Effects Of Intravenous Lipid Emulsion Research Articles

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.

Intravenous lipid emulsion for the treatment of poisonings in 313 dogs and 100 cats (2016-2020).

The aim of this retrospective study was to analyze the effect and potential adverse effects of intravenous lipid emulsion (ILE) in poisoned dogs and cats over a 5 years period. Medical records of 313 dogs and 100 cats receiving ILE between 2016-2020 were analyzed for suspected toxicant, clinical signs, ILE dosages and frequency, the effect and adverse effects of ILE, and patient outcome. Dogs and cats were poisoned with mostly unidentified toxicants (48%), rodenticides (8%), recreational drugs and nuts (7% each) and other toxicants. Clinical signs included neurologic deficits (63%), cardiovascular signs (29%), thermoregulation (21%) or gastrointestinal abnormalities (17%). Treatment with ILE was initiated within a median of 6.0 h (1.0-91.0 h) after poisoning. Dogs and cats received a total amount of median 8.0 mL/kg (1.5-66.6 mL/kg) and 15.8 mL/kg (1.8-69.4 mL/kg) ILE, respectively. A positive effect was observed in 74% of the patients, whereas clinical signs worsened in 4% of the patients after ILE administration. No subjective effect was detected in 22% of the patients. Suspected or possible adverse effects of ILE occurred in 6% of the patients, including neurological signs (temporarily reduced consciousness and ataxia), bradycardia, hyperthermia, vomiting, diarrhea, respiratory distress, worsening of the general behavior, facial swelling, and thrombophlebitis. The overall survival rate was 96%. One dog who potentially experienced adverse events was euthanized. ILE treatment was successful in most patients but can be associated with adverse effects. Administration of ILE should be carefully selected on an individual basis after weighing the possible benefits against potential adverse effects.

The effect of intravenous lipid emulsion (ILE) on the pharmacokinetic/toxicokinetic dispositions of ivermectin and carprofen in rabbits.

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 ± 0.2kg 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 (0.6mg/kg) alone while Group 2 received IVM (0.6mg/kg) and ILE (2.5ml/kg). In the CRP study, Group 3 received CRP (12mg/kg) alone while Group 4 received CRP (12mg/kg) and ILE (2.5ml/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 (2136ng/ml and 360.84ng.d/ml) compared to the IVM alone (1340.63ng/ml and 206ng.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.

Cardioprotective Effect of Intravenous Lipid Emulsion in Bupivacaine-Induced Experimental Cardiac Toxicity

Cardioprotective Effect of Intravenous Lipid Emulsion in Bupivacaine-Induced Experimental Cardiac Toxicity

The clinical effect of intravenous lipid emulsion on rabbits medicated with diazepam

Intravenous lipid emulsions (ILE) have been increasingly used to reverse a wide range of lipophilic drug intoxications. However, it is still unknown if these emulsions interfere with other lipophilic drugs routinely used while treating intoxicated patients, such as diazepam, one of the main antiepileptic drugs. Therefore, the objective of the present study was to evaluate whether the administration of a 20% ILE interferes with diazepam's clinical effect. We randomly allocated thirty rabbits to five groups. Three of those groups received diazepam (1.0 mg/kg, IV), one of which did not receive any additional treatment, while the two remaining groups were treated with ILE or lactated ringer solution (1.5 mL/kg followed by 0.25 mL/kg/min for 30 min). The fourth group only received lipid emulsion, and the fifth only lactated ringer. Successive neurological exams at 20 min intervals for a total of 100 min were performed to assess the rabbits' neurological state. We concluded that the ILE did not interfere with diazepam's clinical effect but, although unlikely, the possibility of recurrence of a sedative effect should be considered.

Effects of intravenous lipid emulsions on the reversal of pacing-induced ventricular arrhythmias and electrophysiological alterations in an animal model of ropivacaine toxicity

Introduction Ropivacaine is considered to have a wider margin of cardiovascular safety. However, several reports of ventricular arrhythmias (VA) due to ropivacaine toxicity have been documented. Intravenous lipid emulsions (ILEs) have recently been used successfully in the treatment of local anesthetic intoxication. The main objective of the present study was to evaluate the efficacy of the ILEs in the prevention of pacing-induced-VA and electrophysiological alterations in an animal model of ropivacaine toxicity. Methods Nineteen pigs were anesthetized and instrumentalized. A baseline programmed electrical ventricular stimulation protocol (PEVSP) to induce VA was performed. Ropivacaine (5 mg·kg−1 + 100 μg·kg−1·min−1) followed by normal saline infusion (control group n = 8) or intralipid 20% (1.5 mL·kg−1 + 0.25 mL·kg−1·min−1) for the ILE group (n = 8), were administered three minutes after the ropivacaine bolus. PEVSP was repeated 25 min after the onset of ropivacaine infusion. Pacing-induced VA and electrophysiological abnormalities were assessed in both groups. A sham-control group (n = 3) without ropivacaine infusion was included. Results Most of the electrophysiological parameters evaluated were affected by ropivacaine: PR interval by 28% (p = 0.001), AV interval by 40% (p = 0.001), sinus QRS by 101% (p = 0.001), paced QRS at a rate of 150 bpm by 258% (p = 0.001), and at 120 bpm by 241% (p = 0.001). Seven animals (87.5%) in the control group and eight animals (100%) in the ILE group developed sustained-VA (p = 0.30). Successful resuscitation occurred in 100% of animals in the ILE group vs. 57% of animals in the control group, p = 0.038. Pacing-induced-VA terminated at the first defibrillation attempt in 75% of the animals in the ILE group vs. 0% in the control group, p = 0.01. Conclusion Ropivacaine strongly altered the parameters of ventricular conduction, thus facilitating the induction of VA. ILEs did not prevent pacing-induced VA. However, facilitated resuscitation and termination of VA were delivered at the first defibrillation attempt compared to the control group.

An Alternative Treatment Method for Poisoning in Veterinary Medicine: Intravenous Lipid Emulsion (ILE)

Animal poison control centers receive numerous complaints about possible consumption of substances that can cause deadly toxicities in the home. In recent years, over-the-counter medications such as ibuprofen, acetaminophen, and herbal supplements are the most common toxic substances consumed by pets. Removal of the toxin and supportive treatment is recommended in case of exposure to a toxin that does not have a known antidote. There have been many studies in both human and veterinary medicine that supporting the use of intravenous lipid emulsions in the treatment of intoxications. Intravenous lipid emulsion (ILE) is an oil-in-water emulsion that consists of egg yolk phospholipids, water, glycerin and various oils such as soybean, fish, coconut and olive oil. It is defined as a microemulsion with a long history of use as a parenteral nutrition formulation in both adult and pediatric patients. Also used as a drug carrier in addition to parenteral nutrition. In recent years, it has been used as an effective antidote for the treatment of intoxications caused by compounds with high oil solubility in both human and veterinary medicine. The first efficacy of the use of intravenous lipid emulsions in treatments was demonstrated in the systemic toxicity of local anesthetics and nowadays it comes to the fore in the poisoning of various drugs and compounds. However, it can also be used as an antidote in various intoxication cases caused by different chemicals that do not have any known antidote. Although clinically positive responses are received, more research is needed to more clearly understand the effect of intravenous lipid emulsion.

Effects of Intravenous Lipid Emulsion on Tramadol-Induced Seizure; a Randomized Clinical Trial

Introduction:There are numerous studies on the efficacy of intralipid emulsion (ILE) in various xenobiotic toxicities. This study aimed to evaluate the potential role of ILE as an antidote in tramadol-induced seizure. Methods:A single-blind clinical trial was undertaken to establish the efficacy and safety of ILE in patients with acute tramadol intoxication, who referred to Booali Hospital in Qazvin. Patients were randomly assigned to 2 groups. The Control group received standard care while the intervention group received intralipid emulsion (ILE) 20% in addition to the standard care. The occurrence of in-hospital seizure was compared between the groups.Results:80 patients who abused tramadol and met the study criteria were randomly assigned to either the intervention (40 cases) or the control (40 cases) group. Seizure occurred in 44 (56%) patients before admission to the emergency department. There were not any statistical differences between the groups regarding sex distribution (p=0.513) and mean age (p=0.19), presenting vital signs (p < 0.05), laboratory findings (p < 0.05), and mean abused dose of tramadol (p = 0.472) as well as occurrence of prehospital seizure (p = 0.7). In-hospital seizure occurred in 15 (18.75%) cases (all in the control group; p < 0.001). The mean duration of admission was 2.01 ± 1.13 days in the control group and 2.15 ± 1.04 days in the intervention group (p = 0.6). The number needed to treat for ILE to prevent tramadol-induced seizure was 2.7 (37.5% absolute risk reduction).Conclusions:The findings of this study supported ILE administration, as an adjunct to standard antidote protocols, in tramadol intoxication to prevent tramadol-induced seizures.

Effect of Intravenous Lipid Emulsion on Clozapine Acute Toxicity in Rats.

ObjectivesMany studies have been reported the efficacy of intravenous lipid emulsion (ILE) as an antidote on acute lipophilic drug toxicity. Clozapine, highly lipophilic dibenzodiazepine neuroleptics, is an important medication in the schizophrenia therapy regimen. Acute intoxication with antipsychotics is one of the main reasons for the referral of poisoned patients to the hospital. We expected that ILE could be used for the therapy of acute clozapine intoxicated patients.MethodsWe used two groups of consisting of six male rats. Both groups received a toxic dose of clozapine (40 mg/kg) intravenously, via the tail vein. After 15 minutes, they were treated with intravenous infusion of 18.6 mg/kg normal saline (NS group), or 18.6 mg/kg ILE 20% (ILE group). We evaluated blood pressure (BP) and heart rate by power lab apparatus through the tail artery, ataxia by a rat rotary circle, seizure scores and death in multiple times after starting clozapine administration. For biochemical and pathological evaluations the samples of tissue and blood were taken.ResultsOur results demonstrated that ILE 20% could return hypotension-induced clozapine better than normal saline. Furthermore, ataxia and seizure have rectified more rapidly and deaths reduced. Clozapine administration causes pancreatitis and lung injury but fat emulsion did not show an optimal effect on tissue damages caused by clozapine toxicity.ConclusionIn conclusion, ILE can remove toxic signs of clozapine same as other lipophilic medicines, however, clinical uses of ILE for this intention requires more appraisement to determine the precise implication and safety.

Four-oil intravenous lipid emulsion effect on plasma fatty acid composition, inflammatory markers and clinical outcomes in acutely ill patients: A randomised control trial (Foil fact)

Data in critically ill patients on the effect of intravenous lipid emulsions (LEs), containing omega-3 polyunsaturated fatty acids (PUFAs), in parenteral nutrition (PN) are scarce and conflicting. This study compared the effects of a four-oil LE (30% soybean oil, 30% medium-chain triglycerides, 25% olive oil and 15% fish oil (FO)) (SMOFlipid®) to those of a 100% soybean oil-based LE in critically ill adult intensive care unit (ICU) patients. In this double-blind, randomised study, patients (n=75) predicted to need PN for more than 5 days were randomised to receive either a four-oil LE (Study Group (SG)) or a 100% soybean oil LE (Control Group (CG)). Isocaloric, isonitrogenous PN was administered continuously for 5 days. FO was provided at a dose of 0.09-0.22g/kg body weight. Measurements included biochemical parameters and sequential organ failure assessment (SOFA) score daily and plasma total phospholipid fatty acids (FAs) and cytokine levels on days 1, 3, 6. Days on mechanical ventilation, length of stay and mortality were also recorded. ANOVA was used to compare response variables between the two groups over the time and Pearson correlation was used to measure relationships between continuous variables. 68 patients completed the study (n=35 SG, n=33 CG), with male predominance (66% SG, 56% CG). Average age was 60.8±13.9 years (SG) versus 55.7±14.8 (CG) (p=0.143). The majority were surgical admissions (85% SG versus 91% CG) followed by medical. Plasma phospholipid oleic acid (p=0.022) and alpha-linolenic acid (p<0.0005) increased in both groups. In the SG, plasma phospholipid EPA and DHA increased (both p<0.001), whereas the omega-6:omega-3 PUFA (n-6:n-3 PUFA) ratio decreased (p<0.001). Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and bilirubin decreased in both treatment groups. Considering only the change from day 1 to day 6 there was a bigger decrease in AST, ALT and bilirubin levels in the SG. Concentrations of TNF-α decreased from day 1 to day 6 in the SG, whereas they increased in the CG, but the change was not statistically significant (p=0.112). A significant negative correlation was found between EPA provision on day 3 and the SOFA score (r=-0.4047, p=0.018). Days on mechanical ventilation (1.24±0.83 days in SG versus 0.88±1.63 days in CG, p=0.385) and ICU LOS (9.5±7.09 days in SG versus 10.7±7.6 days in CG, p=0.490) were not different between groups. PN containing a four-oil LE increased plasma EPA and DHA, decreased n-6:n-3 PUFA ratio, and was safe and well tolerated. The negative relationship between day 3 EPA and SOFA score seems promising, but EPA intake and effects may have been diluted by enteral nutrition which was started in more than half of patients on day 4. There was no significant difference in terms of other biochemical measurements, SOFA score, length of ICU stay and mortality. More research is needed in this patient population, particularly regarding dose, duration and timing of FO and the effects on clinical outcomes.

The effect of intravenous lipid emulsions and mucosal adaptation following massive bowel resection

Aims and objectivesFish oil (FO) lipid emulsion and a new lipid emulsion (SMOF) are important treatments for intestinal failure-associated liver disease. We evaluated the efficacy of FO and SMOF lipid emulsion on intestinal mucosal adaptation using a total parenteral nutrition (TPN)-supported rat model of short bowel syndrome. Material & methodsSprague–Dawley rats underwent jugular vein catheterization and 90% small bowel resection and were divided into three groups: TPN with soy bean oil lipid emulsion (SO group), FO lipid emulsion (FO group), or SMOF (SMOF group). On day 13, the rats were euthanized, and the small intestine was harvested. The microscopic morphology and crypt cell proliferation rate (CCPR) were then evaluated. ResultsThe villus height of the ileum in the SMOF group was significantly higher than in the SO group. The crypt depth of the intestine in the SMOF group was significantly lower than in the SO group. The CCPRs of the intestine in the FO and SMOF groups were both higher than in the SO group. ConclusionsLipid emulsion affected the bowel morphology, such as the mucosa as well as the intestinal smooth muscle. Further studies are needed to clarify the mechanisms.

Four-oil intravenous lipid emulsion effect on plasma fatty acids, inflammatory markers and clinical outcomes in septic patients

Rationale: Data in critically ill patients on the effect of intravenous lipid emulsions (LE) containing omega-3 polyunsaturated fatty acids (PUFA) are scarce and shows conflicting results. This study compared the effects of two LE’s in critically ill adult intensive care unit (ICU) patients.

The Effect of Intravenous Lipid Emulsion in a Rat Model of Verapamil Toxicity

Purpose: Intravenous lipid emulsion (ILE) has been shown to have significant therapeutic effects on calcium channel blocker overdose in animal studies and clinical cases. In this preliminary experiment, we investigated the hemodynamic changes and survival in a rat model of verapamil intoxication. Methods: Fourteen male Sprague-Dawley rats were sedated and treated with ILE or normal saline (control), followed by continuous intravenous infusion of verapamil (20 mg/kg/h). Mean arterial pressure and heart rate of rats were monitored during the infusion. In addition, the total dose of infused verapamil and the duration of survival were measured. Results: Survival was prolonged in the ILE group ($32.43{pm}5.8min$) relative to the control group ($24.14{pm}4.3min$) (p=0.01). The cumulative mean lethal dose of verapamil was higher in the ILE group ($4.3{pm}0.7mg/kg$) than in the control group ($3.2{pm}0.5mg/kg$; p=0.017). Conclusion: ILE pretreatment prolonged survival and increased the lethal dose in a rat model of verapamil poisoning.

In vivo effects of intravenous lipid emulsion on lung tissue in an experimental model of acute malathion intoxication.

Malathion can be ingested, inhaled, or absorbed through the skin, but acute toxicity is maximized when administered orally. Intravenous lipid emulsion (ILE) treatment is used as a new therapeutic method in cases of systemic toxicity caused by some lipid soluble agents. This study aimed to examine the potential treatment effect of ILE on rat lung tissue in a toxicokinetic model of malathion exposure. Twenty-one adult Wistar albino rats were randomly divided into three equal groups. The groups were organized as group I (control), group II (malathion), and group III (malathion + ILE treatment). Malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were evaluated in lung tissues. Immunohistochemical and Western blot analyses were performed to determine the bax, bcl-2, and caspase-3 expression levels. Tissue GSH-Px and SOD activities were decreased and MDA levels were increased in the malathion group. ILE administration increased GSH-Px and SOD activity and decreased MDA levels compared to the malathion group. Furthermore, expression of bax, bcl-2, and caspase-3 significantly increased in the malathion group, and ILE infusion reduced these expression levels. The present study revealed that acute oral malathion administration increased oxidative stress and apoptosis in the lung tissue of rats. ILE infusion prevented oxidative stress and decreased the deleterious effects of malathion. Taken together, the findings of our study suggest that lipid emulsion infusion has treatment efficacy on malathion-induced lung toxicity.

Protective effects of intravenous lipid emulsion on malathion-induced hepatotoxicity.

Organophosphates including malathion can be ingested, inhaled, or absorbed through the skin, but it may be a maximum of acute toxicity when administered by oral intake. Intravenous lipid emulsion (ILE) treatment is used as a new treatment method in cases of systemic toxicity caused by local anesthetics. This study was aimed to examine the potential treatment effect of intravenous lipid emulsion on rat liver tissue in the toxicity of malathion. Twenty-one Wistar albino rats were randomly divided into three equal groups. The groups were organized as Group I (control), Group II (malathion) and Group III (malathion + lipid emulsion treatment). Liver tissues were examinedhistologically, and immunohistochemical analysis was performed to determine the bax, bcl-2, and caspase-3 expression levels. A decrease of PAS positive staining cells, and an increase of liver enzymes, formation of degenerative changes and apoptotic cell deaths occurred in the malathion group. Additionally, a decrease of apoptosis and hepatic parenchymal damage was observed in the malathion + lipid emulsion treatment group. The findings from our study suggested that lipid emulsion treatment had a protective efficacy on the malathion induced liver toxicity (Fig. 5, Ref. 30).

An Evolving Story of Translational Research: A Decade after the Jacobson Promising Investigator Award

THE THIRD JOAN L AND JULIUS H JACOBSON PROMISING INVESTIGATOR AWARDEE, MARK PUDER, MD, PHD, FACS: In 2005, the Surgical Research Committee (SRC) of the American College of Surgeons was tasked with selecting the recipient of a newly established award, "The Joan L and Julius H Jacobson Promising Investigator Award." According to the Jacobsons, the award, funded by Dr Jacobson, should be given at least once every 2 years to a surgeon investigator at "the tipping point," who can demonstrate that his or her research shows the promise of leading to a significant contribution to the practice of surgery and patient safety. Every year, the SRC receives many excellent nominations and has the difficult task of selecting 1 awardee. The first awardee was Michael Longaker, MD, FACS, who, 10 years later, reflected on the award and the impact it had on his career.1 This year, Mark Puder, MD, PhD FACS, the third Jacobson awardee, reflects on his 10-year journey after receiving the award. Dr Puder is now a national and international figure in the field of intestinal failure-associated liver disease and has studied the effect of intravenous lipid emulsions on the etiology and treatment of a once fatal disease in children. Kamal MF Itani, MD, FACS and Brian S Zuckerbraun, MD, FACS, on behalf of the Research Committee of the American College of Surgeons.

Exploring the effect of intravenous lipid emulsion in acute methamphetamine toxicity.

Objective(s):The increasing use of methamphetamine (METH) in the last decades has made it the second most abused drug. Advancs in the area of intravenous lipid emulsion (ILE) have led to its potential application in the treatment of poisoning. The present study aims to investigate the potential role of ILE as an antidote for acute METH poisoning.Materials and Methods:Two groups of six male rats were treated by METH (45 mg/kg), intraperitoneally. Five to seven min later, they received an infusion of 18.6 ml/kg ILE 20% through the tail vein or normal saline (NS). Locomotor and behavioral activity was assessed at different time after METH administration. Body temperature and survival rates were also evaluated. Brain and internal organs were then removed for histological examination and TUNEL assay.Results:ILE therapy for METH poisoning in rats could prevent rats mortalities and returned the METH-induced hyperthermia to normal rates (P<0.05). ILE reduced freezing and stereotyped behaviors and increased rearing responses (P<0.05). Locomotor activity also returned to control levels especially during the last hours of the experiment. ILE administration decreased the prevalence of pulmonary emphysema in the lungs (P<0.05 and P<0.01) and percentages of TUNEL positive cells in the brain (P<0.05), in comparison with the control group.Conclusion:ILE could reduce the severity of METH- induced toxicity as well as mortality rate in the animals. Intravenous infusion of lipid emulsion may save the life of patients with acute METH intoxication who do not respond to standard initial therapy.

The effects of intravenous lipid emulsion on hemodynamic recovery and myocardial cell mitochondrial function after bupivacaine toxicity in anesthetized pigs.

Local anesthetic toxicity is thought to be mediated partly by inhibition of cardiac mitochondrial function. Intravenous (i.v.) lipid emulsion may overcome this energy depletion, but doses larger than currently recommended may be needed for rescue effect. In this randomized study with anesthetized pigs, we compared the effect of a large dose, 4 mL/kg, of i.v. 20% Intralipid® ( n = 7) with Ringer's acetate ( n = 6) on cardiovascular recovery after a cardiotoxic dose of bupivacaine. We also examined mitochondrial respiratory function in myocardial cell homogenates analyzed promptly after needle biopsies from the animals. Bupivacaine plasma concentrations were quantified from plasma samples. Arterial blood pressure recovered faster and systemic vascular resistance rose more rapidly after Intralipid than Ringer's acetate administration ( p < 0.0001), but Intralipid did not increase cardiac index or left ventricular ejection fraction. The lipid-based mitochondrial respiration was stimulated by approximately 30% after Intralipid ( p < 0.05) but unaffected by Ringer's acetate. The mean (standard deviation) area under the concentration-time curve (AUC) of total bupivacaine was greater after Intralipid (105.2 (13.6) mg·min/L) than after Ringer's acetate (88.1 (7.1) mg·min/L) ( p = 0.019). After Intralipid, the AUC of the lipid-un-entrapped bupivacaine portion (97.0 (14.5) mg·min/L) was 8% lower than that of total bupivacaine ( p < 0.0001). To conclude, 4 mL/kg of Intralipid expedited cardiovascular recovery from bupivacaine cardiotoxicity mainly by increasing systemic vascular resistance. The increased myocardial mitochondrial respiration and bupivacaine entrapment after Intralipid did not improve cardiac function.

THU-300 - Nutritional, Metabolic and Immunological Effects of Intravenous Lipid Emulsions in Patients with Advanced Alcohol Related Liver Disease

THU-300 - Nutritional, Metabolic and Immunological Effects of Intravenous Lipid Emulsions in Patients with Advanced Alcohol Related Liver Disease

The effects of intravenous lipid emulsion on prolongation of survival in a rat model of calcium channel blocker toxicity

Context. Intravenous lipid emulsion (ILE) has been shown to ameliorate the toxicity of lipid-soluble agents in animal studies and clinical cases. Objectives. To investigate the therapeutic effects of ILE in a rat model of toxicity from calcium channel blockers (CCBs), including diltiazem and nicardipine. Methods. Two sets of experiments of CCB poisoning were conducted. In the first set, 14 male Sprague-Dawley rats were sedated and treated with ILE or normal saline (NS), followed by continuous intravenous infusion of diltiazem (20 mg/kg/h). In the second experiment, the study protocol was the same except the infusion of nicardipine (20 mg/kg/h). The total dose of infused drug and the duration of survival were measured. In addition, mean arterial pressure and heart rate were monitored. Results. Survival was prolonged in the ILE group (48.4 ± 11.3 vs. 25.0 ± 3.7 min; p = 0.002). Furthermore, the cumulative mean lethal dose of diltiazem was higher in the ILE group (16.1 ± 3.8 mg/kg) than in the NS group (8.3 ± 1.1 mg/kg) (p = 0.002). With nicardipine poisoning, survival was also prolonged in the ILE group (71.0 ± 8.3 min vs. 30.6 ± 6.1 min; p = 0.002). The cumulative mean lethal dose was higher in the ILE group than in the NS group (23.7 ± 2.8 mg/kg vs. 10.2 ± 2.0 mg/kg; p = 0.002). Conclusions. ILE pretreatment prolonged survival and increased the lethal dose in a rat model of CCB poisoning using diltiazem and nicardipine.