NUTRITION IN ICU

Dr Janvi SarmaMBBS MD (ANAES)

INTRODUCTION

• ICU patients are in acute stress • Pre-existing malnutrition (up to 40%) • Altered metabolic pathways• ~ 600 to 900 gm of lean body is lost /day• >30% weight loss(50% lean body mass) is

incompatible to life with 100% mortality.

Nutritional Risk Screening (NRS 2002)

• Initial Screening (yes/no ) -- BMI <20 -- Wt. Loss in last 3mths. -- Decreased intake in last one week -- Severe illness

ESPEN guidelines for nutrition screening 2002 Clin. Nutr.2003:22(4):415-421)

NRS-2002 (final screening)Score Impaired status Treatment

0 Normal nil

1 Wt. Loss>5% ( 3m) 50-70% intake in1w

Oral supplement

2 Wt loss> 5% (2m) 50% intake in 1wk

Artificial feed

3 Wt loss>5% (1m) <25% intake

Artificial feed

(Clinical Nutrition 2003;22(4):415-421)

NUTRITIONAL ASSESSMENT IN

CRITICALLY ILL PATIENTS

Actual energy needs

AEN= BMR*AF*IF

REE= BEE * IF

*AF=Activity factor

*IF= injury factor

Injury Factor Stress Factor

Minor surgery 1.2

Skeletal trauma 1.3

Major sepsis 1.6

Activity Factor use

Out of bed 1.3

Confined to bed 1.2

• Harris-Benedict Equation for calculating BMR

– Men: 66 + (13.7 × W) + (5 × H in cm) - (6.8 × A)

– Women: 655 + (9.6 × W) + (1.8 × H) - (4.7 × A)

Estimating TEE: Simple Formula

Mild stress 20 to 25 kcal/ABW/day

•Moderate stress 25 to 30 kcal/ABW/day

•Severe stress 30 to 35 kcal/ABW/day

Specific method 1. INDIRECT CALORIMETRY:• This is considered the gold standard for caloric assessment. A

computerized “metabolic cart” is used to collect the patient’s expired gases to determine CO2production and O2consumption, which are used to calculate the REE using

• Weir equation: REE = [VO2 (3.941) + VCO2 (1.11)] 1440 min/day

• IC also provides the respiratory quotient (RQ = CO2production divided by O2consumption) which can be further used to monitor the adequacy of nutritional support

• RQ >1• RQ<1• RQ=1• DESIRED IS 0.8-0.9• LIMITATONS2. Curreri formula = 25 * body weight (kg) +

40 * % TBSA burned

PROTEIN REQUIREMENT

• Building block of life• Req= 1-1.5g/kg/day• 6.25g = 1 g of nitrogen1. ratio of non-protein calories : grams of nitrogen.

A typical post-operative patient requires a ratio of 150 carbohydrate calories to 1 gram of nitrogen to prevent the use of protein as an energy source. Critically ill subjects and burn victims may require ratios below 100

2. Nitrogen balance = nitrogen intake – nitrogen output •Nitrogen intake = total protein intake (gm / day) ÷ 6.25 •Nitrogen output = UUN + 4 grams* non urinary nitrogen.

Recommendations

• Level 1 None • Level 2 Initial estimation of caloric needs using 30

kcal/kg/day (or Harris-Benedict Equation (HBE) with appropriate stress factors) and protein needs using 1.5 gm/kg of protein per day is a reasonable and cost free alternative to indirect calorimetry (IC).

• Level 3 Pre-albumin is a practical and accurate marker of

nutritional status due to its short half-life .The Curreri formula should be used to estimate

the caloric needs of patients with burns greater than 20% total body surface area (TBSA).

Indirect calorimetry (IC) and 24 hour urine urea nitrogen (UUN) studies should be utilized to determine the caloric needs of mechanically ventilated patients requiring supplemental nutrition for greater than 7 days.

GOALS OF NUTRITION IN ICU

• Provide substrate for metabolic functions• Positive nitrogen balance • Prevent any deficiency• Improve immune function• Improve organ functions• Modify stress response • Prevent metabolic complications

•ENTERAL Vs PARENTRAL

Defn:-

• Nutritional support via placement through the nose, esophagus, stomach, or intestines (duodenum or jejunum)—Tube feedings—Must have functioning GI tract—IF THE GUT WORKS, USE IT!—Exhaust all oral diet methods first

Enteral Feeding: Advantages

•Prevents atrophy and preserves enzyme function of

intestinal mucosa and pancreas (parenteral feeding alone for

>1 mo produces mucosal atrophy)

•Maintains mucosal protein and DNA concentrations

•Maintains GI IgA secretion

•Prevents cholelithiasis by stimulating gall bladder motility

•Less expensive

Enteral Nutrition: Risks

• High gastric residual volumes

• Bacterial colonization of stomach

• Increased risk of aspiration pneumonia

• Tube obstruction

Routes

Administration

• Bolus• Intermittent• Continuous

Pre-digested Formulas

Monomeric (elemental) formulas

• Contain nitrogen as free amino acids, carbohydrates as

glucose polymers, and minimal amounts of fat as LCT,

usually accounting for <3% of total calories

• Absorbed more efficiently over shorter length of intestine

• Recommended in short bowel syndrome

• Insufficient clinical evidence to justify routine use

Polymeric formulas

• Contain nitrogen as whole proteins, carbohydrate as

glucose polymers, and lipid as LCT with or without MCT

• Blenderized food, milk-based, and lactose-free formulas

Parenteral nutrition

• Routes of Parenteral Nutrition1.TPN2.PPN- 800-900mOsm/kg

VENOUS SITES

• Indications• CI• Advantages

Risks • Mechanical and septic

• Metabolic

– Hyperglycemia and hypoglycemia

– Hyperlipidemia

– Hypercapnia

– Acid-base and electrolyte disturbance

– Manganese, aluminum, vitamin D toxicity

– Deficiencies of selenium, methionine, carnitine, choline, calcium

– Overfeeding

• Others: re-feeding syndrome, gastrointestinal complications (gastroparesis, intestinal

atrophy), hepatobiliary disorders, renal complications, bone disease

Trace ElementsTrace Element Enteral ParenteralChromium 30 μg 10-15 μgCopper 0.9 mg 0.3-0.5 mgFluoride 4 mg Not well definedIodine 150 μg Not well definedIron 18 mg Not routinely addedManganese 2.3 mg 60-100 μgMolybdenum 45 μg Not routinely addedSelenium 55 μg 20-60 μgZinc 11 mg 2.5-5 mg

VitaminsVitamin Enteral ParenteralThiamin (vitamin B1) 1.2 mg 3 mgRiboflavin (vitamin B2) 1.3 mg 3.6 mgNiacin 16 mg 40 mgFolic acid 400 μg 400 μgPantothenic acid 5 mg 15 mgVitamin B-6 1.7 mg 4 mgVitamin B-12 2.4 μg 5 μgBiotin 30 μg 60 μgCholine 550 mg Not definedAscorbic acid 90 mg 100 mgVitamin A 900 μg 1000 μgVitamin D 15 μg 5 μgVitamin E 15 mg 10 mgVitamin K 120 μg 1 mg

ASPEN 2009

Grade of recommendations A. Supported by at least two level I investigations B. Supported by one level I investigation C. Supported by level II investigations only D. Supported by at least two level III investigations E. Supported by level IV or level V evidence

Level of evidence I. Large, randomized trials with clearcut results; low risk of false-

positive (alpha) error or falsenegative (beta) error II. Small, randomized trials with uncertain results; moderate to high

risk of false-positive (alpha) and/or false-negative (beta) error III. Nonrandomized, contemporaneous controls IV. Nonrandomized, historical controls V. Case series, uncontrolled studies, and expert opinion

INITIATE ENTERAL FEEDING

INITIATE ENTERAL FEEDING

Traditional nutrition assessment tools are not validated in critical care (albumin, prealbumin, and anthropometry). Before initiation of feedings, assessment should include

evaluation of weight loss and previous nutrient intake before admission, level of disease severity, comorbid

conditions, and function of the gastrointestinal tract (Grade E).

Nutrition support therapy in the form of EN should be initiated in the critically ill patient who is unable to maintain volitional intake (Grade C).

EN is the preferred route of feeding over parenteral nutrition (PN) for the critically ill patient who requires nutrition support therapy (Grade B).

Enteral feeding should be started early within the first 24–48 hours following admission (Grade C).

The feedings should be advanced toward goal over the next 48–72 hours (Grade E).

In the setting of hemodynamic compromise (patients requiring significant hemodynamic support, including high-dose catecholamine agents, alone or in combination with large volume fluid or

blood product resuscitation to maintain cellular perfusion),

EN should be withheld until the patient is fully resuscitated and/or stable

(Grade E).

• In the ICU patient population, neither the presence nor the absence of bowel sounds and evidence of passage of flatus and stool is required for the initiation of enteral feeding (Grade B).

Either gastric or small bowel feeding is acceptable in the ICU setting. Critically ill patients should be fed via an enteral access tube placed in the small bowel if at high risk of aspiration(Grade C).

Withholding of enteral feeding for repeated high gastric residual volumes alone may be a sufficient reason to switch to small bowel feeding (Grade E).

WHEN TO USE PN

WHEN TO USE PN If early EN is not feasible or available over the

first 7 days following admission to the ICU, no nutrition support therapy (standard therapy) should be provided (Grade C).

In the patient who was previously healthy before critical illness with no evidence of protein-calorie malnutrition, use of PN should be reserved and initiated only after the first 7 days of hospitalization (when EN is not available) (Grade E).

If there is evidence of protein-calorie malnutrition at admission and EN is not feasible, it is appropriate to initiate PN as soon as possible following admission and adequate resuscitation. ( B)

If a patient is expected to undergo major upper gastrointestinal surgery and EN is not feasible, PN should be provided under very specific conditions:

• If the patient is malnourished, PN should be initiated 5–7 days preoperatively and continued into the postoperative period (Grade B).

• Thus, PN should be initiated only if the duration of therapy is anticipated to be 7 days (Grade B).

PN should not be initiated in the immediate postoperative period, but should be delayed for 5–7 days (should EN continue not to be feasible) (Grade B).

PN therapy provided for a duration of 5–7 days would be expected to have no outcome effect and may result in increased risk to the patient. ( B )

DOSING OF ENTERAL FEEDING

DOSING OF ENTERAL FEEDING

The target goal of EN (defined by energy requirements) should be determined and clearly identified at the time of initiation of nutrition support therapy (Grade C). Energy requirements may be calculated by

predictive equations or measured by indirect calorimetry.

Predictive equations should be used with caution, as they provide a less accurate measure of energy requirements than indirect calorimetry in the individual patient.

• In the obese patient, the predictive equations are even more problematic without availability of indirect calorimetry (Grade E).

Efforts to provide 50% to 65% of goal calories should be made to achieve the clinical benefit of EN over the first week of hospitalization (Grade C).

If unable to meet energy requirements (100% of target goal calories) after 7–10 days by the enteral route alone, consider initiating supplemental PN (Grade E). Initiating supplemental PN before this 7–10-day

period in the patient already on EN does not improve outcome and may be detrimental to the patient (Grade C).

Ongoing assessment of adequacy of protein provision should be performed.

The use of additional modular protein supplements is a common practice, as standard enteral formulations tend to have a high non protein calorie: nitrogen ratio.

In patients with body mass index (BMI) 30, protein requirements should be in the range of 1.2–2.0 g/kg actual body weight per day, and may likely be even higher in patients with burn or multiple trauma (Grade E).

In the critically ill obese patient, permissive underfeeding or hypocaloric feeding with EN is recommended.

For all classes of obesity where BMI is 30, the goal of the EN regimen should not exceed 60% to 70% of target energy requirements or 11–14 kcal/kg actual body weight/day (or 22–25 kcal/kg ideal body weight/day).

Protein should be provided in a range 2.0 g/kg ideal body weight/day for class I and class II patients (BMI 30–40), 2.5 g/kg ideal body weight/day for class III (BMI 40).

MONITORING TOLERANCE AND ADEQUACY

MONITORING : TOLERANCE AND ADEQUACY OF EN

In the ICU setting, evidence of bowel motility (resolution of clinical ileus) is not required to initiate EN in the ICU (Grade E).

Patients should be monitored for tolerance of EN (determined by patient complaints of pain and/or distention, physical examination, passage of flatus and stool, abdominal radiographs) (Grade E).

Inappropriate cessation of EN should be avoided (Grade E).

Holding EN for gastric residual volumes 500 mL in the absence of other signs of intolerance should be avoided (Grade B).

Making the patient nil per os surrounding the time of diagnostic tests or procedures should be minimized to prevent inadequate delivery of nutrients and prolonged periods of ileus.

Ileus may be propagated by nil per os status (Grade C).

Use of enteral feeding protocols increases the overall percentage of goal calories provided and should be implemented (Grade C).

Patients placed on EN should be assessed for risk of aspiration (Grade E).

Steps to reduce risk of aspiration should be used (Grade E).

REDUCING RISK OF ASPIRATION

In all intubated ICU patients receiving EN, the head of the bed should be elevated 30°– 45° (Grade C).

For high-risk patients or those shown to be intolerant to gastric feeding, delivery of EN should be switched to continuous infusion (Grade D).

Agents to promote motility, such as prokinetic drugs (metoclopramide and erythromycin) or narcotic antagonists (naloxone), should be initiated where clinically feasible (Grade C).

Diverting the level of feeding by postpyloric tube placement should be considered (Grade C).

Use of chlorhexidine mouthwash twice a day should be considered to reduce risk of ventilator-associated pneumonia (Grade C).

SELECTION OF APPROPRIATE ENTERAL FORMULATION

SELECTION OF APPROPRIATE ENTERAL FORMULATION

Immune-modulating Enteral formulations (supplemented with agents, such as arginine, glutamine, nucleic acid, omega-3 fatty acids, and antioxidants) should be used for the appropriate patient population major elective surgery, trauma, burns, head and neck cancer,

critically ill patients on mechanical ventilation),

being cautious in patients with severe sepsis (for surgical ICU patients Grade A) (for medical ICU patients Grade B).

ICU patients not meeting criteria for immune-modulating formulations should receive standard enteral formulations (Grade B).

Patients with acute respiratory distress syndrome and severe acute lung injury should be placed on an enteral formulation characterized by an antiinflammatory lipid profile (i.e., omega-3 fish oils, borage oil) and antioxidants(Grade A).

To receive optimal therapeutic benefit from the immune-modulating formulations, at least 50% to 65% of goal energy requirements should be delivered (Grade C).

If there is evidence of diarrhea, soluble fiber-containing or small peptide formulations may be used (Grade E).

ADJUNCTIVE THERAPY

ADJUNCTIVE THERAPY Administration of probiotic agents has been

shown to improve outcome (most consistently by decreasing infection) in specific critically ill patient populations involving transplantation, major abdominal surgery, and severe trauma (Grade C).

No recommendation can currently be made for use of probiotics in the general ICU population because of a lack of consistent outcome effect.

A combination of antioxidant vitamins and trace minerals (specifically including selenium) should be provided to all critically ill patients receiving specialized nutrition therapy (Grade B).

The addition of enteral glutamine to an EN regimen (not already containing supplemental glutamine) should be considered in burn, trauma, patients (Grade B).

Soluble fiber may be beneficial for the fully resuscitated, hemodynamically stable critically ill patient receiving EN who develops diarrhea.

Insoluble fiber should be avoided in all critically ill patients.

Both soluble and insoluble fiber should be avoided in patients at high risk for bowel ischemia or severe dysmotility (Grade C).

STEPS TO MAXIMIZE EFFICACY OF PN

STEPS TO MAXIMIZE EFFICACY OF PN

In all ICU patients receiving PN, mild permissive underfeeding should be considered, at least initially.

Once energy requirements are determined, 80% of these requirements should serve as the ultimate goal or dose of parenteral feeding (Grade C).

Eventually, as the patient stabilizes, PN may be increased to meet energy requirements (Grade E).

• In the first week of hospitalization in the ICU, when PN is required and EN is not feasible, patients should be given a parenteral formulation without soy-based lipids (Grade D).

A protocol should be in place to promote moderately strict control of serum glucose when providing nutrition support therapy (Grade B). A range of 110–150 mg/dL may be most appropriate (Grade E).

When PN is used in the critical care setting, consideration should be given to supplementation with parenteral glutamine (Grade C).

In patients stabilized on PN, periodically repeat efforts should be made to initiate EN.

As tolerance improves and the volume of EN calories delivered increases, the amount of PN calories supplied should be reduced.

PN should not be terminated until 60% of target energy requirements are being delivered by the enteral route (Grade E).

SPECIFIC DISEASE STATES

PULMONARY FAILURE Specialty high-lipid low-carbohydrate

formulations designed to manipulate the respiratory quotient and reduce CO2 production are not recommended for routine use in ICU patients with acute respiratory failure (Grade E)

Fluid-restricted calorically dense formulations should be considered for patients with acute respiratory failure (Grade E).

Serum phosphate levels should be monitored closely, and replaced appropriately when needed (Grade E).

RENAL FAILURE

ICU patients with acute renal failure or acute kidney injury should be placed on standard enteral formulations, and standard ICU recommendations for protein and calorie provision should be followed.

If significant electrolyte abnormalities exits or develop, a specialty formulation designed for renal failure (with appropriate electrolyte profile) may be considered (Grade E).

Patients receiving hemodialysis or continuous renal replacement therapy should receive increased protein, up to a maximum of 2.5-3 g/kg/day.

Protein should not be restricted in patients with renal insufficiency as a means to avoid or delay initiation of dialysis therapy (Grade C).

HEPATIC FAILURE Traditional assessment tools should be used

with caution in patients with cirrhosis and hepatic failure, as these tools are less accurate and less reliable

because of complications of ascites, intravascular volume depletion, edema, portal hypertension, and hypoalbuminemia (Grade E).

EN is the preferred route of nutrition therapy in ICU patients with acute and/or chronic liver disease.

Nutrition regimens should avoid restricting protein in patients with liver failure (Grade E).

Standard enteral formulations should be used in ICU patients with acute and chronic liver disease.

The branched chain amino acid formulations should be reserved for the rare encephalopathic patient who is refractory to standard therapy with luminal-acting antibiotics and lactulose (Grade C).

ACUTE PANCREATITIS At admission, patients with acute pancreatitis

should be evaluated for disease severity (Grade E).

Patients with severe acute pancreatitis should have a nasoenteric tube placed and EN initiated as soon as fluid volume resuscitation is complete (Grade C).

Patients with mild to moderate acute pancreatitis do not require nutrition support therapy (unless an unexpected complication develops or there is failure to advance to oral diet within 7 days) (Grade C).

Patients with severe acute pancreatitis may

be fed enterally by the gastric or jejunal

route (Grade C).

Tolerance to EN in patients with severe acute pancreatitis may be enhanced by the following measures: Minimizing the period of ileus after admission

by early initiation of EN (Grade D). Displacing the level of infusion of EN more

distally in the gastrointestinal tract (Grade C). Changing the content of the EN delivered

from intact protein to small peptides, and long-chain fatty acids to medium-chain triglycerides or a nearly fat-free elemental formulation (Grade E).

Switching from bolus to continuous infusion (Grade C).

For the patient with severe acute pancreatitis, when EN is not feasible, use of PN should be considered (Grade C).

PN should not be initiated until after the first 5 days of hospitalization (Grade E).

NUTRITION THERAPY END-OF-LIFESITUATIONS

Tolerance Specialized nutrition therapy is not obligatory in cases of futile care or end-of-life situations.

The decision to provide nutrition therapy should be based on effective patient / family communication, realistic goals, and respect for patient autonomy ( Grade E)

CONCLUSIONS Use a unit specific protocol for initiating EN

Wait till patent is stable, especially if not malnourished

30 degrees head up position to prevent aspiration

Monitor for feed intolerance, keep a watch for non occlusive bowel necrosis

Use prokinetics if required

Use post pyloric feeding only if gastric feeding is not tolerated

Manage diarrhea with a protocol. Most cases don’t require discontinuation of feeds

Monitor for possible drug-nutrient interactions

ESPEN

Enteral nutrition(clinical nutrition:2006)

• Preferred way of feeding the critically ill pts with normal GIT (C).

When is EN indicated?

• All pts who are not expected to be on a full oral diet within 3 days ( C)

Is early EN superior

• Hemodynamically stable critically ill pts with a functioning GIT should be fed early i.e <24hrs ( C)

• EN therapy has to be adjusted to the progression/course of the disease and to gut tolerance

How much of exogenous supply

• During acute/initial phase of critical illness exogenous energy > 20-25kcal/kg/day may be associated with less favourable outcome. (C).

• During anabolic recovery phase,the aim should be to provide 25-30kcal/kg/day

• Pts with a severe undernutrition should receive EN upto 25-30kcal/kg/day

Gastric Vs Jejunal

• No sig diff in the efficacy of jejunal Vs gastric feeding in critically ill pts but when jejunal feeding can be devised easily it shou;d be the 1st choice ( C),but in other pts it is other way round.

Peptide based Vs whole protein

• No clinical advantage of peptide based formula over whole protein formula. ( A)

• Whole protein formula are appropriate in most patients ( C)

• The routine use of peptide based formulas not recommended

Immune modulating formula

• Includes:• Superior in patients with trauma ( A),elective

UGI Sx,ARDS,pts with mild sepsis• No recommendation in burn pts• Pts with very severe illness who do not tolerate

>700ml enteral formulae should not receive an IMF ( B)

Use of trace elements & Glutamine

• Includes• Should be supplemented in a higher than

standard dose in burn pts. ( A)• Glutamine should be added to standard enteral

feed in burn ( A) and trauma ( B) pts.• No recommendation to support glutamine

supplementation in surgical or heterogenous critically ill pts

Use of motility agents

• Routine use of metoclopramide is not supported ( A)

• IV administration of metoclopramide or erythromycin should be considered in pts with intolerance to enteral feeding.( C)

Parenteral nutrition

Whom,When,How

• All pts who are not expected to be on normal nutrition with in 3 days & EN is CI/not tolerated. ( C)

• All pts receiving< than their targeted enteral feeding after 2 days ( C)

• The aim is to provide energy as close as possible to the measured energy expenditure ( B).

How much Carbohydrate

• Min amount req is 2g/kg/day. ( B)• Hyperglycemia should be avoided• High incidence of severe hypoglycemia in

pts treated to the tighter limits ( A)• Kind of carbohydrate ( no

recommendation)

How much lipids

• Lipids are integral part of PN for energy & ensure essential fatty acid provision in long term. ( B)

• IV lipid emulsions (LCT,MCT,mixed) can be administered safely @0.7g/kg to 1.5g/kg over 12-24hrs. ( B)

• The tolerance of mixed LCT/MCT emulsions in standard use is sufficiently documented. ( C)

• Olive oil based PN is well tolerated in critically ill pts ( B)

• Addition of EPA & DHA to lipid emulsions has demostrable effects on cell membrane & inflammatory processes ( C)

• Fish oil enriched lipid emulsiosn probably decrese LOS in critically ill pts. ( C)

Amino acids

• A balanced AA mixture should be infused at approximately 1.3-1.5g/kg IBW/day in conjugation with an adequate energy supply ( C)

• The AA soln should contain 0.2-0.4g/kg/day of L-glutamine(A).

• PN prescriptions should include a daily dose of multi vitamins & trace elements.( C)

Route & Mode

• CVC to administer the high osmolarity PN ( C)

• Peripheral for <850mosm/L• PN should be administed as a complete all

in one bag ( B)

Trace elements,Vitamins & micronutrients

• PN should contain AA,glucose,lipids & some electrolytes.

• Thiamine & vit C deficits do pose special risks ( C)

• Thiamine supplements to high risk patients during 1st 3 days

• Pts with major burns,CRRT wil req additional vit C supplementation.

If the Gut works, use it !

Use it or lose it !

Baskin, Am J Gastroenterol 1992 ; 87 : 1547

Estimating TEE Based on BMIBMI (kg/m2) Energy Requirements

(kcal/kg/day)

<15 35-40

15-19 30-35

20-29 20-25

≥30 15-20

How to Determine Energy and Protein

kcal/ml x ml given = kcal% protein x kcal = kcal as proteinkcal as protein x 1 g/4 kcal = g protein• Example: Patient drinks 200 cc of a 15.3%

protein product that has 1 kcal/ml1 kcal/ml x 200 ml = 200 kcal

0.153 % protein x 200 kcal = 30.6 kcal

30.6 kcal x 1g protein/4 kcal = 7.65 g protein

Enteral Substrates

• Carbohydrates:55-70% calories;corn starch • Fat: 30% calories ; vegetable oils • Proteins : 15% .Polymers or peptides or aa • Micronutrients : adequate in 1.5-2 l/d feed • Fiber : Soy polysaccharides, gum. 5-14 g/l. • Water : 85% water 1cal/ ml 70%

water 2cal/ml

Glutamine – Arginine Dilemma

• Glutamine serves as precursor for de novo production of arginine through citrulline-arginine pathway

• Serves as fuel for immune cells

• Increases human leukocyte antigen-DR expression on

monocytes

• Enhances neutrophil phagocytosis

Arginine

• Affects immune system by stimulating direct or

indirect proliferation of immune cells

• Indirect effect possibly mediated by nitric oxide,

which also enhances macrophage cytotoxicity

Arginine

• Earlier studies with arginine and other immune–enhancing diets

(omega-3 fatty acids) showed lower sepsis and mortality

-- JPEN J Parenter Enteral Nutr 2001;25:299-308

-- Crit Care Med 2000;28:643-8

• Other studies showed detrimental effect, especially in patients with

SIRS, sepsis, organ failure

-- Br J Nutr 2002;87 Suppl 1:S121-S132

-- Am J Crit Care 2004;13:17-23