Nutrition Support in Critically Ill Patients: Supplement Parenteral Nutrition (SPN)

Professor Syed Mahbubul Alam, Kazi Mahmudul Haque
Drugs, Genetics, Industry, Medicine, Patient

19

Mar 25

Introduction

Parenteral nutrition (PN) is a life-saving intervention for patients where oral or enteral nutrition (EN) cannot be achieved or is unacceptable. Parenteral nutrition (PN) support provides calories (usually dextrose and lipids), amino acids, electrolytes, vitamins, minerals, trace elements, and fluids via a parenteral route. A PN admixture contains several active ingredients, meaning that its prescription is one of the most complex routinely used ingredients in the hospital setting. Moreover, PN is considered a high-alert medication, thus its use requires policies, systems, and practices focused on safety to minimize patient risk. Malnutrition is associated with postoperative complications and an increased risk of death after surgery. Many surgical diseases result in malnutrition, particularly those that are associated with a hyper metabolic state. Advanced age is also associated with malnutrition in hospitalized patients, many of whom require emergency operations. For those patients with a gastrointestinal tract that is not functional or that cannot or should not be accessed, PN is indicated.1 A high prevalence of malnutrition has been found in hospitalized patients and is common in critically ill, surgical, and/or cancer patients. Examples of clinical conditions requiring PN are listed in Table 1.

Clinical conditions requiring PN (Table-1)

ConditionMechanism/Indication for PNExample
Short bowel
Intestinal fistula
Extensive intestinal mucosal disease		Reduction of absorption capacity
Loss of nutrients		Short bowel syndrome, ischemic bowel, complications of colorectal or bariatric surgery, high-output stoma, high-output intestinal fistula
Radiation or chemotherapy-related enteritis, mucositis, autoimmune enteropathy, gut graft-versus-host disease
Mechanical bowel obstructionBlockage of intestinal lumen
Recurrent vomiting		Malignant bowel obstruction, intestinal adhesions, stenosis or strictures, inflammatory disease, peritoneal carcinomatosis
Motility disordersFailure to tolerate adequate oral or enteral intake
Recurrent vomiting		Functional gastrointestinal disorders, ileus, scleroderma, acute pancreatitis, post-operatively, gastrointestinal failure associated with critical illness, pseudo-obstruction, adhesive disease
Bowel rest neededNeed to restrict oral or enteral intakeIschemic bowel, perioperative status, acute pancreatitis, chylous fistula
OtherFailure of oral or enteral nutritionUnable to achieve or maintain secure oral or enteral access

Indications for Parenteral Nutrition

PN is indicated in several scenarios:

  1. Non-functioning Gastrointestinal Tract:
    • Conditions such as bowel obstruction, pancreatitis, or severe inflammatory bowel disease.
  2. Inability to Tolerate Enteral Feeding:
    • Patients who are intubated or have significant gastrointestinal dysfunction.
  3. Severe Malnutrition:
    • In cases of pre-existing malnutrition or acute weight loss, where enteral nutrition may not be adequate.
  4. High Nutritional Requirements:
    • Patients with hyper metabolism due to trauma, burns, or sepsis may require additional caloric intake that cannot be met enterally.

 

Understanding Parenteral Nutrition Composition

Standard Components of PN:

  • Macronutrients:
    • Carbohydrates: Usually in the form of dextrose (usually 25-30% of total calories).
    • Proteins: Provided as amino acids (15-20% of total calories).
    • Fats: Delivered as lipid emulsions (20-30% of total calories).
  • Micronutrients:
    • Vitamins: Essential for various metabolic processes (e.g., B vitamins, Vitamin C, Vitamin K).
    • Minerals: Key electrolytes (sodium, potassium, magnesium) and trace elements (zinc, selenium, copper).2

 

Assessing Nutritional Needs

Before supplementing PN, a thorough assessment is required:

  • Caloric Needs: Using formulas such as the Harris-Benedict equation or the Mifflin-St Jeor equation to estimate total daily energy expenditure (TDEE).
  • Protein Needs: Typically range from 1.2 to 2.0 g/kg/day, depending on the patient’s condition (higher for trauma and burn patients).
  • Micronutrient Needs: Based on guidelines and clinical judgment, taking into account any deficiencies or special requirements (e.g., in cases of sepsis or liver dysfunction)

 

Supplementing Macronutrients

  • Additional Carbohydrates:
    • If energy needs are not met, additional dextrose can be infused, but care must be taken to avoid hyperglycemia.
  • Protein Supplementation:
    • If the protein intake is inadequate, consider using higher concentrations of amino acids or specialized formulations (e.g., branched-chain amino acids for liver disease).
  • Lipid Emulsions:
    • Use of omega-3 fatty acid-rich lipid emulsions may be beneficial in critically ill patients to modulate inflammation.3

 

Micronutrient Supplementation

  • Electrolyte Management: Regular monitoring and adjustment of electrolytes based on blood tests. Specific attention to:
    • Sodium: This may need to be supplemented based on losses. Daily requirements: 1 to 2 mEq/kg/day
    • Potassium and Magnesium: Common deficiencies; supplementation may be necessary. Daily requirements: Potassium: 1 to 2 mEq/kg/day, Magnesium: 8 to 20 mEq/day
    • Calcium 10 to 15 mEq/day
    • Phosphorus 20 to 40 mmol/day
    • Chloride and acetate are adjusted for acid-base balance
  • Trace Elements and Vitamins:
    • Zinc and Selenium: Important for immune function; consider supplementation in patients with specific deficiencies or increased needs.
    • Thiamine and Vitamin D: Special attention is needed, especially in patients at risk of refeeding syndrome or critically ill patients with malnutrition.

Transitioning from Parenteral to Enteral Nutrition

  • Once the patient’s gastrointestinal tract is functional, transitioning from PN to enteral nutrition is recommended. This approach helps maintain gut integrity and function while minimizing complications associated with long-term PN.4

 

Complications and Monitoring

 

1.       Refeeding Syndrome (RS) Considerations

  • When transitioning from PN to enteral feeding, be cautious of refeeding syndrome:
    • Start enteral feeds at low rates and gradually increase.
    • Monitor electrolytes closely during this transition, especially phosphorus, potassium, and magnesium.
  • The ASPEN consensus recommendations for RS proposed the following criteria for stratifying patients as moderate and high risk for refeeding
  • Low BMI < 18.5 kg/m2;
  • Recent weight loss of 5% in 1 month or 7.5–10% in 3 to 6 months;
  • None or negligible oral intake for 5–6 days;
  • Caloric intake < 75% estimated for >5 days during acute illness or injury;
  • Caloric intake < 75% estimated energy for >1 month;
  • Abnormal potassium, phosphorus, or magnesium serum concentrations;
  • Loss of subcutaneous fat;
  • Loss of muscle mass;
  • Higher-risk comorbidities (diseases and clinical conditions associated with the presence of the prior criteria, such as alcoholism, eating disorders, cancer, malabsorptive states, etc.).

Depending on the severity of the criteria or presentation with at least one or two criteria, the patient would be classified as a significant or moderate risk for RS. To prevent RS, it is useful to screen at-risk patients before beginning nutritional support.

2.       Hepatobiliary Complications

Disorders of the liver and biliary system are complications commonly reported in patients receiving PN. Parenteral nutrition-associated liver disease (PNALD) is a spectrum of diseases that can range from mild liver enzyme abnormalities to steatosis to eventual fibrosis or cirrhosis. Risk factors and interventions to reduce risk for development of PNALD. There are three primary types of PNALD: steatosis, cholestasis, and gallbladder sludge/stones. Patients may have one of these disorders or a combination of the three. Other terms for PNALD, intestinal failure-associated liver disease (IFALD) and parenteral nutrition-associated cholestasis (PNAC), have been used interchangeably.5 Risk factors and interventions to reduce risk for the development of PNALD (Table 2).

Type of Risk FactorCauseReasonIntervention
Unrelated to PNSepsis and/or insultLiver toxicityInfection prevention
Drugs-induced toxicityDrugs causing liver toxicityIdentify the drug, and change if possible
Related to PNLack of enteral intakeImpaired secretion of bile or biliary obstructionTrophic EN, reintroducing enteral/oral intake
OverfeedingFat accumulation leading to steatosisReduce total energy intake (fat and/or glucose) or change to enriched fish oil IVFE
Lipids with a high phytosterol loadPhytosterols direct/indirect action in the liverChange to lipid with lower phytosterol content and/or reduce lipids

3.       Hyperglycemia

Hyperglycemia remains the most common complication of PN. A high prevalence of hyperglycemia during PN therapy has been reported even in non-critically ill patients. Tight glycemic control of below 110mg/dL has been shown to reduce mortality and morbidity in critically ill patients. However, it was also later shown that intensive glucose control increased hypoglycemic events and mortality, and that glycemic control close to 180 mg/dL resulted in better outcomes compared to lower targets. Poor glycemic control in patients receiving PN has been associated with poor outcomes, both in critically ill and non-critically ill patients. Avoiding high amounts and limiting glucose in PN, as well as adding insulin to PN are also strategies that might prevent hyperglycemic events in patients with PN.6

  1. Hypertriglyceridemia

Lipid overload has been associated with hypertriglyceridemia and liver dysfunction. A normal dose of IVFE is below 1.5 kg/kg/day, including lipids from non-nutritive sources such as propofol, but up to 1 g/kg/day has been recommended in patients at risk of hypertriglyceridemia.

In general, hypertriglyceridemia can occur if the infusion rate of IVFE exceeds the capacity of plasma fat clearance, but also occurs with glucose overfeeding. Factors found to be associated with hypertriglyceridemia include sepsis, renal failure, hyperglycemia, obesity, alcoholism, pancreatitis, high-output fistula, multiple organ failure, pre-existing hyperlipidemia and co-administration of drugs such as corticosteroids, cyclosporine, tacrolimus, sirolimus or Propofol. Acceptable serum triglyceride concentrations for those receiving PN are <400 mg/dL. In patients with triglyceride levels close to 400 mg/dl or higher, IVFE should be reduced or discontinued.7

  1. Catheter-Related Complications (CRBSIs)

One of the most important complications associated with PN. Infections of the central line can lead to sepsis, shock, and death. CRBSIs are a risk factor to be considered when inserting and managing any central VAD as they can increase morbidity, mortality, length of stay, and costs. Recommendation for line care and placement should be implemented and must be followed to minimize the risk of infection. the major recommendations include

  1. cognitive-science-based educating and training healthcare workers who insert and maintain VADs;
    1. using a checklist to improve the adherence to hygiene protocols;
    1. the use of ultrasound guidance in the insertion of VADs;
    1. the use of an antiseptic barrier cap and needleless secure devices;
    1. abandoning the convenience of multi-lumen catheters; and
    1. the use of antimicrobial-antiseptic impregnated VADs

Administration Methods

  • Central Venous Catheter (CVC): Preferred for long-term PN (greater than 7-10 days) as it allows for larger volumes and concentrations of nutrients.
  • Peripheral Intravenous (PIV) Access: Suitable for short-term use (less than 7 days) but with limitations on the concentration of dextrose and osmolarity.8

Types of parenteral nutrition bag systems

Parenteral nutrition (PN) can be delivered using various bag systems designed to meet the nutritional needs of patients while ensuring safety and convenience. Here are the primary types of parenteral nutrition bag systems:

1. Single-Chamber Bag Systems

  • Description: These bags contain a single solution, typically either a dextrose solution, amino acid solution, or lipid emulsion.
  • Use Cases: Suitable for short-term use or for patients who may only require one component of PN (e.g., carbohydrates or fats).
  • Advantages: Simple to prepare and use; may be cost-effective for certain patients.
  • Disadvantages: Less flexibility in meeting comprehensive nutritional needs; potential for increased risk of contamination with multiple setups.9

2. Two-Chamber Bag Systems

  • Description: These bags contain two separate compartments: one for dextrose and one for amino acids or lipids.
  • Use Cases: Ideal for patients needing both carbohydrates and proteins or fats but not all components of full parenteral nutrition.
  • Advantages: Reduces contamination risk by limiting handling; allows for some customization based on patient needs.
  • Disadvantages: Requires manual mixing prior to administration, which can introduce risks.

3. Three-Chamber Bag Systems

  • Description: These bags have three separate compartments for dextrose, amino acids, and lipids, allowing for the simultaneous delivery of all major macronutrients.
  • Use Cases: Commonly used for patients needing complete parenteral nutrition.
  • Advantages: Minimizes contamination risk, simplifies preparation, and reduces the number of connections needed during administration.
  • Disadvantages: Potentially higher costs; must be stored properly to maintain stability.10

 

4. Customized PN Bags

  • Description: These are specially formulated bags created based on individual patient needs and may include varying concentrations of macronutrients, electrolytes, vitamins, and trace elements.
  • Use Cases: Used for patients with specific metabolic disorders or altered requirements (e.g., renal failure, liver disease).
  • Advantages: Tailored to the specific nutritional needs of each patient; can optimize recovery and metabolic outcomes.
  • Disadvantages: Requires more complex preparation and monitoring; may increase costs and require specialized expertise.11

5. Ready-to-Use (RTU) PN Solutions

  • Description: These pre-mixed and pre-measured solutions are designed for immediate use and typically come in single, double, or triple-chamber formats.
  • Use Cases: Suitable for hospitals or clinics with limited pharmacy resources or emergencies.
  • Advantages: Reduces preparation time, limits the risk of contamination, and is convenient for rapid administration.
  • Disadvantages: May have limited customization options compared to individualized PN formulations.12

6. Lipid Emulsion Bags

  • Description: These bags contain lipid emulsions and can be used as a standalone source of fat or combined with other macronutrients.
  • Use Cases: Ideal for patients requiring supplemental fat without full PN.
  • Advantages: Simple and effective method of delivering essential fatty acids and calories; can be given separately or as part of PN.
  • Disadvantages: Not suitable for patients with certain allergies (e.g., egg or soy) unless specific formulations are used.13

7. Dual-Chamber Bags for Lipids and Dextrose/Amino Acids

  • Description: A type of two-chamber bag where one chamber contains lipid emulsions and the other contains either dextrose or amino acids. This system is intended to be combined before administration.
  • Use Cases: Patients needing lipid supplementation alongside dextrose or amino acids but in a controlled and contained manner.
  • Advantages: Easier mixing process reduces handling of multiple bags and minimizes the risk of contamination.
  • Disadvantages: Requires aseptic technique when mixing; must be compatible with the delivery system.14

Summary of Bag Types

Type of BagChambersAdvantagesDisadvantages
Single-Chamber1Simple, cost-effectiveLimited flexibility
Two-Chamber2Reduces contamination riskRequires manual mixing
Three-Chamber3Comprehensive nutrition minimizes handlingPotentially higher cost
Customized PN BagsVariableTailored to individual needsMore complex preparation and monitoring
Ready-to-Use (RTU)VariableQuick preparation, convenientLimited customization
Lipid Emulsion Bags1Effective for fat deliveryAllergy considerations
Dual-Chamber2Controlled mixing, reduced contaminationRequires aseptic technique

 

Guidelines for Parenteral Nutrition with Three-Chamber Bags

The American Society for Parenteral and Enteral Nutrition (ASPEN) and European Society for Clinical Nutrition and Metabolism (ESPEN) provide guidelines for parenteral nutrition (PN), including recommendations specific to the use of three-chamber bags (3CB) for patients requiring nutritional support.15 The guidelines support the use of three-chamber bags as a safe and effective means of delivering parenteral nutrition to critically ill patients. They emphasize the importance of personalized nutrition support, appropriate monitoring, and a structured approach to transitioning from PN to enteral nutrition when feasible. Here are the key points related to the use of three-chamber bags based on guidelines:

 

General Recommendations

  1. Indication for Parenteral Nutrition:
  1. PN should be considered in critically ill patients when oral or enteral feeding is not feasible or adequate.
  2. Early initiation of PN is recommended when the gastrointestinal (GI) tract is not functional for more than 7 days.
  3. Use of Three-Chamber Bags:
  1. Safety and Efficacy: Three-chamber bags are considered safe and effective for delivering total parenteral nutrition (TPN) to patients with high nutritional requirements.
  2. Reduced Risk of Contamination: The design of three-chamber bags minimizes the risk of microbial contamination compared to traditional mixing methods.16

 

Nutritional Composition

  1. Macronutrients:
  1. The 3CB should provide an adequate supply of macronutrients, including carbohydrates, proteins (amino acids), and lipids, to meet the patient’s nutritional needs.
  2. Carbohydrates: Typically provided as dextrose, adjusted according to energy requirements and glycemic control.
  3. Proteins: Amino acids should be adjusted based on the patient’s needs, considering factors such as stress level, recovery, and metabolic conditions.
  4. Lipids: Lipid emulsions can be included to provide essential fatty acids and additional calories. The ESPEN guidelines suggest the use of lipid formulations that are rich in omega-3 fatty acids for critically ill patients.
  5. Micronutrients:
  1. Micronutrients, including vitamins and trace elements, should be added to the 3CB as needed to prevent deficiencies and support overall metabolic functions.
  2. Regular monitoring of micronutrient levels is important, especially in prolonged PN therapy.17

 

Administration and Monitoring

  1. Administration Protocol:
  1. The three-chamber bag should be administered through a sterile technique, with care taken to ensure that the bag is properly mixed before use if required.
  2. Central venous access is recommended for high-calorie solutions, while peripheral access may be used for lower concentrations.
  3. Monitoring:
  1. Continuous monitoring of the patient’s clinical status, including metabolic parameters (electrolytes, liver function, and glucose levels), is critical.
  2. Adjustments to the PN formula may be necessary based on laboratory findings and the patient’s clinical condition.18

 

Special Considerations

  1. Transitioning to Enteral Nutrition:
  1. When the GI tract becomes functional, transitioning from PN to enteral nutrition should be done gradually, monitoring for potential refeeding syndrome.
  2. The transition should ideally begin with enteral feeding while tapering down PN to ensure adequate nutritional support.
  3. Long-Term PN Considerations:
  4. For patients on long-term PN, such as those with chronic conditions, special attention should be given to liver function and the risk of complications associated with prolonged use of lipid emulsions.19

ASPEN and ESPEN recommendations for critically ill patients with PN:

SocietyStart SPN *Start PNProtein g/kg/dayEnergy Kcal/kg/day
ASPENAfter 6 daysAny time1.2–2.012–25 (up to 7–10 days)
ESPENWithin 3–7 daysWithin 3–7 days1.3Not exceeding 70% of EE ** (day 1–3)After day 3: 80–100% EE **

* SPN, supplemental PN; ** EE, estimated energy, calculated by indirect calorimetry.20

Conclusions

  1. Parenteral nutrition is a critical intervention for providing nutritional support to critically ill patients who cannot utilize their gastrointestinal tract.
  2. Supplementing parenteral nutrition in critically ill patients requires a comprehensive understanding of their individual nutritional needs, continuous assessment, and tailored adjustments to optimize clinical outcomes.
  3. Feeding tube complications can arise either early or late with feeding tube use (e.g., gastrostomy, jejunostomy placement). When complications arise, enteral nutrition is often suspended to minimize further complications (e.g., leaking into the abdomen).
  4. Gastrointestinal anastomotic failure may cause peritoneal soiling and peritonitis. Uncontrolled anastomotic leak leads to contamination of the peritoneal cavity and is a contraindication to enteral feeding.
  5. Fish oil and omega-3 fatty acid administration may reduce the triglyceride level through different mechanisms.
  6. Switch to an alternative lipid formulation (e.g., SMOFlipid) with dyslipidemia associated with long-term parenteral nutrition.
  7. The three-chamber bag represents a significant advancement in the delivery of parenteral nutrition.
  8. The ASPEN & ESPEN guidelines endorse the use of three-chamber bags for the delivery of parenteral nutrition due to their safety, efficiency, and ease of use.
  9. Selecting the appropriate parenteral nutrition bag system is crucial for meeting the nutritional needs of patients, particularly those in critical care settings.
  10. The choice depends on individual patient requirements, the duration of therapy, and institutional protocols.
  11. Understanding the advantages and limitations of each system can enhance patient safety and optimize nutritional support.

Authors of this article

  1. Professor Syed Mahbubul Alam, MBBS (DMC) & FCPS (Surgery), Former Principal Dhaka Medical, College & Former Head of the Department (Surgery), Sir Salimullah Medical College Dhaka, & is the Editor-In-Chief of The Coronal.
  • Kazi Mahmudul Haque, B.Pharm(ADUST), M.Pharm(UODA), Unit Manager, Radiant Pharmaceuticals Limited.

References

  1. Drugs and Lactation Database (LactMed®) [Internet]. National Institute of Child Health and Human Development; Bethesda (MD): Jun 21, 2021. Parenteral Nutrition. [PubMed]
  2. Mirtallo J, Canada T, Johnson D, et al. Safe practices for parenteral nutrition. JPEN J Parenteral Enteral Nutri. 2004; 28:S39.
  3. Ayers P, Adams S, Boullata J, et al. A.S.P.E.N. parenteral nutrition safety consensus recommendations. JPEN J Parenter Enteral Nutr 2014; 38:296.
  4. Naylor CJ, Griffiths RD, Fernandez RS. Does a multidisciplinary total parenteral nutrition team improve patient outcomes? A systematic review. JPEN J Parenter Enteral Nutr 2004; 28:251.
  5. Boullata JI, Gilbert K, Sacks G, et al. A.S.P.E.N. clinical guidelines: parenteral nutrition ordering, order review, compounding, labeling, and dispensing. JPEN J Parenter Enteral Nutr 2014; 38:334.
  6. Guenter P, Boullata JI, Ayers P, et al. Standardized Competencies for Parenteral Nutrition Prescribing: The American Society for Parenteral and Enteral Nutrition Model. Nutr Clin Pract 2015; 30:570.
  7. Kuwahara T, Asanami S, Tamura T, Kaneda S. Effects of pH and osmolality on phlebitic potential of infusion solutions for peripheral parenteral nutrition. J Toxicol Sci 1998; 23:77.
  8. Kuwahara T, Asanami S, Tamura T, Kubo S. Dilution is effective in reducing infusion phlebitis in peripheral parenteral nutrition: an experimental study in rabbits. Nutrition 1998; 14:186.
  9. Kovacevich DS, Corrigan M, Ross VM, et al. American Society for Parenteral and Enteral Nutrition Guidelines for the Selection and Care of Central Venous Access Devices for Adult Home Parenteral Nutrition Administration. JPEN J Parenter Enteral Nutr 2019; 43:15.
  10. Safdar N, Kluger DM, Maki DG. A review of risk factors for catheter-related bloodstream infection caused by percutaneously inserted, noncuffed central venous catheters: implications for preventive strategies. Medicine (Baltimore) 2002; 81:466.
  11. Hon K, Bihari S, Holt A, et al. Rate of Catheter-Related Bloodstream Infections Between Tunneled Central Venous Catheters Versus Peripherally Inserted Central Catheters in Adult Home Parenteral Nutrition: A Meta-analysis. JPEN J Parenter Enteral Nutr 2019; 43:41.
  12. Cotogni P, Pittiruti M, Barbero C, et al. Catheter-related complications in cancer patients on home parenteral nutrition: a prospective study of over 51,000 catheter days. JPEN J Parenter Enteral Nutr 2013; 37:375.
  13. Buchman AL, Opilla M, Kwasny M, et al. Risk factors for the development of catheter-related bloodstream infections in patients receiving home parenteral nutrition. JPEN J Parenter Enteral Nutr 2014; 38:744.
  14. Borbolla Foster A, Dixon S, Tyrrell-Price J, Trinder J. Pregnancy and lactation during long-term total parenteral nutrition: A case report and literature review. Obstet Med. 2016 Dec;9(4):181-184. [PMC free article] [PubMed]
  15. Committee on Practice Bulletins-Obstetrics. ACOG Practice Bulletin No. 189: Nausea And Vomiting Of Pregnancy. Obstet Gynecol. 2018 Jan;131(1):e15-e30. [PubMed]
  16. Wells Mulherin D, Walker R, Holcombe B, Guenter P. ASPEN Report on Nutrition Support Practice Processes With COVID-19: The First Response. Nutr Clin Pract. 2020 Oct;35(5):783-791. [PMC free article] [PubMed]
  17. Parienti JJ, Mongardon N, Mégarbane B, Mira JP, Kalfon P, Gros A, Marqué S, Thuong M, Pottier V, Ramakers M, Savary B, Seguin A, Valette X, Terzi N, Sauneuf B, Cattoir V, Mermel LA, du Cheyron D., 3SITES Study Group. Intravascular Complications of Central Venous Catheterization by Insertion Site. N Engl J Med. 2015 Sep 24;373(13):1220-9. [PubMed]
  18. Latif A, Halim MS, Pronovost PJ. Eliminating Infections in the ICU: CLABSI. Curr Infect Dis Rep. 2015 Jul;17(7):491. [PubMed]
  19. Mattioli S, Miglioli M, Montagna P, Lerro MF, Pilotti V, Gozzetti G. Wernicke’s encephalopathy during total parenteral nutrition: observation in one case. JPEN J Parenter Enteral Nutr. 1988 Nov-Dec;12(6):626-7. [PubMed]
  20. Sanchez Acera E, Arenas Villafranca JJ, Abilés J, Faus Felipe V. [Hypersensibility reaction to parenteral nutrition approach; a case report]. Nutr Hosp. 2014 Mar 01;29(3):695-7. [PubMed]