Comparison of two formulations of intravenous lipid emulsions in pediatric intestinal failure.

PURPOSE: The effect of different types of lipid emulsion may guide therapy of patients with intestinal failure (IF) to limit morbidity such as intestinal failure-associated liver disease (IFALD). METHODS: A retrospective chart review of pediatric patients with IF who received soybean oil lipid emulsion (SL) or mixed oil lipid emulsion (ML) was performed. Data over 1 year were collected. RESULTS: Forty-five patients received SL and 34 received ML. There were no differences in the incidence (82 versus 74%, P = 0.35) or resolution (86 versus 92%, P = 0.5) of IFALD between the cohorts. The median dose of ML was higher compared to SL (2 versus 1 g/kg/day, P < 0.001). If resolved, IFALD resolved rapidly in the ML cohort compared to the SL cohort (67 versus 37 days, P = 0.01). Weight gain was higher in the ML compared to the SL cohort at resolution of IFALD or 1 year from diagnosis of IF (P = 0.009). CONCLUSION: The administration of ML did not alter the incidence or resolution of IFALD compared to SL in pediatric IF. There was rapid resolution of IFALD and enhanced weight gain in the ML cohort compared to SL in pediatric IF.

Lipid emulsion treatment for local anesthetic systemic toxicity in pediatric patients: A systematic review.

BACKGROUND: Local anesthetic systemic toxicity (LAST) is rare, but fatal; the current widely used treatment is lipid emulsion (LE). The goal of this study was to analyze and review case reports on LE treatment for LAST in pediatric patients. METHODS: We performed a systematic review using case reports on LE treatment for LAST in pediatric patients, searching PubMed and Scopus databases to March 2023 using the following keywords: ("local anesthetic toxicity" OR "local anesthetic systemic toxicity" OR LAST") AND ("newborn" OR "infant" OR "child" OR "children" OR "adolescent" OR "pediatric") AND ("lipid emulsion" OR "Intralipid"). RESULTS: Our search yielded 21 cases, revealing that nearly 43% patients with LAST were less than 1 year old, and most cases were caused by bupivacaine (approximately 67% cases). "Inadvertent intravascular injection" by anesthesiologists and "overdose of local anesthetics" mainly by surgeons were responsible for 52% and 24% cases of LAST, respectively. LAST occurred in the awake state (52%) and under general anesthesia (48%), mainly causing seizures and arrhythmia, respectively. Approximately 55% of patients received LE treatment in <10 minutes after LAST, mainly improving cardiovascular symptoms. A 20% LE (1.5 mL/kg) dose followed by 0.25 mL/kg/minutes dose was frequently used. LE and anticonvulsants were mainly used in the awake state, whereas LE with or without vasopressors was mainly used under general anesthesia. LE treatment led to full recovery from LAST in 20 cases; however, 1 patient died due to underlying disease. CONCLUSION: Consequently, our findings reveal that LE is effective in treating pediatric LAST.

An Overview of Parenteral Nutrition from Birth to Adolescence Based on a Composite Fish Oil Containing Lipid Emulsion and a Pediatric Amino Acid Solution.

Intestinal failure (IF) is characterized by a critical reduction in functional gut mass below the minimum needed for optimal growth in children. It requires parenteral nutrition (PN) and home-PN (HPN), which is challenging in terms of meeting nutritional needs according to age, growth velocity, clinical situation, and rapid changes in fluid and electrolyte requirements. Due to these complex requirements, age-adapted multi-chamber bags (MCBs) are important additions to the nutrition armamentarium. The launch of composite fish oil (FO)-containing intravenous lipid emulsions (ILEs) heralded the development of MCBs containing these ILEs in combination with a crystalline amino acid solution adapted for pediatric use. The safety and efficacy of lipid and amino acid components in this context have been widely documented in numerous published studies. This narrative manuscript includes a review of the articles published in PudMed, Embase, and Google Scholar up to June 2023 for the age groups of term infants to children and adolescents. Preterm infants with their highly specific demands are not included. It aims to offer an overview of the clinical experience regarding the use of a composite FO-based ILE and a developed specific amino acid solution.

[Research progress on the application of non-nutritional effects of fat emulsion in the treatment of poisoning].

Fat emulsion is a drug commonly used clinically for parenteral nutrition support in critically ill patients.With the development of the pharmaceutical industry, fat emulsion has formed a variety of different formulations, among which different types of fat emulsion have their own metabolic and body energy supply characteristics, and the application indications are also different. In addition to providing the supply of nutrients, the role of fat emulsion in anti-toxicity, immune regulation, anti-inflammatory, anti-shock, cardiopulmonary resuscitation and other aspects has gradually been discovered. This article reviews the existing evidence-based medical evidence and expounds the mechanism and therapeutic role of fat emulsion in the treatment of critically ill patients with poisoning. Its value in the treatment of critically ill patients with poisoning was discussed, and some references were provided for the application of non-nutritional functions of fat emulsion in the future.

High Dose Fish Oil Added to Various Lipid Emulsions Normalizes Superoxide Dismutase 1 Activity in Home Parenteral Nutrition Patients.

(1) Objectives: Intestinal failure in home parenteral nutrition patients (HPNPs) results in oxidative stress and liver damage. This study investigated how a high dose of fish oil (FO) added to various lipid emulsions influences antioxidant status and liver function markers in HPNPs. (2) Methods: Twelve HPNPs receiving Smoflipid for at least 3 months were given FO (Omegaven) for a further 4 weeks. Then, the patients were randomized to subsequently receive Lipoplus and ClinOleic for 6 weeks or vice versa plus 4 weeks of Omegaven after each cycle in a crossover design. Twelve age- and sex-matched healthy controls (HCs) were included. (3) Results: Superoxide dismutase (SOD1) activity and oxidized-low-density lipoprotein concentration were higher in all baseline HPN regimens compared to HCs. The Omegaven lowered SOD1 compared to baseline regimens and thus normalized it toward HCs. Lower paraoxonase 1 activity and fibroblast growth factor 19 (FGF19) concentration and, on the converse, higher alkaline phosphatase activity and cholesten concentration were observed in all baseline regimens compared to HCs. A close correlation was observed between FGF19 and SOD1 in baseline regimens. (4) Conclusions: An escalated dose of FO normalized SOD1 activity in HPNPs toward that of HCs. Bile acid metabolism was altered in HPNPs without signs of significant cholestasis and not affected by Omegaven.

A medium-chain fatty acid analogue prevents hepatosteatosis and decreases inflammatory lipid metabolites in a murine model of parenteral nutrition-induced hepatosteatosis.

BACKGROUND: Parenteral (intravenous) nutrition is lifesaving for patients with intestinal failure, but long-term use of parenteral nutrition often leads to liver disease. SEFA-6179 is a synthetic medium-chain fatty acid analogue designed to target multiple fatty acid receptors regulating metabolic and inflammatory pathways. We hypothesized that SEFA-6179 would prevent hepatosteatosis and lipotoxicity in a murine model of parenteral nutrition-induced hepatosteatosis. METHODS: Two in vivo experiments were conducted. In the first experiment, six-week-old male mice were provided an ad lib fat-free high carbohydrate diet (HCD) for 19 days with orogastric gavage of either fish oil, medium-chain triglycerides, or SEFA-6179 at a low (0.3mmol/kg) or high dose (0.6mmol/kg). In the second experiment, six-week-old mice were provided an ad lib fat-free high carbohydrate diet for 19 days with every other day tail vein injection of saline, soybean oil lipid emulsion, or fish oil lipid emulsion. Mice then received every other day orogastric gavage of medium-chain triglyceride vehicle or SEFA-6179 (0.6mmol/kg). Hepatosteatosis was assessed by a blinded pathologist using an established rodent steatosis score. Hepatic lipid metabolites were assessed using ultra-high-performance liquid chromatography-mass spectrometry. Effects of SEFA-6179 on fatty acid oxidation, lipogenesis, and fatty acid uptake in human liver cells were assessed in vitro. RESULTS: In the first experiment, mice receiving the HCD with either saline or medium-chain triglyceride treatment developed macrovesicular steatosis, while mice receiving fish oil or SEFA-6179 retained normal liver histology. In the second experiment, mice receiving a high carbohydrate diet with intravenous saline or soybean oil lipid emulsion, along with medium chain triglyceride vehicle treatment, developed macrovescular steatosis. Treatment with SEFA-6179 prevented steatosis. In each experiment, SEFA-6179 treatment decreased arachidonic acid metabolites as well as key molecules (diacylglycerol, ceramides) involved in lipotoxicity. SEFA-6179 increased both ß- and complete fatty oxidation in human liver cells, while having no impact on lipogenesis or fatty acid uptake. CONCLUSIONS: SEFA-6179 treatment prevented hepatosteatosis and decreased toxic lipid metabolites in a murine model of parenteral nutrition-induced hepatosteatosis. An increase in both ß- and complete hepatic fatty acid oxidation may underlie the reduction in steatosis.

Effect of SMOF lipid emulsion on physical growth and extrauterine growth retardation in very preterm infants: Insights from a multicenter retrospective cohort study.

OBJECTIVE: The aim of this study was to investigate the effects of soybean, medium-chain triacylglycerols (MCTs), olive oil, and fish oil (SMOF) on short-term clinical outcomes, physical growth, and extrauterine growth retardation (EUGR) in very preterm infants. METHODS: This was a multicenter retrospective cohort study of very preterm infants hospitalized in neonatal intensive care units at five tertiary hospitals in China between January 2021 and December 2021. According to the type of fat emulsion used in parenteral nutrition (PN), eligible very preterm infants were divided into the MCTs/long-chain triacylglycerol (MCT/LCT) group and SMOF group. Change in weight z-score (weight Δz) between measurements at birth and at 36 wk of postmenstrual age or at discharge, the incidence of EUGR, and short-term clinical outcomes between the two groups were compared and analyzed. RESULTS: We enrolled 409 very preterm infants, including 205 in the MCT/LCT group and 204 in the SMOF group. Univariate analysis showed that infants in the SMOF group had significantly longer duration of invasive mechanical ventilation and PN, longer days to reach total enteral nutrition, and a higher proportion of maximum weight loss than those in MCT/LCT group (all P < 0.05). After adjusting for the confounding variables, multifactorial logistic regression analysis of short-term clinical outcomes showed that SMOF had protective effects on PN-associated cholestasis (odds ratio [OR], 0.470; 95% confidence interval [CI], 0.266-0.831) and metabolic bone disease of prematurity (OR, 0.263; 95% CI, 0.078-0.880). Additionally, SMOF was an independent risk factor for lower weight growth velocity (ß = -0.733; 95% CI, -1.452 to -0.015) but had no effect on the incidence of EUGR (OR, 1.567; 95% CI, 0.912 to -2.693). CONCLUSION: Compared with MCT/LCT, SMOF can reduce the risk for PN-associated cholestasis and metabolic bone disease of prematurity in very preterm infants and has a negative effect on growth velocity but has no effect on the incidence of EUGR.

Parenteral Nutrition in the Neonatal Intensive Care Unit: Intravenous Lipid Emulsions.

Intravenous lipid emulsions (ILEs) are a source of nonprotein calories and fatty acids and help promote growth in preterm infants and infants with intestinal failure. An ILE dose and oil source determines its fatty acid, phytosterol, and vitamin E delivery. These factors play a role in the infant's risk for essential fatty acid deficiency and cholestasis, and help modulate inflammation, immunity, and organ development. This article reviews different ILEs and their constituents and their relationship with neonatal health.

In parenteral nutrition-fed piglets, fatty acids vary by lipid emulsion and tissue sampled.

BACKGROUND: Children with intestinal failure without liver disease may be given soy-based lipid emulsion (SLE) or mixed lipid emulsion (MLE; containing soy, medium-chain triglyceride, olive, and/or fish oils). Both differ in essential fatty acid content: MLE has added arachidonic acid (AA) and docosahexaenoic acid (DHA). The aim of this study, in neonatal piglets, was to compare serum and tissue fatty acid composition when the emulsions were given at unrestricted doses. METHODS: We compared SLE (n = 15) and MLE (n = 15) at doses of 10-15 g/kg/day in parenteral nutrition (PN). On day 14 we collected serum and tissues. Using gas-liquid chromatography, percentage fatty acids were measured in serum, brain, and liver phospholipid. Comparisons were made to reference values from litter-matched controls (n = 8). RESULTS: Comparing median values, linoleic acid (LA) was lower for MLE vs SLE in serum (-27%), liver (-45%), and brain (-33%) (P < 0.001). AA was lower for MLE in serum (-25%), liver (-40%), and brain (-10%). DHA was higher for MLE in serum (+50%), liver (+200%), and brain (+10%). AA levels were lower for MLE vs control piglets in serum (-81%), liver (-63%), and brain (-9%). DHA levels were higher in serum (+41%), liver (+38%), and brain (+19%). CONCLUSION: This study in piglets has shown that, at unrestricted doses, MLE treatment is associated with low serum and tissue AA compared with SLE and healthy litter-matched controls. Although not yet proven, low tissue AA levels may have functional consequences, and these data support current practice avoiding MLE dose restriction.

Capillary electrokinetic chromatography for studying interactions between ß-blockers and Intralipid emulsion.

Toxicity of ß-blockers is one of the most common causes of poison-induced cardiogenic shock throughout the world. Therefore, methodologies for in vivo removal of the drugs from the body have been under investigation. Intralipid emulsion (ILE) is a common commercial lipid emulsion used for parenteral nutrition, but it has also been administered to patients suffering from drug toxicities. In this work, a set of ß-blockers of different hydrophobicity's (log KD values ranging from 0.16 to 3.8) were investigated. The relative strength of the interactions between these compounds and the ILE was quantitatively assessed by means of binding constants and adsorption constants of the formed ß-blocker-ILE complexes. The binding constants were determined by capillary electrokinetic chromatography and the adsorption constants were calculated based on different adsorption isotherms. Expectedly, the binding constants were strongly related to the log KD values of the ß-blockers. The binding and adsorption constants also show that less hydrophobic ß-blockers interact with ILE, suggesting that this emulsion could be useful for capturing such compounds in cases of their overdoses. Thus, the use of ILE for treatment of toxicities caused by a larger range of ß-blockers is worth further investigation.

Composite lipid emulsion use and essential fatty acid deficiency in pediatric patients with intestinal failure with high parenteral nutrition dependence: A retrospective cohort study.

BACKGROUND: Reports of essential fatty acid deficiency (EFAD) in patients receiving parenteral nutrition (PN) and a composite lipid (mixed oil intravenous lipid emulsion [MO ILE]) are predominantly when managed by lipid restriction. The objective of this study was to determine the prevalence of EFAD in patients with intestinal failure (IF) who are PN dependent without lipid restriction. METHODS: We retrospectively evaluated patients, ages 0-17 years, followed by our intestinal rehabilitation program between November 2020 and June 2021 with PN dependency index (PNDI) of >80% on a MO ILE. Demographic data, PN composition, PN days, growth, and plasma fatty acid profile were collected. A plasma triene-tetraene (T:T) ratio >0.2 indicated EFAD. Summary statistics and Wilcoxon rank sum test evaluated to compare between PNDI category and ILE administration (grams/kilograms/day). P < 0.05 was considered significant. RESULTS: Twenty-six patients (median age, 4.1 years [interquartile range (IQR) = 2.4-9.6]) were included. The median duration of PN was 1367 days (IQR = 824-3195). Sixteen patients had a PNDI of 80%-120% (61.5%). Fat intake for the group was 1.7 g/kg/day (IQR = 1.3-2.0). The median T:T ratio was 0.1 (IQR = 0.1-0.2) with no values >0.2. Linoleic and arachidonic acid were low in 85% and 19% of patients, respectively; however, Mead acid was normal in all patients. CONCLUSION: This report is the largest to date on the EFA status of patients with IF on PN. These results suggest that, in the absence of lipid restriction, EFAD is not a concern when using MO ILEs in children receiving PN for IF.

Lipid emulsions in parenteral nutrition: does it matter?

PURPOSE OF REVIEW: Recently, clinicians have shown interest in switching patients to nonsoybean-based intravenous lipid emulsion (ILE) formulas for parental nutrition (PN) due to adverse outcomes related to high Omega-6 content in soybean oil (SO) ILE's. This review summarizes recent literature on improved clinical outcomes with new Omega-6 lipid-sparing ILE's in PN management. RECENT FINDINGS: Although there is a paucity of large-scale studies directly comparing Omega-6 lipid sparing ILE's with SO-based lipid emulsion use in PN in ICU patients, there is strong translational and meta-analysis evidence to suggest that lipid formulations containing fish oil (FO) and/or olive oil (OO) have favorable effects on immune function and improve clinical outcomes in ICU populations. SUMMARY: More research is needed to directly compare omega-6-sparing PN formulas with FO and/or OO versus traditional SO ILE's. However, current evidence is promising for improved outcomes using newer ILE's including reduced infections, shorter lengths of stay, and reduced costs.

Effects of mixed oil emulsion on short-term clinical outcomes in premature infants: A prospective, multicenter, randomized controlled trial.

OBJECTIVE: This study compared the clinical effects of two different lipid emulsions in premature infants with gestational age < 32 weeks (VPI) or birth weight < 1500 g (VLBWI) to provide an evidence-based medicine basis for optimizing intravenous lipid emulsion. METHODS: This was a prospective multicenter randomized controlled study. A total of 465 VPIs or VLBWIs, admitted to the neonatal intensive care unit of five tertiary hospitals in China from March 1, 2021 to December 31, 2021, were recruited. All subjects were randomly allocated into two groups, namely, medium-chain triglycerides/long-chain triglycerides (MCT/LCT) group (n = 231) and soybean oil, medium-chain triglycerides, olive oil, and fish oil (SMOF) group (n = 234). Clinical features, biochemical indexes, nutrition support therapy, and complications were analyzed and compared between the two groups. RESULTS: No significant differences were found in perinatal data, hospitalization, parenteral and enteral nutrition support between the two groups (P > 0.05). Compared with the MCT/LCT group, the incidence of neonates with a peak value of total bilirubin (TB) > 5 mg/dL (84/231 [36.4% vs. 60/234 [25.6%]), a peak value of direct bilirubin (DB) ≥ 2 mg/dL (26/231 [11.3% vs. 14/234 [6.0%]), a peak value of alkaline phosphatase (ALP) > 900 IU/L (17/231 [7.4% vs. 7/234 [3.0%]), and a peak value of triglycerides (TG) > 3.4 mmol/L (13/231 [5.6% vs. 4/234[1.7%]]) were lower in the SMOF group (P < 0.05). Univariate analysis showed that in the subgroup analysis of < 28 weeks, the incidence of parenteral nutrition-associated cholestasis (PNAC) and metabolic bone disease of prematurity (MBDP) were lower in the SMOF group (P = 0.043 and 0.029, respectively), whereas no significant differences were present in the incidence of PNAC and MBDP between the two groups at > 28 weeks group (P = 0.177 and 0.991, respectively). Multivariate logistic regression analysis revealed that the incidence of PNAC (aRR: 0.38, 95% confidence interval [CI]: 0.20-0.70, P = 0.002) and MBDP (aRR: 0.12, 95% CI: 0.19-0.81, P = 0.029) in the SMOF group were lower than that in the MCT/LCT group. In addition, no significant differences were recorded in the incidence of patent ductus arteriosus, feeding intolerance, necrotizing enterocolitis (Bell's stage ≥ 2), late-onset sepsis, bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leukomalacia, retinopathy of prematurity and extrauterine growth retardation between the two groups (P > 0.05). CONCLUSIONS: The application of mixed oil emulsion in VPI or VLBWI can reduce the risk of plasma TB > 5 mg/dL, DB ≥ 2 mg/dL, ALP > 900 IU/L, and TG > 3.4 mmol/L during hospitalization. SMOF has better lipid tolerance, reduces the incidence of PNAC and MBDP, and exerts more benefits in preterm infants with gestational age < 28 weeks.

Proinflammatory mediators in lipid emulsions and parenteral nutrition-associated liver disease: Review of leading factors.

Lipid injectable emulsions have been in clinical use for over 60 years. The first product launched was Intralipid, which consisted of an emulsion of soybean oil in water for intravenous administration. It was a key source of essential fatty acids and an alternative source of energy for patients with gastrointestinal dysfunction requiring long-term parenteral nutrition. With clinical experience, a condition known as parenteral nutrition-associated liver disease (PNALD), or intestinal failure-associated liver disease (IFALD), was observed, with a focus on carbohydrate and fat energy. Modifying the daily doses and infusion rates had some salutary effects, but PNALD persisted. Subsequently, on closer inspection of the fatty acids profile and phytosterol concentrations, degradation products arising from chemical and physical stability issues of the available lipid injectable emulsions were implicated. Recently, the US Food and Drug Administration convened an online workshop entitled "The Role of Phytosterols in PNALD/IFALD," with an emphasis on (1) the multifactorial pathophysiology of PNALD/IFALD, (2) risk associated with phytosterols, and (3) regulatory history. The scope of this review includes the multifactorial pathophysiology of PNALD/IFALD as it relates to the pharmaceutical aspects of the various lipid injectable emulsions on the market, with respect to potential proinflammatory components, as well as physical and chemical stability issues that may also affect products' safe intravenous administration to patients.

Clinical effects of multi-oil versus pure soybean oil-based lipid emulsions for preterm infants: An observational study.

BACKGROUND AND OBJECTIVES: Conventional soybean oil-based intravenous lipid emulsions (SO-ILEs) have high polyunsaturated fatty acid (PUFA) contents and phytosterols that may have adverse effects in preterm infants. Recently, the multi-oil-based intravenous lipid emulsion (MO-ILE), SMOFlipid, has been widely utilized in the neonatal intensive care unit (NICU), but significant benefits over SO-ILEs in low gestational age neonates have yet to be demonstrated. This study was performed to compare the effects of the SO-ILE, Intralipid, and the MO-ILE, SMOFlipid, on neonatal health outcomes in preterm infants. METHODS AND STUDY DESIGN: We performed a retrospective review of preterm infants born at gestational week (GW) <32 receiving parenteral nutrition for longer durations (≥14 d) in the NICU between 2016 and 2021. The primary aim of this study was to investigate differences in morbidity between preterm infants receiving SMOFlipid and Intralipid. RESULTS: A total of 262 preterm infants were included in the analysis, with 126 receiving SMOFlipid and 136 receiving Intralipid. The SMOFlipid group had lower rates of ROP (23.8% vs 37.5%, respectively; p=0.017), although the rate of ROP was not different in multivariate regression analysis. The length of hospi-tal stay was significantly shorter in the SMOFlipid than SO-ILE group (median [IQR]=64.8 [37] vs 72.5 [49] days; p<0.001). CONCLUSIONS: The use of SMOFlipid as the lipid emulsion was associated with higher clinical efficacy than SO-ILE in preterm infants.

Effect of a parenteral fish-oil-containing lipid emulsion on liver lipid perioxidation and antioxidative defenses in Lewis rats.

BACKGROUND: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), naturally abundant in fish oil (FO), are known for their anti-inflammatory and potential antioxidant properties. The aim in this article is to evaluate the effect of the infusion of a parenteral FO-containing lipid emulsion on markers of liver lipid peroxidation and oxidative stress in rats undergoing central venous catheterization (CVC). METHODS: After 5-day acclimatization, adult Lewis rats (n = 42) receiving a 20-g/day AIN-93M oral diet were randomly subdivided into four groups: (1) basal control (BC) (n = 6), without CVC or LE infusion; (2) SHAM (n = 12), with CVC but without LE infusion; (3) soybean oil (SO)/medium-chain triglyceride (MCT) (n = 12), with CVC and receiving LE without FO (4.3 g/kg fat); and (4) SO/MCT/FO (n = 12), with CVC and receiving LE containing 10% FO (4.3 g/kg fat). Animals from the BC group were euthanized immediately after acclimatization. The remaining groups of animals were euthanized after 48 or 72 h of surgical follow-up to assess profiles of liver and plasma fatty acids by gas chromatography, liver gene transcription factor Nrf2, F2-isoprostane lipid peroxidation biomarker, and the antioxidant enzymes glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) by enzyme-linked immunosorbent assay. R program (version 3.2.2) was utilized for data analysis. RESULTS: Compared with the other groups, liver EPA and DHA levels were higher in the SO/MCT/FO group, which also showed the highest liver Nrf2, GPx, SOD, and CAT levels and lower liver F2-isoprostane (P < 0.05). CONCLUSION: Experimental delivery of FO via EPA and DHA sources in a parenteral LE was associated with a liver antioxidant effect.

Omega-3 fatty acids in parenteral nutrition - A systematic review with network meta-analysis on clinical outcomes.

BACKGROUND & AIMS: Accumulating scientific evidence supports the benefits of parenteral nutrition (PN) with fish oil (FO) containing intravenous lipid emulsions (ILEs) on clinical outcomes. Yet, the question of the most effective ILE remains controversial. We conducted a network meta-analysis (NMA) to compare and rank different types of ILEs in terms of their effects on infections, sepsis, ICU and hospital length of stay, and in-hospital mortality in adult patients. METHODS: MEDLINE, EMBASE, and Web of Science databases were searched for randomized controlled trials (RCTs) published up to May 2022, investigating ILEs as a part of part of PN covering at least 70% of total energy provision. Lipid emulsions were classified in four categories: FO-ILEs, olive oil (OO)-ILEs, medium-chain triglyceride (MCT)/soybean oil (SO)-ILEs, and pure SO-ILEs. Data were statistically combined through Bayesian NMA and the Surface Under the Cumulative RAnking (SUCRA) was calculated for all outcomes. RESULTS: 1651 publications were retrieved in the original search, 47 RCTs were included in the NMA. For FO-ILEs, very highly credible reductions in infection risk versus SO-ILEs [odds ratio (OR) = 0.43 90% credibility interval (CrI) (0.29-0.63)], MCT/soybean oil-ILEs [0.59 (0.43-0.82)], and OO-ILEs [0.56 (0.33-0.91)], and in sepsis risk versus SO-ILEs [0.22 (0.08-0.59)], as well as substantial reductions in hospital length of stay versus SO-ILEs [mean difference (MD) = -2.31 (-3.14 to -1.59) days] and MCT/SO-ILEs (-2.01 (-2.82 to -1.22 days) were shown. According to SUCRA score, FO-ILEs were ranked first for all five outcomes. CONCLUSIONS: In hospitalized patients, FO-ILEs provide significant clinical benefits over all other types of ILEs, ranking first for all outcomes investigated. REGISTRATION NO: PROSPERO 2022 CRD42022328660.

Intestinal Failure-Associated Liver Disease and Growth Pre- and Post-Transition to a Composite Lipid Emulsion.

OBJECTIVES: Infants with intestinal failure have an increased risk of intestinal failure-associated liver disease (IFALD). Composite intravenous lipid emulsion (ILE) may reduce the risk of cholestasis. The primary outcome was to compare IFALD rates in infants with intestinal failure, between those receiving a composite ILE versus soybean oil ILE. The secondary outcome compared growth between these 2 groups. METHODS: At our 2 tertiary neonatal/pediatric hospitals, we identified all patients (≤1 year old) who received ≥6 weeks parenteral nutrition (PN) from 2010 to 2018. Data included liver and growth parameters. IFALD was defined as serum conjugated bilirubin (CB) >33 µmol/L (≥2 mg/dL). Nonparametric tests were used for all comparisons. RESULTS: Fifty infants (35 composite ILE, 15 soybean oil ILE) were included. Those on composite ILE received PN for longer (10.1 vs 7.6 weeks; P = 0.001) and had higher baseline CB (29 vs 6.5 µmol/L; P = 0.001). No differences were found by 6 weeks (14.5 vs 5 µmol/L; P = 0.54) and by PN cessation (4 vs 4 µmol/L; P = 0.33). The proportion of patients with IFALD decreased from 54% to 20% for composite ILE, while stable given soybean oil ILE (7%). There were no differences in weight, length, or head circumference z scores ( P > 0.05). CONCLUSIONS: In our institutions, over 8 years, chronic intestinal failure was rare. Composite ILE was the predominant lipid choice for infants who needed longer courses of PN or had developed cholestasis. Despite longer PN duration, and higher baseline CB, overall rates of IFALD decreased with composite ILE. Regardless of parenteral lipid used, there were no differences in growth.

Hepatic dysfunction in patients receiving intravenous lipid emulsions.

PURPOSE OF REVIEW: Until recently, intravenous lipid emulsions (ILEs) have consisted of soybean oil (SO) only. This review addresses recent developments in the field, including the problem of intestinal failure associated liver disease (IFALD) that can occur with the use of ILEs in children and adults, and newer ILEs that may minimize and reverse IFALD. RECENT FINDINGS: Cholestasis is the primary manifestation of IFALD in premature infants receiving ILEs, whereas in older children and adults, steatosis is predominant. Two alternative ILEs have been extensively investigated for both safety and efficacy. SMOF, an ILE containing medium chain triglyceride, soybean oil, olive oil and fish oil (FO), is now widely used in both children and adults. A newer FO ILE is approved for use in children only. However, in case reports FO ILE has been shown to improve IFALD in adults. A number of new studies suggest that cholestasis from ILEs is dose-related. IFALD does not improve in many patients after transition from SO to SMOF, but partial or complete replacement with FO can halt and reverse IFALD. SUMMARY: Adverse hepatic effects from ILEs are to some extent dose-related. Overfeeding with fat or with carbohydrate, or simply providing excessive calories in general, may be responsible. More research is needed investigating dose-related effects of macronutrients on liver injury.