Fish Oil-based Lipid Emulsion Research Articles

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

Efficacy comparison of 21 interventions to prevent retinopathy of prematurity: a Bayesian network meta-analysis of randomized controlled trials.

The objective of this study was to evaluate the comparative efficacy of current interventions for the prevention of retinopathy of prematurity (ROP) in premature infants. A network meta-analysis (NMA) was performed. We searched PubMed, Web of Science, Scopus, Embase, and the Cochrane Library for relevant studies from their inception to May 5, 2022. Publications were eligible for our study if they were randomized controlled trials (RCTs) involving preterm infants at <37 weeks of gestational age and reported the incidence of any-stage ROP treated with the interventions of interest. The overall effect was pooled using the random effects model. We identified 106 RCTs (involving 23894 participants). This NMA showed that vitamin A supplementation markedly reduced the incidence of ROP, in comparison with placebo (odds ratio [OR] = 0.59, 95% credible interval [95% CrI] 0.33, 0.85), fish oil-based lipid emulsion (OR = 0.57, 95% CrI 0.24, 0.90), early erythropoietin (OR = 0.51, 95% CrI 0.34, 0.98), probiotics (OR = 0.48, 95% CrI 0.32, 0.97), and human milk (OR = 0.50, 95% CrI 0.21, 0.78). Vitamin A supplementation has the highest probability of being the best option for reducing the ROP risk compared with the other 20 interventions based on its surface under the cumulative ranking curve (SUCRA) value (SUCRA = 92.50%, 95% CrI 0.71, 1.00). Our findings suggest that among 21 interventions, vitamin A supplementation might be the best method of preventing ROP. This NMA offers an important resource for further efforts to develop preventive strategies for ROP.

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.

Factors influencing fish oil-based lipid emulsion effects in cholestatic infants

BackgroundThe efficacy of fish oil-based lipid emulsion (FOLE) in treating intestinal failure-associated liver disease and other cholestasis in children has been established. However, it has been found to be ineffective in some patients. This study aimed to identify factors negatively influencing FOLE administration. MethodsThis study included 21 patients treated with FOLE, who were less than 100 days old, and had direct bilirubin (D. Bil) levels ≥1.0 mg/dL. Differences in patient backgrounds between patients who eventually had a reduction in jaundice and those who did not, as well as factors affecting treatment duration in the reduction group, were investigated. ResultsAll four patients of the non-reduction group died of cholestasis and severe comorbidities. The D. Bil level at treatment initiation was significantly higher in the no-reduction group than in the reduction group (p = 0.006). The duration of FOLE administration in the reduction group was negatively correlated with gestational age (ρ = −0.603, p = 0.01). In contrast, a positive correlation was observed between age (ρ = 0.708, p = 0.002) and the D. Bil level at treatment initiation (ρ = 0.490, p = 0.046). ConclusionsFOLE treatment may be ineffective in patients with severe comorbidities. Preterm birth, high D. Bil levels, and older age at treatment initiation may be factors that result in prolonged treatment duration. Level of evidenceIII

Exclusive Fish Oil Lipid Emulsion Rescue Strategy Improves Cholestasis in Neonates on Partially Fish Oil-Based Lipid Emulsion: A Pilot Study.

Resolution of parenteral nutrition-associated liver disease has been identified in infants receiving SMOFlipid™ or a 100% fish oil lipid emulsion (FOLE). However, the effect of FOLE is unknown when the previous emulsion received is a mixed lipid emulsion containing fish oil. This observational pilot study reports data regarding the use of Omegaven™ after the diagnosis of cholestasis while receiving SMOFlipid™. We conducted a retrospective review of medical charts of neonates in which a partially fish oil-based lipid emulsion was replaced by a fish oil lipid emulsion at 1 g/kg/day due to cholestasis. Thirty-eight infants (92.1% preterm, being 44.7% born below 28 weeks' gestation), received FOLE. Birth weight was 1390 (743.0; 2298) grams. The age that cholestasis diagnosed was 15.0 (10.0; 24.8) days. The fish oil emulsion was administered for 38.5 (11.2; 51.8) days. In 73.7% (28/38) of the neonates, the cholestasis was resolved. In 34.2% (13/38), resolution happened before FOLE discontinuation. In addition, in the rest of the neonates (15) in whom cholestasis resolved, resolution occurred after FOLE discontinuation. Nine of the neonates died. In conclusion, the use of a 100% fish oil-based emulsion in neonates afflicted with cholestasis developed while on a partially fish oil-based emulsion is associated with a bilirubin decrease.

Could early infusion of fish-oil-based lipid emulsion affect the need for intensive care in moderately diseased COVID-19 patients? A randomized clinical trial

BackgroundSixty moderate diseased COVID-19 patients were divided into two equal groups and were enrolled in a randomized double-blind clinical trial. Group C was delivered standard enteral nutrition plus 100 ml/day of 0.9% normal saline. Group L was delivered fish-oil-based lipid emulsion (FOBLE) supplementation to standard enteral nutrition at a dose of 100 ml/day. Both groups infused at a rate of 12.5 ml/h over 8 h for 5 days. We aimed to compare the effect of FOBLE versus placebo in COVID-19 disease to clarify the impact on the number of patients shifted to the ICU, oxygenation, inflammatory markers, and short-term outcomes (7 days).ResultsThe failed conventional care and shift to ICU was significantly lower in group L in comparison to group C (six patients (20.0%) versus 14 patients (46.7%) shifted to ICU, P-value = 0.028). The inflammatory markers were determined and evaluated. Throughout the trial, there were no significant changes with the exception of the 7th day neutrophil/lymphocyte ratio (NLR), when the ratio was lower in group L than in group C (6.10 (3.90–7.20) versus 9.65 (8.30–10.90), respectively, P-value 0.001).ConclusionsIn moderate diseased COVID-19 patients, early administration of parenteral FOBLE as an adjuvant to enteral feeding reduces shifts and so minimizes the burden on the ICU.Trial registrationClinicalTrials.gov PRS (NCT04957940). Registered on 5 July 2021.

Current practices in lipid emulsion utilization in the prevention and treatment of intestinal failure-associated liver disease: A survey of pediatric intestinal rehabilitation and transplant centers.

Newer intravenous lipid emulsions (ILEs), such as fish oil-based intravenous lipid emulsions (FO-ILEs) and soybean oil, medium-chain triglycerides, olive oil, and fish oil-based intravenous lipid emulsions (SMOF-ILEs), provide alternatives to soybean oil-based intravenous lipid emulsions (SO-ILEs). We explored current ILE practice patterns among intestinal rehabilitation and transplant centers. A survey was developed addressing ILE availability, ILE preference in clinical scenarios, and factors influencing ILE choice. This survey was reviewed locally and by the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Intestinal Rehabilitation Special Interest Group, the Intestinal Rehabilitation and Transplant Association scientific committee, and the American Society of Parenteral and Enteral Nutrition pediatric intestinal failure section research committee. We recruited providers nationally and internationally from centers with and without intestinal transplant programs. We included 34 complete responses, 29 from the United States. Sixteen centers performed intestinal transplants. All centers had access to SMOF-ILEs, 85% had access to FO-ILEs, and 91% had access to SO-ILEs. In new patients, 85% use SMOF-ILEs as the first choice ILE. In those with new intestinal failure-associated liver disease (IFALD), FO-ILE was preferred to SMOF-ILE (56% vs 38%). In those developing IFALD on SMOF-ILE, 65% switched to FO-ILE, whereas 24% remained on SMOF-ILE. Centers have routine access to alternative ILEs, and these are quickly replacing SO-ILEs in all circumstances. Future work should focus on how this shift in practice affects outcomes to provide decision support in specific clinical scenarios.

The Metabolic Impact of Two Different Parenteral Nutrition Lipid Emulsions in Children after Hematopoietic Stem Cell Transplantation: A Lipidomics Investigation.

Hematopoietic stem cell transplantation (HSCT) involves the infusion of either bone marrow or blood cells preceded by toxic chemotherapy. However, there is little knowledge about the clinical benefits of parenteral nutrition (PN) in patients receiving high-dose chemotherapy during HSCT. We investigated the lipidomic profile of plasma and the targeted fatty acid profiles of plasma and erythrocytes in children after HSCT using PN with either a fish oil-based lipid emulsion or a classic soybean oil emulsion. An untargeted liquid chromatography high-resolution mass spectrometry platform connected with a novel in silico annotation algorithm was utilized to determine the most relevant chemical subclasses affected. In addition, we explored the interrelation between the lipidomics profile in plasma, the targeted fatty acid profile in plasma and erythrocytes, several biomarkers of inflammation, and antioxidant defense using an innovative data integration analysis based on Latent Components. We observed that the fish oil-based lipid emulsion had an impact in several lipid subclasses, mainly glycerophosphocholines (PC), glycerophosphoserines (PS), glycerophosphoethanolamines (PE), oxidized PE (O-PE), 1-alkyl,2-acyl PS, lysophosphatidylethanolamines (LPE), oxidized PS (O-PS) and dicarboxylic acids. In contrast, the classic soybean oil emulsion did not. Several connections across the different blocks of data were found and aid in interpreting the impact of the lipid emulsions on metabolic health.

Long-term assessment of bilirubin and transaminase trends in pediatric intestinal failure patients during the era of hepatoprotective parenteral nutrition

PurposeThis study aimed to characterize the relationship between hepatoprotective parenteral nutrition (PN) dependence and long-term serum liver tests in children with intestinal failure (IF). MethodsA retrospective review was performed of children with severe IF (> 90 consecutive days of PN) who were followed from 2012 to 2019 at a multidisciplinary intestinal rehabilitation program. Patients were stratified into three groups based on level of PN dependence at most recent follow up: EN (achieved enteral autonomy), mixed (parenteral and enteral nutrition), and PN (> 75% of caloric intake from PN). PN at any point for this cohort was hepatoprotective, defined as soy-based lipids < 1.5 g/kg/day, combination (soy, medium chain fatty acid, olive and fish oil) lipid emulsion, or fish oil-based lipid emulsion. Kaplan-Meier analysis and a generalized estimating equation (GEE) model were utilized to estimate time to normalization and trends, respectively, of two serum markers of liver health: direct bilirubin (DB) and alanine aminotransferase (ALT). ResultsThe study included 123 patients (67 EN, 32 mixed, 24 PN). Median follow up time was 4 years. Based on the Kaplan Meier curve, 100% of EN and mixed group patients achieved normal DB levels by 3 years, while 32% of the PN group had elevated DB levels (Fig. 1). At 5 years, 16% of EN patients had elevated ALT levels compared to 73% of PN patients (p < 0.001, Fig. 2). The PN group's ALT levels were 1.76-fold above normal at 3 years (95%CI 1.48–2.03) and 1.65-fold above normal at 5 years (95%CI 1.33–1.97, Fig. 3). ConclusionsWhile serum bilirubin levels tend to normalize, long-term PN dependence in the era of hepatoprotective PN is associated with a persistent transaminase elevation in an overwhelming majority of patients. These data support continued vigilant monitoring of liver health in children with intestinal failure. Level of evidenceIII

Fish oil-based lipid emulsion alleviates parenteral nutrition-associated liver diseases and intestinal injury in piglets.

Thisstudy aimed to investigate the impact of fish oil-based lipid emulsion (FO) on enterohepatic injuries and intestinal microbiota in piglets of parenteral nutrition (PN). Newborn piglets were divided into three groups, including enteral diet (the controls), PN with 100% FO and PN with medium-chain triglyceride/long-chain triglyceride-based lipid emulsion (MCT/LCT) for 14 days. Serum biochemical indicators, hepatic and intestinal histology, and expression of genes associated with inflammation, oxidative stress, and lipid metabolism were measured. The bile acid (BA) profiles in serum and the taxonomic composition of the gut microbiome in different intestinal segments were analyzed. Compared with MCT/LCT-piglets, FO reduced inflammation, promoted fatty acid oxidation, and decreased oxidative stress in the liver. In the intestine, FO decreased intestinal inflammation and intestinal permeability, leading to reduced lipopolysaccharide entry into the blood circulation relative to MCT/LCT-piglets. PN groups have dominant contents of Proteobacteria and Bacteroides, whereas the control group have Firmicutes at the phylum level. FO altered the taxonomic compositions of the gut microbiome in different segments, increased the relative abundance of Bacteroidaceae in ileum, and Rikenellaceae and Ruminococcaceae in the colon. FO treatment shifted BA composition ratio in serum and had a lower ratio of secondary BAs to primary BAs. FO alleviates PNLAD and intestinal injury by regulating the homeostasis of BAs' enterohepatic circulation and altering microbiota composition in different intestinal segments.

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.

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.

Does the use of fish oil-based lipid emulsion in the clinical setting of total parenteral nutrition and lipid rescue therapy interfere with common laboratory analytes on Roche Cobas 6000?

Lipaemic interference on automated analysers has been widely studied using soy-based emulsion such as Intralipid. Due to the greater adoption of fish oil-based lipid emulsion for total parenteral nutrition in view of improved clinical outcomes, we seek to characterize the optical properties of SMOFlipid 20% (Fresenius Kabi, Bad Homburg, Germany), a fish oil-based emulsion, on the Roche Cobas 6000 chemistry analyser (Roche Diagnostic, Basel, Switzerland). Various amounts of SMOFlipid were spiked into pooled serums. We plotted Roche Cobas Serum Index Gen.2 Lipaemia Index (L-index) against the amount of SMOFlipid added. We then studied the interference thresholds for aspartate aminotransferase, alanine aminotransferase, albumin and renal panel analytes using SMOFlipid. We subjected five levels of spiked lipaemia to high-speed centrifugation and analysed the specimens pre- and post-centrifugation. To postulate whether fish oil-based lipid emulsion interferes with laboratory results in the clinical setting, we calculated concentrations of SMOFlipid post-lipid rescue therapy and steady-state concentration of a typical total parenteral nutrition regime using pharmacokinetic principles. SMOFlipid optical behaviour is similar to Intralipid using the Serum Index Gen.2 L-index, with 1 mg/dL of SMOFlipid representing 1 unit of L-index. Manufacturer-stated interference thresholds are accurate for alanine aminotransferase, aspartate aminotransferase, albumin, urea and creatinine. High-speed centrifugation at 60 min 21,100g facilitates the removal of fish oil-based SMOFlipid. Based on the interference thresholds we verified and pharmacokinetics parameters provided by SMOFlipid manufacturer, total parenteral nutrition may not interfere with chemistry analytes given sufficient clearance, but lipid rescue therapy will interfere. Further studies assessing lipaemic interference on immunoassays are needed.

Fish Oil Monotherapy for Intestinal Failure-Associated Liver Disease on SMOFlipid in the Neonatal Intensive Care Unit.

Intestinal failure-associated liver disease (IFALD) is a life-threatening complication of parenteral nutrition (PN) and is most prevalent in the preterm neonatal population receiving long-term PN. In this study, we report the outcome of our experience with fish oil monotherapy for IFALD in a fish oil-based combination lipid emulsion administered to preterm low birth weight infants. Fasting neonates were administered as PN according to our center’s nutrition protocol. A diagnosis of IFALD was made when the serum direct bilirubin levels were >2.0 mg/dL in two consecutive measurements that were more than one week apart, without evidence of intrinsic causes of liver dysfunction. The management of IFALD was conducted by switching the lipid emulsion from combination lipid emulsion to fish oil monotherapy at 1.0 g/kg/day, infused over 24 h. Fifteen infants met the criteria for IFALD and received fish oil monotherapy. The median gestational age was 27.5 weeks and the median birth weight was 862.5 g. IFALD was successfully reversed in 11 infants (11/15, 73.3%). The median duration of fish oil monotherapy was 39 days. Direct bilirubin values were initially elevated and then steadily declined from the third week of treatment onward. The enteral tolerance increased in varying degrees during the treatment period. The mean weight gain was 26.0 g/day during fish oil monotherapy. Omegaven® (Fresenius Kabi Austria Gmbh, Graz, Austria) at a dose of 1.0 g/kg/day was well tolerated, and no adverse events related to Omegaven use were seen. The reversal of IFALD in preterm infants on combination lipid emulsion containing fish oil was achieved by switching to fish oil monotherapy.

Preconditioning rats with three lipid emulsions prior to acute lung injury affects cytokine production and cell apoptosis in the lung and liver

BackgroundCritically ill patients are at higher risk having acute lung injury (ALI) and more often in need of parenteral nutrition. We sought to study whether preconditioning with representative of lipid emulsions for one week could benefit rats from ALI.MethodsUsing a lipopolysaccharide (LPS)-induced ALI rat model and techniques such as polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining.ResultsPGE2 production in the serum was highest in the LPS group, followed with Intralipid group, and the PGE2 level of these two groups was significantly (P < 0.05) higher than the rest. Intralipid conditioning caused significantly less production of LTB4 than the LPS, Clinoleic, or Omegaven group. In contrast to Intralipid, rats pretreated with Clinoleic or Omegaven significantly decreased their production of inflammatory mediators (IL-1 β, IL-6 and TNF-α), had less apoptosis in the lung tissues, and Omegaven greatly improved liver function upon lipopolysaccharide (LPS) challenge.ConclusionsIn an ALI setting, preconditioning with Omegaven or Clinoleic was better than Intralipid in decreasing the intensity of the cytokine storm and apoptosis caused by LPS challenge, and Omegaven in addition had the potential to improve liver function. The results from the present study set a basis for further investigation of the molecular mechanisms of ALI, including the up- and downstream pathways of proinflammatory factor production, in search of (small) molecules intervening with the pathogenesis of ALI in order to translate relevant research findings into clinical benefit for patients with ALI. The use of Omegaven or Clinoleic, particularly in patients with ALI, is still characterized by uncertainty due to a lack of relevant studies. Future investigations must specifically focus on the route of administration and mode of application (enteral vs. parenteral/bolus vs. continuous), determining an optimal dose of Omegaven or Clinoleic, and the defining the best timepoint(s) for administration. Critically ill patients are at higher risk having acute lung injury (ALI) and more often in need of parenteral nutrition. The effect of lipid emulsion via parenteral nutrition on liver function was first time evaluated in rats in an ALI setting. The comparison of three forms of lipid emulsion in a rat model of acute lung injury was first time studied. The fish oil-based lipid emulsion decrease in PGE 2 and increase in LTB 4 was first time reported.

Something old, something new: liver injury associated with total parenteral nutrition therapy and immune checkpoint inhibitors

Drug-induced liver injury (DILI) is a challenging and constantly changing field. The pathologist plays a key role in interpreting liver biopsies by classifying the pattern of injury, grading the severity of injury, and evaluating for other possible causes. Reports of iatrogenic liver injury are reviewed here with a focus on total parenteral nutrition (ie, intestinal failure-associated liver disease [IFALD]) and immune checkpoint inhibitors (ICIs). The hallmark features of IFALD are cholestasis and steatosis. Cholestasis is more common in infants, whereas steatosis and steatohepatitis are more commonly seen in older children and adults. Infants tend to have a faster progression to fibrosis and cirrhosis. Perivenular fibrosis and ductopenia may also be seen in IFALD. Although fish oil-based lipid emulsions can reverse cholestasis, recent studies have shown persistent or progressive fibrosis. ICI-induced liver injury usually presents as an acute hepatitis with features similar to those seen in idiopathic autoimmune hepatitis and drug-induced autoimmune hepatitis. However, it lacks a prominent plasma cell infiltrate and serological markers of autoimmune hepatitis. Other features such as fibrin ring granulomas and cholangitis have also been reported in association with ICIs. Treatment for ICI-induced liver injury includes corticosteroids and other immunosuppressants.

Trends of INR and Fecal Excretion of Vitamin K During Cholestasis Reversal: Implications in the Treatment of Neonates With Intestinal Failure-Associated Liver Disease.

Vitamin K is a fat-soluble compound that plays important roles in coagulation. In children with intestinal failure-associated liver disease (IFALD), the disrupted enterohepatic circulation can lead to intestinal loss of vitamin K. Fish oil-based lipid emulsion (FOLE) has proven effective in treating IFALD. As biliary excretion is restored during cholestasis reversal, the accelerated vitamin K loss can pose a risk for deficiency. Ten neonates with IFALD and receiving FOLE monotherapy were prospectively enrolled in the study from 2016 to 2018. In addition to weekly measurements of international normalized ratio (INR) and direct bilirubin (DB), ostomy output was collected for determination of fecal concentrations of phylloquinone (PK). Trends of DB, INR, and fecal PK concentrations were summarized with locally estimated scatterplot smoothing. The median time (interquartile range) from FOLE initiation to cholestasis reversal was 59 (19-78) days. During cholestasis reversal, INR remained relatively unchanged, whereas the mean (95% confidence interval) daily fecal excretion of PK increased from 25.1 (5.0-158.5) ng at the time of FOLE initiation to 158.5 (31.6-1000.0) ng at complete reversal. Examination of individual trends in fecal PK excretion and INR revealed little correlation between the 2 measurements (r = -0.10; P = 0.50). Children with IFALD are at risk for vitamin K deficiency during cholestasis reversal. Close monitoring and quantified supplementation of vitamin K may be warranted during this period. However, this should not be guided by INR alone, as it is a poor indicator of vitamin K status.

Intravenous n-3 fatty acids in the critically ill.

Lipid emulsions are an integral part of parenteral nutrition. Enteral nutrition is the preferred route to feed critically ill patients and parenteral nutrition is used in case of contraindications or when enteral nutrition does not reach the nutritional goals. n-3 Lipids are included into some newer lipid emulsions including fish oil or may be added by a fish oil-based lipid emulsion to lipid emulsion without fish oil. This review focuses on recent clinical trials, metaanalyses, and guidelines of parenteral nutrition with n-3 lipids in critically ill patients. Two single-center studies report a mortality benefit of adding fish oil-based lipid emulsions to the parenteral nutrition. Metaanalyses performed without these two studies had demonstrated beneficial effects of n-3 lipids regarding infections, length of stay, and time of mechanical ventilation but not on mortality. However, all metaanalyses judged the database derived from the underlying studies as not sufficient for a firm recommendation. Consecutively, guidelines and expert groups issue very cautious recommendations for the use of n-3 lipids in parenteral nutrition. Beneficial effects of n-3 lipids in trials and metaanalyses became available; however, high-quality multicenter randomized controlled trials are needed before more endorsing recommendation will be available.

A Diet With Docosahexaenoic and Arachidonic Acids as the Sole Source of Polyunsaturated Fatty Acids Is Sufficient to Support Visual, Cognitive, Motor, and Social Development in Mice.

Polyunsaturated fatty acids serve multiple functions in neurodevelopment and neurocognitive function. Intravenous lipid emulsions are administered to children that are dependent on parenteral nutrition to provide the essential fatty acids needed to sustain growth and development. One of these emulsions, derived from fish-oil, is particularly poor in the traditional essential fatty acids, linoleic and alpha-linolenic acids. However, it does contain adequate amounts of its main derivatives, arachidonic acid (ARA) and docosahexaenoic acid (DHA), respectively. This skewed composition has raised concern about the sole use of fish-oil based lipid emulsions in children and how its administration can be detrimental to their neurodevelopment. Using a custom-made diet that contains ARA and DHA as a sole source of polyunsaturated fatty acids, we bred and fed mice for multiple generations. Compared to adult, chow-fed mice, animals maintained on this special diet showed similar outcomes in a battery of neurocognitive tests performed under controlled conditions. Chow-fed mice did perform better in the rotarod test for ataxia and balance, although both experimental groups showed a conserved motor learning capacity. Conversely, mice fed the custom diet rich in DHA and ARA showed less neophobia than the chow-fed animals. Results from these experiments suggest that providing a diet where ARA and DHA are the sole source of polyunsaturated fatty acids is sufficient to support gross visual, cognitive, motor, and social development in mice.

Do carnitine and extra trace elements change stability of paediatric parenteral nutrition admixtures?

High concentrations of trace elements (TE), in particular zinc and selenium, along with carnitine, are often added to parenteral admixtures in paediatric patients on long-term Parenteral Nutrition (PN). We aim to evaluate whether lipid droplet diameters of these admixtures maintain the recommended range of 0.4-1.0μm. Stability studies were carried out on six parenteral admixtures with carnitine, trace elements and electrolytes added in different amounts. Each admixture was formulated with five different lipid emulsions with or without fish oil. Analyses were performed at time 0 (t=0) and 24, 48, 72, 96 (t=96) hours after compounding. Droplet diameters were determined by Light Scattering-Reverse Fourier Optics Technique. Samples, stored at 4°C, were triple tested for a total of 450 analyses. Regression analyses were performed using panel-data techniques. During the 4 days, lipid droplet diameters were in the expected range of 0.4-1.0μm regardless of trace element and carnitine amounts in all admixtures apart from those containing fish-oil based emulsions and calcium concentrations equal to 4.5mmol/L. In these latter admixtures, 12% of droplet diameters were larger than 1.0μm and 2% exceeded 5.0μm immediately after compounding. Carnitine and high concentrations of trace elements do not affect PN admixtures stability and can be safely infused in long-term home-PN paediatric patients and prematures. Only high calcium concentrations in compresence with fish oil based lipid emulsions seem to change PN stability.