0148-6071/90/1401-0079$02.00/0
JOURNAL OF PARENTERAL AND ENTERAL NUTRITION Copyright 0 1990 by the American Society for Parenteral and Enteral Nutrition
Vol. 14, No. 1 Printed in U.S.A.
Vitamin A Sorption to Polyvinyl and Polyolefin Intravenous Tubing DONABY H.
HENTON,
B.S.
AND
RUSSELLJ.
MERRITT,
M.D.,
PH.D.
From the Division of Digestive Diseases and Nutrition, Childrens Hospital of Los Angeles and the Department of Pediatrics, University of Southern California, School of Medicine, Los Angeles, California
ABSTRACT. The loss of vitamin A to plastic infusion tubing from a total parenteral nutrition solution was studied using a n in uitro infusion system and HPLC quantification of vitamin A. Polyolefin tubing was compared to polyvinyl chloride at varied vitamin A concentration, infusion temperature, and flow rate. Significantly enhanced recovery of vitamin A was found with the polyolefin tubing compared to that of the polyvinyl chloride under all conditions tested. After 24 hours under the
varied conditions of the study, vitamin A availability ranged from 47 to 87% with polyolefin and 19 to 74% with polyvinyl chloride. These differences may be expected to result in significantly greater vitamin A delivery from polyolefin compared to polyvinyl chloride tubing to patients treated in neonatal intensive care units. ( J o u r n a l of Parenteral a n d E n t e r a l N u t r i t i o n 14:79-81, 1990)
Numerous studies have shown vitamin A loss to plastic infusion These losses range as high as 80% of the infused vitamin A.' The mechanism is apparently nonspecific absorption onto the surface of the polymer.' The importance of adequate delivery of this fat soluble vitamin is underscored by recent reports of the role of retinol in bronchopulmonary dysplasia (BPD). Low serum retinol has been associated with an increased incidence and severity of the ~ y n d r o m e Retinol .~ levels may remain low despite administration of retinol-containing total parenteral nutrition (TPN).' A recent clinical trial of supplemental intramuscular vitamin A showed promise in the treatment of BPD.7 These studies demonstrate the need for adequate vitamin A delivery, and the difficulty in achieving it. Recently, a new polymer for intravenous infusion systems has become available. Polyolefin (POL) resin, available as an inner sleeve in polyvinyl chloride (PVC) tubing, has been shown to improve recovery of infused insulin.' This result suggested that POL might have less nonspecific binding for hydrophobic substances. We undertook a study to see if this new system would yield improved delivery of vitamin A.
apparatus were protected from light during the course of the infusion. Table I shows the composition of the T P N solution infused through the tubing, which is similar to that used in the neonatal intensive care unit at Childrens Hospital of Los Angeles. The experimental conditions for the infusions are outlined in Table 11. T o vary temperature, the infusion lines were passed through a controlled temperature water bath. Samples were taken from the end of the infusion tubing at 3, 6, 9, and 24 hr. A zero-time sample was taken from the Beckton-Dickinson syringe and considered 100%recovery for comparison purposes. High-pressure liquid chromatography (HPLC) was used to assay retinol using the method of Chow and Omaye,' with minor modifications. In brief, samples were deproteinized using ethanol-containing retinol acetate internal standard (K & K Laboratories, Plainview, NY) and butylated hydroxtoluene (BHT). Vitamin A was then extracted using heptane containing BHT. After evaporation of the organic phase under nitrogen, the extract was redissolved in methanol and injected into the chromatograph. A 15-cm,5-micron ODS steel column (Rainin Instruments, Woburn, MA) was used. Elution solvent was 4/100 H20/MeOH (v/v). Dayto-day variation for retinol determination by this method averaged 6%. Values reported are averages of duplicate infusion experiments. Statistical differences were calculated by paired t-test with a p value less than 0.05 considered significant. The test was applied to the pairs of timed values for each experimental situation.
MATERIALS AND METHODS
Three meter lengths of intravenous extension set tubing were used in the study. The POL tubing was product 128 from MiniMed, Inc, Sylmar, CA, and PVC tubing was product 3M8511, from Travenol, Inc, Glendale, CA. The dead volume of this length of tubing was 0.7 ml for POL, and 0.6 ml for the PVC. An in vitro system was used to compare the two intravenous infusion tubings. The length of tubing was connected to a 50-ml plastic Beckton-Dickinson syringe mounted in a Harvard syringe pump. The tubing and
RESULTS
Vitamin A recovery from POL was greater than that from PVC under all study conditions and a t all time points (Table 111). The observed differences for each experimental condition were statistically significant by paired t-test. The highest percent recovery from both tubings was observed at the higher vitamin A concentration studied. The poorest recovery occurred when the tubing passed through the 37°C water bath. Under sim-
Received for publication, October 17, 1988. Accepted for publication, February 1, 1989. 79
Downloaded from pen.sagepub.com at FLORIDA INTERNATIONAL UNIV on May 24, 2015
80
Vol. 14, No. 1
HENTON AND MERRITT
TABLEI TPN solution components Na phosphate Na chloride K chloride Aminosyn Dextrose Ca gluconate Mg sulfate Zn cu Cr Mn
15 mMoles/liter 30 mEq/liter 30 mEq/liter 21.25 g/liter 200 g/liter 14 mEq/liter 50 mg/liter 2.4 mg/liter 0.16 mg/liter 1.6 pg/liter 80 uelliter
TABLEI1 Experimental conditions Condition no.
Temperature ("C)
Flow rate
Vitamin A
(ml/hr)
(IU/mU
1* 2 3 4
25 25 37 25
4 4 4 10
25 50 25 25
* Experimental condition 1 most closely approximates infusion administered to a low-birth weight neonate of 700 to 1000 g. Experimental conditions 2 to 4 are variants of this condition. TABLE I11 Percentage recovery of vitamin A Condition no.
Line type*
Infusion (hrs)
3
6
9
24
p Value
49.5 44.5 0.004 45.57.$ 38.5 PVC 65.5 72.5 72.5 75.0 POL 70.0 57.0 67.0 73.5 0.016 2 PVC 80.5 76.0 74.0 POL 87.0 32.5 28.0 26.5 19.0 0.022 3 PVC 40.5 46.0 44.0 47.0 POL 61.0 61.0 0.049 57.5 58.0 PVC 4 87.0 72.0 71.5 69.0 POL * PVC, polyvinyl chloride; POL, polyolefin resin. t All values are means of duplicate experiments. $ Values are percent recovery of solutions compared to the concentrations prior to passage through plastic tubing. 1
ulated nursery conditions for a VLBW (condition 1, Table 11),recovery a t the 24-hr time point was 75.0% for POL and 44.5% for PVC. DISCUSSION
Vitamin A stores are low in preterm in infants." Plasma vitamin A concentrations are low a t birth, and fall with the usual nutritional management of these immature, often sick infants. Vitamin A is essential to normal development of epithelial structures including integumental, ocular, and respiratory epithelia.' Many premature infants require total or supplementary intravenous nutrition with resultant dependence on the vitamin A content of the intravenous preparation for maintenance or improvement of vitamin A status. In 1975, the Nutrition Advisory Group of the American Medical Association recommended providing infants 227 IU (68 pg) retinol daily.12 Subsequently, it was found that most of the retinol in parenteral vitamin products never reach the patient due to loss to the intravenous administration set, including tubing.
More recently, it has become clear vitamin A status of premature neonates fed intravenously, as well as enterally, is s~boptimal.'~ Intramuscular injection of supplementary vitamin A in one study improved vitamin A status of neonatal patients and reduced morbidity associated with bronchopulmonary dysplasia.' Given recognition of the effect of current iv multivitamin administration practices, the 1975 recommendations can no longer be accepted as adequate. The results of this present study suggest availability can be improved by the use of POL coated administration systems. Our study and the available literature suggest that the process of vitamin A loss to infusion tubing is probably a saturable one. The percent recovery in experiment 1 is higher than that found for comparable experiments in the literature. A higher concentration of vitamin A was used in our study, and the retinol was exposed only to tubing and not the entire administration set. Experiments 2 and 4 show greater recovery for retinol when compared to experiment 1. Both of these experiments involve larger quantities of vitamin A passing through the tubing and apparent greater saturation of nonspecific binding sites. Given the clinical importance of intravenous delivery of vitamin A for premature neonate^,^ increased recovery of retinol from POL tubing noted in this study is of potential clinical importance. The list cost of the two types of tubing used in this experiment are very similar. It appears that vitamin A availability can be improved by use of a component plastic with less nonspecific binding such as polyolefin resin. This tubing can increase the recovery of vitamin A without the use of solubilizers6 or retinol esters.2 The POL plastic might be efficacious in other infusion components as well. ACKNOWLEDGMENTS
This study was funded in part by Minimed, Inc, Sylmar, CA. REFERENCES 1. Shenai J P , Stahlman MT, Chytil FC: Vitamin A delivery from parenteral alimentation solution. J Pediatr 99:661-663, 1981 2. Gutcher GR, Lax AA, Farrell PM: Vitamin A losses to plastic intravenous infusion devices and an improved method of delivery. Am J Clin Nutr 408-13, 1984 3. Gillis J, Jones G, Pencharz P: Delivery of vitamins A, D, and E in total parenteral solutions. JPEN 7:ll-14, 1983 4. Hartline JV, Zachman RD: Vitamin A deficiency in total parenteral nutrition solution. Pediatrics 58:448-451, 1976 5. Hustead VA, Gutcher GR, Anderson SA, Zachman RD: Relationship of vitamin A (retinol) status to lung disease in the preterm infant. J Pediatr 105:610-614, 1984 6. Greene HL, Phillips BL, Franck L, et al: Persistently low blood retinol levels during and after parenteral feeding of very low birth weight infants: Examination of losses into intravenous administration sets and a method of prevention by addition to a lipid emulsion. Pediatrics 79:894-899, 1987 I . Shenai JP, Kennedy KA, Chytil F, Stahlman MT: Clinical trial of vitamin A supplementation in infants susceptible to bronchopulmonary dysplasia. J Pediatr 111:269-277, 1987 8. Drazin RE, Van Antwerp W, Konopka A, et al: Comparison of PVC and POL catheters for insulin compatibility during continuous subcutaneous insulin infusion. Abstract for the American Di-
Downloaded from pen.sagepub.com at FLORIDA INTERNATIONAL UNIV on May 24, 2015
JanuarylFebruary 1990
VITAMIN A LOSS
abetic Association Meeting, June 1986 9. Chow FI, Omaye ST: Use of antioxidants in the analysis of vitamins A and E in mammalian plasma by HPLC. Lipids 18837-841,1983 10. Olson JA, Gunning DB, Tilton R A Liver concentrations of vitamin A and carotenoids, as a function of age and other parameters of American children who died of various causes. Am J Clin Nutr 39:903-910, 1984 11. Goodman D S Vitamin A and retinoids in health and disease. N
81
Engl J Med 3101023-1031,1984 12. Nutrition Advisory Group, American Medical Association Department of Foods and Nutrition: Multivitamin preparations for parenteral use: a statement by the nutrition advisory group. JPEN 3:258-261,1979 13. Woodruff CW, Latham CB, James EP, Hewett JE: Vitamin A status of preterm infants: The influence of feeding regimen and vitamin supplements. Am J Clin Nutr 44:304, 1986
Downloaded from pen.sagepub.com at FLORIDA INTERNATIONAL UNIV on May 24, 2015
JOURNAL OF PARENTERAL AND ENTERAL NUTRITION Copyright 0 1990 by the American Society for Parenteral and Enteral Nutrition
Vol. 14, No. 1 Printed in U.S.A.
Vitamin A Sorption to Polyvinyl and Polyolefin Intravenous Tubing DONABY H.
HENTON,
B.S.
AND
RUSSELLJ.
MERRITT,
M.D.,
PH.D.
From the Division of Digestive Diseases and Nutrition, Childrens Hospital of Los Angeles and the Department of Pediatrics, University of Southern California, School of Medicine, Los Angeles, California
ABSTRACT. The loss of vitamin A to plastic infusion tubing from a total parenteral nutrition solution was studied using a n in uitro infusion system and HPLC quantification of vitamin A. Polyolefin tubing was compared to polyvinyl chloride at varied vitamin A concentration, infusion temperature, and flow rate. Significantly enhanced recovery of vitamin A was found with the polyolefin tubing compared to that of the polyvinyl chloride under all conditions tested. After 24 hours under the
varied conditions of the study, vitamin A availability ranged from 47 to 87% with polyolefin and 19 to 74% with polyvinyl chloride. These differences may be expected to result in significantly greater vitamin A delivery from polyolefin compared to polyvinyl chloride tubing to patients treated in neonatal intensive care units. ( J o u r n a l of Parenteral a n d E n t e r a l N u t r i t i o n 14:79-81, 1990)
Numerous studies have shown vitamin A loss to plastic infusion These losses range as high as 80% of the infused vitamin A.' The mechanism is apparently nonspecific absorption onto the surface of the polymer.' The importance of adequate delivery of this fat soluble vitamin is underscored by recent reports of the role of retinol in bronchopulmonary dysplasia (BPD). Low serum retinol has been associated with an increased incidence and severity of the ~ y n d r o m e Retinol .~ levels may remain low despite administration of retinol-containing total parenteral nutrition (TPN).' A recent clinical trial of supplemental intramuscular vitamin A showed promise in the treatment of BPD.7 These studies demonstrate the need for adequate vitamin A delivery, and the difficulty in achieving it. Recently, a new polymer for intravenous infusion systems has become available. Polyolefin (POL) resin, available as an inner sleeve in polyvinyl chloride (PVC) tubing, has been shown to improve recovery of infused insulin.' This result suggested that POL might have less nonspecific binding for hydrophobic substances. We undertook a study to see if this new system would yield improved delivery of vitamin A.
apparatus were protected from light during the course of the infusion. Table I shows the composition of the T P N solution infused through the tubing, which is similar to that used in the neonatal intensive care unit at Childrens Hospital of Los Angeles. The experimental conditions for the infusions are outlined in Table 11. T o vary temperature, the infusion lines were passed through a controlled temperature water bath. Samples were taken from the end of the infusion tubing at 3, 6, 9, and 24 hr. A zero-time sample was taken from the Beckton-Dickinson syringe and considered 100%recovery for comparison purposes. High-pressure liquid chromatography (HPLC) was used to assay retinol using the method of Chow and Omaye,' with minor modifications. In brief, samples were deproteinized using ethanol-containing retinol acetate internal standard (K & K Laboratories, Plainview, NY) and butylated hydroxtoluene (BHT). Vitamin A was then extracted using heptane containing BHT. After evaporation of the organic phase under nitrogen, the extract was redissolved in methanol and injected into the chromatograph. A 15-cm,5-micron ODS steel column (Rainin Instruments, Woburn, MA) was used. Elution solvent was 4/100 H20/MeOH (v/v). Dayto-day variation for retinol determination by this method averaged 6%. Values reported are averages of duplicate infusion experiments. Statistical differences were calculated by paired t-test with a p value less than 0.05 considered significant. The test was applied to the pairs of timed values for each experimental situation.
MATERIALS AND METHODS
Three meter lengths of intravenous extension set tubing were used in the study. The POL tubing was product 128 from MiniMed, Inc, Sylmar, CA, and PVC tubing was product 3M8511, from Travenol, Inc, Glendale, CA. The dead volume of this length of tubing was 0.7 ml for POL, and 0.6 ml for the PVC. An in vitro system was used to compare the two intravenous infusion tubings. The length of tubing was connected to a 50-ml plastic Beckton-Dickinson syringe mounted in a Harvard syringe pump. The tubing and
RESULTS
Vitamin A recovery from POL was greater than that from PVC under all study conditions and a t all time points (Table 111). The observed differences for each experimental condition were statistically significant by paired t-test. The highest percent recovery from both tubings was observed at the higher vitamin A concentration studied. The poorest recovery occurred when the tubing passed through the 37°C water bath. Under sim-
Received for publication, October 17, 1988. Accepted for publication, February 1, 1989. 79
Downloaded from pen.sagepub.com at FLORIDA INTERNATIONAL UNIV on May 24, 2015
80
Vol. 14, No. 1
HENTON AND MERRITT
TABLEI TPN solution components Na phosphate Na chloride K chloride Aminosyn Dextrose Ca gluconate Mg sulfate Zn cu Cr Mn
15 mMoles/liter 30 mEq/liter 30 mEq/liter 21.25 g/liter 200 g/liter 14 mEq/liter 50 mg/liter 2.4 mg/liter 0.16 mg/liter 1.6 pg/liter 80 uelliter
TABLEI1 Experimental conditions Condition no.
Temperature ("C)
Flow rate
Vitamin A
(ml/hr)
(IU/mU
1* 2 3 4
25 25 37 25
4 4 4 10
25 50 25 25
* Experimental condition 1 most closely approximates infusion administered to a low-birth weight neonate of 700 to 1000 g. Experimental conditions 2 to 4 are variants of this condition. TABLE I11 Percentage recovery of vitamin A Condition no.
Line type*
Infusion (hrs)
3
6
9
24
p Value
49.5 44.5 0.004 45.57.$ 38.5 PVC 65.5 72.5 72.5 75.0 POL 70.0 57.0 67.0 73.5 0.016 2 PVC 80.5 76.0 74.0 POL 87.0 32.5 28.0 26.5 19.0 0.022 3 PVC 40.5 46.0 44.0 47.0 POL 61.0 61.0 0.049 57.5 58.0 PVC 4 87.0 72.0 71.5 69.0 POL * PVC, polyvinyl chloride; POL, polyolefin resin. t All values are means of duplicate experiments. $ Values are percent recovery of solutions compared to the concentrations prior to passage through plastic tubing. 1
ulated nursery conditions for a VLBW (condition 1, Table 11),recovery a t the 24-hr time point was 75.0% for POL and 44.5% for PVC. DISCUSSION
Vitamin A stores are low in preterm in infants." Plasma vitamin A concentrations are low a t birth, and fall with the usual nutritional management of these immature, often sick infants. Vitamin A is essential to normal development of epithelial structures including integumental, ocular, and respiratory epithelia.' Many premature infants require total or supplementary intravenous nutrition with resultant dependence on the vitamin A content of the intravenous preparation for maintenance or improvement of vitamin A status. In 1975, the Nutrition Advisory Group of the American Medical Association recommended providing infants 227 IU (68 pg) retinol daily.12 Subsequently, it was found that most of the retinol in parenteral vitamin products never reach the patient due to loss to the intravenous administration set, including tubing.
More recently, it has become clear vitamin A status of premature neonates fed intravenously, as well as enterally, is s~boptimal.'~ Intramuscular injection of supplementary vitamin A in one study improved vitamin A status of neonatal patients and reduced morbidity associated with bronchopulmonary dysplasia.' Given recognition of the effect of current iv multivitamin administration practices, the 1975 recommendations can no longer be accepted as adequate. The results of this present study suggest availability can be improved by the use of POL coated administration systems. Our study and the available literature suggest that the process of vitamin A loss to infusion tubing is probably a saturable one. The percent recovery in experiment 1 is higher than that found for comparable experiments in the literature. A higher concentration of vitamin A was used in our study, and the retinol was exposed only to tubing and not the entire administration set. Experiments 2 and 4 show greater recovery for retinol when compared to experiment 1. Both of these experiments involve larger quantities of vitamin A passing through the tubing and apparent greater saturation of nonspecific binding sites. Given the clinical importance of intravenous delivery of vitamin A for premature neonate^,^ increased recovery of retinol from POL tubing noted in this study is of potential clinical importance. The list cost of the two types of tubing used in this experiment are very similar. It appears that vitamin A availability can be improved by use of a component plastic with less nonspecific binding such as polyolefin resin. This tubing can increase the recovery of vitamin A without the use of solubilizers6 or retinol esters.2 The POL plastic might be efficacious in other infusion components as well. ACKNOWLEDGMENTS
This study was funded in part by Minimed, Inc, Sylmar, CA. REFERENCES 1. Shenai J P , Stahlman MT, Chytil FC: Vitamin A delivery from parenteral alimentation solution. J Pediatr 99:661-663, 1981 2. Gutcher GR, Lax AA, Farrell PM: Vitamin A losses to plastic intravenous infusion devices and an improved method of delivery. Am J Clin Nutr 408-13, 1984 3. Gillis J, Jones G, Pencharz P: Delivery of vitamins A, D, and E in total parenteral solutions. JPEN 7:ll-14, 1983 4. Hartline JV, Zachman RD: Vitamin A deficiency in total parenteral nutrition solution. Pediatrics 58:448-451, 1976 5. Hustead VA, Gutcher GR, Anderson SA, Zachman RD: Relationship of vitamin A (retinol) status to lung disease in the preterm infant. J Pediatr 105:610-614, 1984 6. Greene HL, Phillips BL, Franck L, et al: Persistently low blood retinol levels during and after parenteral feeding of very low birth weight infants: Examination of losses into intravenous administration sets and a method of prevention by addition to a lipid emulsion. Pediatrics 79:894-899, 1987 I . Shenai JP, Kennedy KA, Chytil F, Stahlman MT: Clinical trial of vitamin A supplementation in infants susceptible to bronchopulmonary dysplasia. J Pediatr 111:269-277, 1987 8. Drazin RE, Van Antwerp W, Konopka A, et al: Comparison of PVC and POL catheters for insulin compatibility during continuous subcutaneous insulin infusion. Abstract for the American Di-
Downloaded from pen.sagepub.com at FLORIDA INTERNATIONAL UNIV on May 24, 2015
JanuarylFebruary 1990
VITAMIN A LOSS
abetic Association Meeting, June 1986 9. Chow FI, Omaye ST: Use of antioxidants in the analysis of vitamins A and E in mammalian plasma by HPLC. Lipids 18837-841,1983 10. Olson JA, Gunning DB, Tilton R A Liver concentrations of vitamin A and carotenoids, as a function of age and other parameters of American children who died of various causes. Am J Clin Nutr 39:903-910, 1984 11. Goodman D S Vitamin A and retinoids in health and disease. N
81
Engl J Med 3101023-1031,1984 12. Nutrition Advisory Group, American Medical Association Department of Foods and Nutrition: Multivitamin preparations for parenteral use: a statement by the nutrition advisory group. JPEN 3:258-261,1979 13. Woodruff CW, Latham CB, James EP, Hewett JE: Vitamin A status of preterm infants: The influence of feeding regimen and vitamin supplements. Am J Clin Nutr 44:304, 1986
Downloaded from pen.sagepub.com at FLORIDA INTERNATIONAL UNIV on May 24, 2015
