Chapter 29: Nutrition Support

An estimated 40% to 50% of patients admitted to the ICU are undernourished or at risk for malnutrition.¹ Malnutrition is known to impair tissue function, delay wound healing, prolong ventilator dependence, and increase length of hospital stay.^2,3 During critical illness, metabolic changes can lead to hyperglycemia, increased energy expenditure, and protein catabolism. This cytokine-driven and hormone-mediated response to stress is not only vital in stabilizing organ function and preserving immune competency, but it may also contribute to the loss of body mass and development of malnutrition. Therefore, adequate nutrition should aim to reduce severity and duration of the catabolic phase and optimize nutritional status for recovery.

Adult malnutrition is poorly defined and frequently unrecognized, hence the incidence and prevalence are difficult to determine. Clinical terms, such as marasmus, kwashiorkor, and protein-calorie malnutrition have previously been used to identify malnutrition; however, the use of some of these terms is confusing and antiquated. They were originally meant to distinguish the different clinical features of acute malnutrition in children (Table 29–1).

While numerous tools for identifying and classifying malnutrition have been developed, their application has often led to further confusion and misdiagnoses. More recently, focus has shifted away from using prognostic indicators, such as protein stores, as they are not an accurate indicator of nutritional status. The Academy of Nutrition and Dietetics and the American Society for Parenteral and Enteral Nutrition (ASPEN) have developed standardized diagnostic criteria for defining and documenting adult malnutrition in the clinical setting. The consensus defined adult malnutrition in the context of acute illness or injury, chronic diseases or conditions, and starvation-related malnutrition. Since there is no single parameter for identifying malnutrition, presence of 2 or more of the following characteristics is recommended for the diagnosis: insufficient energy intake, weight loss, loss of muscle mass, loss of subcutaneous fat, localized or generalized fluid accumulation, and diminished functional status as measured by hand grip (Table 29–2).⁴

The application of conventional risk and assessment tools is generally not practical in critically ill patients. Use of body weight (BW) as a marker of nutritional status can be problematic because of fluids shifts associated with critical illness. Markers of protein status, such as albumin and prealbumin levels are also of limited use, as they tend to be more reflective of acute phase response than a patient's nutritional status.⁵

A review of weight, caloric intake prior to ICU admission, and gastrointestinal tract function should be conducted prior to initiating any form of nutrition support.^6,7 Risk assessment in critically ill patients should include evaluation of clinical status, length of time on mechanical ventilation, and severity and duration of stress response. Early and adequate nutrition support is important to avoid large cumulative energy deficits, which can lead to increased ventilator days and increased ICU length of stay (LOS).⁷ Avoiding overfeeding in critically ill patients is equally important, as excessive calories can result in hyperglycemia and increased carbon dioxide production, thus exacerbating respiratory insufficiency and prolonged weaning from the ventilator.

Measuring nutrient requirements is the first step in providing adequate nutrition. The use of an established amount of calories per kilogram has historically been applied when calculating energy needs. The most frequently used amount is 25 kcal/kg/day. When using calories per kilogram to determine energy needs, it is important to identify the appropriate weight. The patient's height should first be obtained, followed by calculation of an ideal BW (IBW) (Table 29–3). Once calculated, the IBW should then be compared to the admission dry weight. In patients who weigh less than 90% of their IBW, practitioners should consider using the actual BW to calculate needs and avoid overfeeding, particularly in the early stages of critical illness.

Indirect calorimetry, which measures oxygen consumption and carbon dioxide production to calculate resting energy expenditure, remains the gold standard for estimating needs in the critically ill patient. However, its use is often not practical, due to the expense of the machines, lack of reimbursement, shortage of personnel trained in its use, and length of actual testing. Predictive equations offer another method for estimating calorie needs by using measurable data, including anthropometrics, to calculate estimated energy expenditure. Table 29–4 outlines equations developed for critically ill patients.

Identifying the appropriate method for estimating needs in critically ill overweight and obese patients can be challenging. Table 29–5 outlines the interpretations for BMI classifications. In patients defined with class I to III obesity (BMI > 30), calculating 22 to 25 kcal/kg of IBW has been recommended.^6,7 Adjusted BW calculations should be used with caution as they may be unreliable. In 2013, the ASPEN published guidelines for hospitalized adult patients with obesity, recommending the Penn State University 2010 equation and the modified Penn State University equation for obese patients over 60 years of age. A 70% or greater accuracy was found using Penn State compared to other predictive equations.⁸

Valdation studies have demonstrated improved accuracy with predictive equations, even though they are less accurate than indirect calorimetry. In the absence of indirect calorimetry, Gguidelines suggest using predictive equations or simple weight based equations (kcal/kg) for estimating calorie needs in critically ill patients.7 However, the use of predictive equations can be time consuming, and therefore, less appealing in the clinical setting.

Enteral Nutrition

Enteral feeding is physiologic and the preferred route of providing nutrition in the ICU. In patients who are unable to start oral diet, nutrition support should be initiated, preferably enteral feeding, if the gut is functional. In conditions where enteral nutrition is contraindicated, such as in the case of intestinal obstruction, severe ileus, high-output ileostomy, active gastrointestinal bleeding, or hemodynamic instability, and the patient requires non–per-orem status for more than 7 days, parenteral nutrition (PN) should be considered. However, once these conditions resolve, enteral feeding should be started or resumed.

Enteral feeding maintains gut integrity and function, helps attenuate inflammatory responses, maintains gastrointestinal blood flow and peristalsis, and prevents bacterial translocation. Enteral nutrition should be initiated within the first 24 to 48 hours of ICU admission. In hemodynamically stable patients, providing enteral nutrition may reduce the incidence of infectious complications, reduce ICU and hospital mortality, and may be cost effective.^9,10 ASPEN/SCCM guidelines support the early initiation of enteral feeds with advancement toward goal over the next 48 to 72 hours.^6,7

Enteral feeding is commonly provided via a nasogastric tube, orogastric tube, nasojejunal tube, or endoscopically or surgically inserted gastrostomy (G-tube) or jejunostomy (J-tube) tubes. In practice, gastric feeding is the preferred method for providing nutrition in the ICU because it is more physiological and easier to place than more distal enteral access devices. Intragastric feeds can be given either as a bolus or continuously via pump infusion. Impaired gastric emptying, which is a relatively common problem, may preclude the use of intragastric feeding. Known factors that predispose patients to develop impaired gastric emptying include drugs (sedatives, opioids, anticholinergics, and neuromuscular blocking agents), the presence of metabolic abnormalities (hypokalemia, acidosis, hypothyroidism, and long-standing diabetes), and the presence of anatomic abnormalities, infections, or muscle disease. Symptomatic patients with gastroparesis may benefit from decreasing doses of sedatives and opioid analgesics, or by adding prokinetic drugs, such as metoclopramide, erythromycin, or domperidone, which may help facilitate gastric motility. In severe cases of impaired gastric emptying, such as recurrent vomiting, persistently elevated gastric residual volumes, presence of gastric reflux refractory to medical treatment, or in the presence of severe acute pancreatitis, postpyloric feeding may be favorable and should be considered.

Enteral Formulas

There are several enteral formulas designed for use in the ICU.¹¹ Generally, these formulas differ in their protein and fat content and are classified as standard (polymeric), specialized (disease-specific and immune-enhancing), semielemental (oligomeric), or elemental (monomeric).^11,12 Standard or polymeric enteral formulas contain intact protein, complex carbohydrates, long-chain triglycerides, a balanced amount of micronutrients, and are usually less expensive than specialized formulas. The caloric density of a standard enteral formula can range from 1.0 to 2.0 kcal/mL. Calorie dense products are formulas that contain higher amounts of calories per milliliter and are intended for patients that require less volume of free water, such as in congestive heart failure or renal failure. They can also be used in patients who require nocturnal or bolus feedings to avoid large volumes of feeding being infused at higher rates. Table 29–6 outlines various enteral formulas commonly used in the ICU. Some enteral formulas contain fiber, which may help improve diarrhea; however, studies have revealed conflicting results.^13,14 Guidelines suggest formulas free of soluble and insoluble fiber be used in critically ill patients that are at high risk for bowel ischemia or obstruction.⁷

Specialized enteral formulas are designed for patients with existing medical conditions that may require adjustment of calories, carbohydrate, protein, electrolytes, vitamins, and minerals. Formula selection in patients with renal disease can vary depending on the degree of renal function, the presence or absence of renal replacement therapy, and the patient's nutrient requirement. These patients require formulas that are low in water content, potassium, phosphorus, and magnesium. Patients receiving renal replacement therapy, hemodialysis, or continuous veno-venous hemofiltration have higher protein requirements of up to 2.5 g/kg/day and do not necessarily require fluid restriction from enteral feedings. In the absence of hyperkalemia, hyperphosphatemia, or hypermagnesemia, a standard, high-protein enteral formula should be used.

Enteral formulas that contain a lower amount of carbohydrates and higher fat content are intended for use in patients with diabetes mellitus. There is no significant difference in glycemic control, mortality, ICU LOS, or ventilator days when using diabetic formulas compared to standard formulas.^15,16,17,18 However, some studies showed a trend toward lower infection rate and lower daily insulin requirements in patients receiving the diabetic formula.¹⁸

Hepatic formulas contain increased amounts of branched-chain amino acids, for example, valine, leucine, isoleucine, and reduced amounts of aromatic amino acids, such as phenylephrine, tyrosine, and tryptophan, purposely designed to reduce the neurological symptoms of hepatic encephalopathy. Evidence supporting the use of these formulas is limited and routine use of these branched-chain amino acid–enriched enteral formulas in patients with advanced liver disease, with or without hepatic encephalopathy, are currently not recommended.^19,20

Conflicting evidence limits the routine use of specialized formulas for patients with chronic obstructive pulmonary disease and acute respiratory distress syndrome (ARDS). The enteral formulas for patients with chronic obstructive pulmonary disease, generally, have lower carbohydrate content which theoretically were created to limit carbon dioxide production and reduce ventilatory load. An enteral formula with modified lipid component containing borage and fish oils as well as high amounts of antioxidants, believed to modulate inflammatory response, is also available for use in patients with ARDS. Although previous studies have revealed some evidence of improvement in gas exchange, fewer ventilator days, and lower ICU LOS in patients receiving specialized ARDS formulas, a recent multicenter RCT found that the use of omega 3 fatty acids, linolenic acid, and antioxidant in patients with acute lung injury did not improve clinical outcome (ventilator-free days) and may be harmful.^21,22,23 Therefore, the routine use of these formulas in patients with ARDS should be discouraged.

Although known to be 4 times as costly compared to standard formulas, the use of semielemental and elemental enteral formulas has gained popularity in patients with severe uncontrolled diarrhea and malabsorptive states. Elemental formulas contain amino acids, glucose polymers, and lower amounts of long-chain triglycerides, and were developed mainly for better absorption in patients suffering from malabsorption. They are preferentially used in patients with pancreatitis to avoid exocrine pancreatic stimulation. Semielemental formulas contain hydrolyzed proteins, such as oligopeptides, dipeptides, and tripeptides, simple sugars, glucose polymers, starch, and medium chain triglycerides absorbed directly across the small intestinal mucosa into the portal vein in the absence of lipase or bile salts.¹¹ In clinical studies, both formulas were found to be nonsuperior to standard formulas in providing nutrition and nitrogen balance in patients with malabsorption, and therefore, should be reserved for patients who have failed previous attempts at providing enteral feeding with a standard formula.^24,25,26

Determining Goal Rates

Once the patient's caloric requirement and appropriate enteral formula are chosen, it is important to determine the daily duration of feeding. In the ICU, a 24-hour continuous pump infusion of gastric feeding is commonly employed. Table 29–7 shows an example for calculating the enteral goal rate.

Risks and Complications of Enteral Nutrition

Commonly encountered problems with enteral feeding in the ICU include gastrointestinal complications, mechanical problems, and metabolic derangements. In a multicenter, prospective cohort study of 400 patients evaluating 3700 feeding days, gastrointestinal complications associated with enteral nutrition were found to occur in about 62.8% of cases. These complications included high gastric residuals (39%), constipation (15.7%), diarrhea (14.7%), abdominal distention (13.2%), vomiting (12.2%), and regurgitation (5.5%).²⁷ The occurrence of diarrhea in the ICU is very rarely related to enteral nutrition use alone. Once diarrhea occurs, the investigation should first focus on ruling out pathologic causes as a result of infection, inflammation, or secretory or osmotic mechanisms, which occur in many states of malabsorption. More commonly, diarrhea can be caused by various medications and so obtaining a good drug history is very important to avoid sending unnecessary tests. Drugs that are well known to cause diarrhea include laxatives, magnesium-containing antacids, antibiotics, colchicine, lactose or sorbitol based products, nonsteroidal anti-inflammatory drugs, and prostaglandins. A common infectious cause of diarrhea in the ICU is pseudomembranous colitis caused by Clostridium difficile from prolonged use of antibiotics. Addressing the underlying cause is the first step in the management of diarrhea in the ICU, and once diarrhea is proven to be nonpathologic, adding medications such as bismuth salicylate, loperamide, diphenoxylate/atropine, octreotide, or opium tincture may be practical. Changing the enteral feeds to a more elemental form may also be of potential benefit.

Feeding intolerance often results in withdrawal of enteral nutrition which translates into decreased nutrient intake, longer ICU LOS and higher mortality.²⁸ An association between 12-day caloric adequacy and 60-day hospital mortality found that as the amount of calories delivered increases and reaches at least 80% to 85% of prescribed calories, mortality decreases.^7,29 Essentially, the fewer calories the patient is able to receive, the greater the mortality. These findings validate the importance of receiving adequate nutrition during critical illness and the importance of developing strategies that maximize the benefits and minimize the risk of enteral nutrition. Some strategies developed to optimize delivery of enteral nutrition in the ICU include elevating head of bed at least 30°, proactive use of prokinetic agents, use of small bowel feeding, and implementation of feeding protocols.³⁰

The occurrence of hyperglycemia in patients fed enterally is relatively rare as compared to patients receiving PN. In the ICU, hyperglycemia is mostly multifactorial, a result of a combination of factors commonly seen in the critical setting, eg, use of steroids, insulin resistance during critical illness, and presence of preexisting diabetes mellitus. Evaluating appropriate caloric requirements and correct administration rates as well as reducing inciting medications, and adding insulin, may be necessary in addressing hyperglycemia. Currently, aiming at moderate glycemic control with a blood glucose (BG) target between 140 and 180 mg/dL in critically ill patients is beneficial over strict BG control of 81 to 108 mg/dL.³¹ Electrolytes should also be monitored as imbalances in sodium, potassium, and phosphorus may also occur in patients receiving enteral feedings.

Though relatively rare in commercially available enteral formulas, microbial contamination of enteral feeding decanted in feeding bags occurs and is usually related to poor hand-hygiene of health care providers.^32,33 Commercially prepared enteral formulas are considered sterile until opened. In most clinical settings, implementing strict hand washing and routine change of feeding bags (every 24 hours) are practices employed to reduce the risks of contamination.

Mechanical problems associated with enteral nutrition are generally related to placement and maintenance of enteral access. Difficulties during initial placement of nasogastric tube or nasojejunal tube may result in nasopharyngeal irritation, esophageal irritation and bleeding, tube misplacement, or perforation of the esophagus, stomach, or lungs. At particular risk are patients who are agitated and fail to cooperate during the insertion process. The use of stiffer feeding tubes and stylets may also contribute to these problems. Previously placed temporary feeding tubes should also be monitored for possible migration, kinking, and occlusion, and replaced as needed. Long-term enteral access is also associated with formidable risk that occurs either during initial placement or maintenance of these feeding tubes. Commonly associated complications are abdominal pain, tube leakage, irritation, or infection around the insertion site, peritonitis, fistulas, tube clogging or occlusion, and dislodgment of the tube, collar, or button. Regular use of water flushes may reduce incidence of clogging or occlusion of feeding tubes.

Feeding Protocols in the ICU

Clinical evidence has shown that the use of enteral feeding protocols in the ICU may lead to an overall increase in the utilization of enteral nutrition and improvement in the delivery of enteral feedings to critically ill patients.^34,35 Additionally, the use of protocols and algorithms in enteral feeding increases use of promotility agents and decreases unnecessary feeding interruptions related to intolerance from high gastric residual volume.³⁵

Parenteral Nutrition

PN is intravenous nutrition designed to meet the needs of patients with a compromised GI tract or other conditions that preclude the delivery of enteral nutrition. While the appropriate use of PN may improve patient outcomes, inappropriate use has been associated with infectious complications, increased metabolic abnormalities, and higher medical costs.³⁶ Efforts to reduce the inappropriate use of PN highlight the importance of developing guidelines for initiating PN support, which are carried out by multidisciplinary nutrition support teams who specialize in its provision. Indications for PN include short bowel syndrome, high output enteric fistula, small bowel obstruction, paralytic ileus and intractable vomiting, diarrhea, or high ostomy output.³⁷ Additionally, patients undergoing major upper GI surgery, who are unable to be fed enterally, and are identified as being severely malnourished, have been shown to benefit from perioperative PN. Timing of PN initiation is a controversial topic, specifically in patients who are well nourished prior to ICU admission. In well-nourished patients, delaying PN initiation has been shown to improve outcomes.^6,7,38 In patients identified as having poor nutritional status or severe malnutrition, early PN use should be considered if enteral nutrition is unable to meet a patient's needs.

PN can be administered via central or peripheral venous access. Total PN (TPN) requires central venous access, where the tip of the catheter lies in or close to the superior vena cava allowing for infusion of hypertonic formulations. TPN is intended for patients who require PN support for greater than 7 to 14 days; however, patients can be maintained on PN for extended periods of time, years in some cases.⁵

In patients who require long-term TPN, a peripherally inserted central catheter or a tunneled cuffed catheter is placed for long-term access. Peripheral PN utilizes a peripheral vessel for administration. It is generally designed for short-term use, as the osmolarity of the solution must be less than 800 to 900 mOsm/L to prevent thrombophlebitis.⁵ In the critically ill patient, peripheral PN is generally not practical, as large fluid volumes (2.4-3.0 L) are often required to provide significant calories and protein.

Calculating Needs

Calculating nutrient needs for patients on PN support is similar to that of patients being fed enterally. Providing less than 30 kcal/kg is recommended to avoid overfeeding. As previously stated, 25 kcal/kg is frequently used.

Once the appropriate weight and calories per kilogram are determined, energy needs can be calculated. and divided among carbohydrate and lipids (non-protein calories). The use of nonprotein calories, particularly in PN, is designed to spare protein in order to preserve lean body mass. When dividing estimated energy needs among carbohydrate (dextrose), protein (AA) and fat (lipids), a 60%/40% or 70%/30% 50%/25%/25% ratio is often employed (Table 29-8). However, adjusting protein requirements may result in altered distributions.

The amount of protein provided is calculated according to the underlying condition. In the case of critical illness, 1.5 g protein/kg BW is generally appropriate. In patients with large wounds or pressure ulcers, additional protein is required. Obese patients may require more than 2 g protein/kg. Standard recommendations for estimating protein should be followed for patients with renal failure. Patients on mechanical renal replacement therapy, such as hemodialysis or continuous veno-venous hemofiltration, have higher requirements (≥ 1.5 g/kg BW) due to losses, and protein needs should be adjusted accordingly.

If an institution is equipped with an on-site PN pharmacy, there is greater opportunity for customizing the formulations to meet individualized patient needs. Hospitals without a PN pharmacy on site rely on outside vendors to mix and deliver the formulas to the institution. Turnaround time may be extended in this case; however, more companies are providing these services and meeting the needs of institutions by customizing bags and making timely deliveries.

Fluid and electrolyte requirements in critically ill patients can vary depending on a number of factors, including preexisting medical conditions, presence of renal dysfunction, and overall clinical status. Communication with the ICU team on the addition of fluids and electrolytes is imperative to ensure that PN solutions are consistent with the therapies being provided by the ICU team. No more than 154 mEq/L of sodium is generally provided. Infusing more than 10 mEq/h of potassium should be avoided, unless the patient is severely hypokalemic. Prescribers should proceed with caution when increasing amounts of calcium and phosphorus in the PN solution, and are encouraged to work closely with pharmacy to ensure that formulations are not at risk for developing precipitates. Daily review of lab values is recommended to ensure PN is addressing the constantly changing needs of the patient.³⁹

The inclusion of micronutrients in PN solutions is important to avoid the complications that can result from deficiencies. Standard additions of multivitamins and trace elements are generally included. If serum total bilirubin is more than 4 mg/dL, trace elements can be eliminated to avoid accumulating copper and manganese, which are excreted in bile. Other additives included in PN formulas are H2 blockers, vitamin K, heparin, regular insulin, and carnitine which plays a role in the transport and metabolism of fat.⁴⁰

Risks and Complications of Parenteral Nutrition

The complications associated with PN infusion are generally divided into 3 categories: mechanical, infectious, and metabolic. The most common mechanical complication is catheter occlusion, which can be related to thrombotic and nonthrombotic sources. While catheter-related infections are not common, their occurrence can significantly affect morbidity, mortality, and LOS. Instituting guidelines and following the appropriate standards of care to reduce infectious complications improve outcomes and ensure safe delivery of PN support.^5,40

Hyperglycemia is among the most common metabolic complications of PN infusion. Considerable controversy surrounding optimal BG levels for ICU patients exist. In postoperative cardiac patients, improved outcomes have been observed when implementing measures to maintain tight glycemic control (80-110 mg/dL). However, in most critically ill populations, the complications that result from hypoglycemia can have far more significant consequences. Moderate glycemic control (BG between 140 and 180 mg/dL) helps avoid hypoglycemia and appears to be safer than strict control.^6,7,31,36,41 Steps to avoid hyperglycemia in patients receiving PN support include avoiding glucose infusion rates that exceed 5 mg/kg/min, close monitoring of BG levels, and providing insulin coverage as indicated. The addition of chromium in TPN, for presumed deficiency, may also be considered in patients with unexplained hyperglycemia. When initiating PN a reduced concentration (half-strength) is recommended to observe glycemic response and determine whether insulin therapy is required.

Hypoglycemia is often a result of excess insulin provided either directly in the PN formulation or subcutaneously. A patient who experiences hypoglycemic episodes during PN infusion can be treated with ampules of 50% dextrose or continuous infusion of 10% dextrose. The PN solution may also be discontinued until a reformulation is available. In patients receiving large doses of insulin, who no longer require PN infusion, a 1 to 2 hours taper of PN at half the prescribed rate is helpful in reducing the occurrence of rebound hypoglycemia.⁶

Hypertriglyceridemia results from excessive dextrose infusion or rapid infusion of intravenous fat emulsions (IVFE). It is recommended that IVFE in PN formulations should not exceed 1 g/kg/day. Serum triglycerides should also be obtained prior to advancing IVFE to goal, and monitored weekly for changes. An acceptable serum triglyceride level for patients on PN support is less than 400 mg/dL. Intravenous lipids are considered acceptable for patients with pancreatitis whose serum triglyceride levels are within normal limits.^6,39

PN-associated liver dysfunction (PNALD) refers to liver and biliary dysfunction associated with the initiation of PN support. The 3 hepatobiliary disorders associated with PN infusion are steatosis, cholestasis, and gallbladder sludge/stones. Steatosis generally occurs within 2 weeks of initiation of PN support and may be the result of excessive infusion of calories. Biliary obstruction or impaired biliary secretion can cause cholestasis. In patients who require long-term PN support, cholestasis can progress to cirrhosis and liver failure.

Decreased enteral stimulation and suppression of cholecystokinin as a result of PN infusion can increase the risk for gallbladder sludge/stones.⁴² Patients who are more at risk for developing PNALD include those with intestinal failure, or extensive bowel resection. In patients with suspected PNALD, it is important to avoid overfeeding, particularly of nonprotein calories, which can promote lipogenesis and inhibit lipolysis. Trials of enteral nutrition and ultimate discontinuation of PN should also be explored.^6,7,43

Patients who are PN dependent generally receive IVFE as their source of essential fatty acids. Essential fatty acid deficiency (EFAD) can present within 1 to 3 weeks of receiving IVFE-free formulations, and include dermatitis, alopecia, thrombocytopenia, fatty liver, and anemia. To prevent EFAD, 50 g weekly, eg, 250 mL of 20% IVFE or 500 mL of 10% IVFE should be provided.⁵

Refeeding syndrome occurs when nutrition is reintroduced following a period of severe nutritional deprivation. The rapid delivery of nutrients can lead to glycogen and protein synthesis and quick uptake of glucose and amino acids, resulting in hypokalemia, hypophosphatemia, hypomagnesemia, and symptoms of acute thiamine deficiency. If left untreated, consequences include cardiac failure and neurological complications. Refeeding syndrome occurs in roughly 50% of severely malnourished patients fed orally, enterally, or parenterally. For severely malnourished patients, nutrition should be initiated and steadily increased with close monitoring and aggressive repletion of electrolytes as indicated.⁴⁴

The practical use of immune enhancing products in critically ill patients is controversial. Conflicting results on the variable effects of pharmaconutrients, such as glutamine, arginine, omega 3 fatty acids, and selenium make it difficult to implement routine guidelines for their use. As more data emerge on the potential benefits of these immune modulating agents, more specific guidelines and recommendations for the appropriate dosing, timing, and duration may emerge.⁴⁵