Dosage of Lipid Emulsions as an Antidote to Lipid-Soluble Substances

Introduction: Lipid emulsions are increasingly used as an antidote to lipophilic drug intoxications. The dose recommended by the American Society of Regional Anesthesia is used primarily for the treatment of local anesthetic systemic toxicity. There is insufficient information about what the dose of lipid emulsions (LE) should be in other intoxications depending on their severity. Aim: To determine the LE dose in a shock or haemodynamic instability in patients with acute exogenous intoxications treated with LE. Materials and methods: Forty-nine patients with acute lipophilic drug intoxications were treated with LE in the Clinic of Toxicology at the Naval Hospital in Varna. Statistical analysis was performed using the statistical functions of Excel 2016 and the Statistica 7.0 software package. Results: The percentage of patients receiving a low dose of LE of 0.3 ml/kg (93.87%) was significantly higher than the percentage of patients treated with a medium (2.04%) and a high dose (4.08%) of LF. The high dose of LE of 1.5 ml/kg recommended by the American Society of Regional Anesthesia was administered to two patients (4.08%). In severe intoxications with exotoxic shock, the rate of LE administration varies from 20 ml/h to 40 ml/h. Conclusions: In severe intoxications with cardiotoxic syndrome and haemodynamic instability, LE should be used in the dose as suggested by the American Society of Regional Anesthesia. It is possible to use lower doses of LE in the range of 0.3–0.6 ml/kg in all moderate poisonings administered by continuous intravenous infusion for 12-24-48 hours. No side effects were observed at these doses.

SAFETY AND QUALITY OF INTRAVENOUS LIPIDS FOR NEWBORNS: EFFECTS ON CRITICAL DISEASES AND METABOLIC DISORDERS (PART II)

Premature birth and its complications cause stress in newborns, which restrains their physical growth for several weeks after birth and is associated with chronic morbidity and neurological disability in the future. Preterm infants face such difficulties as respiratory distress, cardiovascular disease, gastrointestinal dysfunction and very low birth weight. Most complications in newborns are associated with oxidative stress that develops during the early period of growth. The formation of free radicals entails oxidative damage to many organs and systems of the body and is the main factor responsible for the development of typical diseases of preterm infants, such as bronchopulmonary dysplasia, patent ductus arteriosus, retinopathy of prematurity, necrotizing enterocolitis, intraventricular hemorrhage, and respiratory distress syndrome. Premature infants depend on adequate early parenteral nutrition, which not only guarantees they will survive but also ensures positive health outcomes later in life. Early use of intravenous lipids helps to prevent essential fatty acid deficiencies, provides energy and substrates for cell membrane synthesis, which are important for the growth and development of infants with very low and extremely low birth weight. This publication represents data on the effect of intravenous lipids on critical conditions and metabolic disorders in newborns. Literature sources are analyzed and the existing evidence of the possible influence of lipid emulsions on critical diseases in newborns is presented: intraventricular hemorrhage; necrotizing enterocolitis, patent ductus arteriosus and thrombocytopenia; glucose metabolism (hypo- and hyperglycemia); hyperbilirubinemia and chronic liver damage. The literature review is aimed at finding optimal strategies for the use of lipid emulsions in intensive care of newborns to improve the quality of care for premature infants. The purpose of this work is to analyze the results of published studies and systematize data on the feasibility and safety of lipid emulsions used in newborns with critical diseases of the perinatal period.

Three Lipid Emulsions Reduce Staphylococcus aureus-Stimulated Phagocytosis in Mouse RAW264.7 Cells

Soybean oil (SO)-, SO medium-chain triglyceride (MCT)-, olive oil (OO)-, and fish oil (FO)-based lipid emulsions are generally applied in clinical practice via intravenous injection for patients with nutritional requirements. The function of lipid emulsions on immune modulation remains inconsistent, and their effects on macrophages are limited. In the present study, we used a model of S. aureus-infected mouse RAW264.7 macrophages to determine the influence of three different compositions of lipid emulsions (Lipofundin, ClinOleic, and Omegaven) on reactive oxygen species (ROS) production, phagocytosis, and bacterial survival. The three individual lipid emulsions similarly enhanced bacterial survival but reduced S. aureus-stimulated ROS, phagocytosis of S. aureus bioparticles conjugate, polymerization of F-actin, and phosphorylation of AKT, JNK, and ERK. Compared with the JNK and ERK inhibitors, the PI3K inhibitor markedly suppressed the phagocytosis of S. aureus bioparticles conjugate and the polymerization of F-actin, whereas it significantly increased the bacterial survival. These results suggest that the three lipid emulsions diminished ROS production and phagocytosis, resulting in increased bacterial survival. PI3K predominantly mediated the inhibitory effects of the lipid emulsions on the phagocytosis of mouse RAW264.7 macrophages.

Biochemical Parameters in Extremely Preterm Infants Receiving Mixed Lipid Emulsions

OBJECTIVE A mixture of soybean, medium-chain triglycerides, olive, and fish oils (SMOF) contains higher α-tocopherol and n-3 polyunsaturated fatty acids and lower phytosterol content compared with conventional soybean oil lipid emulsions (SOLE). We sought to characterize plasma total fatty acid profiles (FAPs) and assess the tolerability of long-term SMOF therapy in extremely preterm infants. METHODS We retrospectively evaluated infants born <28 weeks gestational age who received at least 30 consecutive days of SMOF between July 2016 and June 2019. We evaluated monthly FAPs and biochemical tolerance to SMOF using direct bilirubin (DB) and triglyceride (TG) levels. Growth parameters were evaluated longitudinally until discharge. RESULTS Sixteen patients with median gestational age 24 weeks (IQR, 23–25 weeks) received SMOF for median 76 days (IQR, 52–130 days). Fourteen patients had necrotizing enterocolitis (NEC) requiring surgical intervention and 15 patients received SOLE for median 19 days (IQR, 14–26 days) prior to switching to SMOF. Median docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) levels were elevated, whereas the remaining fatty acid levels fell within reported reference ranges. There were no incidents of essential fatty acid deficiency (triene to tetraene ratio >0.2) or hypertriglyceridemia (TG >200 mg/dL) with a general downtrend in DB after the first month on SMOF. All growth Z-scores declined throughout hospital stay. CONCLUSIONS Infants who received SMOF had a more pronounced elevation in DHA than EPA, of which the clinical significance remains unknown. Growth Z-scores declined with SMOF but were confounded by a high prevalence of surgically treated NEC.

SAFETY AND QUALITY OF INTRAVENOUS LIPIDS FOR NEWBORNS: CURRENT KNOWLEDGE AND FUTURE PROSPECTS

. Premature birth leads to the developmentof "metabolic shock" in a newborn, the severity of whichis inversely opposite to the weight and gestational age.Infants lose the ability to receive nutrients naturally,transplacentally, and the ability to metabolize mother'smilk is limited due to immaturity. The growth up standardof a prematurely born child is intrauterine growth of thefetal brain and body, which requires not only a sufficientamount of essential nutrients, but also their qualitativecomposition. Nutritional support of premature newborns isa difficult task, especially if infants have perinatal diseasesor require mechanical ventilation, which makes theircatabolic state even worse. Stress limits the child's continuedphysical growth during the first few weeks after birth, andis associated with chronic morbidity and neurologicaldisability in the future. One, and sometimes the only way ofsupplying the main nutrients, is parenteral nutrition, highquality performance of which makes it possible to satisfymost of the nutritional needs of premature babies. In recentyears, high-quality parenteral nutrition protocols have beendeveloped, the adherence to which allows to achieve thegoal. They involve a rather aggressive approach to aminoacid and lipid infusion, but there is still concern about theuse of early parenteral nutrition. Especially restrictionsrelate to intravenous lipids, which are based on severaldogmas, indicating that lipid infusion can be associatedwith the damage of the lungs and liver tissues, as wellas the development of sepsis and thrombosis. There areseveral recent reviews that partially refute these dogmas.In our publication we would like to provide a short basicdata on the safety of lipid emulsions used in newborns, andalso to provide data on the positive effect of lipids on somebiochemical processes and conditions, with an emphasison their features, depending on the composition of the fatemulsion. The literature review can be used to view clinicalpractice, to search for optimal strategies of lipid emulsionsusage, taking into account their chemical components,which will improve the quality of nursing prematureinfants. The purpose of this work is to analyze scientificliterature sources to study and systematize data on modernaspects of the use of lipid emulsions in newborns.

Effects of lipid emulsions on the formation of Escherichia coli–Candida albicans mixed-species biofilms on PVC

Patients receiving lipid emulsions are at increased risk of contracting catheter-related bloodstream infections (CRBSIs) in the clinic. More than 15% of CRBSIs are polymicrobial. The objective of this study was to explore the effects of lipid emulsions on the formation of Escherichia coli (E. coli)–Candida albicans (C. albicans) mixed-species biofilms (BFs) on polyvinyl chloride (PVC) surfaces and the underlying mechanism. Mixed-species BFs were produced by coculturing E. coli and C. albicans with PVC in various concentrations of lipid emulsions. Crystal violet staining and XTT assays were performed to test the mixed-species BF biomass and the viability of microbes in the BFs. The microstructures of the BFs were observed by an approach that combined confocal laser scanning microscopy, fluorescence in situ hybridization, and scanning electron microscopy. The study found that lipid emulsions could promote the formation of E. coli–C. albicans mixed-species BFs, especially with 10% lipid emulsions. The mechanism by which lipid emulsions promote mixed-species BF formation may involve significant upregulation of the expression of the flhDC, iha, HTA1, and HWP1 genes, which are associated with bacterial motility, adhesion, and BF formation. The results derived from this study necessitate strict aseptic precautions when handling lipid emulsions and avoiding the use of high concentrations of lipid emulsions for as long as possible.

Smoflipid Is Better Than Lipofundin for Long-Term Neurodevelopmental Outcomes in Preterm Infants

Neurodevelopmental morbidities developed more commonly in low-birth-weight premature infants. We sought to determine the effects of different lipid emulsions on the neurodevelopmental outcomes of children born prematurely. This retrospective cross-sectional study had two intervention legs, Lipofundin® MCT/LCT (LIPO) versus Smoflipid® (SMOF), which are mainly differentiated by fish oil. Data of premature neonates born between 2001 and 2015 from the research database of Chang Gung Memorial Hospital with corresponding individual medical records up to July 2020 were analyzed. Long-term neurodevelopmental outcomes were defined by the international classification of disease codes −9 or −10. The prevalence of diseases was compared between LIPO and SMOF groups at five and five years old and further analyzed by stratification of 1500 g birth weight. The LIPO and SMOF groups each included 1120 neonates. Epilepsy, cerebral palsy, developmental disorder and attention-deficit hyperactivity disorder (ADHD) were significantly decreased at age two years in the SMOF group, and epilepsy, language delay (LD), ADHD and autism spectrum disorder (ASD) were significantly decreased in the SMOF group at age five years. In children with birth weight < 1500 g, ADHD was decreased in the SMOF group at ages two and five years, and ASD was decreased in the SMOF group at age five years. In children with birth weight ≥ 1500 g, epilepsy, LD and ADHD were decreased in the SMOF group at age two years. LD was decreased in the SMOF group at age five years. We conclude that lipid emulsions with fish oil improve the neurodevelopmental outcomes of children born prematurely.