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Background Epinephrine (EPI) or norepinephrine (NOR) is widely used to treat cardiovascular collapse during lipid emulsion (LE) resuscitation for drug toxicity. However, the effect of LE on the vasoconstriction caused by EPI or NOR remains unknown. The purpose of this study was to examine the effect of an LE (Intralipid) on the vasoconstriction caused by EPI and NOR in isolated rat aorta. Methods The effect of LE on the vasoconstriction caused by EPI or NOR in isolated rat aorta was examined. Additionally, the effect of LE on the calcium increase caused by EPI or NOR was investigated. The distribution constant (KD: lipid to aqueous phase) of EPI or NOR between a LE (1%) and an aqueous phase was determined. Results LE (1 and 2%) did not significantly alter vasoconstriction caused by EPI or NOR in isolated endothelium-intact aorta. Moreover, the LE did not significantly alter the increased calcium level caused by EPI or NOR. The log KD of EPI in the LE (1%) was −0.71, −0.99, and −1.00 at 20, 50, and 100 mM ionic strength, respectively. The log KD of NOR in the LE (1%) was −1.22, −1.25, and −0.96 at 20, 50, and 100 mM ionic strength, respectively. Conclusions Taken together, the Intralipid emulsion did not alter vasoconstriction induced by EPI or NOR that seems to be due to the hydrophilicity of EPI or NOR, leading to sustained hemodynamic support produced by EPI or NOR used during LE resuscitation.

Background: Intravenous lipid emulsions are an essential component of nutritional support for very preterm infants. Many neonatal intensive care units have transitioned from traditional soybean oil-only to fish oil-containing multicomponent lipid emulsions, but the neurodevelopmental implications have not been well-explored. The primary aim of this study was to assess extrauterine third trimester brain growth in very preterm infants supported with soybean oil-only compared to fish-oil containing multicomponent lipid emulsions; white matter development and neurobehavioral regulation at term were also investigated. Methods: Human milk-fed very preterm infants (born less than or equal to 32 weeks' gestation) receiving either soybean oil-only (before 2019) or multicomponent (after 2019) lipid emulsions underwent quantitative brain MRI (volumetric growth and white matter development) and neurodevelopmental assessment (Neonatal Intensive Care Unit Network Neurobehavioral Scale) at term-equivalent age. Analyses were adjusted for age at birth and term assessments, as well as clinically significant covariates. Results: 92 infants (61 soybean, 31 multicomponent) were included (mean [SD] birth gestational age: 27.3 [2.3] weeks). Soybean oil-only infants demonstrated smaller brainstem volumes (β [95% CI] = -0.5 [-0.8,-0.1], p =.007); additionally less mature white matter development (mean diffusivity [MD, mm2/second x10− 3] and fractional anisotropy [FA]) in the corpus callosum (MD genu: β = 0.10 [0.01, 0.20], p =.04; splenium: β = 0.14 [0.04, 0.24], p =.006), posterior limbs of internal capsule (MD right (R): β = 0.05 [0.02, 0.08], p =.004, left (L): β = 0.04 [0.01, 0.08], p =.01; FA R: β = -0.03 [-0.06, -0.00], p =.03), and brainstem (FA R: β = 0.07 [0.04, 0.10], p <.001, L: β = 0.05 [0.02, 0.09], p =.002); and lower quality of movement (β = -0.54 [-0.97, -0.11], p =.02) and higher state-related stress (β = 1.41 [0.14, 2.83], p =.04). Conclusions: Very preterm infants supported with a fish-oil containing multicomponent compared to soybean oil-only lipid emulsion demonstrated improved regional brain growth, as well as evidence of enhanced white matter microstructural organization and neurobehavioral regulation, at term corrected age. Trial registration: Clinical trial number: Not applicable. [ABSTRACT FROM AUTHOR]

Objectives: Endometrial scratching (ES) and/or intravenous intralipid therapy (in cases of increased uterine natural killer cells, uNKs) are still conducted in several fertility centers as "add-on" treatments in patients undergoing ART, although convincing evidence for beneficial effects is lacking. Study design: In this retrospective study, associations between ES treatment or additional intralipid therapy and pregnancy and live birth rates of 1,546 patients undergoing 2,821 IVF-/ICSI-treatment cycles with fresh or frozen embryo transfers in a German fertility-center between 1st January 2014 and 31th May 2017 were analyzed. Results: Overall pregnancy and live birth rates for all 2,821 treatment cycles (468 cycles with ES) were 32.8% and 23.5%. There were no statistically significant differences in pregnancy or live birth rates between first treatment cycles with and without ES (p = 0.915 and p = 0.577) or between second cycles following an unsuccessful first cycle with and without ES (p = 0.752 and p = 0.623). These results were confirmed using multivariable generalized estimating equations (GEE) models accounting for non-independency of multiple treatment cycles per patients that included all cycles and showed no significant effect of ES on pregnancy (p = 0.449) or live birth rates (p = 0.976). Likewise, a GEE model revealed no significant effect of intralipid treatment on pregnancy (p = 0.926) and live birth rates (p = 0.727). Conclusions: Our results reveal no evidence that ES increases the pregnancy or live birth rates in women undergoing their first or further IVF cycle with fresh or frozen embryo transfer. Intralipid treatment was also not beneficial. Even if patients explicitly ask for it, these procedures are not recommended outside of clinical studies. [ABSTRACT FROM AUTHOR]

Background: Acute pesticide poisoning has remained a significant public health concern for decades. Supportive care has been the mainstay of treatment. Intravenous lipid emulsion (ILE) therapy offers a potential new strategy. Objectives: This systematic review aimed to evaluate the current research on the efficacy of ILE in treating aluminum phosphide (AlP) poisoning. Methods: A comprehensive electronic search was conducted across various databases including PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Campbell Systematic Reviews, Scopus, Web of Science, Springer Nature, Elsevier, Google Scholar, and regional databases encompassing Mansoura, Zagazig, Ain Shams universities, and Indian publications. Studies published in English language were considered for inclusion (from 2015 to 2023). Inclusion criteria focused on human studies evaluating the use of ILE for AlP intoxication. Results: Five studies met the inclusion criteria, three studies were randomized controlled trials, one was observational cross sectional study, and one was case report encompassing a total of 224 patients. Of these, 102 patients received ILE, with all studies utilizing 20% ILE. Three studies administered ILE as a continuous intravenous infusion at a rate of 10 mL/h. Two other studies employed a bolus dose regimen, ranging from 1-3 mL/kg delivered over one minute, followed by continuous infusion. The overall mortality rate was 68.6% in the ILE group compared to 76.2% in the control group and the need for mechanical ventilation was lower in the ILE group with clinical improvement in the ILE group. Conclusion: Intravenous lipid emulsion represents a novel therapeutic approach in toxicology with the potential to improve patient outcomes. This review suggests ILE may reduce mortality associated with AlP poisoning. Additionally, ILE use might be associated with decreased, need for mechanical ventilation, hospital stay and discharge time among survivors. [ABSTRACT FROM AUTHOR]

Background: Local infiltration analgesia (LIA) is a crucial component of multimodal analgesia that enhances recovery after total hip arthroplasty (THA) and knee arthroplasty (TKA). However, LIA can cause fatal local anesthetic systemic toxicity (LAST). The incidences of LIA-induced LAST in different surgeries and anesthetic agents have not been well investigated. Methods: This observational study enrolled 1,267 adult patients who received LIA with bupivacaine for primary THA or TKA under general anesthesia at a single medical center between January 2020 and October 2021. LAST incidence was graded by severity: severe (refractory seizure or arrhythmia requiring lipid rescue), major (seizure or arrhythmia requiring prompt medication), and minor (all other) events. Patient demographics, surgical and anesthesia details, recovery profiles, and LAST incidences were recorded and analyzed. Results: The incidence of severe LAST events was 2.41 per 1000 in unilateral THA, 0 in TKA, and 3.16 per 1000 in the entire cohort. The odds ratio of developing major LAST events was 4.35 in patients undergoing unilateral THA compared with those undergoing unilateral TKA in a matched comparison. Patients who underwent bilateral THA had the highest risk of developing LIA-induced LAST. Additionally, patients using propofol infusion for anesthesia maintenance had a lower risk of seizures and tremors than those using sevoflurane inhalation. The odds ratio of major LAST events was 0.47 in matched comparisons. Conclusions: LIA was associated with a significantly higher risk of LAST in the THA group than in the TKA group. Propofol maintenance reduces the likelihood of seizures and tremors compared with sevoflurane inhalation. Exploring strategies to reduce the incidence of LIA-induced LAST is essential to improve perioperative patient safety. [ABSTRACT FROM AUTHOR]

Objectives: Optimal imaging of ischemic or inflammed myocardium via 18F-FDG PET imaging requires suppression of background carbohydrate metabolism in normal myocardium. Sole administration of intravenous lipid emulsion has not previously been used to rapidly prepare unfasted patients, such as in emergent clinical situations. In this proof-of-concept pilot, we posited that intravenous fat emulsion suppresses physiological metabolic uptake of in non-ischemic, non-inflammatory myocardium in unprepared and unfasted setting for enhanced cardiac positron emission tomography (PET) imaging. Methods: We conducted an ethics-approved, single-blind, prospective randomized crossover trial of 10 healthy volunteers from January 2020 to June 2021. Participants were unfasted and rendered hyperglycemic before being administered either high dose intravenous lipid emulsion—1.5 ml kg of 20% lipid emulsion, followed by 15 ml/kg/hr for 30mins—or saline prior to 18F-FDG injection and subsequent cardiac PET imaging. Assessors undertook image analysis for maximum standard uptake value (SUVmax), minimum standard uptake value (SUVmin) and qualitative assessment, and groups were compared using univariate analysis. Results: The study population age was 44.5 years [IQR 32.5–56.5], with 50% male and a median BMI of 22.75 [IQR 25.0–28.5] kg/m2. The study was feasible and there were no adverse side effects from the interventions. In these participants with normal myocardium, 18F-FDG uptake was reduced by intravenous lipid emulsion as assessed by SUVmax and qualitative assessment (p = 0.042, r = 0.454 and p = 0.009, r = –0.581, respectively). Conclusions: Intravenous lipid emulsion suppresses background metabolic uptake of 18F-FDG even in unprepared and unfasted patients. Our findings prove and expand the possible applications for cardiac 18F-FDG PET in various settings, including in emergent settings as a means of rapid preparation in place of current more time-consuming standard protocols, allowing time-critical management to be effected. [ABSTRACT FROM AUTHOR]

Background: Congenital gastrointestinal malformation (CGIM) cases require immediate surgical correction after birth and proper nutrition to meet energy demands. Among the macronutrients, lipids are considered the major energy source, playing a vital role in parenteral nutrition. However, the time of their initiation remains unclear. We compared the data of CGIM cases where lipids were given from the first post-surgical day to those where parenteral lipids were initiated on the second or third day of surgery and then reevaluated them on the seventh day of parenteral nutrition. Methods: We collected the data of patients who had undergone surgical correction for CGIM and were kept on parenteral nutrition including lipids from day 1 of surgery labeling them as group 1. Group 2 comprised of neonates having lipid parenteral nutrition started from day 2 or 3 of surgery. Both groups were reevaluated on the 7th day of parenteral nutrition. Statistical analysis was performed. Results: Group 1 had higher total bilirubin (TB) statistically significant (p-value=0.0299), as well as lower lipase (p-value=0.0286), and lower total lipids (p-value=0.0365). The values were lower of triglycerides (pvalue=0.0365), and total lipids (p-value=0.0365), on day 1. Comparing both groups, all biochemical parameters were found to be statistically significant. Conclusion: Lipid deficiency and overload should be carefully evaluated, especially in neonates having undergone recent surgical interventions, which increase their nutritional demands. No adverse effects were seen in our study related to parenteral lipid emulsion administration in post-surgical congenital gastrointestinal malformation cases. Early initiation of parenteral lipid regimens can provide better outcomes. [ABSTRACT FROM AUTHOR]

Malnutrition in critically ill patients represents a major concern as it can lead to adverse outcomes including increased morbidity and mortality. These patients exhibit an impaired immune response accompanied by increased oxidative stress. Nutritional support, including parenteral nutrition (PN), is critical in these patients. Intravenous lipid emulsions (ILEs), a key component of PN, provide energy and intervene in the modulation of inflammation. This was a secondary study of a randomized clinical trial at the Reina Sofia University Hospital (Murcia, Spain) for critically ill patients following major abdominal surgery that were administered PN supplemented with olive-oil-based ILE (OO-ILE, n = 29) or a mixed-lipid ILE (soybean oil, medium chain triglycerides, OO and fish oil, SMOF-ILE, n = 25). The effects on clinical outcomes, metabolic markers, oxidative stress, and inflammation were evaluated. No significant differences were observed between groups in the clinical parameters and outcomes, oxidative stress, or inflammatory markers. The within-group evaluation demonstrated an increase in total antioxidant capacity in both groups, while OO-ILE increased the levels of 15-F2t-isoprostane. In addition, the results showed that both mixtures reduced the release of IL-1β and IL-6. These findings suggest that both treatments had similar effects on oxidative stress and inflammatory response in this type of patient. [ABSTRACT FROM AUTHOR]

Introduction: Hydroxychloroquine has cardiac and cerebral sodium channel- and human ether-à-go-go-related gene (HERG) potassium channel-blocking effects. This causes depolarization delays, resulting in cardiovascular toxicity with potentially fatal consequences. Despite several supportive care options, hydroxychloroquine poisoning remains difficult to treat. Its high lipid solubility suggests that lipid emulsion therapy might be beneficial; however, no clear evidence regarding its efficacy is available. The aim of this review is to assess the evidence, the outcomes, and adverse events regarding the use of intravascular lipid emulsion therapy as a treatment for hydroxychloroquine poisoning. Methods: We conducted a systematic search in PubMed, Embase.com, Cochrane Central Register of Controlled Trials (CENTRAL)/Wiley, Web of Science Core Collection/Clarivate Analytics, and Scopus/Scopus.com from inception until 1 November 2023. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Inclusion criteria encompassed original observational or interventional studies, case series and case reports describing patients receiving lipid emulsion therapy for hydroxychloroquine toxicity. We extracted clinical data and performed a quality assessment of the included cases. We present the results as a narrative synthesis. Results: Of 157 identified articles, 16 case reports met the inclusion criteria, reporting on 18 patients. Lipid emulsion therapy was always associated with additional treatments, and detailed information on the circumstances regarding the administration of intravenous lipid emulsion and its presumed effect was often lacking. Fifteen of 18 patients survived to hospital discharge. Some reports described clear and almost immediate clinical improvement after intravenous lipid emulsion administration. No clear adverse effects were reported. Discussion: A limitation is the reliance on case reports, which varied in the degree of reported details. The administration of multiple therapeutic drugs in most cases made it difficult to attribute survival primarily to lipid emulsion. Publication bias may favour cases with successful outcomes. Conclusion: Among published case reports, most patients who received lipid emulsion for treatment of hydroxychloroquine poisoning survived. The risk of bias, the small number of reports, and the lack of systematic reporting of both favourable and adverse effects limit any conclusions about the effectiveness of lipid emulsion for hydroxychloroquine poisoning. [ABSTRACT FROM AUTHOR]

Objective: To determine whether intravenous lipid emulsion (ILE) therapy significantly reduces the concentration of baclofen, ibuprofen, and/or bromethalin in canine whole blood over time. Animals: Seven 500 mL bags of canine DEA 1.1 negative blood were divided into aliquots of 125 mL and randomly assigned to one of three treatment groups (baclofen, ibuprofen, bromethalin) or four control groups (a positive control for each treatment group and a negative control group). Procedures: Injectable ibuprofen (200 mg/kg), baclofen (8 mg/kg), or bromethalin (3 mg/kg) was apportioned into 125 mL aliquots of canine whole blood and incubated for 30 min at 38.5°C. ILE (12.4 mL, Intralipid®) was added to each sample and the solution vortexed [215 rpm for 15 min at 37°C (98.6°F)]. Samples were obtained at designated time points (0, 15, 30, 60, 180, 360 min), centrifuged, and separated into serum and RBC fractions. Serum samples were ultracentrifuged (22,000 g for 10 min at 37°C) to separate lipid rich and poor fractions. Samples were stored at −80°C prior to analysis. Results: A significant decrease in total drug concentration was established for bromethalin and its metabolite desmethylbromethalin compared to positive controls. ILE significantly reduced desmethylbromethalin at the 30-and 360-min time points. The remainder of the desmethylbromethalin time points did not reach significance. Bromethalin concentration was significantly reduced at all time points compared to positive controls. Neither baclofen nor ibuprofen had significant changes in concentration. Conclusion: ILE therapy was effective at reducing the total drug concentration of bromethalin and its metabolite desmethylbromethalin supporting the lipid sink theory. As a single compartment in vitro study, this study does not evaluate other proposed mechanisms of action of ILE therapy. ILE therapy may have other means of significantly decreasing lipophilic drug concentration in cases of toxicosis. [ABSTRACT FROM AUTHOR]

The use of intravenous lipid emulsion (ILE) is thought to reverse the acute neurological and cardiac toxicities generated by local anesthetic and non-anesthetic drugs. The aim of this review is to provide an updated overview of ILE therapy in the management of the toxic effects of medications on humans. Indications, mechanisms of action, monitoring, dosing, lipid formulations, adverse effects, and contraindications related to ILE are highlighted. Although ILE therapy was initially utilized for local anesthetic toxicity, its use has been extended to patients with overdoses or poisoning induced by various non-local anesthetic drugs. It has been proposed that intravenous lipid droplets generate a discrete lipophilic phase in the bloodstream into which liposoluble drugs preferentially partition. This partitioning effect, known as the lipid sink phenomenon, is thought to decrease the quantity of drug content in tissues in vital organs. At the same time, other studies have also described several molecular mechanisms that may contribute to ILE efficacy. Potential adverse effects of ILE have also been identified, such as pulmonary toxicity, hypertriglyceridemia, acute pancreatitis, interference with laboratory measurements, fat overload syndrome, worsening of systemic absorption of toxin, and hepatic dysfunction. Intravenous lipid emulsion therapy is gaining wider acceptance in critical care units and emergency rooms as a possible treatment modality for liposoluble drug toxicity. Currently, recommendations on ILE administration in clinical toxicology are mainly based on published case reports and animal studies. Thus, further clinical studies are required to increase knowledge about ILE therapy. [ABSTRACT FROM AUTHOR]

Objective: Parenteral nutrition constitutes a crucial advance in intensive care, it is used when the gastrointestinal system is not functional. Parenteral nutrients include macronutrients and micronutrients, delivered via two-in-one or all-in-one systems. Stability is crucial and is assessed by physicochemical, microbiological and galenic stability. This study aims to analyze the galenic stability of a parenteral lipid emulsion after expiration. Methods: 156 expired parenteral nutrition sachets were donated. During the 6 months of expiry, the analysis of galenic stability included: visual verification, droplet size, polydispersity index as well as Zeta potential. Results: During the 6 months of studies after expiration, the visual appearance of the emulsion did not change. Droplet sizes (102 nm to 397.05 nm) and Zeta potential (-23.73 mV to -20.05 mV) also remained within standards. Conclusion: The galenic stability of certain parenteral nutrition formulations can extend beyond the expiration date indicated by the manufacturers. This discovery opens up new prospects for the use of drugs in intensive care units, particularly in resource-limited settings where wastage of medical products is a major concern. The use of parenteral nutrition solutions beyond their expiration date could lead to substantial savings, by reducing waste and optimizing stock utilization. [ABSTRACT FROM AUTHOR]

Background: Intestinal failure-associated liver disease (IFALD) is a complication of long-term PN use, attributed to the use of ω-6 injectable lipid emulsions (ILE). Fish oil (FO) ILE have been successful in reversing liver injury in neonates. Evidence for pure FO ILE use in adult patients is limited. Methods: Case series of the use of FO lipid emulsions in adults with IFALD from the University of Chicago PN registry. Analysis of medical charts and PN formulations was performed. Results: Three cases of IFALD treated with FO ILE were identified. The first case was a 30-year-old man with short bowel syndrome (SBS), hyperbilirubinemia, and biopsy-proven IFALD. Following a change from a soy lipid emulsion to FO lipid emulsion, his liver tests rapidly improved and remained stable over 202 weeks of use. The second case was a 76-year-old woman with intestinal failure (IF) due to a frozen bowel. A change from a soy ILE to a composite lipid and later to a pure FO ILE did not result in improvement in her liver tests. The third case was a 28-year-old man with SBS and biopsy-proven IFALD. Change to a composite ILE and subsequently FO lipid emulsion resulted in a gradual improvement in liver tests. No clinical essential fatty acid (EFA) deficiencies were identified during treatment. Conclusion: FO ILE may be effective in the treatment of adult patients with cholestatic IFALD. Use is safe with no EFA deficiencies detected in up to 4 years of use. [ABSTRACT FROM AUTHOR]

Introduction: Lipid emulsion preparations, known for their clinical utility, are associated with various adverse events related to lipid metabolism. In this study, we analyzed the safety profile of lipid emulsions in clinical practice, using a real-world database. Methods: The US Food and Drug Administration Adverse Event Reporting System database was used to retrieve adverse events associated with lipid emulsion use. The risk of adverse events was evaluated based on the reported odds ratio and time-to-onset analysis. Results: A total of 4,430 relevant adverse event reports were identified. Hepatic dysfunction tended to occur in the early stages after administration, regardless of the lipid emulsion type. The incidence of hepatic dysfunction varies depending on the triglyceride content of the administered lipid emulsion. Infection tended to occur in the early stages of lipid emulsion administration; however, the incidence did not significantly differ depending on triglyceride content. Conclusion: Our study revealed adverse lipid emulsion events, indicating the need for comprehensive safety management, particularly in the early stages, for clinical use. Particularly, patients receiving parenteral nutrition, irrespective of lipid emulsion administration, necessitate thorough monitoring of liver function and triglyceride levels and reassessment of infusion rates. [ABSTRACT FROM AUTHOR]

In recent years, an innovative approach has emerged in the field of toxicology for managing acute intoxications caused by lipophilic substances: intravenous lipid emulsions (ILEs). Through numerous experiments and case reports, the efficacy of lipid emulsions in counteracting toxicities induced by lipophilic agents, including a significant number of antiepileptic (AE) drugs, have become increasingly evident. Data spanning a 10-year period (2010–2020) were analyzed by searching through multiple scientific publication platforms like PubMed, Science Direct, Research Gate, and Springer Link. This study focused on reviewing relevant case reports detailing successful intravenous lipid emulsion (ILE) administration in patients with acute intoxications with antiepileptics, specifically examining the impact of fat emulsions on neurological status, Glasgow Coma Scale (GCS) scores, and corrected QT interval concerning hemodynamic instability. The typical symptoms of antiepileptic toxicity include central nervous system depression, ataxia, and nystagmus. Intravenous lipid emulsion application resulted in an increase in Glasgow Coma Scale scores and enhanced recovery from drug intoxication. This study provides a comprehensive overview of the potential utility of ILE as a component to antidote therapy in cases of acute AE poisoning involving neurotropic drugs. The process involves the engagement of various mechanisms of antitoxic activity. [ABSTRACT FROM AUTHOR]

Intravenous lipid emulsion is used in the rescue treatment of certain poisonings. A complication is interference with laboratory analyses. The aim of this study was to determine the impact of intravenous lipid emulsion on routine laboratory analysis of coagulation parameters ex vivo and determine if any of the analytical techniques remain reliable. Samples were obtained from 19 healthy volunteers and divided in triplicate. One sample served as a control, and the other two were diluted to simulate the treatment of an average adult with Intralipid® 20 per cent Fresenius Kabi 100 mL (dilution-1) or 500 mL (dilution-2). Coagulation tests performed were prothrombin time, activated prothrombin time, D-dimer concentration and fibrinogen. Coagulation testing was performed by three techniques. Test-1 was performed on a Sysmex CN6000 analyzer. Test-2 was performed with a manual mechanical endpoint method using the semi-automated Stago KC4 Delta. Test-3 involved high-speed centrifugation before repeat testing on the Sysmex CN6000 analyzer. For test-1, only nine (47 per cent) samples in dilution-1 could be analyzed for coagulation tests, and no coagulation tests could be analyzed for dilution-2 because of lipaemia. For test-2 and test-3, all samples could be analyzed, and all results of both testing methods fell within the limits of the laboratory reference range. Difficulties in laboratory analysis of patients having received intravenous lipid emulsion are due to multiple factors. Most automated coagulation analyzers use optical measurements, which can be unreliable in the presence of a high intravenous lipid concentration. By altering the lipaemia in the testing solution using high-speed centrifugation or by using manual mechanical endpoint detection, we were able to obtain reliable results. These findings are limited by the use of an ex vivo method and healthy volunteers. This ex vivo model confirms that Intralipid® interferes with routine coagulation studies. It is important that clinicians are aware and inform their laboratories of its administration. [ABSTRACT FROM AUTHOR]

Background: Safe and efficient provision of intravenous lipid emulsion (ILE) requires a strategy to individualize infusion rates. Estimating the maximum acceptable infusion rate (MaxInfRate) of soybean oil–based ILE (SO‐ILE) in individuals by using a triglyceride (TG) kinetic model was reported to be feasible. In this study, we aimed to externally validate and, if needed, update the MaxInfRate estimation. Methods: The maximum TG concentration (TGmax) in patients receiving SO‐ILE at MaxInfRate was evaluated to determine if it met the definition of being <400 mg/dl for 90th percentile of patients. The TG kinetic model was evaluated through prediction performance checks and was subsequently updated using the data set of both the previous model development and present validation studies. Results: Out of 83 patients, 74 had TGmax <400 mg/dl, corresponding to a probability of 89.2% (95% CI, 81.9%–95.2%), and the 90th percentile of TGmax was 400 mg/dl (95% CI, 328–490 mg/dl), closely aligned with the theoretical values. However, the individual TGmax values were biased by the infusion rate because the covariate effects were overestimated in the TG kinetic model, requiring a minor revision. The updated MaxInfRate with the combined data set showed unbiased and more accurate predictions. Conclusion: The MaxInfRate was validated in external inpatients and updated with all available data. MaxInfRate estimation for individuals could be an option for the safe and efficient provision of SO‐ILE. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study is to investigate the effects of Normal Saline (NS), Activated Charcoal (AC) and Intravenous Lipid Emulsion (ILE) in colchicine poisonings that resulted in death. Study Design: The research is an experimental study carried out in a medical school animal laboratory. Materials and Methods: 24 female Sprague-Dawley rats were divided into 4 equal groups. After giving Colchicine (1 mg/kg, PO) to all animals, different treatments (NS, AC, ILE) were given to 3 groups. Group 4 was not treated. Colchicine blood samples (0.8 mL) were taken from the vena jugularis externa at 4, 8 and 24 hr and evaluated by liquid chromatography. Results: While the blood colchicine level decreased in all groups at 24 hr, the highest decrease was observed in the AC group. Compared to the 4th hr, blood colchicine levels at 8 hr decreased by 15.49% in the NS group, 64.55% in the AC group and 34.56% in the ILE group. Blood colchicine levels at 24 hr decreased by 66.1% in the NS group, 73.12% in the AC group, 37.73% in the ILE group and 59.17% in the untreated group compared to the 8th hr. Conclusion: AC administration is very effective in lowering blood colchicine levels. ILE can be used with NS and AC as an early treatment option for colchicine overdoses. However, further studies are needed for more effective methods in the treatment of colchicine overdose. [ABSTRACT FROM AUTHOR]

Medication errors pose significant risks to patients’ health, representing a relevant social and economic issue for the healthcare system. This study focuses on the life-threatening consequences of an overdose of intravenous lipid emulsion (ILE), used as an antidote for suspected bupivacaine intoxication in a young woman undergoing hip surgery. Shortly after administration of the local anesthetic, the woman experienced cardiac arrest and was admitted to the intensive care unit with severe respiratory failure, metabolic acidosis and deep coma. Despite medical intervention, her condition worsened, leading the medical team to administer ILE for suspected bupivacaine intoxication. The patient’s condition did not improve and ultimately resulted in death. The autopsy highlighted a widespread presence of oily material in the vascular system, compatible with an overdose of ILE. At a checking, medical records reported a dose of ILE that was 4-fold higher than the recommended dose in this off-label indication. This case report highlights the important need for healthcare professionals to understand the risks of using ILE as an antidote. Adequate monitoring of these “sentinel events” and their critical evaluation can lead to the implementation of specific clinical risk management protocols to reduce the risk for the patient and contain healthcare costs. [ABSTRACT FROM AUTHOR]

Purpose: Some diseases require that patients receive parenteral nutrition (PN) over a prolonged time period. Long-term administration of PN can further complicate an already complex therapy, posing additional risk of potential complications. This article is based on presentations and discussions held at the International Safety and Quality of PN Summit, providing insights into aspects of home PN (HPN) and examples of good HPN practice. Summary: One critical step in the HPN process is when patients transition from a hospital to a home setting, and vice versa. Generally, electronic PN ordering is not feasible in an HPN setting, leading to potential difficulties in communication and coordination. HPN requires that patients (or their home caregivers) administer PN, and thus their education and competency are crucial. Likewise, the choice of PN formulation is of great importance. For example, using more modern intravenous lipid emulsions containing medium-chain triglycerides, olive oil, and/or fish oil can provide benefits in terms of liver function during long-term HPN. Internationally, there are wide variations in delivery of HPN, with compounded PN dominating in some countries while others make greater use of marketauthorized multichamber bags (MCBs). Patient-related factors, institutional considerations, and the availability of different MCB formulations, are also contributing factors guiding formulation and delivery system preferences. Conclusion: Education and communication remain key components of a successful HPN process. The information shared here may help to motivate efforts to improve HPN processes and to consider the often-differing perspectives of patients and their healthcare professionals. [ABSTRACT FROM AUTHOR]

Purpose: Parenteral nutrition (PN) is an established therapy when oral/enteral feeding is not sufficient or is contraindicated, but nevertheless PN remains a complex, high-alert medication that is susceptible to errors that may affect patient safety. Over time, considerable progress has been made to make PN practices safer. The purpose of this article is to address ongoing challenges to improve the PN use process from prescription to administration and monitoring, and to outline practical aspects fostering the safety, quality, and cost-effectiveness of PN, as discussed at the International Safety and Quality of PN Summit. Summary: Opportunities to improve the PN use process in clinical practice include the promotion of inter-disciplinary communication, vigilant surveillance for complications, staff education to increase competency, and more consistent use of advanced technologies that allow automated safety checks throughout the PN process. Topics covered include considerations on PN formulations, including the value of intravenous lipid emulsions (ILEs), trends in compounding PN, the current and future role of market-authorized multi-chamber PN bags containing all 3 macronutrients (amino acids, glucose/dextrose, and ILE) in the United States and in Europe, and strategies to cope with the increasing global problem of PN product shortages. Conclusion: This review outlines potential strategies to use in clinical practice to overcome ongoing challenges throughout the PN use process, and ultimately promote PN patient safety. [ABSTRACT FROM AUTHOR]

Introduction Aluminum phosphide (ALP) is a highly toxic rodenticide and the mortality rates caused by it have been demonstrated up to 70–100% in various studies. Unfortunately, there is no specific antidote to manage its toxic effects. This study aimed to assess the biochemical and clinical efficacy and safety of intravenous lipid emulsion as an adjuvant therapy in acute aluminum phosphide poisoning. Patients and methods Sixty-four cases with acute ALP poisoning were stratified according to severity by the Poison Severity Score into severe and moderate groups (32 patients each). Patients were then randomly allocated into either receiving intravenous lipid emulsion in addition to the conventional treatment or receiving the conventional treatment only by using block randomization. Results Treatment by ILE resulted in a significant improvement in the survival time, the mean arterial blood pressure, arterial blood gases, and a significant reduction in serum lactate levels. The need for intubation and mechanical ventilation was insignificantly lower in the intervention groups compared to control groups. However, the reduction in mortality rate in the patients of intervention groups compared with control groups was found to be non-significant. Intravenous lipid emulsion use in acute ALP poisoning significantly prolonged the survival time, improved the metabolic acidosis, decreased the serum lactate levels and increased the mean arterial blood pressure and hospital stay in the intervention groups. And insignificantly decreased the mortality rate, need of intubation and mechanical ventilation, and the total dose of vasopressors. [ABSTRACT FROM AUTHOR]

This retrospective study aimed to evaluate the effects on the clinical signs of poisoning and adverse effects of intravenous lipid emulsion treatment in 82 animals (dogs and cats) with suspected poisonings over 18 months. Physical examination parameters and state of consciousness were documented every hour after the intravenous administration of a bolus of 2 ml/kg and 0.25 ml/kg/min over 60 minutes of a 20% intravenous lipid emulsion. The modified Glasgow coma scale and laboratory findings (blood gas analysis, triglyceride, lactate) were evaluated initially and three hours after discontinuing intravenous lipid emulsion administration. A statistical evaluation of the occurrence of adverse effects and the development of laboratory values was performed. A decrease in respiratory rate in the second control (8–12 hours) after ILE was observed. Three hours after completing of the intravenous lipid emulsion, triglyceride concentration increased about 10 times (p <0.001). Venous carbon dioxide partial pressure, bicarbonate, base excess, as well as the electrolytes sodium, potassium and ionized calcium decreased significantly (p <0.001). Patients who experienced a worsening of the modified Glasgow coma scale had a higher increase in triglyceride concentrations (p = 0.041) and plasma lactate (p = 0.034) and a larger decrease in bicarbonate concentrations (p = 0.053) compared to others. About 54% (n = 44) of the patients showed adverse effects which could be attributed to the administration of intravenous lipid emulsion and may be associated with a higher triglyceride increase. All of them were completely reversible within 33 hours. Adverse effects associated with intravenous lipid emulsion therapy were observed in half of the patients and were associated with a higher increase in triglycerides. [ABSTRACT FROM AUTHOR]

Objective: To describe a case of bifenthrin toxicosis in a dog with a successful outcome following the use of therapeutic plasma exchange (TPE) and intralipid therapy. Case Summary: An 8‐month‐old female neutered poodle mix dog ingested an unknown amount of powered bifenthrin, which resulted in acutely altered mentation, cranial nerve deficits, and intractable tremors that persisted in severity despite aggressive medical management to include intravenous fluids, intravenous lipid emulsion, anticonvulsant medications, and methocarbamol. TPE was initiated after lack of significant clinical improvement 12 hours after initial presentation. The dog underwent cardiopulmonary arrest (CPA) following approximately 1 plasma volume equivalent exchange. The dog was successfully resuscitated and showed marked improvement 12 hours postarrest and post‐TPE treatment. Serum bifenthrin concentrations were analyzed prior to TPE (445.38 ng/mL) and ∼10 hours after TPE (51.18 ng/mL), which resulted in an 89% reduction in serum bifenthrin concentration. New Information: TPE may be a promising adjunctive therapeutic modality for bifenthrin toxicosis in dogs. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to investigate the effects of lipemia on clinical chemistry and coagulation parameters in native ultralipemic (NULM) and intravenous lipid emulsion (IVLE) spiked samples. Materials and methods: The evaluation of biochemistry (photometric, ion-selective electrode, immunoturbidimetric method), cardiac (electrochemiluminescence immunoassay method) and coagulation (the viscosity-based mechanical method for prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen and the immunoturbidimetric method for D-dimer) parameters were conducted. In addition to the main pools, five pools were prepared for both types of lipemia, each with triglyceride (TG) concentrations of approximately 2.8, 5.7, 11.3, 17.0 and 22.6 mmol/L. All parameters' mean differences (MD%) were presented as interferographs and compared with the desirable specification for the inaccuracy (bias%). Data were also evaluated by repeated measures of ANOVA. Results: Prothrombin time and APTT showed no clinically relevant interference in IVLE-added pools but were negatively affected in NULM pools (P < 0.001 in both parameters). For biochemistry, the most striking difference was seen for CRP; it is up to 134 MD% value with NULM (P < 0.001) at the highest TG concentration, whereas it was up to - 2.49 MD% value with IVLE (P = 0.009). Albumin was affected negatively upward of 5.7 mmol/L TG with IVLE, while there was no effect for NULM. Creatinine displayed significant positive interferences with NULM starting at the lowest TG concentration (P = 0.028). There was no clinically relevant interference in cardiac markers for both lipemia types. Conclusions: Significant differences were scrutinized in interference patterns of lipemia types, emphasizing the need for careful consideration of lipemia interferences in clinical laboratories. It is crucial to note that lipid emulsions inadequately replicate lipemic samples. [ABSTRACT FROM AUTHOR]

This experimental study was conducted to investigate the effect of 20% Intralipid Emulsion (ILE) treatment on Cerebral Ischemia Reperfusion Injury (CIRI) after reperfusion in acute ischemic stroke. In this experimental study, seven rats without any intervention (control group), seven rats (sham group) for which CIRI was created after the common carotid artery was ligated for 2 hours, and seven rats who were treated with 20% ILE after CIRI (CIRI + ILE group) were sacrificed after 24 hours, and histopathological findings were investigated. In rats that were not treated after CIRI, 52.7% had level-1, 32.7% had level-2. and 14.5% had level-3. histopathological findings. While 72.2% of the rats treated with ILE had level-1 and 27.8% had level-2 findings, no level-3 histopathological findings were detected in any of the rats. While no signs of coagulative necrosis, spongiosis of surrounding tissue and polymorphonuclear leukocytes were observed histopathological in any of the rats given ILE, there was no macrophages finding in 85.6% of the rats. ILE treatment also reduced the histopathological findings of eosinophilic neurons, astrogliosis, neovascularization, vascular thrombosis and mononuclear inflammatory cells. This study showed that 20% ILE treatment reduces the histopathological damage seen in cerebral ischemia and CIRI. [ABSTRACT FROM AUTHOR]

Dextromethorphan (DXM) is used to treat colds and coughs; however, it can cause central nervous system symptoms, such as severe serotonin syndrome (SS). To our knowledge, there is no specific treatment for severe DXM poisoning, and there are no reports on the clinical use of intravenous lipid emulsion (ILE) for its treatment. Herein, we report a case of severe DXM poisoning with SS that was successfully treated with ILE. An older adolescent male visited the emergency department 1 h after ingesting 4500 mg of DXM orally. Physical examination revealed generalized convulsions, muscle rigidity, mydriasis (8.0/8.0 mm), and flushed skin, with a Glasgow Coma Scale score of 8 (E3V1M4). Severe DXM poisoning with SS was diagnosed. The patient was intubated and administered midazolam for continuous convulsions and SS. Activated charcoal was also administered, and body surface cooling was performed. After an 11 h intensive care unit admission, SS with mydriasis (6.0/6.0 mm) did not improve. Subsequently, 1100 mL of 20% soybean oil was injected as an ILE. Mydriasis improved (3.5/3.5 mm) 30 min after ILE administration; simultaneously, blood DXM concentration rapidly increased approximately two-fold. After discontinuing midazolam, the patient's consciousness signs improved, and he was weaned off the ventilator. SS was cured with no recurrence of convulsions. In cases of DXM poisoning with severe central nervous system disorders, such as SS, ILE treatment can potentially be an effective therapeutic option. For oral overdose cases, where the drug may remain in the intestinal tract, measures such as administering activated charcoal should be taken before administering ILE. [ABSTRACT FROM AUTHOR]

Intravenous lipid emulsion (ILE) has been widely used as an effective antidote in both veterinary and human medicine for the treatment of acute intoxications caused by drugs and pesticides with high lipid solubility. This study was conducted to investigate the effect of ILE co-administration on the kinetic dispositions of ivermectin (IVM) and carprofen (CRP) following intravenous bolus administration at subtoxic doses in rabbits. Twenty-four male New Zealand rabbits weighing 2.78 ± 0.2 kg were used in this study. Rabbits were divided into four groups (Group 1: IVM and Group 2: IVM + ILE or Group 3: CRP and Group 4: CRP + ILE), each group consisting of 6 animals. In the IVM study, Group 1 received IVM (0.6 mg/kg) alone while Group 2 received IVM (0.6 mg/kg) and ILE (2.5 ml/kg). In the CRP study, Group 3 received CRP (12 mg/kg) alone while Group 4 received CRP (12 mg/kg) and ILE (2.5 ml/kg). In both drug groups, ILE was administered 3 times as an i.v. bolus at the 10th min and repeated 4th and 8th h after the drug administration. Blood samples were collected from the auricular vein at various times after drug administration. The drug concentrations in plasma samples were determined by high-pressure liquid chromatography. Kinetic parameters were calculated using a non-compartmental model for both CRP and IVM. The C0 and area under the concentration–time curve from zero up to ∞ (AUC0–∞) values were significantly greater with ILE co-administration (2136 ng/ml and 360.84 ng.d/ml) compared to the IVM alone (1340.63 ng/ml and 206 ng.d/ml), respectively. Moreover, the volume of distribution (Vdss) and clearance (Cl) of IVM were reduced by approximately 42% and 46% with ILE co-administration compared to IVM alone resulting in a reduction of the distribution and slower elimination, respectively. Similar differences in C0, and Vdss values were also observed in CRP with ILE co-administration compared to CRP alone. ILE co-administration changed significantly the kinetic profile of both IVM and CRP in rabbits, supporting the lipid sink theory in which highly lipid-soluble compounds are absorbed into the lipid phase of plasma from peripheral organs such as the heart and brain affected by the acute toxicity of the compounds. [ABSTRACT FROM AUTHOR]

Background: Local anaesthetic systemic toxicity (LAST) is a rare but life-threatening complication that can occur after local anaesthetic administration. Various clinical guidelines recommend an intravenous lipid emulsion as a treatment for local anaesthetic–induced cardiac arrest. However, its therapeutic application in pregnant patients has not yet been established. This scoping review aims to systematically identify and map the evidence on the efficacy and safety of intravenous lipid emulsion for treating LAST during pregnancy. Method: We searched electronic databases (Medline, Embase and Cochrane Central Register Controlled Trials) and a clinical registry (lipidrescue.org) from inception to Sep 30, 2022. No restriction was placed on the year of publication or the language. We included any study design containing primary data on obstetric patients with signs and symptoms of LAST. Results: After eliminating duplicates, we screened 8,370 titles and abstracts, retrieving 41 full-text articles. We identified 22 women who developed LAST during pregnancy and childbirth, all presented as case reports or series. The most frequent causes of LAST were drug overdose and intravascular migration of the epidural catheter followed by wrong-route drug errors (i.e. intravenous anaesthetic administration). Of the 15 women who received lipid emulsions, all survived and none sustained lasting neurological or cardiovascular damage related to LAST. No adverse events or side effects following intravenous lipid emulsion administration were reported in mothers or neonates. Five of the seven women who did not receive lipid emulsions survived; however, the other two died. Conclusion: Studies on the efficacy and safety of lipids in pregnancy are scarce. Further studies with appropriate comparison groups are needed to provide more robust evidence. It will also be necessary to accumulate data—including adverse events—to enable clinicians to conduct risk–benefit analyses of lipids and to facilitate evidence-based decision-making for clinical practice. [ABSTRACT FROM AUTHOR]

Background Use of mixed-oil (MO) intravenous fat emulsion (IFE) was shown to inhibit Candida albicans biofilm formation and overall rate of catheter-related bloodstream infections (CR-BSIs) compared with soybean-oil (SO) IFE). We aimed to delineate this inhibitory mechanism and impact of IFE choice on distribution of fungal CR-BSIs. Methods Transcriptional profiling was conducted on C. albicans grown in SO-IFE, MO-IFE, or SO-IFE with capric acid. Overexpression strains of shared down-regulated genes were constructed using a tetracycline-off system to assess hypha and biofilm formation in IFEs. A 5-year retrospective multicenter cohort study was performed to assess differences in CR-BSIs caused by Candida species based on the IFE formulation received in pediatric patients. Results Genes significantly down-regulated in MO-IFE and SO-IFE with capric acid included CDC11 , HGC1 , and UME6. Overexpression of HGC1 or UME6 enabled filamentation in capric acid and MO-IFE. Interestingly, only overexpression of UME6 was sufficient to rescue biofilm growth in MO-IFE. MO-IFE administration was associated with a higher proportion of non- albicans Candida versus C. albicans CR-BSIs (42% vs 33%; odds ratio, 1.22 [95% confidence interval,.46–3.26]). Conclusions MO-IFE affects C. albicans biofilm formation and hyphal growth via a UME6 -dependent mechanism. A numerical but not statistically significant difference in distribution of Candida spp. among CR-BSIs was observed. [ABSTRACT FROM AUTHOR]

Background: Polytherapy in neonatal and pediatric patients requiring parenteral nutrition (PN) administration is a challenging task. Due to limited intravenous access, the Y-site administration of medication with PN admixtures is sometimes inevitable. Aim: This review aims to summarize the evidence on the compatibility of the Y-site of intravenous medications and PN admixtures in neonatal and pediatric settings. Methods: A literature review of the PubMed database was conducted. Articles published between January 1995 and November 2023 concerning the compatibility of intravenous medications in pediatric-dose PN admixtures or with intravenous lipid emulsions only were included. Studies concerning the compatibility/stability of the ingredients of PN admixtures and those concerning unapproved medications were excluded. Based on the methodology used, the quality of the research was assessed. Results: A total of fifteen studies were explored. Among fifty-five different drug substances assessed in the research reviewed, 56% (31/55) were found to be compatible, 13% (7/55) were assigned as incompatible, and for 31% (17/55), the data were ambiguous. None of the studies demonstrated an "A" grade (very high quality), and the grades "B", "C", and "D" were assigned to four, six, and five studies, respectively. The compatibility data are presented in two tables, the first concerning the simultaneous administration of medications with 2-in-1 PN formulations (without lipids) and the second, with 3-in-1 formulations (with lipids) and lipid emulsions. Conclusions: This review presents data on compatibilities between intravenously administered medications and PN mixtures intended for neonates and pediatric patients found in the PubMed database. It should be highlighted, however, that this work has some limitations. The clinical decisions on the simultaneous administration of intravenous medication with PN admixtures should be based not only on this review (including assessment of the quality of evidence) but also on manufacturer data, available electronic databases, and incompatibility data for PN admixtures dedicated to adult patients. [ABSTRACT FROM AUTHOR]

As the prevalence of tramadol toxicity is increasing, managing these patients with the aim of treatment and complete recovery has become a major challenge for health care professionals. This study evaluated the short-term effects of IV lipid emulsion (ILE) administration in cases of tramadol poisoning. In this double-blind, randomized controlled trial, 120 patients with pure tramadol poisoning and a Glasgow Coma (GCS) score ≤ 12 referred to a poisoning center in Tehran, Iran were selected and randomly assigned 1:1 to receive ILE 20% (intervention) or 0.9% saline (control) after admission and primary stabilization. The patient's vital signs, GCS score, hospitalization duration, and rate of seizure occurrence were recorded and compared between the two groups. Mean (SD) age of participants was 25.3 (5.4) years and 84 (70%) were male. Mean (SD) ingested dose of tramadol was 3118 (244) mg, which was not different between the groups. Compared with controls, the ILE group had a higher level of consciousness after treatment (median [interquartile range] GCS score 12 [10–13] vs. 10 [8–12]; p = 0.03). In addition, length of hospitalization (median [interquartile range] (2 [1–3] days vs. 4 [4–6] days; p < 0.01) and rate of seizure occurrence were lower in the intervention group (16/60 vs. 30/60; p < 0.01). In the setting of tramadol poisoning with a decreased level of consciousness and based on our study's findings, administration of ILE is suggested to help manage patients in hospital emergency departments. However, larger trials might be needed to confirm these findings before entering the guidelines. [ABSTRACT FROM AUTHOR]

In preterm neonates unable to obtain sufficient oral nutrition, intravenous lipid emulsion is life-saving. The contribution of post-conceptional level of maturation to pathology that some neonates experience is difficult to untangle from the global pathophysiology of premature birth. In the present study, we determined fetal physiological responses to intravenous lipid emulsion. Fetal sheep were given intravenous Intralipid 20® (n = 4 females, 7 males) or Lactated Ringer's Solution (n = 7 females, 4 males) between 125 ± 1 and 133 ± 1 d of gestation (term = 147 d). Manufacturer's recommendation for premature human infants was followed: 0.5--1 g/kg/d initial rate, increased by 0.5--1 to 3 g/kg/d. Hemodynamic parameters and arterial blood chemistry were measured, and organs were studied postmortem. Red blood cell lipidomics were analyzed by LC-MS. Intravenous Intralipid did not alter hemodynamic or most blood parameters. Compared with controls, Intralipid infusion increased final day plasma protein (P=0.004; 3.5 ± 0.3 vs. 3.9 ± 0.2 g/dL), albumin (P = 0.031; 2.2 ± 0.1 vs. 2.4 ± 0.2 g/dL), and bilirubin (P<0.001; conjugated: 0.2 ± 0.1 vs. 0.6 ± 0.2 mg/dL; unconjugated: 0.2 ± 0.1 vs. 1.1 ± 0.4 mg/dL). Circulating IGF-1 decreased following Intralipid infusion (P<0.001; 66 ± 24 vs. 46 ± 24 ng/mL). Compared with control Oil Red O liver stains (median score 0), Intralipid-infused fetuses scored 108 (P=0.0009). Lipidomic analysis revealed uptake and processing of infused lipids into red blood cells, increasing abundance of saturated fatty acids. The near-term fetal sheep tolerates intravenous lipid emulsion well, although lipid accumulates in the liver. Increased levels of unconjugated bilirubin may reflect increased red blood cell turnover or impaired placental clearance. Whether Intralipid is less well tolerated earlier in gestation remains to be determined. [ABSTRACT FROM AUTHOR]

Purpose: The effect of different types of lipid emulsion may guide therapy of patients with intestinal failure (IF) to limit morbidity such as intestinal failure-associated liver disease (IFALD). Methods: A retrospective chart review of pediatric patients with IF who received soybean oil lipid emulsion (SL) or mixed oil lipid emulsion (ML) was performed. Data over 1 year were collected. Results: Forty-five patients received SL and 34 received ML. There were no differences in the incidence (82 versus 74%, P = 0.35) or resolution (86 versus 92%, P = 0.5) of IFALD between the cohorts. The median dose of ML was higher compared to SL (2 versus 1 g/kg/day, P < 0.001). If resolved, IFALD resolved rapidly in the ML cohort compared to the SL cohort (67 versus 37 days, P = 0.01). Weight gain was higher in the ML compared to the SL cohort at resolution of IFALD or 1 year from diagnosis of IF (P = 0.009). Conclusion: The administration of ML did not alter the incidence or resolution of IFALD compared to SL in pediatric IF. There was rapid resolution of IFALD and enhanced weight gain in the ML cohort compared to SL in pediatric IF. [ABSTRACT FROM AUTHOR]

Purpose Sulbactam/durlobactam is a combination antibiotic designed to target Acinetobacter baumannii , including carbapenem-resistant and multidrug-resistant strains. The objective of this study was to determine the physical compatibility of sulbactam/durlobactam solution during simulated Y-site administration with 95 intravenous (IV) drugs. Methods Vials of sulbactam/durlobactam solution were diluted in 0.9% sodium chloride injection to a volume of 100 mL (the final concentration of both drugs was 15 mg/mL). All other IV drugs were reconstituted according to the manufacturer's recommendations and diluted with 0.9% sodium chloride injection to the upper range of concentrations used clinically or tested undiluted as intended for administration. Y-site conditions were simulated by mixing 5 mL of sulbactam/durlobactam with 5 mL of the tested drug solutions in a 1:1 ratio. Solutions were inspected for physical characteristics (clarity, color, and Tyndall effect), turbidity, and pH changes before admixture, immediately post admixture, and over 4 hours. Incompatibility was defined as any observed precipitation, significant color change, positive Tyndall test, or turbidity change of ≥0.5 nephelometric turbidity unit during the observation period. Results Sulbactam/durlobactam was physically compatible with 38 out of 42 antimicrobials tested (90.5%) and compatible overall with 86 of 95 drugs tested (90.5%). Incompatibility was observed with albumin, amiodarone hydrochloride, ceftaroline fosamil, ciprofloxacin, daptomycin, levofloxacin, phenytoin sodium, vecuronium, and propofol. Conclusion The Y-site compatibility of sulbactam/durlobactam with 95 IV drugs was described. These compatibility data will assist pharmacists and nurses to safely coordinate administration of IV medications with sulbactam/durlobactam. [ABSTRACT FROM AUTHOR]

Background: Flecainide is an anti-arrhythmic medication with a narrow therapeutic index and a high mortality rate when overdosed. Few cases of flecainide toxicity in neonates and children due to medication errors have been reported in the literature. A case of an accidental flecainide overdose in a neonate in Oman was presented. Case Presentation: A 19-day-old newborn girl developed persistent supra ventricular tachycardia (SVT) after receiving nebulized albuterol for acute bronchitis. After unsuccessful treatment with adenosine, she was given flecainide 5.6 mg orally every 24 hours for resolution of the SVT. On day 4 of admission, the child inadvertently received 100 mg of flecainide orally due to a dose calculation error. The child developed wide complex tachyarrhythmia followed by pulseless ventricular tachycardia (VT) requiring cardiopulmonary resuscitation. Sodium bicarbonate intravenous (IV) bolus followed by an infusion was administered. The patient developed two additional episodes of pulseless VT that coincided temporally with two interruptions of the sodium bicarbonate infusion and required a high dose of inotropic support. The patient developed convulsions but her brain ultrasound was normal. Her condition stabilized on day 3 after the toxicity occurred. Repeated echo showed a normal ejection fraction (EF). The patient was discharged on propranolol and levetiracetam and was doing well on outpatient follow up. Conclusion: Flecainide is a potentially lethal medication in overdose due to its sodium channel-blocking properties. Sodium bicarbonate remains an essential component of treatment. [ABSTRACT FROM AUTHOR]

Introduction and purpose: Over the last few years, the number of suicide attempts in Polish women has been steadily increasing. This report presents a case of a 18 years old woman hospitalized in the Toxicology and Cardiology Department due to poisoning with antiarrhythmic drug - Propafenone, taken for suicide purpose. Brief description of the state of knowledge: Propafenone is an antiarrhythmic drug which belongs to class IC according to the Vaughan-Williams classification. The overdose of this drug can cause various symptoms and complications such as cardiac arrhythmias, liver damage, cardiac arrest and even death. This drug has no specific antidote. Conclusions: Propafenone poisoning is a significant clinical challenge and the consequences are often unpredictable and life-threatening. Treatment options such as natrium bicarbonicum, insulin, intravenous lipid emulsion, calcium gluconate seem to be good choices and the effects of treatment with these drugs are promising for the future. [ABSTRACT FROM AUTHOR]

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The intravenous lipid emulsion (ILE) therapy is known to alleviate clinical symptoms in cases of bupivacaine-induced cardiac toxicity. However, there is insufficient information regarding histopathological damage. This study aimed to investigate whether the use of ILE therapy in rats with experimentally induced bupivacaine-related cardiac toxicity can ameliorate histopathological damage. 28 Wistar albino rats were divided into four groups: control (A), lipid (B), bupivacaine (C), and bupivacaine + lipid (D). After providing monitoring in all groups, group B received 1.5 mL ILE + 0.25 µg/kg/min ILE infusion, group C received 3 µg/kg/min bupivacaine infusion, and group D received 3 µg/kg/min bupivacaine infusion followed by 1.5 mL ILE + 0.25 µg/kg/min ILE infusion after observing cardiac toxicity. Heart rate and respiratory rate were recorded. Blood samples were collected post-procedure to measure LDH, CK-MB, and troponin levels. Cardiac tissue samples were obtained for histopathological examination. There was no significant difference in baseline heart rate and respiratory rate among the groups (P>0.05). However, in the second measurements, heart rate and respiratory rate were higher in group D compared to group C (P<0.05). LDH and CK-MB levels were higher in group C compared to the other groups (P<0.05). Irisin and asprosin scores were higher in group D compared to the other groups (P<0.05). ILE was found to have a cardioprotective effect in the treatment of bupivacaine-induced cardiac toxicity, as it improved both clinical and laboratory parameters. However, histologically, cardiac damage persisted. [ABSTRACT FROM AUTHOR]

The administration of intravenous lipid emulsion (ILE) is a proven antidote used to reverse local anesthetic-related systemic toxicity. Although the capacity of ILE to generate blood tissue partitioning of lipophilic drugs has been previously demonstrated, a clear recommendation for its use as an antidote for other lipophilic drugs is still under debate. Venlafaxine (an antidepressant acting as a serotonin–norepinephrine reuptake inhibitor (SNRI)) and quetiapine (a second-generation atypical antipsychotic) are widely used in the treatment of psychotic disorders. Both are lipophilic drugs known to induce cardiotoxicity and central nervous depression. We report the case of a 33-year-old man with a medical history of schizoaffective disorder who was admitted to the emergency department (ED) after having been found unconscious due to a voluntary ingestion of 12 g of quetiapine and 4.5 g of venlafaxine. Initial assessment revealed a cardiorespiratory stable patient but unresponsive with a GCS of 4 (M2 E1 V1). In the ED, he was intubated, and gastric lavage was performed. Immediately after the admission to the intensive care unit (ICU), his condition quickly deteriorated, developing cardiovascular collapse refractory to crystalloids and vasopressor infusion. Junctional bradycardia occurred, followed by spontaneous conversion to sinus rhythm. Subsequently, frequent ventricular extrasystoles, as well as patterns of bigeminy, trigeminy, and even episodes of non-sustained ventricular tachycardia, occurred. Additionally, generalized tonic–clonic seizures were observed. Alongside supportive therapy, antiarrhythmic and anticonvulsant therapy, intravenous lipid emulsion bolus, and continuous infusion were administered. His condition progressively improved over the following hours, and 24 h later, he was tapered off the vasopressor. On day 2, the patient repeated the cardiovascular collapse and a second dose of ILE was administered. Over the next few days, the patient's clinical condition improved, and he was successfully weaned off ventilator and vasopressor support. ILE has the potential to become a form of rescue therapy in cases of severe lipophilic drug poisoning and should be considered a viable treatment for severe cardiovascular instability that is refractory to supportive therapy. [ABSTRACT FROM AUTHOR]

Bupivacaine (BPV) can cause severe central nervous system toxicity when absorbed into the blood circulation system. Rapid intravenous administration of lipid emulsion (LE) could be used to treat local anaesthetic toxicity. This study aimed to investigate the mechanism by which the BDNF-TrkB/proBDNF-p75NTR pathway regulation by LE rescues BPV induced neurotoxicity in hippocampal neurons in rats. Seven- to nine-day-old primary cultured hippocampal neurons were randomly divided into 6 groups: the blank control group (Ctrl), the bupivacaine group (BPV), the lipid emulsion group (LE), the bupivacaine + lipid emulsion group (BPV + LE), the bupivacaine + lipid emulsion + tyrosine kinase receptor B (TrkB) inhibitor group (BPV + LE + K252a), the bupivacaine + lipid emulsion + p75 neurotrophic factor receptor (p75NTR) inhibitor group (BPV + LE + TAT-Pep5). All hippocampal neurons were incubated for 24 h, and their growth state was observed by light microscopy. The relative TrkB and p75NTR mRNA levels were detected by real-time PCR. The protein expression levels of brain-derived neurotrophic factor (BDNF), proBDNF, TrkB, p75NTR and cleaved caspase-3 were detected by western blotting. The results showed that primary hippocampal neuron activity was reduced by BPV. As administration of LE elevated hippocampal neuronal activity, morphology was also somewhat improved. The protein expression and mRNA levels of TrkB and p75NTR were decreased when BPV induced hippocampal neuronal toxicity, while the expression of BDNF was increased. At the same time, BPV increased the original generation of cleaved caspase-3 protein content by hippocampal neurons, while the content of cleaved caspase-3 protein in hippocampal neurons cotreated with LE and BPV was decreased. Thus, this study has revealed LE may reduce apoptosis and promote survival of hippocampal neurons by regulating the BDNF-TrkB pathway and the proBDNF-p75NTR pathway to rescue BPV induced central neurotoxicity in rats. [ABSTRACT FROM AUTHOR]

The article offers information on intravenous lipid emulsion (ILE) therapy. Topics covered include ILE as first-line treatment for local anesthetic systemic toxicity, ILE as rescue treatment for overdose of various drugs, including tricyclic antidepressant, beta-blocker and calcium-channel blocker and buproprion, and the adverse effects of ILE. It also cites how to administer ILE.

The Malassezia species are dimorphic fungi that require lipids such as olive oil for their growth. They are constituents of the normal human skin microbiota and can affix to the host or other surfaces through the establishment of biofilms. Malassezia species are accountable for superficial mycoses like folliculitis. Additionally, they are capable of causing invasive infections, such as of the bloodstream, in neonates and immunocompromised patients, albeit infrequently. Catheter-associated bloodstream infections in neonates are the most commonly reported invasive cases. Remarkably, unlike other invasive fungal infections, neutropenia and the use of broad-spectrum antibiotics do not seem to contribute to the risk of invasive Malassezia infections. Nosocomial outbreaks of Malassezia infections have been reported. While most cases of invasive Malassezia infection are fungemia, they seldom give rise to disseminated lesions in various organs. The diagnosis can be confirmed by the visualization of characteristic yeasts through histologic or cytologic examination of a biopsy or needle aspiration specimen, or via positive culture results from sterile sites. The prognosis for invasive Malassezia infection is generally favorable, with few reports of treatment failure. Nevertheless, due to the limited number of cases, evidence-based treatment recommendations are wanting. Management of invasive Malassezia infections linked to central venous catheters includes removal of the catheter, cessation of intravenous lipid emulsion, and intravenous administration of appropriate antifungal agents. [ABSTRACT FROM AUTHOR]

Currently, lipid emulsion (LE) is widely used to treat local anesthetic systemic toxicity (LAST). LE also ameliorates intractable cardiovascular collapse caused by lipid-soluble non-local anesthetic drug toxicity. This review aims to provide the underlying mechanism of LE resuscitation in drug toxicity (including LAST) and a detailed description of LE treatment and to discuss further research directions. We searched for relevant articles using the following keywords: “local anesthetic systemic toxicity or LAST or toxicity or intoxication or poisoning” and “Intralipid or lipid emulsion.” The underlying mechanisms of LE treatment can be classified into indirect and direct effects. One indirect effect known as the lipid shuttle is a commonly accepted mechanism of LE treatment. The lipid shuttle involves the absorption of highly lipid-soluble drugs (e.g., bupivacaine) from the heart and brain through the lipid phase, which are then delivered to the muscle, adipose tissue, and liver for storage and detoxification. The direct effects include inotropic effects, fatty acid supply, attenuation of mitochondrial dysfunction, glycogen synthase kinase-3β phosphorylation, and inhibition of nitric oxide. These mechanisms appear to act synergistically to treat drug toxicity. The recommended protocol for LE treatment of LAST is as follows: a bolus administration of 20% LE at 1.5 ml/kg over 2–3 min followed by 20% LE at 0.25 ml/kg/min. LAST most commonly occurs after intravenous administration of local anesthetics. However, non-local anesthetic drugs that cause drug toxicity are orally administered. Further studies are needed to determine the optimal dosing schedule of LE treatment for non-local anesthetic drug toxicity.

Objective: This study aimed to assess the potential of intrathecal administration of lipid emulsions as a targeted therapeutic strategy to mitigate the hemodynamic consequences of high or total spinal anesthesia induced by bupivacaine in a rat model. Materials and Methods: After receiving approval from Koç University's Local Ethics Board of Animal Experiments, 14 adult female Wistar Albino rats were randomized into two groups: Lipid and Saline. After inducing a high spinal block, each group was treated with either intrathecal lipid emulsions or isotonic saline solutions, respectively. Hemodynamic parameters such as systolic, diastolic, and mean arterial blood pressures, as well as heart rate, were continuously monitored. A histological analysis was conducted upon completion of the study. Results: The Lipid group exhibited a significant increase in mean systolic (p=0.002), diastolic (p=0.002), and arterial pressures (p=0.002) compared to the Saline group. The mean pulse rate also differed significantly between the groups (p=0.009). Notably, while all rats in the Saline group succumbed, only two fatalities occurred in the Lipid group, with the other five rats surviving (p=0.021). Conclusion: This study suggests that intrathecal administration of lipid emulsions can serve as a rapid and effective intervention to counteract the hypotension and bradycardia induced by high or total spinal anesthesia with bupivacaine in rats. While these findings are promising, further experimentation and clinical trials are required to confirm this method's potential, focusing on its long-term safety, efficacy, and the establishment of an optimal administration protoco. [ABSTRACT FROM AUTHOR]

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

Background: Reports of essential fatty acid deficiency (EFAD) in patients receiving parenteral nutrition (PN) and a composite lipid (mixed oil intravenous lipid emulsion [MO ILE]) are predominantly when managed by lipid restriction. The objective of this study was to determine the prevalence of EFAD in patients with intestinal failure (IF) who are PN dependent without lipid restriction. Methods: We retrospectively evaluated patients, ages 0–17 years, followed by our intestinal rehabilitation program between November 2020 and June 2021 with PN dependency index (PNDI) of >80% on a MO ILE. Demographic data, PN composition, PN days, growth, and plasma fatty acid profile were collected. A plasma triene‐tetraene (T:T) ratio >0.2 indicated EFAD. Summary statistics and Wilcoxon rank sum test evaluated to compare between PNDI category and ILE administration (grams/kilograms/day). P < 0.05 was considered significant. Results: Twenty‐six patients (median age, 4.1 years [interquartile range (IQR) = 2.4–9.6]) were included. The median duration of PN was 1367 days (IQR = 824–3195). Sixteen patients had a PNDI of 80%–120% (61.5%). Fat intake for the group was 1.7 g/kg/day (IQR = 1.3–2.0). The median T:T ratio was 0.1 (IQR = 0.1–0.2) with no values >0.2. Linoleic and arachidonic acid were low in 85% and 19% of patients, respectively; however, Mead acid was normal in all patients. Conclusion: This report is the largest to date on the EFA status of patients with IF on PN. These results suggest that, in the absence of lipid restriction, EFAD is not a concern when using MO ILEs in children receiving PN for IF. [ABSTRACT FROM AUTHOR]

Despite conflicting data, intravenous lipid emulsion has emerged as a potential antidote. The "lipid sink" theory suggests that following intravenous administration of lipid, lipophilic drugs are sequestered in the vascular compartment, thereby reducing their tissue concentrations. This study sought to determine if survival is associated with the intoxicant's degree of lipophilicity. We reviewed all cases in the Toxicology Investigators Consortium's lipid sub-registry between May 2012 through December 2018. Information collected included demographics, exposure circumstances, clinical course, management, disposition, and outcome. The primary outcome was survival after lipid emulsion therapy. Survival was stratified by the log of the intoxicant's octanol-water partition coefficient. We also assessed the association between intoxicant lipophilicity and an increase in systolic blood pressure after lipid emulsion administration. We identified 134 patients, including 81 (60.4%) females. The median age was 40 years (interquartile range 21-75). One hundred and eight (80.6%) patients survived, including 45 (33.6%) with cardiac arrest during their intoxication. Eighty-two (61.2%) were hypotensive, and 98 (73.1%) received mechanical ventilation. There was no relationship between survival and the log of the partition coefficient of the intoxicant on linear analysis (P = 0.89) or polynomial model (P = 0.10). Systolic blood pressure increased in both groups. The median (interquartile range) systolic blood pressure before lipid administration was 68 (60-78) mmHg for those intoxicants with a log partition coefficient < 3.6 compared with 89 (76-104) mmHg after lipid administration. Among those drugs with a log partition coefficient > 3.6, the median (interquartile range) was 69 (60-84) mmHg before lipid and 89 (80-96) mmHg after lipid administration. Most patients in this cohort survived. Lipophilicity was not correlated with survival or the observed changes in blood pressure. The study did not address the efficacy of lipid emulsion. [ABSTRACT FROM AUTHOR]

Objective To analyze the clinical characteristics of neonatal lactic acidosis and thrombocytopenia induced by multi-oil fat emulsions （SMOF), aiming to deepen clinicians’ understanding of adverse reactions to this drug. Methods Clinical data of two male neonates who suffered from lactic acidosis and/or thrombocytopenia after using intravenous SMOF for more than two weeks were analyzed. Literature review was conduced from PubMed, SinoMed, CNKI, Wanfang Data and CMAPH using the keywords of “neonate”, “multi-oil fat emulsions”, “lactic acidosis”, and “thrombocytopenia” in both Chinese and English. Clinical data of retrieved cases were collected and analyzed. Results Blood lactate, acidosis, and platelets returned to normal in two cases after terminating SMOF. Eight cases of fat overload syndrome caused by fat emulsion injection were retrieved by literature review, and one of them was treated with SMOF. All eight cases were improved after terminating intravenous fat emulsion, and four of them also received blood exchange therapy. Conclusions SMOF can cause neonatal lactic acidosis and/or thrombocytopenia. Clinicians should deepen the understanding of adverse reactions to this drug and lower the misdiagnosis and mistherapy rates. [ABSTRACT FROM AUTHOR]

Background: Distinguishing primary bloodstream infections (BSIs) related to central venous access devices (CVADs) from those that occur through other mechanisms, such as a damaged mucosal barrier, is difficult. Methods: Secondary analysis was conducted on data from patients with CVADs that were collected for a large, randomized trial. Patients were divided into two groups: those who received parenteral nutrition (PN)–containing intravenous lipid emulsion (ILE) and those who did not have PN‐containing ILE. This study investigated the influence of PN‐containing ILE (ILE PN) on primary BSIs in patients with a CVAD. Results: Of the 807 patients, 180 (22%) received ILE PN. Most (627/807; 73%) were recruited from the hematology and hematopoietic stem cell transplant unit, followed by surgical (90/807; 11%), trauma and burns (61/807; 8%), medical (44/807; 5%), and oncology (23/807; 3%). When primary BSI was differentiated as a central line‐associated BSI (CLABSI) or mucosal barrier injury laboratory‐confirmed BSI (MBI‐LCBI), the incidence of CLABSI was similar in the ILE PN and non–ILE PN groups (15/180 [8%] vs 57/627 [9%]; P = 0.88) and the incidence of MBI‐LCBI was significantly different between groups (31/180 [17%] ILE PN vs 41/627 [7%] non–ILE PN; P < 0.01). Conclusion: Our data indicate that twice as many primary BSIs in ILE PN patients are due to MBIs than CVADs. It is important to consider the MBI‐LCBI classification, as some CLABSI prevention efforts aimed at CVADs for the ILE PN population may be better directed to gastrointestinal tract protection interventions. [ABSTRACT FROM AUTHOR]