Parenteral Nutrition

Chapter 4
Parenteral Nutrition

Joanne Louise Price


Although parenteral nutrition (PN) in a paediatric patient was first described in 1944 [1], it first became available for general use in the 1960s. Problems with infusion of high concentration hyperosmolar carbohydrate solutions into peripheral veins meant that severe phlebitis limited the length of time PN could be used. However, in 1968 Wilmore and Dudrick [2] and Dudrick et al. [3] described the provision of intravenous nutrients to an infant via a central venous catheter. Since that time intravenous lipids have been developed, improving energy density in iso-osmolar solutions. The 1970s saw the development of crystalline amino acid solutions, reducing the risk of anaphylaxis.

PN is now an established therapy, to which many patients of all ages owe their lives. It has transformed the outcome for many previously fatal conditions including feeding preterm infants and postsurgical neonates with short bowel syndrome [4].

The composition of PN continues to be researched, developed and refined. As with many lifesaving procedures PN is not without its risks and it is associated with fatal complications (Table 4.1). PN should therefore not be used casually, but in a disciplined and organised manner in carefully selected patients [5, 6]. Paediatric PN should be prescribed only where there is an experienced multidisciplinary team of doctors, dietitians, pharmacists and nurses contributing to the provision and monitoring of the PN therapy, preferably in an experienced paediatric centre.

Table 4.1 Some complications of parenteral nutrition

Gut related Solution related Line related
Villous atrophy
Decreased digestive enzyme activity
Bacterial overgrowth/bacterial translocation
Fluid/electrolyte imbalance
Metabolic bone disease
Over/under delivery of nutrients
Micronutrient toxicity
Toxic effects of non-nutrient components of solutions
Growth failure
Refeeding syndrome
Metabolic bone disease
Catheter occlusion
Accidental line removal
Site infection

Nutrition support teams

It is generally agreed that paediatric parenteral feeding requires considerable clinical, pharmaceutical and nursing skills, with many centres now following the principle of a multidisciplinary nutrition support team (NST) facilitating treatment with PN [6, 7]. However, a report from the National Confidential Enquiry into Patient Outcome and Death (NCEPOD) of a case based observational peer review of PN clinical practice in England, Wales and Northern Ireland found wide variability in practice [8]. Seventy children and 264 neonates in 74 hospitals (as well as 877 adults) were surveyed. Good practice, defined as ‘a standard that the reviewer would accept from themselves and their trainees in their institution’ was found in only 24% of those neonates surveyed. Areas of concern raised included delayed commencement of PN, inconsistent nutrient provision and inconsistent monitoring and review.

NCEPOD stated that it would be valuable to develop a team approach to parenteral nutritional support, recognising that this should be a multidisciplinary exercise with sharing of expertise. The report also recommends that a large scale national audit of PN care in children in the UK should be undertaken to determine the quality of PN care in this group of patients.

Good interdisciplinary communication is paramount if patient care is to be of the highest standard. Improvement in outcome of PN has been demonstrated where a multidisciplinary NST is involved [7, 9–12]. Core members of the team and their roles:

  • paediatric consultant—often a paediatric gastroenterologist oversees patient care
  • paediatric surgeon—inserts feeding lines and advises regarding surgical management as required; many PN dependent children have a surgical diagnosis and will be under the overall care of a paediatric surgeon
  • paediatric dietitian—see below
  • medical specialist paediatric registrar—advises on prescription of PN and many other aspects of care
  • PN pharmacist—responsible for production and checking of solutions, advises regarding prescription when necessary
  • PN nurse—trains carers and staff, coordinates patient care
  • biochemist—advises on monitoring and interpretation of blood biochemistry and appropriate biochemical tests.

The NST produces protocols and procedures and organises audit and reviews of the PN service; it may be monitored by the hospital’s nutrition steering committee.

Other key members of the NST to include as required are psychologists, speech and language therapists, play specialists. These have a particularly important role with children undergoing long term PN.

The role of the dietitian in paediatric parenteral nutrition

As a key member of the NST [[12, 13]] the dietitian ensures the child’s nutritional requirements are met in order to maintain adequate growth and development. There is also a role in the development of the child’s oral feeding skills. The dietitian will:

  • set targets for enteral and parenteral feeding and devise a feeding plan
  • monitor that correct volumes of prescribed enteral feeds/PN are received
  • calculate total nutrient intake and compare with the individual’s requirements
  • use appropriate centile charts to plot the child’s height, weight and head circumference. It is imperative that inadequate growth is recognised and discussed with the NST at the earliest opportunity
  • advise regarding suitable adjustments to feeding regimens to enhance intake and absorption and if necessary advise on changes to feeds in cases of malabsorption or feed intolerance
  • review the nutritional biochemistry and contribute to the discussion and decision making with regard to nutrient intakes and adjustments to the PN

The NST usually reviews the child’s progress at least weekly, with daily reviews by some specialties as necessary. In centres where NSTs have been established, reported benefits include a reduction in mechanical line problems, reduced sepsis, fewer metabolic complications, shorter courses of PN (due to faster transition to appropriate enteral formulas) and savings on the cost of providing PN [9–11].

Indications for parenteral nutrition in children

Indications for PN are given in Table 4.2. This is not an exhaustive list. PN is a hazardous and expensive form of nutritional support in children and is indicated only where enteral nutrition cannot prevent or reverse growth failure. The timing and duration of PN is dependent upon the child’s nutritional reserves, expected duration of starvation and severity of illness. PN is normally built up over 2–4 days and therefore it is neither reasonable nor clinically indicated to routinely prescribe PN for less than 5 days [[14]]. Some long term patients will require PN for a number of years, sometimes into adulthood.

Table 4.2 Indications for parenteral nutrition in children

Intestinal failure Other common indications Patients requiring additional nutrition support
Short bowel syndrome
Surgical and gastrointestinal abnormalities, e.g. gastroschisis, intestinal atresia
Necrotising enterocolitis
Protracted diarrhoea
Malabsorption syndromes
Inflammatory bowel disease
Chronic pseudo-obstruction
Functional immaturity in preterm infants
Chemotherapy (leading to acute intestinal failure)
Chronic aspiration due to gastro-oesophageal reflux
Trauma, burns
Chronic kidney disease
Liver disease
Malignant disease

Considerations in paediatric parenteral nutrition

Enteral nutrition

PN is associated with many complications and for this reason it is widely accepted that enteral nutrition should always be given where possible. If the gut works, it should be used, even if only minimal feeds are tolerated [15]. Absence of luminal nutrients has been associated with atrophic changes in the gut mucosa and it is well recognised that enteral feeding is the single most effective way of preventing many gut related complications.

Nutritionally insignificant volumes of enteral nutrition have been found to have a trophic effect on the gut, encouraging intestinal adaptation, and have been linked to enhanced gut motility, decreased incidence of PN induced cholestasis and decreased bacterial translocation [16–18]. After gastrointestinal surgery, particularly that resulting in short bowel syndrome, intraluminal nutrients and luminal substrates are essential for optimal intestinal adaptation [19]. Initiation of enteral feeding is strongly recommended early in the postoperative period.

Breast milk or standard infant formulas are indicated unless there has been previous evidence of malabsorption or feed intolerance. Short frequent breast feeds or small boluses of expressed breast milk or infant formula, as little as 1–2 mL/hour, are beneficial. If there are signs of malabsorption a hydrolysed protein feed, which is also lactose free and has a proportion of its fat as medium chain triglycerides, may be indicated, e.g. Pregestimil Lipil, Pepti-Junior. It may be advantageous to deliver the feed continuously via an enteral feeding pump to aid absorption. (More detailed management of intestinal failure is discussed in Chapter 8.)


Malnutrition in children results in impaired growth and development. All children on PN should be weighed and measured regularly and the measurements recorded and plotted on appropriate centile charts to ensure appropriate growth is maintained.

Nutritional requirements and demands vary considerably with age and size, with critical periods in infancy and puberty when growth is fastest. The majority of brain growth occurs in the last trimester of pregnancy and the first 2 years of life. Extra special care should be taken to avoid malnutrition and biochemical abnormalities at this time as poor nutrition during these critical periods not only results in slowing and stunting of growth but may permanently affect neurological development [20, 21].

Infants are at considerable risk due to their limited energy reserves and the commencement of PN in a small infant who cannot tolerate enteral feeds is a matter of urgency. A preterm infant weighing 1 kg has only 1% body fat and may survive for only 4 days if starved [22].

Equally adolescents are at significant risk of not achieving their growth potential if nutrient requirements are not met at the onset of and during puberty.

Cholestasis and liver disease

The prevalence of PN associated liver disease (PNALD) is much greater in children than in adults. It has been reported that up to 65% of infants on PN develop abnormal liver function tests within 2–3 weeks of starting PN [23, 24]. The pathogenesis of PNALD is not completely understood. The aetiology is thought to be multifactorial and can progress to cirrhosis and end stage liver failure in some cases [25]. The early introduction of enteral feeding is the most important measure that can be taken to help reduce the risk of cholestasis [6, 26].

In preterm neonates enteral feeding may be delayed or withheld in order to help prevent necrotising enterocolitis (NEC); this has been an area of much debate. A recent Cochrane analysis found that delaying enteral feeds increased length of stay, prolonged use of PN and increased the incidence of cholestasis [27]. Results of a UK multicentre trial (ADEPT) concluded that ‘Early introduction of enteral feeds in growth-restricted preterm infants results in earlier achievement of full enteral feeding and does not appear to increase the risk of NEC’ [28]. Therefore enteral feeding should be introduced as early as possible, even in preterm infants. Recent American guidelines recommend that all preterm babies over 1000 g are commenced on minimal feeds by the second day of life [29].

As well as lack of enteral feeds, PNALD is associated with intrauterine growth retardation, prematurity, immature enterohepatic circulation, underlying disease, number of infections/septic episodes, number of surgical procedures and number of blood transfusions [30, 31]. PN solutions themselves may have a role to play in the development of liver disease; lipid emulsions have been implicated [32] and overfeeding of glucose has been associated with hepatic steatosis [25]. High risk for PNALD is also associated with PN dependency from a young age, very short bowel and predicted prolonged PN.

Cyclical, rather than continuous, PN (p. 64) and cycling of lipid in particular (and sometimes restricting lipid to certain nights of the week) may afford some protection to the liver and is common practice in patients on long term PN, particularly those who have PN at home. This usually involves giving the PN over a shorter period allowing some hours off. There are obvious implications to energy intake and tolerance of solutions and these need to be monitored carefully. Due to the implications on growth, particularly where lipid is restricted, cycling should only be used in long term stable patients who have an experienced NST looking after them. Cases of PNALD which do not improve should be referred to a supraregional liver unit for assessment at the earliest opportunity. Other measures taken to prevent or reverse PNALD include the use of ursodeoxycholic acid, a synthetic bile acid, and treatment of bacterial overgrowth caused by intestinal stasis. This will help to prevent recurrent sepsis from translocation of bacteria across the gastrointestinal wall.

PN related bone disease

Children on long term PN can develop a type of bone disease resembling rickets. The aetiology is multifactorial and may be related to physical inactivity, underlying disease, disordered vitamin D metabolism, hypercalcuria, raised alkaline phosphatase and hypophosphataemia.

Regular biochemical monitoring including measurements of urinary calcium, plasma calcium, plasma phosphorus, plasma parathyroid hormone, vitamin D concentrations and serum alkaline phosphatase activity along with dual-energy x-ray absorptiometry scanning is recommended to evaluate these children [13, 33]. Referral to an endocrine/metabolic specialist may be necessary in cases of concern.

Oral hypersensitivity

Oral hypersensitivity occurs when the oral route is not used for feeding for lengthy periods of time. Lack of stimulation together with unpleasant oral procedures/experiences such as intubations, suction, vomiting, choking may lead to long term feeding problems. Steps to prevent oral feeding aversion will help progress onto enteral feeding and subsequent reduction in PN.

Early involvement of a specialist speech and language therapist to advise regarding oral desensitisation is recommended, particularly in cases of refusal to feed or distress during feeding. A play specialist can work with children around oral desensitisation using messy play and play involving food. In addition to these specialist techniques early and sustained oral feeding when safe to do so, use of dummies (pacifiers), sips and tastes should always be employed (where safe to do so) to maintain oral function, especially in infancy.

Nutrient requirements and solutions

Recommended requirements vary and tend to be based on clinical experience [6, 8, 20, 34, 35]. The European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guidelines [13] are the most recent with regard to paediatric PN at the time of writing.

Fluid and electrolytes

Age, size, fluid balance, the environment and clinical conditions are all factors affecting fluid requirements. Recommendations are given in Table 4.3. Cardiac impairment, renal disease and respiratory insufficiency are examples of conditions that may limit fluid volumes, whereas high fluid losses due to diarrhoea, high output fistula/stoma and fever may all increase fluid needs. Also additional fluid may be needed if radiant heaters/phototherapy are used.

Table 4.3 Summary of parenteral fluid and electrolyte requirements for children

Age/weight Fluid (mL/kg/day) Na (mmol/kg/day) K (mmol/kg/day)
<1500 g 140–180 2.0–3.0 1.0–2.0
>1500 g 140–160 3.0–5.0 1.0–3.0
Preterm to 2 months 140–160 2.0–5.0 1.5–5.0
2 months to 1 year 120–180 2.0–3.0 1.0–3.0
1–2 years 80–150 1.0–3.0 1.0–3.0
3–5 years 80–100 1.0–3.0 1.0–3.0
6–12 years 60–80 1.0–3.0 1.0–3.0
13–18 years 50–70 1.0–3.0 1.0–3.0

Source: Adapted from [13].

Infants have immature organ systems and require high volumes of fluid in order to excrete electrolytes sufficiently. Young children are physiologically unable to concentrate urine and conserve fluid as effectively as adults. Maximum urine concentrations are 550 mOsm/L in preterm infants and 700 mOsm/L in term infants compared with 1200 mOsm/L in adults [36]. Electrolyte requirements are often higher, but dehydration and metabolic acidosis can occur if these are given without adequate fluid. Care should always be taken that fluid requirements are met.

Electrolyte requirements vary with age, clinical condition and blood biochemistry. Electrolyte solutions are usually added to PN in response to each individual child’s blood biochemistry.

Due to very tight homeostatic mechanisms, sodium depletion is not always reflected in blood biochemistry. Sodium depletion can be a direct cause of poor growth. Monitoring of urinary sodium excretion to assess total body sodium is useful especially in cases of high sodium losses such as high output fistula or cystic fibrosis. A low (<20 mmol/L) urinary sodium concentration indicates the need for increased enteral/parenteral sodium provision.

The available fluid volume for PN may influence the choice of nutrient solutions and the route of delivery. Some of the available fluid for PN may be taken up by medications. If concentrated PN solutions are needed to provide adequate nutrition (due to fluid restrictions), then the peripheral route for delivering the solutions may be contraindicated as there is a risk that they will cause thrombophlebitis. Children who are severely fluid restricted will only receive adequate nutrition if the necessarily concentrated PN is delivered via a central venous catheter.


Recommendations for macronutrient intakes are summarised in Table 4.4.

Table 4.4 Summary of recommended daily intakes of macronutrients from PN

Energy Amino acids Lipid CHO
Age (kcal/kg) Age (g/kg) Age (g/kg) Weight (kg) (g/kg)
Prem 110–120 Prem 1.5–4 Prem 3–4 Up to 3 Up to 18
0–1 years 90–100 Term 1.5–3 Infants 3–4 3–10 16–18
1–7 years 75–90 2 months to 3 years 1.0–2.5

10–15 12–14
7–12 years 60–75

15–20 10–12

20–30 <12
12–18 years 30–60 3–18 years 1.0–2.0 Older children 2–3 >30 <10

Prem, preterm; CHO, carbohydrate. 1 kcal = 4.18 kJ.

Source: Adapted from [13].


Diet induced thermogenesis reflects the amount of energy needed for food digestion and absorption and usually accounts for about 10% of daily energy needs. Generally parenteral energy requirements are around 10% less than enteral requirements for this reason.

If energy intakes are inadequate protein accretion falls and dietary/intravenous protein will be metabolised for energy. The child may become catabolic using body tissue protein stores for fuel. This results in linear growth failure. Adequate energy intake will promote weight gain, but will not always promote linear growth in the absence of adequate protein.

Many well infants and children will achieve their expected growth rate if the energy intakes shown in Table 4.4 are provided. An appropriate gain in weight for the age, sex and size of the individual child, taking the clinical condition into consideration, is likely to indicate that the prescription is adequate.

In the disease state these requirements will vary and research suggests that actual energy requirements for many children are less than originally thought [37]. It is recommended that energy intakes should be adapted for those disease states found to increase resting energy expenditure, e.g. head injury, burn injury, pulmonary and cardiac disease [13]. Also extremely low birthweight neonates requiring ventilation have been found to have significantly increased rates of energy expenditure [38]. Uncomplicated surgery does not significantly increase energy requirements [39, 40]. In critically ill children energy requirements vary from day to day [41]. The very sick child may not have significantly increased resting energy expenditure as the catabolic process inhibits growth [42]. Recommendations specifically relating to neonates can be found elsewhere [13, 43, 44].

Whichever estimate of energy requirement is used for an individual child it is essential to monitor closely to ensure appropriate growth is achieved without adverse biochemical consequences.


Lipid preparations provide a concentrated source of energy in an isotonic solution: 2 kcal (8 kJ)/mL in a 20% lipid solution compared with only 0.8 kcal (3 kJ)/mL in a 20% carbohydrate solution. When the fluid volume is limited, maximum energy intake can only be achieved via a central venous catheter by using dextrose and fat mixtures. Lipid emulsions normally contribute 25%–40% of non-protein energy. However, lipid emulsion via a peripheral vein can help provide sufficient energy for growth, avoiding the complications associated with central venous access, and it may prolong the life of peripheral lines in infants [45].

Intravenous lipid particles in solution resemble endogenously produced chylomicrons in terms of size and are hydrolysed by lipoprotein lipase. Intravenous lipids provide essential fatty acids (EFAs) and improve net nitrogen balance compared with glucose alone as a source of non-protein energy [25]. Current ESPGHAN guidelines [13] make no specific recommendation about the type of lipid used but suggest that a minimum linoleic acid intake of 0.25 g/kg/day should be given to preterm infants and 0.1 g/kg/day to term infants and older children to prevent EFA deficiency. In premature infants, due to low stores, EFA deficiency can occur within 72 hours of birth [46].

Intravenous lipid emulsions available in the UK that are considered safe for use in paediatric PN are given in Table 4.5. All solutions contain glycerol and phospholipids and are available as 10% and 20% emulsions.

Table 4.5 20% lipid emulsions*

Name Manufacturer Composition TG (g/L) Energy (kcal/mL) Soya oil (g/L) Olive oil (g/L) Fish oil (g/L) MCT (g/L) α-tocopherol (mg/L)
Intralipid Fresenius Kabi Soya 200 2 200 0 0 0 240
ClinOleic Baxter 80% olive
20% soya
200 2 40 160 0 0 No data
Lipofundin MCT/LCT B Braun 50% soya
50% coconut
200 2 100 0 0 100 170 ± 40
SMOF Fresenius Kabi 30% soya
30% coconut
25% olive
15% fish
200 2 60 50 30 60 169–225
Lipidem B Braun 40% soya
50% coconut
10% fish
200 2 80 0 20 100 190 ± 30
Omegaven Fresenius Kabi 100% fish 200 2 0 0 200 0 130–296

TG, triglycerides; MCT, medium chain triglycerides; LCT, long chain triglycerides. 1 kcal = 1.48 kJ.

* Some 10% emulsions are available but are not recommended due to the high phospholipid/triglycerides ratio [13].

Omegaven is to be used as a supplement, not a complete source of lipid.

Higher concentration emulsions are advantageous where there is fluid restriction and also deliver less phospholipid per gram of triglyceride, leading to more normal plasma phospholipids and cholesterol levels [47]. In children it is recommended that 20% or higher concentrations of lipid emulsions are used due to the higher phospholipids:triglyceride ratio found in 10% emulsions [13].

Lipid emulsions currently used are either based on long chain triglycerides (LCT) or long chain and medium chain triglycerides (MCT) mixed together. Both LCT and MCT/LCT solutions are considered safe to use in paediatrics.

Soya oil emulsions have been available for many years and are the most commonly used. There have been some concerns over the effect of the highly polyunsaturated, unphysiological fatty acid supply from soybean oil. The development of PNALD seems to be associated with the composition of the soybean oil based lipid emulsion, possibly as a result of the pro-inflammatory metabolites of ω6 fatty acids. There is mounting evidence that the ω6 polyunsaturated fatty acids (PUFA) most prevalent in soybean oil may in part have a role in the onset of liver injury [32].

Olive oil emulsions may produce more physiological levels of linoleic and oleic acid and better antioxidant status [48]. However, there is currently not enough evidence to recommend one particular solution above another.

Coconut oil emulsions (MCT) have the advantage of carnitine independent uptake by the mitochondria and therefore have a more rapid clearance from the plasma after infusion. Solutions with 50% MCT have been used in paediatric PN for many years. MCT solutions contain approximately 50% less EFAs than LCT solutions alone, yet measured plasma EFAs and their derivatives (linoleic and alpha linolenic acid) were similar compared with LCT solutions [49–51].

Fish oil emulsions contain a significant amount of ω3 PUFA. A number of paediatric reports have cited improvements in liver function tests and a drop in conjugated bilirubin and reversal of PNALD when patients were switched from soybean based lipid solutions to fish oil containing solutions [52–55]. There is an emulsion of fish oil alone (Omegaven) which may be used temporarily as mono therapy, but due to risks of EFA deficiency it cannot be recommended for long term use and is used as a ‘rescue therapy’ in PNALD [56].

SMOF (Fresenius Kabi) will provide just 30% and Lipedem (BBraun) 40% of EFAs contained in Intralipid due to the relatively lower soya oil content of these solutions. This is still adequate at normal volumes but may quickly become inadequate if lipid intake is restricted. To date there has been no published multicentre randomised control trial to assess the long term physiological effects of fish oil solutions. There are also reports that fibrosis seen on liver biopsy may persist despite the improved liver function tests [57, 58]. As such these lipid solutions are recommended for compassionate use in carefully selected individuals and those at high risk of PNALD [56, 59] (p. 185).

Serum lipid levels should be monitored to ensure adequate clearance and hence utilisation. Clearance of lipids from the plasma is limited by the rate of activity of lipoprotein lipase. The amount of fat infused should be adapted to the lipid oxidation capacity, approximately 3–4 g/kg/day [5, 13]. Hyperlipidaemia will result if the enzyme is saturated by excessive doses of fat or by rapid infusion [60]. Gradually increasing the volume of the lipid emulsion by 1 g/kg/day over 3–4 days and maintaining a steady rate of infusion helps prevent possible hypertriglyceridaemia. Tolerance of lipid emulsions has been found to be improved if given continuously in preterm infants [61] although it is usual practice to give 4 hours off the infusion per 24 hours to allow all administered fat to clear the circulation before the next infusion begins. Serum lipids should be monitored as the volume of fat given increases and should always be taken 4 hours after the infusion is completed. Peak levels of triglyceride and free fatty acids normally occur towards the end of the infusion, returning to fasting levels 2–4 hours later. Once they are stable, weekly monitoring is likely to be sufficient.

In malnourished children, it is good practice to assess baseline serum lipids prior to starting PN as children who have failed to thrive or lost weight due to suboptimal intake frequently have raised triglyceride levels that return to normal when sufficient energy is provided. Restricting lipid, and therefore energy, would not be beneficial in this case. A reduced lipid dose may be indicated for children with a marked risk of hyperlipidaemia, e.g. low birth weight infants, sepsis, catabolism [13].

EFA deficiency can be prevented with as little as 0.5–1.0 g/kg total lipid/day [13, 62], although suboptimal energy intake will be the limiting factor. As discussed above, reduction in lipid intake may improve abnormal liver function; however, this cannot be sustained over a long period due to suboptimal energy provision and a long term effect on growth.

If reducing intake for any reason including treating PNALD the source of lipid is an important consideration; as discussed, not all solutions contain equivalent long chain triglyceride levels and subsequently vary in their EFA content (see above).

Some intravenous medication may be given in fat emulsions, e.g. the sedative propofol or the antifungal amphotericin. Consideration should be made of the fat (and therefore energy) content of this.

Apr 1, 2017 | Posted by in NUTRITION | Comments Off on Parenteral Nutrition

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