka, Crit Care Med, 23:901, 1995

Suppression of CytokinesPreventing 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 SystemGut-associated lymphoid tissue

Intraepithelial lymphocytes

Lamina propria lymphoid tissue

Peyer’s patches

Mesenteric lymph nodes

GALT SystemIntraepithelial 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 SystemBowel 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 (translocation), with an adverse host response.


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

HoursO nset of Pain

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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

Documents

Nutrition Support in Critically Ill Later Nutritional Needs and Metabolic Aberrations in Ventilated Patients John P. Grant, MD, CNSP Director Nutrition