Parenteral nutrition

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7 Parenteral nutrition

S.J. Harwood, A.G. Cosslett

Key points

• Parenteral nutrition is indicated in people who are malnourished or at risk of malnutrition due to a non-functional, inaccessible or perforated gastro-intestinal tract or who have inadequate or unsafe enteral nutritional intake.
• Combinations of oral diet, enteral feeding and parenteral nutrition, either peripherally or centrally, may be appropriate.
• Parenteral nutrition regimens should be tailored to the nutritional needs of the patient and should contain a balance of seven essential components: water, l-amino acids, glucose, lipid with essential fatty acids, vitamins, trace elements and electrolytes.
• Advances in technology alongside expertise in pharmaceutical stability often permit the required nutrients to be administered from a single container. Increasingly, standard formulations are used, including licensed preparations.
• Parenteral nutrition must be compounded under validated aseptic conditions by trained specialists.
• Prescriptions are guided by baseline nutritional assessment, calculation of requirements using a range of algorithms, knowledge of the patient’s disease status and ongoing monitoring.
• The incidence of complications with parenteral nutrition is reducing; knowledge of management is improving.

Introduction

Malnutrition

Malnutrition can be described as a deficiency, excess, or imbalance of energy, protein, and other nutrients that causes measurable adverse effects on body tissue, size, shape, composition, function and clinical outcome.

In UK hospitals, most malnutrition appears to be a general undernutrition of all nutrients (protein, energy and micronutrients) rather than marasmus (insufficient energy provision) or kwashiorkor (insufficient protein provision). Alternatively, there may be a specific deficiency, such as thiamine in severe hepatic disease.

Multiple causes may contribute to malnutrition. They may include inadequate or unbalanced food intake, increased demand due to clinical disease status, defects in food digestion or absorption, or a compromise in nutritional metabolic pathways. Onset may be acute or insidious.

Even mild malnutrition can result in problems with normal body form and function with adverse effects on clinical, physical and psychosocial status. Symptoms may include impaired immune response, reduced skeletal muscle strength and fatigue, reduced respiratory muscle strength, impaired thermoregulation, impaired skin barrier and wound healing. In turn, these predispose the patient to a wide range of problems including infection, delayed clinical recovery, increased clinical complications, inactivity, psychological decline and reduced quality of life. As symptoms may be non-specific, the underlying malnutrition may be left undiagnosed. Early nutrition intervention is associated with reduced average length of hospital stay and linked cost savings.

Nutrition screening

Routine screening is recommended by the Malnutrition Advisory Group of the British Association of Parenteral and Enteral Nutrition (BAPEN). This group has worked to promote awareness of the clinical significance of malnutrition and has produced guidelines to monitor and manage malnutrition. A range of screening criteria and tools have been developed and refined to assess nutritional status. Examples include the relatively simple and reproducible body mass index tool with consideration of other key factors (Table 7.1), and the BAPEN ‘MUST’ tool (Malnutrition Universal Screening Tool; BAPEN, 2003). Body weight should not be used in isolation; significant weight fluctuations may reflect fluid disturbances, and muscle wasting may be due to immobility rather than undernutrition. More complex anthropometry measurements are sometimes indicated to track changes.

Table 7.1 Body mass index as a screening tool

BMI (kg/m2) BMI category
<18.5 Underweight
18.5–25 Ideal BMI
25–29.9 Overweight
>30 Obese

Body mass index (BMI) = weight (kg)/height (m)2

Incidence of undernutrition

The incidence of undernutrition in hospitalised patients is not accurately known, although it is estimated as being between 20% and 40%.

Indications for parenteral nutrition (PN)

PN is a nutritionally balanced aseptically prepared or sterile physicochemically stable solution or emulsion for intravenous administration. It is indicated whenever the gastro-intestinal tract is inaccessible, perforated or non-functional or when enteral nutrition is inadequate or unsafe. PN should be considered if the enteral route is not likely to be possible for more than 5 days. PN may fulfill the total nutritional requirements or may be supplemental to an enteral feed or diet.

The simplest way to correct or prevent undernutrition is through conventional balanced food; however, this is not always possible. Nutritional support may then require oral supplements or enteral tube feeding. Assuming the gut is functioning normally, the patient will be able to digest and absorb their required nutrients. These include water, protein, carbohydrate, fat, vitamins, minerals and electrolytes; however, if the gut is not accessible or functioning adequately to meet the patient’s needs, or gut rest is indicated, then PN may be used. While the enteral route is the first choice, this may still fail to provide sufficient nutrient intake in a number of patients. Complications and limitations of enteral nutrition need to be recognised.

A decision pathway can be followed to guide initial and ongoing nutritional support. While many are published, a locally tailored and regularly updated pathway is favoured. A useful starting point may be found at Fig. 7.1.

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Fig. 7.1 Decision pathway to guide initial and ongoing nutritional support.

Close monitoring should ensure the patient’s needs are met; a combination of nutrition routes is sometimes the best course. Where possible, patients receiving PN should also receive enteral intake, even minor gut stimulation has been linked with a reduction in the incidence of bacterial translocation through maintaining gut integrity and preventing overgrowth and cholestatic complications. PN should not be stopped abruptly but should be gradually reduced in line with the increasing enteral diet.

Nutrition support teams

A report published by the Kings Fund Report (1992) highlighted the issue of malnutrition both in the hospital and home setting. The findings led to the development of the British Association of Enteral and Parenteral Nutrition (BAPEN) and nutrition support teams throughout the UK. These multidisciplinary nutrition support teams comprise a doctor, nurse, pharmacist and dietitian. They function in a variety of ways, depending on the patient populations and resources. In general, they adopt either a consultative or an authoritative role in nutrition management. Many studies have shown their positive contribution to the total nutritional care of the patient through efficient and appropriate selection and monitoring of feed and route.

Components of a PN regimen

In addition to water, six main groups of nutrients need to be incorporated in a PN regimen (Table 7.2). The aim is to provide appropriate sources and amounts of all the equivalent building blocks in a single daily admixture.

Table 7.2 Oral and equivalent parenteral nutrition source

Oral diet Parenteral nutrition source
Water Water
Protein L-amino acids mixture
Carbohydrate Glucose
Fat with essential fatty acids Lipid emulsions with essential fatty acids
Vitamins Vitamins
Minerals Trace elements
Electrolytes Electrolytes

Water volume

Water is the principal component of the body and accounts for approximately 60% and 55% of total body weight in men and women, respectively. Usually, homeostasis maintains appropriate fluid levels and electrolyte balance, and thirst drives the healthy person to drink; however, some patients are not able physically to respond by drinking and so this homeostasis is ineffective. There is risk of over- or underhydration if the range of factors affecting fluid and electrolyte balance is not fully understood and monitored. In general, an adult patient will require 20–40 ml/kg/day fluid; however, Table 7.3 describes other factors that should be considered in tailoring input to needs.

Table 7.3 Factors affecting fluid requirements

Consider increasing fluid input Consider reducing fluid input
Signs/symptoms of dehydration Signs/symptoms of fluid overload
Fever: increased insensible losses from lungs in hyperventilation and from skin in sweating. Allow 10–15% extra water per 10°C above normal High humidity: reduced rate of evaporation
Acute anabolic state: increased water required for increased cell generation Blood transfusion: volume input
High environmental temperature or low humidity: increased rate of evaporation Cardiac failure: may limit tolerated blood volume
  Drug therapy: assess volume and electrolyte content of infused drug
Abnormal GI loss (vomiting, wounds, ostomies, diarrhoea): consider both volume loss and electrolyte content  
Burns or open wound(s): increased water evaporation  
  Renal failure: fluid may accumulate so reduce input accordingly or provide artificial renal support
Blood loss: assess volume lost and whether replaced by transfusion, colloid, crystalloid  

Amino acids

Twenty l-amino acids are required for protein synthesis and metabolism, and the majority of these can be synthesised endogenously. Eight are called ‘essential’ amino acids because they cannot be synthesised (isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan and valine). A further group of ‘conditionally essential’ amino acids (arginine, choline, glutamine, taurine and S-adenosyl-l-methionine) are defined as the patient’s needs exceed synthesis in clinically stressed conditions. Also, due to the immature metabolic pathways of neonates, infants and children, some other amino acids are essential in the young patient, and these include histidine, proline, cysteine, tyrosine and taurine. Immature neonatal metabolism does not fully metabolise glycine, methionine, phenylalanine and threonine and so requirements are reduced.

To balance the patient’s amino acid requirements and the chemical characteristics of the amino acids (solubility, stability and compatibility), a range of commercially available licensed solutions has been formulated containing a range of amino acid profiles (Table 7.4). Aminoplasmal®, Aminoven, Synthamin® and Vamin® are designed for adult patients. The amino acid profiles of Primene® and Vaminolact® are specifically tailored to neonates, infants and children (reflecting the amino acid profile of maternal cord blood and breast milk, respectively).

Table 7.4 Examples of amino acid and consequential nitrogen content of licensed amino acid solutions available in the UK

Name Nitrogen content (g/L) Electrolytes present
Aminoplasmal® 5% E 8 Potassium, magnesium, sodium and dihydrogen phosphate
Aminoplasmal® 10% 16  
Aminoven® 25 25.7  
Glamin® 22.4  
Hyperamine® 30 30 Sodium
Primene® 10% 15  
Synthamin® 9 9.1 Potassium, magnesium, sodium and acid phosphate
Synthamin® 9 EF 9.1  
Synthamin® 14 14 Potassium, magnesium, sodium and acid phosphate
Synthamin® 14 EF 14  
Synthamin® 17 17 Potassium, magnesium, sodium and acid phosphate
Synthamin® 17 EF 17  
Vamin® 9 Glucose 9.4 Potassium, magnesium, sodium and calcium
Vamin® 14 13.5 Potassium, magnesium, sodium and calcium
Vamin® 14EF 13.5  
Vamin® 18EF 18  
Vaminolact® 9.3  

l-glutamine was initially excluded from formulations due to its low solubility and relatively poor stability in the aqueous environment; however, it is recognised that there is a clinical need for this amino acid in catabolic stress, and it is now available as an additive (Dipeptiven®) and as an amino acid solution containing a dipeptide form of glutamine (Glamin®) in which the peptide bond cleaves in the blood, releasing free l-glutamine. Research is also considering the rationale and merits of supplementing arginine, glutathione and ornithine α-ketoglutarate.

For adults, PN solutions are generally prescribed in terms of the amount of nitrogen they provide, rounding to the nearest gram; for example, 9, 11, 14 or 18 g nitrogen regimens may be prescribed. Assuming adequate energy is supplied, most adult patients achieve nitrogen balance with approximately 0.2 g nitrogen/kg/day, although care should be taken with overweight patients.

A 24-h urine collection can be used as an indicator of nitrogen loss, assuming all urine is collected and urea or volume output is not compromised by renal failure; however, a true nitrogen output determination requires measurement of nitrogen output from all body fluids, including urine, sweat, faeces, skin and wounds. Nitrogen balance studies can indicate the metabolic state of the patient (positive balance in net protein synthesis, negative balance in protein catabolism). Urinary urea constitutes approximately 80% of the urinary nitrogen. The universally accepted conversion factor for nitrogen to protein is 1 g nitrogen per 6.25 g of protein.

Amino acid solutions are hypertonic to blood and should not be administered alone into the peripheral circulation.

Energy

Many factors affect the energy requirement of individual patients and these include age, activity and illness (both severity and stage). Predictive formulae can be applied to estimate the energy requirement, for example, the Harris Benedict equation or the more commonly used Schofield equation, which is shown below in Table 7.5.

Table 7.5 Schofield equation

Age (years) Male Female
15–18 BMR = 17.6 × weight (kg) + 656 BMR = 13.3 × weight (kg) + 690
18–30 BMR = 15.0 × weight (kg) + 690 BMR = 14.8 × weight (kg) + 485
30–60 BMR = 11.4 × weight (kg) + 870 BMR = 8.1 × weight (kg) + 842
>60 BMR = 11.7 × weight (kg) + 585 BMR = 9.0 × weight (kg) + 656

BMR, basal metabolic rate.

Alternatively, calorimetry techniques can be used; however, no single method is ideal or suits all scenarios. Often it is found that two methods result in different recommendations. The majority of adults can be appropriately maintained on 25–35 non-protein kcal/kg/day. There is debate over whether to include amino acids as a source of calories since it is simplistic to assume they are either all spared for protein synthesis or fed into the metabolic pathways (Krebs cycle) and contribute to the release of energy-rich molecules. In general, we refer to ‘non-protein energy’ and sufficient lipid and glucose energy is supplied to spare the amino acids. As a rough guide, the non-protein energy-to-nitrogen ratio is approximately 150:1, although an ideal ratio for all patients has not been absolutely defined. A lower ratio is considered for critically ill patients, while higher ratios are considered for less catabolic patients.

Dual energy

In general, energy should be sourced from a balanced combination of lipid and glucose; this is termed ‘dual energy’ and is more physiological than an exclusive glucose source. Typically, the fat-to-glucose ratio remains close to the 60:40–40:60 ranges.

Dual energy can minimise the risk of giving too much lipid or glucose since complications increase if the metabolic capacity of either is exceeded. A higher incidence of acute adverse effects is noted with faster infusion rates and higher total daily doses, especially in patients with existing metabolic stress. It is, therefore, essential that the administered dose complements the energy requirements and the infusion rate does not exceed the metabolic capacity.

While effectively maintaining nitrogen balance, lipid inclusion is seen to confer a number of advantages (Box 7.1). Some patients, notably long-term home patients, do not tolerate daily lipid infusions and need to be managed on an individual basis. Depending on the enteral intake and nutritional needs, lipids are prescribed for a proportion of the days. A trial with the newer generation lipid emulsions may be appropriate.

Box 7.1 Examples of the advantages of dual energy systems over glucose-only energy systems

Minimise risk of hyperglycaemia and related complications
Prevent and reverse fatty liver (steatosis)
Reduce carbon dioxide production and respiratory distress
Meet higher calorie requirements of septic and trauma patients when glucose oxidation reduced and lipid oxidation increased
Reduce metabolic stress
Support immune function
Improve lean body mass and reduce water retention
Permit peripheral administration, through reduced tonicity
Facilitate fluid restriction, as lipid is a concentrated source of energy
Are a source of essential fatty acids, preventing and correcting deficiency

Glucose

Glucose is the recommended source of carbohydrate (1 g anhydrous glucose provides 4 kcal). Table 7.6 indicates the energy provision and tonicity for a range of concentrations. Glucose 5% is regarded as isotonic with blood. The higher concentrations cause phlebitis if administered directly to peripheral veins and should, therefore, be given by a central vein or in combination with compatible solutions to reduce the tonicity.

Table 7.6 Energy provision and tonicity of glucose solutions

Concentration (w/v) Energy content (kcal/L) Osmolarity (mOsmol/L)
5% 200 278
10% 400 555
20% 800 1110
50% 2000 2775
70% 2800 3885

The glucose infusion rate should generally be between 2 and 4 mg/kg/min. An infusion of 2 mg/kg/min (equating to approximately 200 g (800 kcal) per day for a 70 kg adult) represents the basal glucose requirement, whereas 4 mg/kg/day is regarded as the physiological optimal rate. Higher levels are tolerated by some patients especially those at home on PN, but monitoring of blood glucose is required at least initially. Care needs to be taken as glucose oxidation occurs, but there is an increased conversion to glycogen and fat. If excess glucose is infused and the glycogen storage capacity exceeded, the circulating glucose level rises, de novo lipogenesis occurs (production of fat from glucose) and there is an increased incidence of metabolic complications.

Lipid emulsions

Lipid emulsions are used as a source of energy and for the provision of the essential fatty acids, linoleic and alpha-linolenic acid. Supplying 10 kcal energy per gram of lipid, they are energy rich and can be infused directly into the peripheral veins since they are relatively isotonic with blood.

Typically, patients receive up to 2.5 g lipid/kg/day. For practical compounding reasons, and assuming clinical acceptance, this tends to be rounded to 100 g or 50 g. Details of lipid emulsions available within the UK can be found in Table 7.7.

Table 7.7 Examples of licensed lipid emulsions available in the UK

Lipid emulsion type Details of products with kJ per litre
Soybean oil Intralipid® 10% (4600), 20% (8400), 30% (12600)
Purified olive oil/soybean oil ClinOleic® 20% (8360)
Medium chain triglycerides/soybean oil Lipofundin® MCT/LCT 10% (4430), 20% (8000)
Purified structured triglycerides Structolipid® 20% (8200)
Omega-3-acid triglycerides/soybean oil/medium chain triglycerides Lipidem® (7900)
Highly refined fish oil Omegaven® (4700)
Fish oil/olive oil/soybean oil/medium chain triglycerides SMOFLipid® (8400)

Lipid emulsions are oil-in-water formulations. Figure 7.2 shows the structure of triglycerides (three fatty acids on a glycerol backbone) and a lipid globule, stabilised at the interface by phospholipids. Ionisation of the polar phosphate group of the phospholipid results in a net negative charge of the lipid globule and an electromechanically stable formulation. The lipid globule size distribution is similar to that of the naturally occurring chylomicrons (80–500 nm), as indicated in Fig. 7.3.

image

Fig. 7.2 Triglyceride structure and composition of lipid emulsion globule.

image

Fig. 7.3 Lipid globule size distribution curve of Ivelip® 20%.

The first-generation lipid emulsions have been in use since the 1970 s and utilise soybean oil as the source of long chain fatty acids. More recent research on lipid metabolic pathways and clinical outcomes has indicated that the fatty acid profile of soybean oil alone is not ideal. For example, it is now recognised that these lipid emulsions contain excess essential polyunsaturated fatty acids, resulting in a qualitative and quantitative compromise to the eicosanoid metabolites that have important roles in cell structure, haemodynamics, platelet function, inflammatory response and immune response.

The molecular structure of the fatty acids has an important impact on the patient’s oxidative stress. Two strategies have been applied to overcome this: a reduction in the polyunsaturated fatty acid content through an improved balance of fatty acids or the inclusion of medium chain fatty acids. This has resulted in the development of lipid emulsions that include olive oil (rich in monounsaturated oleic acid and antioxidant α-tocopherol with an appropriate level of essential polyunsaturated fatty acids), fish oil (rich in omega 3 fatty acids) and medium chain triglycerides or structured triglycerides (reduced long chain fatty acid content). Clinical application of these newer lipid emulsions depends upon good clinical studies within the relevant patient population. Such studies should evaluate the efficacy of energy provision and clinical tolerance and report improvements in the eicosanoid-dependent functions or oxidative stress.

Both egg and soybean phospholipids include a phosphate moiety. There is a debate as to whether this is bioavailable. Therefore, some manufacturers include the phosphate content in their stability calculations, while others do not.

The 20% lipid emulsions are favoured, especially in paediatrics, as they contain less phospholipid than the 10% emulsions in relation to triglyceride provision. If there is incomplete clearance of the infused phospholipids, lipoprotein X, an abnormal phospholipid-rich low-density lipoprotein, is generated and a raised blood cholesterol observed. The incidence of raised lipoprotein X levels is greater with the 10% emulsions as they present proportionally more phospholipid.

Lipid clearance monitoring is particularly important in patients who are at risk of impaired clearance, including those who are hyperlipidaemic, diabetic, septic, have impaired renal or hepatic function or are critically ill (Crook, 2000).

Micronutrients

Micronutrients have a key role in intermediary metabolism, as both co-factors and co-enzymes. For example, zinc is required by over 200 enzyme systems and affects many diverse body functions including acid–base balance, immune function and nucleic acid synthesis. It is evident, therefore, that the availability of micronutrients can affect enzyme activity and total metabolism. When disease increases the metabolism of the major substrates, the requirement for micronutrients is increased. Some of the micronutrients also play an essential role in the free radical scavenging system. These include the following:

• copper, zinc and manganese, in the form of superoxide dismutase, dispose of superoxide radicals
• selenium, in the form of glutathione peroxidase, removes hydroperoxyl compounds
• vitamin C is a strong reducing agent
• vitamins A, E and ß-carotene react directly with free radicals

By the time a patient starts PN, they may have already developed a deficiency of one or more essential nutrients. By the time a specific clinical deficiency is observed, for example, depigmentation of hair in copper deficiency or skin lesions in zinc deficiency, the patient will already have tried to compensate to maintain levels, compromised intracellular enzyme activity and antioxidant systems and expressed non-specific symptoms such as fatigue and impaired immune response. A summary of factors that affect micronutrient needs is presented in Box 7.2.

Box 7.2 Factors affecting micronutrient requirements

Baseline nutritional state on starting parenteral nutrition

• Acute or chronic onset of illness
• Dietary history
• Duration and severity of inadequate nutritional intake

Increased loss

• Small bowel fistulae/aspirate: rich in zinc
• Biliary fluid loss: rich in copper
• Burn fluid loss: rich in zinc, copper, selenium

Increased requirement

• Increased metabolism: acute in anabolic phase following catabolic phase of critically ill
• Active growth

Organ function

• Liver failure: copper and manganese clearance reduced
• Renal failure: aluminium, chromium, zinc and nickel clearance reduced

Measuring blood levels of vitamins and trace elements in acutely ill patients is of limited value. It is recommended that these are measured every 1–6 months depending on levels, and in patients at home on PN (NICE, 2006). Deficiency states are clinically significant but, with non-specific symptoms, they are often difficult to diagnose.

Micronutrient experts prefer to prevent a deficit developing and compromising the clinical state, rather than perform regular monitoring of blood results.

Micronutrients should be included daily from the start of the PN. The requirements are increased during critical illness and in chronically depleted patients. Patients with major burns and trauma or with artificial renal support can quickly become depleted. Their supplementation may influence the outcome of the disease. Even if the patient has reasonable levels and reserves initially, they can quickly become depleted if they are not supported by daily administration. Additional oral or enteral supplements may be considered if there is some intestinal absorption. However, copper deficiency can increase iron absorption and zinc intake can decrease copper absorption.

The micronutrients naturally fall into two groups: the trace elements and vitamins. Micronutrients should be added to all PN infusions under appropriate, controlled, environmental conditions prior to administration (NICE, 2006).

Trace elements

Trace elements are generally maintained at a relatively constant tissue concentration and are present to a level of less than 1 mg/kg body weight. They are essential; deficiency results in structural and physiological disorders which, if identified early enough, can be resolved by re-administration. Ten essential trace elements are known: iron, copper, zinc, fluorine, manganese, iodine, cobalt (or as hydroxycobolamin), selenium, molybdenum and chromium. Adult reference ranges for daily requirements of trace metals can be found in Table 7.8. Currently two preparations are commercially available for adults (Decan®, Additrace®) together with a single paediatric preparation (Peditrace®).

Table 7.8 Adult daily reference range for trace elements

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