4. Lipids - ESPEN

1 4. LipidsMETHODSL iterature SearchTimeframe: publications from 1992 2003, in addition rele-vant publications from 1971 and after 2003 were of publications: original paper, meta-analyses : Words: parenteral nutrition, lipid/fat emulsions, paediat-rics, lipoprotein lipase, free fatty emulsions are used in paediatric parenteralnutrition (PN) as a non-carbohydrate source of energyin a low volume and with low osmolarity. In addition theyprovide essential fatty acids. The use of lipid emulsionsdecreases CO2production compared with parenteralnutrition containing a high carbohydrate content (1 3).Net-nitrogen balance can be improved by the addition oflipid emulsions to PN solutions (1,4,5).Composition of MacronutrientsFat oxidation depends on the total energy intake andexpenditure, the total intake of carbohydrates and tri-glycerides and the carbohydrate/fat ratio administered((1,2) (LOE 1)).

2 As carbohydrate intake increases fatoxidation diminishes in favour of lipid storage. In infantsnet lipogenesis occurs at glucose intakes above 18 g/kgper day, whereas it occursat lower glucose intakesin older children (1,6). Maximum fat oxidation occurswhen intravenous lipid emulsions provide 40% of thenon-protein PN calories in newborns (3) and 50% ininfants (1). Generally a lipid intake of 25 to 40% of non-protein calories is recommended in fully parenterally IntakeOmission of lipid emulsions from total parenteralnutrition may lead to biochemical evidence of essentialfatty acid deficiency within a few days in preterm infants(7 9).In order to prevent biochemical evidence of EFA(essential fatty acids) deficiency, g/kg per daylinoleic acid should be given to preterm infants (7,9).

3 In term infants and older children the supply of g/kgper day linoleic acid may be sufficient to prevent EFAdeficiency. When prescribing lipid emulsions the differentLA content of the available lipid emulsions needs totaken into account (see annex).Minimum requirements of plasma alpha-linolenic acidare difficult to define. Most of the data about alpha-linolenic acid deficiency is derived from animal studies(10). In children there is one case report of alpha-linolenic acid deficiency in a 6 years old girl (11). InEurope, all lipid emulsions used for children containalpha-linolenic upper limit of lipid administration is difficult todetermine. In preterm infants a lipid supply of 3 g/kg perday as continuous infusion was tolerated well based onmeasurement of serum triglycerides, cholesterol and molarratios of free fatty acids/albumin (12 14).

4 However pre-term infants weighing less than 1000 g deserve specialattention because their tolerance to intravenous Lipids maybe limited (15) (LOE 2 3).In term infants fat oxidation reaches a maximum at4 g/kg per day, given that the maximum glucose intakedoes not exceed maximal oxidative glucose disposal ofabout 18 g/kg per day (1,2). However, especially inpremature and VLBW infants, a lipid supply exceedingfat oxidation may be desirable to achieve fat metabolic utilisation of intravenous Lipids varieswith gestational and postnatal age, severity of diseaseand other factors. Therefore, monitoring of indicators ofRecommendations Lipid intake should usually provide 25 40% ofnon-protein calories in fully parenterally D Glucose intakes above 18 g/kg per day, whichtend to induce net lipogenesis in infants, shouldusually be avoided in BRecommendation Lipid emulsions are an integral part of paediatricparenteral nutrition providing high energy needswithout carbohydrate overload and supplementingessential fatty DJournal of Pediatric Gastroenterology and Nutrition41:S19 S27 November 2005 ESPGHAN.

5 Reprinted with utilisation such as plasma triglycerides (or ideallylipid oxidation) may help in defining adequate intakes(LOE 3 4).ApplicationThe triglyceride portion of lipid emulsion particles ishydrolyzed by endothelial lipoprotein lipase (LPL). Theliver rapidly removes lipid emulsion fatty acids (FFAs) and glycerol are metabolized ina similar way to enteral Lipids (16 18). FFAs can becaptured by the adjacent tissues or circulate bound to al-bumin, for use in other tissues or uptake by the liver. Therate of hydrolysis varies according to the type of thetriglyceride substrate ( , length of the fatty acid, degreeof saturation, position of the fatty acid on the glycerol)(19). The amount and type of phospholipid emulsifiermay also interfere with the rate of hydrolysis of the lipidparticles of intravenous the lipid emulsion is infused at a rate that is equalto or less than the rate of hydrolysis, a marked changein plasma triglyceride concentration reflecting accumu-lation of the infused triglyceride emulsion is , if the rate of infusion exceeds the rate ofhydrolysis, plasma triglyceride concentration will riseand may cause adverse effects.

6 Furthermore, if the rateof hydrolysis exceeds the rate at which the released freefatty acids are taken up and oxidized, the plasma con-centration of free fatty acids will also increase. Therewere case reports about a condition called fat overloadsyndrome , which may appear with rapid infusion ofhigh dosages of lipid emulsions and may present withcoagulopathies, hepatomegaly, elevated liver enzymes,hyperbilirubinaemia, respiratory distress and thrombo-cytopenia (20,21).In preterm infants tolerance of lipid emulsions isimproved by continuous infusion over 24 hours versus anintermittent regimen with lipid-free intervals (12,14,22).Although there are no comparable studies in older children,continuous infusion of lipid emulsions is recommendedwhenever possible.

7 However, under stable conditions, lipidemulsions may also be well tolerated when given in-termittently as part of cyclic home PN (LOE 4). There isno evidence that gradual increments in the infusion rate oflipids improve fat tolerance (22). An incremental increasein lipid infusion of to 1 g/kg per day may help tomonitor for possible of lipid emulsions from the blood dependson the activity of LPL. Post heparin lipoprotein lipaseactivity can be increased by relatively high doses ofheparin (23,24). However, heparin does not improveutilization of intravenous Lipids . The increase in LPLactivity by heparin leads to an increase in FFAs, whichmay exceed the infants ability to clear the products oflipolysis and may weaken the binding of LPL to theendothelium (24 26).

8 Lipid metabolism results in lipid peroxidation andfree radical formation (27 29). The enhancement of fatutilisation by reducing thecarbohydrate-fat ratio, atstable lipid intakes, and thus reducing energy intakereduces lipid peroxidation and free radical production(30). Soybean oil based lipid emulsions contain onlysmall amounts of alpha-tocopherol (biologically activeform of vitamin E), unless they are supplemented (31),whereas olive oil based lipid emulsions are higher inalpha-tocopherol content (32). Patients on PN should besupplemented with a multi-vitamin preparation that in-cludes vitamin E (alpha-tocopherol) which acts as a freeradical scavenger and anti-oxidant (33 35).MonitoringPlasma clearance of infused triglycerides can beassessed by measurement of plasma triglyceride concen-trations.

9 However, it is unclear at what serum level oftriglycerides adverse effects may occur (36). In infantsfed human milk or formula, triglyceride concentrationsRecommendations In order to prevent EFA deficiency a minimumlinoleic acid intake of g/kg per day should begiven to preterm infants and g/kg per day toterm infants and older D Parenteral lipid intake should usually be limitedto a maximum of 3 4 g/kg per day ( g/kgper hour) in infants (GOR B) and 2 3 g/kg per day( g/kg per hour) in older DRecommendations Dosage of lipid emulsions should not exceed thecapacity for lipid clearance and should be adaptedif marked hyperlipidaemia B In infants, newborns and premature babies lipidemulsions should usually be administered contin-uously over about 24 B. If cyclic PNis used, for example in home PN, lipid emulsionsshould be given over the same duration as theother PN D There is no evidence that gradual increments inthe infusion rate of Lipids improve fat tolerance.

10 Iflipid infusion is increased in increments of to1 g/kg per day, it may be possible to monitor D Heparin does not improve utilisation of intrave-nous Lipids and should not be given with lipidinfusion on a routine basis, unless indicated forother BS20 GUIDELINES ON PAEDIATRIC PARENTERAL NUTRITIONJ Pediatr Gastroenterol Nutr, Vol. 41, Suppl. 2, November 2005of 150 to 200 mg/dl are frequently encountered (14,37).However, it seems reasonable to accept slightly highertriglyceride levels of 250 mg/dl during lipid infusion asthe upper limit in newborns, premature and term infants(LOE 4). For older children, serum levels of triglyceridesof 300 400 mg/dl may be acceptable based on the factthat lipoprotein lipase is saturated at around 400 mg/dl(38) (LOE 4). Checking serum triglyceride levels shouldbe considered with each increase of g/kg per day ofintravenous Lipids and weekly after the maximum doseis Lipid EmulsionsThe lipid emulsions currently used contain soybean oilwith egg yolk phospholipid as the emulsifier and glycerolto make the emulsion isotonic (see annex).