Intravenous Lipid Emulsion Infusion Research Articles

Glyphosate: Hepatotoxicity, Nephrotoxicity, Hemotoxicity, Carcinogenicity, and Clinical Cases of Endocrine, Reproductive, Cardiovascular, and Pulmonary System Intoxication.

Glyphosate (GLP) is an active agent of GLP-based herbicides (GBHs), i.e., broad-spectrum and postemergent weedkillers, commercialized by Monsanto as, e.g., Roundup and RangerPro formulants. The GBH crop spraying, dedicated to genetically engineered GLP-resistant crops, has revolutionized modern agriculture by increasing the production yield. However, abusively administered GBHs' ingredients, e.g., GLP, polyoxyethyleneamine, and heavy metals, have polluted environmental and industrial areas far beyond farmlands, causing global contamination and life-threatening risk, which has led to the recent local bans of GBH use. Moreover, preclinical and clinical reports have demonstrated harmful impacts of GLP and other GBH ingredients on the gut microbiome, gastrointestinal tract, liver, kidney, and endocrine, as well as reproductive, and cardiopulmonary systems, whereas carcinogenicity of these herbicides remains controversial. Occupational exposure to GBH dysregulates the hypothalamic-pituitary-adrenal axis, responsible for steroidogenesis and endocrinal secretion, thus affecting hormonal homeostasis, functions of reproductive organs, and fertility. On the other hand, acute intoxication with GBH, characterized by dehydration, oliguria, paralytic ileus, as well as hypovolemic and cardiogenic shock, pulmonary edema, hyperkalemia, and metabolic acidosis, may occur fatally. As no antidote has been developed for GBH poisoning so far, the detoxification is mainly symptomatic and supportive and requires intensive care based on gastric lavage, extracorporeal blood filtering, and intravenous lipid emulsion infusion. The current review comprehensively discusses the molecular and physiological basics of the GLP- and/or GBH-induced diseases of the endocrine and reproductive systems, and cardiopulmonary-, nephro-, and hepatotoxicities, presented in recent preclinical studies and case reports on the accidental or intentional ingestions with the most popular GBHs. Finally, they briefly describe modern and future healthcare methods and tools for GLP detection, determination, and detoxification. Future electronically powered, decision-making, and user-friendly devices targeting major GLP/GBH's modes of actions, i.e., dysbiosis and the inhibition of AChE, shall enable self-handled or point-of-care professional-assisted evaluation of the harm followed with rapid capturing GBH xenobiotics in the body and precise determining the GBH pathology-associated biomarkers levels.

LIPID EMULSION THERAPY FOR LIFE-THREATENING FLECAINIDE TOXICITY

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: We present a case of flecainide (FLC) toxicity secondary to renal failure treated with intravenous lipid emulsion (ILE) therapy. CASE PRESENTATION: The patient is a 63 year old female with a history of stage IVB uterine carcinosarcoma, chronic kidney disease and supraventricular tachycardia (SVT) on FLC. She was admitted with intra-abdominal hemorrhagic metastases. A rapid response was called due to hypotension, and she was noted to be oliguric for the previous 24 hours with a serum creatinine 2.5 mg/dL (baseline 1.3 mg/dL) and hyponatremic (126 mmol/L). EKG showed a new wide complex rhythm, at 78bpm, QRS widening to 280ms, and prolonged QTc of 631. She subsequently suffered a wide complex tachyarrhythmic cardiac arrest (CA), refractory to two shocks, with return of spontaneous circulation after treatment with sodium bicarbonate (NaHCO3). FLC was discontinued and the patient was started on a hypertonic NaHCO3 drip, but frequent NaHCO3 pushes were required to correct widening of the QRS complex. The hypotension progressed requiring high dose infusions of epinephrine (15 mcg/min) and norepinephrine (90 mcg/min). ILE infusion was started, 20% lipid 1.5 mL/kg administered over 5 minutes, followed by an infusion of 0.25 mL/kg/minute over two hours. A serum FLC level was drawn during ILE infusion and came back elevated at 1.35 mcg/mL (therapeutic level 0.20-1.0 mcg/mL). In the 48 hours following ILE, there was resolution of the wide complex arrhythmias, and vasopressor requirements were reduced by more than 50% DISCUSSION: FLC is a class 1C antiarrhythmic that inhibits Na+ channels and is used for prevention of SVT. It has a narrow therapeutic range and about 30% is renally excreted making acute kidney injury a risk for toxicity. Other risk factors for toxicity are hyponatremia and hypokalemia. Characteristic signs of toxicity include hypotension, lethargy and EKG changes such as QRS widening and PR prolongation. These changes can progress to wide complex brady or tachyarrhythmic CA as seen in our patient. Standard of care is administration of hypertonic NaHCO3 which acts both as a Na+ load to compete with FLC for binding at Na+ channels and as an alkalinizing agent which decreases the ionized receptor-binding form of FLC. However, when NaHCO3 treatment fails, there are few other well studied options. One is VA-ECMO for which our patient was not a candidate. The other is lipid emulsion therapy, which is hypothesized to work by creating a lipid sink to sequester the drug and also has some positive ionotropy. CONCLUSIONS: In our patient, administration of ILE resulted in significant clinical improvement. Unfortunately, the clinical improvement did not sustain after several days and due to overall poor prognosis, the patient was eventually transitioned to comfort measures. REFERENCE #1: Subedi R, Dean R, Chaudhary A. Flecainide toxicity in renal failure. Proc (Bayl Univ Med Cent). 2018 May 9;3(3):328-330. REFERENCE #2: Ghataoura R, Patil S. Flecainide toxicity: a presentation to the emergency department with literature review. BMJ Case Rep. 2020 Feb 28;13(2):e232691. doi: 10.1136/bcr-2019-232691. PMID: 32114494; PMCID: PMC7050315. REFERENCE #3: Valentino MA, Panakos A, Ragupathi L, Williams J, Pavri BB. Flecainide Toxicity: A Case Report and Systematic Review of its Electrocardiographic Patterns and Management. Cardiovasc Toxicol. 2017 Jul;17(3):260-266. doi: 10.1007/s12012-016-9380-0. PMID: 27435408. DISCLOSURES: No relevant relationships by Rebecca Fieles, source=Web Response No relevant relationships by David Gerber, source=Web Response No relevant relationships by Brian Park, source=Web Response No relevant relationships by Harry Rockower, source=Web Response No relevant relationships by Diana Solomon, source=Web Response No relevant relationships by Yanika Wolfe, source=Web Response

Resuscitation Following a Bupivacaine Injection for a Cervical Paravertebral Block.

BackgroundCardiac arrest related to nerve blockade using a local anaesthetic is a rare event. We report a case of bupivacaine severe cardiovascular toxicity following cervical paravertebral nerve block.Case presentationA 44-year-old female was admitted to Republican Vilnius University Hospital, with symptoms of sustained severe pain in her neck that radiated to both arms. Multiple cervical intervertebral hernias with spinal stenosis were confirmed by magnetic resonance imaging. Following infiltration of the subcutaneous tissue with a 0.5 % bupivacaine solution, an 18-gauge spinal needle was used to perform the paravertebral block at the C6 level. Bupivacaine was injected in incremental doses to a total of 10 mL. Rapid loss of consciousness and cardiovascular collapse suggested a neuraxial injection of bupivacaine. Long-lasting cardiopulmonary resuscitation, including chest compressions, defibrillation attempts for refractory ventricular fibrillation, medications, mechanical ventilation, and intravenous lipid emulsion infusion, was successful. No severe adverse outcomes other than acute kidney injury and chest pain related to prolonged chest compressions were documented.ConclusionsThis case report emphasizes the necessity of ensuring adequate safety precautions to avoid local anaesthetic systemic toxicity. Lipid emulsion preparations should be available in all hospital settings where local anaesthetics are used for regional anaesthesia or pain management.

Low-dose intravenous lipid emulsion as a safe treatment for lipophilic intoxications in five cats

The use of a low-dose infusion of intravenous lipid emulsion (ILE) in five young cats presented with acute neurotoxicity is reported. Suspected toxic compounds were permethrin (three, dermal), fipronil/eprinomectin/praziquantel (one,...

Intravenous lipid emulsion infusion in acute intoxication with fenitrothion

Acute intoxications with organophosphorus pesticides (OPs) are a challenge for the clinical toxicology, because they are common, severe and with high lethality. Most OPs are lipophilic. In recent years, intravenous lipid emulsion (ILE) has been successfully used to treat acute poisoning with lipophilic xenobiotics. A clinical case of a 64-year-old male hospitalized after oral intake of 50 ml of fenitrothion is reported. He had been hospitalized with tachypnea and depressed consciousness - 8 by Glasgow coma scale (GCS). Standardized for this type of intoxication treatment was initiated. On the 3rd hour treatment with Intralipid 20% was started, with a bolus dose of 1.5 ml/kg followed by infusion at a rate of 0.25 ml/kg/min to a total dose of 1000 ml. At the 16th hour consciousness was restored to GCS-15. In severe FTO intoxications ILE can be used as an additional method of controlling cardiotoxic and neurotoxic effects.

Intravenous Lipid Emulsion Overdose in Infancy: A Case Report and Overview of Opportunities, Challenges and Prevention.

Medication errors remain among the major problems seen in hospitals. Such errors can relate to the prescription, dispensation, or administration of drugs. Human factors account for most of these mistakes, but other factors such as infusion pump programming defects should always be considered. Worldwide, medication errors have been reported to affect 2–30% of patients, depending on the institution. Intravenous lipid emulsion (ILE) infusion is frequently used as part of total parenteral nutrition in patients of all ages with feeding and gastrointestinal issues. ILE overdose has been previously reported, with variable clinical outcomes. We report a case of accidental ILE (Intralipid) overdose in a 3-month-old male infant who fully recovered after single-volume blood exchange transfusion. We also review reported cases and summarize potential solutions for ILE overdose. Our review indicates that ILE infusion is a high-risk medication, and opportunities for errors remain even in the best hospital set-ups. Attention should be directed towards proper prescription, dosing, dispensation, and administration. Most of the cases indicate the safety breach was at the nursing drug-administration level, with improper pump use or programming, together with other fluid infusion rate switching, being the main possible defects. Strategies targeting the areas of weakness in the drug-delivery pathway are needed. Special attention should be paid towards nursing duties and working hours. In addition, nursing staff should receive frequent education sessions and should be required to pass competency modules regularly. An error-prevention plan should be established and implemented. This plan needs full collaboration between physicians, pharmacists, and nursing staff.

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.

Sudden Deaths of Neonates Receiving Intravenous Infusion of Lipid Emulsion Contaminated with Citrobacter freundii.

At an intensive care unit, four neonates died consecutively within 80 minutes. Citrobacter freundii was isolated from blood samples of the 4 patients. It was also cultured from the leftover SMOFlipid that had been infused intravenously into the patients. In this in vitro study, we evaluated the bacterial growth kinetics and change in size of fat globules in SMOFlipid contaminated with C. freundii. Following the growth of bacteria, pH of SMOFlipid decreased to < 6, and the number of fat globules larger than 5 µm increased. Pulmonary fat embolism is proposed as a possible cause of the sudden deaths as well as fulminant sepsis.

THE ROLE OF LIPID EMULSION IN TREATMENT OF ACUTE TRAMADOL TOXICITY IN ADULT MALE ALBINO RATS

Tramadol is a synthetic centrally acting analgesic for treatment of moderate to severe acute or chronic pain. In tramadol overdose, there are seizures and hypotension. Intravenous lipid emulsion (ILE) is a recognized, effective treatment for local anesthetic-induced cardiovascular collapse, and treating overdoses of parasiticides, and herbicides. The aim of this work was to evaluate the role of ILE in acute tramadol toxicity as regarding hemodynamic instability and seizures in adult male albino rats. Eighty adult male albino rats were used. Rats were divided into five groups: Group I (-ve control group). Group II (+ve control group), divided into; normal saline, ILE10, ILE19 subgroups. Group III (tramadol treated group). Group IV: (tramadol and normal saline treated group). Group V: divided into tramadol+ILE10 and tramadol+ILE19 subgroups. Measurement of blood pressure, monitoring of heart rate and observation for occurrence of seizures were recorded. Different doses of ILE significantly normalized DBP and HR. After infusion of ILE 20%, MAP was significantly stabilized. The ILE10 group had higher MAP at 6 hours, whereas such effect was seen only in ILE19 after 24 hours. There was a decrease in seizures occurrence in ILE treated groups. Serum CPK levels were significantly raised after tramadol toxicity and reduced to normal ranges when ILE was administered in both doses. Tramadol causes Hemodynamic instability and appearance of seizures after once administration (150 mg/kg). ILE could significantly normalize Hemodynamic and seizures of tramadol toxicity.

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.

Adverse events associated with a large dose of intravenous lipid emulsion for suspected local anesthetic toxicity

Background: Intravenous lipid emulsion (ILE) has gained favor as a rescue treatment for cardiovascular collapse due to intravenous local anesthetic overdose, however, goals of ILE therapy are still being defined. We describe a case of a girl given 66 mL/kg of 20% lipid emulsion (ILE) in the treatment of presumed mepivacaine toxicity.Case report: An 11-year-old girl weighing 55.6 kg developed pallor, rolling back of the eyes, and rhythmic muscle twitching after receiving a mandibular nerve block injection with a 1.8 mL ampule of 3% mepivacaine. With concern for persistent seizures she was given three 1 mL/kg boluses of ILE, followed by an infusion of 0.25 mL/kg/min. The total dose ultimately administered was 3670 mL (66 mL/kg) over 7 h. A serum triglyceride concentration, drawn 2 h after cessation of ILE infusion, was estimated to be 16,583 mg/dL (429 mmol/L) after several dilutions; her blood was grossly lipemic. Notable signs included hypersomnolence, tachypnea, and tachycardia. Other complications included apparent metabolic acidosis (serum bicarbonate of 5 mmol/L) with hyperlactatemia (lactate 7.0 mmol/L), difficulty with serum laboratory interpretation, and a non-contrast brain magnetic resonance imaging showing high signal in the dural venous sinuses. The lipemia cleared over three days and the patient recovered uneventfully.Case discussion: This case demonstrates a unique neurologic and metabolic toxicity associated with ILE given as an antidote in a high total dose, and highlights the need for cautious antidotal application of lipid emulsion infusions. Until more data is available, clinicians are advised to take great care if considering a dose in excess of 12.5 mL/kg/day, the maximum daily dosage recommended by the U.S. Food and Drug Administration for nutritional supplementation. Careful monitoring of total doses administered across institutions and hospital wards during transfers is paramount to avoid inadvertent overdose of antidotes.

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 treatment of a patient with intravenous lipid emulsion infusion after amitryptiline overdose which caused in QRS interval prolongation; a case report

Amitryiptiline which is a member of tricyclic antidepressant(TCA) drug group can cause electrocardiographic (ECG)changes like prolongation of QRS and QTc interval, increment of R/S ratio on derivation AVR besides of arrythmias such as supraventricular tachycardia(SVT) and ventricular tachycardia(VT) on overdose. In this paper;we present a case about the treatment of QRS interval prolongation caused by intentional use of high dose amitryiptiline with intravenous lipid emulsion(ILE) infusion.

Prolonged Use of Intravenous Lipid Emulsion in a Severe Tricyclic Antidepressant Overdose

Intravenous lipid emulsion (ILE) resuscitation is now frequently being used for severe overdoses due to lipophilic drugs. However, the optimal dose, duration, and safety are still unclear. A patient with refractory cardiovascular collapse following an amitriptyline overdose was treated with ILE with initial improvement. Instability recurred after ILE discontinuation and lipid therapy was restarted, but high-dose treatment was complicated by severe lipemia. A low-dose infusion was instead used, and the patient did not experience further toxicity despite amitriptyline levels in the toxic range for 21days. He survived to discharge without long-term sequelae. A low-dose infusion of ILE was well tolerated and may have successfully prevented recurrent toxicity in a case of severe tricyclic antidepressant overdose.

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.

Impact of intravenous lipid emulsion infusion on the stratum corneum barrier function in patients receiving parenteral nutrition.

The importance of the lipid matrix of stratum corneum (SC) in epidermal barrier function is well documented. Intravenous lipid emulsions (ILE) provide essential fatty acids (EFAs), main components of the SC lipid matrix. The objective of this study was to investigate the influence of ILE upon SC barrier function. The skin barrier was assessed by measuring transepidermal water loss (TEWL). Patients receiving lipid-containing parenteral nutrition (LCPN) were compared to patients receiving lipid-free PN (LFPN). In addition, a before/after LCPN introduction study was set up to limit the influence of inter-individual variability. Twenty-six patients receiving LCPN and seven patients receiving LFPN were included. Medianagewas not significantly different between the two groups. The TEWL of theLCPNgroup(9.05g/m2/h) was significantly lower than the TEWL of the LFPN group(12.1g/m2/h; Wilcoxon test: p=0.016). The relative variation of TEWL before and after ILE treatment of 5studied patients was 21.29±10.28 %. ILE improve epidermal barrier function when compared to lipid-free parenteral treatments. Results of the before/after study confirm this conclusion and the usefulness of ILE intake for preventing excessive TEWL. SC barrier function improvement could be a choice criterion between the different ILE generations, in particular in burn patients and premature neonates.

An assessment of the in vivo effects of intravenous lipid emulsion on blood drug concentration and haemodynamics following oro-gastric amitriptyline overdose

Background. Overdose with lipophilic drugs, such as amitriptyline, may cause cardiotoxicity in overdose. Severe poisoning can be resistant to traditional treatments. Intravenous lipid emulsion (ILE) has been recommended as a novel therapy for the treatment of such overdoses; however, a little is known about the effects of ILE-infusion on drug concentration and haemodynamics in the early/absorptive phase after oral poisoning. Method. Thirty minutes after oro-gastric administration of amitriptyline (70 mg/kg), either 20% intravenous lipid emulsion (ILE), 8.4% sodium bicarbonate or Hartmann's solution was infused to anaesthetized and ventilated rodents (n = 10 per group). Heart rate, blood pressure, cutaneous ECG – QRS interval duration (QRS-d), and survival were serially recorded over 120 min. Blood drug concentrations were also collected during this period. Continuous variables were compared using one-way ANOVA. Results. ILE infusion significantly decreased the survival compared to other treatments (10% ILE vs 70% bicarbonate vs 70% Hartmann's solution, p = 0.005). There was a gradual prolongation of QRS-d and fall in blood pressure over time compared to baseline (T0) measurement for both ILE and Hartmann's solution treatments. This was associated with significantly increased blood AMI concentration with ILE treatment at T60, T90 and T120 min to the other treatments (p < 0.02). Conclusion. Administration of ILE early after oral amitriptyline overdose resulted in worse survival and no improvement in haemodynamics. In addition, blood amitriptyline concentrations were higher in the ILE-treated group. This suggests that either drug absorption from the gastrointestinal-tract was facilitated or drug redistribution was retarded when ILE was given early after oral poisoning.

Usefulness of Intravenous Lipid Emulsion for Cardiac Toxicity from Cocaine Overdose

The investigators describe the clinical course of a 26-year-old-man who was brought to the emergency department in a comatose state with status epilepticus after smoking a large amount of crack cocaine. In the emergency department, he was intubated because of depressed mental status and respiratory acidosis. His troponin I remained negative, and electrocardiography showed wide-complex tachycardia with a prolonged corrected QT interval. Because of the corrected QT interval prolongation and wide-complex tachycardia, the patient was started on intravenous magnesium sulfate and sodium bicarbonate. Despite these interventions, no improvement in cardiac rhythm was observed, and electrocardiography continued to show wide-complex tachycardia. The patient became more unstable from a cardiovascular standpoint, with a decrease in blood pressure to 85/60 mm Hg. He was then given 100 ml of 20% lipid emulsion (Intralipid). Within 10 minutes of starting the infusion of 20% lipid emulsion, wide-complex tachycardia disappeared, with an improvement in systemic blood pressure to 120/70 mm Hg. Repeat electrocardiography after the infusion of intravenous lipid emulsion showed regular sinus rhythm with normal QRS and corrected QT intervals. The patient was successfully extubated on day 8 of hospitalization and discharged home on day 10. His cardiac rhythm and blood pressure remained stable throughout his further stay in the hospital.

Effect of intravenous lipid emulsion on bupivacaine plasma concentration in humans

Intravenous lipid emulsion is the recommended treatment for severe local anaesthetic intoxication. Lipid emulsion may entrap lipid soluble drugs by functioning as a 'lipid sink', but its effect on bupivacaine pharmacokinetics remains unknown. In this randomised, double-blind, crossover study, eight healthy male volunteers were infused bupivacaine 0.5mg.kg(-1) intravenously over 20 min, followed by an infusion of either intravenous lipid emulsion or Hartmann's solution for 30 min. At 20 and 30 min after the start of the infusion, the total plasma bupivacaine concentration was lower while receiving lipid emulsion than Hartmann's solution (mean difference 111 (95% CI 55-167) μg.l(-1) and 75 (95% CI 26-124 μg.l(-1) at 20 and 30 min, respectively; p<0.02). However, there were no differences in un-entrapped (non-lipid bound) or free (non-protein bound) bupivacaine plasma concentrations during the infusion. Intravenous lipid emulsion infusion reduced the context-sensitive half-life of total plasma bupivacaine from 45 (95% CI 32-76)min to 25 (95% CI 20-33)min; p=0.01. We observed no significant adverse effects of lipid emulsion. In conclusion, lipid emulsion may slightly increase the rate of bupivacaine tissue distribution. No 'lipid sink' effect was observed with the non-toxic dose of bupivacaine used.

Clinical Experience with Intravenous Lipid Emulsion for Drug-Induced Cardiovascular Collapse

Intravenous lipid emulsion (ILE) is an emerging therapy for refractory cardiotoxicity due to lipid-soluble drugs. The purpose of this study was to assess survival to hospital discharge, effects on hemodynamic parameters, and adverse event occurrence for patients who were treated with ILE as part of the resuscitative effort for drug-induced cardiotoxicity. This is a multicenter retrospective chart review of inpatients at three tertiary referral medical centers receiving ILE for drug-induced cardiotoxicity between November 2007 and March 2009. Nine cases with drug-induced cardiovascular collapse, defined as cardiac arrest or refractory shock, were selected for review if patients received either bolus or infusion of ILE in any combination. No interventions were done. The main outcome measures were survival to hospital discharge, effect on hemodynamic parameters, and adverse event. Hemodynamic vital signs (heart rate, systolic blood pressure, diastolic blood pressure, calculated mean arterial pressure [MAP]) were measured before administration of ILE and up to five measurements (if available) were recorded after administration of ILE. Attribution of adverse events was determined by assignment of Naranjo adverse drug reaction (ADR) likelihood score (3) with adjudication of three medical toxicologists; disagreements were settled by majority consensus. Of nine cases identified based on inclusion criteria (three cardiac arrest, six refractory shock), five (55%) survived to hospital discharge. ILE regimens were bolus alone in five patients and bolus plus infusion in four patients. Hemodynamic trends in response to ILE demonstrated no difference in MAP immediately pre- and post-administration of ILE (p = NS). Administration of infusion (versus boluses alone) did not demonstrate a statistically significant improvement in MAP. Adverse events due to ILE therapy that were categorized as "possible" or "probable" based on Naranjo scores included lipemia, digit amputation, lung injury, renal failure, and deep venous thrombosis. ILE administered to patients with drug-induced cardiovascular collapse was associated with 55% survival but with clinically significant adverse effects. At this time, ILE should be restricted to cardiotoxicity involving cardiac arrest or refractory shock until further prospective studies can better evaluate risks and benefits of ILE therapy.