Intravenous Lipid Emulsion Group 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.

Sodium bicarbonate reverts electrophysiologic cardiotoxicity of ropivacaine faster than lipid emulsions in a porcine model.

Ropivacaine has been described as a safer local anaesthetic (LA); however, serious cardiotoxic accidents have been reported. Intravenous-lipid-emulsion (ILE) therapy during LA intoxication seems to act as an antidote. Sodium bicarbonate is the standard treatment for sodium channel blocker drug toxicity. We compared both antidotes on the reversion of electrophysiologic toxicity induced by ropivacaine. Ropivacaine 5mg kg-1 was administered in 24 pigs, and 3min later, the animals received ILE: 1.5ml kg-1 + 0.25 ml kg-1 min-1 (ILE group); sodium bicarbonate: 2mEq kg-1 + 1mEq kg-1 h-1 (NaHCO3 group); saline solution (CTL group). Electrophysiological parameters were evaluated for 30 min. The area under the curve (AUC) for the first 5 or 30 min was compared between groups. Ropivacaine induced a lengthening of the PR interval by 17% (P= 0.0001), His-ventricle-interval by 58% (P= 0.001), sinus QRS complex by 56% (P= 0.0001), paced QRS at 150 bpm by 257% (P= 0.0001), and at 120 bpm by 143% (P= 0.0001) in all groups. At 5min after treatment, sinus QRS in the NaHCO3 group was shorter than that in the CTL group (AUCQRS5 , P= 0.003) or ILE group (AUCQRS5 , P= 0.045). During the first minute, seven of the animals in the NaHCO3 group vs. two in the ILE or 0 in the CTL group recovered more than 30% of the sinus QRS previously lengthened by ropivacaine (P= 0.003). Sodium bicarbonate reversed the electrophysiological toxicity of ropivacaine faster than ILE and control groups.

Lipid emulsion for the treatment of acute organophosphate poisoning: an Open-Label randomized trial

Introduction Many organophosphate (OP) pesticides are lipid-soluble; therefore, intravenous lipid emulsion (ILE) has been evaluated as a possible treatment for acute poisoning. A single bolus dose of 100 ml of 20% ILE was found safe in a pilot observational study. This randomized trial aimed to assess the effectiveness and safety of an extended dose of ILE in acute OP poisoning. Methods This was an investigator-initiated, parallel-group, open-label, randomized controlled trial conducted at PGIMER, Chandigarh (India), from January 2019 to June 2020, in patients aged above 13 years with acute OP poisoning. The primary efficacy outcome was to study the change in atropine dose requirement (total and over the first 24 h) for cholinergic crisis after giving an initial bolus dose of 100 ml of 20% ILE followed by an infusion of 100 ml of 20% ILE over 6 h in addition to the standard care. The secondary efficacy outcomes were to detect the effects on hemodynamic variables, length of hospital stay, and duration of mechanical ventilation required. The incidence of adverse events was evaluated. Results A total of 45 patients were assigned to receive either ILE (intervention group, n = 23) or normal saline (control group, n = 22) in addition to standard treatment. Baseline variables in both groups were comparable. The median dose of atropine (in mg) in the first 24 h and at complete resolution in the ILE group were similar to the control group (124.0 versus 141.8, p-value 0.916; and 150.8 versus 175.0, p-value 0.935). Hemodynamic variables (systolic and diastolic blood pressures, mean arterial pressure, and pulse rate) over 24, 48, and 72 h of treatment, length of hospital stay, and duration of mechanical ventilation were also unaffected by ILE. Case fatality was 4 and not statistically different between intervention and control groups (1 versus 3, p-value 0.346). There was no excessive fever, dyspnea, elevation of serum amylase, or pancreatitis from ILE. Conclusion ILE has no apparent benefit in acute OP poisoning. However, an extended dose appears safe for the indication.

Olive oil–based lipid emulsion is noninferior to soybean oil–based lipid emulsion in the acute care setting: A double-blind randomized controlled trial

ObjectivesOlive oil (OO)–based intravenous lipid emulsion (IVLE) may have biological advantages for nutrition and inflammation status compared with soybean oil (SO)–based IVLE. We aimed to compare prealbumin levels during infusion of OO- or SO-based IVLE in patients receiving parenteral nutrition in the acute-care setting. MethodsIn this prospective, noninferiority, double blind randomized controlled efficacy trial, patients received either OO-based or SO-based IVLE after providing consent. Biochemical and nutrition parameters were collected at baseline and at 7 to 10 d after initiation of parenteral nutrition. Results are expressed as means (standard deviations). ResultsA total of 210 patients completed the study: 102 patients in the SO-based IVLE group and 108 patients in the OO-based IVLE group. Both groups had a significant increase in prealbumin levels from baseline (SO: 0.10 [0.06] versus 0.15 [0.08] g/L; P < 0.0001; OO: 0.11 [0.06] versus 0.16 [0.08] g/L; P < 0.0001), but mean changes between groups were not different (P = 0.53). OO-based IVLE was noninferior to SO-based IVLE in maintaining or increasing serum prealbumin levels, with 20% as the noninferiority margin at follow-up (least square geometric mean ratio [95% CI], 1.10 [0.83,1.47]; P = 0.50). There was a significant improvement in C-reactive protein levels from baseline within each group (SO: 83.24 [69.72] versus 53.4 [59.78] mg/dL; P < 0.0001; OO: 85.13 [68.14] versus 58.75 [60.11] mg/dL; P = 0.004), but mean changes between the groups were not different (P = 0.836). Mortality, length of stay, and infection rates were not different for both groups. ConclusionsIn this study, OO-based IVLE was not inferior to SO-based IVLE in maintaining or increasing the prealbumin level. The improvement of C-reactive protein levels and other clinical outcomes were not different for both groups.

Combination therapy of the granulocyte colony stimulating factor and intravenous lipid emulsion protect the hippocampus after global ischemia in rat: focusing on CA1 region

Brain stroke is one of the causes of human death and disability worldwide. Global ischemia results in the accumulation of free radicals in the neurons. It leads to histologically brain damage. The CA1 region of the hippocampus is a sensitive area for free radicals. This study investigated the combined therapy of the Granulocyte colony stimulating factor (G-CSF) and the Intravenous lipid emulsion (ILE). These neuroprotective agents play a role in the regeneration of neurons. They improve the learning ability and memory in rats induced global ischemia. We divided 35 rats into five groups. The groups were sham group, ischemia group, G-CSF group, ILE group, and G-CSF plus ILE group. Ischemia was induced by occlusion of the bilateral common carotid about 10min. The drugs applied on days 1, 3 and 7. The treated groups received subcutaneous injection of 20μg/kgG-CSF and intravenous injection of 5ml/kg ILE. After two weeks, the memory and learning ability of the rats was evaluated by the shuttle box. Hematoxylin and Eosin and Nissl and TUNEL stainings were used to determine the necrosis, normal and apoptotic cells. The combined therapy increased normal cells compared to the ischemia group. They decreased the number of necrotic and apoptosis cells in other groups. The combined group improved the passive avoidance test compared to the other groups. The combination therapy of G-CSF plus ILE is more effective than each alone.

Impact of Intravenous Omega-3-Enriched Lipid Emulsion on Liver Enzyme and Triglyceride Serum Levels of Children Undergoing Gastrointestinal Surgery.

PurposeTo investigate the impact of omega-3-enriched lipid emulsion (LE) on liver enzyme (aspartate transaminase [AST] and alanine aminotransferase [ALT]) and triglyceride (TG) levels of children undergoing gastrointestinal surgery.MethodsThis experimental randomized controlled group pretest-posttest design study included 14 children who underwent gastrointestinal surgery due to duodenal atresia, jejunal atresia, esophageal atresia, and need for parenteral nutrition for a minimum of 3 days at RSUD Dr. Soetomo Surabaya between August 2018 and January 2019. These children were divided into two groups, those who received standard intravenous LE (medium-chain triglyceride [MCT]/long-chain triglyceride [LCT]) and those who received intravenous omega-3-enriched LE. Differences in AST, ALT, and TG levels were measured before surgery and 3 days after the administration of parenteral nutrition.ResultsLiver enzyme and TG levels in each group did not differ significantly before versus 3 days after surgery. However, TG levels were significantly lower in the omega-3-enriched intravenous LE group (p=0.041) at 3 days after surgery, and statistically significant difference in changes in TG levels was noted at 3 days after surgery between MCT/LCT intravenous LE group and the omega-3-enriched intravenous LE group (p=0.008).ConclusionThe intravenous omega-3-enriched LE had a better TG-lowering effect than the MCT/LCT intravenous LE in children undergoing gastrointestinal surgery.

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.

Effect of alternative intravenous lipid emulsion in clinical outcome in non-critically ill patients

Most studies on alternative intravenous lipid emulsion (IVLE) versus conventional IVLE have been conducted in the critically ill patients. The benefits of alternative IVLE in non-critically ill patients is uncertain. We aim to determine clinical outcome difference between alternative IVLE versus conventional IVLE in non-critically ill patients. All patients on parenteral nutrition (PN) from July 2007 to September 2010 were identified. Patients were stratified into two groups: conventional IVLE (soybean oil-based) and alternative IVLEs, namely MCT oil-based, olive oil-based and fish oil-containing IVLE. Three hundred and eighty-eight patients were included in the study. Ninety-one patients received soybean-based IVLE, 59 patients received MCT oil-based IVLE, 141 patients received olive oil-based IVLE and 97 patients received fish oil-containing IVLE. Adjusting the effect of baseline covariates in separate multiple linear/logistic regression models, there were no differences in mortality, readmission, length of stay and infection between conventional IVLE group and alternative IVLEs group, the adjusted p-value was 0.64, 0.06, 0.36 and 0.18 respectively. However, there was a significant change in day 5 CRP between these two groups (8.43g/L (SD 112.2) vs-41.2 (SD 106.4); adjusted p-value=0.01). There was no difference in day 5 albumin between these two group (-1.03 (SD 5.1) vs-0.1 (SD 5.3); adjusted p-value=0.08). Our study showed that pertinent clinical outcomes in non-critically ill patients who received either conventional IVLE or alternative IVLEs were the same. However, there was significant reduction in day-5 CRP in alternative IVLE compared to conventional IVLE.

Improved dialytic removal of protein-bound uremic toxins by intravenous lipid emulsion in chronic kidney disease rats.

Protein-bound uremic toxins (PBUTs) have received extensive attention, as their accumulation leads to pleiotropic toxic biological effects, while the removal of these solutes by conventional dialysis therapies is severely hampered. This study aimed to examine whether increased removal of PBUTs could be achieved with intravenous lipid emulsion (ILE). PBUTs such as 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF), p-cresyl sulfate (PCS) and indoxyl sulfate (IS) were spiked with human serum albumin (HSA) solution and the inhibitory effects of free fatty acid (FFA) on the binding of CMPF, PCS and IS to HSA were examined separately in vitro by ultrafiltration. In vitro dialysis of albumin solution was then performed to investigate the effects of fatty acid (FAs) mixtures infusion on the fractional removal of PBUTs. Finally, the inhibitory effect of FFA on the binding of PBUTs to albumin was examined in uremic rats, and blood purification therapy was conducted to calculate the reduction ratio (RR) and the total solute removal (TSR) of solutes. The percentage protein binding of CMPF, PCS and IS decreased significantly with increasing FFAs concentrations, and the inhibitory effect was more remarkable with the addition of oleic acid or linoleic acid than that of eicosapentaenoic acid and docosahexaenoic acid. In vitro infusion of FAs increased the fractional removal of CMPF to 14.40 ± 2.38%. PCS, IS and indole-3-acetic acid removal increased from 8.00 ± 2.43%, 11.68 ± 1.54% and 15.38 ± 3.97%, respectively, at baseline to 28.21 ± 5.99%, 35.42 ± 5.27% and 40.18 ± 5.05%, respectively, when FAs were present. In vivo, rat serum concentrations of free PBUTs were significantly higher in the ILE group than in the control group, and administration of ILE resulted in higher RRs and more TSR for PBUTs after 3 h of hemodialysis (HD) therapy compared with the control group. Administration of ILE effectively increased the dialytic removal of PBUTs. This method could be applied to current HD therapy.

Influence of n-3 Fish Oil-Enriched Intravenous Lipid Emulsion on Length of Stay and Mortality in Infants Post Intestinal Surgery

Background: Parenteral nutrition plays an important role in the infants post intestinal surgery. Currently, n-6 soybean oil-based intravenous lipid emulsion (IVLE) is used as a standard. n-6 have been shown increases biomarkers of inflammation while n-3 have shown positively influence clinical outcomes due to their immunomodulatory action. The aim of this study is to investigate the influence of n-3 fish oil-enriched IVLE on mortality and length of stay in infants post intestinal surgery. Methods: A medical record retrospective study was undertaken in infants post intestinal surgery at Dr. Soetomo Hospital in 2016-2017. Infants with intestinal atresia who had PN for at least three days were included. The n-6 soybean oil-based and n-3 fish oil-enriched IVLE were used. Incomplete data was excluded. Results: There were 19 infants (12/19 boys) included in this study. 10/19 infants received the n-6 soybean oil-based IVLE. The duration and dose of IVLE used were 16.52±11.34 days and 1.80±0.44 g/kg/day. Mortality rate was significantly lower in n-3 fish oil-enriched IVLE group (P=0.02) while there was no difference on length of stay (P=0.484).Conclusion: Infants who received the n-3 fish oil-enriched IVLE have a lower mortality rate but there is no difference on length of stay. Keywords: Infants, Intestinal surgery, Intravenous lipid emulsion, Length of stay, Mortality

Comparative effectiveness of methylene blue versus intravenous lipid emulsion in a rodent model of amlodipine toxicity

Context: Calcium channel blocker (CCB) poisonings are the leading cause of death from cardiovascular medication-related overdoses. Current treatments (calcium salts, vasopressors, inotropes) are often insufficient. Intravenous lipid emulsion (ILE) and methylene blue (MB) show promise in treating CCB overdoses unresponsive to conventional therapy.Objective: To compare the effectiveness of MB versus ILE in a rodent model of amlodipine (AML) poisoning with survival as the primary outcome and hemodynamic parameters as secondary outcomes.Materials and methods: Sixty-four adult male albino rats were anesthetized and cannulated for non-invasive hemodynamic measurement. Rats received amlodipine intraperitoneally (42 mg/kg). We then divided the rats into four groups: AML only without antidote, AML followed by ILE (24.8 mL/kg over 10 min), AML followed by normal saline (an equivalent volume of ILE), and AML followed by IV MB (2 mg/kg over 5 min). They received study treatments at 5, 30, and 60 minutes from the start of the protocol and with observation for 2 hours.Results: Survival time in ILE group was greater than in the control and NS groups. Differences between ILE and MB and between MB and NS were not significant. Hemodynamic parameters significantly increased in ILE group compared to the MB group at the 30, 60 and 120 min assessments but not after induction of AML poisoning and at 5 min assessment.Conclusions: Survival was greatest in rats treated with ILE. Both MB and NS had little effect on survival when compared to control animals. Both ILE and MB improved hemodynamics.

The Effects of Intravenous Lipid Emulsion Therapy in the Prevention of Depressive Effects of Propofol on Cardiovascular and Respiratory Systems: An Experimental Animal Study.

Background and objectives: Although there are several hypotheses about the mechanism of action, intravenous lipid emulsion (ILE) therapy has been shown to be effective in the treatment of toxicities due to local anaesthetics and many lipophilic drugs. In this study, we had hypothesized that ILE therapy might also be effective in preventing mortality and cardiorespiratory depressant effects due to propofol intoxication. Materials and methods: Twenty-eight Sprague-Dawley adult rats were randomly divided into four groups. Saline was administered to the subjects in the control group. The second group was administered propofol (PP group); the third group was administered ILE (ILE group), and the fourth group was administered propofol and ILE therapy together (ILE+PP group). Systolic blood pressure (SBP), diastolic blood pressure (DBP), respiratory rate (RR), heart rate (HR), and mortality were recorded at 10 time-points during a period of 60 min. A repeated measures linear mixed-effect model with unstructured covariance was used to compare the groups. Results: In the PP group; SBP, DBP, RR, and HR levels declined steadily; and all rats in this group died after the 60-min period. In the ILE+PP group, the initially reduced SBP, DBP, RR, and HR scores increased close to the levels observed in the control group. The SBP, DBP, RR, and HR values in the PP group were significantly lower compared to the other groups (p < 0.01). The mortality rate was 100% (with survival duration of 60 min) for the PP group; however, it was 0% for the remaining three groups. Conclusions: Our results suggest that the untoward effects of propofol including hypotension, bradycardia, and respiratory depression might be prevented with ILE therapy.

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.

ROLE OF INTRAVENOUS LIPID EMULSION ON CARDIOVASCULAR TOXICITY INDUCED BY COMBINED AMITRIPTYLINE AND CITALOPRAM OVERDOSES IN ADULT MALE ALBINO RATS

Toxicity from antidepressant agents is considered a common phenomenon. The aim of this study was to estimate the role of intravenous lipid emulsion (ILE) as compared to sodium bicarbonate (Na bicarbonate) as a main line or as an adjunctive therapy for treatment of cardiovascular toxicity induced by concurrent single oral administration of amitriptyline and citalopram in rats. The intoxicated rats were equally divided into three groups. Group1 received a bolus dose of 2mEq/kg Na bicarbonate then by infusion of 0.25ml/kg/min. Group 2 received a bolus dose of 1.5ml /kg of 20% ILE followed by infusion of 0.25 ml/kg/min and increased stepwise to 12.4 ml/kg. Group 3 received Na bicarbonate + ILE by the same pattern and doses. All therapies were injected for 60 min. Mean arterial blood pressure (MAP), heart rate (HR) and electrocardiogram for QRS duration were assessed across all intervals with comparison of pH recordings before and after therapies. The results showed significant improvement of MAP and QRS prolongation after the iv bolus dose, along infusion period and even after 10 min of the follow up. HR was not changed in all groups while pH showed significant improvement after the end of therapies administration in all groups. No significant differences were found between Na bicarbonate and ILE groups while there was a highly significant improvement in Na bicarbonate + ILE group as compared to the other groups. In conclusion, ILE can be used alone or as an adjunctive therapy with Na bicarbonate which is preferred to reverse the cardiovascular toxicity induced by combined antidepressant agents in adult rats

Effect of lipid emulsion infusion on paliperidone pharmacokinetics in the acute overdose rat model: A potential emergency treatment for paliperidone intoxication

Paliperidone prolongs cardiac repolarization in a concentration-dependent manner. Meanwhile, continuous infusion of intravenous lipid emulsion (ILE) has been established as a detoxification therapy for lipophilic drugs. However, this change in pharmacokinetics of various drugs following ILE administration remains to be clarified. Our objective is to clarify the effect of continuous infusion of ILE on the pharmacokinetics of overdosed paliperidone in rats. Paliperidone (20mg/kg) was administered orally to free-moving male Wistar rats. Continuous infusion (initial loading dose: 4ml/kg for 10min, followed by 4ml/kg/h for 12h) of ILE or acetated Ringer's solution (AR) was initiated 30min after paliperidone administration. Plasma concentration profile of paliperidone was monitored for 12h after administration. The plasma concentration and tissue/plasma concentration ratios of paliperidone were compared between ILE and AR groups. The rat group infused with ILE showed a higher area under the concentration–time curve (mean [S.D.]: 6102 [900.9] vs. 3407 [992.1]nghml−1, p=0.02) and longer elimination half-time (t1/2) (4.1 [0.9] vs. 2.2 [0.4]h, p=0.02) compared with the AR group. Tissue/plasma concentration ratios of paliperidone were lower in ILE rats than in AR rats (1.98 [0.70] vs. 3.82 [1.47] in the heart, p=0.04; 0.28 [0.29] vs. 1.27 [0.58] in the brain, p<0.001). In conclusion, continuous infusion of ILE would reduce tissue distribution and prolonged the t1/2 of paliperidone in rats. These results suggest that continuous infusion of ILE has potential as an emergency treatment for acute paliperidone intoxication.

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.

Evaluating the effects and safety of intravenous lipid emulsion on haloperidol-induced neurotoxicity in rabbit.

There are many reports on the effect of intravenous lipid emulsion (ILE) as an antidote in drugs related toxicities. We determined the effects of ILE on neurotoxicity of haloperidol (HA), a highly lipophilic antipsychotic, as a model of antipsychotics poisoning. We used six groups of five male rabbits. Two groups received distilled water intravenously followed by infusions of either 18 mL/kg of normal saline or ILE 20%, after 30 minutes. The third group received 18 mL/kg of normal saline after HA (2.6 mg/kg) administration. The three other groups received ILE 20% solution (6, 12, and 18 mL/kg) following HA injection. Catalepsy scores, temperature, pupil size, and mortality rate were measured at 0, 0.5, 1, 2, 3, 4, 8, and 24 hours after HA administration began. Blood and tissue samples were taken from all animals at 24 hours or at death time for biochemical, cell count, and pathological studies. ILE reversed cataleptic scores, miotic pupils, and hypothermia of HA intoxication much faster than normal saline (P < 0.001). Biochemical complications and mortality rate of the animals were significantly higher in the HA + 18 mL/Kg ILE group. ILE reversed sings of HA neurotoxicity; however, synergistic effect of high dose of ILE and HA increased complications and mortality.

Pretreatment With Intravenous Lipid Emulsion Reduces Mortality From Cocaine Toxicity in a Rat Model

We compare the effects of intravenous lipid emulsion and normal saline solution pretreatment on mortality and hemodynamic changes in a rat model of cocaine toxicity. We hypothesize that intravenous lipid emulsion will decrease mortality and hemodynamic changes caused by cocaine administration compared with saline solution. Twenty male Sprague-Dawley rats were sedated and randomized to receive intravenous lipid emulsion or normal saline solution, followed by a 10 mg/kg bolus of intravenous cocaine. Continuous monitoring included intra-arterial blood pressure, pulse rate and ECG tracing. Endpoints included a sustained undetectable mean arterial pressure (MAP) or return to baseline MAP for 5 minutes. The log-rank test was used to compare mortality. A mixed-effect repeated-measures ANOVA was used to estimate the effects of group (intravenous lipid emulsion versus saline solution), time, and survival on change in MAP, pulse rate, or pulse pressure. In the normal saline solution group, 7 of 10 animals died compared with 2 of 10 in the intravenous lipid emulsion group. The survival rate of 80% (95% confidence interval 55% to 100%) for the intravenous lipid emulsion rats and 30% (95% confidence interval 0.2% to 58%) for the normal saline solution group was statistically significant (P=.045). Intravenous lipid emulsion pretreatment decreased cocaine-induced cardiovascular collapse and blunted hypotensive effects compared with normal saline solution in this rat model of acute lethal cocaine intoxication. Intravenous lipid emulsion should be investigated further as a potential adjunct in the treatment of severe cocaine toxicity.

Comparison of Intravenous Lipid Emulsion, Bicarbonate, and Tailored Liposomes in Rabbit Clomipramine Toxicity

Liposome (LIP)-like lipid dispersions have emerged as useful detoxification vehicles in vitro. The authors compare resuscitation with tailored LIPs, 20% intravenous lipid emulsion (ILE), and sodium bicarbonate (BIC), in a rabbit model of clomipramine toxicity. Sedated, instrumented New Zealand white rabbits underwent clomipramine infusion at 3.2mg/kg/min to 50% baseline mean arterial pressure (MAP) and then at 1.6mg/kg/min for 30minutes. BIC (3mL/kg 8.4%), ILE (3mL/kg 20%), or LIP (24mg/kg) were infused as rescue treatments at toxicity and were repeated at 10minutes (n=5 in each group). Thirty-minute MAP was greatest in ILE-treated animals: 61mmHg ILE (interquartile range [IQR]= 49 to 64mmHg), 43mmHg LIP (IQR= 36.5 to 49mmHg), and 10mmHg BIC (IQR= 10 to 44mmHg; all p=0.02). Two of the five BIC-treated animals survived to 30minutes, compared with all five of the ILE-treated animals and all five of the LIP-treated animals (p=0.044). Both ILE and LIPs improved hemodynamic recovery compared with bicarbonate in clomipramine-induced cardiotoxicity in rabbits. Greater 30-minute MAP was observed in the ILE group.

Intravenous Lipid Emulsion Does Not Reverse Dabigatran‐induced Anticoagulation in a Rat Model

The anticoagulant dabigatran has no reversal agent and may cause life-threatening bleeding in patients with trauma or closed-space hemorrhage. Intravenous lipid emulsion (ILE) is thought to create a lipid compartment in serum that sequesters lipophilic drugs. Dabigatran is lipophilic, and its anticoagulant effects are concentration dependent. The study objective was to determine if ILE therapy reverses dabigatran's anticoagulant effects. Twenty rats were selected at random, 10 in the ILE group and 10 in a normal saline (NS) control group. Animals had a baseline tail bleeding time (T0), followed by oral dabigatran administration (15mg/kg). At 45minutes (T45), a second tail bleed time measurement was performed, followed by a 7-minute infusion of 15mL/kg ILE or NS. A final 60-minute (T60) bleed time measurement was obtained. An ILE-only group of five animals had bleeding times assessed prior to (T0) and 15minutes after (T15) ILE therapy. A mixed-effect repeated-measures analysis of variance modeling the effect of time, group, and the interaction of group and time on bleed times was conducted. There was a significant within-subject change in bleeding time across the assessment points (F(2,36)=33; p<0.001), but there were no effect of group (F(1,18)=1.42, p=0.25) or an interaction between group and assessment point on mean bleeding time (F(2,36)=0.59, p=56). Between T0 and T45, average bleeding times increased from 109.5seconds (95% confidence interval [CI]=94 to 125seconds) to 231.8seconds (95% CI=193 to 271seconds; p<0.0001) for both the ILE group and the NS control group. Between T45 and T60, bleeding times in the ILE group decreased by 31.5seconds (95% CI=-77 to 14seconds) and by 6seconds (95% CI=-67 to 55seconds) in the NS group (p=0.46). In the five ILE-only animals, the average bleeding time at T0 was 114seconds (95% CI=62 to 166seconds), which increased significantly at T15 to 237seconds (95% CI=161 to 313seconds; p=0.02). The anticoagulant effects of dabigatran are not reversed with ILE therapy. Although ILE itself significantly prolonged bleeding times, when administered to dabigatran-anticoagulated rats, bleeding times did not change significantly. There may be a complex interaction of ILE with dabigatran that this study was not able to elucidate.