Administration Of Intravenous Fat Emulsion Research Articles

Parenteral MCT/ω-3 Polyunsaturated Fatty Acid-Enriched Intravenous Fat Emulsion Is Associated With Cytokine and Fatty Acid Profiles Consistent With Attenuated Inflammatory Response in Preterm Neonates: A Randomized, Double-Blind Clinical Trial.

Soybean oil-based intravenous fat emulsion (IVFE) administered to preterm neonates can induce oxidative stress and inflammatory response, which are associated with severe complications of prematurity. This study aimed to test the hypothesis that administration of medium-chain triglyceride (MCT)/ω-3 polyunsaturated fatty acid (PUFA)-enriched IVFE in preterm neonates is associated with a cytokine and fatty acid (FA) profile consistent with attenuated inflammatory response. In a double-blind randomized study, 60 preterm neonates (gestational age 26-32 weeks) were randomized to receive either MCT/ω-3 PUFA-enriched IVFE (intervention group) or soybean oil-based IVFE (control group). Serum biochemistry, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-8, α-tocopherol, and FAs were assessed at baseline, on day of life 15, and day of life 30 or at the end of intervention. All cytokine levels changed significantly across the 3 time points, whereas the type of IVFE had a significant effect on final IL-6 and IL-8 levels, which were lower in the intervention group. The difference in final IL-6 and IL-8 levels remained significant after controlling for bronchopulmonary dysplasia and/or infection. α-Tocopherol and FA values changed significantly over time. MCT/ω-3 PUFA-enriched IVFE administration was associated with significantly higher α-tocopherol, eicosapentaenoic acid, docosahexaenoic acid, and ω-3 PUFAs and lower linolenic acid, total PUFA, and ω-6/ω-3 PUFA values compared with soybean oil-based IVFE. Both IVFEs were well tolerated. Compared with the soybean oil-based IVFE, the MCT/ω-3 PUFA-enriched IVFE is associated with a more favorable cytokine and FA profile consistent with attenuated inflammatory response in preterm neonates.

Life-Threatening Diphenhydramine Toxicity Presenting With Seizures and a Wide Complex Tachycardia Improved With Intravenous Fat Emulsion

Diphenhydramine toxicity manifests with signs of anticholinergic toxicity; therapy is generally supportive. In rare cases, patients can also present with a wide complex tachycardia due to sodium channel blockade. Treatment involves sodium bicarbonate. Lidocaine and hypertonic saline are used for arrhythmias refractory to sodium bicarbonate. Although intravenous fat emulsion (IFE) therapy is proposed as an adjunctive therapy due to the lipophilicity of diphenhydramine (octanol/water partition coefficient of 3.3), successful use of IFE after a confirmed sole ingestion of diphenhydramine is not previously reported. We present the case of a 30-year-old woman presenting with seizures, a wide complex tachycardia, and cardiovascular collapse after an ingestion of diphenhydramine refractory to other therapies with rapid improvement after IFE administration.

Analysis of risk factors for lipid intolerance of intravenous fat emulsion in very low birth weight infants.

In order to prevent fatty acid deficiency and to supply enough energy, intravenous fat emulsion is necessary for parenteral nutrition in preterm neonates. However, parenteral administration of intravenous fat emulsion can induce lipid intolerance. The purpose of this study was to analyze risk factors for lipid intolerance in very low birth weight infants. This retrospective study included 80 preterm neonates whose birth weight was less than 1,500 g. Subjects were divided into 2 categories: those with a serum triglyceride level of ≥ 200 mg/dl (n = 33, 41%) and those with a serum triglyceride level of < 200 mg/dl (n = 47, 59%). We conducted logistic regression analysis using variables which were significant in univariate analysis. All statistical analyses were processed in SPSS version 19.0. Four risk factors for lipid intolerance were obtained through analysis of the electronic medical record. Lipid intolerance occurred more frequently in neonates with sepsis; those with a birth weight less than 1,000 g; those who was administered intravenous fat emulsion more than 2.6 g/kg/day; and those whose gestational age was less than 28 weeks. It is suggested that serum triglyceride levels should be closely monitored to prevent lipid intolerance in preterm neonates with the aforementioned characteristics.

Infectious Complications With Nondaily Versus Daily Infusion of Intravenous Fat Emulsions in Non–Critically Ill Adults

Increased risk for infection has been associated with the administration of intravenous fat emulsion (IVFE). Typically, IVFE is infused daily as part of the parenteral nutrition (PN) regimen. However, a national IVFE shortage in 2010 compelled institutions to restrict administration to nondaily. This retrospective study evaluated the rate of infections associated with the nondaily as compared to daily IVFE infusion in hospitalized adult patients. Patients in the study group received nondaily IVFE during the shortage period, and patients in the control group received daily IVFE. The primary outcomes were the development of catheter-related bloodstream infections (CR-BSIs) or any bloodstream infection (BSI). Secondary outcomes were the development of respiratory, urinary, wound, or other infections. Included in the study were 52 patients, 33 patients in the study group and 19 patients in the control group. There were no CR-BSIs reported. BSIs occurred in 1 patient in the study group. The total number of infections and urinary tract infections (UTIs) per 1000 catheter days were not different between the 2 groups (45.28 vs 21.24, P = .203) and (24.39 vs 5.525, P = .099), respectively. Survival analyses showed no difference between the 2 groups for the time to first infection (11.24 vs 6.59 days, P = .30) and time to first UTI (11.97 vs 7 days, P = .093), respectively. Nondaily vs daily IVFE infusion did not have a significant effect on the risk of infection or time to development of infection; however, results are limited due to the small sample size. Large prospective randomized clinical trials are needed to further evaluate the effect of daily as compared to nondaily IVFE infusion on infectious complications.

Life-Threatening Bupropion Ingestion: Is There a Role for Intravenous Fat Emulsion?

Intravenous fat emulsion (IFE) is emerging as a novel antidote in clinical toxicology. Its current usage is extending beyond local anaesthetic toxicity into management of severe toxicity from some lipophilic drugs. We present a 51-year-old woman with severe bupropion toxicity whose haemodynamic status transiently improved after IFE. Serum analysis demonstrated an increase in serum concentration of hydroxybupropion, an active metabolite of bupropion, after IFE administration, lending support to one of the proposed mechanisms of IFE. A 51-year-old woman presented to the emergency department with generalised tonic-clonic convulsions lasting approximately 30 sec., and a wide complex rhythm on her ECG that was suggestive of myocardial sodium channel blockade. Despite sodium bicarbonate therapy, the patient developed profound hypotension refractory to high-dose norepinephrine. IFE was administered with haemodynamic improvement over the course of 30 min., followed by a significant decrease in norepinephrine requirement. The patient had an episode of ventricular tachycardia 24 hr after presentation, and received a second infusion of IFE. Analysis of serum for a panel of myocardial sodium channel blocking drugs revealed that significant bupropion ingestion had occurred. Bupropion poisoning may produce life-threatening clinical effects, and IFE may be considered in cases of severe haemodynamic instability. Further studies would be instrumental in determining the optimal clinical situations for utilisation of IFE.

Fatal Poisoning with Glyphosate-Surfactant Herbicide

A 29-year-old man was admitted following deliberate ingestion of approximately 300 mL of ‘Roundup Ace,’ a herbicide containing glyphosate. On presentation, he was agitated and required intubation and admission to ICU. He developed severe and persistent lactic acidosis, hyperkalaemia, hypotension, torrential watery diarrhoea and abdominal distension in the first 24 hours. The patient was supported with a continuous noradrenaline infusion and continuous veno-venous haemodiafiltration. The clinical course was further complicated by cardiac arrhythmias and an episode of cardiac arrest. By day three, he had bone-marrow, liver and worsening respiratory failure. There was no hope of recovery; therefore, noradrenaline was discontinued, and the patient died 15 minutes later. Glyphosate-surfactant herbicide (GlySH) is a general-purpose herbicide with no anticholinesterase effect and no organophosphate-like CNS effects. GlySH intoxication has a case fatality rate of between 3.2% and 29.3%. There is no antidote and the mainstay of treatment for systemic toxicity is decontamination and aggressive supportive therapy. Early renal replacement therapy may improve prognosis but there is no evidence to support this. There is one published case of a patient who survived severe GlySH poisoning following administration of intravenous fat emulsion. Glyphosate-surfactant herbicide, commercially known as ‘Roundup’ is a widely available herbicide commonly used in both professional and domestic settings. This is a case of a young man who deliberately ingested GlySH at home and rapidly developed multi-organ failure, culminating in his death.

Intentional overdose with cardiac arrest treated with intravenous fat emulsion and high-dose insulin

Introduction. Nebivolol, a beta blocker with 3–10 times more β1 cardioselectivity than metoprolol, has caused hypotension and bradycardia in overdose. We report a nebivolol-induced cardiac arrest in the setting of a polydrug ingestion, successfully resuscitated with intravenous fat emulsion (IFE) and high-dose insulin (HDI). Case report. A 48-year-old man was brought to the emergency department after ingesting nebivolol and ethanol, along with possibly diazepam and cocaine. He had a heart rate of 71/min and a blood pressure of 98/61 mmHg. The initial ECG showed sinus rhythm with a QTc of 483 ms and a QRS of 112 ms. Over the subsequent 4 h, he became bradycardic and hypotensive and developed bradyasystolic cardiac arrest. Standard resuscitation including epinephrine had no effect. Spontaneous circulation returned 30 s after a 100 mL bolus of 20% IFE, and the patient then became briefly hypertensive and tachycardic with heart rate and blood pressure measured as high as 123/min and 251/162 mmHg, respectively. His care included IFE infusion along with HDI bolus and infusion with doses as high as 21.8 units/kg/h. With subsequent hypotension, vasopressors were withheld in favor of HDI and supportive care. He was discharged with baseline neurologic function. Discussion. We hypothesize that after the administration of IFE the epinephrine was able to exert its effect on receptors previously occupied with the nebivolol. This would be congruent with the lipid sink theory of IFE mechanism. Conclusion. We report an overdose involving nebivolol in a polydrug ingestion resulting in cardiac arrest, successfully treated with IFE and a very HDI infusion.

Effect of 24-hour intravenous tubing set change on the sterility of repackaged fat emulsion in neonates.

Duration of intravenous fat emulsion (IVFE) infusions, precise method of administration (manufactured bottle vs repackaged syringe), and interval for administration set change continue to be debated. To determine the contamination rate associated with replacing IVFE administration sets every 24 hours in newborn infants receiving fat emulsion repackaged into unit-of-use syringes. This was a prospective, microbiologic study of 90 administration sets used in 19 neonates. IVFE samples were obtained from administration sets at the end of a 19- to 23-hour infusion and prior to daily tubing set change from infants who received repackaged IVFE. Samples of IVFE (1-3 mL) were aseptically removed at the catheter connection site proximal to the patient, transferred into BACTEC PEDSPlus culture media, and continuously monitored for 5 days to detect gram-positive and gram-negative organisms, as well as yeast. Two samples (2.27%) grew coagulase-negative Staphylococcus. Both samples were from the same asymptomatic patient and were obtained on consecutive days. A blood sample obtained through this infant's central catheter grew the same organism and suggested catheter hub colonization as the primary site of microbe origin. Microbial contamination of IVFE infusion sets changed at 24-hour intervals, using unit-of-use syringes in neonates, was low at 2.2%.

The Fat Overload Syndrome: Successful Treatment with Plasma Exchange

Excerpt The fat overload syndrome is a rare complication of the intravenous administration of fat emulsion. It is characterized by sudden elevation of the serum triglyceride level associated with f...

Secondary Carnitine Deficiency in Handicapped Patients Receiving Valproic Acid and/or Elemental Diet

We examined serum-free carnitine (SFC) concentrations and serum acylcarnitine (SAC)/SFC ratios in 40 severely handicapped patients, aged 2 to 36 years, and 69 age-matched control subjects. SFC levels in the patients treated with valproic acid (VPA) and/or receiving carnitine-deficient elemental diets (ED) were significantly lower, and their SAC/SFC ratios were significantly higher than in the other patients or in control subjects. There were 6 patients whose SFC levels were less than the -2SD level (15.8 +/- 6.7 microM, range 6.3-25.5) of those in control subjects (52.1 +/- 11.5 microM). They had no clinical symptoms of carnitine deficiency such as non-ketotic hypoglycemia, hepatomegaly, muscle weakness or cardiac function impairment, and showed normal transaminase, lipid and ammonia levels. In two cases (SFC = 11.0, 13.4 microM), the ketogenic responses to intravenous administration of fat-emulsion were impaired, but they were restored after D-,L-carnitine supplementation (30 mg/kg/day, po) for 1 month. However, in one case with the lowest SFC level (6.3 microM), the ketogenic responses to fat-emulsion infusion or fasting were normal, and dicarboxylic aciduria was not detected. These results indicate that 1) SFC levels are reduced in handicapped patients receiving VPA and/or ED, although clinical symptoms of carnitine deficiency do not easily develop, 2) some of these hypocarnitinemic cases show a subclinical impairment of hepatic fatty acid metabolism, not always correlated with the degree of SFC reduction, which can be restored by exogenous carnitine supplements, and therefore 3) in patients with acquired hypocarnitinemia, carnitine therapy should be considered, although a low SFC level alone may not imply an immediate indication.

The effect of intravenous administration of fat emulsion on the flow rate and composition of thoracic duct lymph in the dog

In seven dogs weighing 17–25 kg, the terminal segment of the thoracic duct was isolated, under total pentobarbital anesthesia, so as to collect lymph continuously before, during and after infusion of a 20% fat emulsion Intralipid ® (Vitrum). Arterial blood and lymph were withdrawn simultaneously for analysis of total protein, amylase, cholesterol, triglycerides, urea and AST. The lymph flow rate was calculated in ml/min. Compared with the control period, during which a 5% glucose solution was administered, a two-hour infusion of the fat emulsion did not change the lymph flow rate nor the levels of biochemical parameters monitored in lymph. These results distinguish intravenous administration of a fat emulsion from a situation, in which fat is administered orally. The unchanged lymph amylase levels following fat administration suggest that no significant stimulation of external pancreatic secretion occurs after this route of fat administration.

Hematologic disorders following prolonged use of intravenous fat emulsions in children.

Abnormalities in hematologic parameters, associated with prolonged utilization of intravenous fat emulsion (IVFE), were observed in seven children on long-term cyclic total parenteral nutrition (TPN). All patients were receiving IVFE (Intralipid 20%) 1 to 2 g/kg/24 hr as part of TPN, during 3 to 18 months. Recurrent thrombocytopenia occurred in all seven patients. Platelet lifespan, as measured with 111 Indium was reduced. Sea-blue histiocytes containing granulations and hemophagocytosis were seen on bone marrow smears. Scans taken after injection of autologous erythrocytes labeled with technetium-99 showed bone marrow sequestration of these cells. Taken together, this constellation of hematologic abnormalities suggests that long-term IVFE administration induces hyperactivation of the monocyte-macrophage system.

Use of Intravenous Fat Emulsions in Pediatric Patients

Intravenous fat preparations are used in the nutrition of those requiring parenteral alimentation. Although parenteral nutrition is recognized as a limited substitute for oral alimentation, and should be used for as short a time as possible, widespread use has resulted in some adverse effects. Fat has the highest caloric density of any nutrient. In addition, intravenously infused fat emulsions exert negligible osmotic effects. Thus, for a number of years, the possibility of providing calories by the intravenous administration of fat emulsions has been an attractive one. In fact, one of the first attempts at intravenous nutrition was infusion of various nonemulsified oils.1 Approximately 30 years ago, a fat emulsion suitable for intravenous use was developed and used extensively. Although it was efficacious as an intravenous calorie source, it was unstable and the serious, short-term effects of this instability resulted in its withdrawal from the market in the late 1960s. Subsequently, advances in manufacturing technology allowed preparation of stable fat emulsions, and several such preparations are available today. All currently available emulsions are efficacious calorie sources; moreover, they appear to be extremely stable and have been associated with relatively few adverse effects.2-5 All allow delivery of lipid to patients requiring parenteral nutrition. In fact, they may make it possible to deliver adequate nutrients solely by peripheral vein, thus avoiding in many patients the use of central vein catheters and their associated complications.6 This possibility, plus the possibility of providing linoleic acid and thereby preventing essential fatty acid deficiency, which occurs with fat-free total parenteral nutrition,7,8 has generated considerable enthusiasm for these products.

低体重仔犬における脂肪乳剤輸注の影響第 1 報

低体重仔犬における脂肪乳剤輸注の影響第 1 報

Electron microscopic observations on the mouse liver after intravenous administration of fat emulsion.

Artificial fat emulsion was injected into mice and their uptake by the liver was observed electron microscopically.At 5min after the injection, Kupffer cells took up lipid particles by pinocytosis, but no liver cells showed a sign of lipid uptake. At 30 and 60min after the injection, numerous osmiophilic particles (300-1, 000A) appeared in the cisternal ends of rough endoplasmic reticulum, smooth endoplasmic reticulum proper and Golgi apparatus of the liver cells. The particles were also found in the space of Disse. At 6hrs after the injection, the particles were no longer found in the liver cells but many large 0.5-2μ lipid droplets accumulated in the cell matrix.It was suggested that the injected lipids were taken into the liver cells by simple diffusion after hydrolysis and incorporated into lipoproteins which were secreted into the circulation.

Hyperlipoproteinemia in rabbits induced by intravenous administration of fat emulsions and heparin

Summary The data presented show that intravenous infusion of triglycerides into normal rabbits in the presence of heparin induces elevation in the concentration of plasma very low density lipoproteins. No exogenous free fatty acid mobilizing hormone was given. The effect is therefore referred to metabolic consequences of the fat infusion itself. The data are compatible with the possibility that rapid hepatic uptake of triglycerides, like uptake of free fatty acids, stimulates production and secretion of lipoproteins, but other possible mechanisms cannot be ruled out.

The Effects of Choline on Hepatic Ultrastructural Changes Associated with the Intravenous Administration of Fat

Abstract : The administration of intravenous fat emulsion to rats produces dilatation of the hepatic rough endoplasmic reticulum similar to that which occurs in choline deficiency. In the present study the changes occurring in the livers of rats receiving multiple injections of an intravenous fat emulsion while maintained on choline-deficient, cholinerich and stock diets were determined by light and electron microscopy. Severe fatty metamorphosis of the liver developed in all rats on choline-deficient diets. This fatty change was increased by intravenous injection of Intralipid. Dilatation of the hepatic rough endoplasmic reticulum was produced in rats on a stock diet given injections of Intralipid, as well as in rats on choline-deficient diets, rats on choline-deficient diets given injections of Intralipid and in rats on choline-rich diets given injections of Intralipid. Dilatation of the rough endoplasmic reticulum associated with the intravenous administration of Intralipid was not prevented by dietary supplementation with choline. This indicates that the mechanism by which Intralipid produces dilatation of the hepatic rough endoplasmic reticulum is more complex than simply the production of a relative choline deficiency. A possible explanation for dilatation of the rough endoplasmic reticulum is presented on the hypothesis that rough endoplasmic reticulum undergoes morphologic and quantitative enzymatic change to become smooth endoplasmic reticulum. This is thought to be a compensatory phenomenon of the hepatocyte to metabolize the increased intracellular lipid. (Author)

Long-Term Intravenous Administration of Fat Emulsions in Dogs and Single Infusions in Man

Long-Term Intravenous Administration of Fat Emulsions in Dogs and Single Infusions in Man

Changes in Plasma and Erythrocyte Lipids During Short-Term Administration of Intravenous Fat Emulsion and Its Subfractions

Changes in Plasma and Erythrocyte Lipids During Short-Term Administration of Intravenous Fat Emulsion and Its Subfractions

Mechanism of removal of intravenously injected fat. Its relationship to toxioity.

The intravenous administration of fat emulsions has come to be an accepted method for supplying calories to patients who cannot take food by mouth. From the onset, the preparation of intravenous fat emulsions has been a difficult problem. The first difficulty arises in the preparation of a stable emulsion. The high interfacial tension between fat and water makes it necessary to add emulsifying agents. These surface-active agents make possible the preparation of an emulsion of fine particle size. Emulsifying agents are toxic in direct proportion to their ability to lower surface tension.1Therefore, the best emulsifying agents are the most toxic. Lipid is an integral part of the cell membrane. The emulsifying agents tend to widen the interstices between the lipid molecules in the cell membrane and in this way to increase the permeability of the cell. They may even cause the dispersion of the lipid portion of the