Intralipid Group Research Articles

Cardioprotection with Intralipid During Coronary Artery Bypass Grafting Surgery on Cardiopulmonary Bypass: A Randomized Clinical Trial.

Coronary artery bypass grafting (CABG) on cardiopulmonary bypass (CPB) is associated with myocardial ischemia-reperfusion injury (IRI), which may limit the benefit of the surgery. Both experimental and clinical studies suggest that Intralipid, a lipid emulsion commonly used for parenteral nutrition, can limit myocardial IRI. We therefore aimed to investigate whether Intralipid administered at reperfusion can reduce myocardial IRI in patients undergoing CABG on CPB. We conducted a randomized, double-blind, pilot trial in which 29 adult patients scheduled for CABG were randomly assigned (on a 1:1 basis) to receive either 1.5ml/kg Intralipid 20% or Ringer's Lactate 3min before aortic cross unclamping. The primary endpoint was the 72-h area under the curve (AUC) for troponin I. Of the 29 patients randomized, 26 were included in the study (two withdrew consent and one was excluded before surgery). The 72-h AUC for troponinI did not significantly differ between the control and Intralipid group (546437 ± 205518 versus 487561 ± 115724 arbitrary units, respectively; P = 0.804). Other outcomes (including 72-h AUC for CK-MB, C-reactive protein, need for defibrillation, time to extubation, length of ICU and hospital stay, and serious adverse events) were similar between the two groups. In patients undergoing CABG on CPB, Intralipid did not limit myocardial IRI compared to placebo. ClinicalTrials.gov Identifier: NCT02807727 (registration date: 16 June 2016).

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.

Abstract 13329: Intralipid Protects the Heart in Late Pregnancy Against Ischemia/Reperfusion Injury via Inducing Mir122 by Targeting Pkm2

INTRODUCTION: We have shown hearts of late-pregnant (LP) rats have higher vulnerability to ischemia-reperfusion injury (IRI) compared to non-pregnant (NP) rats, and administration of intralipid (ITLD), a clinically safe fat emulsion, at the onset of reperfusion protects the LP rat heart against IRI. Our goal is to decipher the mechanisms for the ITLD-mediated cardioprotection in LP against IRI. Methods: We occluded the left anterior descending coronary artery of female Sprague-Dawley rats (2-3 months old NP and LP, 20-21 days pregnant) for 45 minutes followed by 3 hours reperfusion. The ITLD group was given ITLD at the onset of reperfusion (5mg/kg of 20%). We assessed myocardial necrosis via TTC staining and sent the hearts for microRNA-microarray profiling (Ocean Ridge Biosciences). In vitro, female cardiomyocytes were transfected either miR122 mimic, miR122 inhibitor, or scramble control (40uM), followed by 3 hours hypoxia and 6 hours reoxygenation. We collected human blood samples from NP, LP, and LP coronary heart disease (CHD) patients. P&lt;0.05 was considered statistically significant. Values are expressed as mean±SEM. Results: MicroRNA-microarray profiling showed microRNA-122-5p (miR122) is downregulated 4-fold in the heart of LP rats subjected to IRI compared to healthy pregnant rats and upregulated 10-fold in the heart of LP rats that received ITLD at reperfusion, which we confirmed with qPCR (0.32±0.12, 90.2±10.3, n=5 animals/group). miR122 is significantly decreased in the plasma of healthy LP women compared to healthy NP women (0.6±0.16, LP n=9, NP n=7) and decreased in LP women with CHD compared to healthy LP (0.43±0.13, CHD n=5). TargetScan showed PKM2 to be a target of miR122. We confirmed significantly increased PKM2 in LP IRI rat myocardium compared to NP IRI (1.88±0.32) and significantly decreased in LP IRI rat administered ITLD (0.32±0.18). MiR122 overexpression in female cardiomyocytes subjected to hypoxia/reoxygenation (H/R) significantly decreased PKM2 (0.35±0.12), apoptosis (0.77±0.12) and oxidative stress (0.51±0.12), while miR122 knockdown expressed the opposite effect (n=4). Conclusions: Intralipid protects the heart in late pregnancy against ischemia/reperfusion injury by upregulating miR122, which targets PKM2.

KALİTELİ EMBRİYO TRANSFERİNE RAĞMEN BAŞARISIZ IVF SİKLUSU OLAN KADINLARDA İN VİTRO FERTİLİZASYON (IVF) TEDAVİSİ BOYUNCA İV LİPİD (SMOFLIPID®) KULLANIMININ ETKİSİ: VAKA KONTROL ÇALIŞMASI

Objectives: Since recurrent implantation failure (RIF) is a challenging fact, effects of different therapeutic immunomodulatory agents are being investigated to overcome this problem. This study aimed to evaluate the effect of intralipid on pregnancy outcomes of IVF patients with RIF.&#x0D; Methods: 116 of the participants who received only the short antagonist protocol allocated in the control group, whereas 106 patients were in intralipid group by additionally receiving intravenous lipid (SMOFlipid®). Intralipid was given on the day of embryo transfer, on the day of positive pregnancy test and continued weekly until the tenth week of pregnancy. Implantation rate, biochemical pregnancy rate, clinical pregnancy rate and live birth rate were evaluated.&#x0D; Results: The positive pregnancy test, clinical pregnancy rate and live birth rate were statistically significantly higher (p0.05).&#x0D; Conclusions: This study revealed that intralipid therapy has better pregnancy outcomes in patients with RIF compared to patients undergo standard IVF protocol only. Further prospective studies are needed to suggest the routine use of intralipid in patients with RIF.

Investigation of Changes in Liver Microanatomy in the Steatosis Model Created by Permanent Canula in Rats

Objective: The knowledge of nonalcoholic fatty liver disease (NAFLD) and Nonalcoholic Steatohepatitis (NASH) is limited to the findings from available suitable models for this disease. A number of rodent models have been described in which relevant liver pathology develops in an appropriate metabolic context. In this experimental study, it was aimed to create a new liver fat model by giving fat from the portal vein of rats and to visualize the changes in the liver with advanced microscopic techniques. &#x0D; Methods: 28 female rats were used in the study. Permanent intraabdominal cannulas were inserted into the portal vein of the rats. Rats were randomly divided four group. Intralipid 20% substance was injected through cannula to the experimental groups during the test period. Control group received saline at the same rate. At the end of the experiment, the animals were visualized with a laser speckle microscope and livers were divided into sections according to the stereological method. The sections were painted with Hematoxylin-Eosin, Oil red o, Masson trichoma, Bodipy, Nile red. Sections were evaluated under a microscope. &#x0D; Results: Ballooning, inflammation and fibrosis were observed in the 2 week intralipid group. In the 1 week intralipid group, the rate of parenchyma decreased while the sinusoid rate increased, and sinusoid rate increased significantly in the 2 week intralipid (p˂0.05). &#x0D; Conclusion: According to the findings, steatohepatitis was detected in the 2 week intralipid, whereas only steatosis was observed in the 1 week intralipid. Thus, it was concluded that the newly formed rat model causes steatosis.

SMOFlipid Impact on Growth and Neonatal Morbidities in Very Preterm Infants.

The soybean oil, medium-chain triglycerides, olive oil, and fish oil lipid (SMOFlipid) is increasingly being used worldwide without definite evidence of its benefits. We examined the effect of SMOFlipid on growth velocity and neonatal morbidities in very preterm infants. Very preterm infants who received soybean-based lipid emulsion between January 2015 and 2018 were compared with those who received SMOFlipids between 2019 and January 2022 in our neonatal tertiary center. Linear regression analysis was conducted to analyze the association between type of lipid emulsion and growth velocity. Modified log-Poisson regression with generalized linear models and a robust variance estimator (Huber–White) were applied to adjust for potential confounding factors. A total of 858 infants met our inclusion criteria. Of them, 238 (27.7%) received SMOFlipid. SMOFlipid was associated with lower growth velocity between birth and 36-week corrected gestational age compared with intralipid Δ weight z-score (adjusted mean difference (aMD) −0.67; 95% CI −0.69, −0.39). Subgroup analysis indicated that mainly male infants in the SMOFlipid–LE group had a lower Δ weight z-score compared to those in the intralipid group (p < 0.001), with no difference observed in females (p = 0.82). SMOFlipid was associated with a lower rate of bronchopulmonary dysplasia (BPD) (aRR 0.61; 95% CI 0.46, 0.8) and higher rate of late-onset sepsis compared with intralipid (aRR 1.44; 95% CI 1.22–1.69). SMOFlipid was associated with lower growth velocity and BPD but higher rate of late-onset sepsis—it is a double-edged sword.

Hepatic Function in Premature Lambs Supported by the Artificial Placenta and Total Parenteral Nutrition.

The artificial placenta (AP) promotes organ development and reduces organ injury in a lamb model of extreme prematurity. This study evaluates hepatic outcomes after AP support with total parenteral nutrition (TPN) administration. Premature lambs (116-121 days estimated gestational age; term = 145) were cannulated for 7 days of AP support. Lambs received TPN with SMOFlipid (n = 7) or Intralipid (n = 5). Liver function and injury were compared between the two groups biochemically and histologically. Groups were compared by ANOVA with Tukey's multiple comparisons or linear-mixed effects models. From baseline to day 7, total bilirubin (Intralipid 2.6 ± 2.3 to 7.9 ± 4.4 mg/dl; SMOFlipid 0.3 ± 0.1 to 5.5 ± 2.3 mg/dl), alanine aminotransferase, and gamma-glutamyl transferase increased in both groups ( p < 0.001 for all). Direct bilirubin (0.3 ± 0.2 to 1.8 ± 1.4 mg/dl; p = 0.006) and AST (27 ± 5 to 309 ± 242 mg/dl; p < 0.001) increased in SMOFlipid group (not measured in Intralipid group). On liver histology, Intralipid showed more cholestasis than SMOFlipid; both groups showed more than tissue controls. The Intralipid group alone showed hepatocyte injury and had more congestion than controls. Lambs supported by the AP with TPN administration maintain normal hepatic function and sustain minimal hepatic injury. SMOFlipid is associated with decreased cholestasis and hepatic injury versus Intralipid.

Subanesthetic Dose of Propofol Activates the Reward System in Rats.

Propofol has addictive properties, even with a single administration, and facilitates dopamine secretion in the nucleus accumbens (NAc). Activation of the dopaminergic circuits of the midbrain reward system, including the ventral tegmental area (VTA) and NAc, plays a crucial role in addiction. However, the effects of propofol on synaptic transmission and biochemical changes in the VTA-NAc circuit remain unclear. We investigated the effects of subanesthetic doses of propofol on rat VTA neurons and excitatory synaptic transmission in the NAc using slice patch-clamp experiments. Using immunohistochemistry and western blot analyses, we evaluated the effects of intraperitoneal propofol administration on the expression of addiction-associated transcription factor ΔFosB (truncated form of the FBJ murine osteosarcoma viral oncogene homolog B protein) in the NAcs in 5-week-old rats. In the current-clamp mode, a subanesthetic dose (0.5-5 µmol/L) of propofol increased the action potential frequency in about half the VTA neurons (excited neurons: control: 9.4 ± 3.0 Hz, propofol 0.5 µmol/L: 21.5 ± 6.0 Hz, propofol 5 µmol/L: 14.6 ± 5.3 Hz, wash: 2.0 ± 0.7 Hz, n = 14/27 cells; unchanged/suppressed neurons: control: 1.68 ± 0.94 Hz, propofol 0.5 µmol/L: 1.0 ± 0.67 Hz, propofol 5 µmol/L: 0.89 ± 0.87 Hz, wash: 0.16 ± 0.11 Hz, n = 13/27 cells). In the voltage-clamp mode, about half the VTA principal neurons showed inward currents with 5 µmol/L of propofol (inward current neurons: control: -20.5 ± 10.0 pA, propofol 0.5 µmol/L: -62.6 ± 14.4 pA, propofol 5 µmol/L: -85.2 ± 18.3 pA, propofol 50 µmol/L: -17.1 ± 39.2 pA, washout: +30.5 ± 33.9 pA, n = 6/11 cells; outward current neurons: control: -33.9 ± 14.6 pA, propofol 0.5 µmol/L: -29.5 ± 16.0 pA, propofol 5 µmol/L: -0.5 ± 20.9 pA, propofol 50 µmol/L: +38.9 ± 18.5 pA, washout: +40.8 ± 32.1 pA, n = 5/11 cells). Moreover, 0.5 µmol/L propofol increased the amplitudes of evoked excitatory synaptic currents in the NAc, whereas >5 µmol/L propofol decreased them (control: 100.0 ± 2.0%, propofol 0.5 µmol/L: 118.4 ± 4.3%, propofol 5 µmol/L: 98.3 ± 3.3%, wash [within 10 min]: 70.7 ± 3.3%, wash [30 minutes later]: 89.9 ± 2.5%, n = 13 cells, P < .001, Dunnett's test comparing control and propofol 0.5 µmol/L). Intraperitoneally administered subanesthetic dose of propofol increased ΔFosB expression in the NAc, but not in VTA, 2 and 24 hours after administration, compared with the Intralipid control group (propofol 2 hours: 0.94 ± 0.15, 24 hours: 0.68 ± 0.07; Intralipid 2 hours: 0.40 ± 0.03, 24 hours: 0.37 ± 0.06, P = .0002 for drug in the 2-way analysis of variance). Even a single administration of a subanesthetic dose of propofol may cause rewarding change in the central nervous system. Thus, there is a potential propofol rewarding effect among patients receiving anesthesia or sedation with propofol, as well as among health care providers exposed to propofol.

The cardioprotective effect of intralipid in decreasing the ischemic insults during off-pump coronary artery revascularization

BackgroundOff pump coronary artery revascularization (OPCAB) surgeries have benefits over the conventional on pump cardiac surgery, because it avoids the trauma caused by cardiopulmonary bypass (CPB) and minimize aortic manipulation. However, some disadvantages of OPCAB include the concern of ineffective coronary revascularization. Some drugs have shown the ability to protect the myocardium in different studies, by different methods. The usage of intralipid has been shown to make a better functional recovery of the cardiac muscles and help to decrease the myocardial infarct size, it shortens the action potential time, which show polyunsaturated fatty acids diets mechanism as an antiarrhythmic drug, and are associated with low incidence of coronary artery disease.MethodsWe divided patients into two groups according to the randomization envelopes: intralipid group (group A) received 1.5 ml/kg intralipid 20% through central venous line after sternotomy over 1 h and during infusion, blood pressure, heart rate, and temperature were monitored all through the infusion time. Control group (group B) received normal saline 0.9% in the same volume over the same duration.ResultsThis study showed that infusion of 1.5 ml/kg intralipid after sternotomy in off pump coronary artery revascularization given as preconditioning agent improve the myocardial ischemia reperfusion injury, decrease the need for high doses of nor adrenaline infusion after revascularization, earlier normalization in troponin levels starting 24 h after surgery and higher values of cardiac index were measured in ICU using PICCO.ConclusionsThis study showed the benefits of infusion of 1.5 ml/kg of intralipid after sternotomy, in preconditioning during OPCABG. Preconditioning with intralipid proved to decrease reperfusion injury in myocardium expressed by improvement in cardiac functions (EF and cardiac index) and normalization of specific cardiac marker (cardiac troponin I).

Effect of etomidate on the reuniens neuronal activity.

To explore the effect of etomidate on the neuronal activity of ventral thalamic reuniens nucleus and the underlying mechanisms. Whole-cell patch clamp method was used to explore the effect of etomidate on the activity of ventral thalamic reuniens neurons in the acute brain slices obtained from 4-5 weeks old C57BL/6J mice. The electrophysiological characteristics of ventral thalamic reuniens neurons were recorded in the current clamp mode, and then the effects of etomidate (0.5, 2.0, 8.0 μmol/L etomidate groups) and intralipid (intralipid group) on the discharge frequency and membrane potential of ventral thalamic reuniens neurons were recorded. During the experiment, the ventral thalamic reuniens neuron firing rates (RNFRs) were recorded as FB, FD and Fw before, after administration, and after elution; and the membrane potential was recorded as MPB and MPD before, after administration. The chlorine channel of gamma-amino butyric acid Type A (GABAA) receptor was blocked with 100 μmol/L picrotoxin (PTX). The RNFRs were recorded as FBS, FETO and FETO+PTX before, after perfusing etomidate with sub-anesthesia concentration (0.5 μmol/L) and after perfusing both PTX and etomidate. In the intralipid group, there was no significant difference among the FB, FD and Fw (P>0.05). But in the etomidate groups (0.5, 2.0, 8.0 μmol/L), the FD was less than the FB, there was significant difference (all P<0.01); the Fw was higher than the FD, there was significant difference (all P<0.05). Moreover, there was significant difference in the inhibitory degree of the RNFRs between the 0.5 μmol/L etomidate group and the 8.0 μmol/L etomidate group (P<0.05). In the experiment to explore the mechanism of etomidate (0.5 μmol/L), the FETO was compared with the FBS, there was significant difference (P<0.01); but when the FETO+PTX was compared with the FBS, there was no significant difference (P>0.05). Etomidate can inhibit the activity of ventral thalamic reuniens neurons in concentration-dependent manner, and which is reversible. Etomidate with sub-anesthetic concentration inhibits the activity of ventral thalamic reuniens neurons via targeting the GABAA receptor.

Expression and Regulation of the GABAA Receptor/STEP61 Signaling Pathway in Cerebral Cortical Neurons Treated with Emulsified Isoflurane In Vitro.

Emulsified isoflurane (EISO) is an intravenous anesthetic. However, researchers have not clearly determined how emulsified isoflurane affects the central nervous system during the process of anesthesia. The aim of this study was to explore changes in the gamma-aminobutyric acid type A receptor subunit (GABAA), 61 kD isoform of striatal-enriched protein phosphatase (STEP61) signaling pathway, and epigenetic regulation in cortical neurons after treatment with emulsified isoflurane. After immunological identification, the isolated neurons were randomly divided into three groups: the blank group (Con), intralipid treatment group (FE), and emulsified isoflurane treatment group (EISO). Neuron viability was assayed using cell counting kit-8 (CCK-8). The expression levels of target nucleic acids, proteins, and corresponding ligands were detected. Using real-time polymerase chain reaction (PCR) to assess the promoter methylation of ion channel proteins in the cerebral cortex of rats anesthetized with EISO, we observed changes in promoter methylation of the genes encoding gamma-aminobutyric acid type A receptor α1 subunit (GABAAα1), N-methyl-d-aspartate receptor subunit 1 (NMDAR1), and mu opioid receptor 1 (OPRM1), accompanied by changes in the levels of their messenger ribonucleic acids (mRNAs) and proteins. The levels of ligands for these receptors were also altered. EISO altered the methylation rate of the promoter region of channel protein-coding genes involved in the GABAA/STEP61 signaling pathway in cerebral cortical neurons to regulate gene expression. The ligands for the receptors were also changed.

Choice of Lipid Emulsion Determines Inflammation of the Gut-Liver Axis, Incretin Profile, and Insulin Signaling in a Murine Model of Total Parenteral Nutrition.

The aim of this study is to test whether the choice of the lipid emulsion in total parenteral nutrition (TPN), that is, n-3 fatty acid-based Omegaven versus n-6 fatty acid-based Intralipid, determines inflammation in the liver, the incretin profile, and insulin resistance. Jugular vein catheters (JVC) are placed in C57BL/6 mice and used for TPN for 7 days. Mice are randomized into a saline group (saline infusion with oral chow), an Intralipid group (IL-TPN, no chow), an Omegaven group (OV-TPN, no chow), or a chow only group (without JVC). Both TPN elicite higher abundance of lipopolysaccharide binding protein in the liver, but only IL-TPN increases interleukin-6 and interferon-γ, while OV-TPN reduces interleukin-4, monocyte chemoattractant protein-1, and interleukin-1α. Insulin plasma concentrations are higher in both TPN, while glucagon and glucagon-like peptide-1 (GLP-1) were higher in IL-TPN. Gluconeogenesis is increased in IL-TPN and the nuclear profile of key metabolic transcription factors shows a liver-protective phenotype in OV-TPN. OV-TPN increases insulin sensitivity in the liver and skeletal muscle. OV-TPN as opposed to IL-TPN mitigates inflammation in the liver and reduces the negative metabolic effects of hyperinsulinemia and hyperglucagonemia by "re-sensitizing" the liver and skeletal muscle to insulin.

SMOFlipid vs Intralipid 20%: Effect of Mixed-Oil vs Soybean-Oil Emulsion on Parenteral Nutrition-Associated Cholestasis in the Neonatal Population.

Parenteral nutrition (PN) is critical for the growth and development of premature neonates who are unable to reach nutrition goals enterally. Using soybean-oil emulsions in PN is a risk factor for cholestasis, leading to alternative dosing strategies including a reduction in total lipid prescribed. Recently, SMOFlipid has been utilized with the goal of avoiding cholestasis while maintaining energy intake. The aim of our study was to compare the incidence of PN-associated cholestasis (PNAC) in patients admitted to the neonatal intensive care unit (NICU) who received either Intralipid 20% or SMOFlipid. This single-center, retrospective study evaluated all NICU patients who received PN for ≥14days. Patients who received SMOFlipid were compared with those who received Intralipid. The primary end point was incidence of PNAC. Secondary end points included (1) prevalence of elevated liver function tests; (2) effect on select laboratory parameters; (3) development of PNAC by age; and (4) incidence of retinopathy of prematurity. A total of 136 neonates were included. Nine of 55 patients (16.4%) in the Intralipid group and 2 of 81 patients (2.5%) in the SMOFlipid group developed cholestasis, defined asdirect bilirubin > 2mg/dLor direct bilirubin > 20% of total bilirubin,when total bilirubin is >5mg/dL,on or before 30days post initiation of PN (P = .007). Use of SMOFlipid as the lipid emulsion component of PN may be beneficial in prevention of PNAC in NICU patients that are receiving PN for ≥2 weeks.

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.

Pharmacological preconditioning with intralipid in patients undergoing off-pump coronary artery bypass surgery

Aims and Objectives:The objective of the study was to determine the preconditioning myocardial protective effects of intralipid (IL) in off-pump coronary artery bypass (OPCAB) surgery by measuring highly sensitive troponin T (hsTnT) and cardiac-specific creatine kinase (CK-MB) as markers of myocardial injury.Materials and Methods:Thirty patients, scheduled to undergo elective OPCAB surgery, were randomly assigned to the IL group (n = 15) or control (C) group (n = 15); the IL group received an infusion of 20% IL 2 ml/kg, 30 min prior to revascularization and the control group received an equivalent volume of normal saline. Serum levels of hsTnT and CK-MB were measured before surgery and at 6 h, 24 h, 48 h, and 72 h postoperatively. Also, intraoperative hemodynamic parameters, inotrope use, ventilatory hours, ICU stay, postoperative left ventricular ejection fraction, postoperative lipid profile, renal and hepatic function tests were measured.Results:The hsTnT values at the 24 h, 48 h, and 72 h in IL group were significantly lower as compared with the control group. The decline in plasma levels of CK-MB mirrored the hsTnT levels post revascularization at 24 h and 48 h in the IL group compared with the control group; however, at 72 h, level was comparable in both the groups. None of the treated patients had abnormal lipid metabolism, deranged renal, and hepatic function.Conclusion:The study revealed Intralipid as a safe pharmacological preconditioning agent for OPCAB surgeries which can reduce the postischemic myocardial injury indicated by the reduction in postischemic cardiac enzymes hsTnT and CK-MB.

Intralipid Immunotherapy for Repeated IVF Failure

The intravenous fat emulsion, intralipid, has been hypothesised to be an effective and safe treatment for repeated in vitro fertilisation (IVF), implantation failure and pregnancy loss. This exploratory, retrospective cohort study determined pregnancy outcomes and documented adverse events associated with intralipid use. Ninety-three women were identified as having received intralipid for a history of repeated unsuccessful IVF cycles and pre-viable pregnancy loss in two Australian IVF units that independently recruited between October 2014 and July 2016. Pregnancy outcomes and adverse events were recorded in fresh and frozen embryo transfer cycles in which the infusion was administered. The 93 women who received intralipid had a clinical pregnancy rate of 40.0%, compared with 35.0% in 651 age-matched controls undergoing IVF, which was not significantly different. The intralipid group had a livebirth rate of 35.7%. Apart from flushing, which was experienced by one individual, there were no adverse events associated with intralipid use. As a prelude to definitive evidence of benefit, we did not identify a safety concern or reduced pregnancy rates in intralipid users compared to controls. Indeed, these outcomes were better than expected in a poor prognosis group. This data supports an argument for large, randomised controlled trials to determine the benefit of intralipid in the treatment of recurrent implantation failure or miscarriage.

Determination of the Effect of High-Dose Intralipid in Compared to Its Gradual Dose in Very Low Birth Weight Newborns: A Case-control Study

Objective: The aim of this study was to determine the effect of high dose intralipid in compared to its gradual dose in very low birth weight newborns in Iran. &#x0D; Methods: This study was a case-control study that conducted on 104 very low birth weight infants (&lt;1500 g) referred to Akbarabadi hospital of Tehran (Iran) in 2016. The infants were randomly assigned to two groups (case group: 52 vs. control group: 52). The control group received intralipid 20% with a dose of 1 g/kg/24 h in the first and second day of the study, then from 3rd day to 3 g/kg /24h was raised. But, the case group received 3 g/kg/24 h of intralipid 20% from the first day and continued until the end of the study. In both groups, the study lasted for up to 30 days. Data were collected and analyzed using SPSS22 software. Also P-Value &lt;0.05 was considered as a significant level.&#x0D; Results: The results showed mean daily weight gain in case group is higher than control group and this difference was significant statistically (P-Value &lt; 0.05). Also, although the mean of blood sugar, triglyceride, HCO3, the number of positive blood culture and the number of positive CPR in case group were higher than control group, but these differences were not statistically significant (P-Value &gt;0.05).&#x0D; Conclusion: Given that the better and faster growth of newborns in the intralipid group with high-dose in compared to intralipid group with gradual dose, the use of higher initial doses is recommended in newborns with very low birth weight.

Early Enteral Administration of a Complex Lipid Emulsion Supplement Prevents Postnatal Deficits in Docosahexaenoic and Arachidonic Acids and Increases Tissue Accretion of Lipophilic Nutrients in Preterm Piglets.

Preterm delivery and current nutrition strategies result in deficiencies of critical long-chain fatty acids (FAs) and lipophilic nutrients, increasing the risk of preterm morbidities. We sought to determine the efficacy of preventing postnatal deficits in FAs and lipophilic nutrients using an enteral concentrated lipid supplement in preterm piglets. Preterm piglets were fed a baseline diet devoid of arachidonic acid (AA) and docosahexaenoic acid (DHA) and randomized to enteral supplementation as follows: (1) Intralipid (IL), (2) complex lipid supplement 1 (CLS1) with an AA:DHA ratio of 0.25, or (3) CLS2 with an AA:DHA ratio of 1.2. On day 8, plasma and tissue levels of FAs and lipophilic nutrients were measured and ileum histology performed. Plasma DHA levels decreased in the IL group by day 2. In contrast, DHA increased by day 2 compared with birth levels in both CLS1 and CLS2 groups. The IL and CLS1 groups demonstrated a continued decline in AA levels during the 8-day protocol, whereas AA levels in the CLS2 group on day 8 were comparable to birth levels. Preserving AA levels in the CLS2 group was associated with greater ileal villus height and muscular layer thickness. Lipophilic nutrients were effectively absorbed in plasma and tissues. Enteral administration of CLS1 and CLS2 demonstrated similar increases in DHA levels compared with birth levels. Only CLS2 maintained AA birth levels. Providing a concentrated complex lipid emulsion with an AA:DHA ratio > 1 is important in preventing postnatal AA deficits.

The effect of administration of intravenous intralipid on pregnancy outcomes in women with implantation failure after IVF/ICSI with non-donor oocytes: A randomised controlled trial

ObjectiveDoes the administration of intravenous intralipid in women with previous implantation failure at the time of embryo transfer improve pregnancy outcomes in terms of biochemical pregnancy rate, clinical pregnancy rate, ongoing pregnancy rate, and ongoing pregnancy rate? Study DesignThis was a single blinded randomised controlled trial of 105 subjects with previous failed IVF undergoing self donor oocyte IVF/ICSI from January 2017 to May 2018. Randomisation was by computer generated sequence after oocyte pickup. Results were analysed for 102 women, excluding three women due to poor embryo quality. Women in the study arm(n = 52) received 2 doses of 20% intravenous intralipid (Fresenius Kabi), 4 ml diluted in 250 ml normal saline by slow infusion. The first dose was given immediately after oocyte recovery, and the second dose was given on the day of embryo transfer, 1 h prior to the transfer. The control group (n = 50) received normal saline. Flexible ovarian stimulation protocols were used. All the women received routine luteal phase support with micronised vaginal progesterone. Results102 women underwent analysis, 52 in the study group and 50 in control group. There was no significant difference in the baseline characteristics. There was a significant difference in the biochemical pregnancy rate in the intralipid group (40.38%) versus control (16%) [(p = 0.006), RR = 2.5 (1.23–5.16 CI)], clinical pregnancy rate [(34.62% vs 14%), p = 0.006, RR = 2.5(1.13–5.40 CI)], implantation rate [(16.6% vs 6.6%), p = 0.012, RR = 2.5(1.18 to 5.41 CI)], and take home baby rate [28.8% vs 10%, p = 0.024, RR = 2.8(1.1–7.3)]. The adjusted odds ratio for clinical pregnancy in women who received intralipid vs placebo was 3.1 (1.02–9.70 95% CI), p = 0.046. No adverse effects of intralipid were observed. ConclusionThis study shows a statistically significant increase in implantation rate and live birth rate in women who receive intravenous intralipid with prior implantation failure after IVF/ICSI. These findings concur with other studies; however, literature is limited. The effect of intralipid on the immunological abnormalities in women who experience recurrent implantation failure needs to be investigated further.

Effect of intralipid administration on calcium therapy in verapamil toxicity.

Lipid emulsions are promising with regard to the treatment of toxicity by agents of high lipophilic nature. Our objective is to investigate the efficacy of intralipid 20% and calcium administration at different times when symptoms of cardiac toxicity occur during verapamil infusion. 24 adult male Spraque-Dawley rats were randomly divided into 4 different groups, the control group, calcium group, calcium following 20% intralipid group and concomitant 20% intralipid and calcium group. Following monitoring under ketamine anesthesia, all groups were administered 37.5 mg kg-1 h-1 verapamil infusion until a 50% decrease occurred in MAPb. At the end of the infusion, verapamil infusion was decreased down to 15 mg kg-1h-1 and the treatment agents predetermined for the groups were administered concomitantly. There is no statistically significant difference between the administration of 20% intralipid synchronized with calcium or as a pretreatment, but both groups provided a higher survival rate when compared to the other groups. The administration of calcium alone in verapamil toxicity is not sufficient; when calcium and 20% intralipid are administered together, there is no difference between the administration of lipid and calcium concomitantly and the administration of lipid prior to calcium (Tab. 1, Fig. 2, Ref. 23).