Physiology of Trunk Fluids

Bruce M. Koeppen Physician, PhD , Bruce A. Stanton PhD , in Renal Physiology (Fifth Edition), 2013

Osmolarity and Osmolality

Osmolarity and osmolality are frequently confused and incorrectly interchanged. Osmolarity refers to the number of solute particles per 1 L of solvent, whereas osmolality is the number of solute particles in 1 kg of solvent. For dilute solutions, the difference between osmolarity and osmolality is insignificant. Measurements of osmolarity are temperature dependent because the book of solvent varies with temperature (i.due east., the volume is larger at college temperatures). In dissimilarity, osmolality, which is based on the mass of the solvent, is temperature independent. For this reason, osmolality is the preferred term for biologic systems and is used throughout this and subsequent capacity. Osmolality has the units of Osm/kg H 2O. Because of the dilute nature of physiologic solutions and because h2o is the solvent, osmolalities are expressed every bit milliosmoles per kilogram of water (mOsm/kg HtwoO).

Tabular array i-one shows the relationships among molecular weight, equivalence, and osmoles for a number of physiologically significant solutes.

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Miscellaneous Physical, Chemical, and Microbiological Test Methods

Vitthal S. Kulkarni Ph.D. , Charles Shaw Ph.D. , in Essential Chemistry for Formulators of Semisolid and Liquid Dosages, 2016

11.i.4 Osmolality (USP<785>)

Osmolarity and osmolality are units of solute concentration that are often used in reference to biochemistry and body fluids, and are related to the tonicity of the formulation. If the tonicity is too far from isotonic, certain products (e.g., ophthalmic solutions and suspensions) will cause stinging on awarding. Sodium chloride is often used to arrange the osmolality of a formulation. Osmolality is measured using an osmometer by, for example, freezing point low of the solution. As with pH, osmolality can exist measured and adjusted on the majority cloth, and measured and monitored on the finished product at the fourth dimension of release and on storage.

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Disturbances of Free Water, Electrolytes, Acrid-Base Residuum, and Oncotic Pressure

In Veterinary Medicine (Eleventh Edition), 2017

Isotonic, Hypertonic, and Hypotonic Crystalloid Solutions

The tonicity of the solution is an of import clinical outcome. Consummate understanding of the tonicity concept requires differentiation of 2 terms, osmolality and osmolarity. Osmolality is the number of dissolved particles per kilogram of solution and is expressed as mOsm/kg of solution. The normal plasma osmolality in big animals is approximately 285 mOsm/kg, and plasma osmolality is aggressively defended by increasing water intake (osmolality >285 mOsm/kg) or promoting free water excretion (osmolality <285 mOsm/kg). The right term in plasma and extracellular fluid is osmolality, because this gene is measured in the laboratory; however, oft the term osmolarity is used because ane 50 of lactated Ringer's solution closely approximates 1 kg of lactated Ringer's solution and because osmolarity can be easily calculated from the concentration of electrolytes in the fluid solution. Osmolarity is the number of particles per liter of solution and is expressed every bit mOsm/L of solution.

I kilogram (i 50) of plasma from an adult large animal has 2 components, 70 chiliad of protein and 930 g of plasma h2o. Accordingly, the osmolality of normal plasma (285 mOsm/kg) is equivalent to a plasma h2o osmolarity of 306 mOsm/L ({285 mOsm/kg}/{0.93 L/kg}). Ringer'southward solution, 0.ix% NaCl, and one.3% NaHCO3 are therefore considered isotonic solutions because they distribute in plasma water and have calculated osmolarities of 309, 308, and 310 mOsm/Fifty, respectively.

The normal plasma osmolarity for solutions to be administered to large animals is approximately 306 mOsm/50; solutions tin can therefore be divers as isotonic (300–312 mOsm/L), hypertonic (>312 mOsm/L), or hypotonic (<300 mOsm/Fifty). Using this categorization, it is readily apparent that some routinely used crystalloid solutions are hypotonic; in particular, lactated Ringer'southward solution (275 mOsm/L) is mildly hypotonic and 5% dextrose (250 mOsm/50) is moderately hypotonic, although, every bit glucose is metabolized, v% dextrose becomes an increasingly hypotonic solution. Erythrocytes are resistant to increases in plasma osmolarity, whereas they are susceptible to mild decreases in osmolarity; this is the basis of the red claret cell fragility test in which red blood prison cell suspensions are placed in solutions of decreasing osmolarity. Because of hypotonic-induced hemolysis, parenterally administered fluids should ideally exist isotonic or hypertonic.

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Sodium Disorders

Jamie M. Burkitt Creedon DVM, DACVECC , in Small Animal Critical Care Medicine (Second Edition), 2015

Osmolality and Osmotic Pressure

An osmole is 1 mole of any fully dissociated substance dissolved in water. Osmolality is the concentration of osmoles in a mass of solvent. In biologic systems, osmolality is expressed as mOsm/kg of water and tin can be measured using an osmometer. Osmolarity is the concentration of osmoles in a book of solvent and in biologic systems is expressed equally mOsm/L of water. In physiologic systems at that place is no appreciable divergence between osmolality and osmolarity, and then the term osmolality volition be used for the rest of this word for simplicity. Every molecule dissolved in the total body water contributes to osmolality, regardless of size, weight, charge, or limerick. 3 The almost abundant osmoles in the extracellular fluid are sodium (and the accompanying anions chloride and bicarbonate), glucose, and urea. Because they are the about plentiful, these molecules are the main determinants of plasma osmolality in healthy dogs and cats.

Plasma osmolality (mOsm/kg) in healthy animals tin be calculated by the equation shown in Box 50-ane. 4,5 As this equation shows, plasma sodium concentration is the major determinant of plasma osmolality.

Osmoles that practise non cross the jail cell membrane freely are considered effective osmoles, whereas those that do cross freely are termed ineffective osmoles. The water-permeable jail cell membrane is functionally impermeable to sodium and potassium. Equally a event, sodium and potassium molecules are effective osmoles and they exert osmotic force per unit area across the cell membrane. The net movement of water into or out of cells is dictated by the osmotic pressure gradient. Osmotic force per unit area causes water molecules from an area of lower osmolality (higher water concentration) to move to an area of college osmolality (lower h2o concentration) until the osmolalities of the compartments are equal.

When sodium is added to the extracellular space at a concentration greater than that in the extracellular fluid, intracellular volume decreases (the cell shrinks) equally water leaves the jail cell along its osmotic pressure gradient. Conversely, cells swell when gratis water is added to the interstitial infinite and water moves intracellularly along its osmotic pressure gradient.

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Disorders of Sodium and H2o

Stephen P. DiBartola , in Fluid, Electrolyte, and Acrid-Base Disorders in Pocket-sized Animate being Practice (Fourth Edition), 2012

Osmolality

The osmolality of a solution refers to the concentration of osmotically active particles in that solution. Osmolality is a function only of the number of particles and is non related to their molecular weight, size, shape, or accuse. I mole of a nondissociating substance (e.k., glucose or urea) dissolved in 1   kg of water decreases the freezing betoken of the resultant solution by one.86° C. Such a solution has an osmolality of i Osm/kg or chiliad mOsm/kg.

The term osmolarity refers to the number of particles of solute per liter of solution, whereas the term osmolality refers to the number of particles of solute per kilogram of solvent. When considering the physiology of body fluids, the divergence between osmolality and osmolarity is negligible considering body fluids typically are dilute aqueous solutions. In clinical medicine, the term osmolality is used, and the osmolality of body fluids usually is measured by freezing-point depression osmometry. A solution is said to exist hyperosmotic if its osmolality is greater than that of the reference solution (often plasma) and hypoosmotic if its osmolality is less than that of the reference solution. An isosmotic solution has an osmolality identical to that of the reference solution.

The normal plasma osmolality of dogs and cats is slightly college than that of humans and ranges from 290 to 310 mOsm/kg in dogs and from 290 to 330 mOsm/kg in cats. In one study, xx dogs under resting conditions had plasma osmolality values of 292 to 308 mOsm/kg with a mean value of 301 mOsm/kg. 67 In a study of the effects of sodium bicarbonate infusion in cats, baseline serum osmolality ranged from 290 to 330 mOsm/kg. 22 Plasma osmolality can be estimated from the equation:

Calculated Plasma Osmolality = 2 Na + BUN 2.8 + glucose 18

where BUN is claret urea nitrogen. In this equation, the concentrations of urea and glucose in milligrams per deciliter are converted to millimoles per liter by the conversion factors 2.eight and 18. The measured osmolality should not exceed the calculated osmolality by more than than 10 mOsm/kg. 42, 149 If it does, an abnormal osmolal gap is said to exist nowadays. This occurs when an unmeasured solute (i.e., one non accounted for in the equation) is nowadays in big quantity in plasma (east.g., mannitol or metabolites of ethylene glycol) or when hyperlipemia or hyperproteinemia results in pseudohyponatremia (run across section on Hyponatremia with Normal Plasma Osmolality). 42, fifty, 56

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Homo Immunoglobulin Preparations

Matthew Due south. Karafin Md , Beth H. Shaz MD , in Transfusion Medicine and Hemostasis (Second Edition), 2013

Preparation and Administration

Production

IVIG production is strictly regulated by IUIS/WHO (International Union of Immunological Societies/Earth Health Organization) and multiple requirements are necessary for advisable IVIG product. Specifically, IVIG requires the following:

•

the source fabric must exist plasma obtained from a minimum pool of 10,000 donors;

•

the product must be free of prekallikrein activator, kinins, plasmin, preservatives, or other potentially harmful contaminants;

•

IgA content and IgG aggregate levels need to exist every bit low as possible;

•

the product must incorporate at least 90% intact IgG;

•

the IgG should maintain opsonin activity, complement bounden, and other biological activities;

•

the IgG subclasses should exist present in similar proportions to those in normal pooled plasma;

•

antibody levels against at least ii species of bacteria (or toxins) and two viruses should be adamant;

•

the product must demonstrate at least 0.i IU of hepatitis B antibody per ml and a hepatitis A radioimmunoassay titer of at least ane:thou;

•

the manufacturer should specify the contents of the final production, including the diluent and other additives, and any chemical modification of the IgG.

Plasma Collection

IVIG is derived from pools of plasma collected either by whole blood donations as recovered plasma (xx%) or by apheresis every bit source plasma (80%).

Processing

Manufacturers differ in the steps used to fractionate, purify, and stabilize Ig; methods used to inactivate and/or remove viruses; and formulation of the final product. Cold ethanol is commonly used for fractionation; then the product is purified by filtration, chromatography, and/or atmospheric precipitation. Viral inactivation is achieved by rut and chemical/enzymatic methods. To limit IgG aggregates, ion exchange chromatography, treatment with pepsin at a pH of 4, polyethylene glycol, and/or stabilizers such equally sucrose, glucose, glycine, maltose, sorbitol, and/or albumin are used.

Selecting a Production

Products are available in liquid or lyophilized forms. The lyophilized forms can exist reconstituted to a multifariousness of dissimilar concentrations and osmolarities depending on the amount of liquid used and the choice of liquid (sterile water, 5% dextrose, or 0.9% saline), depending on the manufacturers' instructions. No other medications or fluids should be mixed with IVIG. Dissimilar IVIG products have differences in concentration of additives, IgA content, osmolarity, osmolality, and pH. These factors should be considered based on the patient's clinical history (Tabular array 37.2). For instance, IVIG with glucose should be used with care in diabetics. Additionally, the antibody titers and biologic function of different products are not typically tested, fifty-fifty though there may be potentially clinically significant differences between products. Most hospital pharmacies just stock a limited number of IVIG products.

TABLE 37.2. Variables to Consider When Choosing an IVIG Product

Variable Clinical Significance
Sucrose The FDA issued a warning letter of the alphabet stating that the assistants of sucrose- containing products may increase the take a chance of development of astute renal failure. Patients at increased gamble include those with whatever degree of pre-existing renal insufficiency, diabetes mellitus, age &gt;65 years, volume deletion, sepsis, paraproteinemia, and concomitant nephrotoxic drugs.
Sorbitol Patients with hereditary fructose intolerance who receive sorbitol- or fructose-containing products may develop irreversible multi-organ failure.
Glucose Glucose-containing products should be used with caution in patients with diabetes or renal dysfunction and the elderly.
Glycine Glycine-containing products are associated with increased frequency of vasomotor events.
Maltose Some glucose monitors may interpret maltose as glucose and give falsely elevated results, which may result in iatrogenic insulin overdose.
Sodium High sodium products should be cautiously given to patients with heart failure or renal dysfunction, neonates, young children, the elderly, and those at take chances for thromboembolism.
pH Low pH products should be administered cautiously to those with compromised acrid-base compensatory mechanisms, such every bit neonates or those with renal dysfunction.
Osmolality and osmolarity The osmolality and osmolarity should exist considered in patients with heart disease or renal dysfunction, young children, the elderly, and those at risk for thromboembolism.
Volume The book should exist considered when administering IVIG to book-sensitive patients, including patients with renal dysfunction, heart disease, the elderly, neonates, and small children.

Modified from Hillyer CD, Silberstein LE, Ness et al. (eds). (2007). Blood Banking and Transfusion Medicine: Basic Principles &amp; Practice, 2nd edition. San Diego, CA: Elsevier.

Administration

The FDA has approved IM and Iv Ig products; subcutaneous administration is an off-label utilise that may exist helpful when venous admission is difficult or for home self-administration. The IVIG infusion line used should be divide from other infusion lines. The charge per unit of infusion for those not previously exposed to IVIG should exist low and tin can be increased gradually as defined past the specific IVIG product used (see manufacturers' instructions). Infusion rates in the elderly, patients at risk for renal dysfunction, or patients at risk for thrombosis, should also exist deadening. Vital signs should be monitored every xv minutes for the outset hr and then every 30–60 minutes.

Adverse Events

Adverse effects occur in approximately 3–15% of infusions. Most of the mutual adverse reactions, such as headache, nausea, vomiting, chills, fever, and malaise, seem to be related to the rate and/or dose of infusion. Other common adverse reactions include erythema, phlebitis, eczema, myalgias, flushing, rash, diaphoresis, puritus, bronchospasm, chest pain, back pain, dizziness, and blood pressure changes.

Agin reactions that are dose related (see below) may be ameliorated by decreasing the rate of infusion or assistants of the total dose over ii–five days. In improver, adverse reactions differ among different preparations, such that patients may tolerate 1 product amend than some other product. Lastly, improved manufacturing processes currently in place render IVIG complimentary of enveloped and not-enveloped viruses and should not be considered equally a risk of IVIG apply.

While rare, known astringent complications can occur with IVIG administration. The main complications are reviewed beneath.

Anaphylactic Reactions

Individuals who are IgA deficient and have anti-IgA may take anaphylactic reactions to IVIG products. These patients develop astringent symptoms including hypotension, wheezing, and shortness of breath. These reactions require halting the infusion and providing epinephrine, antihistamines, corticosteroids, fluids, and oxygen as the clinical situation requires. There are products with low IgA levels (≤2.2 μg/ml) for utilise in IgA scarce individuals.

Aseptic Meningitis

This is characterized by astringent headache, nuchal rigidity, drowsiness, fever, photophobia, painful eye movements, nausea, and vomiting beginning vi–48 hours after infusion. The etiology of this complication is unknown but may be due in part to the osmotic changes inside the brain due to the IVIG infusion. Patients with a history of migraine and who take received high-dose Ig handling appear more than susceptible. Certain IVIG brands are more prone to this complexity. The cerebrospinal fluid demonstrates pleocytosis and elevated poly peptide. The symptoms resolve in hours to days, and may exist prevented prophylactically with a premedication of steroids and anti-migraine medications, slowing charge per unit, and/or dividing dose over more than days.

Hemolytic Transfusion Reactions

A recent review demonstrated a ane.6% incidence of decreased hemoglobin after IVIG administration, especially in not-group O women in an inflammatory land receiving large doses of IVIG. The proposed mechanism is from passively transfused anti-A and/or anti-B antibodies within the production.

Infectious Disease Manual

The hazard of infectious disease transmission is near zero due to donor interview and testing, fractionation, and boosted pathogen inactivating and removal steps (such as ultrafiltration).

Passively Acquired Antibodies

Patients who receive IVIG may passively larn a diversity of antibodies, including anti-HBc and anti-CMV, and therefore this may result in false positive serologic testing. The testing tin can either be repeated at a later on fourth dimension interval or nonserologic methods tin can be used to make up one's mind the presence of the infectious amanuensis. Claret group antibodies may also exist passively caused, specially anti-A and/or anti-B, resulting in a positive directly antiglobulin examination or rarely significant hemolysis.

Renal Failure

The FDA issued a warning alphabetic character in 1998 regarding the association of administration of sucrose-containing IVIG products and astute renal failure (Table 37.2).

Thromboembolic Events

IVIG has been associated with deep venous thrombosis, myocardial infarction, cerebrovascular accidents, transverse sinus thrombosis, and pulmonary embolism, possibly related to increase in blood viscosity later on IVIG administration. Patients who received large doses speedily as well as elderly, overweight or immobilized patients and patients with cardiovascular illness are thought to be at highest risk for this complication.

Transfusion-Related Acute Lung Injury (TRALI)

A single case written report of possible TRALI occurred after IVIG administration.

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Enteral Feeding

D.L. Waitzberg , R.S. Torrinhas , in Encyclopedia of Nutrient and Wellness, 2016

Formulation

The EN can be administered intermittently or continuously. Selection of pathway for EN administration and the type of infusion to exist adopted will influence its conception design. This also involves determining the total period for nutrition administration, the volume to be infused, infusion charge per unit, if gravity baste will be used, and in which form it will be provided (infusion pump or by bolus). Table 2 outlines the programming of EN according to feeding tube positioning in pre- or postpyloric location.

Table two. Programming of EN according to feeding tube positioning

Tube feeding position Book Osmolality Fractionation Assistants time
Breadbasket Allows loftier-volume supply Hyperosmolar solutions are tolerated, but the higher solution osmolality the slower tummy emptying Depends on the total book/twenty-four hour period and patient tolerance. Lower fractionation (4 to half-dozen times per mean solar day) and higher volume in each supply may exist used About 120 drops per min (or time (min)   =   total volume (ml)/6) from the beginning of therapy
Postpyloric During intermittent supply, the volume should not exceed 300   ml   h−   1 in adjusted patients Improve tolerance for formulations with less than 550   mOsm   l−   i; dripping of hyperosmolar solutions should be strictly controlled by using infusion pump Continuous or intermittent fractionation, more often than not between six and eight supplies per day in each three   h Initial phase: sixty drops/min (or fourth dimension (min)   =   full volume (ml)/three); 'adapted' phase: 120 drops per min (or time (min)   =   total volume (ml)/six)

Enteral formulations should be nutritionally complete when used as exclusive nutrition or as a supplement to patients with normal oral ingestion; or nutritionally incomplete when used but as a supplement diet. The evaluation of the digestive and absorbent capacity of the patient should be performed for better enteral formula pick ( Scheme two ).

Scheme 2. Planning for selection of enteral diets.

Several enteral formulations are based on fresh nutrient, candy food, or both fresh and processed food. Therefore, nutrients comprising EN are more often than not the same constituents of a normal diet, consumed by the oral route, including sugar (40–60% total free energy needs), poly peptide (14–20% total energy needs), fat (xv–30% energy needs), and cobweb (40–20   one thousand   fifty−   1 ). Different factors should be considered to facilitate the choice of the most appropriate enteral formulation for patients with EN indication, such as caloric density, osmolarity and osmolality, administration pathway, source and complication of nutrients, and disease.

The EN caloric density (kcal   ml−   i) should be based on the patient's full calorie needs versus the volume of enteral diets to be administered per 24-hour interval. Enteral diets with higher free energy density have a lower corporeality of water, which can range from 690 to 860   ml   l−   one diet. The categorization of enteral formulas, according to its energy density, is shown in Table 3 .

Table 3. Categorization of enteral formulas co-ordinate to its energy density

Energy density Value (kcal   ml−   one) Formula
Very low &lt;   0.6 Sharply hypocaloric
Low 0.6–0.8 Hypocaloric
Standard 0.9–one.2 Normocaloric
Loftier 1.3–ane.5 Hypercaloric
Very high &gt;   1.5 Sharply hypercaloric

Vitamin and mineral supply varies according to the specific needs of the patients and their affliction. In the specific nutritional needs, you should evaluate the indication of boosted micronutrient supplementation, even when the conception, per se, achieves those values recommended past the Recommended Dietary Assart (RDA). Clinical nutritional patient evaluation should include objective and/or subjective indicators to place, as early as possible, whatever take a chance of specific micronutrient deficiency for it to be immediately corrected and/or prevented.

Some specialized and very specific formulations to particular clinical situation (eastward.g., renal failure) are insufficient in some vitamin and mineral supply. Therefore, EN dietary planning attends to the need for supplementation or not of these micronutrients. For the long-term utilize of incomplete enteral feeding, the supplemental vitamins and minerals should be indicated.

In patients with malabsorption syndromes, investigate the possible fat soluble vitamins (A, D, E, and One thousand) deficiency to correct it before long. There is a lack of specific vitamin and mineral recommendations for critically ill patients. Withal, in such a condition, the needs of antioxidant nutrients are increased due the oxidative stress, and it is recommended to supplement vitamins A, C, and E, zinc, and selenium.

EN osmolality (mmol   l−   1 solution) and osmolality (mOsm   kg−   1 water) are associated with its digestive tolerance. Although the stomach tolerates diets with college osmolality, more distal portions of the gastrointestinal tract respond better to isosmolares formulations. Therefore, hyperosmolar diets infused by gastrostomy or nasogastric feeding tube have better digestive tolerance when compared with assistants by postpyloric or jejunal probes.

The nutrients that nigh affect the osmolality of a solution are simple carbohydrates (mono- and disaccharides), which have greater osmotic consequence than the higher molecular weight carbohydrates (starch); minerals and electrolytes, due the property of its dissociation into smaller particles (e.k., sodium, potassium, and chloride); hydrolyzed proteins; crystalline amino acids; as well as medium-chain triglycerides, because they are more soluble than long-chain triglycerides. The more hydrolysates components contains the formulation, the higher its osmolality.

Enteral diets should non exceed the value of the renal solute load tolerated past the kidneys (800–1200   mOsm, in normal state of affairs). Renal solute load can be calculated past adding ane   mOsm for each mEq of sodium/potassium/chloride, and 5.7   mOsm (adults) or 4   mOsm (children) for each gram of protein from its formula. Special attending should be given to critical clinical situations, such every bit sepsis, postoperative, polytrauma, and severe burn down, where the urine becomes very dense, with high osmolality (around 500–1000   mOsm   kg−   one), even under appropriate hydration.

Importantly, the influence of the medication osmolality is usually neglected. The mean osmolality of liquid medications administered orally or past feeding tube ranges from 450 to ten   950   mOsm   kg−   1 water. Sure manifestations of gastrointestinal intolerance may exist related to the medication, although it is often attributed to enteral formulation.

In specific clinical situations, there may exist demands for change in the types of nutrients used; the quantity and/or course these should exist presented. In such cases, nutritional therapy becomes more than specialized. These adaptations involve changes from uncomplicated source of nutrients used until its physicochemical and structural modifications. Thus, specialized formulations for enteral utilise may provide different sources of vitamins, minerals, carbohydrates, lipids, and proteins, and these nutrients may be presented in their entirety or hydrolyzed (wholly or partly) structure.

Some specialized EN formulations are part of immunonutrition. The immunonutrition is a nutritional intervention that explores the item activity of diverse nutrients in alleviating inflammation and modulating the immune system, in which are included the omega-3 fatty acids, arginine, glutamine, nucleotides, and antioxidants. There is a current consensus that perioperative immunonutrition can beneficiate constituent surgical patients, especially those malnourished patients submitted to major gastrointestinal surgery. In these patients, administration of enteral diets containing n-three PUFA, nucleotides and arginine contributes to subtract postoperative infectious and noninfectious complications and must be initiated 5–7 days preop (500–one thousand   ml twenty-four hours−   ane) and maintained in the postoperative period.

Although the benefit of using this enteral formula combining different nutrients with immunomodulatory functions is well established in surgical patients, data are lacking to confirm or guide the constructive and safe apply of enteral diets containing isolated immunonutrients in different clinical populations, including arginine and glutamine. In hemodynamically stable status, arginine may offer immunologic and metabolic benefits, but its participation in the synthesis of nitric oxide may constitute a potential adventure for septic patients. Enteral glutamine should be considered to treat burn patients and trauma victims, but at that place is not sufficient evidence for its employ in critically ill patients with failure of multiple systems.

Other nutrients that may etch specialized EN formulations include the branched chain amino acids (BCAAs). BCAAs provide main fuel for skeletal musculus during stress and sepsis. Therefore, leucine, isoleucine, and valine may be added to specialized EN formulas as supplemental metabolic sources to nourish the metabolic needs of skeletal muscle during hypermetabolic atmospheric condition.

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