Energy

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

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.

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.