A prospective study of intrapulmonary fat accumulation in the newborn lung following intralipid infusion

In order to assess the safety and stability of a parenteral fat emulsion (Intralipid) in total parenteral nutrition (TPN), 29 infants were infused Vamin glucose and Dextrose electrolyte solution as well as one of two isocaloric regimens; either 25% Dextrose (Group I) or 10% Intralipid (Group II). Regular biochemical monitoring was performed in all cases and no infants became lipaemic nor developed abnormally high levels of total free fatty acid. Eight infants died and only those who had received fat emulsion had lipid staining material distending the pulmonary vessels. One infant having low infusion rates of Intralipid had massive fat accumulation in the lungs, but biochemistry during life had been normal. We speculate that in ill infants the emulsion becomes less stable and agglomeration of fat particles occurs which are then fully filtered out by the lungs before metabolism of the exogenous fat can occur.     

Pigment deposition in the reticuloendothelial system after fat emulsion infusion.

In 2 infants who had received Intralipid fat emulsion as part of a total parenteral hyperalimentation regimen, a pigmented material was deposited in the macrophages of their reticuloendothelial systems. The histochemical characteristics of this pigment were similar to those seen after experimental infusion of fat emulsions. The possible implications of this finding and its effect on host resistance are briefly considered.     

Acinetobacter junii causes life-threatening sepsis in preterm infants

Acinetobacter junii caused sepsis in six preterm infants in our neonatal unit within 48 h. Each infant with clinical signs of systemic infection and activation of the acute phase response had two positive blood cultures with Acinetobacter junii. The sudden onset, the short duration of the outbreak and the fact that none of the infants were colonized by A. junii suggested a common source of A. junii administered directly into the blood. The only feature shared by all six affected newborns was an intravenous fat emulsion (Intralipid 10%), which was shown to be an excellent growth medium for A. junii. Sepsis did not occur in four infants with 20% fat emulsion or amino acids only. Vaminolact^® did not support growth of the outbreak strain. The immediate source of the outbreak could not be identified: samples of the actual feeds given were not available for investigation, but A. junii was not isolated from parenteral solutions with identical batch numbers used in the septic infants. We conclude that Acinetobacter junii can cause a life-threatening infection in preterm neonates. Contaminated intravenous fat emulsion is implicated as a possible source of the infection. As a part of rigid infection control, intravenous feedings should be prepared under aseptic conditions.     

Effect of intravenous lipid emulsions on hepatic cholesterol metabolism

BACKGROUND: Total parenteral nutrition offers the chance of survival to children who have had extensive gut resections or gut failure. However, in infants it is often associated with serious complications including cholestatic liver disease. The causes of these complications remain unclear, although it has been suggested that the lipid emulsions used in total parenteral nutrition may be responsible. METHODS: An in vitro system was developed to study the effect of lipid emulsions on hepatic cholesterol metabolism using cultured hepatocytes. RESULTS: Incubations of Hep G2 cells with medium containing Intralipid (Pharmacia and Upjohn, Milton Keynes, UK) demonstrated that the fat emulsion mediated a powerful dose-dependent but reversible inhibition of cholesterol uptake. In addition Intralipid was shown to stimulate the efflux of cholesterol from Hep G2 cells. The component or components of the Intralipid responsible for these effects and the mechanism by which they act remain to be established. CONCLUSIONS: Intravenous lipid emulsions may interfere with hepatic cholesterol metabolism in vivo. This may have implications for the development of total parenteral nutrition-associated cholestasis in neonates.     

UTILIZATION OF FAT EMULSION DURING TOTAL PARENTERAL NUTRITION IN CHILDREN

ABSTRACT: Forget, P., Fernandes, J. and Haverkamp Begemann, P. (Department of Paediatrics, Sophia Children's Hospital and Neonatal Unit, Erasmus University, Rotterdam, the Netherlands). Utilization of fat emulsion during total parenteral nutrition in children. Acta Paediatr Scand, 64: 377, 1975.–Tolerance for Intralipid fat emulsion during total parenteral nutrition (PN) was studied in 6 children. The Intralipid dose was monitored by the daily determination of plasma Intralipid levels. Fat removal was investigated at the start of and during the PN period by the intravenous fat tolerance test (IVFTT) and by determining the plasma postheparin lipoprotein lipase (LPL) activity. When the plasma Intralipid levels exceeded a value of 100 mg/100 ml, hyper pre-βT lipoproteinaemia, hypertriglyceridaemia, hypercholesterolemia and hyperphospholipidaemia appeared. During PN most patients showed marked increases of postheparin LPL. Return to normal values occurred after discontinuation of PN. Maximal LPL activities were found to correlate significantly with total daily caloric intake ( r =0·95, 0.05相似文献   

Pulmonary fat embolism after intralipid therapy--a post-mortem artefact? Light and electron microscopic investigations in low-birth-weight infants

The lungs of 22 low-birth-weight infants were investigated, mean gestational age 29 weeks (range 25 to 35). Thirteen of the 22 newborns had been treated with Intralipid--10% for an average of 20 days (range 3 hours to 75 days). The mean maximum rate of fat infusion was 2.0 g/kg/day (range 0.5 to 3.6). Nine of the 22 newborns had been fed formula and given supplemental amounts of amino acids and glucose intravenously, but no Intralipid. The lungs were fixated in situ immediately after death with glutaraldehyde. Neither in the Intralipid group nor in the non-Intralipid controls was intravascular fat accumulation identified, either by light microscopy or by electron microscopy. It is speculated that an agglomeration of lipoprotein globules to larger stainable lipid droplets cannot take place in the short interval between the actual time of death and the time of fixation of the lung tissue. Thus, fat globules found in lungs of premature infants and described as fat embolism might have been post mortem artefacts.     

Pulmonary Fat Embolism after Intralipid Therapy– a Post-Mortem Artefact?

The lungs of 22 low-birth-weight infants were investigated, mean gestational age 29 weeks (range 25 to 35). Thirteen of the 22 newborns had been treated with Intralipid®–10 % for an average of 20 days (range 3 hours to 75 days). The mean maximum rate of fat infusion was 2.0 g/kg/day (range 0.5 to 3.6). Nine of the 22 newborns had been fed formula and given supplemental amounts of amino acids and glucose intravenously, but no Intralipid. The lungs were fixated in situ immediately after death with glutaraldehyde. Neither in the Intralipid group nor in the non-Intralipid controls was intravascular fat accumulation identified, either by light microscopy or by electron microscopy. It is speculated that an agglomeration of lipoprotein globules to larger stainable lipid droplets cannot take place in the short interval between the actual time of death and the time of fixation of the lung tissue. Thus, fat globules found in lungs of premature infants and described as fat embolism might have been post mortem artefacts.     

多种油脂肪乳在超低出生体重儿中应用的疗效分析

目的 分析多种油脂肪乳(SMOF)在超低出生体重(ELBW)儿中应用的疗效.方法 回顾性选取2018年1月1日至2020年7月30日收治的ELBW儿49例为研究对象,入院时日龄≤14 d,接受胃肠外营养时间>14 d.根据应用的脂肪乳剂种类,分为SMOF组(n=26)和中长链脂肪乳(MCT/LCT)组(n=23),比较...     

不同胎龄早产儿生后早期对脂肪乳的耐受性研究

目的分析不同出生胎龄早产儿生后早期对脂肪乳的耐受性。方法 98例早产儿分为超早产儿组(n=17)、早期早产儿组(n=48)和中晚期早产儿组(n=33),再根据脂肪乳剂量分为低剂量脂肪乳与高剂量两个亚组,留取脐血及生后前3 d的血干滤纸片,用串联质谱法检测短、中、长链酰基肉碱含量。结果超早产儿组与早期早产儿组脐血及生后前3 d长链酰基肉碱浓度均低于中晚期早产儿组(P0.05),且长链酰基肉碱浓度与胎龄呈正相关(P0.01)。超早产儿低剂量脂肪乳组生后第2天的短、中、长链酰基肉碱浓度均高于高剂量组(P0.05),而早期早产儿与中晚期早产儿不同剂量脂肪乳亚组的生后3 d短、中、长链酰基肉碱浓度差异均无统计学意义。结论超早产儿和早期早产儿生后前3 d对长链脂肪酸的代谢能力均低于中晚期早产儿;早期早产儿与中晚期早产儿生后早期可以耐受高剂量脂肪乳,但超早产儿生后早期对高剂量脂肪乳代谢能力可能不足。     

Clinical and metabolic consequences of two regimens of total parenteral nutrition in the newborn

The clinical and metabolic effects of two regimens of total parenteral nutrition delivering the same amino-acid (2·8 g/kig per 24 h), fat (4·8 g/kg per 24 h), and glucose (12 g/kg per 24 h) load over 24 hours were studied. The regimens differed in the distribution of the infusate during the 24-hour period. With the continuous regimen (7 infants) all nutrients were infused together at a constant rate, whereas with the sequential regimen (9 infants) the daily doses of Vamin/glucose and Intralipid were infused together, followed by the glucose dose. The infants studied had a mean birthweight of 2·8 kg and mean gestational age of 37·9 weeks. Blood levels of glucose, lactate, pyruvate, 3-hydroxybutyrate, acetoacetate, alanine, glycerol, and insulin were measured longitudinally from day 1 to day 21 of total parenteral nutrition. The 7 infants who received the continuous regimen had blood metabolite levels comparable with those of infants fed enterally, with minor fluctuations. Insulin levels were higher than in enterally-fed infants. The 9 infants who received the sequential regimen had wide fluctuations in alanine, glycerol, insulin, 3-hydroxybutyrate, and acetoacetate levels with high peak levels of ketones at the end of the Vamin/glucose and Intralipid infusion, falling to low levels at the end of the 24-hour cycle. There was a gradual reduction in the peak ketone levels from day 6-8 to day 18-21. Clinically unsuspected hypoglycaemia occurred on 6 occasions in each group of infants. There was no significant difference in the incidence of jaundice or infection between the two groups, and the weight velocity during total parenteral nutrition was similar. Wide fluctuations in the infusion rates of individual substrates should be avoided during total parenteral nutrition in the newborn.     

Carnitine deficiency in premature infants receiving total parenteral nutrition: effect of L-carnitine supplementation

To investigate whether L-carnitine supplementation may correct nutritional carnitine deficiency and associated metabolic disturbances in premature infants receiving total parenteral nutrition, an intravenous fat tolerance test (1 gm/kg Intralipid over four hours) was performed in 29 premature infants 6 to 10 days of age (15 receiving carnitine supplement 10 mg/kg . day L-carnitine IV, and 14 receiving no supplement). Total carnitine plasma values were normal or slightly elevated in supplemented but decreased in nonsupplemented infants. In both groups, fat infusion resulted in an increase in plasma concentrations of triglycerides, free fatty acids, D-beta-hydroxybutyrate, and short-chain and long-chain acylcarnitine, but total carnitine values did not change. After fat infusion, the free fatty acids/D-beta-hydroxybutyrate ratios were lower and the increase of acylcarnitine greater in supplemented infants of 29 to 33 weeks' gestation than in nonsupplemented infants of the same gestational age. This study provides evidence that premature infants of less than 34 weeks' gestation requiring total parenteral nutrition develop nutritional carnitine deficiency with impaired fatty acid oxidation and ketogenesis. Carnitine supplementation improves this metabolic disturbance.     

Complications of the prolonged use of lipid emulsion in children on parenteral nutrition

In 8 children who were fed exclusively for an average of 30 months with parenteral nutrition containing 25% of the energetic intake as lipid emulsion (Intralipid) acute complications similar to those observed in the fat storage syndrome occurred. One child died from gastrointestinal bleeding. In the other cases, evolution was dramatically improved by corticosteroid therapy. An histiocytic hyperactivation induced by the artificial emulsion might be responsible for these complications. The authors emphasize the risks of long-term use of lipid emulsion and the preventive measures which should be taken in children under prolonged parenteral nutrition.     

Hazards of parenteral treatment: do particles count?

After prolonged parenteral nutrition a 12 month old infant died with pulmonary hypertension and granulomatous pulmonary arteritis. A review of necropsy findings in 41 infants who had been fed parenterally showed that two of these also had pulmonary artery granulomata, while none of 32 control patients who died from sudden infant death syndrome had similar findings. Particulate contaminants have been implicated in the pathogenesis of such lesions and these were quantified in amino acid/dextrose solutions and fat emulsions using automated particle counting and optical microscope counting respectively. Parenteral feed infusions compounded for a 3000 g infant according to standard nutritional regimens were found to include approximately 37,000 particles between 2 and 100 microns in size in one day's feed, of which 80% were derived from the fat emulsion. In-line end filtration of intravenous infusions may reduce the risk of particle associated complications. A suitable particle filter is required for use with lipid.     

Plasma lecithin: cholesterol acyltransferase and plasma lipolytic activity in preterm infants given total parenteral nutrition with 10% or 20% Intralipid

The effect of 10% or 20% Intralipid on lipid clearing enzymes, plasma lipids and apoproteins was investigated during the first 5 days after birth in 37 premature infants maintained on total parenteral nutrition; 21 infants received 20% and 16 received 10% Intralipid, respectively. Lipid was infused over a 20-h period at rates of 1, 2 and 3 g/kg/day on consecutive days. Plasma lecithin: cholesterol acyltransferase (LCAT) activity was low and increased significantly (p < 0.05) only during infusion of 3 g/kg/day in both groups of infants. Plasma lipolytic activity was generally not affected by the regimen orpreparation(10% or 20%) of Intralipid infused, except for higher (p < 0.05) levels at 3 g/kg/ day of 20% compared with prelipid infusion. Plasma triglyceride concentrations were similar after 10% or 20% Intralipid, whereas plasma total cholesterol was significantly higher during infusion of 2 and 3 g/ kg/day of 10% compared with 20% Intralipid. The efficient clearing of 20% Intralipid might be related to the lower lecithin: triglyceride ratio which is compatible with the low LCAT activity of premature infants. Apoprotein A-J, apoprotein B, cholesterol, LCAT, plasma lipolytic activity, triglycerides     

The effect of three intravenous fat emulsions containing different concentrations of linoleic and alpha-linolenic acids on the plasma total fatty acid profile of neonates.

We determined the fatty acid profile of total plasma lipids in infants who received one of three intravenous fat emulsions that differed primarily in their linoleic and alpha-linolenic acid content: (I) a safflower oil emulsion, (II) a 50:50 mixture of safflower and soybean oils, or (III) a soybean oil emulsion. After 2 weeks of fat therapy, oleic acid, expressed as a percentage of total plasma lipid fatty acids, decreased in all groups, but less so in group III (p less than 0.01). The linoleic acid percentage increased in all groups, but group I had the greatest increase (p less than 0.05). Group II patients had higher percentages of the linoleic acid metabolites, dihomo-gamma-linolenic acid (II greater than I, p less than 0.05; II greater than III, p less than 0.01) and arachidonic acid (II greater than III, p less than 0.05). Group II patients also had higher levels of alpha-linolenic acid (II greater than I, p less than 0.05) and its metabolite, eicosapentaenoic acid (II greater than I, p less than 0.05). Another alpha-linolenic acid metabolite, docosahexaenoic acid, however, increased in group III, remained stable in group II, and decreased in group I (III and II greater than I, p less than 0.05). We conclude that the content of linoleic acid and alpha-linolenic acid in intravenous fat emulsions results in statistically significant changes in the fatty acid profile of total plasma lipids in infants receiving total parenteral nutrition.     

Total parenteral nutrition-associated cholestasis: acute studies in infant and adult rabbits

To assess the basis of cholestasis associated with total parenteral nutrition (TPN), we studied the short-term effect of the component solutions on bile flow and bile salt secretion in infant and adult rabbits. Groups of four to six adult and infant rabbits received intravenously 154 mM NaCl (control), 2.5% amino acid, 10% glucose, or 10% fat emulsion alone or in combination. Bile was collected directly from the common bile duct for 3 h. Solutions containing both amino acids and glucose significantly (p less than 0.05) reduced bile flow and bile salt secretion in both age groups. Glucose alone also decreased bile flow and bile salt secretion, whereas amino acids as the sole infusate significantly (p less than 0.05) decreased bile flow only. The suppressive effect of the amino acid-glucose solutions on bile flow was more pronounced in infants than in adults. Fat emulsion alone had no effect on bile formation. Our findings demonstrate that short-term intravenous administration of nutrient solutions containing amino acids and glucose reduces bile flow and bile salt secretion, suggesting that these components are responsible for TPN-associated cholestasis.     

Subdural collection of intravenous fat emulsion in a neonate. Complication of central venous catheterization for total parenteral nutrition

An infected subdural collection of intravenous fat emulsion (Intralipid) was diagnosed in a 5-week-old premature infant who was receiving total parental nutrition (TPN) through a facial vein cutdown. This fluid was successfully drained and the infection, due to Staphylococcus epidermidis, was treated with vancomycin. We postulate that the subdural collection occurred as a result of septic thrombosis of the internal jugular vein with subsequent retrograde flow and infiltration of Intralipid from the bridging veins into the subdural space. This complication of central TPN has not been reported previously.     

Lecithin:cholesterol acyltransferase (LCAT) activity during lipid infusion in premature infants

Plasma cholesterol and lecithin concentrations are regulated by the serum enzyme lecithin: cholesterol acyltransferase (LCAT). LCAT activity is low in cord blood of premature infants, suggesting that in these infants the hypercholesterolemia associated with Intralipid infusion might be due to low LCAT activity. The serum LCAT activity has not been quantitated in preterm infants receiving intravenous fat emulsions. We have therefore quantitated LCAT activity in eleven premature infants maintained on total parenteral nutrition (TPN). Ten infants were studied during the first 2 weeks after birth; they received daily infusions of Intralipid at a rate of 0.5-2.0 g/kg/day over 15 h. One infant received 3.8 g/kg/day during the second week. In addition to LCAT, serum apoprotein A1 (the cofactor of LCAT), cholesterol, triglycerides, and free fatty acids were quantitated. Blood specimens were taken before the start of the infusion and 15-45 min before its completion. The LCAT activity and apoprotein A1 concentrations remained, respectively, 21-24% and 30-35% of adult levels. However, serum cholesterol levels remained in the normal range during the fat infusion. It remains to be established whether low LCAT activity and apoprotein A1 levels are due to the administration of Intralipid (which lowers LCAT activity in rats), to the lack of enteral feedings, or to prematurity per se. Our data suggest that administration of Intralipid at a rate not exceeding 1-2 g/kg/day does not impair the clearing of Intralipid-lecithin and the metabolism of cholesterol.     

Normal macrophage function in infants receiving Intralipid by low-dose intermittent administration

The effect of soybean oil emulsion (Intralipid) therapy on serum complement levels was determined in infants who received Intralipid therapeutically (1 gm/kg over 12 hours, every other day). The effect of Intralipid on macrophage priming for increased superoxide anion production was studied in a mouse model. Intralipid administration did not affect either macrophage function. Serum levels of C2 and C4, complement components synthesized and secreted exclusively in macrophages, were not decreased either during the week the infants received Intralipid or in the week following administration. Macrophages from mice that had received Intralipid produced similar amounts of superoxide anion, as did macrophages from mice that had received saline solution. Our data suggest that macrophages in infants receiving Intralipid in this regimen will function normally.     

Comparison of the clinical and biochemical effect of increased alpha-linolenic acid in a safflower oil intravenous fat emulsion

We report the results of a randomized comparison of two intravenous safflower oil (fat) emulsions in neonates who required total parenteral nutrition. The fat emulsions differed only in their content of alpha-linolenic acid: in one emulsion the alpha-linolenic acid content of the oil was 0.1% of fatty acids, while in the other emulsion the alpha-linolenic acid content of the oil was 3.0 +/- 1.5% (SD) of fatty acids. Group 1 and 2 patients received the "low" and "high" alpha-linolenic acid emulsions, respectively. Ten patients were studied in each group. The mean daily fat dosage was 1.70 g/kg in patients of Group 1 and 1.56 g/kg in those of Group 2. No significant difference in the clinical effects of either fat emulsion could be detected between the two study groups. Both emulsions prevented or corrected biochemical signs of essential fatty acid deficiency. The major statistically significant difference between study groups was in the level of alpha-linolenic acid and its metabolite, eicosapentaenoic acid. After 2 weeks of fat therapy, these fatty acids were increased in the high alpha-linolenic acid group; however, another metabolite of linolenic acid, docosahexaenoic acid, decreased during intravenous fat therapy in both study groups. Both study groups had significantly decreased arachidonic acid levels and increased linoleic to arachidonic acid ratios.