Impact of Intravenous Fat Emulsion Choice on Candida Biofilm, Hyphal Growth, and Catheter-Related Bloodstream Infections in Pediatric Patients.

BACKGROUND: Use of mixed-oil (MO) intravenous fat emulsion (IFE) was shown to inhibit Candida albicans biofilm formation and overall rate of catheter-related bloodstream infections (CR-BSIs) compared with soybean-oil (SO) IFE). We aimed to delineate this inhibitory mechanism and impact of IFE choice on distribution of fungal CR-BSIs. METHODS: Transcriptional profiling was conducted on C. albicans grown in SO-IFE, MO-IFE, or SO-IFE with capric acid. Overexpression strains of shared down-regulated genes were constructed using a tetracycline-off system to assess hypha and biofilm formation in IFEs. A 5-year retrospective multicenter cohort study was performed to assess differences in CR-BSIs caused by Candida species based on the IFE formulation received in pediatric patients. RESULTS: Genes significantly down-regulated in MO-IFE and SO-IFE with capric acid included CDC11, HGC1, and UME6. Overexpression of HGC1 or UME6 enabled filamentation in capric acid and MO-IFE. Interestingly, only overexpression of UME6 was sufficient to rescue biofilm growth in MO-IFE. MO-IFE administration was associated with a higher proportion of non-albicans Candida versus C. albicans CR-BSIs (42% vs 33%; odds ratio, 1.22 [95% confidence interval, .46-3.26]). CONCLUSIONS: MO-IFE affects C. albicans biofilm formation and hyphal growth via a UME6-dependent mechanism. A numerical but not statistically significant difference in distribution of Candida spp. among CR-BSIs was observed.

Delivery of carbohydrates, amino acids, and lipids via intravenous catheters is necessary for some patients to supply daily caloric needs. These nutrient-dense parenteral solutions can promote microbial biofilm growth on the catheter surface, which may seed subsequent catheter-related bloodstream infection (CR-BSI). In fact, receipt of parenteral nutrition is an established risk factor for CR-BSI caused by the polymorphic fungal pathogen Candida albicans. New intravenous fat emulsions (IFEs) have gained market share and IFEs containing capric acid (mixed-oil [MO] IFE) compared with those without (soybean-oil [SO] IFE) impair the C. albicans yeast-to-hypha switch­a trait strongly associated with pathogenicity and biofilm formation. In this study, we found that MO-IFE and capric acid reduced expression of a transcriptional regulator involved in hyphal extension (UME6) and down-regulated genes involved in cell partitioning (HGC1). Overexpression of these genes enabled hyphal growth in MO-IFE. Secondly, we sought to determine whether the type of IFE administered was associated with the clinical incidence of CR-BSIs caused by C. albicans or other common non-albicans Candida species. There was a nonsignificant numerical reduction in C. albicans infections in patients administered MO-IFE compared with SO-IFE. Collectively, this work shows that IFEs differentially affect Candida biology with potential infectious consequences for the patient.

Comparison of Two Lipid Emulsions on the Incidence of Parenteral Nutrition Associated Cholestasis in Neonates.

OBJECTIVE: Lipid emulsion contributes to parenteral nutrition associated cholestasis (PNAC). For decades, soybean oil-based intravenous lipid emulsion (SO-ILE) was the predominant product. Recently, a multicomponent lipid emulsion containing soybean oil, medium-chain triglycerides, olive oil and fish oil (SMOF-ILE) has been used off-label in neonatal care. This study evaluates the incidence of PNAC in neonates who received SMOF-ILE or SO-ILE. METHODS: This was a retrospective review of neonates who received SMOF-ILE or SO-ILE for at least 14 days. Patients receiving SMOF-ILE were matched based on gestational age (GA) and birth weight to a historical cohort receiving SO-ILE. The primary outcomes were the incidences of PNAC among all patients and patients without intestinal failure. The secondary outcomes were clinical outcomes and incidence of PNAC stratified by GA. Clinical outcomes included liver function tests, growth parameters, and development of retinopathy of prematurity and intraventricular hemorrhage. RESULTS: Forty-three neonates who received SMOF-ILE were matched to 43 neonates who received SOILE. There were no significant differences in baseline characteristics. The incidence of PNAC in the total population was 12% in the SMOF-ILE cohort and 23% in the SO-ILE cohort (p = 0.26). The lipid dosage of SMOF-ILE was significantly higher at time of peak direct serum bilirubin concentration compared with SO-ILE cohort (p = 0.05). Clinically significant differences were noted in laboratory endpoints in several subgroups. CONCLUSIONS: There was no significant difference in the incidence of PNAC among neonates in a SMOFILE cohort compared with a historical SO-ILE cohort.

Mechanisms underlying lipid emulsion resuscitation for drug toxicity: a narrative review.

Currently, lipid emulsion (LE) is widely used to treat local anesthetic systemic toxicity (LAST). LE also ameliorates intractable cardiovascular collapse caused by lipid-soluble non-local anesthetic drug toxicity. This review aims to provide the underlying mechanism of LE resuscitation in drug toxicity (including LAST) and a detailed description of LE treatment and to discuss further research directions. We searched for relevant articles using the following keywords: "local anesthetic systemic toxicity or LAST or toxicity or intoxication or poisoning" and "Intralipid or lipid emulsion". The underlying mechanisms of LE treatment can be classified into indirect and direct effects. One indirect effect known as the lipid shuttle is a commonly accepted mechanism of LE treatment. The lipid shuttle involves the absorption of highly lipid-soluble drugs (e.g., bupivacaine) from the heart and brain through the lipid phase, which are then delivered to the muscle, adipose tissue, and liver for storage and detoxification. The direct effects include inotropic effects, fatty acid supply, attenuation of mitochondrial dysfunction, glycogen synthase kinase-3ß phosphorylation, and inhibition of nitric oxide. These mechanisms appear to act synergistically to treat drug toxicity. The recommended protocol for LE treatment of LAST is as follows: a bolus administration of 20% LE at 1.5 ml/kg over 2-3 min followed by 20% LE at 0.25 ml/kg/min. LAST most commonly occurs after intravenous administration of local anesthetics. However, non-local anesthetic drugs that cause drug toxicity are orally administered. Further studies are needed to determine the optimal dosing schedule of LE treatment for non-local anesthetic drug toxicity.

Caracterización del uso de emulsiones lipídicas como terapia antidotal en intoxicaciones diferentes a anestésicos locales en un centro de alta complejidad en Medellín / Characterization of the use of lipid emulsions as antidotal therapy in intoxications other than local anesthetics in a high complexity center in Medellin

Introducción. Las emulsiones lipídicas intravenosas (ELI) son unas emulsiones grasas no tóxicas con fosfolípidos, actualmente aprobadas para su uso en el tratamiento de intoxicaciones, específicamente en las producidas por anestésicos locales. El propósito de este estudio es la caracterización del uso de ELI en pacientes mayores de 18 años, que presentaron intoxicación por sustancias y medicamentos diferentes a anestésicos locales, en un hospital de alta complejidad de la ciudad de Medellín, durante el periodo comprendido entre 2015 y 2020. Metodología. Se realizó un estudio descriptivo, retrospectivo, de casos que recibieron ELI como tratamiento para su intoxicación. Se hizo revisión de las historias clínicas de la población objeto de estudio. Se recolectó información acerca de variables sociodemográficas, clínicas y paraclínicas, y de atención. Se hizo análisis univariado de las variables de interés. Resultados. Del total de 1.966 intoxicaciones, se incluyeron 51 (2,6 %) casos de intoxicación por sustancias y medicamentos diferentes a anestésicos locales, que recibieron la terapia con ELI entre 2015 y 2020. La mediana de edad de los participantes fue de 27 años. Un 74,5 % de los participantes presentó intoxicación por medicamentos. El promedio de la dosis de ELI recibida fue de 1.036 mL en 24 horas, dosis inferior a la calculada por kilo de peso que debían recibir, de 1.149 mL en promedio. Un 86,3 % (n=44) de los casos presentaron neurotoxicidad, y 76,5 % (n=39) presentaron cardiotoxicidad. La neurotoxicidad mejoró en el 34,7 % y la cardiotoxicidad en el 59,1 % de los individuos que recibieron terapia con ELI. Conclusión. La aplicación de las ELI se hizo en personas en su mayoría intoxicadas por antipsicóticos, hombres, jóvenes; menos de la mitad tenía compromiso de la ventilación, y hubo mejoría en la cardiotoxicidad y neurotoxicidad. Hubo una diferencia entre la dosis recibida y la que debían recibir ajustada por el peso

Introduction. Intravenous lipid emulsions (IVLE) are non-toxic fatty emulsions with phospholipids, currently approved for use in the treatment of poisoning, specifically those produced by local anesthetics. The purpose of this study is to characterize the use of IVLE in patients over 18 years of age, who presented intoxication by substances and medications other than local anesthetics, in a high complexity hospital in the city of Medellín, during the period between 2015 and 2020. Methodology. A retrospective descriptive study was carried out on cases that received IVLE as a treatment for their poisoning. The clinical records of the study population were reviewed. Information was collected about sociodemographic, clinical and paraclinical variables, and care. Univariate analysis of the variables of interest was performed. Results. Of the total of 1,966 poisonings, 51 (2.6%) cases caused by substances and medications other than local anesthetics, received ELI therapy between 2015 and 2020 and were included in the study. The median age of the participants was 27 years. 74.5% of the participants presented drug poisoning. The average IVLE dose received was 1,036 mL in 24 hours, a lower dose than the one calculated per kilo of weight, which had been on average 1,149 mL. 86.3% (n=44) of the cases presented neurotoxicity, and 76.5% (n=39) presented cardiotoxicity. Neurotoxicity improved in 34.7% and cardiotoxicity in 59.1% of individuals receiving ELI therapy. Conclusion. The application of IVLE was made in people mostly poisoned by antipsychotics, men, young people, less than half had compromised ventilation, and there was improvement in cardiotoxicity and neurotoxicity. There was a difference between the dose received and the one they should have received adjusted for weight

Comparison of catheter-related bloodstream infection rates in pediatric patients receiving parenteral nutrition with soybean oil-based intravenous fat emulsion versus a mixed oil fat emulsion.

STUDY OBJECTIVE: To compare rates of catheter-related bloodstream infections (CR-BSI) in pediatric patients who received parenteral nutrition (PN) with either soybean oil-based intravenous fat emulsion (SO-IFE) or mixed oil-IFE (MO-IFE). We hypothesized that the use of MO-IFE would be independently associated with reduced infection rates compared with SO-IFE. DESIGN: Retrospective cohort study. SETTING: Tertiary referral children's hospital and its associated gastrointestinal rehabilitation clinic (01 January, 2015-31 July, 2019). PATIENTS: Days of IFE exposure were counted for patients aged <18 years on IFE initiated during the review period, who had a central venous catheter (CVC) placed for PN administration, received IFE at least three times weekly, and for at least 7 days. MEASUREMENTS: The primary outcome included total and categorical CR-BSI rates expressed as the average with standard error (SE) number of infections per 1000 fat emulsion days. The following categories were specified: Candida albicans, non-albicans Candida spp., coagulase-negative Staphylococcus (CoNS), Enterobacterales, methicillin-resistant S. aureus, methicillin-susceptible S. aureus, and Pseudomonadales. Average infection rate comparisons were quantified as incidence rate ratios (IRR) using generalized linear mixed modeling with a Poisson distribution. MAIN RESULTS: Seven hundred and forty-three SO-IFE and 450 MO-IFE exposures were reviewed from 1131 patients, totaling 37,599 and 19,796 days of therapy, respectively. From those found significantly different, the average rate of infections with CoNS was 3.58 (SE 0.5)/1000 days of SO-IFE and 1.39 (SE 0.45)/1000 days of MO-IFE (IRR [95% confidence interval, CI]: 0.27 [0.16-0.46]; p < 0.01). Total average rates of infection were 7.33 (SE 0.76)/1000 days of SO-IFE and 4.52 (SE 0.75)/1000 days of MO-IFE (IRR [95% CI]: 0.60 [0.44-0.81]; p < 0.01). Other factors associated with higher infection rates include female gender, neonatal age, and inpatient-only IFE exposure. CONCLUSIONS: Receipt of MO-IFE was associated with lower rates of CoNS and total CR-BSIs compared with SO-IFE in pediatric patients. These findings could have major implications on IFE selection for pediatric patients receiving PN.

Pilot analysis of intravenous lipid infusion role in COVID-19 mortality.

INTRODUCTION: How to reduce the fatality of coronavirus disease (COVID-19) is still challenging. A proper nutritional support has been always a matter of attention in critically ill patients. MATERIAL AND METHODS: We assessed COVID-19 patients who had received intralipid infusion due to medical indications and compared them with those who did not receive it regarding fatality rate and prognosis. As a part of a data mining project using data of observational cohort of COVID-19 patients hospitalized in the educational centers of Iran University of Medical Sciences, Tehran, Iran, an inferential case series was performed. A total of 19 patients with SARS-CoV-2 infection were selected from the cohort. Briefly, 13 patients survived and 6 patients died, and 12 patients were admitted in intensive care unit (ICU). All dead cases were ICU admitted. The association of intralipid infusion and survival rate was examined using Fisher exact test. No association was observed between intralipid infusion and survival. CONCLUSIONS: No significant protecting effect was observed for patients who received intralipid for medical indications. Since intralipid was administered according to medical indications, surviving of all the non-ICU admitted patients despite having underlying diseases was remarkable. Despite the fact, due to several bias factors that could not be controlled in such a retrospective study, the results might be accidental. We suggest to assess such an effect retrospectively in other centers as well.

Uso de emulsiones lipídicas en el tratamiento exitoso de un caso de intoxicación por difenhidramina / Use of lipid emulsions in the successful treatment of a case of diphenhydramine poisoning / Uso de emulsões lipídicas no sucesso do tratamento de um caso de intoxicação por difenidramina

La difenhidramina tiene efectos antihistamínico anti-H1 específico y antimuscarínico que pueden ocasionar un desenlace fatal según la dosis total ingerida. Se reporta un caso de intoxicación por difenhidramina tratado de forma exitosa con emulsiones lipídicas a pesar de ingesta de dosis letal. Se presenta el caso de un paciente de 19 años que ingresó por intoxicación por difenhidramina a dosis de 25 mg/kg (1.5 g) después del tiempo de descontaminación, con toxidrome anticolinérgico, con neurotoxicidad, cardiotoxicidad (QRS y QT prolongados) y sin respuesta al enfoque inicial, se iniciaron emulsiones lipídicas y, a su vez, se logró alta temprana por evolución clínica favorable y resolución de la prolongación del intervalo QTc y del cuadro anticolinérgico. La emulsión lipídica es una opción terapéutica para disminuir la morbimortalidad y la estancia hospitalaria por contrarrestar la cardiotoxicidad y neurotoxicidad producidas por moléculas lipofílicas como la difenhidramina.

Diphenhydramine has specific anti-H1 antihistamine and antimuscarinic effects that can be fatal depending on the total dose ingested. A case of diphenhydramine poisoning successfully treated with lipid emulsions despite ingesting a lethal dose is presented. We present the case of a 19-year-old patient who was admitted for diphenhydramine intoxication at a dose of 25 mg/kg (1.5 g) after the decontamination time, with anticholinergic toxidrome, with neurotoxicity, cardiotoxicity (prolonged QRS and QT) and without response to initial approach. Lipid emulsions were started and, in turn, early discharge was achieved due to favorable clinical evolution and resolution of the prolongation of the QTc interval and the anticholinergic symptoms. Lipid emulsion is a therapeutic option to reduce morbidity and mortality and hospital stay by counteracting cardiotoxicity and neurotoxicity produced by lipophilic molecules such as diphenhydramine.

A difenidramina tem efeitos anti-histamínicos e antimuscarínicos anti-H1 específicos que podem ser fatais dependendo da dose total ingerida. Relata-se um caso de intoxicação por difenidramina tratada com sucesso com emulsões lipídicas apesar da ingestão de uma dose letal. Apresentamos o caso de uma paciente de 19 anos que foi internada por intoxicação por difenidramina na dose de 25 mg/kg (1,5 g) após o tempo de des-contaminação, com toxina anticolinérgica, neurotoxicidade, cardiotoxicidade (QS e QT prolongados) e sem resposta na abordagem inicial, iniciaram-se emulsões lipídicas e, por sua vez, obteve-se alta precoce devido à evolução clínica favorável e resolução do prolongamento do intervalo QTc e dos sintomas anticolinérgicos. A emulsão lipídica é uma opção terapêutica para reduzir a morbimortalidade e o tempo de internação por neutralizar a cardiotoxicidade e a neurotoxicidade produzidas por moléculas lipofílicas como a difenidramina.

Validity of Random Triglyceride Levels in Infants Receiving Parenteral Nutrition.

Background: Intravenous lipid emulsions (IL) are an important part of parenteral nutrition (PN) to meet essential fatty acid (EFA) requirements and metabolic demands of neonates and preterm infants. Some critically-ill neonates may not metabolize IL effectively which can lead to hypertriglyceridemia. Risks associated with this include increased pulmonary vascular resistance, displaced bilirubins, and platelet or macrophage dysfunction. Serum triglyceride (TG) concentration is used as a marker for lipid tolerance and predictor of potential complications involved with IL administration, but the clinical significance of this is still debated. Management of TG levels with regard to timing of laboratory tests, the ideal goal range, and duration of infusion of IL varies across institutions and is not standardized. Methods: Single-center, retrospective study of newborn infants receiving parenteral nutrition (PN). Fasting and non-fasting TG levels were drawn during the same lipid infusion of 2-3g/kg/day. The primary outcome was the difference between fasting and non-fasting TG levels. Statistical assessment of continuous data was done with student t-test and nominal data was evaluated using X2-test and logistic regression. Results: Forty infants were included with mean gestational age at birth of 29.5 ± 3.4 weeks and mean birth weight of 1.3 ± 0.5 kg. Mean time between lab draws while on same IL dose was 11.6 ± 0.2 h with resulting mean fasting and non-fasting (random) TG levels 82 ± 40 mg/dL (95% CI 68.4, 97.6) and 101 ± 40 mg/dL (95% CI 88.5, 115.8), respectively. Mean difference between TG levels during lipid-free interval and during infusion was -18.6 ± 51.2 mg/dL (95% CI -35.0, -2.3; p = 0.03). Conclusion: We concluded there is no difference in the management of IL, when TG level was drawn randomly or as fasting sample. Obtaining TG level during routine lab draws is appropriate. We extrapolated that the administration of IL over 24 h will not interfere with TG level.

Clinical application of fish-oil intravenous lipid emulsion in adult home parenteral nutrition patients.

BACKGROUND: High-ω-6 polyunsaturated fatty acids (PUFAs) are noted to contribute to development of intestinal failure-associated liver disease (IFALD) in home parenteral nutrition (HPN). Fish oil (FO) has been added to latest generation of lipid injectable emulsion (ILE) to increase ω-3:ω-6 PUFA ratio; however, appropriate dose of FO to treat IFALD is unknown. METHODS: After approval of exclusive FO ILE in the US for pediatric patients, we noted 2 adult patients with ongoing IFALD despite transition to mixed-oil (MO) ILE. They were transitioned to off-label FO ILE after review of literature regarding use of FO ILE in adult HPN patients was conducted to guide management. RESULTS: The first case involves a 40-year-old female receiving HPN with IFALD refractory to MO ILE. MO ILE (with 15% FO) was provided at 50 g/d for 3 d/wk and combined with FO ILE at 50 g/d for 4 d/wk. This combination resulted in improvement in liver studies and allowed for decrease in dextrose calories. The second case involves a 49-year-old male receiving HPN (secondary to complications of necrotizing pancreatitis) who developed IFALD. FO ILE was used as the sole source of lipids and led to improvement in liver function tests. No evidence of essential fatty acid deficiency was found in either case. CONCLUSIONS: Current case presentations and review of literature support the use of FO ILE to increase ω-3 PUFAs in patients with IFALD refractory to MO ILE. Additional research is necessary to delineate the dose of FO ILE necessary to achieve benefit.

Lipid Emulsion Therapies and Type 1 Hypersensitivity Reactions: Risk Assessment and Management.

Over the past decades, awareness and attention given to food allergies has extended further into the realm of pharmacotherapy. Despite the presence of similar ingredients, different intravenous lipid emulsion (ILE)-based medication products have a wide variety of warnings and contraindications for patients with food allergies. Only limited literature is available to guide clinicians in making appropriate medication therapy adjustments to reduce the risk of hypersensitivity reactions in atopic patient populations. Therefore, the authors sought to develop a comprehensive review of potential risk factors or approaches for management of patients with atopic history and need for ILE therapy. Through thorough review of available literature published worldwide, a description of potential contraindications, risk factors, and evaluation methods is presented. Although the current state of knowledge remains relatively poor, this review aims to provide clinicians a better understanding of which risk factors related to the development of hypersensitivity reactions are relevant to lipid emulsion products and how to best manage patients who may be at risk for severe reaction based on their history. Evaluating personal atopic history is essential to the development of an appropriate risk classification system and approaching an individual's therapeutic options. By applying this assessment to local populations, providers should be able to develop an institutional guideline for screening and minimizing risk of substantial hypersensitivity reactions. Finally, a brief review of methods for managing type 1 hypersensitivity reactions is provided in the event that a breakthrough reaction does occur.

Update on the Use of Filters for Parenteral Nutrition: An ASPEN Position Paper.

Intravenous in-line filters play a critical role in promoting patient safety during parenteral nutrition (PN) administration. Guidelines for using filters for PN have been issued by a number of professional organizations and manufacturers of PN components. Yet despite this guidance, filter use remains controversial. Recent changes in recommendations for filtering lipid injectable emulsions have added to confusion and created considerable variation in practice. This Position Paper aims to review past guidance regarding the filtration of PN, examine the clinical consequences of infusing particulate matter, discuss the challenges and issues related to filtration, and clarify the American Society for Parenteral and Enteral Nutrition (ASPEN) recommendations for the use of filters for PN administration. This paper was approved by the ASPEN Board of Directors.

Phytosterolaemia associated with parenteral nutrition administration in adult patients.

Vegetable lipid emulsions (LE) contain non-declared phytosterols (PS). We aimed to determine PS content depending on the brand and LE batch, and in adult hospitalised patients treated with parenteral nutrition (PN), to establish the association between plasma and administered PS. Part I was the LE study: totals and fractions of PS in three to four non-consecutive batches from six LE were analysed. Part II was the patient study: patients with at least 7 previous days of PN with 0·8 g/kg per d of an olive/soyabean (O/S) LE were randomised (day 0) 1:1 to O/S or 100 % fish oil (FO) at a dose of 0·4 g/kg per d for 7 d (day 7). Plasma PS, its fractions, total cholesterol on days 0 and 7, their clearance and their association with PS administered by LE were studied. In part I, LE study: differences were found in the total PS, their fractions and cholesterol among different LE brands and batches. Exclusive soyabean LE had the highest content of PS (422·36 (sd 130·46) µg/ml). In part II, patient study: nineteen patients were included. In the O/S group, PS levels were maintained (1·11 (sd 6·98) µg/ml) from day 0 to 7, while in the FO group, significant decreases were seen in total PS (-6·21 (sd 4·73) µg/ml) and their fractions, except for campesterol and stigmasterol. Plasma PS on day 7 were significantly associated with PS administered (R2 0·443). PS content in different LE brands had great variability. PS administered during PN resulted in accumulation and could be prevented with the exclusive administration of FO LE.

Case Report: Transitioning to a Mixed-Oil Intravenous Lipid Emulsion in an Adult Patient Receiving Home Parenteral Nutrition.

A potential risk of long-term parenteral nutrition (PN) is intestinal failure-associated liver disease (IFALD). One recommendation for mitigating risk is limiting the fat dose to reduce the harmful effects of the ω-6 fatty acids, which are the main ingredient in traditional fats. SMOFlipid (SMOF) (Kabi-Fresenius, Bad Homburg, Germany) is a combination of soybean oil, medium-chain triglycerides, olive oil, and fish oil emulsion. This fat source may alleviate the risk of IFALD and improve liver function tests. A patient with a long history of PN reliance and IFALD is presented in this case report. After 4 months on SMOF, total and direct bilirubin levels improved.

Lipid emulsion, but not propofol, induces skeletal muscle damage and lipid peroxidation.

PURPOSE: Prolonged propofol infusion induces skeletal muscle damage. However, it is well known that the lipid emulsion that is the solvent of propofol causes various types of tissue damage via lipid peroxidation, and that propofol, conversely, has an anti-lipid peroxidative effect. The purpose of this study was to determine whether propofol or the lipid emulsion is the cause of muscle damage following prolonged administration. METHODS: Rats were divided into four groups: NI group (no intervention), Cath group (venous catheter insertion only), Prop group (1% propofol (Maruishi) intravenous infusion at 10 mg/kg/h), and Lipid group (10% Lipofundin® intravenous infusion at 100 mg/kg/h) (n = 10, each group). 1% Propofol (Maruishi) or Lipofundin was infused at 1 mL/kg/h for 72 h. The solvent of 1% propofol (Maruishi) is a 10% lipid emulsion. Lipofundin consists of 50% long-chain triacylglycerols and 50% medium-chain triacylglycerols, similar to the propofol solvent. Plasma concentrations of creatine kinase and myoglobin, superoxide production level, and 4-hydroxynonenal and malondialdehyde expression in the gastrocnemius muscle were evaluated 72 h after the interventions. RESULTS: Plasma concentrations of creatine kinase and myoglobin in the Lipid group were significantly higher than those in the other three groups. The superoxide production level, and 4-hydroxynonenal and malondialdehyde expression in the Lipid group were also significantly higher than in the other three groups. CONCLUSION: Lipofundin induces skeletal muscle damage via lipid peroxidation, and 1% propofol (Maruishi) conversely suppresses the muscle damage via antioxidant effects.

Fish oil-based injectable lipid emulsions containing medium-chain triglycerides or added α-tocopherol offer anti-inflammatory benefits in a murine model of parenteral nutrition-induced liver injury.

BACKGROUND: Fish oil (FO) intravenous lipid emulsions (ILEs) are used as a monotherapy to treat parenteral nutrition (PN)-associated liver disease and provide essential fatty acids (EFAs) needed to sustain growth and prevent EFA deficiency (EFAD). Studies have suggested that medium-chain triglycerides (MCTs) and α-tocopherol have anti-inflammatory properties. OBJECTIVE: The purpose of this study was to test whether FO-ILEs containing MCTs and/or additional α-tocopherol decrease the inflammatory response to an endotoxin challenge compared with FO-ILE alone and preserve the ability to prevent PN-induced liver injury in mice. METHODS: A murine model of PN-induced hepatosteatosis was used to compare the effects of ILEs formulated in the laboratory containing varying ratios of FO and MCTs, and subsequently FO- and 50:50 FO:MCT-ILE plus 500 mg/L α-tocopherol (FO + AT and 50:50 + AT, respectively). C57BL/6 mice receiving unpurified diet (UPD), PN-equivalent diet (PN) + saline, and PN + soybean oil (SO)-ILE served as controls. After 19 d, mice received an intraperitoneal saline or endotoxin challenge 4 h before being killed. Serum and livers were harvested for histologic analysis, fatty acid profiling, and measurement of systemic inflammatory markers (tumor necrosis factor-α, interleukin-6). RESULTS: All ILEs were well tolerated and prevented biochemical EFAD. Livers of mice that received saline and SO developed steatosis. Mice that received 30:70 FO:MCT developed mild hepatosteatosis. All other FO-containing ILEs preserved normal hepatic architecture. Mice that received FO- or SO-ILE had significantly elevated systemic inflammatory markers after endotoxin challenge compared with UPD-fed controls, whereas 50:50 FO:MCT, 30:70 FO:MCT, FO + AT, and 50:50 + AT groups had significantly lower inflammatory markers similar to those seen in UPD-fed controls. CONCLUSIONS: Mixed FO/MCT and the addition of α-tocopherol to FO improved the inflammatory response to endotoxin challenge compared with FO-ILE alone while still preventing PN-induced liver injury and EFAD in mice. There was no synergistic relation between α-tocopherol and MCTs.

A quality improvement program with nutrition therapy: restriction of lipid emulsions in cardiac surgical patients.

BACKGROUND: To evaluate the effect of restriction of soybean-based intravenous fat emulsions (IVFEs) in clinical outcomes in cardiac surgical patients. METHODS: This was a before-and-after interventional study comparing the clinical outcomes regarding the intervention of IVFEs restriction. Before August 2015, parenteral nutrition (PN) using a soy-based lipid emulsion was routinely implemented if patients failed to meet >60% of energy requirements in 48 h post cardiac surgery (Period A). Beginning in August 2015, a lipid restriction strategy was implemented in our cardiac surgery intensive care unit (CSICU) unless enteral route could not be established within 7 days (Period B). The ICU and hospital mortality, nosocomial infections during ICU stay, length of ICU and hospital stay, ICU and hospital cost, mechanical ventilation time and postoperative complications were compared between two periods. RESULTS: A total of 761 patients (370 patients in Period A and 391 patients in Period B) were ultimately enrolled in this study. There were no significant differences in demographic characteristics and intraoperative and postoperative parameters between the two groups. After the implementation of IVFEs restriction, the overall ICU mortality and hospital mortality were similar between two groups. Nosocomial infection rate was significantly reduced (3.84% vs. 7.84%, P=0.021). The mean length of ICU stay (3.15 vs. 3.74 days, P<0.001) and hospital stay (12.14 vs. 13.24 days, P<0.001) were significantly lower. The mean in-hospital cost (133,368 vs. 139,383 Yuan, P=0.037) was found to be reduced after implementation of IVFEs restriction. The duration of mechanical ventilation was shorter in the latter period (35.23±10.43 vs. 47.63±12.54 hours, P=0.011). IVFEs restriction was also associated with reduced cholestasis (2.81% vs. 6.76%, P=0.013). CONCLUSIONS: The implementation of soybean-based IVFEs restriction in cardiac surgical patients was associated with reduced postoperative nosocomial infection rate. It also led to reductions in the length of ICU/hospital stay, hospital costs and mechanical ventilation time and a lower incidence of cholestasis. Further studies are required to validate the conclusions.

Sudden Deaths of Neonates Receiving Intravenous Infusion of Lipid Emulsion Contaminated with Citrobacter freundii.

At an intensive care unit, four neonates died consecutively within 80 minutes. Citrobacter freundii was isolated from blood samples of the 4 patients. It was also cultured from the leftover SMOFlipid that had been infused intravenously into the patients. In this in vitro study, we evaluated the bacterial growth kinetics and change in size of fat globules in SMOFlipid contaminated with C. freundii. Following the growth of bacteria, pH of SMOFlipid decreased to < 6, and the number of fat globules larger than 5 µm increased. Pulmonary fat embolism is proposed as a possible cause of the sudden deaths as well as fulminant sepsis.

Physicochemical Stability and Sterility of Standard Parenteral Nutrition Solutions and Simulated Y-Site Admixtures for Neonates.

BACKGROUND: Parenteral nutrition (PN) is frequently needed in neonatal intensive care. The use of standard PN has emerged as an easy-to-prescribe approach that allows one to have on-site, ready-to-use PN. The aim of this study was to test the physicochemical stability and sterility of 2 specific PN solutions as well as simulate Y-site compatibility with lipid injectable emulsions (ILE). METHODS: Our study considered 2 standard ILE-free PN solutions according to neonatal weight. These solutions were prepared in duplicate and stored at 4°C. The following physicochemical parameters were tested: visual alterations, turbidity, pH, osmolarity, and calcium concentration. Sterility was assessed by means of agar blood culture and glucose concentration determination. In addition, we assessed the stability of simulated Y-site admixtures. For each standard ILE-free PN solution, 2 3-in-1 PN admixtures were designed, considering extreme values of fluid requirements (50 and 150 ml/kg/d) and a fat supply of 2 g/kg/24 h. The physicochemical parameters tested were phase separation and fat mean droplet size distribution. RESULTS: No alterations were detected by visual inspection. Calcium concentrations, turbidity, pH, and osmolarity values remained stable in all the determinations. All agar blood cultures were negative and glucose concentration was constant over time. Physical stability of simulated Y-site admixtures was considered acceptable as mean droplet size distribution remained below 500 nm in all the emulsions. CONCLUSION: The 2 tested standard ILE-free PN solutions for neonates are physicochemically stable and sterile for 31 days under refrigeration (4°C). These solutions are also stable in case of Y-site administration with ILE at the conditions tested.

Long-Term Use of Mixed-Oil Lipid Emulsion in Adult Home Parenteral Nutrition Patients: A Case Series.

BACKGROUND: Despite providing significant benefits, home parenteral nutrition (HPN) can be associated with complications such as infections, intestinal failure-associated liver disease, and metabolic abnormalities. Soybean oil (SO)-based intravenous lipid emulsion (ILE) has been noted to contribute to some of these complications, leading to the development of alternative sources of ILE. Mixed-oil (MO) ILE has recently been approved for use in adults with short-term studies revealing a benefit over SO ILE. Currently there is a paucity of data regarding long-term use in the HPN population. METHODS: The current study reports our experience with MO ILE in 9 HPN patients. RESULTS: A total of 9 patients (3 women and 6 men) with average age of 48.1 ± 15.1 years and a median HPN use of 9.9 years (9.0 months-30.7 years) were transitioned from SO ILE to MO ILE as a result of intolerance. The 9 patients tolerated MO ILE well for 140.7 ± 29.7 days. The percentage of calories provided through ILE increased from 7.6 ± 6.5% to 18.4 ± 8.2% (P = .003), whereas the dextrose decreased from 66.9 ± 8.4% to 56.9 ± 5.5% (P = .0007). Although statistical significance was not reached, there was a trend toward improvement in alkaline phosphatase from 138.0 (52-884) to 106 (47-512; P = .09). CONCLUSION: MO ILE was well tolerated in this small cohort and led to improvement in the macronutrient composition of HPN while providing a trend toward improvement in liver studies. These results are promising; however, additional randomized control trials are needed to delineate the true benefit.