Parenteral Nutrition in Adults



Prescription for PN

Does your patient require PN?

Determining if your patient needs PN is not always straightforward. Despite improvements in outcomes for better nourished patients compared to malnourished patients, the heterogeneity of the patient population requiring artificial nutrition support, and the limitations of the research in this area mean there can be a lack of evidence to support decision making in individual clinical situations.

Determining if your patient needs PN is not always straightforward. Despite improvements in outcomes for better nourished patients compared to malnourished patients, the heterogeneity of the patient population requiring artificial nutrition support, and the limitations of the research in this area mean there can be a lack of evidence to support decision making in individual clinical situations.

Both ESPEN (the European Society for Clinical Nutrition and Metabolism) and NICE (the National Institute for Health and Care Excellence) guidelines refer to patients who are nutritionally at risk as being eligible for PN if enteral or oral intake is inadequate.

Both ESPEN (the European Society for Clinical Nutrition and Metabolism) and NICE (the National Institute for Health and Care Excellence) guidelines refer to patients who are nutritionally at risk as being eligible for PN if enteral or oral intake is inadequate.







Screening for nutritional risk in adults

BAPEN (the British Association for Parenteral and Enteral Nutrition) refers to nutritional screening as ‘a rapid, general, often initial evaluation undertaken by nurses, medical or other staff, to detect significant risk of malnutrition and to implement a clear plan of action such as simple dietary measures or referral for expert advice.’2 This is in contrast to nutritional assessment which involves a more detailed evaluation of nutritional status so a specific nutritional plan can be implemented. Nutritional assessments are generally undertaken by specialists in this field.

A number of tools are available to screen for nutritional risk in adults and for adherence to NICE quality standards, and the selected screening tool should be a validated one.3 Details of the available screening tools are outside the scope of this e-learning material, however some examples are mentioned below.

The NICE definitions of malnutrition and risk of malnutrition in adults are based on nutritional history, body mass index (BMI) and clinical condition.1





The Nutritional Risk Screening 2002 (NRS 2002) tool enables the assignment of a nutritional risk score based upon nutritional status and disease severity. This tool was produced by ESPEN for use in the hospital setting. ‘MUST’ (the Malnutrition Universal Screening Tool’) has been developed in the UK by BAPEN; its use has been endorsed by NICE. Alternatively, though not exhaustively, the Subjective Global Assessment (SGA) is a validated tool which may also be used.







Refeeding problems

Problems associated with refeeding can manifest as Refeeding Syndrome and Wernicke–Korsakoff Syndrome.

Refeeding problems occur because prolonged starvation causes adaptive changes in metabolic and hormonal functions accompanied by deficiences in trace elements, vitamins and electrolytes.1,4 These changes are reversed by the provision of nutritients but this causes an increase in demand for electrolytes and nutrients, and a shift of water and sodium out of cells.1 PN can cause refeeding problems because it can be easy quickly administer a large nutrient load.

Refeeding syndrome is a potentially lethal complication of over-rapid or unbalanced nutrition support following a period of undernutrition.4

Refeeding syndrome – a range of life threatening clinical and biochemical abnormalities may present:1

  • Cardiac failure, pulmonary oedema and dysrhythmias
  • Fluid overload, or fluid depletion
  • Hypophosphataemia*
  • Hypokalaemia*
  • Hypomagnesaemia*
  • Hyperglycaemia
  • Hypercapnia, respiratory failure
*Note: Phosphate, potassium and magnesium are predominantly intracellular cations. During starvation, serum levels may remain normal while total body levels are low. Refeeding causes cellular uptake of these electrolytes resulting in low serum levels.
Upon refeeding starving cells

Upon refeeding starving cells, which havepreviously used non-carbohydrate substrates for energy, revert to carbohydrate metabolism . Thiamine is an essential coenzyme in carbohydrate metabolism and acute thiamine deficiency may result due to increased demand.1,4 This deficiency can result in the Wernicke–Korsakoff syndrome which presents as one or more of the following:

  • Apathy and disorientation
  • Nystagmus, ocular abnormalities
  • Ataxia
  • Confabulation, severe impairment of short term memory
For patients at high risk of developing refeeding problems
  • Energy
  • Fluid
  • Electrolytes
  • Amino acids
  • Glucose
  • Lipid (fat)
  • Vitamins
  • Trace elements

For patients at high risk of developing refeeding problems, NICE recommends the following (Note – intravenous recommendations are provided here, for oral guidance please refer to NICE Clinical Guideline 32, Available at http://www.ncbi.nlm.nih.gov/books/NBK49269/pdf/Bookshelf_NBK49269.pdf):1

  • Provision of full daily dose intravenous vitamin B immediately before and for the first 10 days of feeding, plus daily multivitamins and trace elements.
  • Commencing nutrition support at a maximum of 10kcal/kg/day, increasing levels slowly to meet needs by 4-7 days
  •  In extreme cases (e.g. BMI < 14Kg/m2 or negligible intake for more than 15 days) use only 5kcal/kg/day at the start of feeding and monitor cardiac rhythm continually
  • Monitor cardiac rhythm continually in patients who have or develop cardiac arrythmias
  • Rehydrate carefully and closely monitor fluid balance and clinical status
  • Unless pre-feeding levels are high, supplement potassium (2-4mmol/kg/day), phosphate (0.3-0.6mmol/kg/day) and magnesium (0.2mmol/kg/day intravenous, oral dose differs – refer to NICE guidance)
  • Correction of electrolyte and fluid imbalances prior to feeding is not necessary; this can be done whilst feeding


When to consider a prescription for PN - National and International guideline recommendations1,5,6

Guideline Group Patient population Recommendation Year of publication
Nice All patients

Healthcare professionals should consider the use of PN in people who are malnourished or at risk of malnutrition and meet either of the following criteria:

  • Inadequate or unsafe oral and/or enteral nutritional intake
  • A non-functional, inaccessible or perforated (leaking) gastrointestinal tract
2006
ESPEN ICU

All patients not expected to be on normal nutrition within 3 days should receive nutritional support within 24-48hrs following admission to ICU.

All ICU patients who are not expected to be on normal nutrition within 3 days – Parenteral Nutrition should be commenced within 24-48 hrs if EN is contra-indicated or not tolerated.

2009
ESPEN Surgical patients

Pre-operative PN is indicated in severely undernourished patients who cannot be adequately orally or enterally fed – several studies have documented 7-10 days pre-op PN improves post-op outcome in patients with severe malnutrition.

Post-operative PN:

  • Undernourished patients in whom EN is not feasible or tolerated
  • Patients with post-operative complications impairing GI function who are unable to receive and absorb adequate amounts of oral/enteral feeding for at least 7 days
  • For patients requiring post-operative artificial nutrition, enteral feeding or a combination of EN and PN is the first choice
  • Combinations of EN and PN should be considered in patients in whom there is an indication for nutritional support and in whom >60% of energy needs cannot be met via enteral route (e.g. high output fistula, or in patients in whom benign or malignant GI lesions are partly obstructing and do not allow enteral refeeding)
  • In patients with prolonged GI failure PN is life saving
2009





What constitutes inadequate enteral feeding?

The administration of enteral feeds is associated with practical problems and frequently results in insufficient feed delivery.15,16 Delivering target calories via the enteral route can be particularly challenging in the ICU. International studies have demonstrated maximum calorie intakes of between 52% and 70% of prescribed calories being delivered via the enteral route to ICU patients.16

At the time of writing there is no apparent universally agreed definition as to what constitutes inadequate oral or enteral feeding. The ESPEN guidelines in non-surgical oncology patients discuss an oral daily calorie intake of less than 60% REE (resting energy expenditure) as being inadequate,8 and recommend the use of SPN (supplemental parenteral nutrition) in surgical patients achieving less than 60% of their daily target enteral intake.6 In critically ill patients, successful enteral feeding has been defined as ‘maintenance feeding of ≥40ml/hr with four hourly NG[nasogastric] aspirates totalling <250ml.’17




Nutritional Requirements

Parenteral Nutrition Provides:

  • Energy
  • Fluid
  • Electrolytes
  • Amino acids
  • Glucose
  • Lipid (fat)
  • Vitamins
  • Trace elements

Energy

In the UK, the energy supplied by PN is measured in kilocalories. Total energy is the combined sum of the kilocalories provided by amino acids, glucose and lipid intake.[as visual, total calories = amino acid Kcal + glucose Kcal + lipid Kcal ??? bags, PN bag, also other infusions?] The term ‘non-protein calories’ may also be referred to which is simply the sum of glucose and lipid calories; there is a perception this term should no longer be used as it can contribute to overfeeding.23

The amount of daily calories that should be supplied to different patient populations requiring nutritional support has been extensively deliberated in the last few decades. In particular, requirements for critically ill patients are still very much debated. During the 1970s and ‘80s ‘hyperalimentation’ was used with the aim of suppressing endogenous glucose production and sparing amino acids in critically ill patients. The liberal use of PN and massive infusions of glucose particularly in the pre-glycaemic control era resulted in complications.

Overfeeding via the parenteral route has been shown to cause: 15,16,23

  • Hyperglycaemia
  • Hepatic steatosis (fatty liver)
  • Excess carbon dioxide production
  • Increased number of infectious complications compared to enteral nutrition

Increased number of infectious complications compared to enteral nutrition

How much energy does my adult patient require?

The body's response to stress

The body’s response to stress, injury or trauma produces a hypermetabolic state.24-26 The degree of hypermetabolism varies but ESPEN refers to an average maximum of 110-120% of predicted resting metabolic rates in acute and chronic illness.6 In individual patients however, dependent upon the severity and stage of the disease or trauma this value may be very different.

The presence of hypermetabolism

The presence of hypermetabolism does not necessarily translate into increased energy requirements. There are many determinants of energy expenditure and it is possible the increase in energy requirements due to hypermetabolism may be offset by other factors.27 The various treatments used in the medical management of patients can increase or decrease energy expenditure; this in the context of the pathological state plus individual patient factors makes the prediction of energy expenditure questionable. Interestingly, measurements of resting energy expenditure in critically ill patients have shown values similar to ‘normal’ resting energy expenditures.27

Daily energy requirements

Daily energy requirements can be measured by indirect calorimetry. This technique determines the oxidation of carbohydrate, fat and protein based on measurements of oxygen consumption and carbon dioxide production and is considered to be the ‘gold standard’ in critical care. Not all units have access to the equipment required or the availability of personnel trained in interpreting the measurements.

Indirect calorimetry

If indirect calorimetry is not available then equations are used to predict energy expenditure. Alternatively, the nutrition societies’ guidelines can be used.










Fluid

Water accounts for approximately 60% of human body weight.30 Body water is broadly divided into two compartments; the extracellular (EC) and intracellular (IC) space.

Types of fluids

Under normal physiological conditions, fluid balance and distribution is tightly controlled by neurohormonal mechanisms and a haemodynamic regulatory cycle involving the cardiovascular system, nervous system and the kidneys.30 Different disease states can result in abnormalities in fluid handling.

Disturbances of water and electrolytes have a more profound and immediate effect on health than nutrients.29

For maintenance, NICE recommends 30-35ml fluid/kg/ day with allowances for positive or negative fluid balances.1 In patients with fever, 2-2.5ml/kg/24 hours should be added for each 1˚C rise in temperature above 37˚C per 24 hour period.29a

PN typically provides large volumes of fluid so accurate fluid balances are essential. [wondering if we can add in picture of PN bag with xxxxxxml] When calculating requirements, all fluids (oral, enteral and IV intake including drug infusions) should be considered to prevent over-prescription. Excess sodium and water is a common cause of oedema, prolonged ileus and other complications.1 Additional IV fluids should only be prescribed when there has been an active assessment of the volume of PN already being administered and there is a clear indication that additional fluids and/or electrolytes are required.14

Time Oral input IVI input Cumulative input Urine output Bowels output Vomit output Cumulative output
08.00 Water 150ml Normal saline 0.9% 250ml 550ml 550ml
09.00 100ml 350ml
10.00 Coffee 150ml 100ml 600ml 250ml 800ml
11.00 Water 300ml IVI tissued 900ml 150ml 950ml
12.00 Verillon sited ??? 350ml 1,300ml
13.00 100ml 1,000ml
14.00 Tea 150ml 1,150ml 100ml 1,400ml
15.00 100ml 1,250ml
16.00 Water 75ml 100ml 1,425ml
17.00 100ml 1,525ml 200ml 1,600ml
18.00 Tea 150ml 100ml 1,775ml 100ml 1,700ml



Electrolytes

The electrolytes required by the body can be supplied within a PN formulation. NICE guidelines recommend full electrolyte requirements be provided from the outset of nutritional support.1

In critical illness electrolyte requirements are highly variable. ESPEN recommends the requirements of critically ill patients be determined by plasma electrolyte monitoring.5

Electrolyte Function Electrolyte Function Standard requirement in adults29* (mmol/Kg BW/day)
Sodium Principal extracellular cation, key osmotic agent 1-1.5
Potassium Principal intracellular cation 1-1.5
Magnesium Essential cofactor , contained in bone 0.1-0.2
Phosphate Most abundant anion in the body, located in the skeleton and intracellular fluid. Required for energy metabolism, regulation of enzyme activity and membrane stability. 0.3-0.5
Calcium Most abundant cation in the body, 99% located in the skeleton. Involved in blood clotting, neural conductivity, muscle contraction and hormone secretion 0.1-0.15
Chloride Most abundant extracellular anion 1-1.5

*For patients with normal hepatic and renal function, without abnormal losses and normal blood electrolyte concentrations as confirmed by regular monitoring







Amino acids

Proteins consist of long chains of amino acids. Under normal physiological conditions, these chains are broken down by hydrolysis during digestion and absorption in the gastrointestinal tract. Following absorption, the individual amino acids are used to synthesise other proteins and biological entities, or are oxidised to urea and carbon dioxide as a source of energy.

Functions of proteins in the body

Structural and functional component of all body tissues

  • Structural proteins – keratin, collagen, elastin
  • Muscle contractile proteins – actin, myosin
  • Cell membrane proteins – glycoproteins
  • Enzymes
  • Membrane carriers
  • Hormones
  • Immune molecules (antibodies)
  • Oxygen carriers (Hb, myoglobin)

Required for all essential body processes such as water balancing, nutrient and oxygen transport

Amino acids act as precursors for coenzymes, hormones, nucleic acids and neurotransmitters

Source of energy (4kcl/g)

Production of glucose and fat

Sources & fates of amino acids

PN provides amino acids as monopeptides. Infused amino acids go directly into the bloodstream and contribute to the amino acid pool. In the UK, a range of amino acid solutions is available for parenteral use. These solutions all contain the nine amino acids deemed to be essential but differ in their content of non-essential amino acids. The difference in content of non-essential amino acids is not thought to be clinically significant.

Different concentrations of amino acid solutions for parenteral administration are available, typically labelled by the amount of nitrogen they provide. For example Aminoven® 25 contains approximately 25g of nitrogen (equating to 150g amino acids) per litre of solution. Amino acid solutions are included in three-in-one and two-in-one ‘convenience’ products supplied by the PN manufacturers. One gram of protein provides approximately 0.625g of Nitrogen.

The first step in designing a PN regimen is usually calculating the protein requirements. Protein requirements can vary dependent upon metabolic needs and pathology.

Protein metabolism in stress or trauma

Protein metabolism in stress or trauma

In health, substrates are utilised largely by availability, but following stress (including major surgery) or trauma profound changes in metabolism occur. Though a series of neurohormonal and inflammatory pathways, catabolism is increased and there is resistance to anabolic signals.24 These changes result in alterations in substrate use and body composition. The provision of exogenous nutrients does not suppress the metabolic changes; the aim of nutritional support is to provide energy and essential nutrients to support cell and organ function.31

The liver increases glucose production through the breakdown of glycogen stores and the recycling of amino acid and lipid components (gluconeogenesis). In addition to increased production of glucose, insulin resistance ensues contributing to hyperglycaemia. These changes are believed to be an adaptive mechanism primarily aimed at maintaining the supply of glucose to the vital organs that are unable under stress conditions to use other energy substrates.24, 26

Catabolism of lean body mass is accelerated to provide amino acids for the synthesis of acute phase proteins, wound healing, delivery of glutamine and gluconeogenesis.24,25,31 Loss of muscle mass results from an imbalance between muscle proteolysis and protein synthesis.32

Trauma of sepsis

Immobility also contributes to the loss of non-fat mass. The functional limitations often seen in patients up to several years post ICU discharge are believed to be associated with skeletal muscle wasting and possibly ICU acquired muscle weakness.24

Lipid metabolism increases, though not to the same extent as carbohydrate metabolism. The breakdown of lipid (lipolysis ) produces free fatty acids and glycerol. Glycerol is metabolised in the liver for the production of glucose.24,26 Fatty acids are either oxidised in the liver or muscle (although incomplete oxidation can ultimately contribute to organ damage24), converted into ketone bodies (concurrently producing energy) or re-esterified in the liver to form triglycerides.26

Protein metabolism in different disease states

Outside the ICU, other disease states are associated with changes in protein metabolism.

Increased metabolic rates have been demonstrated in patients with alcoholic steatohepatitis and liver cirrhosis, resulting in an increase in protein requirements above that of a healthy adult.7 Changes in the ratio of different amino acids (particularly aromatic acids and branched chain amino acids) due to metabolic alterations seen in liver cirrhosis have been theorised as being responsible for hepatic encephalopathy.33 ESPEN guidelines recommend consideration of use of parenteral solutions rich in branched chain amino acids or low in aromatic amino acids, methionine and tryptophan in encephalopathy grades III-IV. 7 In acute liver failure plasma levels of amino acids are raised three to four fold; ESPEN do however recommend the use of amino acids (0.8-1.2g/kg/day) in acute or subacute liver failure in order to support protein synthesis.7

Substrate metabolism in severe acute pancreatitis is similar to that in response to severe sepsis or trauma and protein catabolism is increased.11

Patients with renal failure represent a heterogeneous group. Acute kidney injury is associated with protein catabolism, alterations in the metabolism of various amino acids and several amino acids (e.g. tyrosine, histidine) become essential. Patients with acute kidney injury on renal replacement therapy and PN require additional protein to account for losses of approximately 0.2g/kg/day plus the 10-15% infused amino acids lost in the dialysate or ultrafiltrate.12 Protein energy wasting can be associated with chronic kidney disease but restriction of intake is necessary in patients who are not dialysed to manage uraemia.12

How much amino acid to give to adult patients requiring nutrition support?

NICE recommends 0.8-1.5g (corresponding to approximately 0.13-0.24 grams of nitrogen from amino acids in intravenous nutrition) to provide sufficient protein for most patients in both hospital and community settings.1

The nutritional societies have produced guidance in different pathological states:

ICU (general)5 1.3-1.5g/Kg 1.3-1.5g/Kg ideal body weight per day
Obese patients with metabolic stress28 Obese patients with metabolic stress28 Initial protein intakes:
BMI< 40: 2g/Kg ideal body weight per day
BMI>40: 2.5g/Kg ideal body weight per day
Though not for patients with hepatic or renal disease, care with a history of diabetic ketoacidosis.
Acute pancreatitis11 In severe acute pancreatitis 1.2-1.5g/Kg body weight per day. Parenteral glutamine supplementation should be considered. Reduce to 0.8-1.2g/Kg body weight per day in the case of hepatic or renal failure
Renal failure12 Acute Kidney Injury:
Conservative therapy, mild catabolism: 0-6-0.8 (max 1.0)g/kg/day
Extracorporeal therapy, moderate catabolism: 1.0-1.5g/kg/day
Continuous renal replacement therapy, severe hypercatabolism: up to a maximum of 1.7g/kg/day
Non-dialysis Chronic Kidney Disease Glomerular filtrate rate <70ml/min: 0.55-0.60g/kg/day
Chronic Kidney Disease with haemodialysis: 1.1- 1.4g/kg/day
Non-surgical oncology8 The majority of cancer patients requiring PN for only a short period of time do not need a special formulation
Surgery6 In illness/stressed conditions: 1.5g/kg ideal body weight per day or approximately 20% of total energy requirements to limit nitrogen losses
Home parenteral nutrition (HPN)29 (HPN)29 In unstressed adult HPN patients: 0.8-1.0g/Kg body weight per day
Hepatology7 Hepatic steatohepatitis and cirrhosis: 1.2-1.5g/Kg body weight per day Acute or sub-acute liver failure: 0.8-1.2 g/Kg body weight per day

References

  1. Norman K, Pichard C, Lochs H, Pirlich M. Prognostic impact of disease-related malnutrition. Clin Nutr. 2008 Feb; 27(1):5-15. Epub 2007 Dec 3.
  2. Wischmeyer PE. Malnutrition in the acutely ill patient: is it more than just protein and energy? S Afr J Clin Nutr. 2011; 24(3): S1-S7.
  3. Macdonald K, Page K, Brown L, Bryden D. Parenteral nutrition in critical care. Contin Educ Anaesth Crit Care Pain [internet]. 2012 Nov 21 [cited 2016 Feb 1]. Available from doi:10.1093/bjaceaccp/mks056.
  4. Cederholm T, Jägrén C, Hellström K. Outcome of protein-energy malnutrition in elderly medical patients. Am J Med. 1995 Jan; 98(1): 67-74.
  5. Brotherton A, Simmonds N, Stroud M. Malnutrition Matters Meeting Quality Standaf
      rds in Nutritional Care. Redditch: BAPEN; 2010.
    • National Collaborating Centre for Acute Care (UK). Nutrition Support for Adults: Oral Nutrition Support, Enteral Tube Feeding and Parenteral Nutrition. London: National Collaborating Centre for Acute Care (UK); 2006 Feb. (NICE Clinical Guidelines, No. 32.) Available from http://www.ncbi.nlm.nih.gov/books/NBK49269/pdf/Bookshelf_NBK49269.pdf
    • ASPEN Board of Directors and the Clinical Guidelines Task Force. Guidelines for the use of parenteral and enteral nutrition in adult and pediatric patients. JPEN J Parenter Enteral Nutr. 2002 Jan-Feb; 26 (1 Suppl): 1SA-138SA. Erratum in: JPEN J Parenter Enteral Nutr 2002 Mar-Apr; 26(2): 144.