Administration Of Lipid Emulsion Research Articles

The Lipid Intensive Drug Therapy for Sepsis Phase II Pilot Clinical Trial.

Low cholesterol levels in early sepsis patients are associated with mortality. We sought to test if IV lipid emulsion administration to sepsis patients with low cholesterol levels would prevent a decline or increase total cholesterol levels at 48 hours. Phase II, adaptive, randomized pilot clinical trial powered for 48 patients. Emergency department or ICU of an academic medical center. Sepsis patients (first 24 hr) with Sequential Organ Failure Assessment greater than or equal to 4 or shock. Patients meeting study criteria, including screening total cholesterol levels less than or equal to 100 mg/dL or high-density lipoprotein cholesterol (HDL-C) + low-density lipoprotein cholesterol (LDL-C) less than or equal to 70 mg/dL, were randomized to receive one of three doses of lipid emulsion administered twice in 48 hours or no drug (controls). The primary endpoint was a change in serum total cholesterol (48 hr - enrollment) between groups. Forty-nine patients were enrolled and randomized. Two patients randomized to lipid emulsion were withdrawn before drug administration. Data for 24 control patients and 23 lipid emulsion patients were analyzed. The mean change in total cholesterol from enrollment to 48 hours was not different between groups and was 5 mg/dL (sd 20) for lipid emulsion patients, and 2 mg/dL (sd 18) for control patients (p = 0.62). The mean changes in HDL-C and LDL-C were similar between groups. Mean change in triglycerides was elevated in lipid emulsion patients (61 mg/dL, sd 87) compared with controls (20 mg/dL, sd 70, p = 0.086). The 48-hour change in SOFA score was -2 (interquartile range [IQR] -4, -1) for control patients and -2 (IQR -3, 0) for lipid emulsion patients (p = 0.46). Administration of IV lipid emulsion to early sepsis patients with low cholesterol levels did not influence change in cholesterol levels from enrollment to 48 hours.

Anti-Obesity Potentials of Methanol Extracts of Phragmanthera Incana Leaves Hemi-Parasitic on Guava, Cashew, Kolanut and Mango Trees in High-Fat Diet-Induced Obese Rats

The anti-obesity potential of methanol extracts of Phragmanthera incana leaves hemi-parasitic on guava Psidium guajava (PIPG), cashew Anacardium occidentale (PIAO), mango Mangifera indica (PIMI) and kolanut Cola acuminata (PICA) trees were evaluated. Thirty high-fat diet-induced rats were grouped into six; four experimental, negative control and positive controls were orally administered lipid emulsion (5 mL/kg). Experimental received 400 mg/kg body weight from each of the four methanol extracts in addition to the lipid emulsion, positive control received 120 mg/kg bw Orlistat in addition to lipid emulsion while negative control received lipid emulsion alone. Blood samples were collected from ophthalmic venous plexus at 0, 90, and 180 minutes to determine plasma pancreatic lipase (PL) activity, alpha amylase activity and lipid profiles. PL inhibitory activity of the four methanol extracts showed that methanol extracts of PICA and PIAO had greater than 50% inhibition at 400 µg/mL. The α-amylase inhibitory activity of PICA was significantly higher (p < 0.05) when compared with PIAO, PIPG and PIMI. A significant decrease (p < 0.05) in total cholesterol, low density Lipoprotein-cholesterol levels and atherogenic index of plasma of PICA when compared with other treatment groups after 180 minutes of extracts administration was observed. Methanol extract of PICA was found to exhibit higher inhibitory pancreatic lipase and α-amylase activities and higher hypocholesterolemic activity when compared with those of guava (PIPG), cashew (PIAO) and mango (PIMI). This indicates that methanol extract of P. incana leaves could serve as a source of phyto-compounds that could be developed as antiobesity drugs.

Impact of lipid emulsions in parenteral nutrition on platelets: a literature review.

Lipid emulsions are essential components of parenteral nutrition solutions that provide energy and essential fatty acids. The complexity of the formulations of lipid emulsions may lead to adverse outcomes such as platelet reactivity and changes in platelet aggregation and related coagulation. Platelets are responsible for haemostasis; they activate and demonstrate morphological changes upon extracellular factors to maintain blood fluidity and vascular integrity. Although parenteral nutrition lipid emulsions are generally found safe with regard to modulation of platelet activity, studies are still accumulating. Thus, this review aims to investigate platelet-related changes by parenteral nutrition lipid emulsions in human studies. Studies have pointed out patients at risk of bleeding and increased platelet aggregation responses due to the administration of lipid emulsions. Lipid emulsions may further benefit patients at high risk of thrombosis due to anti-thrombotic effects and should be cautiously used in patients with thrombocytopenia. The reported platelet-related changes might be associated with the fatty acid change in the plasma membranes of platelets following changes in platelet synthesis and plasma levels of eicosanoids. In conclusion, studies investigating platelets and parenteral nutrition should be supported to minimize the adverse effects and to benefit from the potential protective effects of parenteral nutrition lipid emulsions.

Evaluation of the effectiveness of third-generation lipid emulsion therapy for early pregnancy loss

BACKGROUND: Immune mechanisms play an important role in the pathogenesis of early pregnancy loss. To regulate disorders of immune homeostasis, immunoefferent therapy is used, such as immunocytotherapy, plasmapheresis, and intravenous administration of immunoglobulins and lipid emulsions, which may help to overcome infertility and recurrent miscarriage. Third-generation lipid emulsion (TGLE) is the modern “gold standard” of parenteral lipid therapy. It contains high concentrations of omega-3-polyunsaturated fatty acids, which can directly or indirectly affect the activity of natural killer (NK) cells. The literature comprises contradictory data on the efficacy of TGLE for repeated implantation failure. This may be due to the determination of biochemical parameters for its use and the selection of criteria for assessing the effectiveness of this therapy.
 AIM: The aim of this study was to evaluate the effectiveness of TGLE therapy in patients with a history of early pregnancy loss.
 MATERIALS AND METHODS: This prospective randomized controlled study enrolled 140 patients with early pregnancy loss (recurrent miscarriage and repeated implantation failure) at the Research Institute of Obstetrics, Gynecology and Reproducto logy named after D.O. Ott, Saint Petersburg, Russia from 2021 to 2023. Group 1 consisted of 50 women with TGLE therapy, and group 2 included 90 women without therapy. Patients of group 1 received lipid therapy according to the following regimen: TGLE 20% IV 6 ml per kilogram of body weight once a month for two months on end. Inclusion criteria: women from 18 to 45 years of age with two cases of reproductive failure – pregnancy loss up to 12 weeks of gestation and/or unsuccessful in vitro fertilization attempts (embryo transfers without effect) with normal karyotypes of the spouses. Exclusion criteria: women with miscarriage with an abnormal karyotype of the fetus, with anatomical abnormalities in the development of the reproductive apparatus, with an abnormal karyotype of any of the spouses, with hypersensitivity to omega-3 polyunsaturated fatty acids. We assessed the omega-3 index, functional characteristics of NK cells in the peripheral blood, and the effectiveness of lipid therapy based on biochemical and immunological parameters, as well as the clinical onset of pregnancy.
 RESULTS: The difference in the omega-3 index before and after treatment with TGLE was significant (p = 0.0002), this parameter being increased by 1.23 times compared to the initial level. The functional activity of NK cells in the blood was significantly different after the administration of TGLE: NK (CD3–CD(16+56+)) (p = 0.0041), NKT (CD3+CD(16+56+)) (p = 0.0498), and spontaneously activated NK (CD107a) (p = 0.0498). These parameters decreased by 1.63, 1.29, and 2.07 times relative to their initial levels. In group 1 of patients receiving TGLE therapy, clinical pregnancy occurred twice as often as compared to those who did not receive this therapy (56.41%, n = 22 vs. 31.25%, n = 20; p = 0.01).
 CONCLUSIONS: TGLE has shown effectiveness in pregnancy rates by increasing the omega-3 index and reducing the functional activity of NK cells in women with early pregnancy loss.

Effects of Intravenous Lipid Emulsion Administration in Acute Tramadol Poisoning: A Randomized Controlled Trial

BackgroundAs 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. ObjectiveThis study evaluated the short-term effects of IV lipid emulsion (ILE) administration in cases of tramadol poisoning. MethodsIn 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. ResultsMean (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). ConclusionsIn 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.

BDNF-TrkB/proBDNF-p75NTR pathway regulation by lipid emulsion rescues bupivacaine-induced central neurotoxicity in rats

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.

Lipid emulsion therapy during management of the critically-ill poisoned patient: a prospective cohort study

Background 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. Methods 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. Results 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. Conclusion 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.

Administration of lipid emulsion reduced the hypnotic potency of propofol more than that of thiamylal in mice.

Administration in a lipid emulsion can modify the pharmacodynamics of drugs via a process known as lipid resuscitation. However, the detailed mechanism remains unclear. We studied the volume and another pharmacodynamic effect, the lipid sink, using propofol and thiamylal. Male adult mice (ddY) were intravenously administered 10 ml/kg propofol or thiamylal diluted with physiological saline, 10% soybean oil, or 20% soybean oil. The 50% effective dose (ED50) for achieving hypnosis was calculated using probit analysis. To investigate the volume effect, 0, 10, or 20 ml/kg of saline or soybean oil was administered, either simultaneously or beforehand. Next, a two- or three-fold dose of the anesthetics was administered and the durations of anesthesia were measured. Finally, at 30 s after the first injection, supplemental soybean oil was administered. The mean (± SE) ED50 values of propofol and thiamylal were 5.79 mg/kg (0.61) and 8.83 mg/kg (0.84), respectively. Lipid dilution increased the ED50 values of both anesthetics. After injection of a dose two-fold the ED50 value, the respective mean (± SD) durations of anesthesia were 125 ± 35 s and 102 ± 38 s. Supplemental administration of soybean oil significantly shortened the duration of anesthesia of propofol, but not that of thiamylal. The results indicate that administration of a lipid emulsion vitiated the anesthetic effect of propofol by reducing the non-emulsified free fraction in the aqueous phase, which may elucidate the lipid resuscitation likely caused by the lipid sink mechanism.

Lipid emulsions prevent postoperative abdominal adhesions

IntroductionAdhesions are the most common cause of long-term morbidity after abdominal surgery and most often cause various forms of intestinal passage disorders ranging from partial obstruction to complete, life-threatening intestinal obstruction. The aim of the present study was to evaluate the protective effect of intraperitoneally administered lipid emulsions on the formation of adhesions in larger animal model, as the lubricating effect of phospholipids and the mechanical barrier of the lipid component are combined with the anti-inflammatory effect of fish oil. MethodsThirty-one female domestic pigs were randomly divided into three groups. At the end of the surgical procedure, a lipid emulsion or saline solution was applied intraperitoneally. After 14 days, an independent macroscopic, histological and immunohistochemical evaluation of the adhesions were performed. ResultsIntraperitoneal administration of lipid emulsions significantly reduced the incidence of intra-abdominal adhesions. Microscopic examination demonstrated a significant reduction in the number of inflammatory elements and the amount of collagen in the adhesions, especially after administration of the fish oil-based emulsion. A simultaneous decrease in neovascularization was observed in the adhesions. Evaluation of the intestinal anastomosis did not reveal significant differences in healing between the groups. ConclusionIntraperitoneal administration of lipid emulsions can reduce the development of postoperative intra-abdominal adhesions by the combined action of phospholipids as important lubricants and lipids as a mechanical barrier. Their effect is caused by a reduction in proinflammatory and profibrotic mediators. At the same time, intraperitoneal administration of lipid emulsions does not impair healing of the anastomosis in larger animal model.

Sudden quadriparesis after non-overdose local anesthesia

BackgroundA well-known anesthetic, lidocaine is the most widely used local anesthetic. Local anesthetic systemic toxicity (LAST) is a life-threatening event with common and prominent presentations of central nervous system (CNS) toxicity and cardiovascular toxicity. The most frequent and prominent early warning signs and symptoms of LAST are central nervous system symptoms. While rare, cases quadriparesis after the administration of lidocaine has been reported.Case presentationIn this paper, we report a very rare case of quadriparesis after local anesthesia administration for vocal cord cyst-removal surgery, which dramatically improved after treatment. LAST can occur during various routes of lidocaine administration, such as local spray. A possible mechanism of our case could be the local diffusion of lidocaine to the spinal cord, which caused the symptoms to mimic anterior cord syndrome.ConclusionsOur case presented a favorable outcome following the administration of intravenous lipid emulsion (ILE) for non-over dose local anesthetic drug induced spinal cord inhibition symptoms. These findings highlight the need for further research on the use of ILE to reverse LAST and other adverse effects of local anesthetics.

Cardio Protective Effects of Lipid Emulsion against Ropivacaine-Induced Local Anesthetic Systemic Toxicity-An Experimental Study.

Inadvertent intravascular injection of local anesthetics (LA) during regional anesthesia causes Local Anesthetic Systemic Toxicity (LAST). Theories of lipid rescue in the case of LAST proved that the administration of lipids in LAST has beneficial effects. One possible mechanism of action is based on the lipophilic properties of LA which allow plasma-free LA to be bound by the molecules of Lipid Emulsion (LE). The association LA–LE is shuttled towards organs such as liver and the kidneys, and the half-life of LA is shortened. The main objective of this experimental study was to assess the possible cardio-prophylactic effect of LE administration before the induction of LAST by intravenous administration of Ropivacaine. This was an experimental, interventional, prospective, and non-randomized study. The subjects were divided into groups and received, under general anesthesia, LE 20% first 0.3–0.4 mL, followed by 0.1 mL Ropivacaine 2 mg/mL, or Ropivacaine alone. At the end of the experiment, the subjects were sacrificed, and tissue samples of kidney, heart and liver were harvested for histopathological examination. LE, when administered as prophylaxis in Ropivacaine-induced LAST, had protective cardiac effects in rats. The LE known side effects were not produced if the substance was administered in the low doses used for LAST prophylaxis.

Superior Dialytic Removal of Bilirubin and Bile Acids by Free Fatty Acid Displacement and Its Synergy With Albumin-Based Dialysis.

One of the cardinal features of any liver replacement therapy is the ability to remove accumulated metabolites. However, an unsolved problem is the low dialyzability of lipophilic toxins. This study aimed to explore whether bilirubin and bile acids removal can be increased by free fatty acid (FFA) displacement and its synergy with albumin dialysis. First, we found that the protein binding of both bilirubin and bile acids decreased significantly with increasing FFA concentrations when co-incubated directly. Then, in vitro dialysis showed that fatty acid mixtures infusion prefilter effectively increased the fractional removals of bilirubin and bile acids, showing higher efficiency compared with albumin-based hemodialysis (HD); in vivo dialysis in liver failure rats showed that lipid emulsion administration resulted in higher reduction ratios and more total solute removals for bilirubin and bile acids after 4 h HD compared with control, which were also superior to albumin-based HD. Finally, the highest dialysis efficacy was always observed by their synergy whether in vitro or in vivo . These findings highlight that FFA displacement-based HD could efficiently improve the dialytic removal of bilirubin and bile acids, which might even be more efficient than albumin-based HD. Their synergy may represent a promising strategy to maximize the removal of circulating bilirubin and bile acids accumulated in liver failure.

Fatal accidental lipid overdose with intravenous composite lipid emulsion in a premature newborn: a case report

BackgroundTenfold or more overdose of a drug or preparation is a dreadful adverse event in neonatology, often due to an error in programming the infusion pump flow rate. Lipid overdose is exceptional in this context and has never been reported during the administration of a composite intravenous lipid emulsion (ILE).Case presentationTwenty-four hours after birth, a 30 weeks’ gestation infant with a birthweight of 930 g inadvertently received 28 ml of a composite ILE over 4 h. The ILE contained 50% medium-chain triglycerides and 50% soybean oil, corresponding to 6 g/kg of lipids (25 mg/kg/min). The patient developed acute respiratory distress with echocardiographic markers of pulmonary hypertension and was treated with inhaled nitric oxide and high-frequency oscillatory ventilation. Serum triglyceride level peaked at 51.4 g/L, 17 h after the lipid overload. Triple-volume exchange transfusion was performed twice, decreasing the triglyceride concentration to < 10 g/L. The infant’s condition remained critical, with persistent bleeding and shock despite supportive treatment and peritoneal dialysis. Death occurred 69 h after the overdose in a context of refractory lactic acidosis.ConclusionsMassive ILE overdose is life-threatening in the early neonatal period, particularly in premature and hypotrophic infants. This case highlights the vigilance required when ILEs are administered separately from other parenteral intakes. Exchange transfusion should be considered at the first signs of clinical or biological worsening to avoid progression to multiple organ failure.

Improved Dialysis Removal of Protein-Bound Uraemic Toxins with a Combined Displacement and Adsorption Technique

Introduction: Protein-bound uraemic toxins (PBUTs) are poorly removed by conventional dialytic techniques, given their high plasma protein binding, and thus low, free (dialysable) plasma concentration. Here, we evaluated and compared PBUTs removal among conventional haemodialysis (HD), adsorption-based HD, displacement-based HD, and their 2 combinations both in vitro and in vivo. Methods: The removal of PBUTs, including 3-carboxy-4-methyl-5-propyl-2-furan-propanoic acid (CMPF), p-cresyl sulphate (PCS), indoxyl sulphate (IS), indole-3-acetic acid (3-IAA), and hippuric acid, was first evaluated in an in vitro single-pass HD model. Adsorption consisted of adding 40 g/L bovine serum albumin (Alb) to the dialysate and displacement involved infusing fatty acid (FA) mixtures predialyser. Then, uraemic rats were treated with either conventional HD, Alb-based HD, lipid emulsion infusion-based HD or their combination to calculate the reduction ratio (RR), and the total solute removal (TSR) of solutes after 4 h of therapy. Results: In vitro dialysis revealed that FAs infusion prefilter increased the removal of PCS, IS, and 3-IAA 3.23-fold, 3.01-fold, and 2.24-fold, respectively, compared with baseline and increased the fractional removal of CMPF from undetectable at baseline to 14.33 ± 0.24%, with a dialysis efficacy markedly superior to Alb dialysis. In vivo dialysis showed that ω-6 soybean oil-based lipid emulsion administration resulted in higher RRs and more TSRs for PCS, IS, and 3-IAA after 4-h HD than the control, and the corresponding TSR values for PCS and IS were also significantly increased compared to that of Alb dialysis. Finally, the highest dialysis efficacy for highly bound solute removal was always observed with their combination both in vitro and in vivo. Conclusions: The concept of combined displacement- and adsorption-based dialysis may open up new avenues and possibilities in the field of dialysis to further enhance PBUTs removal in end-stage renal disease.

Changes in the heart rate of rats treated with verapamil overdose and resuscitated with lipid emulsion

Introduction: Verapamil is a drug that is used often due to its wide spectrum of action. Many authors consider it to be the most dangerous of the calcium channel blockers due to its negative chronotropic and inotropic effect on the heart, leading to severe cardiodepression. Overdose is difficult to treat and is associated with high mortality despite existing treatment options. Over the last 15 years, lipid emulsions (LEs) have been increasingly used for resuscitation after overdosing with lipophilic drugs such as verapamil. Despite the convincing results and the improved patient status, the association of the administration of LE with the recovery of patients may be questioned since LE was given in addition to standard therapy. Aim: The aim of this article is to conduct an evaluation of the self-cardioprotective effect of LE in acute verapamil overdose (15 mg/kg) in rats by measurement of the heart rate and survival at the recommended LE dose of 1.5 mL/kg and 7 times the recommended LE dose (10 mL/kg). Material and Methods: The experiment was performed on 30 male Wistar rats, provided by the Medical University of Varna. Instrumental methods included monitoring the heart rate of rats using an electrocardiographic monitor. The statistical analysis was performed using the statistical functions in Excel 2016 and Statistica 7.0. Results: A survival rate of 100% was observed in rats pretreated and treated with low and high LE dose. The high LE dose (10 mL/kg) showed a faster improvement in cardiac function as the highest mean heart rates were established. Conclusion: Pretreatment and resuscitation with low or high LE dose reduce toxicity and prevent dose-dependent asystole induced by verapamil. The administration of a high LE dose (10 mL/kg) proved to be more effective in terms of heart rate in rats.

Withdrawal

One of the cardinal features of any liver replacement therapy is the ability to remove accumulated metabolites. The removal of water-soluble substances by dialysis procedures is well established. However, an unsolved problem is the low dialyzability of lipophilic toxins. This study aimed to explore whether bilirubin and bile acids removal can be increased by free fatty acid (FFA) displacement and its combination with albumin dialysis. First, we found that the protein binding of both bilirubin and bile acids decreased significantly with increasing FFA concentrations when co-incubated directly. Then, in vitro dialysis showed that fatty acid mixtures ([linoleic acid] / [oleic acid] = 2) infusion pre-filter effectively increased the fractional removal of bilirubin and bile acids from 1.43 ± 0.07% and 2.50 ± 0.12%, to 10.04 ± 0.29% and 6.12 ± 0.07%, respectively, which were significantly higher than albumin-based hemodialysis (HD); in vivo dialysis showed that lipid emulsion administration resulted in higher reduction ratios and more total solute removals for bilirubin and bile acids after 4 h HD compared with control, which was also superior to albumin-based HD. Finally, the highest dialysis efficacy was always observed by their combination whether in vitro or in vivo. These findings highlight that FFA displacement-based HD could efficiently improve the dialytic removal of bilirubin and bile acids, whilst its dialysis efficacy might even be superior to albumin-based HD. The concept of their combination may open up new avenues and possibilities in the field of dialysis to further enhance lipophilic toxins removal in liver failure.

Depletion and enrichment of phytosterols in soybean oil lipid emulsions directly associate with serum markers of cholestasis in preterm parenteral nutrition-fed pigs.

Clinical reports show a positive correlation between phytosterol concentrations and severity of cholestatic liver disease markers in infants during long-term administration of parenteral lipid emulsions. Establishing a causal link between phytosterols and cholestasis has been complicated by confounding factors of lipid emulsion load, fatty acid composition, and vitamin E in many of these studies. The goal of this study is to determine whether altering the phytosterol concentration within a common soybean oil-based emulsion will alter the onset and severity of cholestasis in parenterally fed preterm piglets. Preterm piglets were administered, for 21 days, either enteral nutrition (ENT) or parenteral nutrition (PN) prepared from a soybean oil-based emulsion containing either 24.0% (depleted [DEP]), 100% (Intralipid; normal phytosterol [NP] concentration), or 144% (enriched [ENR]) total phytosterol concentration. At the end of the study, plasma and liver phytosterol concentrations were highest in the ENR group, followed by NP and then DEP and ENT. Serum direct bilirubin, serum bile acids, and γ-glutamyltransferase were higher in the ENR and NP groups compared with either DEP or ENT groups. All PN lipid groups showed evidence of mild hepatic steatosis but no change in hepatic expression of proinflammatory cytokines or Farnesoid X receptor target genes. The increase in serum direct bilirubin was lower in the DEP group vs the lipid emulsions with normal or ENR phytosterols. Our results provide additional evidence that phytosterols are linked to an increase in serum markers of cholestasis in preterm PN-fed pigs.

Microbial growth and importance of flushing inside closed-type infusion devices during administration of lipid emulsion in vitro setting.

Background: We investigated the extent of growth of microorganisms with simultaneous administration of lipid emulsions with infusions for Total Parenteral Nutrition (TPN), assuming that the lipid emulsions contaminated with microorganisms are stagnant in a closed-type infusion device. We also investigated if bacterial growth can be prevented in the infusion device by flushing the inside of the infusion device with saline solution after the administration of lipid emulsion from the side tube in vitro setting.Methods: We made a preparation by adding Escherichia coli to the lipid emulsion and started the infusion simultaneously with the infusion solution for TPN and lipid emulsion with the piggyback method. Immediately after the completion of lipid emulsion infusion, we conducted flushing with saline solution. The volume of saline solution was none, 5, 10, or 20 mL at a flow rate of 1 mL/s. Infusion solution that was stagnant in the infusion device was collected immediately before completing the lipid emulsion infusion and 20 h after flushing, i.e., 24 h after starting the infusion for TPN, and the number of viable bacteria was determined.Results: The number of viable E. coli increased in the infusion device of all three species used in this experiment 24 h after starting the lipid emulsion infusion without flushing. We found that bacterial growth could be prevented through flushing with saline solution after the completion of lipid emulsion infusion and flushing out the stagnant infusion solution in the closed-type infusion device.Conclusions: We found that if E. coli was present in the closed-type infusion device, it would multiply. We also found that the number of viable bacteria varied according to the variety and internal structure of the closed-type infusion device as well as the liquid volume used for flushing, although flushing can prevent the growth of microorganisms. Proper management and manipulation of infusion is required to prevent infection.

How to perform appropriate flushing after lipid emulsion administration using totally implantable venous access devices in long-term total parenteral nutrition and home parenteral nutrition.

There has been no clear evidence regarding the appropriate method of flushing catheters and totally implantable venous access devices (TIVADs) after lipid emulsion (LE) administration. Therefore, the aim of the study was to identify appropriate methods of flushing to minimize residual LE when using TIVADs to ensure the safety of long-term total parenteral nutrition (TPN) and home parenteral nutrition (HPN). A soybean oil LE containing indocyanine green (ICG) was administered from the injection site of the primary infusion set for flowing TPN, and LE dynamics were evaluated by a fluorescence imaging system. TIVADs were connected to the end of the infusion sets. After LE administration, the tubes and chambers were flushed from the injection site using saline at various speeds (20, 40, 60mL/min), with and without pulsation. The washout effect of TPN solution after LE administration followed by flushing was examined, as was the washout effect of size differences in the infusion sets. When the LE was flushed with 20mL of saline immediately after administering the LE using a standard infusion set (inner diameter 2.5mm), the LE still remained in the tubes and chambers under any flushing condition. Flushing the LE from the injection site with 10mL of saline and then flowing >240mL of TPN solution were effective for minimizing residual LE inside the tubes and chambers. When using an infusion set with a small inner diameter (1.0mm), the LE inside the tubes and chambers was almost discharged with ≥20mL of saline immediately after administering the LE. In all settings, flushing with/without pulsation did not affect LE washout efficacy. Flushing immediately with saline ≥10mL and then flowing >240mL of primary PN solution after soybean oil LE administration using the standard infusion set or flushing with 20mL saline immediately after administering the soybean oil LE using the infusion set with a small inner diameter are effective for minimizing the residual LE in the catheter and TIVAD, ensuring the safety of long-term TPN and HPN.

Lipid intensive drug therapy for sepsis pilot: A Bayesian phase I clinical trial.

ObjectivesCholesterol may be protective in sepsis. Patients with early sepsis may have critically low cholesterol levels that are associated with poor outcomes. The study objective was to test the safety of a fish oil–containing lipid injectable emulsion for stabilizing early cholesterol levels in sepsis.MethodsPhase I Bayesian optimal interval design trial of adult patients with septic shock (Sequential Organ Failure Assessment score ≥4 or vasopressor dependence). Using sequential dose escalation, participants received 2 doses of 1.0 to 1.6 g/kg of lipid emulsion (Smoflipid 20% lipid emulsion) within 48 hours of enrollment. Cholesterol levels, function, and organ failure were assessed serially during the first 7 days of hospital admission.Measurements and Main ResultsA total of 10 patients with septic shock were enrolled. One patient withdrew for social reasons. Another patient had an unrelated medical complication and received 1 drug dose. Of 9 patients, mean age was 58 years (SD 16), median Sequential Organ Failure Assessment was 8, and 28‐day mortality was 30%. No serious adverse events related to lipid infusion occurred. The six occurrences of non‐serious adverse events possibly related to lipid infusion included hyperglycemia (1), elevated triglycerides (3), anemia (1), and vascular access redness/pain (1) for all doses. The mean change in total cholesterol levels from enrollment was −7 (SD 16.6) at 48 hours and 14 (SD 25.2) at 7 days.ConclusionsFish oil–containing lipid emulsion administration during early septic shock was safe. Further studies are needed to assess effects on cholesterol levels, function, and organ failure.Clinical Trial RegistrationNCT03405870.