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

Excess lipid availability causes insulin resistance. We examined the effect of acute exercise on lipid-induced insulin resistance and TBC1 domain family member 1/4 (TBCD1/4)-related signaling in skeletal muscle. In eight healthy young male subjects, 1 h of one-legged knee-extensor exercise was followed by 7 h of saline or intralipid infusion. During the last 2 h, a hyperinsulinemic-euglycemic clamp was performed. Femoral catheterization and analysis of biopsy specimens enabled measurements of leg substrate balance and muscle signaling. Each subject underwent two experimental trials, differing only by saline or intralipid infusion. Glucose infusion rate and leg glucose uptake was decreased by intralipid. Insulin-stimulated glucose uptake was higher in the prior exercised leg in the saline and the lipid trials. In the lipid trial, prior exercise normalized insulin-stimulated glucose uptake to the level observed in the resting control leg in the saline trial. Insulin increased phosphorylation of TBC1D1/4. Whereas prior exercise enhanced TBC1D4 phosphorylation on all investigated sites compared with the rested leg, intralipid impaired TBC1D4 S341 phosphorylation compared with the control trial. Intralipid enhanced pyruvate dehydrogenase (PDH) phosphorylation and lactate release. Prior exercise led to higher PDH phosphorylation and activation of glycogen synthase compared with resting control. In conclusion, lipid-induced insulin resistance in skeletal muscle was associated with impaired TBC1D4 S341 and elevated PDH phosphorylation. The prophylactic effect of exercise on lipid-induced insulin resistance may involve augmented TBC1D4 signaling and glycogen synthase activation.

Background Small studies suggest differences in efficacy and safety exist between olive oil-based (OLIVE) and soybean oil-based (SOYBEAN) parenteral nutrition regimens in hospitalized adult patients. This large, prospective, randomized (1:1), open-label, multi-center, noninferiority study compared the delivery, efficacy, and safety of OLIVE ( N  = 226) with SOYBEAN ( N  = 232) in Chinese adults (≥18 years) admitted to a surgical service for whom parenteral nutrition was required. Methods Treatments were administered for a minimum of 5 days up to 14 days (to achieve approximately 25 kcal/kg/day, 0.9 g/kg/day amino acids, 0.8 g/kg/day lipid). Impact of treatment on anabolic/catabolic and serum inflammatory, chemistry, and hematological markers, safety, and ease of use were assessed. The primary efficacy variable was serum prealbumin level at Day 5. Results OLIVE ( n  = 219) was not inferior to SOYBEAN ( n  = 224) based on the prealbumin least square geometric mean [LSGM] ratio [95 % CI] 1.12 [1.06, 1.19]; P  = 0.002), improved the anabolic/catabolic status of patients enrolled in the study, and was well tolerated compared with SOYBEAN. Improved anabolic status was supported by significantly higher levels of prealbumin at Day 5, albumin at Day 5 and IGF-1 at Day 14 in the OLIVE group, while catabolism was similar between groups. C-reactive protein, intercellular adhesion molecule-1, procalcitonin, and oxidation were similar in each group, but infections were significantly lower with OLIVE (3.6 % versus 10.4 %; P  < 0.01). Conclusions OLIVE provided effective nutrition, was well tolerated, was associated with fewer infections, and conferred greater ease-of-use than SOYBEAN. Trial registration NTC 01579097 .

Background Home parenteral nutrition (HPN) is a life-preserving therapy for patients with chronic intestinal failure (CIF) indicated for patients who cannot achieve their nutritional requirements by enteral intake. Intravenously administered lipid emulsions (ILEs) are an essential component of HPN, providing energy and essential fatty acids, but can become a risk factor for intestinal-failure-associated liver disease (IFALD). In HPN patients, major effort is taken in the prevention of IFALD. Novel ILEs containing a proportion of omega-3 polyunsaturated fatty acids (n-3 PUFA) could be of benefit, but the data on the use of n-3 PUFA in HPN patients are still limited. Methods/design The HOME study is a prospective, randomized, controlled, double-blind, multicenter, international clinical trial conducted in European hospitals that treat HPN patients. A total of 160 patients (80 per group) will be randomly assigned to receive the n-3 PUFA-enriched medium/long-chain triglyceride (MCT/LCT) ILE (Lipidem/Lipoplus® 200 mg/ml, B. Braun Melsungen AG) or the MCT/LCT ILE (Lipofundin® MCT/LCT/Medialipide® 20%, B. Braun Melsungen AG) for a projected period of 8 weeks. The primary endpoint is the combined change of liver function parameters (total bilirubin, aspartate transaminase and alanine transaminase) from baseline to final visit. Secondary objectives are the further evaluation of the safety and tolerability as well as the efficacy of the ILEs. Discussion Currently, there are only very few randomized controlled trials (RCTs) investigating the use of ILEs in HPN, and there are very few data at all on the use of n-3 PUFAs. The working hypothesis is that n-3 PUFA-enriched ILE is safe and well-tolerated especially with regard to liver function in patients requiring HPN. The expected outcome is to provide reliable data to support this thesis thanks to a considerable number of CIF patients, consequently to broaden the present evidence on the use of ILEs in HPN. Trial registration ClinicalTrials.gov, ID: NCT03282955 . Registered on 14 September 2017.

AbstractThe American Society of Regional Anesthesia and Pain Medicine's Third Practice Advisory on local anesthetic systemic toxicity is an interim update from its 2010 advisory. The advisory focuses on new information regarding the mechanisms of lipid resuscitation, updated frequency estimates, the preventative role of ultrasound guidance, changes to case presentation patterns, and limited information related to local infiltration anesthesia and liposomal bupivacaine. In addition to emerging information, the advisory updates recommendations pertaining to prevention, recognition, and treatment of local anesthetic systemic toxicity.What’s New in This Update?This interim update summarizes recent scientific findings that have enhanced our understanding of the mechanisms that lead to lipid emulsion reversal of LAST, including rapid partitioning, direct inotropy, and post-conditioning. Since the previous practice advisory, epidemiological data have emerged that suggest a lower frequency of LAST as reported by single institutions and some registries, nevertheless a considerable number of events still occur within the general community. Contemporary case reports suggest a trend toward delayed presentation, which may mirror the increased use of ultrasound guidance (fewer intravascular injections), local infiltration techniques (slower systemic uptake), and continuous local anesthetic infusions. Small patient size and sarcopenia are additional factors that increase potential risk for LAST. An increasing number of reported events occur outside of the traditional hospital setting and involve non-anesthesiologists.

The aim of this study was to evaluate the effect of parenteral nutrition containing medium- and long-chain triglycerides on the function of the respiratory system and to investigate mechanisms involved in this process. We studied 13 patients with acute respiratory distress syndrome (ARDS), 8 receiving lipid and 5 placebo, and 6 without ARDS, receiving lipid. Bronchoalveolar lavage (BAL) was performed before and 1 hour after administration of lipid or placebo. In patients with ARDS, lipid administration resulted in deterioration of oxygenation (Pa(O(2))/FI(O(2)): from 129 +/- 37 to 95 +/- 42), compliance of respiratory system (from 39.2 +/- 12 to 33.1 +/- 9.2 ml/cm H(2)O), and pulmonary vascular resistance (from 258 +/- 47 to 321 +/- 58 dyne x s x cm(-5)). In the BAL fluid of the same group, an increase in total protein and phospholipid concentrations, phospholipase activities, platelet-activating factor and neutrophils, as well as alterations in BAL lipid profile were observed. No significant changes were observed in the control or in the ARDS-Placebo groups. In conclusion, this study indicates that administration of medium- and long-chain triglycerides in patients with ARDS causes alterations in lung function and hemodynamics. Inflammatory cells, possibly activated by lipids, release phospholipase A(2) and platelet-activating factor, enhancing edema formation, inflammation, and surfactant alterations.

Background: The clinical safety and the uptake of ω-3 polyunsaturated fatty acids (PUFA) into the serum phospholipids and erythrocyte membranes after administration of fish-oil-supplemented parenteral nutrition (PN) was investigated in colorectal surgical patients. Methods: Forty patients undergoing colorectal surgery (n = 40) and with an indication for PN were enrolled in a prospective, double-blind, randomized study to receive an ω-3 PUFA-supplemented 20% lipid emulsion (Lipoplus; B. Braun Melsungen, Melsungen, Germany; test group, n = 19) for 5 days postoperatively. The control group received a standard 20% fat emulsion (Lipofundin MCT/LCT, B. Braun Melsungen, Melsungen, Germany, control group, n = 21). Clinical outcome parameters and safety were assessed by means of adverse events recording clinical parameters and hematologic analyses. The contents of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), as well as arachidonic acid (AA), in phospholipid fractions in plasma and in erythrocytes were analyzed preoperatively, on postoperative days 1, 6, and 10 using liquid gas chromatography. Results: Both fat emulsions were well tolerated, and none of the adverse events was considered to be related to treatment. Postoperative infectious complications occurred in 4 patients of the ω-3 PUFA group vs 7 patients in the control group. As compared with the control group, the ω-3 PUFA group had significantly increased levels of EPA in the membranes of the erythrocytes in postoperative day 6 (2.0% ± 0.9% vs 0.8% ± 0.5% fatty acid methyl esters, [FAME]) and postoperative day 10 (2.1% ± 0.8% vs 0.9%± 0.7% FAME, p < .05). Also, the EPA levels in the serum phospholipids were significantly higher than in the control group on the same postoperative days (7.0% ± 2.6% vs 1.3% ± 0.8% and 3.6%± 1.0% vs 1.0% ± 0.4% FAME, p < .05). The DHA levels in the serum phospholipids were significantly higher in theω -3 PUFA group compared with the control on postoperative days 6 and 10 (11.8% ± 1.9% vs 8.4% ± 1.5% and 11.2% ± 1.6% vs 8.5% ± 1.4% FAME, p < .05). AA levels were not significantly different in the both groups. Conclusions:Ω -3-fatty-acids-supplemented fat emulsions for parenteral administration are safe and very well tolerated. This study demonstrates that parenteral administration of ω-3-PUFA-enriched fat emulsions leads to increased incorporation of EPA and DHA into phospholipids in serum and erythrocytes, whereas AA levels remain unchanged. Thus, postoperative parenteral administration of ω-3-PUFA-enriched lipid emulsions could have an impact on the postoperative inflammatory response after abdominal surgery and could be used in standard postoperative care when PN is indicated. Ω-3-fatty-acids-supplemented fat emulsions in parenteral nutrition for 5 days after surgery are clinically safe and lead to alteration of the fatty acid profile in serum phospholipids and phospholipids of the erythrocyte membranes.

ABSTRACTThe experimental use of lipid emulsion for local anesthetic toxicity was originally identified in 1998. It was then translated to clinical practice in 2006 and expanded to drugs other than local anesthetics in 2008. Our understanding of lipid resuscitation therapy has progressed considerably since the previous update from the American Society of Regional Anesthesia and Pain Medicine, and the scientific evidence has coalesced around specific discrete mechanisms. Intravenous lipid emulsion therapy provides a multimodal resuscitation benefit that includes both scavenging (eg, the lipid shuttle) and nonscavenging components. The intravascular lipid compartment scavenges drug from organs susceptible to toxicity and accelerates redistribution to organs where drug (eg, bupivacaine) is stored, detoxified, and later excreted. In addition, lipid exerts nonscavenging effects that include postconditioning (via activation of prosurvival kinases) along with cardiotonic and vasoconstrictive benefits. These effects protect tissue from ischemic damage and increase tissue perfusion during recovery from toxicity. Other mechanisms have diminished in favor based on lack of evidence; these include direct effects on channel currents (eg, calcium) and mass-effect overpowering a block in mitochondrial metabolism. In this narrative review, we discuss these proposed mechanisms and address questions left to answer in the field. Further work is needed, but the field has made considerable strides towards understanding the mechanisms.

Fat overload syndrome is a rare but serious complication associated with intravenous lipid emulsion in parenteral nutrition. Timely identification of causes, recognition of symptoms, close monitoring of complications, and appropriate management are vital for improving outcomes and preventing recurrence. This case series reviews etiologies, complications, management, and outcomes in pediatric patients who developed fat overload syndrome as well as those identified to be at risk of this condition. A retrospective chart review was performed over a five-year period at a tertiary care hospital, including 11 pediatric patients who received lipid emulsions at infusion rates exceeding the recom-mended limit. Data on patient demographics, lipid emulsion details, clinical presentations, laboratory results, managements, and outcomes were collected and analyzed. Eleven patients were included, ranging in age from 9 months to 15 years, with a male-to-female ratio of 7:4. The identified causes of intravenous lipid administration incidents were inadvertent switching of infusion rates between the parenteral nutrition solution bag and the lipid bag, and incorrect infusion pump programming. Fat overload syndrome was identified in one patient, presenting with oliguria and metabolic acidosis. Management primarily consisted of discontinuing intravenous lipid emulsions and providing supportive care. Although most patients had no complications, four required additional supportive interventions. Although uncommon, fat overload syndrome requires prompt recognition and timely intervention. This case series underscores the importance of careful parenteral lipid administration and vigilant monitoring of at-risk patients. Root cause analysis is critical to preventing recurrence of such incidents.

ABSTRACTThe American Society of Regional Anesthesia and Pain Medicine (ASRA) periodically revises and updates its checklist for the management of local anesthetic systemic toxicity. The 2017 update replaces the 2012 version and reflects new information contained in the third ASRA Practice Advisory on Local Anesthetic Systemic Toxicity. Electronic copies of the ASRA checklist can be downloaded from the ASRA Web site (www.asra.com) for inclusion in local anesthetic toxicity rescue kits or perioperative checklist repositories.