Chapter outlines

INTRODUCTION

DEFINITION

BASIC PRINCIPLES OF NUTRITION

1. Avoid malnutrition as it is harmful [1].
2. If the intestines are functioning properly, utilize them. When possible, it is recommended to use enteral nutrition instead of parenteral nutrition. However, ensuring the safe and sufficient delivery of nutrition is of higher priority than the route of delivery.
3. Avoid overfeeding, as it can cause significant complications. Excess carbohydrates can cause hyperglycemia, hepatic steatosis, and increased CO2 production; excess protein can cause azotemia and metabolic acidosis, and excess fat can cause hyperlipidemia [2, 3].
4. While planning PN, more critical factors are the method of delivery, timing, and the type of formula rather than the specific amounts of nutrients provided.
5. During acute stress, the body mobilizes endogenous amino acids and energy stores. It is not possible to make catabolic patients anabolic entirely. The goal of nutritional support is to prevent the wasting of protein and to provide essential and conditionally essential nutrients.

Importance of avoiding malnutrition

1. Malnutrition leads to increased morbidity and mortality and should be avoided. In addition, it leads to increased susceptibility to infection, poor wound healing, pulmonary complications (weakness of respiratory muscles leading to the decreased ventilatory drive, reduction of vital capacity, and depressed lung defense due to reduces cough pressure and removal of secretions), electrolyte disturbances, and postoperative complications.
2. Malnutrition leads to a prolonged recovery period and a longer duration of hospitalization.
3. It can negatively impact the quality of life and is associated with higher morbidity and mortality.

Goals of parenteral nutrition

1. To sustain or improve nutrition by administering all necessary nutrients such as proteins, carbohydrates, lipids, electrolytes, minerals, trace elements, and vitamins.
2. To decrease the negative impacts of catabolism, it is essential to maximize protein synthesis, limit the breakdown of body protein, and slow down the rate of weight loss.
3. To boost the immune function and to improve wound healing.
4. Restoring glycogen storage increases the strength of cardiac and diaphragmatic muscles and improves cardiopulmonary function.
5. To maintain or correct acid-base and electrolyte disturbances.
6. To accelerate recovery and improve the quality of life. 

ENTERAL NUTRITION VS. PARENTERAL NUTRITION

Preference of EN over PN

1. Maintains mucosal integrity: Provides nutrients that are needed in the intestinal lumen to maintain the structural and functional integrity of the gastrointestinal (GI) tract. Enteral feeding prevents the atrophy of intestinal mucosa and maintains mucosal functions of the gut. Intact mucus membrane preserves the barrier functions of the bowel and prevents bacterial translocation, and therefore prevents the possible risk of sepsis.
2. Unlike standard PN, EN provides gut-preferred fuels such as glutamate and short-chain fatty acids.
3. More physiological as the liver is not bypassed. The complete volume of nutrient-rich venous blood from all parts of the gastrointestinal tract passes from the liver before it returns to the heart. So hepatic take-up, process, and storing of various nutrients from the venous blood and subsequent release on neural or hormonal command is maintained with EN.
4. Prevents cholelithiasis by stimulating gall bladder motility.
5. Fewer serious complications and avoids known and potential complications of PN.
6. Less costly and easier to maintain than PN. Because of the potential advantages of EN, the provision of even “token” enteral supplementation is recommended to patients receiving total PN support whenever possible.

Contraindications EN

1. Gastrointestinal causes: Active severe gastrointestinal bleeding, small or large bowel obstruction, perforation, generalized peritonitis, severe paralytic ileus, high output external fistula, and intractable vomiting or diarrhea refractory to medical management.
2. Cardiac causes: Active shock or severe hemodynamic instability with poor end-organ perfusion and hypotensive patients on a high dose of inotropes/vasopressors. Avoid EN in patients who are hemodynamically unstable and not fully resuscitated [4, 5], but due to multiple benefits of EN [6, 7], initiate EN after adequately fluid resuscitation once the patient is stable and/or doses of vasopressors are declining [8, 9].
3. Lack of access: Unobtainable safe access to the gastrointestinal tract.
4. Complications of enteral feeding: Patients with enteral feeding complications (i.e., pulmonary aspiration, severe diarrhea, and intestinal ischemia or infarct precipitated by enteral feeding in patients with ischemic bowel syndrome) should not be fed by the enteral route.

Advantages of PN over EN

1. Ensured desired volume delivery of nutrients without the concerns of gastrointestinal intolerance or compliance with transnasal feeding tubes.
2. Improved metabolic, electrolyte, and micronutrient management.
3. Better acid-base manipulation.
4. Drug delivery capabilities (histamine H2 blockers, metoclopramide, insulin, heparin, etc.).

1. Age and premorbid state (healthy or otherwise).
2. Nutritional status, including endogenous fuel (fat) and protein (muscle) stores, weight loss, and serum albumin value.
3. Duration of starvation and degree of the anticipated insult.
4. Underlying disease, its severity, and concomitant medical therapy.
5. Gastrointestinal function and the possibility of resuming normal intake soon. 

INDICATIONS OF PARENTERAL NUTRITION

ADVANTAGES AND DISADVANTAGES OF PARENTERAL NUTRITION

1. Lifesaving when the GI tract cannot be used.
2. Ensured desired volume delivery of nutrients when:
   • GI intolerance prevents oral or EN.
   • Less than 2 to 3 feet of the small intestine.
3. Easier correction of fluid and electrolyte disturbances.

1. High cost.
2. Catheter-associated infections and complications.
3. Fluid overload and electrolyte abnormalities.
4. More risk of metabolic problems like hyperglycemia, hypercholesterolemia, hepatic dysfunction, and refeeding syndrome.
5. Leads to intestinal mucosal atrophy, causing damage to the gut barrier. Loss of this first line of defense predisposes patients on PN to risk bacteremia and infection.
6. Daily PN is cumbersome.

CONTRAINDICATIONS OF PARENTERAL NUTRITION

General contraindications

1. If enteral or oral nutrition meets the patient’s nutritional requirements.
2. Patients are well-nourished, stable, non-catabolic, and within the short term (five to seven days), oral or enteral nutrition is likely to be initiated. For Most patients who require short-term support, the risks of PN outweigh the benefits.
3. Severe liver failure, cardiac failure, cardiogenic shock, and blood dyscrasias.
4. Cautious use in hemodynamic instability, volume overload, azotemia (BUN >100 mg/dL), severe hyperglycemia (glucose >300 mg/dL), or electrolyte disturbances (Na+ >150 mEq/L, K+ <3 mEq/L, Cl- <85 mEq/L and phosphorus <2 mg/dL), where administration of PN carries high risk.
5. Undue high risk in the insertion of catheter solely for PN.
6. To prolong life in terminally ill patients with a poor expected outcome when there is little prospect of good quality of life.

Disease-specific contraindications

1. Excess use of carbohydrates results in the production of a large amount of carbon dioxide and therefore should be avoided in patients with compromised pulmonary function and with ventilator support during the weaning period.
2. Use lipid administration with caution if the triglyceride level is consistently more than 350 mg/dL or in patients with severe sepsis, a moderate degree of jaundice, low platelet count (<50,000 to 60,000/mm), and ARDS or severe respiratory disease.
3. Avoid the use of excess PN volume in patients with heart or kidney failure.
4. In patients with hepatic encephalopathy and severe renal failure, modified amino acids are preferred over standard amino acids. It is important to remember that parenteral nutrition must not be undertaken lightly. It is potentially harmful and dangerous if not administered with due precautions.

Timing of parenteral nutrition initiation

NUTRITIONAL REQUIREMENTS

Fluid requirements

Energy requirements

1. By using a simple calculation based on calories per kilogram of body weight.
2. By using Harris-Benedict (HB) equation to calculate resting energy expenditure, plus additional calories for activity and illness or,
3. By calculating energy expenditure with indirect calorimetry.

1. Severe hyperglycemia: Overfeeding can lead to severe hyperglycemia, resulting in glycosuria, osmotic diuresis, and dehydration.
2. Increased risk of infections: Hyperglycemia caused by overfeeding can elevate the risk of nosocomial infections.
3. Increased oxygen consumption: Excessive calorie administration can lead to increased oxygen consumption and carbon dioxide production. This heightened metabolic rate may necessitate increased respiratory effort, potentially causing problems in patients with compromised lung function.
4. Hepatic steatosis: Overfeeding and excess calorie intake can contribute to the accumulation of fat in the liver, leading to hepatic steatosis. This condition can result in long-term hepatic dysfunction [17].

Carbohydrates

A. Caloric value, preparations, and requirements

B. Functions and advantages

1. Low cost: Dextrose is the least expensive macronutrient and hence, most commonly used.
2. Supplies calories: Parenteral carbohydrate in the form of dextrose in PN is the primary source of calories. Many tissues, such as erythrocytes, white blood cells, and renal medulla, rely primarily on glucose as an energy source and cannot easily use alternative fuels. Brain tissues, red blood cells, immune cells, and renal medulla preferentially use glucose as fuel [19]. So, it is safer to provide a minimum of 100–150 gm (about 2 gm/kg body weight) of dextrose per day to meet these demands [18].
3. Nitrogen-sparing effect: Adequate carbohydrate supplementation has an important nitrogen-sparing effect, especially in patients with metabolic stress. When calories are provided as glucose, it stimulates insulin secretion, reduces muscle protein breakdown, and reduces the release of glucose from the liver. Thus, dextrose prevents protein catabolism by inhibiting the release of amino acid precursors from skeletal muscle for gluconeogenesis. In addition, glucose oxidation is also stimulated, thus sparing the oxidation of amino acids. 

C. Disadvantages

1. Low-calorie supply: Dextrose is a poor source of calories (3.4 kcal/gm of dextrose vs. 9.0 kcal/gm of fat). So to meet the total calorie requirements, the patient either needs a larger fluid volume (if we use diluted dextrose solution) or a highly concentrated dextrose solution (which can cause thrombophlebitis).
2. Hyperglycemia: The development of hyperglycemia is the most common drawback of dextrose in PN. The risk and severity of hyperglycemia are greater with IV dextrose than with the same amount of oral or enteral administration because IV dextrose bypasses the entero-insular axis. Hyperglycemia due to a larger amount of dextrose limits the increment in the dose of dextrose in PN.
3. Increased CO2 production (high respiratory quotient): Carbohydrates produce more carbon dioxide compared to lipids, which increases the work of respiratory muscles to eliminate carbon dioxide. Therefore, carbohydrate is not preferred as an only source of calorie in respiratory compromised patients and patients weaning from ventilator support.
4. Thrombophlebitis: Concentrated dextrose solution (above 10%) has high osmolarity as compared to plasma osmolarity (280 mOsm/L), so it can cause thrombophlebitis, requiring a central line for administration.

D. Administration of dextrose infusion and monitoring

E. Example of calculation of carbohydrate/dextrose requirements

1. Total caloric requirements will be 60×25=1500 kcal/day, and carbohydrate requirement will be 900 (60% of 1500) kcal/day as dextrose.
2. Divide caloric requirements from carbohydrates by 3.4 (there is 3.4 kcal/gm of dextrose) to determine the gm of dextrose required. 900 divided by 3.4 = 264.7 gm of dextrose/day.
3. D50% has 50 gm of dextrose per 100 ml. So to provide 264.7 gm of dextrose/day required volume of D50 will be about 529 ml/day (22 ml per hour). 

Protein

A. Calorie value and preparations

B. Requirements

C. Functions and advantages

1. Protein synthesis: The main function of protein is the growth and maintenance of cells and tissues in a steady stage.
2. Reduces the rate of protein catabolism: In critically ill patients, protein catabolism exceeds protein synthesis and leads to net protein loss. Administration of an adequate amount of protein along with calories decreases body protein loss but does not prevent the loss completely.
3. Calorie supplementation: 1 gm of protein provides 4 kcal energy. Patients receiving inadequate calories from carbohydrates and lipids will utilize protein for energy production. Thus, excess protein is needed for nitrogen balance when energy intake is low.

D. Contraindications and adverse effects

1. Hepatic insufficiency: In patients with hepatic insufficiency, infusion of standard amino acids may cause metabolic alkalosis, increased levels of ammonia, stupor, or coma.
2. Renal failure: A patient with impaired renal function may develop a marked rise in BUN.
3. Metabolic or respiratory alkalosis may be exacerbated by the excess acetate ions present in amino acid solutions.
4. Rapid administration may cause nausea, vomiting, headache, chills, or fever.
5. Administration of excess protein or insufficient calorie supplementation results in the production of an increased amount of urea. Renal loss of excess nitrogen leads to water loss and may cause hypertonic dehydration (especially in young children) unless extra water is provided.

E. Monitoring

F. Example of calculation of protein/amino acid solution requirements

1. Total daily protein requirements will be 60 kg × 1.0 gm/kg = 60 gm per day.
2. 100 ml solution of 5% and 10% of amino acid preparation provides 5 gm and 10 gm of amino acid, respectively. So, to provide 60 gm of amino acid/day required volume of 5% and 10% of amino acid preparations will be 1200 and 600 ml/day, respectively. 

Lipids

A. Contents of lipid emulsion

B. Caloric values, preparations, and requirements

C. Functions and advantages

1. Dense calorie supplementation: IV lipid emulsion is a concentrated calorie source (9 kcal/gm), so it is the other major calorie-rich fuel that provides energy effectively. Providing more energy in a given volume (compared to IV dextrose fluids) is an essential advantage of lipid emulsion in critically ill, volume overloaded patients.
2. Avoids hyperglycemia: Lipid emulsion provides a portion of the total calorie requirement, thereby allowing a lower rate of dextrose infusion and reducing the potential adverse effects of infusing excess glucose for calories.
3. Protein sparing effect: IV lipid emulsion is more effective than IV dextrose in providing energy. In PN, adequate supplementation of calories by curtailing protein oxidation prevents protein catabolism and exerts a protein-sparing effect.
4. Less CO2 production (lower respiratory quotient): Compared to carbohydrates, lipids produce less CO2 and, therefore, are preferred in respiratory compromised patients. Lipids’ respiratory quotient (RQ) is the least (RQ of lipids 0.7 vs. 0.8 for proteins and 1.0 for carbohydrates). The respiratory quotient is the ratio of CO2 production to O2 consumption.
5. So, IV lipid emulsion has the advantages of better glucose tolerance, less hyperinsulinemia, less fatty infiltration of the liver, and less production of CO2. Because of these benefits, lipid emulsion is widely utilized in patients with hyperglycemia, diabetes, liver disease, and respiratory failure.
6. Prevention of essential fatty acid deficiency: Lipid emulsion assists in wound healing, the production of red blood cells (RBC), and prostaglandin synthesis. PN administration without lipid supplementation for more than 2 weeks should be avoided because it can lead to essential fatty acid deficiency, causing dry, scaly skin rash, hair loss, thrombocytopenia, anemia, poor wound healing, and increased susceptibility to infection. To prevent essential fatty acid deficiency, supplement about 2% to 4% of total caloric intake as linoleic acid and 0.25% to 0.5% as alpha-linolenic acid beyond 2 weeks of administering PN.
7. Reduced risk of thrombophlebitis due to lower osmolality: Hypertonic solutions are irritant to veins, thus increasing the risk of thrombophlebitis. Unlike the hypertonic dextrose solutions, the osmolarity of lipid emulsion is low (260 mOsm/L), almost the same as that of plasma. So the addition of lipid emulsion reduces the osmolarity and, therefore, reduces the risk of thrombophlebitis due to PN. Besides, lipid emulsion exerts a protective effect on vascular endothelium. For the same reason, lipid emulsion is an important component of solutions for peripheral parenteral nutrition (PPN).

D. Adverse effects and disadvantages

1. Increased triglyceride levels: Infusion of lipid emulsion causes an increase in plasma triglycerides, cholesterol, phospholipids, and concentration of lipoproteins. When lipid emulsion is infused rapidly and/or in high doses, the rate of infusion of triglyceride exceeds the rate of hydrolysis of triglyceride by endothelial enzyme lipoprotein lipase and, therefore, can cause hypertriglyceridemia [36].
2. Sepsis: Lipid emulsion carries a risk of infection when administered separately over a prolonged time.
3. Fat embolism: Lipid is less stable when infused with amino acids and glucose as a combined “three-in-one solution”. Destabilized particles of fat coalesce into larger droplets and subsequently form fat emboli. For the same reason, a three-in-one solution has a shorter storage life, and improperly mixed or delayed in the use of solution carries the risk of fat embolism.
4. Less frequent complications: Immediate or early adverse reactions include dyspnea, cyanosis, nausea or vomiting, headache, allergic reactions, chest and back pain, or thrombocytopenia. Delayed complications with prolonged administration include hepatic dysfunction, fat overload syndrome, pancreatitis, and delayed gastric emptying.

E. Indications

F. Contraindications

G. Administration and monitoring

H. Selection of lipid emulsions (ILE)

I. Example of calculation of lipids/lipid emulsion requirements

1. Total caloric requirements will be 60 × 25 = 1500 kcal/day, and lipid requirement will be 450 (30% of 1500) kcal/day.
2. 10% and 20% of lipid emulsions provide 1.1 kcal/cc and 2.0 kcal/cc, respectively. So, to provide 600 kcal/day required volume of 10% and 20% of lipid emulsion will be about 409 ml (450 ÷ 1.1) and 225 ml (450 ÷ 2.0) respectively.

Diseases-specific amino acids

A. For hepatic encephalopathy

• Compared with non-branched chain amino acids (Non-BCAAs), which are metabolized by the liver, BCAAs are uniquely oxidized chiefly in skeletal muscle and adipose tissues (and not in the liver). BCAAs enhances detoxification and removal of ammonia in skeletal muscles, reduces plasma ammonia concentration, and may reduce hepatic encephalopathy [43].
• In hepatic insufficiency due to liver cirrhosis, high aromatic amino acids (AAA) and low BCAAs/AAA ratio play an important role in developing hepatic encephalopathy [44]. BCAAs and aromatic amino acids are transported into the brain via the same carrier [45]. So, BCAAs compete with aromatic amino acids, potentially decreasing the passage of aromatic amino acids across the blood-brain barrier, reducing the release of neurotransmitters, notably serotonin, and thereby having beneficial effects on brain function [46, 47].

B. For acute kidney injury (AKI)

Immunomodulators

A. Glutamine

B. Omega 3 fatty acids

C. Arginine

Micronutrients

Electrolytes

Trace elements

Vitamins

REFERENCES

1. Saunders J, Smith T. Malnutrition: causes and consequences. Clin Med (Lond). 2010;10(6):624–627.
2. Griffiths RD. Too much of a good thing: the curse of overfeeding. Crit Care. 2007;11(6):176.
3. Preiser JC, van Zanten AR, Berger MM, et al. Metabolic and nutritional support of critically ill patients: consensus and controversies. Crit Care. 2015;19(1):35.
4. McClave SA, Taylor BE, Martindale RG, et al. Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.). JPEN J Parenter Enteral Nutr 2016;40(2):159–211.
5. Reignier J, Boisramé-Helms J, Brisard L, et al. Enteral versus parenteral early nutrition in ventilated adults with shock: a randomised, controlled, multicentre, open-label, parallel-group study (NUTRIREA-2). Lancet 2018;391(10116):133–143.
6. Windsor AC, Kanwar S, Li AG, et al. Compared with parenteral nutrition, enteral feeding attenuates the acute phase response and improves disease severity in acute pancreatitis. Gut. 1998;42(3):431–435.
7. Khalid I, Doshi P, DiGiovine B. Early enteral nutrition and outcomes of critically ill patients treated with vasopressors and mechanical ventilation. Am J Crit Care 2010;19:261–268.
8. Merchan C, Altshuler D, Aberle C, et al. Tolerability of enteral nutrition in mechanically ventilated patients with septic shock who require vasopressors. J Intensive Care Med. 2017;32(9):540–546.
9. Simo Es Covello LH, Gava-Brandolis MG, Castro MG, et al. Vasopressors and nutrition therapy: safe dose for the outset of enteral nutrition? Crit Care Res Pract. 2020;2020:1095693.
10. ASPEN Board of Directors and the Clinical Guidelines Task Force. Guidelines for the use of parenteral and enteral nutrition in adult and pediatric patients [erratum in JPEN J Parenter Enteral Nutr. 2002;26(2):144.
11. Wilkinson RE, Dickerson RN. “New” Indications for Parenteral Nutrition. Hosp Pharm. 2016;51(10):795–797.
12. Worthington P, Balint J, Bechtold M, et.al. When is parenteral nutrition appropriate? JPEN J Parenter Enteral Nutr. 2017;41(3):324–377.
13. Appropriate Dosing for Parenteral Nutrition: ASPEN Recommendations. American Society Parenteral and Enteral Nutrition 2019. http://www.nutritioncare.org/uploadedFiles/Documents/Guidelines_and_Clinical_Resources/PN%20Dosing%201-Sheet-FINAL.pdf.
14. Gupta RD, Ramachandran R, Venkatesan P, et al. Indirect calorimetry: from bench to bedside. Indian J Endocrinol Metab. 2017;21(4):594–599.
15. Delsoglio M, Achamrah N, Berger MM, et al. Indirect calorimetry in clinical practice. J Clin Med. 2019;8(9):1387.
16. Achamrah N, Delsoglio M, De Waele E, et al. Indirect calorimetry: the 6 main issues. Clin Nutr 2020.
17. Nowak K. Parenteral nutrition-associated liver disease. Clin Liver Dis (Hoboken). 2020;15(2):59–62.
18. Singer P, Blaser AR, Berger MM, et al. ESPEN guideline on clinical nutrition in the intensive care unit. Clin Nutr. 2019;38(1):48–79.
19. Singer P, Berger MM, Van den Berghe G, et al. ESPEN guidelines on Parenteral Nutrition: intensive care. Clin Nutr 2009;33:246e51.
20. American Diabetes Association. 15. Diabetes care in the hospital: Standards of Medical Care in Diabetesd2020. Diabetes Care 2020;43(Suppl. 1):S193–S202.
21. Gosmanov AR, Umpierrez GE. Management of hyperglycemia during enteral and parenteral nutrition therapy. Curr Diab Rep. 2013;13(1):155–162.
22. Li F, Zhang W, Liu B, et al. Management of glycemic variation in diabetic patients receiving parenteral nutrition by continuous subcutaneous insulin infusion (CSII) therapy. Sci Rep 2018;8:5888.
23. McCulloch A, Bansiya V, Woodward JM. Addition of insulin to parenteral nutrition for control of hyperglycemia. JPEN J Parenter Enteral Nutr. 2018;42(5):846–854.
24. Cerra FB, Benitez MR, Blackburn GL, et al. Applied nutrition in ICU patients. A consensus statement of the American College of Chest Physicians. Chest. 1997;111(3):769–78.
25. Raman M, Almutairdi A, Mulesa L, et al. Parenteral nutrition and lipids. Nutrients. 2017;9(4):388.
26. Mundi MS, Salonen BR, Bonnes SL, et al. Parenteral nutrition lipid emulsions and potential complications. Practical Gastroenterology 2017;41(8):32–37.
27. Hippalgaonkar K, Majumdar S, Kansara V. Injectable lipid emulsions- advancements, opportunities and challenges. AAPS PharmSciTech. 2010;11(4):1526–1540.
28. Fell GL, Nandivada P, Gura KM, et al. Intravenous lipid emulsions in parenteral nutrition. Adv Nutr. 2015;6(5):600–610.
29. Klek S. Omega-3 fatty acids in modern parenteral nutrition: a review of the current evidence. J Clin Med. 2016;5(3):34.
30. Calder PC, Adolph M, Deutz NE, et al. Lipids in the intensive care unit: recommendations from the ESPEN Expert Group. Clin Nutr. 2018;37(1):1–18.
31. Sadu Singh BK, Narayanan SS, Khor BH, et al. Composition and functionality of lipid emulsions in parenteral nutrition: examining evidence in clinical applications. Front Pharmacol. 2020;11:506.
32. Calder PC, Waitzberg DL, Klek S, et al. Lipids in parenteral nutrition: biological aspects. JPEN J Parenter Enteral Nutr. 2020;44(1):S21–S27.
33. Mirtallo JM, Ayers P, Boullata J, et al. ASPEN lipid injectable emulsion safety recommendations, part 1: background and adult considerations. Nutr Clin Pract. 2020;35(5):769–782.
34. Adolph M, Heller AR, Koch T, et al. Lipid emulsions - Guidelines on Parenteral Nutrition, Chapter 6. Ger Med Sci. 2009;7:Doc22.
35. Koretz RL, Lipman TO, Klein S. American Gastroenterological Association. AGA technical review on parenteral nutrition. Gastroenterology. 2001;121(4):970–1001.
36. Anez-Bustillos L, Dao DT, Baker MA, et al. Intravenous fat emulsion formulations for the adult and pediatric patient: understanding the differences. Nutr Clin Pract. 2016;31(5):596–609.
37. Infection Control Manual. UNC Health Care. February 2018. https://spice.unc.edu/wp-content/uploads/2018/05/Intravascular-Catheter-Related-Infections-IC0032.pdf.
38. Mayer K, Klek S, Martindale RG, et al. Lipid use in hospitalized adults requiring parenteral nutrition. JPEN J Parenter Enteral Nutr. 2020;44(Suppl 1):S28–S38.
39. Martindale RG, Berlana D, Boullata JI, et al. Summary of proceedings and expert consensus statements from the international summit “Lipids in Parenteral Nutrition”. JPEN J Parenter Enteral Nutr. 2020;44(Suppl 1):S7–S20.
40. Pradelli L, Mayer K, Klek S, et al. ω-3 Fatty-Acid enriched parenteral nutrition in hospitalized patients: systematic review with meta-analysis and trial sequential analysis. JPEN J Parenter Enteral Nutr 2020;44(1):44–57.
41. Goulet O, Antébi H, Wolf C, et al. A new intravenous fat emulsion containing soybean oil, medium-chain triglycerides, olive oil, and fish oil: a single-center, double-blind randomized study on efficacy and safety in pediatric patients receiving home parenteral nutrition. JPEN J Parenter Enteral Nutr. 2010;34(5):485–95.
42. Plauth M, Schuetz T, Working group for developing the guidelines for parenteral nutrition of The German Association for Nutritional Medicine. Hepatology - Guidelines on Parenteral Nutrition, Chapter 16. Ger Med Sci. 2009;7:12.
43. Dam G, Aamann L, Vistrup H, et al. The role of Branched Chain Amino Acids in the treatment of hepatic Encephalopathy. J Clin Exp Hepatol. 2018;8(4):448–451.
44. Dejong CH, van de Poll MC, Soeters PB, et al. Aromatic amino acid metabolism during liver failure. J Nutr. 2007;137(6 Suppl 1):1579S–1585S.
45. Holeček M. Branched-chain amino acids in health and disease: metabolism, alterations in blood plasma, and as supplements. Nutr Metab (Lond). 2018;15:33.
46. Fernstrom JD. Branched-chain amino acids and brain function. J Nutr. 2005;135(6 Suppl):1539S–46S.
47. Varshney P, Saini P. Role of Branched Chain Amino Acids supplementation on quality of life in liver cirrhosis patients. Research J. Pharm. and Tech. 2020;13(7):3516–3519.
48. Naylor CD, O’Rourke K, Detsky AS, et al. Parenteral nutrition with branched-chain amino acids in hepatic encephalopathy. A meta-analysis. Gastroenterology 1989;97:1033.
49. Gluud LL, Dam G, Les I, et al. Branched-chain amino acids for people with hepatic encephalopathy. Cochrane Database Syst Rev 2017;5:CD001939.
50. EASL Clinical Practice Guidelines on nutrition in chronic liver disease. J Hepatol. 2019;70(1):172–193.
51. Kellum JA, Lameire N, Aspelin P, et al. KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl. 2012;2(1):1–138.
52. Stein J, Boehles HJ, Blumenstein I, et al. Amino acids – Guidelines on Parenteral Nutrition, Chapter 4. GMS Ger Med Sci 2009;7:24.
53. Calder PC. Immunonutrition. BMJ. 2003;327(7407):117–118.
54. Dushianthan A, Cusack R, Burgess VA, et al. Immunonutrition for acute respiratory distress syndrome (ARDS) in adults. Cochrane Database Syst Rev. 2019;1(1):CD012041.
55. Cruzat V, Macedo Rogero M, Keane KN, et al. Glutamine: metabolism and immune function, supplementation and clinical translation. Nutrients. 2018;10(11):1564.
56. Andrews PJ, Avenell A, Noble DW, et al. Randomised trial of glutamine, selenium, or both, to supplement parenteral nutrition for critically ill patients. BMJ 2011;342:d1542.
57. Wernerman J, Kirketeig T, Andersson B, et al. Scandinavian glutamine trial: A pragmatic multi-centre randomised clinical trial of intensive care unit patients. Acta Anaesth. Scand. 2011;55:812–818.
58. Heyland D, Muscedere J, Wischmeyer PE, et al. Canadian Critical Care Trials Group. A randomized trial of glutamine and antioxidants in critically ill patients. N Engl J Med. 2013;368(16):1489–97.
59. Heyland DK, Elke G, Cook D, et al. Canadian Critical Care Trials Group. Glutamine and antioxidants in the critically ill patient. JPEN Parenter. Enter. 2015;39(4):401–9.
60. van Zanten AR, Sztark F, Kaisers UX, et al. High-protein enteral nutrition enriched with immune-modulating nutrients vs standard high-protein enteral nutrition and nosocomial infections in the ICU: A randomized clinical trial. JAMA. 2014;312(5):514–24.
61. De Waele E, Malbrain MLNG, Spapen H. Nutrition in Sepsis: A Bench-to-Bedside Review. Nutrients. 2020;12(2):395.
62. Canadian clinical practice guidelines for nutrition support in the mechanically ventilated, critically ill adult, 9.4a composition of PN: Glutamine (CCCN) 2015 https://www.criticalcarenutrition.com/docs/CPGs%202015/4.1c%202015.pdf.
63. Novak F, Heyland DK, Avenell A, et al. Glutamine supplementation in serious illness: a systematic review of the evidence. Crit Care Med 2002;30:2022–9.
64. Manzanares W, Dhaliwal R, Jiang X, et al. Antioxidants micronutrients in the critically ill: a systematic review and meta-analysis. Crit Care 2012;16:R66.
65. Pradelli L, Iannazzo S, Zaniolo O, et al. Effectiveness and cost-effectiveness of supplemental glutamine dipeptide in total parenteral nutrition therapy for critically ill patients: a discrete event simulation model based on Italian data. Int J Technol Assess Health Care. 2012;28(1):22–8.
66. Wischmeyer PE, Dhaliwal R, McCall M, et al. Parenteral glutamine supplementation in critical illness: a systematic review. Crit Care. 2014;18(2):R76.
67. Stehle P, Ellger B, Kojic D, et al. Glutamine dipeptide-supplemented parenteral nutrition improves the clinical outcomes of critically ill patients: a systematic evaluation of randomised controlled trials. Clin Nutr ESPEN 2017;17:75–85.
68. Stehle P, Kuhn KS. Glutamine: an obligatory parenteral nutrition substrate in critical care therapy. BioMed Res Int. 2015:ID545467.
69. Wernerman J. Glutamine supplementation. Ann Intensive Care. 2011;1(1):25.
70. Singer P, Berger MM, Van den Berghe G, et al. ESPEN guidelines on parenteral nutrition: intensive care. Clin Nutr. 2009;28(4):387–400.
71. Mayer K, Klek S, García-de-Lorenzo A, et al. Lipid use in hospitalized adults requiring parenteral nutrition. JPEN J Parenter Enteral Nutr. 2020;44(1):S28–S38.
72. Wu GH, Gao J, Ji CY, et al. Cost and effectiveness of omega-3 fatty acid supplementation in Chinese ICU patients receiving parenteral nutrition. Clinicoecon Outcomes Res. 2015;7:369–375.
73. Pradelli L, Muscaritoli M, Klek S, et al. Pharmacoeconomics of parenteral nutrition with ω-3 fatty acids in hospitalized adults. JPEN J Parenter Enteral Nutr. 2020;44(S1):S68–S73.
74. Casaer MP, Van den Berghe G. Nutrition in the acute phase of critical illness. N Engl J Med. 2014;370(13):1227–36.
75. Canadian Clinical Practice Guidelines for Composition of Enteral Nutrition. 4.1a EN composition: Diets supplemented with arginine and select other nutrients. (CCCN) 2015 https://www.criticalcarenutrition.com/docs/systematic_reviews_2018/4.1a%20%20Arginine_2018.pdf.
76. Weimann A, Braga M, Carli F, et al. P. ESPEN guideline: Clinical nutrition in surgery. Clin Nutr. 2017;36(3):623–650.
77. Lapointe M. Iron supplementation in the intensive care unit: when, how much, and by what route? Crit Care. 2004;8 Suppl 2(Suppl 2):S37–S41.
78. Singh H, Duerksen DR. Vitamin K and nutrition support. Nutr Clin Pract. 2003;18:359–365.
79. Shearer MJ. Vitamin K in Parenteral Nutrition. Gastroenterology2009;137:S105–S118.