Use Of Intravenous Lipid Emulsions Research Articles

Lipid Emulsion Treatment for Drug Toxicity in Pediatric Patients

Medication mistakes continue to be one of the most serious issues in hospitals. Such mistakes can occur during the prescription, distribution, or administration of medications. Lipid emulsions are commonly utilized in whole or partial parenteral feeding initially, Following convincing results from animal models and effective case reports in humans, the use of intravenous lipid emulsions (ILEs) as an antidote in local anesthetic systemic toxicity has acquired considerable acceptance. Although intravenous lipid emulsion (ILE) was initially employed to treat life-threatening local anesthetic (LA) toxicity, its application has broadened to cover non-LA poisoning and less severe symptoms of toxicity. However, in recent years, the function of lipid emulsions in the treatment of lipophilic chemical toxicity and overdose has been established. In addition to typical poisoning treatment, lipid emulsion therapy was employed. The observed sequence of events provides substantial support for the importance of ILE treatment in the effective management of both instances. However, further study is needed in this area to provide definite guidelines for the use of intravenous lipid emulsions in pediatric lipophilic agent poisoning. The body of data supporting the use of ILEs in acute drug intoxication is growing. The current data supports the use of ILEs only when there is an imminent threat to life from local anesthetic systemic toxicity or lipophilic cardio-toxin poisoning. Lipid emulsion therapy is a potential and less expensive alternative in cases of acute lipophilic poisoning where a specific antidote is unavailable.

An Alternative Treatment Method for Poisoning in Veterinary Medicine: Intravenous Lipid Emulsion (ILE)

Animal poison control centers receive numerous complaints about possible consumption of substances that can cause deadly toxicities in the home. In recent years, over-the-counter medications such as ibuprofen, acetaminophen, and herbal supplements are the most common toxic substances consumed by pets. Removal of the toxin and supportive treatment is recommended in case of exposure to a toxin that does not have a known antidote. There have been many studies in both human and veterinary medicine that supporting the use of intravenous lipid emulsions in the treatment of intoxications. Intravenous lipid emulsion (ILE) is an oil-in-water emulsion that consists of egg yolk phospholipids, water, glycerin and various oils such as soybean, fish, coconut and olive oil. It is defined as a microemulsion with a long history of use as a parenteral nutrition formulation in both adult and pediatric patients. Also used as a drug carrier in addition to parenteral nutrition. In recent years, it has been used as an effective antidote for the treatment of intoxications caused by compounds with high oil solubility in both human and veterinary medicine. The first efficacy of the use of intravenous lipid emulsions in treatments was demonstrated in the systemic toxicity of local anesthetics and nowadays it comes to the fore in the poisoning of various drugs and compounds. However, it can also be used as an antidote in various intoxication cases caused by different chemicals that do not have any known antidote. Although clinically positive responses are received, more research is needed to more clearly understand the effect of intravenous lipid emulsion.

Lipids in Parenteral Nutrition: Introduction.

Thank you for reading this supplement, Lipids in Parenteral Nutrition, which is based upon the international summit “Lipids in Parenteral Nutrition” held on November 2–4, 2018 (Miami, FL, USA). A total of 18 international nutrition and metabolism experts participated in the summit, presenting and discussing topics concerning lipid emulsions in parenteral nutrition.1 The purpose of the summit was to bridge the gap between formal guideline recommendations from several nutrition societies and the practical use of lipid emulsions as part of parenteral nutrition in everyday clinical practice. The summit format allowed for the rapid elucidation of practical and clinical issues, with a range of international multidisciplinary experts presenting on a variety of topics, followed by the formulation of related statements that were voted on anonymously using a Likert-type scale. The statements were based on clinical and scientific evidence, and on the practical clinical experience of the experts when evidence was lacking. Thus, the consensus statements complement formal recommendations, and represent the opinion of the experts, not those of a national or international nutrition society or formal guideline committee. The topics covered by the summit encompassed the general role of lipids in parenteral nutrition, and with a particular focus on their clinical use in different patient populations, including adult and pediatric age groups, and various settings (hospitals and home parenteral nutrition). Although all lipid emulsions were discussed, the topic of lipid emulsions containing fish oil was of special interest because of recent popularity of research in this area and its expanded availability in many countries. Other non-clinical presentations at the summit concerned a review of the biological science of lipid emulsions, the practical handling of lipid emulsions in parenteral nutrition, and the pharmacoeconomics of ω-3 fatty-acid containing lipid emulsions. The summary of proceedings and expert consensus statements from the summit forms the first article in this supplement.1 Thereafter, other reviews have been included based on presentations at the summit, including additional information from the literature. These are: lipids in parenteral nutrition: biological aspects,2 lipid use in hospitalized adults requiring parenteral nutrition,3 the use of lipids in adult patients requiring parenteral nutrition in the home setting,4 use of lipids in neonates requiring parenteral nutrition,5 lipid emulsion use in pediatric patients requiring long-term parenteral nutrition,6 pharmacoeconomics of parenteral nutrition with ω-3 fatty acids in hospitalized adults,7 and the use of intravenous lipid emulsions with parenteral nutrition: practical handling aspects.8 It is hoped that reviewing these areas and formulating these recommendations will help to guide international practice regarding the use of lipid emulsions in parenteral nutrition. Although these recommendations complement rather than take the place of formal nutrition guidelines, we trust that this information may help clinicians and other healthcare professionals to improve the safety and effectiveness of parenteral nutrition. Finally, we would like to thank Fresenius Kabi Deutschland GmbH (Bad Homburg, Germany) for their generosity in funding the international summit, Lipids in Parenteral Nutrition.

Summary of Proceedings and Expert Consensus Statements From the International Summit "Lipids in Parenteral Nutrition".

The 2018 Lipids in Parenteral Nutrition summit involved a panel of experts in clinical nutrition, lipid metabolism, and pharmacology, to assess the current state of knowledge and develop expert consensus statements regarding the use of intravenous lipid emulsions in various patient populations and clinical settings. The main purpose of the consensus statements is to assist healthcare professionals by providing practical guidance on common clinical questions related to the provision of lipid emulsions as part of parenteral nutrition (PN). The summit was designed to allow interactive discussion and consensus development. The resulting consensus statements represent the collective opinion of the members of the expert panel, which was informed and supported by scientific evidence and clinical experience. The current article summarizes the key discussion topics from the summit and provides a set of consensus statements designed to complement existing evidence-based guidelines. Lipid emulsions are a major component of PN, serving as a condensed source of energy and essential fatty acids. In addition, lipids modulate a variety of biologic functions, including inflammatory and immune responses, coagulation, and cell signaling. A growing body of evidence suggests that lipid emulsions containing ω-3 fatty acids from fish oil confer important clinical benefits via suppression of inflammatory mediators and activation of pathways involved in the resolution of inflammation. This article provides a set of expert consensus statements to complement formal PN guideline recommendations.

Use of Intravenous Lipid Emulsions With Parenteral Nutrition: Practical Handling Aspects.

A number of topics important to the handling of intravenous lipid emulsions (ILEs) were discussed at the international summit. ILE handling includes the preparation and the administration steps in the typical use of parenteral nutrition (PN). The discussion and consensus statements addressed several issues, including standardization of the PN process, use of commercially available multi-chamber PN or compounded PN bags, the supervision by a pharmacist with expertise, limiting ILE repackaging, and infusion duration.

Intravenous Lipid Emulsion Therapy In Paediatric Poisoning

Lipid emulsions are traditionally used as a part of total or partial parenteral nutrition. However in the past few years role of lipid emulsions has been identified in the management of poisoning and overdose caused by the lipophilic agents. Although most of the evidence comes from the various case reports. We are reporting 2 cases of poisoning in the paediatric age group. In both the cases multiple poisoning agents were involved with tricyclic antidepressants being the common agent in either case. Lipid emulsion therapy was used as an adjunct in addition to the traditional poisoning management. Both the girls recovered completely without any neurological deficit. The sequence of events observed provides a considerable evidence regarding the role of ILE therapy in the successful management of both the cases. However more research is required in the area to develop definitive guidelines regarding the use of Intravenous lipid emulsions in paediatric poisoning caused by lipophilic agents.

Nutritional support in patients with extracorporeal life support and ventricular assist devices.

Extracorporeal life support (ECLS) including venovenous and venoarterial extracorporeal membrane oxygenation (ECMO) and ventricular assist devices (VAD) provide mechanical pulmonary and circulatory support, respectively, in patients with acute pulmonary or cardiovascular failure. This review discusses recently published data regarding specific topics of nutritional support in patients with ECLS and VAD. ECLS may aggravate loss of endogenous and exogenous micronutrients and macronutrients. Observational studies have shown that enteral nutrition is feasible and most commonly used in patients with ECLS. Indirect calorimetry may be feasible for measuring energy expenditure during ECLS. Specific tools are available to assess malnutrition or nutrition risk in patients with VAD but require further validation in the perioperative setting. If parenteral nutrition is indicated, the use of intravenous lipid emulsions may be associated with membrane oxygenator dysfunction of the ECLS device or increased infectious risk in patients with VAD. Despite the exponential use of ECLS and VAD over the last decade, the role of nutrition on clinical outcome in this patient population remains an important but yet underinvestigated field.

Intravenous lipid infusion in toxicological practice

The use of intravenous lipid emulsions (ILEs) is a relatively new method of treatment in toxicology. Initially, it was applied to control the resistant to other therapeutic methods systemic toxicity of local anesthetics. In the last decade this therapeutic method has been approved and recommended. Thereafter, attempts have been made to clarify the effect of ILEs in cases of acute intoxications with lipophilic xenobiotics, other than the local anesthetics.

Effects unrelated to anti-inflammation of lipid emulsions containing fish oil in parenteral nutrition for adult patients.

Several reviews and meta-analyses on modulated inflammatory and immunologic responses after the administration of omega-3 polyunsaturated fatty acids (PUFAs) in different diseases and conditions have been published. However, omega-3 PUFAs exert several other actions which are not directly related to immunologic or inflammatory responses. The aim of this paper was to review the effects which are not directly related to immunologic and inflammatory responses of intravenous lipid emulsions (IVLEs) containing fish oil (FO) in parenteral nutrition (PN) for adult patients. IVLEs containing FO could have a role in the prevention of alterations in liver enzyme tests (LETs) or PN-associated liver disease (PNALD). Studies using FO doses of ≥ 0.150 mg/kg/day or IVLEs with high FO concentration reported more positive results than those with lower doses. Once PNALD was developed, the use of IVLEs exclusively composed of FO at doses of 0.25-1 g of FO/kg/day for several weeks could attenuate or even eradicate cholestasis and liver alteration. IVLEs containing FO seemed to have faster blood clearance, and this could be beneficial for some patients. Some studies also suggested a possible improvement of respiratory function by the administration of these IVLEs. In general, IVLEs containing FO were safe. Their use did not increase oxidative stress but, in contrast, increased plasma tocopherol content. They did not alter insulin sensitivity or glycemic control, and studies have found no relevant clinical effect on platelet aggregation or hemostasis. In conclusion, the use of IVLEs containing FO in PN may be beneficial with regard to older IVLEs, in addition to the modulation of systemic inflammation response.

Lipid Emulsion Infusion in Resuscitation for Local Anesthetic and Other Drug Overdose

Abstract The use of intravenous lipid emulsions (ILEs) as antidote in local anesthetic systemic toxicity has gained widespread support following convincing data from animal models, and successful case reports in humans. An injection of a simple, intravenous nutritional solution could be acutely life-saving for a patient with severe drug overdose. But dozens of published case reports support this observation, the first ones made more than a decade ago in a rodent model of bupivacaine toxicity. It is even more surprising that such a simple formulation can rapidly reverse severe clinical toxicity from a variety of vastly disparate medications with distinct pharmacodynamics and mechanisms of action. This review will focus on the clinical application of lipid emulsion therapy in resuscitation from drug-related toxicity and will provide an introduction to the development of a method, guidelines for its use, and insights into potential controversies and future applications [1].

Should we consider the infusion of lipid emulsion in the resuscitation of poisoned patients?

The use of intravenous lipid emulsions (ILEs) as antidote in local anaesthetic systemic toxicity has gained widespread support following convincing data from animal models, and successful case reports in humans. Proposed beneficial mechanisms of action for ILEs include intravascular sequestration of intoxicant and subsequent enhanced redistribution to biologically inert tissues, augmentation of fatty acid utilisation for ATP synthesis in the context of metabolic poisoning, and direct cardiotonic and ion channel effects. The evidence base for use of ILEs in acute drug intoxication is evolving. The present evidence supports use of ILEs only in local anaesthetic systemic toxicity and in lipophilic cardiotoxin intoxication when there is an immediate threat to life, and other therapies have proven ineffective.

Intravenous Lipid Emulsion to Reverse Acute Drug Toxicity in Pediatric Patients

To identify and summarize published cases in which intravenous lipid emulsion was used to treat pediatric patients with acute drug toxicities. PubMed, SCOPUS, and EMBASE were searched up to December 2012 for relevant publications using the terms fat emulsion, lipid emulsion, Intralipid, Liposyn, Medialipide, Medialipid, lipid rescue, ILE, IVLE, IFE, IVFE, or lipid and intoxication, overdose, poisoning, toxicity, resuscitation, antidote, and rescue that were limited to reports in humans aged 18 years or younger. A publication was included if an intravenous lipid emulsion was used to treat acute-onset drug toxicity as reported in prospective or retrospective observational studies, case reports, and abstracts for patients aged 18 years or younger. Fourteen case reports were identified in which intravenous lipid emulsion was used to treat toxicities due to local anesthetics and other medications (amitriptyline, diltiazem, bupropion, dosulepin, lamotrigine, quetiapine, and verapamil). Thirteen cases demonstrated a beneficial response in reversing systemic toxicity; 1 of these patients developed hypertriglyceridemia and pancreatitis. The dosage regimens used in this series were dissimilar. There is an increasing interest in use of intravenous lipid emulsions to treat life-threatening toxicity from several lipophilic drugs in adults and children. Although most of the literature describes adult cases, intravenous lipid emulsion has been used in neonates and adolescents, with generally positive outcomes. Given the life-threatening, sometimes near-death situations in which an intravenous lipid emulsion is typically used after conventional resuscitation is unsuccessful and the dramatic positive response to this therapy in most published cases, its use likely will continue. Continued reporting of pediatric cases will guide the optimal use and safety profile of intravenous lipid emulsion for the emergent reversal of drug toxicity.

Parenteral lipid administration to very-low-birth-weight infants—early introduction of lipids and use of new lipid emulsions: a systematic review and meta-analysis

The use of intravenous lipid emulsions in preterm infants has been limited by concerns regarding impaired lipid tolerance. As a result, the time of initiation of parenteral lipid infusion to very-low-birth-weight (VLBW) infants varies widely among different neonatal intensive care units. However, lipids provide energy for protein synthesis and supply essential fatty acids that are necessary for central nervous system development. The objective was to summarize the effects of initiation of lipids within the first 2 d of life and the effects of different lipid compositions on growth and morbidities in VLBW infants. A systematic review and meta-analysis of publications identified in a search of PubMed, EMBASE, and Cochrane databases was undertaken. Randomized controlled studies were eligible if information on growth was available. The search yielded 14 studies. No differences were observed in growth or morbidity with early lipid initiation. We found a weak favorable association of non-purely soybean-based emulsions with the incidence of sepsis (RR: 0.75; 95% CI: 0.56, 1.00). The initiation of lipids within the first 2 d of life in VLBW infants appears to be safe and well tolerated; however, beneficial effects on growth could not be shown for this treatment nor for the type of lipid emulsion. Emulsions that are not purely soybean oil-based might be associated with a lower incidence of sepsis. Large-scale randomized controlled trials in preterm infants are warranted to determine whether early initiation of lipids and lipid emulsions that are not purely soybean oil-based results in improved long-term outcomes.

The Significance of Particle/Globule-Sizing Measurements in the Safe Use of Intravenous Lipid Emulsions

ABSTRACT Intravenous lipid emulsions (IVLEs) are an integral part of the clinical care of acutely ill patients who are unable to sustain nutrient homeostasis by mouth for protracted periods of time. They are oil-in-water emulsions stabilized by an emulsifier that imparts a net negative charge to the surface of the globules which stabilizes the dispersion. The mean droplet size of commercial IVLEs is approximately 300 nm. When the emulsion becomes unstable, these homogenously distributed droplets begin to aggregate and ultimately coalesce into large fat globules. Phase separation typically occurs when the volume-weighted percent fat greater than five micrometers (PFAT >5 μm) exceeds 0.4% of the total lipid present in a formulation. Moreover, when the size of the droplets reaches a dimension of 5 μm or larger, the infused globules may lodge into the pulmonary capillaries and produce a fat embolism syndrome. Thus, in the assessment of stability and the subsequent safety of IVLEs, any particle sizing measurement technique must be able to reliably quantify the volume-weighted fraction of the coalesced fat globules that statistically comprise the distribution tail of the largest diameter droplets of the emulsion. Of the four common particle sizing methods reviewed, light obscuration or light extinction, is the only one that measures fat globules accurately enough to determine the clinical safety of IVLEs.

Novel triglycerides for special medical purposes.

The clinical use of intravenous lipid emulsions have been routine for over 25 years. For most of that time period the use of the vegetable oils, soybean and safflower, were the exclusive lipid source for these emulsions. Recently intravenous medium-chain triglycerides have been commercially available. This review will discuss several important new research developments coming from the laboratory which should prove to enhance the nutritional effectiveness as well as minimize the adverse effects of lipid emulsions. The use of medium-chain triglycerides either enterally or parenterally has shown them to be superior energy sources when compared to long-chain triglycerides. Under experimental conditions of burn injury, their support of certain aspects of protein metabolism is superior to that of the current emulsions. This may be due to their rapid and preferential oxidation and poor storage into adipose tissue, and increased thermogenesis which has been observed from either enteral or parenteral administration in humans. This increased metabolic rate is not accompanied by an increase in temperature. Lipid emulsions have been described as having many different effects on variable aspects of the immunologic system. Some of these could be considered to be beneficial or without harm, and others are considered potentially deleterious. We have focused on the effects of parenteral lipid emulsions, in animals as well as in humans, on the function of the reticuloendothelial system.(ABSTRACT TRUNCATED AT 250 WORDS)