Soybean Oil-based Lipid Emulsion Research Articles

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

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. 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. 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. 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.

Association between two different lipid injectable emulsions and parenteral nutrition-associated cholestasis in very low birth weight infants: A retrospective cohort study.

Using soybean oil-based lipid emulsions (Intralipid), which contain higher amounts of ω-6 fatty acids and phytosterols in parenteral nutrition, is a risk factor for cholestasis (parenteral nutrition-associated cholestasis [PNAC]). An alternative form of a mixed lipid emulsion (SMOFlipid) has been developed to reduce the risk of PNAC, but significant benefits over Intralipid in very low birth weight (VLBW) infants have yet to be demonstrated. The aim of this study was to compare the differences in PNAC incidence in VLBW infants receiving SMOFlipid vs Intralipid. The study was conducted in Sir Run Run Shaw Hospital of the Zhejiang University School of Medicine, Hangzhou, China, from January 2016 to March 2022. In total, 235 VLBW infants were administered SMOFlipid or Intralipid for ≥21 days and were included in the study. The primary outcome was the incidence of PNAC. Secondary outcomes included bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, late-onset sepsis, length of stay, weight 28 days after birth, severity of PNAC, and the time to reversal of PNAC. Forty-four VLBW infants (35.5%) in the SMOFlipid group vs 41 (36.9%) in the Intralipid group achieved PNAC (P = 0.817). The subgroup analysis showed that the peak direct bilirubin level was lower (median [interquartile range] 55.6 [36.4] vs 118.4 [77.2] μmol/L; P < 0.001), and the time to reversal of PNAC was shorter (44 [49] vs 96 [61]; P < 0.001) in the SMOFlipid group than in the Intralipid group. SMOFlipid may represent a better alternative for VLBW infants who require prolonged parenteral nutrition.

Parenteral nutrition with fish oil-based versus soybean oil-based lipid emulsion in neonates: Effectiveness and safety

Parenteral nutrition with fish oil-based versus soybean oil-based lipid emulsion in neonates: Effectiveness and safety

Clinical and neurodevelopmental outcomes in premature infants exposed to intravenous fish- and soybean oil-based lipid emulsions.

The optimal composition of lipid emulsions in parenteral nutrition (PN) for premature infants remains controversial. This study examined the effects of a combination of soybean oil-based (SoyLE) and fish oil-based (FishLE) lipid emulsions compared to FishLE as monotherapy on the lipid and fatty acid profiles and clinical outcomes of premature infants requiring prolonged PN. 42 premature infants received FishLE+SoyLE or FishLE. Serum concentrations of lipoproteins and 29 fatty acids (FA) were measured at baseline, 4, and 8 weeks of PN and growth and neurodevelopmental outcomes were measured at 3, 6, 12, 18, and 24 months of life. Lipid profiles were similar between groups. Plasma concentrations of ω-6 fatty acids tended to decrease over time in both groups. Concentrations of most ω-3 fatty acids, in particular docosapentaenoic acid, eicosapentaenoic acid, and docosahexaenoic acid, were significantly increased over time in the FishLE+SoyLE group whereas they did not change in the FishLE alone group. However, serum concentrations of almost all fatty acids were similar between groups at the end of the study period. No differences in growth parameters including weight, height, fronto-occipital circumference (FOC), body mass index (BMI) were observed up to two years of age. Similarly, there were no differences in neurodevelopmental test scores at 6, 12, 18, and 24 months of age. No substantial differences in lipid profiles and short clinical outcomes were found in infants exposed to FishLE+SoyLE when compared to FishLE.

The Development of Magnolol-Loaded Intravenous Emulsion with Low Hepatotoxic Potential.

Intestinal failure-associated liver disease (IFALD) is a severe liver injury occurring due to factors related to intestinal failure and parenteral nutrition administration. Different approaches are studied to reduce the risk or ameliorate the course of IFALD, including providing omega-3 fatty acids instead of soybean oil-based lipid emulsion or administering active compounds that exert a hepatoprotective effect. This study aimed to develop, optimize, and characterize magnolol-loaded intravenous lipid emulsion for parenteral nutrition. The preformulation studies allowed for chosen oils mixture of the highest capacity of magnolol solubilization. Then, magnolol-loaded SMOFlipid was developed using the passive incorporation method. The Box-Behnken design and response surface methodology were used to optimize the entrapment efficiency. The optimal formulation was subjected to short-term stress tests, and its effect on normal human liver cells and erythrocytes was determined using the MTT and hemolysis tests, respectively. The optimized magnolol-loaded SMOFlipid was characterized by the mean droplet diameter of 327.6 ± 2.9 nm with a polydispersity index of 0.12 ± 0.02 and zeta potential of -32.8 ± 1.2 mV. The entrapment efficiency of magnolol was above 98%, and pH and osmolality were sufficient for intravenous administration. The magnolol-loaded SMOFlipid samples showed a significantly lower toxic effect than bare SMOFlipid in the same concentration on THLE-2 cells, and revealed an acceptable hemolytic effect of 8.3%. The developed formulation was characterized by satisfactory stability. The in vitro studies showed the reduced cytotoxic effect of MAG-SMOF applied in high concentrations compared to bare SMOFlipid and the non-hemolytic effect on human blood cells. The magnolol-loaded SMOFlipid is promising for further development of hepatoprotective lipid emulsion for parenteral nutrition.

Change to Mixed-Lipid Emulsion From Soybean Oil–Based Lipid Emulsion in Pediatric Patients

Critically ill pediatric patients often require parenteral nutrition (PN) in the intensive care unit (ICU). Literature suggests mixed lipid emulsions (LE) with soybean oil reduction strategies may improve outcomes. To examine the association of a hospital-wide switch to a mixed-lipid formula (4-OLE) with pediatric outcomes. Retrospective cohort study at a large US academic referral center. Pediatric patients aged 1 month to 17 years requiring parenteral nutrition from May 2016 to September 2019 were included. Data were analyzed from October 2020 to February 2023. In 2017, Duke University Health System fully converted to a soybean oil/MCT/olive/fish oil lipid (4-OLE) from pure soybean oil-based LE in pediatric patients. Pediatric patients before the change (Intralipid [IL] group) were compared with patients after (4-OLE group). Clinical outcomes were compared between treatment periods via multivariable regression models. The primary outcome was hospital length of stay (LOS). Fourteen secondary outcomes included hospital mortality of any cause, 30-day or 90-day readmission, pneumonia, urinary tract infections (UTIs), total caloric delivery, and liver function tests (aspartate aminotransferase, alanine transaminase, alkaline phosphatase, and total bilirubin). A total of 684 children dependent on PN were identified (342 were critically ill), with 30% (206 children) in the preswitch (IL) period and 70% (478 children) in the postswitch (4-OLE) period; 123 were male (59.7%). In comparing IL vs 4-OLE, there was a significant difference in median (IQR) age (4.0 [1.2-13.0] vs 3.0 [0.8-9.0] years, respectively; P = .04), without difference in body mass index or baseline comorbidities except for significant differences in cancer diagnosis (26 patients in the IL group [12.6%] vs 29 patients in the 4-OLE group [6.1%]; P = .004) and chronic obstructive pulmonary disease (24 patients in the IL group [11.7%] vs 30 patients in the 4-OLE group [6.3%]; P = .02). In the all children cohort, 4-OLE was associated with shorter hospital LOS (IRR, 0.81; 95% CI, 0.05-0.78), and reduced UTI risk (OR, 0.33; 95% CI, 0.18-0.64). In the ICU cohort, 4-OLE was associated with shorter hospital LOS (IRR, 0.81; 95% CI, 0.78-0.83), and reduced UTI risk (OR, 0.23; 95% CI, 0.11-0.51). Other secondary outcomes were not significant. In this observational study of clinical outcomes among children dependent on PN, a switch to 4-OLE in a large academic hospital was associated with a significant decrease in hospital LOS in ICU and non-ICU patients. These findings suggest switching to a soy-LE sparing strategy using 4-OLE is feasible, safe, and associated with improved clinical outcomes in pediatric PN patients.

Novel lipid emulsion for total parenteral nutrition based on 18-carbon n–3 fatty acids elicits a superior immunometabolic phenotype in a murine model compared with standard lipid emulsions

While lipid emulsions in modern formulations for total parenteral nutrition (TPN) provide essential fatty acids and dense calories, they also promote inflammation and immunometabolic disruptions. We aimed to develop a novel lipid emulsion for TPN use with superior immunometabolic actions compared with available standard lipid emulsions. A novel lipid emulsion [Vegaven (VV)] containing 30% of 18-carbon n-3 fatty acids (α-linolenic acid and stearidonic acid) was developed for TPN (VV-TPN) and compared with TPN containing soybean oil-based lipid emulsion (IL-TPN) and fish-oil-based lipid emulsion (OV-TPN). In vivo studies were performed in instrumented male C57BL/6 mice subjected to 7-d TPN prior to analysis of cytokines, indices of whole-body and hepatic glucose metabolism, immune cells, lipid mediators, and mucosal bowel microbiome. IL-6 to IL-10 ratios were significantly lower in liver and skeletal muscle of VV-TPN mice when compared with IL-TPN or OV-TPN mice. VV-TPN and OV-TPN each increased hepatic insulin receptor abundance and resulted in similar HOMA-IR values, whereas only VV-TPN increased hepatic insulin receptor substrate 2 and maintained normal hepatic glycogen content, effects that were IL-10-dependent and mediated by glucokinase activation. The percentages of IFN-γ- and IL-17-expressing CD4+ T cells were increased in livers of VV-TPN mice, and liver macrophages exhibited primed phenotypes when compared with IL-TPN. This immunomodulation was associated with successful elimination of the microinvasive bacterium Akkermansia muciniphila from the bowel mucosa by VV-TPN as opposed to standard lipid emulsions. Assay of hepatic lipid mediators revealed a distinct profile with VV-TPN, including increases in 9(S)-hydroxy-octadecatrienoic acid. When co-administered with IL-TPN, hydroxy-octadecatrienoic acids mimicked the VV-TPN immunometabolic phenotype. We here report the unique anti-inflammatory, insulin-sensitizing, and immunity-enhancing properties of a newly developed lipid emulsion designed for TPN use based on 18-carbon n-3 fatty acids.

Hospital change to mixed lipid emulsion from soybean oil-based lipid emulsion for parenteral nutrition in hospitalized and critically ill adults improves outcomes: a pre–post-comparative study

IntroductionEarly data suggest use of a mixed lipid emulsion (LE) with a soybean oil reduction strategy in parenteral nutrition (PN) may improve clinical outcomes. Duke University Hospital made a full switch to a Soybean oil/MCT/Olive/Fish Oil lipid (4-OLE) from pure soybean oil-based LE (Intralipid, Baxter Inc) in May 2017. Since 4-OLE has limited evidence related to its effects on clinical outcome parameters in US hospitals, evidence for clinical benefits of switching to 4-OLE is needed. Therefore, we examined the clinical utility of a hospital-wide switch to 4-OLE and its effect on patient outcomes.MethodsWe conducted a single-center retrospective cohort study among adult patients (> 18 years) requiring PN from 2016 to 2019. Our primary exposure was treatment period (1-year pre-4-OLE switch versus 2-year post). We used multivariable regression models to examine our primary outcomes, the association of treatment period with hospital length of stay (LOS), and secondary outcomes liver function, infections, and ICU LOS. Analyses were stratified into critically ill and entire adult cohort.ResultsWe identified 1200 adults hospitalized patients. 28% of PN patients (n = 341) were treated pre-4-OLE switch and 72% post-4-OLE (n = 859). In the adult cohort, 4-OLE was associated with shorter hospital LOS (IRR 0.97, 95% CI 0.95–0.99, p = 0.039). The ICU cohort included 447 subjects, of which 25% (n = 110) were treated pre-4-OLE switch and 75% (n = 337) were post-switch. ICU patients receiving 4-OLE were associated with shorter hospital LOS (IRR 0.91, 95% CI 0.87–0.93, p < 0.0001), as well as a shorter ICU LOS (IRR 0.90, 95% CI 0.82–0.99, p = 0.036). 4-OLE ICU patients also had a significantly lower delta total bilirubin (− 1.6, 95% CI − 2.8 to − 0.2, p = 0.021) and reduced urinary tract infection (UTI) rates (OR 0.50, 95% CI 0.26–0.96, p = 0.038). There were no associations in AST, ALT, or total bilirubin in ICU and all adult patients.Conclusion4-OLE was successfully implemented and reduced soybean oil LE exposure in a large academic hospital setting. The introduction of 4-OLE was associated with reduced LOS, UTI rates, and mitigated hepatic dysfunction in critically ill patients. Overall, these findings prove a switch to a soybean oil-LE sparing strategy using 4-OLE is feasible and safe and is associated with improved clinical outcomes in adult PN patients.

A secondary Outcome Analysis of a Randomized Trial Using a Mixed Lipid Emulsion Containing Fish Oil in Infants with Extremely Low Birth Weight: Cognitive and Behavioral Outcome at Preschool Age

To evaluate the impact of a parenteral lipid emulsion containing fish oil compared with a soybean oil based-lipid emulsion on the cognitive outcome and behavior of preschool children with extremely low birth weight. This was a retrospective secondary outcome analysis of a randomized controlled trial performed between June 2012 and June 2015. Infants with extremely low birth weight received either a mixed (soybean oil, medium chain triglycerides, olive oil, fish oil) or a soybean oil-based lipid emulsion for parenteral nutrition. Data from the Kaufman Assessment Battery for Children II, the Child Behavior Checklist 1.5-5, and anthropometry were collected from medical charts at 5.6years of age. At discharge, 206 of the 230 study participants were eligible. At 5years 6months of age, data of 153 of 206 infants (74%) were available for analysis. There were no significant differences in Kaufman Assessment Battery for Children II scores for Sequential/Gsm, Simultaneous/Gv, Learning/Glr, and Mental Processing Index (mixed lipid: median, 97.5 [IQR, 23.5]; soybean oil: median, 96 [IQR, 19.5]; P=.43) or Child Behavior Checklist 1.5-5 scores for internalizing problems, externalizing problems, or total problems (mixed lipid: median, 37 [IQR, 12.3]; soybean oil: median, 37 [IQR, 13.5]; P=.54). A RandomForest machine learning regression analysis did not show an effect of type of lipid emulsion on cognitive and behavioral outcome. Parenteral nutrition using a mixed lipid emulsion containing fish oil did not affect neurodevelopment and had no impact on child behavior of infants with extremely low birth weights at preschool age. ClinicalTrials.gov: NCT01585935.

Fecal sphingolipids predict parenteral nutrition-associated cholestasis in the neonatal intensive care unit.

Parenteral nutrition-associated cholestasis (PNAC) in the neonatal intensive care unit (NICU) causes significant morbidity and associated healthcare costs. Laboratory detection of PNAC currently relies on elevated serum conjugated bilirubin levels in the aftermath of impaired bile flow. Here, we sought to identify fecal biomarkers, which when integrated with clinical data, would better predict risk for developing PNAC. Using untargeted metabolomics in 200 serial stool samples from 60 infants, we applied statistical and machine learning approaches to identify clinical features and metabolic biomarkers with the greatest associative potential for risk of developing PNAC. Stools were collected prospectively from infants receiving PN with soybean oil-based lipid emulsion at a level IV NICU. Low birth weight, extreme prematurity, longer duration of PN, and greater number of antibiotic courses were all risk factors for PNAC (P < 0.05). We identified 78 stool biomarkers with early predictive potential (P < 0.05). From these 78 biomarkers, we further identified 12 sphingomyelin lipids with high association for the development of PNAC in precholestasis stool samples when combined with birth anthropometry. We demonstrate the potential for stool metabolomics to enhance early identification of PNAC risk. Earlier detection of high-risk infants would empower proactive mitigation with alterations to PN for at-risk infants and optimization of energy nutrition with PN for infants at lower risk.

Treatment of preadipocytes with fish oil, mixed oil, or soybean oil-based lipid emulsions have differential effects on the regulation of lipogenic and lipolytic genes in mature 3T3-L1 adipocytes

The key adipose tissue characteristics are established during early development, where lipids play an essential role. Lipid emulsions used in total parenteral nutrition have different omega-(n) 6 to n-3 fatty acid ratios. A lower n-6:n-3 fatty acid decreases lipid accumulation; however, the effects of lipid emulsions with different n-6 to n-3 fatty acid ratios on the programming of preadipocytes to affect lipid accumulation in mature adipocytes is not known. This study compared the effects of Fish oil (FO), Mixed oil (MO), and Soybean oil (SO) based lipid emulsion on genes involved in adipogenesis, lipogenesis, lipolysis, and β-oxidation in 3T3-L1 adipocytes. Preadipocytes were treated with specific lipid emulsions and then differentiated to mature adipocytes in the absence of lipid emulsions. In a separate experiment, mature 3T3-L1 adipocytes were treated with lipid emulsions to investigate the effects on genes involved in lipolysis. Fatty acid composition, triacylglycerol levels, and the mRNA expression of genes involved in adipogenesis, lipogenesis, lipolysis, and β-oxidation were measured. Preadipocytes and mature adipocytes treated with FO showed higher incorporation of n-3 polyunsaturated fatty acids, lower triacylglycerol levels, and decreased mRNA expression of adipogenic and lipogenic genes, followed by MO and SO. FO and MO increased the mRNA expression of carnitine palmitoyltransferase-1, while FO decreased the mRNA expression of lipolytic genes compared to untreated cells. Our findings suggest that FO programs preadipocytes to prevent adipose tissue dysfunction in mature adipocytes; the effects of FO-based lipid emulsion were followed by MO and SO.

Is soybean therapy better than ClinOleic for reducing recovery time in cats with permethrin toxicosis?

PICO question&#x0D; Is soybean oil-based intravenous lipid emulsion (IVLE) therapy more effective than olive oil-based (ClinOleic IVLE therapy) for reducing time to recovery in cats with permethrin toxicosis?&#x0D; &#x0D; Clinical bottom line&#x0D; Category of research question&#x0D; Treatment&#x0D; The number and type of study designs reviewed&#x0D; Five case reports and one randomised clinical trial&#x0D; Strength of evidence&#x0D; Weak&#x0D; Outcomes reported&#x0D; Soybean oil-based and ClinOleic IVLE therapies can be used safely as adjuvant treatments to reduce time to recovery in cats with permethrin intoxication. However, the evidence collected suggests that soybean oil-based IVLE therapy is better in reducing the recovery time after permethrin toxicosis as compared to ClinOleic IVLE therapy&#x0D; Conclusion&#x0D; The overall findings showed that the average recovery time after soybean oil-based IVLE therapy across patients with permethrin intoxication was 8.5 hours and the average time to recovery after olive oil-based emulsions (ClinOleic therapy) was 39 hours. This may suggest that soybean oil-based formulations are a better option for reducing the recovery time in cats after permethrin toxicity. Dermal decontamination, supportive care, muscle relaxers, and anticonvulsant drugs are examples of recommended treatments before the administration of any intralipid therapies and must be used based on the clinical signs of each patient&#x0D; &#x0D; How to apply this evidence in practice&#x0D; The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources.&#x0D; Knowledge Summaries are a resource to help reinforce or inform decision making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.&#x0D; &#x0D;

Improved Dialysis Removal of Protein-Bound Uraemic Toxins with a Combined Displacement and Adsorption Technique

Introduction: Protein-bound uraemic toxins (PBUTs) are poorly removed by conventional dialytic techniques, given their high plasma protein binding, and thus low, free (dialysable) plasma concentration. Here, we evaluated and compared PBUTs removal among conventional haemodialysis (HD), adsorption-based HD, displacement-based HD, and their 2 combinations both in vitro and in vivo. Methods: The removal of PBUTs, including 3-carboxy-4-methyl-5-propyl-2-furan-propanoic acid (CMPF), p-cresyl sulphate (PCS), indoxyl sulphate (IS), indole-3-acetic acid (3-IAA), and hippuric acid, was first evaluated in an in vitro single-pass HD model. Adsorption consisted of adding 40 g/L bovine serum albumin (Alb) to the dialysate and displacement involved infusing fatty acid (FA) mixtures predialyser. Then, uraemic rats were treated with either conventional HD, Alb-based HD, lipid emulsion infusion-based HD or their combination to calculate the reduction ratio (RR), and the total solute removal (TSR) of solutes after 4 h of therapy. Results: In vitro dialysis revealed that FAs infusion prefilter increased the removal of PCS, IS, and 3-IAA 3.23-fold, 3.01-fold, and 2.24-fold, respectively, compared with baseline and increased the fractional removal of CMPF from undetectable at baseline to 14.33 ± 0.24%, with a dialysis efficacy markedly superior to Alb dialysis. In vivo dialysis showed that ω-6 soybean oil-based lipid emulsion administration resulted in higher RRs and more TSRs for PCS, IS, and 3-IAA after 4-h HD than the control, and the corresponding TSR values for PCS and IS were also significantly increased compared to that of Alb dialysis. Finally, the highest dialysis efficacy for highly bound solute removal was always observed with their combination both in vitro and in vivo. Conclusions: The concept of combined displacement- and adsorption-based dialysis may open up new avenues and possibilities in the field of dialysis to further enhance PBUTs removal in end-stage renal disease.

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

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. 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. 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-1β 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). 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.

Parenteral nutrition with fish oil-based lipid emulsion reduces the risk of cholestasis in preterm infants.

ObjectivePreterm infants receive long-term parenteral nutrition (PN) for gastrointestinal immaturity. This study aimed to determine if mixed lipid emulsions containing fish oil decrease the incidence of PN-associated cholestasis by reducing oxidative stress and providing an anti-inflammatory effect.MethodsThis retrospective cohort study enrolled 399 very low birth weight premature infants (gestational age ≤32 weeks) between January 2009 and November 2017 at a single neonatal intensive care unit. Preterm infants received total PN with either mixed lipid emulsion including fish oil (SMOFlipid®, n = 195) or soybean oil-based lipid emulsion (Lipovenoes®, n = 204) for at least 7 days. We compared the outcomes of PN-associated cholestasis, comorbidities, and mortality between the groups.ResultsThe incidence of PN-associated cholestasis was significantly lower in the SMOFlipid group than in the Lipovenoes group. The duration to full feeding days was significantly shorter in the SMOFlipid group compared with the Lipovenoes group. Relevant complications, such as severe retinopathy of prematurity and bronchopulmonary dysplasia, were also significantly reduced in the SMOFlipid group compared with the Lipovenoes group.ConclusionIn premature infants, PN with fish oil-based lipid emulsions is associated with a lower incidence of PN-associated cholestasis compared with soybean oil-based lipid emulsions.

Olive oil–based lipid emulsion is noninferior to soybean oil–based lipid emulsion in the acute care setting: A double-blind randomized controlled trial

ObjectivesOlive oil (OO)–based intravenous lipid emulsion (IVLE) may have biological advantages for nutrition and inflammation status compared with soybean oil (SO)–based IVLE. We aimed to compare prealbumin levels during infusion of OO- or SO-based IVLE in patients receiving parenteral nutrition in the acute-care setting. MethodsIn this prospective, noninferiority, double blind randomized controlled efficacy trial, patients received either OO-based or SO-based IVLE after providing consent. Biochemical and nutrition parameters were collected at baseline and at 7 to 10 d after initiation of parenteral nutrition. Results are expressed as means (standard deviations). ResultsA total of 210 patients completed the study: 102 patients in the SO-based IVLE group and 108 patients in the OO-based IVLE group. Both groups had a significant increase in prealbumin levels from baseline (SO: 0.10 [0.06] versus 0.15 [0.08] g/L; P < 0.0001; OO: 0.11 [0.06] versus 0.16 [0.08] g/L; P < 0.0001), but mean changes between groups were not different (P = 0.53). OO-based IVLE was noninferior to SO-based IVLE in maintaining or increasing serum prealbumin levels, with 20% as the noninferiority margin at follow-up (least square geometric mean ratio [95% CI], 1.10 [0.83,1.47]; P = 0.50). There was a significant improvement in C-reactive protein levels from baseline within each group (SO: 83.24 [69.72] versus 53.4 [59.78] mg/dL; P < 0.0001; OO: 85.13 [68.14] versus 58.75 [60.11] mg/dL; P = 0.004), but mean changes between the groups were not different (P = 0.836). Mortality, length of stay, and infection rates were not different for both groups. ConclusionsIn this study, OO-based IVLE was not inferior to SO-based IVLE in maintaining or increasing the prealbumin level. The improvement of C-reactive protein levels and other clinical outcomes were not different for both groups.

Comparison of neonatal outcomes with use of a soybean oil-based injectable lipid emulsion vs a 4-oil emulsion product.

Results of a study comparing the safety and efficacy outcomes with use of a soybean oil-based injectable lipid emulsion (SO-ILE) vs a 4-oil alternative product in a neonatal population are presented. In an institutional review board-approved, multicenter retrospective review, the medical records of 328 patients who were born at a gestational age of ≤34 weeks, had a birth weight of 500 to 2,000 g, were admitted to one of 2 neonatal intensive care units (NICUs) within a large health system, and received at least 7 days of a parenteral nutrition containing either lipid emulsion product were reviewed: 151 (46%) had received SO-ILE and 177 (54%) had received SMOFlipid (Fresenius Kabi). The primary outcome of the study was a composite of development of cholestasis and development of hypertriglyceridemia. Secondary outcomes included total duration of cholestasis treatment with ursodiol and change in body weight from initiation to completion of lipid emulsion treatment. The primary outcome of development of cholestasis or hypertriglyceridemia occurred in 14.6% of patients in the SO-ILE group and 18.1% of patients in the SMOFlipid group (P = 0.393). There were no statistically significant differences between the groups in total days of ursodiol treatment or average body weight change during the course of lipid emulsion treatment. In preterm neonates weighing 500 to 2,000 g, use of SMOFlipid did not significantly reduce the incidence of cholestasis or hypertriglyceridemia relative to the incidence with use of SO-ILE. Further research to validate these results is needed.

Syntheses of Analogues of Propofol: A Review

AbstractPropofol (2,6-diisopropylphenol) is an intravenous sedative/hypnotic agent that is used extensively for introduction and maintenance of general anaesthesia, sedation of critically ill patients and procedural sedation (e.g., endoscopy). Propofol has a rapid onset and offset of action and shows only minimal accumulation upon prolonged use. Propofol is only sparingly soluble in water and is currently marketed in 10% soybean oil-based lipid emulsion. Propofol’s anaesthetic properties were discovered over forty years ago, and it has been in clinical use for over thirty years. The main use of propofol remains as an anaesthetic but, over the years, analogues have been developed with varying properties from anticancer, anticonvulsant and antioxidant. In addition, large synthetic efforts have been made towards improving propofol’s water-solubility, its activity, and elucidating its structure–activity­ relationship and exact mechanism of action have been made. This review provides an overview of the research pertaining to propofol-like molecules and covers the efforts of synthetic chemists towards propofol analogues over the last 40 years.1 Introduction2 History3 Early Work4 Improving Water Solubility5 The Importance of the Phenol6 Exploring the Structure–Activity Relationship and Attempts to Improve Activity7 Anticancer Activity8 Anticonvulsant Properties9 Antioxidant Activity10 Photoactive Labelling to Elucidate Mechanism of Action11 Photoregulation12 Conclusion

A Randomized Trial of Parenteral Nutrition Using a Mixed Lipid Emulsion Containing Fish Oil in Infants of Extremely Low Birth Weight: Neurodevelopmental Outcome at 12 and 24 Months Corrected Age, A Secondary Outcome Analysis

To examine whether parenteral nutrition using a mixed lipid emulsion containing fish oil improves the neurodevelopmental outcomes of extremely low birth weight infants. The study is a secondary outcome analysis of a double-blind randomized trial of 230 extremely low birth weight infants performed at a single level IV neonatal care unit (Medical University Vienna; June 2012 to June 2015). Participants received either a mixed lipid emulsion composed of soybean oil, medium chain triglycerides, olive oil, and fish oil, or a soybean oil-based lipid emulsion for parenteral nutrition. Neurodevelopment of study participants was assessed at 12 and 24months corrected age (August 2013 to October 2017) using the Bayley Scales of Infant-Toddler Development, third edition. At discharge, 206 of the 230 study participants were eligible. At 12 and 24months corrected age, 174 of 206 (85%) and 164 of 206 (80%) infants were evaluated. At 12months, there was no significant difference in cognitive (mixed lipid: median, 95 [IQR, 85-101]; soybean oil: median, 95 [IQR, 85-100]; P=.71), language (mixed lipid: median, 86 [IQR, 77-94], soybean oil: median, 89 [IQR, 79-94]; P=.48), or motor scores (mixed lipid: median, 88 [IQR, 76-94], soybean oil: median, 88 [IQR, 79-94]; P=.69). At 24months, there was again no significant difference in cognitive (mixed lipid: median, 95 [IQR, 80-105], soybean oil: median, 95 [IQR, 90-105]; P=.17), language (mixed lipid: median, 89 [IQR, 75-97], soybean oil 89 [IQR, 77-100]; P=.54), and motor scores (mixed lipid: median, 94 [IQR, 82-103], soybean oil: median, 94 [IQR, 85-103]; P=.53). Parenteral nutrition using a mixed lipid emulsion containing fish oil did not improve neurodevelopment of extremely low birth weight infants at 12 and 24months corrected age. ClinicalTrials.gov: NCT01585935.

Novel Strategies to Prevent Total Parenteral Nutrition-Induced Gut and Liver Inflammation, and Adverse Metabolic Outcomes.

Total parenteral nutrition (TPN) is a life-saving therapy administered to millions of patients. However, it is associated with significant adverse effects, namely liver injury, risk of infections, and metabolic derangements. In this review, the underlying causes of TPN-associated adverse effects, specifically gut atrophy, dysbiosis of the intestinal microbiome, leakage of the epithelial barrier with bacterial invasion, and inflammation are first described. The role of the bile acid receptors farnesoid X receptor and Takeda G protein-coupled receptor, of pleiotropic hormones, and growth factors is highlighted, and the mechanisms of insulin resistance, namely the lack of insulinotropic and insulinomimetic signaling of gut-originating incretins as well as the potentially toxicity of phytosterols and pro-inflammatory fatty acids mainly released from soybean oil-based lipid emulsions, are discussed. Finally, novel approaches in the design of next generation lipid delivery systems are proposed. Propositions include modifying the physicochemical properties of lipid emulsions, the use of lipid emulsions generated from sustainable oils with favorable ratios of anti-inflammatory n-3 to pro-inflammatory n-6 fatty acids, beneficial adjuncts to TPN, and concomitant pharmacotherapies to mitigate TPN-associated adverse effects.