Parenteral Nutrition

PARENTERAL NUTRITION

MODERATOR : DR. Rajesh Sharma

Presenter : Dr. Tuhin Mistry

INTRODUCTIOn

• The prevalence of malnutrition among critically ill patients has remained largely unchanged over the last two decades.

• The metabolic response to stress, injury, surgery, or inflammation cannot be accurately predicted and these metabolic alterations may change during the course of illness.

Introduction(contd…)

• Both underfeeding and overfeeding are common in ICUs, resulting in large energy and other nutritional imbalances.

• Systematic research and clinical trials on various aspects of nutritional support in the ICU are limited and make it challenging to compile evidence-based practice guidelines.

Why do we require nutrition?• Energy production.

• Growth / wound healing.

• Maintain good health.

• Maintain good immunity system.

• Physical and mental development.

• To provide raw materials for synthesis of various substances. e.g. enzymes, hormones, antibodies etc.

In critically ill patients Consumption > Supply of nutrients. Break down of body tissues Negative Nitrogen Balance Reduced immunity ↑ Infection ↓ Wound healing Increases morbidity with poor outcome Prolongs hospital stay of critical patients.

Definition & typesParenteral Nutrition(PN): feeding someone via their blood stream ‘intravenously’.

Partial or Peripheral Parenteral Nutrition(PPN): simultaneous intravenous nutrition with enteral nutrition.

Total Parenteral Nutrition(TPN): feeding a patient solely via the intravenous route.

indications

Relative indications

contraindications

PRACTICAL CONSIDERATIONS IN IV SITE SELECTION

PERIPHERAL Vein

Peripheral Vein(contd…)

ADVANTAGES:• Least expensive• Easily placed and

removed.• Lowest risk for catheter

related infections

DISADVANTAGES:• High levels of phlebitis and

vein damage• Need to change frequently

(48–72 hours)• Kcals usually limited due to

volume restriction.• Limited to one lumen.• Limits infusion osmolality to

600–900 mOsm/L and infusion pH between 5 & 9


• Ideally the peripheral veins are suitable for administration of isotonic fat emulsions and hypocaloric dextrose solutions (i.e., < 10% dextrose)

• Hence, they are limited to preventing starvation adaptation and minimizing nitrogen loss.*

* Isaacs JW, Millikan WJ, Stackhouse J, Hersh T, Rudman D. Parenteral nutrition of adults with a 900 milliosmolar solution via peripheral veins. Am J Clin Nutr 1977;30:552-9.


• As a rule of thumb: If peripheral access has been changed 2–3 times within the first 48 hours following admission on standard IV fluids, PPN should not be attempted.

• Combinations of heparin(1500 U) and hydrocortisone(15 mg) added to the PPN formulation, with or without the use of a nitroglycerin patch(0.1 mg/hr) placed proximal, and as close as possible to the catheter site, have been used to extend the viability of peripheral catheters. *

* Tighe MJ, Wong C, Martin IG, et. al. Do heparin, hydrocortisone, and glyceryl trinitrate influence thrombophlebitis during full intravenous nutrition via a peripheral vein? J Parent Enteral Nutr, 1995;19(6):507-509.

Central vein• Central venous catheters provide temporary or

longterm access to large diameter veins with blood flows in the range of 2–6 L/min.

• This rapid blood flow allows infusion of formulations with osmolarities > 900 mOsm/L.

• If multiple lumens catheter is used, a single lumen should be designated for PN use only.

Central Vein(contd…)

• The Subclavian Vein is the most suitable vein for parenteral nutrition.

• This is comfortable to the patient and carries less risk of dislodgement compared to the IJV and Femoral venous catheter.

• It has less thrombophlebitis risk compared to the Femoral vein.

Central Vein(contd…)

• A central venous line should be placed with strict aseptic precautions after cleaning the skin with chlorhexidine and dressed with sterile dressing (changed every 48 hours).

• The European Society for Clinical Nutrition and Metabolism (ESPEN) has issued specific guidelines on the use of Central Venous Catheters with regard to access, care, diagnosis and therapy of complications.

Requirements, recommendations &

FORMULATION

ENERGY REQUIREMENTS• Requirement of energy: 30 kcal/kg/day (± 5kcal)

• Indirect calorimetry is considered as the gold standard for the measurement of metabolic rate and substrate utilisation.

• Harris-Benedict equation is a more practical means of estimating the Basal Energy Expenditure (BEE) in adults.*

* Harris JA, Benedict FG. Biometric Studies of Basal Metabolism in Man. Publication No. 270. Washington, DC: Carnegie Institution of Washington; 1919.

Energy Requirements(contd…)

• Men : BEE = 66.67 + 13.75W + 5H – 6A*

• Women: BEE = 655.1 + 9.56W + 1.85H – 4.68A*

H = height in cmW = weight in kgA = age in years

Stress factors have to be added to this BEE

* Harris JA, Benedict FG. Biometric Studies of Basal Metabolism in Man. Publication No. 270. Washington, DC: Carnegie Institution of Washington; 1919.


Hunter DC, Jaksic T, Lewis D, Benotti PN, Blackburn GL, Bistrian BR. Resting energy expenditure in the critically ill: estimations versus measurement. Br J Surg 1998;75:875-8.


Ideal body weight (Hamwi method):

• Men : 106 lb (for first 5 ft) + 6 lb (for each additional inch past 5 ft) or 48.0 kg + 2.7 kg per inch over 5 ft.

• Women : 100 lb (for first 5 ft) + 5 lb (for each additional inch past 5 ft) or 45.5 kg + 2.2 kg per inch over 5 ft.


• A much easier method is computation of the IBW by Broca’s index:

Men : Wt in Kg = (Height in cm) – 100 Women: Wt in Kg = (Height in cm) – 105

• Adjusted Body Weight:

IBW + 0.4(Actual Body Weight – IBW)

FLUID REQUIREMENT• Depends on the hydration status of the patient and the

clinical conditions, such as, renal failure, congestive heart failure etc.

• Generally TPN orders should be reviewed twice daily on a 12-hour basis, so that changes in electrolytes or acid-base balance can be addressed appropriately without wastage of costly TPN solutions.

• Requirement of water = 30 ml/kg/day or 1 ml/kcal

CARBOHYDRATE REQUIREMENTS• Carbohydrate is generally provided in amounts up

to 60% of total kcals/day.

• In the hospitalized patient, initial dextrose in PN solutions should not exceed 7.2 g/kg/day (5 mg/kg/minute) to minimize the occurrence of fatty liver and hyperglycemia.

• Diabetic patients are at a greater risk for development of hyperglycemia, hypertriglyceridemia and an increased RQ of > 1.0 if carbohydrates are used in excess.

Carbohydrate Requirements(contd…)

• Dextrose monohydrate, in concentrations from 2.5 to 70%, is the most common form in which carbohydrate is administered parenterally.

• 1 gram of Dextrose provides 3.4 Kcalories.

• Most TPN regimens utilise ≤ 25% dextrose, while the PPN utilise ≤ 10% dextrose solutions for safe osmolarity infusion.

Carbohydrate Requirements(contd…)

• Fructose, sorbitol, xylitol and glycerol as carbohydrate sources for parenteral nutrition have been and are being studied, but none of them have been seen to have any decisive advantage over dextrose and do not have the US Food and Drug Administration(USFDA) approval for use.*

* Karlstad MD, DeMichele SJ, Bistrian BR, Blackburn GL. Effect of total parenteral nutrition with xylitol on protein and energy metabolism in thermally injured rats. JPEN J Parenter Enteral Nutr 1991;15:445-9.

Dextrose Solutions• The carbohydrate source for TPN is dextrose.

• The dextrose solutions must be concentrated to provide enough calories to satisfy daily requirements.

• The standard solution is 50% dextrose, or D50.

• These solutions are hyperosmolar, and must be infused through large central veins.

Dextrose Solutions(contd…)

PROTEIN REQUIREMENTS• Healthy adults = 0.8–1.0 g/kg/day

• Parenteral proteins were earlier provided as casein solutions, which had higher microbicidal growth rates due to contamination.

• But now they are provided in the form of crystalline amino acids, which have better nitrogen balance and do not promote microbial growth.

Protein Requirements(contd…)

• Critically ill patients(without hepatic or renal dysfunction) = 1.5 g/kg/day.

• Acute Renal Failure : 1.5–1.6 g/kg/day

• Chronic Renal Failure = 0.6–0.8 g/kg/day.

• Renal replacement therapy = 2.5 g/kg/day

• In the past, restricting protein in patients with liver failure was the standard practice. however, it is now accepted that this may worsen the underlying liver disease, and does not aid hepatic encephalopathic episodes.

Amino Acid Solutions• Utilized for protein synthesis only. Not for energy

production.(4kcal/g)

• Correct / prevent Negative Nitrogen balance.

• Protein is provided as amino acid solutions that contain varying mixtures of essential(N=9), semi-essential (N=4), and nonessential (N=10) amino acids.

Amino Acid Solutions(contd…)

Essential AA1.Isoleucine2.Leucine3.Valine4.Lysine 5.Methionine 6.Phenylalanine7.Threonine 8.Tryptophane9.Histidine

Non EAA1. Alanine2. Glycine3. Cystine4. Proline5. Serine6. Tyrosine7. Asparagine8. Aspartic acid9. Glutamic acid10.Glutamine

Semi-Essential1.Arginine2.Tyrosine3.Histidine4.Cysteine


• Should be given with energy providing Nutrients. • Should have EAA, NEAA, BCAA. + Electrolytes

• Hyperosmolar solutions:

Osmolarity : 5% - 10% - 490 mosmol/L 990 mosmol/L


GLUTAMINE:

• Principal metabolic fuel for rapidly dividing cells like intestinal epithelial cells & vascular endothelial cells.

• Maintains the integrity of the bowel mucosa.

• Recommended as a daily nutritional supplement in ICU patients (0.2–0.4 g/kg/day).*

* Singer P, Berger MM, Van den Berghe G, et al. ESPEN guidelines on parenteral nutrition: Intensive care. Clin Nutr 2009; 387–400.

FAT REQUIREMENTS• Lipids are used to provide 30% of daily caloric

requirements, and 4% of the daily calories should be provided as linoleic acid to prevent essential fatty acid deficiency(EFAD).

• EFAD may develop within 3 weeks of fat free parenteral nutrition.

• Soybean / safflower oil, egg yolk phospholipids in 10%, 20% & 30% concentrations are the common sources for lipids in TPN.

Fat Requirements(contd)

• Propofol and parenteral intralipids must be used with caution because they are mainly composed of soybean oil or omega-six fatty acids, which have been seen to be immunosuppressive.

• Long chain triglycerides (LCT) were the main source of lipids used in TPN earlier, but subsequent studies have suggested that the LCTs impair the immune system, specifically the reticuloendothelial system.

Fat Requirements(contd)

• Structured lipids(combination of long and medium chain fatty acids) have been found to improve LFT and maintain LDL and HDL ratio.

• The CDC recommends that intralipid infusions be given within 12 hours once started, to avoid gram-negative sepsis.*

*Brown DH, Simkover RA. Maximum hang times for i.v. fat emulsions. Am J Hosp Pharm 1987;44:282,284.

Lipid Emulsions• Lipids are provided as emulsions composed of submicron

droplets of cholesterol, phospholipids, and triglycerides.

• The triglycerides are derived from vegetable oils (safflower or soybean oils) and are rich in linoleic acid, an essential fatty acid

• lipid emulsions are available in 10% and 20% strengths.

• The 10% emulsions provide approximately 1 kcal/mL, and the 20% emulsions provide 2 kcal/mL.

Lipid Emulsions(contd…)

• The lipid emulsions are available in unit volumes of 50 to 500 mL, and can be infused separately (at a maximum rate of 50 mL/hour) or added to the dextrose–amino acid mixtures.

• The triglycerides introduced into the bloodstream are not cleared for 8 to 10 hours, and lipid infusions often produce a transient, lipemic appearing plasma.

Lipid Emulsions(contd…)

MICRONUTRIENT REQUIREMENTS

• Electrolytes,

• Trace elements and

• Vitamins

Micronutrient Requirements(contd…)


• calcium is provided as a gluconate and magnesium is provided as a sulphate, due to improved solubility and compatibility.

• Renal failure, cardiac problems, intestinal losses, hydration status of the patient along with clinical judgement should be factors in considering altering these normal recommendations for electrolytes.



• Copper, zinc, selenium and chromium are the common trace elements that are supplemented in PN.

• Many of these trace elements are monitored monthly in case of patients on prolonged PN, and subsequent action is taken in the forthcoming month.


• Manganese and copper may be withheld in patients with hepatic dysfunction.

• Selenium and chromium intake is restricted in cases of renal failure.

• Iron is incompatible with lipid containing formulations of PN and is usually administered as iron dextran in solution containing dextrose.


• Iodine is often omitted from PN, given that an adequate amount of iodine is absorbed into the skin, due to use of iodine containing disinfectants/ detergents during hospital stay.

• Molybdenum supplementation is required in neonates / infants on prolonged PN.



• Multivitamin preparations that are commercially available can be added to PN solutions.

• Many of these lack vitamin K, which needs to be added separately into the PN bag once a week.

• Thiamine is excessively lost in patients on dialysis and merits individual supplementation in such patients.


• It is common for intensivists to err on the side of over provision of large amounts of vitamin C, thiamine and perhaps zinc; considering their role in wound healing and improvement in the general condition;

• But this at times may be deleterious, as excessive amounts of these, especially vitamin C, may lead to increased oxidative stress.

Preparations available

Single nutrient solution

Dextrose – 5%,10%, 25%, 50%.

Lipid -10%, 20%. Amino Acid solution – 5%, 10%.

Two-in-one Solution Two chambered bag

1. Amino Acid Solution + (Electrolytes)2. Dextrose solution. Contents of both chambers are mixed

together just before infusion.

Volume = 1.5 – 2LCal = 1500 - 2000 kcal

Requires fat to be infused.

Three-in-one solution

Three chambered bag-

•All three components – Dextrose, Fat, Amino Acids and electrolytes are supplied in a single three chambered pack.

•Mixed together just before I.V. infusion with many advantages.

•Volume – 2L•Calorie – 2000kcal

CREATING A TPN REGIMEN

Creating a TPN Regimen(contd…)

STEP 1:

• Determine the daily requirement for calories and protein.

• The daily requirement for calories is 25 kcal/kg.

• The daily protein requirement is 1.2–1.6 g/kg.


• For the 70 kg patient, We will use actual body weight, and a daily protein requirement of 1.4 g/kg.Therefore, the daily requirement for calories and protein will be:

Calories: 25 X 70 = 1,750 Kcal/dayProtein: 1.4 X 70 = 98 grams/day


STEP 2:

• Take a standard mixture of 10% amino acids (500 mL) and 50% dextrose (500 mL) and determine the volume of this mixture that is needed to deliver the estimated daily protein requirement.


• The volume of the A10-D50 mixture that will provide the daily protein requirement is:

98/50 = 1.9 L

• If this mixture is infused over 24 hours, the infusion rate will be:

1900 ml /24 hr = 81 ml/hr


STEP 3:

• Now, determine how many nonprotein calories will be provided by 1.9 liters of A10-D50.

• Dextrose in 1.9 liters of A10-D50:

250 g/L X 1.9 L = 475 gms D

• Now, using an energy yield of 3.4 kcal/g for dextrose, calculate the calories provided by 475 grams of dextrose:

475 X 3.4 = 1,615 kcal/day


STEP 4:

• Daily requirement = 1750 kcal• Daily dextrose calories = 1615 kcal• Deficit = 1750 – 1615 = 135 kcal• The remaining 135 Kcalories will be provided

by lipids.


• If a 10% lipid emulsion (1 kcal/mL)is used, the volume will be 135 mL/day.

• Lipid emulsions are available in unit volumes of 50 mL, so the volume can be adjusted to 150 mL to avoid wastage.

• The maximum infusion rate is 50 mL/hr.


STEP 5:

• The TPN orders for this example can be written as follows:

1. A10-D50 to run at 80 mL/hour.

2. 10% Intralipid, 150 mL, to infuse over 3 hours.

3. Add standard electrolytes, multivitamins, and trace elements.

INITIATION, MAINTENANCE AND

MONITORING OFPARENTERAL NUTRITION

• It would be prudent to start it as soon as one appreciates that the patient is in requirement of TPN, that is, nutritionally compromised.

• Strict aseptic precautions should be followed during introduction of the central line; the external dressing should be changed every 48 hours using sterile precautions. The external tubing should be changed every 24 hours starting with the first feed of the day.

• The lumen being used for TPN should be exclusively reserved for it and no drugs / infusions (except insulin infusion) should be allowed in that lumen.

• An interdisciplinary nutrition team, comprising of the treating physician, intensivist, nutritional therapist and critical care nurse should monitor the patient’s nutritional status regularly on a day-to-day basis.

Mirtallo JM. Introduction to parenteral nutrition. In: Gottschlich MM, Ed. The Science and Practice of Nutrition Support: A Case-Based Core Curriculum. Dubuque, IA: Kendall/Hunt Publishing Co.;2001: 211–223

• Blood lipid levels may be monitored twice weekly.

• Liver function tests must be monitored weekly.

• Patients on long-term TPN need monthly monitoring of vitamin, mineral and trace element status.

• Monitoring should be highly individualised to the existing needs and co-morbidities of the patient.

COMPLICATIONS OF TPN

• Catheter-Related Complications

• Carbohydrate Related Complications

• Lipid Related Complications

• Hepatobiliary Complications

• Bowel Sepsis

Catheter-Related Complications

A) Due to insertion - Injury to Nerves, blood vessels, pneumothorax, infusion of PN solution into plueral cavity.

B) Infection – sepsis, septicaemia, septic shock.

C) Thrombophlebitis – peripheral vein

D) Air Embolism.

Carbohydrate Related Complications

• HYPERGLYCEMIA & hypoglycaemia.

• Tight glycemic control is not recommended in critically ill patients.

• The target range of blood glucose = 140–180 mg/dl.

Carbohydrate Related Complications(contd…)

INSULIN THERAPY:

• A continuous infusion of regular insulin is preferred for critically ill patients who are unstable or have T1DM to prevent wide swings in glucose levels.

• This can be accomplished by adding insulin to the TPN solutions.

• Subcutaneous insulin can be used for patients who are stable.

• Regimens will vary in each patient, but the combination of an intermediate or long-acting insulin with a rapid-acting insulin, when needed, is a popular for hospitalized patients.


HYPOPHOSPHATEMIA:

• The movement of glucose into cells is associated with a similar movement of phosphate into cells, and this provides phosphate for co-factors (e.g., thiamine pyrophosphate) that participate in glucose metabolism.

• This intracellular shift of phosphate can result in hypophosphatemia if extracellular phosphate levels are marginal.


RE-FEEDING SYNDROME:

• The potentially fatal shifts in fluids and electrolytes in malnourished patients receiving artificial refeeding (whether enterally or parenterally).

• These shifts result from hormonal and metabolic changes caused by rapid refeeding and may cause serious clinical complications.

• Observed in patients kept NPO for >7–10 days, chronic alcoholics and those with severe systemic derangements on initiation of TPN.

• Hallmark is hypophosphataemia.

• Abnormal Na+ and fluid balance; changes in glucose, protein, and fat metabolism; thiamine deficiency; decrease serum K+ & Mg2+.

NICE Guidelines for Management of Refeeding Syndrome

PREVENTION(NICE guidelines):-

• Refeeding should be started at a low level of energy replacement(<50 %).

• Vitamin supplementation should also be started with refeeding and continued for at least 10 days.

• Correction of electrolyte and fluid imbalances before feeding is not necessary; it should be done alongside feeding.


HYPERCAPNIA:

• Excess carbohydrate intake promotes CO2 retention in patients with respiratoryinsufficiency.

• However, CO2 retention is a consequence ofoverfeeding, and not only overfeeding with carbohydrates.

Lipid Related Complications

• Hypertriglyceridemia

• Essential fatty acid deficiency(EFAD)

• Promote inflammation: Lipid emulsions used in TPN regimens are rich in oxidizable lipids. oxidation of infused lipids will trigger an inflammatory response.

Hepatobiliary ComplicationsHEPATIC STEATOSIS:

• Fat accumulation in the liver is common in patients receiving longterm TPN.

• It is believed to be the result of chronic overfeeding with carbohydrates and lipids.

• CHOLESTASIS :

• The absence of lipids in the proximal small bowel prevents cholecystokinin-mediated contraction of the gallbladder.

• Bile stasis and the accumulation of sludge in the gallbladder can lead to acalculous cholecystitis.

Bowel Sepsis

Lose of functional and structural integrity of gut:

The absence of nutritional bulk in the GI tract leads to atrophic changes in the bowel mucosa, and impairs bowel-associated immunity, and these changes can lead to the systemic spread of enteric pathogens.

Guidelines

ESPEN recommendations

ESPEN Recommendations(contd…)

Summary• Critically sick patients are in catabolic phase, require more

energy and nutrients.

• PN is a valuable and necessary medical treatment for providing both nutritional sustenance and life extension at a time when it is not possible to sustain them any other way.

• By focusing on the essential elements of PN management, this form of nutrition support can be applied successfully with minimal complications.

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Education

Parenteral Nutrition