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Immunonutrition:

modulate the immune system

facilitate wound healing

reduce oxidative stress

contain certain compounds:

l-glutamine l-arginine omega-3 fatty antioxidants

ASPEN/ESPEN: Immune-modulating enteral formulations (supplemented with agents such as arginine, glutamine, nucleic acid,ω-3 fatty acids, and antioxidants) should be used for the appropriatepatient population (major elective surgery, trauma, burns, head andneck cancer, and critically ill patients on mechanical ventilation),with caution in patients with severe sepsis.

To receive optimal therapeutic benefit from the immune-modulatingformulations, at least 50%–65% of goal energy requirements shouldbe delivered daily.

L-ARGININE

plays fundamental roles in protein metabolism

polyamine synthesis

critical substrate for nitricoxide (NO) production

stimulates the release ;

growth hormone

insulin growth factor and insulin

all of which may stimulate protein synthesis and promote wound healing.

The enzyme, l-arginase, metabolizes l-arginine to l-ornithine, an amino acid implicated in wound healing.

Guidelines for arginine supplementation can be summarized as follows:

Higher than normal (supraphysiologic) l-arginine

supplementation is necessary

. Normal l-arginine intake is 3 to 5 g/d.

Dietary supplementation with l-arginine alone should not be used, as only diets

Immunonutrition incorporating supraphysiologic quantities Of l-arginine ideally should be started preoperatively as an oral dietary supplement and continued in the postoperative

A clear benefit of l-arginine-containing immunonutrition has

not been observed in medical patients, particularly those withsepsis.All elective surgical patient populations, including

patientsundergoing operations for head and neck cancer and patientsundergoing cardiac or GI surgery, appear to benefit from the useof immunonutrition formulas containing l-arginine.

Risk vs Benefit Arginine

OMEGA-3 FATTY ACIDSincorporated into phospholipids and thereby

influence the structure and function of cellular membranes.as substrates for the enzymes

cyclooxygenase, lipoxygenase, and cytochrome P450 oxidaseincreasing the quantity of omega-3 fatty

acids(found in fish oils) in the diet reduces platelet aggregation, slows blood clotting, and limits the production of proinflammatory cytokines.

.

administration of dietary lipids rich in omega-3 fatty acids can modify the lipid profile and favorably affect clinical outcome a mong critically ill patients with ARDS

L-GLUTAMINE:The amino acid, l-glutamine, plays a

central role in nitrogen transport within the body.

used as a fuel by rapidly dividing cells, particularly

lymphocytes and gut epithelial cells.substrate for synthesis of the important

endogenous antioxidant

translocation of enteric bacteria and endotoxins is reduced and infective complications less frequent.

l-Glutamine unfortunately is unstable in aqueous solutions.

To overcome this problem, l-glutamine is added to TPN solutions as adipeptide (l-alanyl-l-glutamine).

In patients receiving EN, l-glutamine powder can be dissolved into the nutrition formulation.

Glutamine (enteral):All: The addition of enteral glutamine to an EN regimen (not alreadycontaining supplemental glutamine) should be considered inthermally injured, trauma, and mixed ICU patients.

Selenium; is an essential component of the most importantextra- and intra-cellular antioxidant enzyme family, the glutathione peroxidases (GPX).doses of 750–1000 mcg/day should probably not be exceeded in the critically ill, and aministration of supraphysiological ddoses should perhaps be administratlimited to 2 weeks.

20-60 mcg

Ascorbic acid (C) 200 mg

Vitamin A 3300 IU

Vitamin D 5 mg

Vitamin E 10 IU

Recommended Daily Intake

Which Nutrient for Which Population?

ElectiveSurgery

Critically Ill

General Septic Trauma Burns Acute Lung Injury

Arginine Benefit No benefit Harm(?)

(Possible benefit)

No benefit

No benefit

Glutamine Possible Benefit

PN BeneficialRecom-mend

… EN Possibly

Beneficial:Consider

EN Possibly

Beneficial:Consider

…

Omega 3 FFA

… … … … … Recom-mend

Anti-oxidants

… Consider … … … …

Canadian Clinical Practice Guidelines

ADULT : NUTRITIONAL REQUIREMENTS

Age Activity level Current nutritional status Current metabolic and disease states

The nutritional requirements of each patient will depend upon a number of factors including:

Metabolic cart

predictive equations

1)Calorie Requirements:

If available, indirect calorimetry can be used to measure energy expenditure using gas exchange

When indirect calorimetry is not possible, there are many possible predictive equations

whichever method (indirect calorimetry or predictive equation) is used, the optimal energy provision for hospitalized patients has yet to be determined

Metabolic cart (28, 29): Indirect calorimetry using a “metabolic cart” measures actual energy expenditure by collecting, measuring and analyzing the oxygen consumed (VO2) and the carbon dioxide (VCO2) expired. From these measurements the respiratory quotient (RQ) is calculated

a. RQ = VOz/VCOz

b. REE = (3.94 [VOz] + 1.1 [VCOz]) 1.44 - (2.17 [UUN])

Note: Patient has to be intubated for the test to be performed

FIO2<60%, no air leak

chest tube leak.

PREDICTIVE EQUATIONS

Harris-Benedict

Miflin St. Jeor (MSJ)

Use of Indirect Calorimetry vs. Predictive Equations PCG: 2013 Recommendation: There are insufficient data to make a recommendation on the use of indirect calorimetry vs. predictive equations for determining energy needs for nutrition or to guide when nutrition is to be supplemented in critically ill patients.

Conclusions:

The use of indirect calorimetry compared to

predictive equations to meet enteral nutrition needs has

no effect on mortality.

Predictive equations should be used withcaution, as they provide a less

accurate measure of energy requirements than indirect

calorimetry in the individual patient.

(A.S.P.E.N)

Calorie Requirements:

CALORIE REQUIREMENTS IN MOST HOSPITALIZED PATIENTS

Resting energy expenditure (REE)—the energy expenditure while resting in the supine position with eyes open

About 10% greater than BEE

Sleeping energy expenditure (SEE)

It is usually 10% to 15% lower than REE

Activity energy expenditure (AEE)

During maximum exercise it can be 6- to 10-fold greater than the BEE.

Total energy expenditure (TEE)

the sum of energy expended during periods of sleep, resting, and activity.

eREE = eBEE • stress factor

eTEE = eREE • activity factorestimated total energy expenditure

estimated resting energy expenditure;

Stress FactorsMajor surgery: 15%-25%

Infection: 20%

Long bone fracture: 20%-35%

Malnutrition: Subtract 10%-15%Burns: Up to 120% depending on extent

Sepsis: 30%-55%Major trauma: 20%-35%

COPD: 10%-15%Sedated mechanically ventilated patients: Subtract 10%-15%.

Activity Factors

Sedated mechanically ventilated patients: 0-5%Bedridden, spontaneously breathing nonsedated patients: 10%-15%Sitting in chair: 15%-20%Ambulating patients: 20%-25%

Daily Caloric Requirements Using Measured or

Estimated REEUsing Body Weight

Sedated mechanically ventilated patients 1.0-1.2 • REE 20-24 kcal/kg

Unsedated mechanically ventilated patients 1.2 • REE 22-24 kcal/kg

Spontaneously breathing critically ill patients 1.2-1.3 • REE 24-26 kcal/kg

Spontaneously breathing ward patients (maintenance)

1.3 • REE 24-26 kcal/kg

Spontaneously breathing ward patients (repletion) 1.5-1.7 • REE 25-30 kcal/kg

University of Kentucky Medical Center

KCAL/Kg

HBE or MSJ x Injury factor

KCAL/Kg Wound Healing: 30-35 kcal/kg, increase to

35-40 kcal/kg if the pt is underweight or losing weight.

Sepsis and Infection: 30-40 kcal/kg Trauma: 25-30 kcal/kg Acute Spinal Cord Injury (SCI) 23kcal/kg or

HBE w/o stress factor Chronic SCI: 20-23kcal/kg depending on

activity Stroke: 19-20kcal/kg or (HBE x .95-1.15) COPD: 25-30 kcal/kg

University of Kentucky Medical Center

ARF: 25-35 kcal/kg

Hepatitis: 25-35 kcal/kg if well-nourished 30kcal/kg), 30-40 kcal/kg if malnourished

Cirrhosis without encephalopathy: 25-35 kcal/kg

Cirrhosis with encephalopathy: 35 kcal/kg

Severe Acute Pancreatitis: 35 kcal/kg

Organ Transplant: 30-35 kcal/kg

Cancer: Sedentary/normal wt = 25-30 kcal. Hypermetabolic, need to gain weight, or anabolic = 30-35 kcal/kg.

Hypermetabolic, malabsorption, severe stress: > 35 kcal/kg

. Obese = 21-25 kcal/kg

Major Elective HBE x 1.2 - 1.3

Major Non-elective HBE x 1.3 - 1.5

Minor Elective HBE x 1.2

Minor Non-elective HBE x 1.2 - 1.3 Infection w/temp HBE x 1.2 - 1.3

Estimated Calorie Needs: HBE or MSJ x Injury factor

Traumatic Brain Injury (CHI) HBE x 1.4

Multiple trauma & CHI HBE x 1.4 – 1.6

Pentobarbital coma HBE x 1.0 – 1.2

Stroke and SAH HBE x 1.0- 1.2

Pneumonia (or ARDS) HBE x 1.2 - 1.3

Neuromuscular Blockade HBE x 1

Energy:

Use 25-30kcal/kg, or predictive equations, or

indirect calorimetry.

ASPEN

Consider hypocaloric feeding in critically ill obese (BMI >30kg/m2), e.g. 60-70% of target energy requirements, or 11-14kcal/kg actual body weight, or 22-25kcal/kg ideal body weight.

ESPEN : 20-25kcal/kg in acute phase

of critical illness.

25-30kcal/kg in recovery phase.

Carbohydrates

provide 4 kcal/g (IV dextrose = 3.4 kcal/g) with an RQ of 1.0.

Between 40% and 60% of total caloric needs (or 70% of nonprotein calories)

Minimum 2g/kg ESPEN 2009Maximal glucose oxidation rate is 4-7 mg/kg/minute/24hours. Ideally keep to ≤5mg/kg/minute/24hours

Protein

1. Normal patient = 0.8 to 1.0 g/kg

2. Postsurgical, mild trauma = 1.25 to 1.5 g/kg

3. Severe trauma, sepsis, organ failure = 1.5 to 2.0 g/kg

4. Burn (>20%) or severe head injury ~2.0 g/kg

1.3-1.5g protein/kg. ESPEN

1.2-2.0g protein/kg if BMI<30kg/m2. ASPEN2g/kg ideal weight if BMI 30-40kg/m2. 2.5g/kg ideal weight if BMI >40kg/m2.

Fat

provides 9 kcal/g with an RQ of 0.7.

Between 20% and 30% of totalcaloric requirements (or 30% of

nonprotein calories)

0.7-1.5g/kg. ESPEN

ENTERAL NUTRITION

1)Oral intake is contraindicated

Dysphagia, mechanical ventilation, mandibular fractures, head & neck surgery, neurological impairment, demyelinating diseases such as amyotrophic lateral sclerosis, muscular dystrophy, etc.

Examples

INDICATIONS FOR INITIATION OF ENTERAL NUTRITION

2)Inability to meet markedly increased nutritional needs

with oral intake

Burns, trauma, radiation therapy, chemotherapy, sepsis/infection,

closed head injury

Examples

3)Inability to meet basic nutritional needs with oral intake alone

Anorexia, cancer, head and neck tumors

Examples

4)Need to bypass part of the GI tract to allow enteral nutrition

Examples

Pancreatitis, gastric outlet obstruction, esophageal cancer, gastroparesis

5)The need for supplemental nutrition due to decreased

absorption Examples

Short bowel syndrome, inflammatory bowel disease, fat

malabsorption or other malabsorptive syndromes such

as cystic fibrosis

Benefits of Enteral Nutrition (compared with Parenteral Nutrition) Stimulates immune barrier function Physiologic presentation of nutrients Maintains gut mucosa Attenuates hypermetabolic response Simplifies fluid/electrolyte management More “complete” nutrition than parenteral nutrition o iron, fiber, glutamine, etc. are not provided. Less infectious complications (and costs associated with these complications) Stimulates return of bowel function Less expensive

Delivery Method:

Continuous or cyclic:

Intermittent feeding

Bolus feeding

Continuous or cyclic

18-24 h

25cc/h

8-24h double

125-150cc/h

Intermittent feedingusually 240-480ml, over a 45-60 minute period 5-8 times per day. Preferred by ambulatory patients.Disadvantage includes: poor tolerance since a larger feeding volume is administered over a short time.

rapid infusion via syringe through a gastrostomy tube

Bolus feeding

may result in nausea, diarrhea, distention, cramps, or aspiration

300-500cc3-5h5-10min

Bolus feeding is discouraged in the ICU.

Carbohydrate (CHO):

Concentration & form of CHO constitute major differences between formulas Forms of CHO include:

Simple sugars and monosaccharides

(glucose and fructose). Disaccharides (sucrose, lactose, and maltose) require enzymatic conversion to monosaccharides in the intestinalbrush border prior to absorption.

Polysaccharides and oligosaccharides

, produced from hydrolysis of starch, result in glucose polymers of intermediate chain lengths.

Starch hydrolysis increases the solubility and osmolality of the product

Protein:

Three major categories are classified by degree of digestion required: Intact protein, found in whole

foods, requires complete digestion.

Crystalline amino acids – theoretically require minimal

digestion. The small particle size increases the osmolality

Hydrolyzed protein –enzymatically hydrolyzed to smaller peptide fragments and free amino acids, partially hydrolyzed protein requires digestion while di and tri-peptides are absorbed directly.

Useful in conditions such as:short bowel and Crohn's disease and

pancreatic insufficiency.

Fat:

Increases the caloric density but does not contribute to the osmolality.

Most formulas contain long chain triglycerides (LCT) with variable

amounts of medium-chain triglycerides (MCT) and mono and diglycerides.

MCT are transported via the portal system directly into the blood stream

they are oxidized to ketones and carbon dioxide.

MCT does not require emulsification for absorption

their use is indicated with CF, liver disease, pancreatitis,and other disorders where fat absorption may be impaired.

Timing of enteral nutrition

All: EN should be started within the first 24–48 hours

following admission

PCG

2013 Recommendation: Based on 16 studies, we recommend early enteral nutrition (within 24-48 hours following admission to ICU) in critically ill patients.

Conclusions:

1) Early enteral nutrition, when compared to delayed nutrient intake is associated

with a trend towards a reduction in mortality in critically ill patients.

2) Early enteral nutrition, when compared to delayed nutrient intake is

associated with a significant reduction in infectious complications

3) Early enteral nutrition, when compared to delayed nutrient intake

has no effect on ICU or hospital length of stay.

4) Early enteral nutrition, when compared to delayed nutrient intake

improves nutritional intake

PCG

There were no new randomized controlled trials since the 2009 update and hence there are no

changes to the following summary of evidence.

Achieving Target Dose of Enteral Nutrition

Dosage of enteral feeding

ASPEN: The feedings should be advanced toward the

patient’s goalover the next 48–72 hours

Efforts to provide > 50%–65% of goal energy should be made in

order to achieve the clinical benefit of EN over the first week of hospitalisation.

ESPEN:

No general amount can be recommended as EN therapy

hasto be adjusted according to the

progression/course of the disease

and to gut tolerance

ASPEN/CCPG: If unable to meet energy requirements (100%

of target goal energy) after 7–10 days by the enteral route

alone, consider initiating supplemental parenteral nutrition ESPEN: All patients who do not meet their

nutritional needs after 2 days should receive supplemental PN.

Haemodynamically unstable patientsASPEN: In the setting of haemodynamic compromise :patients requiring significant haemodynamic support including high dose catecholamine agents, alone in combination with large volumefluid or blood product resuscitation to maintain cellular perfusion),EN should be withheld until the patient is fully resuscitated and/or stable.

Immune-modulating enteral formulations

ASPEN/ESPEN: Immune-modulating enteral formulations supplementaed with agents such s arginine, glutamine, nucleic acid, ω-3 fatty acids, and antioxidants) should be used for the appropriatepatient population (major elective surgery, trauma, burns, head and neck cancer, and critically ill patients on mechanical ventilation),with caution in patients with severe sepsis

Complications of overfeeding include (but not limited to):

. Hyperglycemia

. Lipogenesis

Fluid and fat gain rather than lean body mass gain

Fatty liver

Immunosuppression (with excessive lipid and linoleic acid intake)

Increased minute ventilation (VE)

Excessive CO2 production impairing pulmonary status/vent wean

DRUG NUTRIENT INTERACTIONS WITH ENTERAL PRODUCTS

Only administer sucralfate (CarafateR), omeprazole, antacids, iron salts, and ketoconazole (NizoralR) into the stomach

Stop continuous tube feedings for 1 hour before and 1 hour after each phenytoin (DilantinR) dose to maximize the drugabsorption.

When diarrhea occurs, determine if any medication contains excessive quantities of sorbitol. Examples include:acetaminophen elixir, codeine solution, diazepam solution, LomotilR, furosemide solution, guaifenesin syrup, lithium citratesyrup, metoclopramide syrup, morphine sulfate solution potassium chloride elixirs, and some theophylline solutions.

GENERAL GUIDELINES FOR ADMINISTERING MEDICATIONS WITH ENTERAL FEEDINGS:

1)Stop the tube feeding prior to administration of meds.

2)Flush the feeding tube with 20-30 ml of warm water or appropriate volume before and after giving medication through the tube.

3)If more than one medication is being given at the same time, give

each medication separately and flush the tube with 5-15 ml of warm

water between medications. 4)Use liquid preparation if

possible (if patient does not have diarrhea).

5)If a tablet form must be used, be sure it is finely crushed and dispersed

in warm water.

6)Do not crush enteric-coated, sublingual, or sustained-release tablets, if in doubt check with PharmD.

7)tube feeding when done giving medications.

7)Most liquid medications are hypertonic and should be diluted

with 30-60ml of water prior to administration

8)tube feeding when done giving medications.

Categories of Enteral Formulas

Return up to 250 ml gastric residuals to the patient.

Notify physician if feedings held twice in 24 hours.

-500ml

ASPEN

Holding EN for gastric residual volumes< 500 mL in the absence of other signs of intolerance should beavoided.

For high-risk patients or those shown to be

intolerant to gastric feeding, delivery of ENshould be switched to continuous infusion. Agents to promote motility such

as prokineticdrugs (metoclopramide and erythromycin)or narcotic antagonists (naloxone and alvimopan)should be initiated where clinicallyfeasible.

Diverting the level of feeding by post-pyloric

tube placement should be considered.

Use of chlorhexidine mouthwash twice a day shouldbe considered to reduce risk of ventilator-

associatedpneumonia.

In the ICU setting, evidence of bowel motility(resolution of clinical ileus) is not required in order toinitiate EN in the ICU.

Critically ill patients should be fedvia an enteral access tube placed in the small bowel if at high risk for aspiration or after showing intoleranceto gastric feeding.

Parenteral nutrition is usually indicated in the following situations:

1)Documented inability to absorb adequate nutrients via the gastrointestinal tract

Massive small-bowel resection / Short bowel syndrome (at least initially) Radiation enteritis Severe diarrhea

2)Complete bowel obstruction

3)Severe catabolism with or without malnutrition when gastrointestinal tract is not

usable within 5-7 days

4)Inability to obtain enteral access 5)Inability to provide sufficient nutrients/fluids enterally 6) Pancreatitis in the setting of intolerance to jejunal delivery of nutrients 7) Persistent GI hemorrhage 8) Acute abdomen/ileus

9)High output enterocutaneous fistula and EN access cannot be obtained distal to the site. 10) Trauma requiring repeat surgical procedures / NPO status

Parenteral nutrition may be indicated in the following situations:

Enterocutaneous fistula as above Inflammatory bowel disease

unresponsive to medical therapy Hyperemesis gravidarum when

nausea and vomiting persist longer than 5 -7 days and enteral nutrition is not possible

Partial small bowel obstruction Intensive chemotherapy /

Contraindications for Parenteral Nutrition:

1)Functioning gastrointestinal tract 2)Treatment anticipated for less than 5 days in patients without severe malnutrition 3)Inability to obtain venous access 4)A prognosis that does not warrant aggressive nutrition support 5)When the risks of PN are judged to exceed the potential benefits

COMPONENTS OF PARENTERAL NUTRITION:

A. MACRONUTRIENTS

1)CARBOHYDRATE

2. PROTEIN

3)FAT

Dextrose contains 3.4 kcal/g (CHO is given as a dextrose monohydrate)

Requirements: Minimum: 1 mg/kg/minute 1440 mg/kg/24hrs Maximum: 5 mg/kg/minute 7200mg/kg/24hrs OR 7 g/kg/day OR 24 dextrose kcal/kg/day.

CARBOHYDRATE

Consequences of excess CHO administration: Hyperglycemia

Glucosuria

Synthesis and storage of fat

Hepatic steatosis

Increased carbon dioxide production impairing pulmonary status/vent wean

Requirements:

Approximately 16% of protein or amino acids are nitrogen.

The goal should be to provide adequate protein to maintain a positive (2 to 4 g)

Requirements range from 0.8 g/kg/day to 2.5 g/kg/day.

Generally 15 – 20% of the daily caloric intake should come from protein.

PROTEIN

Amino acid = 4 kcal/g

Protein calories should be included when calculating total caloric requirements

FAT

Minimum: To prevent essential fatty acid deficiency (EFAD), 2% to 4% of the total caloric requirement should come from linoleic acid (25 to 100 mg/kg/day)

Maximum: Maximal fat dosage should not exceed 60% of calories OR 1.0 - 2.5 g/kg/day

Lipids should be used with caution in patients with serum triglycerides (TG) > 400mg/dl.

Use with caution in patients allergic to eggs.

Lipids are generally administered over a 24 hour period

Guidelines for rate of infusion are < 0.11 g / kg / hr

Consequences of excess lipid administration:

Fat overload syndrome with neurologic, cardiac, pulmonary, hepatic and renal dysfunction

Thrombocyte adhesiveness

Accumulation of lipid in the reticuloendothelial system (RES), leading to RES dysfunction

Impaired immune response

MICRONUTRIENTS:

PARENTERAL NUTRITION CALCULATIONS:

CUSTOM PN:

Step 1 – Determine protein and calorie needs

Step 2 – Subtract protein calories (grams protein x 4) from total calories

Step 3 – Subtract lipid calories* from remaining calories

Step 4 – remaining will be dextrose calories

Minimum flow rates: Dex/50 + g Pro/215 + 5 = minimum flow rate Central: [(Dextrose kcals X 0.42) + (grams of protein X 10)] ÷ 24 = minimum hourly flow rate. Add 5 ml/hour for MVI, trace elements, etc. Round up to nearest increment of 5. Peripheral: [(Dextrose kcals x 0.15) + grams of protein] ÷ 2.1 = minimum hourly flow rate. Add 5 ml/hour for MVI, trace elements, etc. Round up to nearest increment of 5.

COMPLICATIONS ASSOCIATED WITH PARENTERAL NUTRITION :

Metabolic complications; hyperglycemia is the most common – tight blood glucose control is optimal.

Gastrointestinal complications: steatohepatitis, cholestasis

Pharmacological complications

Manganese toxicity is possible with prolonged use of PN

Infection / sepsis

Metabolic bone disease

Nutritional modifications in diseaseA. Diabetes. Low simple sugar. high fiber. and high fat to minimize hyperglycemia.B. Renal failure. High calorie. low protein. and low electrolytes (phosphorus.potassium) to prevent volume overload. hyperammonemia. and electrolyteimbalance. However, in patients on dialysis. protein requirementsmay actually increase.C. Liver failure. Low protein. high branch chain amino acids to preventencephalopathy.D. Respiratory failure. High calorie, high fat (low carbohydrate) to prevent CO2accumulation.E. Pancreatitis. Enteral. postpyloric (nasojejunal) feeding is superior to TPN.F. Other GI diseases. If nonfunctional GI tract, may require TPN.G. Trauma. Consider immune-enhancing diet.

Grade 1 ascites Mild ascites only detectable by ultrasound No treatment

Grade 2 ascites Moderate ascites evident by moderate symmetricaldistension of abdomen Restriction of sodium intake and diuretics

Grade 3 ascites Large or gross ascites with marked abdominaldistensionLarge-volume paracentesis followed by restriction of sodium intake and diuretics (unlesspatients have refractory ascites)