Intravenous Fat Emulsion Research Articles

Lipid On-line Hemodiafiltration (Experimental study)

Objective: to develop technology for the transmembrane mass transfer of fat-soluble substances with emulsified solution of the essential lipids exposed to dialysis. Materialaadmethods. The pharmacopoeia lipofundin MCT/LCT (20% intravenous fat emulsion) (B. Braun, Germany) was used at all study stages. Coaclusioa. Bicarbonate hemodialysis-modified lipofundin solution contains no triglycerides; its osmolarity is normalized and the solution is ready to use for lipid on-line hemodiafiltration, which allows fat-soluble substances that accumulate in acute liver failure to be removed. Key words: lipid hemodi-afiltration, lipofundin, acute liver failure.

Utilization of Hyperinsulinemia Euglycemia and Intravenous Fat Emulsion Following Poison Center Recommendations

Hyperinsulinemia euglycemia (HIE) and intravenous fat emulsion (IFE) may be beneficial in the treatment of calcium channel (CCB) and beta receptor (BB) antagonist toxicity. Many poison control centers (PCC) now recommend use. Healthcare providers may be unfamiliar with these treatments and may not institute them despite recommendations. We sought to determine how often HIE and IFE are recommended by a statewide PCC in CCB and BB toxicity, how often those recommendations are implemented, and whether a faxable information sheet increased adherence. All cases of CCB and BB exposure from January 2005-July 2011 where insulin or "other therapy" was coded were reviewed. Exclusion criteria included an incomplete PCC record, miscoding, and insulin administration as other than cardiovascular drug antidotal therapy. There were 215 CCB or BB exposures initially identified using the search criteria. HIE was recommended in 71 cases and started in one case prior to PCC recommendation. HIE was subsequently used in 30 cases after PCC recommendation (42 %). IFE was recommended by the PCC in 30 cases and implemented 10 times (33 %). In six cases, both HIE and IFE were implemented after recommendation. There was no statistical difference when recommendation was made via telephone or by faxable information sheet for HIE or IFE. HIE and IFE are two therapies that are potentially beneficial in the treatment of BB and CCB toxicity. Current national organization guidelines for use are limited. Exploration of reasons for not following recommendations and additional efforts to improve clinician education regarding HIE and IFE may be required to increase the utilization of these potentially lifesaving antidotes.

Plasma Fatty Acids in Premature Infants With Hyperbilirubinemia

Infants who are dependent on parenteral nutrition (PN) sometimes develop PN-associated cholestasis (PNAC). A compassionate use protocol, approved by the U.S. Food and Drug Administration and the institutional review board, guided enrollment of hospitalized infants with PNAC (<1 year of age, PN dependence for >3 weeks). Plasma concentrations of essential fatty acids were monitored before and after a soybean-based PN lipid, infused at 3 g/kg body weight/d, was replaced by an experimental fish oil-based intravenous fat emulsion (FO-IVFE) at 1.0 g/kg/d. All participants were born premature (n = 10; 20% male). At enrollment, infants were (mean ± SD) 86.5 ± 53.5 days of life and weighed 2.24 ± 0.87 kg; direct bilirubin was 5.5 ± 1.3 mg/dL. After treatment, blood concentrations significantly increased from baseline (P < .017) for circulating eicosapentaenoic acid (6.3 ± 3.0 to 147.8 ± 53.1 µg/mL), docosahexaenoic acid (20.7 ± 6.5 to 163.7 ± 43.4 µg/mL), pristanic acid (0.01 ± 0.01 to 0.17 ± 0.03 µg/mL), and phytanic acid (0.06 ± 0.03 to 0.64 ± 0.15 µg/mL). In contrast, total plasma ω-6 fatty acids (including linoleic acid) decreased (P < .017). The triene/tetraene ratio remained below the threshold value of 0.2 that defines ω-6 deficiency. No adverse effects were observed attributable to FO-IVFE. Discontinuation of FO-IVFE was typically due to infants (body weight 3.76 ± 1.68 kg) transitioning to enteral feeding rather than for resolution of hyperbilirubinemia (direct bilirubin 7.9 ± 4.8 mg/dL). These exploratory results suggest that FO-IVFE raises circulating ω-3 fatty acids in premature infants without development of ω-6 deficiency in the 8.3 ± 5.8-week time frame of this study.

Physiochemical Stability of Intravenous Fat Emulsion in Combination with Medications Used for Resuscitation

Objective: Intravenous fat emulsion (IFE) is a potential therapy for lipophilic drug overdose. IFE stability with drugs commonly used in resuscitation has not been assessed. This study’s purpose is to examine the in vitro physiochemical stability of various combinations of IFE and medications commonly used in resuscitation by measuring the proportion of enlarged droplets greater than 5 micrometers (PFAT5) in IFE after mixture. Methods: We compared, in vitro, PFAT5 in various IFE-medication mixtures and a control (IFE alone). In order to assess the degree of coalescence, globule-size distribution was assessed according to method II of United States Pharmacopeia (USP) chapter 729. IFE was mixed in a 1:1 ratio with standard concentrations of medications. IFE- medication mixtures with PFAT5 >0.05% at time 0 and 1 hour were considered coalesced. If any results of method II exceeded PFAT5 of the control, analysis of the globule-size distribution data was conducted using a one tailed Student’s T test with a level of significance set at p<0.05. Results: At time zero, the PFAT5 of calcium chloride (p<0.001), dextrose 50% (p=0.03), glucagon (p<0.001), lidocaine (p=0.001), magnesium sulfate (p=0.02) and sodium bicarbonate (p<0.001) were significantly higher compared to control. At time 1 hour the PFAT5 of, amiodarone (p=0.02), calcium chloride (p<0.001), D50W (p<0.001), epinephrine (p<0.001), glucagon (p<0.001), insulin regular (p<0.001), magnesium sulfate (p<0.001), naloxone (p=0.02), sodium bicarbonate (p=0.01) and vasopressin (p<0.001) were significantly higher compared to control. Conclusion: IFE should be administered in a separate

A Life‐Threatening Flecainide Overdose Treated with Intravenous Fat Emulsion

Flecainide is a Vaughan Williams Class Ic antidysrhythmic associated with PR, QRS, and QTc prolongation on the electrocardiogram and development of life-threatening cardiac toxicity in overdose. The cornerstone of treatment is fluid resuscitation and the administration of magnesium and sodium bicarbonate. We report a case of flecainide overdose associated with life-threatening hemodynamic compromise successfully treated with intravenous fat emulsion (IFE) therapy. IFE should be considered as a novel adjunctive therapy in patients with life-threatening toxicity following flecainide overdose.

Chewing the fat: A case report on intravenous lipid emulsion to reverse cardiotoxicity from intentional amitriptyline overdose.

Abstract Introduction Tricyclic antidepressant overdoses are a common presenting problem to emergency centres in South Africa. Case history A 20-year-old female was brought to the emergency centre in status epilepticus due to tricyclic antidepressant toxicity. Discussion Toxicity was manifested as severe haemodynamic instability that did not respond to standard therapy, and was subsequently treated with intravenous fat emulsion (ILE) therapy. The patient recovered with a survival to hospital discharge, neurologically intact.

Response to: ‘Intravenous Fat Emulsion Therapy: Can It be Tried Without Sufficient First‐Line Treatment Modalities?’

We wish to thank Dr. Zamani for his comments and the opportunity to clarify the treatment of poisoned patients. While we agree that at this moment the use of intravenous fat emulsion (IFE) therapy for patients with life-threatening poisoning from cardiotoxic lipophilic drugs should be only considered after routine care is provided, we emphatically disagree with Dr. Zamani's definition of routine care. Although the use of calcium 1 and glucagon 2 is frequently recommended for calcium channel blocker and beta-adrenergic antagonist toxicity, there are no controlled trials that establish their optimal dosing. Furthermore, the use of either calcium and/or glucagon in bupropion toxicity is entirely unknown. The patient we described had failed acceptable initial doses of calcium and glucagon that would have been used for empiric treatment of cardiotoxic overdose and was receiving high doses of norepinephrine at the time IFE therapy was considered. Increasing norepinephrine further may have improved the blood pressure at the cost of end-organ vasoconstriction and subsequent ischaemia. Instead, we chose to administer IFE, based on published success 3 in hopes of sequestering a lipid-soluble toxin and obviating the need for another toxic drug (norepinephrine). Finally, most of the adverse effects associated with IFE, as noted in the article cited by Dr. Zamani, are with prolonged total parenteral nutrition and therefore cannot be extrapolated to short administration of lipid resuscitation therapy 4.

Intravenous Fat Emulsion Therapy: Can It Be Tried Without Sufficient First‐Line Treatment Modalities?

Intravenous Fat Emulsion Therapy: Can It Be Tried Without Sufficient First‐Line Treatment Modalities?

A Double‐Blind Randomized Study Comparing the Efficacy and Safety of a Composite vs a Conventional Intravenous Fat Emulsion in Postsurgical Gastrointestinal Tumor Patients

Composite intravenous fat emulsion, a fat emulsion composed of soybean oil, medium-chain triglycerides (MCT), olive oil, and fish oil, was evaluated for metabolic efficacy, immune modulation, clinical efficacy, safety, and tolerance in surgical gastrointestinal (GI) tumor patients. In a prospective, randomized, double-blind study, 40 patients were randomized after elective digestive surgery to receive isonitrogenous, isoenergetic parenteral nutrition for 5 days postoperatively with either composite 20% IVFE (composed of soybean, MCT, olive, and fish oils) or a conventional long-chain triglyceride (LCT)/MCT 20% IVFE (LCT/MCT IVFE); IVFE was dosed at 1-2 g/kg body weight. Safety and efficacy parameters were assessed on operation day (day 0) and at the end of study (day 6). Adverse events were documented daily and clinical outcomes were recorded and compared between the groups. Metabolic parameters, laboratory parameters, proinflammatory cytokine levels, adverse events, and clinical outcomes did not differ between the 2 groups, with the exception that postoperative low-density lipoprotein levels decreased significantly in the composite IVFE group (93.2 ± 24.3 vs 110.5 ± 26.4 mg/dL, P = .038). composite IVFE was comparable with conventional LCT/MCT IVFE in efficacy, safety, tolerance, and clinical outcomes in surgical GI tumor patients.

Effect of intravenous fat emulsion therapy on glyphosate-surfactant–induced cardiovascular collapse

Intravenous fat emulsion (IFE) therapy is an adjunct therapy administered to hemodynamically compromised patients with glyphosate-surfactant intoxication when they respond poorly to conventional therapies such as fluid resuscitation or vasopressors [1,2]. However, the use of IFE as an adjunct therapy in collapsed patients with glyphosate intoxication has not been reported previously. Here, we describe the case of a patient with glyphosate-surfactant–induced cardiovascular collapse who responded to IFE.

A.S.P.E.N. Position Paper

The currently available, standard soybean oil (SO)-based intravenous fat emulsions (IVFEs) meet the needs of most parenteral nutrition (PN) patients. There are alternative oil-based fat emulsions, such as medium-chain triglycerides (MCTs), olive oils (OOs), and fish oils (FOs), that, based on extensive usage in Europe, have an equivalent safety profile to SO. These alternative IVFEs are metabolized via different pathways, which may lead to less proinflammatory effects and less immune suppression. These alternative oil-based IVFEs are not currently available in the United States. Many patients who require IVFEs are already in a compromised state. Such patients could potentially have better clinical outcomes when receiving one of the alternative IVFEs to diminish the intake of the potentially proinflammatory ω-6 fatty acid-linoleic acid-which comprises more than 50% of the fatty acid profile in SO. Further research is needed on these alternative oil-based IVFEs to identify which IVFE oils or which combination of oils may be most clinically useful for specific patient populations.

Parenteral Nutrition Therapy Over the Next 5–10 Years

Parenteral nutrition (PN) is one of the most complex medical therapies prescribed by healthcare professionals because it is dependent on the compounding of multiple base solutions to arrive at the final formulation. The delivery of PN is associated with errors in ordering, transcribing, compounding, and delivery of the PN formulations. New compounding technologies will attempt to minimize the potential for these errors. In addition, the associated infectious complications associated with PN therapy need to be minimized. Commercially prepared, premixed, terminally sterilized PN solutions may have an impact. Broader decontamination technologies will be implemented to reduce the incidence of overall nosocomial infections. Modification of PN nutrients, particularly intravenous fat emulsions, will be provided by alternative biological sources, creating fats that may have an improved impact on the patient's immune system and ultimately affecting clinical outcomes.

Parenteral Nutrition Ordering Processes

Parenteral nutrition (PN) is a complex prescription consisting of many components such as dextrose, amino acids, electrolytes, vitamins, trace elements, and/or intravenous fat emulsions. The ordering process is inconsistent and has led to PN errors. PN prescriptions require knowledge, education for prescribers, and standardized processes.

Safety and role of ketogenic parenteral nutrition for intractable childhood epilepsy

To retrospectively evaluate the safety and role of ketogenic parenteral nutrition in patients with intractable childhood epilepsy. The ketogenic parenteral nutrition was given to 10 patients who were unable to absorb nutrients through the intestinal tract because of various gastrointestinal disorders and required complete bowel rest. This nutrition consisted of conventional intravenous fat emulsion (20% Lipision) plus dextrose and amino acid (6% Trophamine) hyperalimentation in a 4:1 (or 3:1) lipid to non-lipid ratio, infused during the bowel rest. If the ketogenic parenteral nutrition allowed normal daily functioning or resolved the underlying problems, we soon changed it to the enteral ketogenic diet (KD). The mean (±SD) duration of the ketogenic parenteral nutrition was 4.1 (±1.5) days. Although a brief span of several days, all patients could maintain ketosis and the efficacy of the previous enteral KD during the ketogenic parenteral nutrition. Complications included elevated aspartate aminotransferase and/or alanine aminotransferase in one patient. Amylase and lipase increased in one patient. Serum triglyceride level increased to the level of 1885mg/dl in one patient, but normalized in one week after discontinuation of the ketogenic parenteral nutrition and resuming of the enteral KD. Nine patients (90%) remained on the enteral KD after the ketogenic parenteral nutrition (the mean follow-up period was 9months), including 2 patients who successfully completed the diet with seizure free state. Only one patient discontinued the ketogenic parenteral nutrition because of persistent increase of the amylase and lipase levels. The ketogenic parenteral nutrition proved to be a relatively safe short-term method of continuing KD to maintain ketosis for seizure control, while patients were unable to absorb nutrients through their intestinal tract.

A Randomized Trial of Micropreemies Receiving Higher Amounts of Intravenous Fat Emulsion During the First Week of Life

Objective. The goal of this study was to determine if micropreemies could tolerate higher infusion rates of intravenous fat emulsions (IVFEs) during the first week of life by maintaining their serum triglyceride levels at &lt;200 mg/dL. Methods. This was a randomized controlled trial of 19 infants who were classified as appropriate for gestational age and had birth weights between 500 and 750 g. The primary clinical outcome was serum triglyceride levels; secondary outcomes also were monitored. Results. A total of 19 micropreemies completed the study (experimental group: n = 10; control group: n = 9). Of the infants in the experimental group, 100% had developed hypertriglyceridemia (&gt;201 g/dL) during the first week of life compared with only 44.4% of the infants in the control group. The experimental group experienced a lower weight loss of 8.6% ± 3.10% as compared with 16.22% ± 8.04% in the control group during the first week of life. Initially, the experimental group was given significantly higher infusion rates of IVFEs, but at the end of the week, the control group was receiving significantly higher infusion rates of IVFEs. Calorie intake was significantly better initially for the experimental group, but because of the incidences of hypertriglyceridemia and a reduction of IVFEs, the control group had significantly better calorie intake at the end of the study period. Conclusions. Micropreemies do not tolerate initial higher infusion rates of IVFEs during the first week of life because of their potential risk for developing hypertriglyceridemia.

Intravenous fat emulsion as treatment for ivermectin toxicosis in three dogs homozygous for the ABCB1–1Δ gene mutation

To describe the outcome of 3 cases of ivermectin toxicosis in dogs homozygous for the ABCB1-1Δ gene mutation treated with intravenous fat emulsion (IFE). One Australian Shepherd and 2 Miniature Australian Shepherds were treated for naturally occurring ivermectin toxicosis with IFE. All 3 dogs were homozygous for the ABCB1-1Δ gene mutation. Serum ivermectin concentrations confirmed ivermectin exposure in each case. All 3 dogs exhibited tremors, ptyalism, and central nervous system depression, which progressed over several hours to stupor in 2 dogs, and to a comatose state requiring mechanical ventilation in the remaining dog. A 20% formulation of IFE(a) was administered as an IV bolus (1.5 mL/kg) followed by a slow IV infusion (7.5-15 mL/kg [0.25-0.5 mL/kg/m], over 30 minutes). No change was observed in the neurologic status of any patient. Lipemia visible upon blood sampling persisted for 36 hours in 1 dog however, no other adverse effects were noted. Flumazenil (0.01 mg/kg IV), followed by a constant rate infusion(CRI) of 0.01 mg/kg/h IV was administered in 1 case, without any apparent clinical benefit or adverse effect. IFE was ineffective in the treatment of ivermectin toxicosis in these ABCB1-1Δ homozygous mutant dogs. Further investigation is necessary to determine why IFE treatment was unsuccessful in these cases and whether its use can be optimized to yield better results.

Comparison of the Effects of Different Intravenous Fat Emulsions in Patients With Systemic Inflammatory Response Syndrome and Sepsis

In this study, the authors aimed to compare the effects that a medium- and long-chain triglyceride (MCT/LCT) fat infusion and a fish oil-based (ω-3) fat infusion for parenteral nutrition (PN) had on systemic inflammation, cytokine response, and hepatic steatosis in mixed intensive care unit (ICU) patients. This was a single-center, placebo-controlled, randomized clinical trial in a university hospital. Four patient groups, including systemic inflammatory response syndrome (SIRS) and sepsis patients, were assigned to receive PN employing the MCT/LCT fat infusion or the fish oil-based fat infusion over 7 days. Blood biochemistry and liver steatosis were evaluated. Twenty sepsis and 20 SIRS patients were included in this study. There was no statistically significant difference in terms of biochemical values and Acute Physiology and Chronic Health Evaluation II scores between the different feeding groups. Sepsis groups who received MCT/LCT revealed higher grades of liver steatosis by ultrasound on days 7 and 10 (P < .05). Tumor necrosis factor (TNF)-α and interleukin (IL)-6 values in sepsis group 1 (S1) were higher than in sepsis group (S2) on day 7, whereas IL-1 values were higher on days 3, 7, and 10 in group S1 than in group S2. Conversely, IL-10 values on days 3 and 7 were significantly higher in group S2. Fish oil-based fat emulsions might have anti-inflammatory and hepatoprotective effects in hyperinflammatory disease such as sepsis.

Intravenous Fat Emulsions Reduction for Patients with Parenteral Nutrition–Associated Liver Disease

To test the hypothesis that implementation of a marked reduction in intravenous fat will result in reversal of parenteral nutrition-associated liver disease (PNALD) in infants. Prospective study of intravenous fat emulsion reduction in parenteral nutrition to 1 g/kg/d 2 times per week in neonates diagnosed with PNALD. Primary outcome measure was total bilirubin levels compared with gestational age, birth weight, and diagnosis-matched historical controls receiving 3 g/kg/d of intravenous lipids. Intravenous fat emulsion reduction resulted in a significant decline in total bilirubin levels compared with controls. Comparison of growth in the 2 groups was similar. Mild essential fatty acid deficiency was detected in 8 of 31 infants and was reversed with additional days of lipid infusion. No significant adverse events were noted. An association between intravenous lipid emulsion administration and the development of PNALD seems probable. Use of intravenous fat emulsion reduction is a potential approach to reverse PNALD in young infants. Frequent monitoring of essential fatty acid deficiency is needed with the use of this regimen.

Hypersensitivity to Total Parenteral Nutrition Fat-Emulsion Component in an Egg-Allergic Child

Immunoglobulin E (IgE)-mediated food allergies affect 6% to 8% of children in the United States with symptoms ranging from localized hives to life-threatening anaphylaxis. Intravenous fat emulsions (IFEs) are a vital component of total parental nutrition, because they provide essential fatty acids. IFE is a sterile fat emulsion that contains egg-yolk phospholipids. Although egg allergy is listed as a contraindication, adverse reactions are uncommon. We report here the case of a hypersensitivity to IFE in a 2-year-old patient with previously undocumented egg allergy. Our patient was placed on total parental nutrition and a 20% IFE postoperatively and developed diffuse pruritus 14 days after initiation of therapy. She showed transient improvement with intravenous antihistamine, but her symptoms did not resolve until the IFE was stopped. On the basis of clinical history, including aversion to egg, we performed skin-prick testing, the results of which were positive for egg white allergy. Serum testing confirmed allergy to both egg yolk and egg white. To our knowledge, this is the first reported case of a pediatric patient with a history suggestive of egg allergy, positive skin-prick and serum testing to egg, and reaction to IFE infusion. Although ingestion of egg lecithin in cooked food is generally tolerated by egg-allergic people, administration of intravenous egg-containing lipid emulsions may cause significant adverse reactions.

Fatty acids antagonize bupivacaine - induced INa blockade

Theories regarding the mechanism of intravenous fat emulsion for bupivacaine cardiotoxicity include creation of an intravascular lipid sink into which the cardiotoxic drug is sequestered, an improvement of impaired cardiac metabolism, and restoration of cardiomyocyte function by increasing intracellular calcium. However, work in this area is inconclusive and a more mechanistic explanation is desirable. We used a heterologous expression system (HEK-293 cells) and voltage clamp techniques to study the electrophysiologic effects of bupivacaine, polyunsaturated, and saturated fatty acids on sodium current (INa) in stable cell lines expressing human cardiac sodium channels. Linolenic (polyunsaturated) and stearic (saturated) fatty acids were selected for study as they are components of commonly used lipid infusions. Bupivacaine - induced significant tonic and use dependent INa block, as expected. Linolenic and stearic fatty acids directly modulated INa, inducing primarily tonic block. Greater block was seen with linolenic acid as compared with stearic acid. Simultaneous exposure to bupivacaine and fatty acids reduced both the tonic and use dependent block compared with bupivacaine alone. Reduction of bupivacaine - induced INa block was greatest in cells treated with linolenic acid. These results suggest that the salutary effects of intravenous fat emulsion may be, in part, due to a direct modulatory effect of fatty acids on cardiac sodium channels.