A four-oil intravenous lipid emulsion improves markers of liver function, triglyceride levels and shortens length of hospital stay in adults: a systematic review and meta-analysis.

Clinical trials have reported that a four-oil intravenous lipid emulsion (SMOFlipid) play a positive role in immune function, but showed inconsistent outcomes compared to other lipid emulsions. A systematic review and meta-analysis was conducted to evaluate the effect of SMOFlipid on liver function, triglycerides (TG), inflammatory markers, and clinical outcomes in hospitalized adults after short-term use compared to others. A search of the PubMed, Medline, Embase, China National Knowledge Infrastructure, and Wanfang databases was performed to identify the included randomized controlled trials. Trials with adults who were administrated a short-term course of SMOFlipid were included. A meta-analysis on liver function markers, TG, inflammatory markers, and clinical outcomes was conducted. A total of 18 randomized controlled trials with 1188 patients were included. Compared to other lipid emulsions, SMOFlipid was associated with a significant reduction in ALT, AST, γ-glutamyltransferase, total bilirubin, TG, C-reactive protein and length of hospital stay. No effect on serum interleukin-6 levels or adverse events were observed. For adult patients, our meta-analysis indicated that SMOFlipid may be beneficial to the liver and prone to prevent hyperlipidemia. The SMOFlipid also shortened length of hospital stay.

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.

Validation of suPAR turbidimetric assay on Cobas® (c502 and c702) and comparison to suPAR ELISA.

suPAR is a plasma marker of chronic inflammation, and an elevated suPAR is consistently associated with worse outcome in a variety of clinical conditions. Quantification of suPAR is useful for determining patient risk in triage, but there is no fast automatized method for quick determination of suPAR. We developed and validated a rapid latex particle-enhanced turbidimetric immunoassay for quantification of plasma suPAR on the c502 and the c702 Roche Cobas® 8000 measurment systems. The turbidimetric assay was validated against the suPARnostic® ELISA (ViroGates, Denmark). This validation demonstrates suPAR can be analysed by turbidimetry giving very similar results (<15% difference) compared to the ELISA method and the observed correlations (n = 103) were strong, r > 0.95. Roche Cobas® 8000 instruments demonstrated repeatability and repoducibility, CV % at 3.4-4.1 and 5.7-11.4, respectively. The estimated limit of detection was 1.30 µg/L and 1.31 µg/L for the Cobas® c502 and c702, respectively. Dilution tests showed linearity of suPAR from 1.8 to 26.5 µg/L. The acceptable concentrations of Bilirubin, Intralipid and Hemoglobin, were 350 µmol/L, 3.3 g/L and 1.4 g/L, respectively. suPAR can be quantified reproducibly within 10 min using a turbidimetry assay. This assay is faster than ELISA with similar results, making it suitable for clinical routine analysis.

Influence of Human Milk and Parenteral Lipid Emulsions on Serum Fatty Acid Profiles in Extremely Preterm Infants.

BACKGROUND: Infants born prematurely are at risk of a deficiency in ω-6 and ω-3 long-chain polyunsaturated fatty acids (LC-PUFAs) arachidonic acid (AA) and docosahexaenoic acid (DHA). We investigated how fatty acids from breast milk and parenteral lipid emulsions shape serum LC-PUFA profiles in extremely preterm infants during early perinatal life. METHODS: Ninety infants born < 28 weeks gestational age were randomized to receive parenteral lipids with or without the ω-3 LC-PUFAs eicosapentaenoic acid (EPA) and DHA (SMOFlipid: Fresenius Kabi, Uppsala, Sweden, or Clinoleic: Baxter Medical AB, Kista, Sweden, respectively). The fatty acid composition of infant serum phospholipids was determined from birth to postmenstrual age 40 weeks, and in mother's milk total lipids on postnatal day 7. Enteral and parenteral intake of LC-PUFAs was correlated with levels in infant serum. RESULTS: Infants administered parenteral ω-3 LC-PUFAs received 4.4 and 19.3 times more DHA and EPA, respectively, over the first 2 weeks of life. Parenteral EPA but not DHA correlated with levels in infant serum. We found linear relationships between dietary EPA and DHA and infant serum levels in the Clinoleic (Baxter Medical AB) group. The volume of administered SMOFlipid (Fresenius Kabi) was inversely correlated with serum AA, whereas Clinoleic (Baxter Medical AB) inversely correlated with serum EPA and DHA. CONCLUSIONS: There appears to be no or low correlation between the amount of DHA administered parenterally and levels measured in serum. Whether this observation reflects serum phospholipid fraction only or truly represents the amount of accreted DHA needs to be investigated. None of the parenteral lipid emulsions satisfactorily maintained high levels of both ω-6 and ω-3 LC-PUFAs in infant serum.

Effect of changing the lipid component of home parenteral nutrition in adults.

BACKGROUND: The effect of different lipid emulsions (LEs) within the parenteral nutrition (PN) regimen of adult home PN (HPN) patients is not clear. This study investigated the effect of changing adult HPN patients from a soybean oil based LE (Intralipid) to either a fish oil containing LE (providing n-3 fatty acids) (SMOFLipid) or an olive oil based LE (ClinOleic). METHODS: Thirty two adults receiving long-term HPN with Intralipid as the LE were transferred to receive either SMOFLipid (n = 13) or ClinOleic (n = 19) for 60 days. Liver function markers, cholesterol, triglycerides, a full profile of fatty acids, and several cytokines were measured at study entry and after 60 days. RESULTS: SMOFLipid did not affect liver function markers, blood lipids or plasma cytokines. ClinOleic lowered both gamma-glutamyltranspeptidase (P = 0.044) and interleukin-8 (P = 0.030) concentrations. Both LEs induced marked changes in the fatty acid profile of plasma. SMOFLipid resulted in significant decreases in the proportions of linoleic acid, several other n-6 fatty acids and the essential fatty acid (EFA) deficiency indicator mead acid and significant increases in the proportions of the n-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid. ClinOleic resulted in significant decreases in the proportions of some saturated fatty acids, linoleic acid, several n-6 fatty acids, all n-3 fatty acids and mead acid and a significant increase in the proportion of oleic acid. The ratio of mead to arachidonic acid in plasma was not altered by either SMOFLipid or ClinOleic. No patient had a mead acid to arachidonic acid ratio of >0.2, the cut-off used to indicate EFA deficiency. CONCLUSION: Both SMOFLipid and ClinOleic significantly alter the fatty acid profile of plasma in adult HPN patients previously using Intralipid. Neither LE induces EFA deficiency in these patients. SMOFLipid did not alter liver function markers or inflammation. In contrast, ClinOleic decreased some, though not all, markers of liver function and inflammation. SMOFLipid and ClinOleic may both be considered for use in adult HPN patients.

Camelia oil and soybean-camelia oil blend enhance antioxidant activity and cardiovascular protection in hamsters.

OBJECTIVES: The aim of this study was to examine the effects of several vegetable oils and blended oil composed of soybean and camellia oils on blood lipid reduction and antioxidative activity. METHODS: Forty male hamsters were fed an AIN-93 G diet for 1 wk, followed by dividing into five groups: control group-1 was fed a low-fat diet containing 5% oil for 6 wk, and the other four groups were fed high-fat diets with group-2 containing 14% palm oil, group-3 containing 14% camellia oil, group-4 containing 14% soybean oil, and group-5 containing 14% blended oil (8.4% soybean oil and 5.6% camellia oil) along with 0.2% cholesterol and 0.1% bile acid. RESULTS: High-fat diets raised serum triacylglycerol, total cholesterol, and aspartate aminotransferase in hamsters without affecting alanine aminotransferase. Compared with palm oil-containing diet, the other three high-fat diets reduced serum total cholesterol, low-density lipoprotein cholesterol, and the ratio of low-density lipoprotein to high-density lipoprotein cholesterol with an opposite trend for liver total cholesterol. However, compared with the control group, the serum high-density lipoprotein cholesterol level was raised for all four high-fat diets. The higher the degree of oil unsaturation, the higher the serum thiobarbituric acid reactive substances and the lower the liver triacylglycerol level and activities of fatty acid synthase, glucose 6-phosphate dehydrogenase, and malic enzymes. Both soybean and blended oils lowered the antioxidative activity of liver. CONCLUSION: Camellia and blended oils were more efficient than soybean oil in elevating serum high-density lipoprotein cholesterol and decreasing the ratio of low-density lipoprotein to high-density lipoprotein cholesterol in hamsters.

Structural difference of palm based Medium- and Long-Chain Triacylglycerol (MLCT) further reduces body fat accumulation in DIO C57BL/6J mice when consumed in low fat diet for a mid-term period.

Medium-and-Long Chain Triacylglycerol (MLCT) is a type of structured lipid that is made up of medium chain, MCFA (C8-C12) and long chain, LCFA (C16-C22) fatty acid. Studies claimed that consumption of MLCT has the potential in reducing visceral fat accumulation as compared to long chain triacylglycerol, LCT. This is mainly attributed to the rapid metabolism of MCFA as compared to LCFA. Our study was designed to compare the anti-obesity effects of a enzymatically interesterified MLCT (E-MLCT) with physical blend of palm kernel and palm oil (B-PKOPO) having similar fatty acid composition and a commercial MLCT (C-MLCT) made of rapeseed/soybean oil on Diet Induced Obesity (DIO) C57BL/6J mice for a period of four months in low fat, LF (7%) and high fat, HF (30%) diet. The main aim was to determine if the anti-obesity effect of MLCT was contributed solely by its triacylglycerol structure alone or its fatty acid composition or both. Out of the three types of MLCT, mice fed with Low Fat, LF (7%) E-MLCT had significantly (P<0.05) lower body weight gain (by ~30%), body fat accumulation (by ~37%) and hormone leptin level as compared to both the LF B-PKOPO and LF C-MLCT. Histological examination further revealed that dietary intake of E-MLCT inhibited hepatic lipid accumulation. Besides, analysis of serum profile also demonstrated that consumption of E-MLCT was better in regulating blood glucose compared to B-PKOPO and C-MLCT. Nevertheless, both B-PKO-PO and E-MLCT which contained higher level of myristic acid was found to be hypercholesterolemic compared to C-MLCT. In summary, our finding showed that triacylglycerol structure, fatty acid composition and fat dosage play a pivotal role in regulating visceral fat accumulation. Consumption of E-MLCT in low fat diet led to a significantly lesser body fat accumulation. It was postulated that the MLM/MLL/LMM/MML/LLM types of triacylglycerol and C8-C12 medium chain fatty acids were the main factors that contributed to the visceral fat suppressing effect of MLCT. Despite being able to reduce body fat, the so called healthful functional oil E-MLCT when taken in high amount do resulted in fat accumulation. In summary, E-MLCT when taken in moderation can be used to manage obesity issue. However, consumption of E-MLCT may lead to higher total cholesterol and LDL level.

High trans but not saturated fat beverage causes an acute reduction in postprandial vascular endothelial function but not arterial stiffness in humans.

A diet high in trans-fatty acids (TFAs) is associated with a higher risk of cardiovascular disease (CVD) than a diet high in saturated fatty acids (SFAs), but the mechanisms remain unclear. We hypothesized that a beverage high in TFAs would cause a larger reduction in postprandial endothelial function and an increase in arterial stiffness, in part from greater reductions in insulin sensitivity, compared with a beverage high in SFAs. Eleven healthy adults (aged 47±5 years) ingested a warm test beverage (520 kcal, 56 g total fat, 5 g carbohydrate, 1 g protein) high in either TFAs or SFAs in a randomized cross-over study. Ingestion of the beverage high in TFAs (p<0.01) but not high in SFAs (p=0.49) decreased endothelial function (brachial artery flow-mediated dilation, mmΔ) at 3-4 hours (p<0.01 for time; p=0.034 for interaction), but did not alter aortic stiffness or carotid ß-stiffness. The homeostasis model of insulin resistance (interaction p=0.062) tended to decrease after SFAs but not TFAs. A beverage high in TFAs but not SFAs results in a postprandial reduction in endothelial function and a trend for decreased insulin sensitivity, potentially explaining the higher risk of CVD with a diet high in TFAs.

The Effect of Lipid Emulsion on Pharmacokinetics of Bupivacaine in Rats: Long-Chain Triglyceride Versus Long- and Medium-Chain Triglyceride.

BACKGROUND: Lipid infusions have been proposed to treat local anesthetic-induced cardiac toxicity. This study compared the effects of long-chain triglyceride (LCT) emulsions with those of long- and medium-chain triglyceride (LCT/MCT) emulsions on the pharmacokinetics of bupivacaine in a rat model. METHODS: After administration of intravenous infusion of bupivacaine at 2 mg·kg·min for 5 minutes in Sprague-Dawley (SD) rats, either Intralipid 20%, an LCT emulsion (LCT group, n = 6), or Lipovenoes 20%, an LCT/MCT emulsion (LCT/MCT group, n = 6), was infused at 2mg·kg·min for 5 minutes. The concentrations of total plasma bupivacaine and bupivacaine that were not bound by lipid (lipid unbound) were measured by a liquid chromatography-tandem mass spectrometric method. A 2-compartmental analysis was performed to calculate the lipid-bound percentage of bupivacaine and its pharmacokinetics. RESULTS: In the LCT group, the clearance (15 ± 2 vs 10 ± 1 mL·min·kg, P = .003) was higher; the volume of distribution (0.57 ± 0.10 vs 0.36 ± 0.11 L·kg, P = .007) and K21 (0.0100 ± 0.0018 vs 0.0070 ± 0.0020 min, P = .021, P' = .032) were larger; and the area under the blood concentration-time curve 0 - t; (605 ± 82 vs 867 ± 110 mgL·min, P =.001) and the area under the blood concentration-time curve (0 - ∞) (697 ± 111 vs 991 ± 121 mgL·min, P =.001) were less, when compared with the LCT/MCT group. CONCLUSIONS: LCT emulsions are more effective than LCT/MCT emulsions in the metabolism of bupivacaine through demonstration of a superior pharmacokinetic profile.

Intravenous Lipid Infusion Induces Endoplasmic Reticulum Stress in Endothelial Cells and Blood Mononuclear Cells of Healthy Adults.

BACKGROUND: Endoplasmic reticulum (ER) stress and the subsequent unfolded protein response may initially be protective, but when prolonged, have been implicated in atherogenesis in diabetic conditions. Triglycerides and free fatty acids (FFAs) are elevated in patients with diabetes and may contribute to ER stress. We sought to evaluate the effect of acute FFA elevation on ER stress in endothelial and circulating white cells. METHODS AND RESULTS: Twenty-one healthy subjects were treated with intralipid (20%; 45 mL/h) plus heparin (12 U/kg/h) infusion for 5 hours. Along with increased triglyceride and FFA levels, intralipid/heparin infusion reduced the calf reactive hyperemic response without a change in conduit artery flow-mediated dilation consistent with microvascular dysfunction. To investigate the short-term effects of elevated triglycerides and FFA, we measured markers of ER stress in peripheral blood mononuclear cells (PBMCs) and vascular endothelial cells (VECs). In VECs, activating transcription factor 6 (ATF6) and phospho-inositol requiring kinase 1 (pIRE1) proteins were elevated after infusion (both P<0.05). In PBMCs, ATF6 and spliced X-box-binding protein 1 (XBP-1) gene expression increased by 2.0- and 2.5-fold, respectively (both P<0.05), whereas CHOP and GADD34 decreased by ≈67% and 74%, respectively (both P<0.01). ATF6 and pIRE1 protein levels also increased (both P<0.05), and confocal microscopy revealed the nuclear localization of ATF6 after infusion, suggesting activation. CONCLUSIONS: Along with microvascular dysfunction, intralipid infusion induced an early protective ER stress response evidenced by activation of ATF6 and IRE1 in both leukocytes and endothelial cells. Our results suggest a potential link between metabolic disturbances and ER stress that may be relevant to vascular disease.

Essential Fatty Acid Deficiency in 2015: The Impact of Novel Intravenous Lipid Emulsions.

The fatty acids, linoleic acid (18:2ω-6) and α-linolenic acid (18:3ω-3), are essential to the human diet. When these essential fatty acids are not provided in sufficient quantities, essential fatty acid deficiency (EFAD) develops. This can be suggested clinically by abnormal liver function tests or biochemically by an elevated Mead acid and reduced linoleic acid and arachidonic acid level, which is manifested as an elevated triene/tetraene ratio of Mead acid/arachidonic acid. Clinical features of EFAD may present later. With the introduction of novel intravenous (IV) lipid emulsions in North America, the proportion of fatty acids provided, particularly the essential fatty acids, varies substantially. We describe a case series of 3 complicated obese patients who were administered parenteral nutrition (PN), primarily using ClinOleic 20%, an olive oil-based lipid emulsion with reduced amounts of the essential fatty acids, linoleic and α-linolenic, compared with more conventional soybean oil emulsions throughout their hospital admission. Essential fatty acid profiles were obtained for each of these patients to investigate EFAD as a potential cause of abnormal liver enzymes. Although the profiles revealed reduced linoleic acid and elevated Mead acid levels, this was not indicative of the development of essential fatty acid deficiency, as reflected in the more definitive measure of triene/tetraene ratio. Instead, although the serum fatty acid panel reflected the markedly lower but still adequate dietary linoleic acid content and greatly increased oleic acid content in the parenteral lipid emulsion, the triene/tetraene ratio remained well below the level, indicating EFAD in each of these patients. The availability and use of new IV lipid emulsions in PN should encourage the clinician to review lipid metabolism based on the quantity of fatty acids provided in specific parenteral lipid emulsions and the expected impact of these lipid emulsions (with quite different fatty acid composition) on measured fatty acid profiles.

The evaluation and comparison of consecutive high speed centrifugation and LipoClear® reagent for lipemia removal.

BACKGROUND: The aim of this study was to evaluate and compare the efficiency of high speed centrifugation and LipoClear® reagent for lipemia removal in plasma samples spiked with Intralipid®, for 26 biochemistry analytes. MATERIALS AND METHODS: A plasma pool was collected. Aliquots of the pool were spiked with Intralipid® (final concentrations of 300mg/dL and 500mg/dL Intralipid®). The lipemia was removed from the aliquots by high speed centrifugation or LipoClear® reagent. 26 analytes were determined in native, lipemic plasma and in samples after lipemia removal. The bias from the concentration in the native sample was calculated for each parameter for Intralipid® concentrations, 300 and 500mg/dL of Intralipid®, respectively. Also, the recovery for each parameter after processing the samples using high speed centrifugation and LipoClear® was calculated. The biases and test recoveries were compared with the desirable specification for imprecision (DSI) according to Ricos available at the Wesgard's website. The bias and recovery for procalcitonin were compared with DSI according to Barassi and colleagues. RESULTS: The bias of the spiked samples exceeded the DSI at 300mg/L Intralipid® for creatinine, glucose, total protein, iron and albumin; and for all previously mentioned parameters including CK-MB, sodium, potassium, chlorides, magnesium and ALP at concentration of 500mg/L Intralipid®. For the test recovery the DSI criteria were not met for calcium, total protein, sodium and chlorides after high speed centrifugation and for glucose, calcium, phosphates, magnesium, sodium, potassium, chlorides, ALP, GGT, CK-MB, total protein, albumin and troponin T after using LipoClear®. CONCLUSIONS: LipoClear® is not suitable for lipemia removal from samples designated for glucose, sodium, potassium, chlorides, phosphates, magnesium, CK-MB, ALP, GGT, total protein, albumin, CRP and troponin T measurements. High speed centrifugation should be used for lipemia removal instead for glucose, potassium, phosphates, magnesium, CK-MB, ALP, GGT, albumin, CRP and TnT measurements.

Fish Oil (SMOFlipid) and olive oil lipid (Clinoleic) in very preterm neonates.

OBJECTIVES: Fat emulsions used in Australia for parenteral nutrition in preterm neonates have been based on either soybean oil or olive oil (OO). OO lipid Clinoleic has a high ratio of n-6 to n-3 fatty acids (9:1); this may not be ideal for long-chain polyunsaturated fatty acids supply. Newly available SMOFlipid has an appropriate ratio of n-6 to n-3 fatty acids (2.5:1). SMOFlipid also contains OO (25%), coconut oil (30%), and soybean oil (30%). The aims of the study were to evaluate the safety of the SMOFlipid and to test the hypothesis that SMOFlipid would lead to increased omega-3 long-chain polyunsaturated fatty acid levels and reduced oxidative stress as compared with Clinoleic in preterm neonates (<30 weeks). METHODS: Preterm neonates (23-30 weeks) were randomised to receive Clinoleic or SMOFlipid emulsion for 7 days. Investigators and outcome assessors were masked to allocation. Plasma F2-isoprostanes (lipid peroxidation marker), red blood cell fatty acids, and vitamin E were measured before and after the study. Blood culture positive sepsis and growth were monitored for safety. RESULTS: Thirty of 34 participants completed the study. Both emulsions were well tolerated without any adverse events. F2-isoprostane levels were reduced in the SMOFlipid group as compared with baseline. Eicosapentanoic acid and vitamin E levels were significantly increased in the SMOFlipid group. Oleic acid and linoleic acid levels were increased in both groups. No significant differences were noted in poststudy docosahexaenoic acid levels in both groups despite higher levels of docosahexaenoic acid in SMOFlipid. CONCLUSIONS: SMOFlipid was safe, well tolerated, and showed beneficial effect in terms of reduction of oxidative stress by reducing lipid peroxidation levels in high-risk preterm neonates.

A model of chronic nutrient infusion in the rat.

Chronic exposure to excessive levels of nutrients is postulated to affect the function of several organs and tissues and to contribute to the development of the many complications associated with obesity and the metabolic syndrome, including type 2 diabetes. To study the mechanisms by which excessive levels of glucose and fatty acids affect the pancreatic beta-cell and the secretion of insulin, we have established a chronic nutrient infusion model in the rat. The procedure consists of catheterizing the right jugular vein and left carotid artery under general anesthesia; allowing a 7-day recuperation period; connecting the catheters to the pumps using a swivel and counterweight system that enables the animal to move freely in the cage; and infusing glucose and/or Intralipid (a soybean oil emulsion which generates a mixture of approximately 80% unsaturated/20% saturated fatty acids when infused with heparin) for 72 hr. This model offers several advantages, including the possibility to finely modulate the target levels of circulating glucose and fatty acids; the option to co-infuse pharmacological compounds; and the relatively short time frame as opposed to dietary models. It can be used to examine the mechanisms of nutrient-induced dysfunction in a variety of organs and to test the effectiveness of drugs in this context.

The influence of insulin infusion on the metabolism of amyloid ß peptides in plasma.

BACKGROUND: Accumulating body of evidence suggests pathophysiologic links between Alzheimer's disease and diabetes mellitus (DM). For example, the two crucial peptides playing a role in both degenerative disorders, amyloid ß (Aß) and insulin, are metabolized by the same enzyme, insulin degrading enzyme. Euglycemic hyperinsulinemic clamp is a method of estimating insulin sensitivity, based on the assumption that during steady-state hyperinsulinemic euglycemia, glucose infusion rate equals tissue glucose uptake, that is, the higher the glucose infusion rate, the higher the insulin sensitivity. OBJECTIVE: The aim of this study was to analyze the influence of insulin on the plasma concentrations of Aß peptides. METHODS: Blood samples were collected from 20 healthy young male volunteers before insulin infusion (clamp) and then at 120 and 360 minutes. In the second protocol, insulin was accompanied by Intralipid, which is mainly a mixture of triacylglycerols, and heparin, given as an activator of lipoprotein lipase, inducing insulin resistance. Analyses of plasma Aß1-42, Aßx-42, Aß1-40, and Aßx-40 were performed with multiplexing technology. Furthermore, concentrations of the Aß peptides in healthy persons were compared with those in 16 type 1 DM patients receiving chronic insulin therapy. RESULTS: When applied alone (i.e., without Intralipid), insulin infusion increased concentrations of Aß42 (full length and N-terminally shortened) but not of Aß40. When combined with Intralipid, infusion of insulin resulted in increased concentrations of all peptides (nonsignificant tendency in case of Aßx-40). We did not observe differences between Aß peptide concentrations in healthy subjects and those in type 1 DM patients. CONCLUSION: Infusion of insulin in nonphysiologic high doses increases plasma concentrations of Aß peptides; in case of Aß40, only when applied together with Intralipid, which perhaps might be explained by hypothetical shift of insulin degrading enzyme activity from degradation of Aß peptides to the degradation of insulin.

Acute elevation of lipids does not alter exercise hemodynamics in healthy men: A randomized controlled study.

OBJECTIVE: Exaggerated exercise blood pressure (BP) predicts mortality. Some studies suggest this could be explained by chronic hyperlipidemia, but whether acute-hyperlipidemia effects exercise BP has never been tested, and was the aim of this study. METHODS: Intravenous infusion of saline (control) and Intralipid were administered over 60 min in 15 healthy men by double-blind, randomized, cross-over design. Brachial and central BP (including, pulse pressure, augmentation pressure and augmentation index), cardiac output and systemic vascular resistance were recorded at rest and during exercise. RESULTS: Compared with control, Intralipid caused significant increases in serum triglycerides, very low density lipoproteins and free fatty acids (p < 0.001 for all). However, there was no significant difference for any exercise hemodynamic variable (p > 0.05 for all). CONCLUSION: Acute-hyperlipidemia does not significantly change exercise hemodynamics in healthy males. Therefore, the association between raised lipids and increased exercise BP is likely due to the chronic effects of hyperlipidemia.

Analytical interferences resulting from intravenous lipid emulsion.

CONTEXT: Lipid resuscitation therapy using intravenous lipid emulsion (IVLE) for drug overdoses has gained widespread use. However, there is little information regarding its adverse effects. OBJECTIVES: We performed lipemic interference studies on typical automated platforms to investigate the potential of lipid resuscitation therapy to interfere with the reliability and turnaround time of analytes that would be of interest in acute intoxications. We also tested methods to minimize interferences. MATERIALS AND METHODS: Serum pools were supplemented with increasing concentrations of Intralipid-20%(®) (0-30%). Analyses were performed on Beckman-Coulter DXC800 and DXI and Roche Modular-P. Analytes demonstrating significant interference were re-measured after centrifugation (14 000 × g for 10 minutes). RESULTS: Triglyceride and glycerol-blanked triglyceride concentrations were similar in IVLE-free samples. However, with addition of IVLE, concentrations were markedly different (139 vs. 76 mmol/L). There was no appreciable interference on the troponin-I, sodium, potassium, chloride, calcium, bicarbonate or urea assays. Albumin and magnesium assays demonstrated significant interference. Amylase, lipase, phosphate, creatinine, total protein, ALT, CK and bilirubin became unmeasurable in IVLE-supplemented samples. Whereas glucose measurement by potentiometry was free of interference, colorimetric methodology was error prone. Centrifugation removed > 90% of glycerol-blanked triglyceride (max = 5.8 mmol/L), dramatically reducing lipid interferences. DISCUSSION: IVLE results in appreciable analytical interferences at concentrations demonstrated in lipid resuscitation therapy. Of particular concern is the marked interference on glucose and magnesium, which may result in unsuccessful and potentially harmful interventions. Major implications for patient care include reporting of incorrect results and delays in the reporting of time-sensitive results. Whenever possible, blood samples should be collected prior to initiating lipid therapy. Interferences can be minimized by brief centrifugation at relatively low speeds on equipment readily available in most core labs.

A mixed (long- and medium-chain) triglyceride lipid emulsion extracts local anesthetic from human serum in vitro more effectively than a long-chain emulsion.

BACKGROUND: Lipid emulsion infusion reverses cardiac toxicity of local anesthetics. The predominant effect is likely creation of a "lipid sink." This in vitro study determined the extent to which Intralipid® (Fresenius Kabi, Uppsala, Sweden) and Lipofundin® (B. Braun Melsungen AG, Melsungen, Germany) sequester anesthetics from serum, and whether it varies with pH. METHODS: Bupivacaine, ropivacaine, and mepivacaine were added to human drug-free serum (pH 7.4) at 10 µg/ml. The lipid emulsions were added, and the mixture shaken and incubated at 37°C. Lipid was removed by ultracentrifugation and drug remaining in the serum measured. Additional experiments were performed using 100 µg/ml bupivacaine and at pH 6.9. RESULTS: Lipofundin® extracted all three anesthetics to a greater extent than Intralipid® (34.7% vs..22.3% for bupivacaine, 25.8% vs..16.5% for ropivacaine, and 7.3% vs..4.7% for mepivacaine). By increasing either concentration of bupivacaine or lipid, there was an increase in drug extraction from serum. Adjusting the pH to 6.9 had no statistically significant effect on the percentage of bupivacaine sequestered. CONCLUSIONS: Bupivacaine, ropivacaine, and mepivacaine were sequestered to an extent consistent with their octanol:water partition constants (logP). In contrast with previous studies of extraction of lipids from buffer solutions, an emulsion containing 50% each of medium- and long-chain triglycerides extracted local anesthetics to a greater extent from human serum than one containing exclusively long-chain triglycerides, calling into question recent advanced cardiac life support guidelines for resuscitation from anesthetic toxicity that specify use of a long-chain triglyceride. The current data also do not support recent recommendations to delay administration until pH is normalized.