Fat overload syndrome following intravenous lipid emulsion administration as antidote in suspected anesthetic intoxication: insights from a clinical and forensic case experience.

Abstract: Medication errors pose significant risks to patients' health, representing a relevant social and economic issue for the healthcare system. This study focuses on the life-threatening consequences of an overdose of intravenous lipid emulsion (ILE), used as an antidote for suspected bupivacaine intoxication in a young woman undergoing hip surgery. Shortly after administration of the local anesthetic, the woman experienced cardiac arrest and was admitted to the intensive care unit with severe respiratory failure, metabolic acidosis and deep coma. Despite medical intervention, her condition worsened, leading the medical team to administer ILE for suspected bupivacaine intoxication. The patient's condition did not improve and ultimately resulted in death. The autopsy highlighted a widespread presence of oily material in the vascular system, compatible with an overdose of ILE. At a checking, medical records reported a dose of ILE that was 4-fold higher than the recommended dose in this off-label indication. This case report highlights the important need for healthcare professionals to understand the risks of using ILE as an antidote. Adequate monitoring of these "sentinel events" and their critical evaluation can lead to the implementation of specific clinical risk management protocols to reduce the risk for the patient and contain healthcare costs.

External validation and updating of the infusion rate individualization of soybean oil-based intravenous lipid emulsion: A descriptive cohort study.

BACKGROUND: Safe and efficient provision of intravenous lipid emulsion (ILE) requires a strategy to individualize infusion rates. Estimating the maximum acceptable infusion rate (MaxInfRate) of soybean oil-based ILE (SO-ILE) in individuals by using a triglyceride (TG) kinetic model was reported to be feasible. In this study, we aimed to externally validate and, if needed, update the MaxInfRate estimation. METHODS: The maximum TG concentration (TGmax) in patients receiving SO-ILE at MaxInfRate was evaluated to determine if it met the definition of being <400 mg/dl for 90th percentile of patients. The TG kinetic model was evaluated through prediction performance checks and was subsequently updated using the data set of both the previous model development and present validation studies. RESULTS: Out of 83 patients, 74 had TGmax <400 mg/dl, corresponding to a probability of 89.2% (95% CI, 81.9%-95.2%), and the 90th percentile of TGmax was 400 mg/dl (95% CI, 328-490 mg/dl), closely aligned with the theoretical values. However, the individual TGmax values were biased by the infusion rate because the covariate effects were overestimated in the TG kinetic model, requiring a minor revision. The updated MaxInfRate with the combined data set showed unbiased and more accurate predictions. CONCLUSION: The MaxInfRate was validated in external inpatients and updated with all available data. MaxInfRate estimation for individuals could be an option for the safe and efficient provision of SO-ILE.

Hyperuricemia and intravenous fat emulsion are risk factors for gout flares during active gastrointestinal bleeding: a case control study.

OBJECTIVE: It is well-established that patients with a history of gout are more susceptible to experiencing gastrointestinal bleeding. Gout flare during active gastrointestinal bleeding poses a significant challenge due to the gastrointestinal side effects of anti-inflammatory therapy. This study sought to investigate the risk factors associated with gout flares during episodes of gastrointestinal bleeding. METHODS: We conducted a retrospective observational study involving 94 patients who experienced active gastrointestinal bleeding and had a history of gout. This study was conducted at Jinhua Municipal Central Hospital from January 2019 to October 2022. We collected and recorded demographic information and clinical characteristics. RESULTS: Among the gout flare patients, hyperuricemia and intravenous fat emulsion therapy were more prevalent compared to those who remained stable (81.6% vs. 57.8% and 46.9% vs. 24.4%, p < 0.05). Multivariate logistic regression analysis revealed that both hyperuricemia (odds ratio 2.741, 95% CI 1.014-7.413, p = 0.047) and intravenous fat emulsion therapy (odds ratio 2.645, 95% CI 1.046-6.686, p = 0.040) were independent predictors of gout flares. Furthermore, gout attacks occurred sooner in patients receiving intravenous fat emulsion therapy compared to those not receiving it (median: 4 days (interquartile range: 2) vs. median: 5 days (interquartile range: 2.25), p = 0.049). CONCLUSION: Our study revealed a high incidence of gout flares during episodes of active gastrointestinal bleeding, with patients undergoing intravenous fat emulsion therapy and those with hyperuricemia being at increased risk.

The effects of parenteral fish oil on neurodevelopment in preterm infants: A narrative review.

OBJECTIVE: This narrative review aimed to summarize studies assessing the effects of parenteral fish oil on neurodevelopment in preterm infants. METHODS: PubMed was searched (July 1985 to October 2023). We reviewed randomized controlled trials, and observational studies assessing intravenous lipid emulsion with fish oil in preterm infants (born less than 37 weeks' gestation), that reported long-term neurodevelopmental outcomes. RESULTS: We identified four publications relating to three randomized controlled trials in addition to four cohort studies. Study designs and outcomes were heterogenous and precluded meta-analyses. Results of trials were null for a selection of neurodevelopmental outcomes, however possible benefits of parenteral fish oil supplementation for neurodevelopment was reported in three cohort studies. Certainty of the evidence is hindered by methodological limitations of available trials and observational studies. CONCLUSIONS: Further research is required to firmly establish the effects of parenteral fish oil on preterm neurodevelopment.

Clinical effects and adverse effects of intravenous lipid emulsion treatment in dogs and cats with suspected poisoning.

This retrospective study aimed to evaluate the effects on the clinical signs of poisoning and adverse effects of intravenous lipid emulsion treatment in 82 animals (dogs and cats) with suspected poisonings over 18 months. Physical examination parameters and state of consciousness were documented every hour after the intravenous administration of a bolus of 2 ml/kg and 0.25 ml/kg/min over 60 minutes of a 20% intravenous lipid emulsion. The modified Glasgow coma scale and laboratory findings (blood gas analysis, triglyceride, lactate) were evaluated initially and three hours after discontinuing intravenous lipid emulsion administration. A statistical evaluation of the occurrence of adverse effects and the development of laboratory values was performed. A decrease in respiratory rate in the second control (8-12 hours) after ILE was observed. Three hours after completing of the intravenous lipid emulsion, triglyceride concentration increased about 10 times (p <0.001). Venous carbon dioxide partial pressure, bicarbonate, base excess, as well as the electrolytes sodium, potassium and ionized calcium decreased significantly (p <0.001). Patients who experienced a worsening of the modified Glasgow coma scale had a higher increase in triglyceride concentrations (p = 0.041) and plasma lactate (p = 0.034) and a larger decrease in bicarbonate concentrations (p = 0.053) compared to others. About 54% (n = 44) of the patients showed adverse effects which could be attributed to the administration of intravenous lipid emulsion and may be associated with a higher triglyceride increase. All of them were completely reversible within 33 hours. Adverse effects associated with intravenous lipid emulsion therapy were observed in half of the patients and were associated with a higher increase in triglycerides.

Prevention of Parenteral Nutrition-associated Cholestasis Using Reduced Dose Soybean Lipid Emulsion: A Multicenter Randomized Trial.

INTRODUCTION: Reducing soybean lipid emulsion (SLE) dose may prevent parenteral nutrition-associated cholestasis (PNAC) but effects on growth and neurodevelopment are unknown. The purpose of this study was to evaluate the effect of reduced dose SLE on growth and neurodevelopment. METHODS: Surgical neonates at 4 centers were randomized to standard SLE (3 g/kg/day) or reduced SLE (1 g/kg/day) over a 12-week period. Bilirubin levels and growth parameters were measured baseline and weekly while on study. The effects of time and group on direct bilirubin and growth were evaluated with a linear mixed effects model. Neurodevelopmental outcomes were assessed at 12- and 24-months corrected gestational age. RESULTS: Twenty-one individuals were randomized (standard dose = 9, reduced dose = 12). Subjects in the reduced dose group had slower rates of direct bilirubin increase and overall levels decreased earlier than those in the standard dose group. There was a trend toward a faster direct bilirubin decrease in the reduced dose group (p = 0.07 at day 84). There were no differences in the rates of change in weight (p = 0.352 at day 84) or height Z-scores (p = 0.11 at day 84) between groups. One subject in the reduced dose group had abnormal neurodevelopmental testing at 24 months. CONCLUSIONS: Surgical neonates randomized to a reduced dose of SLE had improved trends in direct bilirubin levels without clinically significant differences in overall growth and neurodevelopment. TYPE OF STUDY: Randomized Controlled Trial. LEVEL OF EVIDENCE: II.

The Lipid Intensive Drug Therapy for Sepsis Phase II Pilot Clinical Trial.

OBJECTIVES: Low cholesterol levels in early sepsis patients are associated with mortality. We sought to test if IV lipid emulsion administration to sepsis patients with low cholesterol levels would prevent a decline or increase total cholesterol levels at 48 hours. DESIGN: Phase II, adaptive, randomized pilot clinical trial powered for 48 patients. SETTING: Emergency department or ICU of an academic medical center. PATIENTS: Sepsis patients (first 24 hr) with Sequential Organ Failure Assessment greater than or equal to 4 or shock. INTERVENTIONS: Patients meeting study criteria, including screening total cholesterol levels less than or equal to 100 mg/dL or high-density lipoprotein cholesterol (HDL-C) + low-density lipoprotein cholesterol (LDL-C) less than or equal to 70 mg/dL, were randomized to receive one of three doses of lipid emulsion administered twice in 48 hours or no drug (controls). The primary endpoint was a change in serum total cholesterol (48 hr - enrollment) between groups. MEASUREMENTS AND MAIN RESULTS: Forty-nine patients were enrolled and randomized. Two patients randomized to lipid emulsion were withdrawn before drug administration. Data for 24 control patients and 23 lipid emulsion patients were analyzed. The mean change in total cholesterol from enrollment to 48 hours was not different between groups and was 5 mg/dL ( sd 20) for lipid emulsion patients, and 2 mg/dL ( sd 18) for control patients ( p = 0.62). The mean changes in HDL-C and LDL-C were similar between groups. Mean change in triglycerides was elevated in lipid emulsion patients (61 mg/dL, sd 87) compared with controls (20 mg/dL, sd 70, p = 0.086). The 48-hour change in SOFA score was -2 (interquartile range [IQR] -4, -1) for control patients and -2 (IQR -3, 0) for lipid emulsion patients ( p = 0.46). CONCLUSIONS: Administration of IV lipid emulsion to early sepsis patients with low cholesterol levels did not influence change in cholesterol levels from enrollment to 48 hours.

Comparative effectiveness of two lipid emulsions in preventing retinopathy of prematurity in preterm infants requiring parenteral nutrition.

OBJECTIVES: The main aim was to compare the effects of 2 parenteral lipid emulsions on retinopathy of prematurity (ROP) incidence, severity, and need for treatment. Secondary aim was to compare the effect on weight gain in the first 6 weeks of life. METHODS: Single-center, observational, retrospective study analyzing preterm infants with a gestational age (GA) <31 weeks and a birth weight <1251 g born between April 2015 and December 2018. The infants' medical records were reviewed to collect clinical data. Parenteral nutrition (PN) details were obtained from the hospital pharmacy database. RESULTS: In total, 180 patients were included: 90 received ClinOleic® and 90 received SMOFlipid®. No significant differences were observed for the incidence of ROP (40% in ClinOleic® group and 41% in SMOFlipid® group, p=.88) or ROP requiring treatment (4% and 10%, respectively, p=.152). Weekly weight gain was similar in the 2 groups. CONCLUSIONS: This study showed no difference between the 2 groups regarding ROP, ROP requiring treatment, or weekly weight gain in the first 6 weeks of life.

Emulsiones lipídicas en la intoxicación por anestésicos locales y otros fármacos. Revisión sobre mecanismos de acción y recomendaciones de uso / Lipid emulsions in the treatment of intoxications by local anesthesics and other drugs. Review of mechanisms of action and recommendations for use

La emulsiones lipídicas intravenosas (ELI) se han utilizado ampliamente para el tratamiento de la intoxicación por anestésicos locales (AL) y se han propuesto como tratamiento de la intoxicación por otros fármacos. Sin embargo, el grado de evidencia de este tipo de terapias no es sólido, ya que proviene en su mayoría de casos clínicos. El objetivo de esta revisión narrativa es describir los mecanismos de acción propuestos para las ELI en la intoxicación por AL y otros fármacos, y evaluar los estudios recientes realizados en animales que sustentan las recomendaciones de su uso y la experiencia en humanos que apoyan el empleo de las ELI tanto en la intoxicación por AL como por otros fármacos. Para ello, se llevó a cabo una búsqueda en las bases de datos Embase, Medline, Cochrane y Google Scholar abarcando los artículos relevantes durante los últimos 10 años. En caso de intoxicación por AL, se recomienda aplicar los protocolos dictados por las guías internacionales, sabiendo que el grado de evidencia no es muy elevado. En la intoxicación por otros fármacos, las ELI están aconsejadas en situaciones graves inducidas por xenobióticos liposolubles que no responden al tratamiento estándar.(AU)

Intravenous lipid emulsions (ILEs) have been used widely for the treatment of local anesthetic (LA) poisoning and have been proposed as a treatment for intoxication by other drugs. However, the degree of evidence for this kind of therapy is not strong, as it comes mostly from clinical cases. The aim of this narrative review is to describe the proposed mechanisms of action for ILEs in poisoning by LA and other drugs and to evaluate recent studies in animals that support the recommendations for their use and the experience in humans that support the use of ILESs in both LA and other drug poisoning. For this purpose, a search was performed in the Embase, Medline and Google Scholar databases covering relevant articles over the last 10 years. In the case of AL poisoning, we recommend applying the protocols dictated by international guidelines, knowing that the degree of evidence is not very high. In poisoning by other drugs, ILEs are recommended in serious situations induced by liposoluble xenobiotics that do not respond to standard treatment.(AU)

The effects of different parenteral nutrition lipid formulations on clinical and laboratory endpoints in patients receiving home parenteral nutrition: A systematic review.

BACKGROUND: Home parenteral nutrition (HPN) is a life-sustaining therapy for individuals with intestinal failure in a community setting. It refers to the intravenous infusion of macronutrients, micronutrients, fluids and electrolytes. Routinely used HPN solutions contain different quantities of these components. Consequently, each HPN solution may have different impacts on metabolism, inflammation and oxidative stress. Long-term use of HPN can lead to a number of adverse health outcomes including the development of metabolic bone disease, intestinal failure associated liver disease and poor quality of life but whether, and how, the composition of HPN solutions contributes to these health sequelae is poorly understood. The aim of this study is to systematically review and evaluate the evidence for the differential effects of HPN solutions and to understand what features are associated with differences in clinical endpoints. METHODS: A systematic literature search was conducted between September and December 2020, and updated in July 2021 using the MEDLINE (Ovid), EMBASE, Scopus, and Web of Science databases. Studies were selected according to the following criteria (a) adult participants (>18 years old) dependent on HPN; (b) randomised controlled trials, prospective cohort and cross-sectional study designs; (c) primary research comparing two or more HPN solutions and (d) published in English language. Data were extracted and study quality assessed using Cochrane Collaboration's tools: Risk of Bias for Randomised Controlled Trials (RCTs); Risk of Bias in Non-Randomised Studies of Interventions; and the Newcastle Ottawa Scale for cross-sectional studies. RESULTS: Of the 5148 articles identified, seven RCTs, two prospective cohort and one cross-sectional study were included with a total of 295 participants. Studies varied in terms of duration (one to 60 months) and sample size (n = 5 to 88). Ten studies compared lipid emulsions (LE) and one study also compared LE with lipid-free HPN. No studies were found that compared the amino acid, vitamin, trace element or electrolyte components of HPN. In general, LE were well tolerated with no significant adverse effects. LE containing olive +/or fish oil were associated with a lower ω-6:ω-3 fatty acid ratio, positive reductions in markers of liver function, and changes in blood and cell fatty acid profiles. CONCLUSIONS: Despite the increasing use of HPN, there is surprisingly little evidence available to guide the provision of macro and micronutrients in the adult population requiring this therapy. Although LE containing olive +/or fish oil show promise with regards to liver function and blood and cell fatty acid profiles, further studies are needed before drawing definitive conclusions on the clinical value of these emulsions. It is likely that one type of HPN solution alone cannot be uniformly applied to patient care, and each patient should be assessed on an individual basis.

A Mixed-Lipid Emulsion Containing Fish Oil for the Parenteral Nutrition of Preterm Infants: No Impact on Visual Neuronal Conduction.

Fish oil is rich in omega-3 fatty acids and essential for neuronal myelination and maturation. The aim of this study was to investigate whether the use of a mixed-lipid emulsion composed of soybean oil, medium-chain triglycerides, olive oil, and fish oil (SMOF-LE) compared to a pure soybean oil-based lipid emulsion (S-LE) for parenteral nutrition had an impact on neuronal conduction in preterm infants. This study is a retrospective matched cohort study comparing preterm infants <1000 g who received SMOF-LE in comparison to S-LE for parenteral nutrition. Visual evoked potentials (VEPs) were assessed longitudinally from birth until discharge. The latencies of the evoked peaks N2 and P2 were analyzed. The analysis included 76 infants (SMOF-LE: n = 41 and S-LE: n = 35) with 344 VEP measurements (SMOF-LE: n= 191 and S-LE n = 153). Values of N2 and P2 were not significantly different between the SMOF-LE and S-LE groups. A possible better treatment effect in the SMOF-LE group was seen as a trend toward a shorter latency, indicating faster neural conduction at around term-equivalent age. Prospective trials and follow-up studies are necessary in order to evaluate the potential positive effect of SMOF-LE on neuronal conduction and visual pathway maturation.

Microbial growth and importance of flushing inside closed-type infusion devices during administration of lipid emulsion in vitro setting.

Background: We investigated the extent of growth of microorganisms with simultaneous administration of lipid emulsions with infusions for Total Parenteral Nutrition (TPN), assuming that the lipid emulsions contaminated with microorganisms are stagnant in a closed-type infusion device. We also investigated if bacterial growth can be prevented in the infusion device by flushing the inside of the infusion device with saline solution after the administration of lipid emulsion from the side tube in vitro setting. Methods: We made a preparation by adding Escherichia coli to the lipid emulsion and started the infusion simultaneously with the infusion solution for TPN and lipid emulsion with the piggyback method. Immediately after the completion of lipid emulsion infusion, we conducted flushing with saline solution. The volume of saline solution was none, 5, 10, or 20 mL at a flow rate of 1 mL/s. Infusion solution that was stagnant in the infusion device was collected immediately before completing the lipid emulsion infusion and 20 h after flushing, i.e., 24 h after starting the infusion for TPN, and the number of viable bacteria was determined. Results: The number of viable E. coli increased in the infusion device of all three species used in this experiment 24 h after starting the lipid emulsion infusion without flushing. We found that bacterial growth could be prevented through flushing with saline solution after the completion of lipid emulsion infusion and flushing out the stagnant infusion solution in the closed-type infusion device. Conclusions: We found that if E. coli was present in the closed-type infusion device, it would multiply. We also found that the number of viable bacteria varied according to the variety and internal structure of the closed-type infusion device as well as the liquid volume used for flushing, although flushing can prevent the growth of microorganisms. Proper management and manipulation of infusion is required to prevent infection.

Local Anesthetic Systemic Toxicity during Labor, Birth, and Immediate Postpartum: Clinical Review.

ABSTRACT: Local anesthetic systemic toxicity (LAST) is a life-threatening event caused by elevated local anesthetic plasma concentration. It is often unrecognized or misdiagnosed. Peripartum women are at increased risk for toxicity due to pregnancy-related physiological changes. Rising serum drug levels can cause cellular level impairment of mitochondria and voltage-gated ion channels leading to a cascade of symptoms that can end in cardiac arrest. Local anesthetic systemic toxicity can mimic other maternal pathologies but may be considered if local anesthetics have been used. Published treatment guidelines for this event include lipid emulsion which is approved for use in pregnant women. We review LAST in the maternity care setting, published treatment protocols, management of maternity patients with toxicity, and recommendations to increase awareness among maternity care clinicians for this medical emergency.

Smoflipid Is Better Than Lipofundin for Long-Term Neurodevelopmental Outcomes in Preterm Infants.

Neurodevelopmental morbidities developed more commonly in low-birth-weight premature infants. We sought to determine the effects of different lipid emulsions on the neurodevelopmental outcomes of children born prematurely. This retrospective cross-sectional study had two intervention legs, Lipofundin® MCT/LCT (LIPO) versus Smoflipid® (SMOF), which are mainly differentiated by fish oil. Data of premature neonates born between 2001 and 2015 from the research database of Chang Gung Memorial Hospital with corresponding individual medical records up to July 2020 were analyzed. Long-term neurodevelopmental outcomes were defined by the international classification of disease codes -9 or -10. The prevalence of diseases was compared between LIPO and SMOF groups at five and five years old and further analyzed by stratification of 1500 g birth weight. The LIPO and SMOF groups each included 1120 neonates. Epilepsy, cerebral palsy, developmental disorder and attention-deficit hyperactivity disorder (ADHD) were significantly decreased at age two years in the SMOF group, and epilepsy, language delay (LD), ADHD and autism spectrum disorder (ASD) were significantly decreased in the SMOF group at age five years. In children with birth weight < 1500 g, ADHD was decreased in the SMOF group at ages two and five years, and ASD was decreased in the SMOF group at age five years. In children with birth weight ≥ 1500 g, epilepsy, LD and ADHD were decreased in the SMOF group at age two years. LD was decreased in the SMOF group at age five years. We conclude that lipid emulsions with fish oil improve the neurodevelopmental outcomes of children born prematurely.

Effects of different lipid emulsions on serum adipokines, inflammatory markers and mortality in critically ill patients with sepsis: A prospective observational cohort study.

BACKGROUND & AIMS: Intravenous lipid emulsions in parenteral nutrition may cause different metabolic responses and immune effects in critically ill patients with sepsis. The aim of this study is to investigate the effects of different lipid emulsions on changes in concentrations of adipokine and cytokine and their relationship with mortality in patients. METHODS: Patients enrolled in this prospective, single-center, observational cohort study, were estimated to require more than ten days of parenteral nutrition. They were treated with soybean oil-based or olive oil-based parenteral lipid emulsions. Adipokine and cytokine concentrations of septic patients were determined at enrollment and ten days after, in accordance with the diagnostic criteria of SEPSIS-3. The concentrations levels were measured in an enzyme-linked immunosorbent assay. Mortality was analyzed using the Kaplan-Meier method and Cox regressions. RESULTS: Over a 25-month period, 145 patients were assessed for eligibility and consequently, 40 patients were analyzed. On admission, both groups had comparable physiological scores, comorbidities, malnutrition risk, anthropometric measurements, metabolic/hematologic biomarkers and concentrations of adipokines and cytokines (p > .05). Serum leptin, resistin, and cytokines (IL-6, IL-10, IL-1ß and TNF-α) decreased significantly in the entire cohort over ten days following sepsis (p < .05). Serum resistin decreased in both olive oil-based and soybean oil-based lipid emulsions groups. Serum adiponectin only decreased in soybean oil-based lipid emulsions group (p < .05). There was association between survival and percentage changes in adiponectin, resistin and visfatin concentrations (log rank test: p < .05). CONCLUSION: Adipokine and cytokine responses are affected by medical nutritional therapy in the sepsis process and adipokines may represent functional prognostic biomarkers in critically ill patients with sepsis.

Clinical, randomized, double blind clinical trial to study the effect of parenteral supplementation with fish oil emulsion in the nutritional support in esophagectomized patients.

INTRODUCTION: Esophagectomy is a major surgery with a high degree of catabolic and post-surgical inflammatory response accompanied by high morbidity and significant mortality. Post-surgical nutritional support via enteral administration of ω-3 fatty acids has been seen to be effective although its bad tolerance. There are few clinical trials with parenteral ω-3 fatty acids in these patients. We propose to investigate the effect of combining a parenteral fish oil lipid emulsion with the standard enteral nutrition (EN) support. MATERIALS AND METHODS: Prospective, single-center, randomized, double-blind study in esophagectomized patients, and treated after surgery with parenteral lipid emulsions of ω-3 fatty acids or a mixture of ω-6 long-chain triglycerides/short-chain triglycerides 50%. These emulsions will be added to the standard nutritional support in continuous infusion until 5 days of treatment have been completed. Patients will be randomized 1:1:1 in Group A receiving 0.4 g/kg/d of fish-oil lipid emulsion and 0.4 g/kg/d of a lipid emulsion mixture of ω-6 long-chain fatty acids (LCT) plus medium-chain fatty acids (MCT) (total dose of 0.8 g/kg/d of lipid emulsion); Group B receiving 0.8 g/kg/d of fish oil lipid emulsion and Group C receiving 0.8 g/kg/d of LCT/MCT emulsion.The main objective is to determine whether 5 days administration of intravenous ω-3 fatty acid lipid emulsion is effective in normalizing interleukin-6 levels compared with LCT/MCT emulsions, and whether a 0.8 g/kg/d dose is more effective than 0.4 g/kg/d. Secondary outcomes include other inflammatory markers such as C-reactive protein, tumor necrosis factor alpha and interleukin-10, and parameters of morbidity, safety, nutrition and mortality.Samples will be collected at the time when surgery is indicated and on days 0, 1, 3, 5 and 21 to determine inflammatory, nutritional, hepatic and safety parameters. In addition, clinical follow-up will be continued throughout the hospital admision and up to 1 year after surgery. DISCUSSION: Studies of ω-3 fatty acids administered parenterally in esophagectomized patients are scarce. This study proposes to investigate the effect of combining fish-oil lipid emulsions administered parenterally with EN support. Potential benefits include fast incorporation of lipids to the cellular membranes and to the inflammatory cascade, and the use of only 1 pharmaconutrient. TRIAL REGISTRATION: FAR-NP-2017-01 EudraCT number: 2016-004978-17.https://reec.aemps.es/reec/public/detail.html searching the EudraCT number. VERSION IDENTIFIER: Version 2, 08/06/2017.

Intravenous Lipid Emulsions in the Prevention and Treatment of Liver Disease in Intestinal Failure.

The development of intestinal failure-associated liver disease (IFALD) in pediatric and adult patients on parenteral nutrition is usually multifactorial in nature due to nutritional and non-nutritional causes. The role of lipid therapy as a contributing cause is well-established with the pathophysiological pathways now better understood. The review focuses on risk factors for IFALD development, biological effects of lipids, lipid emulsions and the mechanisms of lipid toxicity observed in laboratory animals followed by a synopsis of clinical studies in pediatric and adult patients. The introduction of fish oil-based lipid emulsions that provide partial or complete lipid replacement therapy has resulted in resolution of IFALD that had been associated with soybean oil-based therapy. Based on case reports and cohort studies in pediatric and adult patients who were at risk or developed overt liver disease, we now have more evidence that an early switch to partial or complete fish oil-based lipid therapy should be implemented in order to successfully halt and reverse IFALD.