8. Vitamins - ESPEN

1 8. VitaminsMETHODSL iterature SearchTime frame of publication search: 1992 2004; relevantpublications from 1984 1992 were Words: parenteral nutrition [MESH] AND Vitamins [MESH] with limits (English language, infant, children,18years).VITAMINSI ntroductionParenteral Vitamins are usually applied as a mixture ofdifferent Vitamins . Vitamins pose particular pharmaco-logical problems, when given intravenously, since somemay adhere to the tubing and/or be degraded by light. Alsostability in regard to admixture and ingredients mayhave an effect. Therefore the actual amount of vitaminsdelivered to the patient may be much lower than theintended dose, particularly in the case of retinol (vitaminA) and in premature infants who receive solutions withslow infusion rates. The optimal parenteral vitamin re-quirements for children and neonates have never beendetermined. While there are several parenteral vitaminpreparations for adults and older children, there are just afew multivitamin preparations available for preterm in-fants and neonates.

2 The available products for infantscontain the same relative amount of lipid soluble vitaminsdespite different pharmacological properties in differentpreparations (combined water and fat soluble vitaminsolution versus only fat soluble vitamin preparation).Adult formulations containing propylene glycol and thepolysorbate additives are not recommended for use ininfants because of concerns on potential toxicity. There islittle data on vitamin needs of children with acute andchronic diseases whose requirements might concentrations in the effluents of the applica-tion sets are the result of a complex interaction of severalfactors, including flow rates, tubing materials and sizes,intensity of light exposition, environmental humidity andtemperature as well as the relative content of each new data has been published in this area duringthe last 20 years. Therefore, this chapter cannot providea fully evidence based recommendation but tries toprovide a reasonable framework for the pediatrician whoprescribes parenteral Vitamins and to point out particularareas of problems.

3 All studies determining vitamin levelsduring intravenous supply have been undertaken withcommercially available mixtures, either given in theglucose amino acid solution or in the lipid , current recommendations are based on thecomposition of specific the lack of adequate evidence, it is recommen-ded to maintain, for the time being, parenteral vitamindosages that have been previously recommended ((1 3)(LOE 4)) and have been used without apparent harmfuleffects in clinical practice for a number of years, with theexception of thiamine where needs may be higher thanpreviously assumed. (GOR D)Fat Soluble VitaminsA sufficient supply of Vitamins is essential for growthand development. Infants and particularly low birth weightinfants have low body stores of Vitamins at birth due toa limited transfer of lipid-soluble substrates across thematernal placenta. Therefore, a sufficient supply of vita-mins to preterm infants from the first days of life isrecommended.

4 The parenteral vitamin supply to pre-mature infants is extensively exposed to light and oxygenand to the lipophilic surfaces of tubing materials due tothe small infusion Infants and children receiving PN should receiveparenteral D When possible water and lipid soluble vitaminsshould be added to the lipid emulsion or a mixturecontaining lipids to increase vitamin D Intermittent substitution twice or three timesa week has not been studied. There is a hypothet-ical risk of adverse effects by transient high recommendations are based on dailyinfusion. An exception is vitamin K, which canbe given D Optimal doses and conditions of infusion forvitamins in infants and children have not beenestablished, therefore, recommendations in and are based on expert D Measurement of vitamin concentrations in in-dividual parenterally fed children may be neededbased on clinical indications and in patients onlong term parenteral nutrition, but in otherpatients routine monitoring is not recommendedbecause of lack of evidence on adequate DJournal of Pediatric Gastroenterology and Nutrition41:S47 S53 November 2005 ESPGHAN.

5 Reprinted with A is most vulnerable to degradation by lightemitted near its absorption maximum at wavelengths of330 to 350 nm, vitamin E at 285 to 305 nm. Red plasticbags offered for protecting the syringes are imperviousfor wavelengths from 190 to 590 nm and amber lightprotecting tubing material absorb wavelengths from 290to 450 nm. The most detrimental factor for Vitamins Aand E is intensive sunlight, consisting of the whole light-spectrum including the ultraviolet range. In contrast,neon light illuminating the intensive care unit at night ismainly emitting wavelengths in the visible part of thelight spectrum, and the phototherapy lamp used emitsmainly wavelengths of 400 and 450 to 460 nm, respec-tively. Both light sources have little degrading effect onvitamin to tubing and light degradation depend onwhether Vitamins are given with a lipid emulsion or in theglucose amino acid mixture and vary for different lipidsoluble AVitamin A plays an essential role in normal differen-tiation and maintenance of epithelial cells and adequateimmune function.

6 Prophylactic supplementation of vita-min A was reported to protect against bronchopulmonarydysplasia and to reduce the requirement for oxygensupport ((4) (LOE 3); (5) (LOE 2)).The adequate supply of vitamin A for premature neo-nates remains controversial. The adequate concentra-tion of plasma vitamin A in very low birth weight infantsis not known. Serum concentrations below 200mg/L( ) have been considered to indicate deficiencyin premature infants and concentrations below 100mg/L( ) indicate severe deficiency and depletedliver stores. The range of normal values for children olderthan 6 months of age (including adults) is 300 800 the plasma retinol binding protein (RBP) response((6) (LOE 3); (7) (LOE 3)) and the relative rise in serumretinol concentration (8) following intramuscular ( ) vitamin A administration have been described as usefultests to assess functional vitamin A of vitamin A is complicated by substantialphoto-degradation and adsorptive loss when given incombination with the water soluble Vitamins as part ofthe glucose-amino acid infusion.

7 Loss to tubing alsodepends on the tubing material. Alternative methods ofdelivery have been proposed to ensure the application ofreproducible amounts of vitamin A to premature neo-nates by using shorter IV tubing and a shorter infusiontime with reduced duration of exposure to light andtubing material or by supplying the more stable vitaminA ester retinyl palmitate or the multivitamin solutionwith the lipid emulsion ((9 11) (LOE 2)).The total delivery of retinol from parenteral infusionshas been consistently reported to be below 40% of theintended dose (9,12,13). Contradictory results have beenreported by different authors on the effects of light pro-tection on vitamin A release under ambient light con-ditions that were usually not specified or quantified inthe published studies. Thus, light protection should onlybe considered for protection of retinol exposed to strongdirect day light. Under artificial lighting conditions, theuse of light protecting tubing materials will have only amarginal influence on retinol delivery compared to theamounts lost by extensive adsorption onto the palmitate in the lipid emulsion provides repro-ducible amounts delivered during the infusion period,indicating that it is a stable ester of vitamin A and that itis further protected by the lipid emulsion, presumablybecause lipid droplets disperse the light and thus protectthe vitamin .

8 The major proportion of retinol losses is dueto adsorption onto the tubing materials within the firsthour of infusion, whereas retinyl palmitate tends to ad-sorb to tubing material to a lesser extent. A smaller sur-face of tubing and less passage time of the infusionthrough the tubing provide improved delivery. However,the available micro tubing made of polyurethane aremore prone to adsorb lipophilic substances than standardPE tubing (14). PE and PVC tubing materials seem tohave comparable adsorption behaviors. Supplying vita-min A in a lipid emulsion is the most feasible way toreduce infants an intravenous vitamin A supply of about920 IU/kg per day together with the water solubleTABLE intakes for parenteral supply oflipid soluble Vitamins for infants and children(2,24,27,29,43 45)Infants (Dose/kgbody weight per day)Children(Dose per day) vitamin A (mg)*150 300150 vitamin D (mg) (32 IU)10 (400 IU) vitamin E (mg) K (mg)10 (recommended, but200currently not possible)**1mg RE (retinol equivalent) = 1mg all-trans retinol = IUvitamin intakes for parenteral supply ofwater soluble Vitamins for infants and children (2,30,33,38)Infants (Dose/kg bodyweight per day)Children(Dose per day)Ascorbic acid (mg)15 2580 Thiamine (mg) (mg) (mg) (mg) (mg) acid (mg) (mg) acid (mg)56140S48 GUIDELINES ON PAEDIATRIC PARENTERAL NUTRITIONJ Pediatr Gastroenterol Nutr, Vol.

9 41, Suppl. 2, November 2005mixture or 230 500 IU/kg per day with the lipidemulsion are often used. Since losses are quite variableand losses are higher in the water soluble mixture, theamount delivered to the patient may be estimated to beapprox. 300 to 400 IU/kg per day for both vitamin A as retinyl palmitate (1000 IU/dVitamin A) in premature infants for 28 days in addition toparenteral nutrition (400 IU/day) and enteral supply(1500 IU/day) led to significantly higher serum levelsthan at birth but with a wide range of variation. 32% stillhad levels below 20mg/dL ((15) (LOE 3)). vitamin A supplementation for preventing morbidityand mortality in very low birth weight evidence exists only for VLBW infant with gestationalage,32 weeks or birth weight,1500 g. A Cochranereview (16) found an association of vitamin A supply anda reduction in death or oxygen requirement at one monthof age and of oxygen requirement of survivors at 36weeks post-menstrual age, with this latter outcome beingconfined to infants with a birth weight,1000 eligible trials supplemented vitamin A intramus-cularly soon after birth over the next 28 days in variousdoses of 4000 5000 IU three times a week to 2000 IUevery other day.

10 One study supplemented vitamin A asretinyl palmitate in lipid emulsion at approx. 700 RE/kgper day for the first two weeks and 600 700 RE/kg perday for the next two weeks. Control and study infantsalso received Standard vitamin A. The conclusion ofthe review was that whether clinicians decide to userepeat intramuscular doses of vitamin A to prevent chroniclung disease may depend upon local incidence of thisoutcome and the value attached to achieving a modestreduction in this outcome balanced against the lack ofother proven benefits and the acceptability of the treat-ment. The benefits, in terms of vitamin A status, safetyand acceptability of delivering vitamin in an intravenousemulsion compared with repeated intramuscular injec-tion should be assessed in a further NICHD trial necessitates 12 intramuscular injec-tions with 5000 IU (17). Compared with this regimen,once-per week (15 000 IU) worsened, and a higher dose(10,000 IU 3x per week) did not reduce vitamin Adeficiency (serum retinol,20mg/dL, RBP, mg/dL,and/or ) (18).