Marjolain Pineault

Protecting solutions of parenteral nutrition from peroxidation

BACKGROUND Light exposure induces the generation of peroxides in solutions of total parenteral nutrition (TPN). Peroxide toxicity has been documented in cell, in tissue, and in isolated organs. To decrease the infused peroxide load and to protect the quality of the parenteral nutrients, we tested the photoprotective properties of different infusion sets. METHODS Solutions of fat-free TPN and all-in-one total nutrient admixture (TNA) were run through sets of bags (clear and covered) and tubings (clear and colored: black, orange, and yellow) offering different levels of protection against light. Peroxide levels were determined by ferrous oxidation of xylenol orange, thiol functions by the 5,5,-dithiobis(2-nitrobenzoic acid) technique, and absorbance of tubings by spectroscopy. RESULTS Protection of only the bag had little effect on peroxide generation. In fat-free TPN solutions kept in covered bags, peroxide concentrations were 1.5 to 2 times higher when run through clear compared with colored tubings. When exposed to phototherapy or in the presence of lipids, peroxides were two to three times higher with the clear compared with the black tubing; meanwhile, orange and yellow tubings offered varying levels of protection related to their light-absorbing properties. Colored tubings offered a greater protection against the disappearance of thiol functions. CONCLUSIONS Covering bags and using orange and yellow tubings may be a practical solution to reduce infused peroxide loads from about 400 to 100 microM. This is especially relevant in patients with an immature or a compromised antioxidant capacity or when phototherapy or preparations of TNA are used.

Total parenteral nutrition in the newborn infant: Energy substrates and respiratory gas exchange*

The hypothesis that a high-fat parenteral regimen was beneficial for respiratory gas exchanges, in comparison with a high-glucose regimen, was tested in a paired crossover design. Ten parenterally fed newborn infants with no respiratory problems received two 5-day isoenergetic and isonitrogenous regimens that differed in their nonprotein source of energy; the level of fat intake (low fat (LF) 1 gm.kg-1.day-1; high fat (HF) 3 gm.kg-1.day-1) varied inversely with that of glucose. Continuous transcutaneous PO2 (tcPO2) and PCO2 (tcPCO2), respiratory gas exchange (indirect calorimetry), and plasma arachidonate metabolites were measured at the end of each regimen. Oxygen consumption and resting energy expenditure were not affected by modification of the source of energy. However, carbon dioxide production (VCO2) was higher during LF than during HF (6.9 +/- 0.2 vs 6.2 +/- 0.1 ml.kg-1.min-1; p less than 0.01), as was the respiratory quotient (1.08 +/- 0.02 vs 0.96 +/- 0.02; p less than 0.001). Despite the differences in VCO2, the tcPCO2 was not affected, suggesting adequate pulmonary compensation during LF, as documented by the higher minute ventilation (160 +/- 7 vs 142 +/- 5 ml.kg-1.min-1; p less than 0.01). The lower tcPO2 during the HF regimen (73.8 +/- 2.8 vs 68.8 +/- 2.6 mm Hg; p less than 0.015) indicated a disturbance at the alveolocapillary level induced by the lipid emulsion. No differences were found in circulating levels of prostaglandins and thromboxanes. The substitution of glucose for lipid did not modify fat storage (2.1 +/- 0.3 vs 2.1 +/- 0.3 gm.kg-1.day-1). We conclude that the supposed beneficial effect of a fat emulsion on respiratory gas exchange is questionable.

Effect of amino acid composition of parenteral solutions on nitrogen retention and metabolic response in very-low-birth weight infants

To evaluate the influence of amino acid preparations on the metabolic response of parenterally fed immature newborn infants, nitrogen retention and plasma amino acid concentrations were compared in very-low-birth-weight infants given two parenteral regimens differing only by the composition of the infused amino acids (Travasol 10% blend B and Vamin 7%). The intakes of fluid, nitrogen, and calories were comparable. The nitrogen retention was 72% +/- 7% with Vamin and 65% +/- 6% with Travasol. The differences in plasma amino acid concentrations were consistent with the composition of the amino acid solutions. During the infusion of Vamin the increased intake of aromatic amino acids resulted in high plasma levels of tyrosine (256 +/- 233 mumol/L, range 67 to 894 mumol/L). The infusion of Travasol resulted in high plasma levels of methionine (114 +/- 39 mumol/L, range 53 to 260 mumol/L) and an elevated load of glycine, which was accompanied by an abnormally high urinary loss of this amino acid. Despite these metabolic imbalances, the growth rate over the whole study was adequate. These results emphasize the importance of the composition of amino acid solutions on the metabolic response of the very immature preterm infant.

Metabolic and clinical consequences of changing from high-glucose to high-fat regimens in parenterally fed newborn infants*

To evaluate the metabolic and clinical consequences of changing from high-glucose to high-fat regimens during initiation of parenteral nutrition, we performed 22 studies in 11 newborn infants (birth weight (mean +/- SD) 2.54 +/- 0.54 kg, gestational age 37 +/- 3 weeks, postnatal age 8 +/- 3 days) maintained in a constant thermal environment. In a paired design, two isoproteinic (2.4 +/- 0.2 gm/kg/day) and isocaloric (64 +/- 6 kcal/kg/day) regimens differing by source of energy (high glucose vs high lipid) were infused on consecutive days. Environmental and body temperatures were recorded during a 4-hour period, and 24-hour urinary excretions of catecholamines, nitrogen, and C peptide were measured. Despite constant incubator and average skin temperatures, the rectal and interscapular temperatures rose significantly when the high-glucose regimen was changed to a high-lipid regimen. The specific locations of these changes in body temperature suggested brown fat activation. A significant drop in nitrogen retention (63 +/- 9% vs 56 +/- 10%) during the lipid infusion could be further evidence of a metabolic adaptation to the rapid change in energy substrates.

Beneficial Effect of Coinfusing a Lipid Emulsion on Venous Patency

The hypothesis that infused fat could prolong venous patency was tested in a paired crossover design. Parenterally fed newborn infants received, for a given level of energy, (60 vs 80 kcal/kg/day), two 6-day isocaloric and isonitrogenous (434 +/- 3.4 mg/kg/day, n = 32) regimens differing only by the fat intake (LF: 1.03 +/- 0.02, HF: 2.78 +/- 0.05 g/kg/day). Paired comparisons of osmolarities within isocaloric (60 or 80 kcal/kg/day) infusions showed that high fat regimens were associated with significantly lower osmolarities. A paired comparison of patency times showed that the drop in osmolarity produced by the high fat regimen at 60 kcal/kg/day led to a significantly longer venous patency time. The comparison of patency times between regimens (LF, 60 kcal/kg/day) and HF, 80 kcal/kg/day) with same osmolarities (702 mOsm/liter) and glucose intakes (11 g/kg/day) documented that the fat emulsion per se had a vascular protective effect. This observation demonstrates that the coinfusion of a lipid emulsion exerts a beneficial effect, whether biochemical or biophysical, on the vascular endothelium of peripheral veins.

Influence of energy substrates on respiratory gas exchange during conventional mechanical ventilation of preterm infants

OBJECTIVE The purpose of this study was to determine the optimal parenteral feeding regimen for infants with compromised respiratory function. METHODS We studied the influence of varying the source of energy on respiratory gas exchange in 10 infants who were supported by mechanical ventilation and who received intravenous feedings. Two isoenergetic parenteral regimens were infused consecutively; the level of fat intake was varied inversely with that of glucose. Under similar ventilator settings, transcutaneous partial pressures of oxygen and carbon dioxide, as well as indirect calorimetry were measured during each regimen. RESULTS Despite the higher carbon dioxide production during the glucose-rich regimen (8.9 +/- 0.7 vs 7.9 +/- 0.4 ml/kg per minute, p < 0.05 by analysis of variance), transcutaneous partial pressure of carbon dioxide remained unaffected, suggesting ventilatory compensation as documented by the increased (p < 0.002) alveolar ventilation. This was not associated with a detectable rise in oxygen consumption, but with a significant change in partial pressure of oxygen (77 +/- 5 vs 66 +/- 3 mm Hg, p < 0.05). CONCLUSIONS Ventilator-dependent infants with early and mild bronchopulmonary dysplasia, who receive intravenous feedings of a moderate load of glucose-based energy, can compensate for enhanced carbon dioxide production by increasing their respiratory drive, with a beneficial effect on oxygenation compared with that observed when energy is derived from lipid-based solutions.

Total Parenteral Nutrition in the Newborn: Energy Substrates and Plasma Total Fatty Acids

ABSTRACT: Carbohydrate and lipid intakes have both been found to modulate the metabolism of long-chain fatty acids. To define the respective infuence of these two energy substrates on plasma fatty acid concentrations, 32 studies were performed in 16 parenterally fed newborn infants (mean ± SEM, birth wt: 2.15 ± 0.1 kg, age: 10 ± 1 d). In a paired cross-over design, the infants received for a given level of energy (60 versus 80 kcal/kg/d) two 6-d isonitrogenous and isocaloric regimens constructed so that the level of fat intake, 1 or 3 g/kg/d varied inversely with that of glucose. Total plasma fatty acid levels did not reflect the composition of the emulsion and varied with energy substrates. Plasma levels of three fatty acids rose inversely to the lipid intake, during the high glucose regimen: 16:lw7, 20:3w9 biologic markers of essential fatty acid deficiency, and 20:3w6 a derivative of 18:2w6. Glucose intake could exert its influence on 20:3w9 and 20:3w6 via insulin, an activator of A6 desaturase. Both glucose and fat should be taken into account when evaluating plasma fatty acid profile.

Total Parenteral Nutrition in Very Low Birth Weight Infants with Travasol 10% Blend C

Ten very low birth weight (VLBW) infants (birth weight: 994 +/- 66 g, gestational age: 27 +/- 0.5 wk) requiring total parenteral nutrition (TPN) were studied in order to evaluate their metabolic response to the amino acid solution Travasol 10% blend C. These patients received the solution at a constant rate, providing 2.61 +/- 0.02 g/kg/day of amino acids and 76 +/- 1 kcal/kg/day. Plasma amino acids analysis was performed after 4.6 +/- 0.3 day of infusion and compared to values reported previously with Travasol blend B. The new solution (blend C) showed a significantly lower (p less than 0.001) glycinemia (485 +/- 24 vs 993 +/- 69 mumol/liter), methioninemia (39 +/- 2 vs 114 +/- 12 mumol/liter) and phenylalaninemia (67 +/- 3 vs 92 +/- 5 mumol/liter) related to the lower intake of these amino acids. Despite the provision of 47.5 mmol/liter of serine with blend C no changes in plasma level (182 +/- 15 vs 196 +/- 41 mumol/liter) were noted. The increased molar arginine/glycine ratio (blend C: 0.48 vs blend B 0.22) could have contributed to keep ammoniemia within normal levels (55.1 +/- 4.2 mumol/liter). Wide variations in insulin response (9.9 to 26.4 microU/ml) allowed for a correlation between its plasma concentration and those of sensitive amino acids, underlining its role in protein metabolism. Despite the immaturity of the study population no short-term metabolic imbalance has been encountered with the Travasol blend C solution.

CLINICAL BENEFITS OF CO-INFUSING A LIPID EMULSION WITH AMINO ACIDS-DEXTROSE SOLUTIONS IN NEWBORN INFANTS

Metabolic consequences of infusing lipids have been widely investigated. We evaluated the local effects of varying the proportions of parenteral glucose and fat on the venous tolerance or patency of infusion sites. Thirty-two observations were made in 16 infants; (X±SEM, birthweight:2.15±0.1 kg, gestational age: 34± 1 wk).In a paired cross over design the patients received for a given level of energy (60 vs 80 kcal/kg/d), two 6 day isocaloric and isonitrogenous (434±3.4 mg/kg/d, n=32) regimens differing only by the fat intake (LIP-1: 1.03±0.02, LIP-3: 2.78±0.05 g/kg/d). Minutes between changes in infusion sites (T), and osmolarity of the mixtures (Osm, mOsm/1) were compared between each treatment.These data show that the lipid emulsion significantly reduces the final osmolarity of the mixture and thereby increases the patency of the infusion sites. Moreover, for a same osmolarity and glucose intake, the addition of lipids (60 kcal LIP-1 vs 80 kcal LIP-3) increases the infusion time significantly (p<0.05). Whether biochemical or physical, this protective effect of the lipid emulsion demonstrates that the quality of fuel mixtures has an important role on the patients comfort.

715 PARENTERAL FAT AS NITROGEN SPARER IN LOW BIRTHWEIGHT(LBT) INFANTS

The nitrogen sparing effect of calories has been documented, however the influence of the quality of these calories has not been studied in LBW infants. The aim of this study was to compare the metabolic response of glucose and fat in parenterally fed LBW infants. In a paired design, 6 LBW infants (mean ± SD, birthweight: 2055±586; gestational age: 34±2wk; age: 19±20d) received 2 isoproteinic (Travasol C: 2.8±0.1g/kg.d) and isocaloric (67±13kcal/kg.d) regimens over 12 days. During a high glucose phase (CHO) 77±3% of nonproteinic energy was infused as glucose, versus 56±10% as fat during a high lipid phase (LIP). Nitrogen retention (N2 Ret)> triglycerides (TG), plasma phenylalanine (PHE) and tyrosine (TYR), insulin (INS), pCO2 (n=4, free of RDS) were compared:No significant plasma amino acid imbalance was noted. Lipogenesis, a NADPH dependent process, was suggested by the higher PHE/TYR ratio found during CHO. Free fatty acids provided by a high fat (3g/kg.d) fuel mixture, produced a better N2 Ret without compromising the respiratory function. The results emphasize the relation between the composition of infused energy and the quality of growth in parenterally fed infants as opposed to adults.