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Hwang Y, Sohn JT. Effect of lipid emulsion on neuropsychiatric drug-induced toxicity: A narrative review. Medicine (Baltimore) 2024; 103:e37612. [PMID: 38489675 PMCID: PMC10939703 DOI: 10.1097/md.0000000000037612] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Revised: 02/13/2024] [Accepted: 02/23/2024] [Indexed: 03/17/2024] Open
Abstract
Lipid emulsion has been shown to effectively relieve refractory cardiovascular collapse resulting from toxic levels of nonlocal anesthetics. The goal of this study was to examine the effect of lipid emulsions on neuropsychiatric drug-induced toxicity using relevant case reports of human patients, with a particular focus on the Glasgow Coma Scale (GCS) score and corrected QT interval, to analyze drugs that frequently require lipid emulsion treatment. The following keywords were used to retrieve relevant case reports from PubMed: "antidepressant or antipsychotic drug or amitriptyline or bupropion or citalopram or desipramine or dosulepin or dothiepin or doxepin or escitalopram or fluoxetine or haloperidol or olanzapine or phenothiazine or quetiapine or risperidone or trazodone" and "lipid emulsion or Intralipid." Lipid emulsion treatment reversed the corrected QT interval prolongation and decreases in Glasgow Coma Scale scores caused by toxic doses of neuropsychiatric drugs, especially lipid-soluble drugs such as amitriptyline, trazodone, quetiapine, lamotrigine, and citalopram. The log P (octanol/water partition coefficient) of the group which required more than 3 lipid emulsion treatments was higher than that that of the group which required less than 3 lipid emulsion treatments. The main rationale to administer lipid emulsion as an adjuvant was as follows: hemodynamic depression intractable to supportive treatment (88.3%) > lipophilic drugs (8.3%) > suspected overdose or no spontaneous breathing (1.6%). Adjuvant lipid emulsion treatment contributed to the recovery of 98.30% of patients with neuropsychiatric drug-induced toxicity. However, further analyses using many case reports are needed to clarify the effects of lipid emulsion resuscitation.
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Affiliation(s)
- Yeran Hwang
- Department of Anesthesiology and Pain Medicine, Gyeongsang National University College of Medicine, Gyeongsang National University Hospital, Jinju-si, Republic of Korea
| | - Ju-Tae Sohn
- Department of Anesthesiology and Pain Medicine, Gyeongsang National University College of Medicine, Gyeongsang National University Hospital, Jinju-si, Republic of Korea
- Institute of Health Sciences, Gyeongsang National University, Jinju-si, Republic of Korea
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Akyol BA, Gokbulut C. The effect of intravenous lipid emulsion (ILE) on the pharmacokinetic/toxicokinetic dispositions of ivermectin and carprofen in rabbits. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2024; 397:1841-1852. [PMID: 37768375 DOI: 10.1007/s00210-023-02738-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Accepted: 09/20/2023] [Indexed: 09/29/2023]
Abstract
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 ± 0.2 kg 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 (0.6 mg/kg) alone while Group 2 received IVM (0.6 mg/kg) and ILE (2.5 ml/kg). In the CRP study, Group 3 received CRP (12 mg/kg) alone while Group 4 received CRP (12 mg/kg) and ILE (2.5 ml/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 (2136 ng/ml and 360.84 ng.d/ml) compared to the IVM alone (1340.63 ng/ml and 206 ng.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.
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Affiliation(s)
- Busra Aslan Akyol
- Department of Veterinary Pharmacology and Toxicology, Institute of Health Sciences, Balikesir University, CoHE 100/2000 Scholarship Holder, University Rectorate Çağış Campus 17. Km, Bigadiç Caddesi, 10145, Balikesir, Turkey
| | - Cengiz Gokbulut
- Department of Medical Pharmacology, Faculty of Medicine, Balikesir University, University Rectorate Çağış Campus 17. Km, Bigadiç Caddesi, 10145, Balikesir, Turkey.
- Department of Veterinary Pharmacology and Toxicology, Institute of Health Sciences, Balikesir University, University Rectorate Çağış Campus 17. Km, Bigadiç Caddesi, 10145, Balikesir, Turkey.
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Wang L, Wang Y, Zhang RY, Wang Y, Liang W, Li TG. Management of acute carbamazepine poisoning: A narrative review. World J Psychiatry 2023; 13:816-830. [DOI: 10.5498/wjp.v13.i11.816] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2023] [Revised: 09/23/2023] [Accepted: 10/11/2023] [Indexed: 11/17/2023] Open
Abstract
Standard management protocols are lacking and specific antidotes are unavailable for acute carbamazepine (CBZ) poisoning. The objective of this review is to provide currently available information on acute CBZ poisoning, including its management, by describing and summarizing various therapeutic methods for its treatment according to previously published studies. Several treatment methods for CBZ poisoning will be briefly introduced, their advantages and disadvantages will be analyzed and compared, and suggestions for the clinical treatment of CBZ poisoning will be provided. A literature search was performed in various English and Chinese databases. In addition, the reference lists of identified articles were screened for additional relevant studies, including non-indexed reports. Non-peer-reviewed sources were also included. In the present review, 154 articles met the inclusion criteria including case reports, case series, descriptive cohorts, pharmacokinetic studies, and in vitro studies. Data on 67 patients, including 4 fatalities, were reviewed. Based on the summary of cases reported in the included articles, the cure rate of CBZ poisoning after symptomatic treatment was 82% and the efficiency of hemoperfusion was 58.2%. Based on the literature review, CBZ is moderately dialyzable and the recommendation for CBZ poisoning is supportive management and gastric lavage. In severe cases, extracorporeal treatment is recommended, with hemodialysis as the first choice.
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Affiliation(s)
- Luan Wang
- Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - Yang Wang
- Department of General Surgery, The 4th Affiliated Hospital of China Medical University, Shenyang 110032, Liaoning Province, China
| | - Ruo-Ying Zhang
- Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - Yao Wang
- Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - Wei Liang
- Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - Tie-Gang Li
- Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
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Chhabria BA, Bhalla A, Shafiq N, Kumar S, Dhibar DP, Sharma N. Lipid emulsion for acute organophosphate insecticide poisoning – a pilot observational safety study. Clin Toxicol (Phila) 2018; 57:318-324. [DOI: 10.1080/15563650.2018.1520997] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
Affiliation(s)
- Bharath A. Chhabria
- Department of Internal Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Ashish Bhalla
- Department of Internal Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Nusrat Shafiq
- Department of Clinical Pharmacology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Susheel Kumar
- Department of Internal Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Deba Prasad Dhibar
- Department of Internal Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Navneet Sharma
- Department of Internal Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India
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Tse C, Chan Y, Lau F. Intravenous Lipid Emulsion as Antidote: Experience in Hong Kong. HONG KONG J EMERG ME 2017. [DOI: 10.1177/102490791502200204] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Objective Intravenous lipid emulsion (ILE) is an emerging therapy in the field of toxicology. The purpose of this study was to report the accumulated local experience on using ILE in the management of patients suffering from poisoning by pharmaceutical agents other than local anaesthetics. Design Case series. Setting Local poison information centre. Methods Ten patients were identified from the database of Hong Kong Poison Information Centre. The patients were managed in 6 Hong Kong public hospitals during a 4-year study period (July 2008-June 2012). Results Nine of them presented with drug-induced cardiotoxicity, defined as either cardiac arrest (n=3) or hypotension refractory to other treatments (n=6). The overall survival rate is 30%. Possible adverse events from ILE included mild derangement of liver function, elevated amylase and hyperlipidaemia were observed. Conclusions About 30% of severe poison-induced cardiotoxicity treated with ILE can survive with no major adverse effects. The use of ILE remains to be a treatment option for lipid-soluble drug induced severe toxicity not responsive to standard resuscitation measures. (Hong Kong j. emerg.med. 2015;22:100-107)
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Xia F, Xia Y, Chen S, Chen L, Zhu W, Chen Y, Papadimos TJ, Xu X, Liu L. Lipid emulsion mitigates impaired pulmonary function induced by limb I/R in rats through attenuation of local cellular injury and the subsequent systemic inflammatory response/inflammation. BMC Anesthesiol 2017. [PMID: 28629353 PMCID: PMC5477350 DOI: 10.1186/s12871-017-0375-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Background Limb ischemia/reperfusion causes inflammation and elicits oxidative stress that may lead to local tissue damage and remote organ such as lung injury. This study investigates pulmonary function after limb ischemia/reperfusion and the protective effect of a lipid emulsion (Intralipid). Methods Twenty-four rats were divided into three groups: sham operation group (group S), ischemia/reperfusion group (group IR), and lipid emulsion treatment group (group LE). limb ischemia/reperfusion was induced through occlusion of the infrarenal abdominal aorta for 3 h. The microvascular clamp was removed carefully and reperfusion was provided for 3 h. Results The mean arterial pressure in group LE was higher than group IR during the reperfusion period (P = 0.024). The heart rate of both group LE and IR are significantly higher than group S during the ischemia period(P < 0.001, P < 0.001, respectively). The arterial oxygen pressure of group LE was significantly higher than group IR (P = 0.003), the arterial carbon dioxide pressure of group LE were lower than that of group IR (P = 0.005). The concentration of plasma interleukin-6, tumor necrosis factor-α and malondialdehyde in group LE were significantly lower than group IR (P < 0.001, P = 0.009 and 0.029, respectively). The plasma superoxide dismutase activity in group LE was significantly higher than group IR (P = 0.029). The myeloperoxidase activity in lung tissues of group LE was significantly less than group IR (P = 0.046). Both muscle and lung in group IR were damaged seriously, whereas lipid emulsion (Intralipid) effectively reversed the damage. In summary, Intralipid administration resulted in several beneficial effects as compared to group IR, such as the pulmonary gas exchange and inflammatory. Conclusions The ischemic/reperfusion injury of limb muscles with resultant inflammatory damage to lung tissue can be mitigated by administration of a lipid emulsion (Intralipid, 20%, 5 ml/kg). The mechanisms attenuating such a physiological may be attributed to reduction of the degree of limb injury through a decrease in the release of local inflammatory mediators, a reduction of lipid peroxidation, and a blunting of the subsequent remote inflammatory response.
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Affiliation(s)
- Fangfang Xia
- Department of Anesthesiology, the First Affiliated Hospital of Wenzhou Medical University, Zhejiang, China
| | - Yun Xia
- Department of Anesthesiology, the First Affiliated Hospital of Wenzhou Medical University, Zhejiang, China
| | - Sisi Chen
- Department of Anesthesiology, the First Affiliated Hospital of Wenzhou Medical University, Zhejiang, China
| | - Lulu Chen
- Department of Anesthesiology, the First Affiliated Hospital of Wenzhou Medical University, Zhejiang, China
| | - Weijuan Zhu
- Department of Anesthesiology, the First Affiliated Hospital of Wenzhou Medical University, Zhejiang, China
| | - Yuanqing Chen
- Department of Anesthesiology, the First Affiliated Hospital of Wenzhou Medical University, Zhejiang, China
| | - Thomas J Papadimos
- Department of Anesthesiology, the First Affiliated Hospital of Wenzhou Medical University, Zhejiang, China
| | - Xuzhong Xu
- Department of Anesthesiology, the First Affiliated Hospital of Wenzhou Medical University, Zhejiang, China
| | - Le Liu
- Department of Anesthesiology, the First Affiliated Hospital of Wenzhou Medical University, Zhejiang, China.
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Lam SH, Majlesi N, Vilke GM. Use of Intravenous Fat Emulsion in the Emergency Department for the Critically Ill Poisoned Patient. J Emerg Med 2016; 51:203-14. [DOI: 10.1016/j.jemermed.2016.02.008] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2016] [Accepted: 02/05/2016] [Indexed: 11/25/2022]
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Tse J, Ferguson K, Whitlow KS, Erickson K. The use of intravenous lipid emulsion therapy in acute methamphetamine toxicity. Am J Emerg Med 2016; 34:1732.e3-4. [DOI: 10.1016/j.ajem.2015.12.055] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2015] [Accepted: 12/18/2015] [Indexed: 12/19/2022] Open
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Bartlett D. Intravenous lipids: antidotal therapy for drug overdose and toxic effects of local anesthetics. Crit Care Nurse 2016; 34:62-6; quiz 67. [PMID: 25274765 DOI: 10.4037/ccn2014755] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022]
Abstract
Intravenous lipid emulsion is an accepted therapy for the treatment of severe cardiac toxic effects caused by local anesthetics. Lipid emulsion therapy has also been used successfully to treat cardiac arrest and intractable arrhythmias caused by overdoses of antiepileptic drugs, cardiovascular drugs, and psychotropic medications, but experience with intravenous lipids as antidotal therapy in these clinical situations is limited. However, intravenous lipids are relatively safe, widely available, and easy to administer, and many published case reports document their dramatic effectiveness. Patients who have not responded to standard therapies have been quickly revived by administration of intravenous lipids. Use of lipids most likely will increase, and critical care nurses should be familiar with lipid therapy.
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Affiliation(s)
- Dana Bartlett
- Dana Bartlett is a certified specialist in poison information at the Connecticut Poison Control Center, Farmington, Connecticut.
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Levine M, Hoffman RS, Lavergne V, Stork CM, Graudins A, Chuang R, Stellpflug SJ, Morris M, Miller-Nesbitt A, Gosselin S. Systematic review of the effect of intravenous lipid emulsion therapy for non-local anesthetics toxicity. Clin Toxicol (Phila) 2016; 54:194-221. [DOI: 10.3109/15563650.2015.1126286] [Citation(s) in RCA: 73] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Affiliation(s)
- Michael Levine
- Department of Emergency Medicine, Section of Medical Toxicology, University of Southern California, Los Angeles, CA, USA
| | - Robert S. Hoffman
- Division of Medical Toxicology, Ronald O. Perelman Department of Emergency Medicine, New York University School of Medicine, New York, NY, USA
| | - Valéry Lavergne
- Department of Medical Biology, Sacré-Coeur Hospital, University of Montreal, Montreal, Canada
| | - Christine M. Stork
- Department of Emergency Medicine, Upstate Medical University, New York and Upstate New York Poison Center, New York, NY, USA
| | - Andis Graudins
- Department of Medicine, School of Clinical Sciences at Monash Health, Clinical Toxicology Service at Monash Health and Monash Emergency Translational Research Group, Monash University, Clayton, Victoria, Australia
| | - Ryan Chuang
- Department of Emergency Medicine, University of Calgary, Poison and Drug Information Service, Calgary, Canada
| | | | - Martin Morris
- Schulich Library of Science and Engineering, McGill University, Montreal, Canada; and
| | - Andrea Miller-Nesbitt
- Schulich Library of Science and Engineering, McGill University, Montreal, Canada; and
| | - Sophie Gosselin
- Department of Emergency Medicine, McGill University Health Centre & Department of Medicine, McGill University, Montreal, Canada
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Eisenkraft A, Falk A. The possible role of intravenous lipid emulsion in the treatment of chemical warfare agent poisoning. Toxicol Rep 2016; 3:202-210. [PMID: 28959540 PMCID: PMC5615427 DOI: 10.1016/j.toxrep.2015.12.007] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2015] [Revised: 11/29/2015] [Accepted: 12/24/2015] [Indexed: 12/19/2022] Open
Abstract
Organophosphates (OPs) are cholinesterase inhibitors that lead to a characteristic toxidrome of hypersecretion, miosis, dyspnea, respiratory insufficiency, convulsions and, without proper and early antidotal treatment, death. Most of these compounds are highly lipophilic. Sulfur mustard is a toxic lipophilic alkylating agent, exerting its damage through alkylation of cellular macromolecules (e.g., DNA, proteins) and intense activation of pro-inflammatory pathways. Currently approved antidotes against OPs include the peripheral anticholinergic drug atropine and an oxime that reactivates the inhibited cholinesterase. Benzodiazepines are used to stop organophosphate-induced seizures. Despite these approved drugs, efforts have been made to introduce other medical countermeasures in order to attenuate both the short-term and long-term clinical effects following exposure. Currently, there is no antidote against sulfur mustard poisoning. Intravenous lipid emulsions are used as a source of calories in parenteral nutrition. In recent years, efficacy of lipid emulsions has been shown in the treatment of poisoning by fat-soluble compounds in animal models as well as clinically in humans. In this review we discuss the usefulness of intravenous lipid emulsions as an adjunct to the in-hospital treatment of chemical warfare agent poisoning.
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Affiliation(s)
- Arik Eisenkraft
- NBC Protection Division, IMOD, Israel.,Israel Defense Forces Medical Corps, Israel.,The Institute for Research in Military Medicine, The Faculty of Medicine, The Hebrew University, Jerusalem, Israel
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Abstract
BACKGROUND Lipid emulsion (LE) has been successfully used for resuscitation of local anesthetic cardiotoxicity caused by bupivacaine overdose. Opioid receptors have been shown to play a key role in cardio protection. We explored whether this rescue action of LE is mediated through opioid receptors. METHODS Asystole was induced by bupivacaine (10 mg/kg over 20 seconds, IV) in young male Sprague-Dawley rats, and resuscitation with LE (intralipid 20%; 5 mL/kg bolus and 0.5 mL/kg/min maintenance) was started immediately. The rats were pretreated 2 minutes before inducing asystole with nonselective opioid receptor antagonists such as naloxone and naloxone methiodide, as well as highly selective opioid receptor antagonists for subtype κ, δ, and µ or phosphate buffer solution as a control. Heart rates and ejection fractions were measured using echocardiography. RESULTS LE rescue of bupivacaine cardiotoxicity was prevented by high-dose (1 mg/kg) naloxone but not by lower doses of naloxone (1, 5, and 10 µg/kg), by naloxone methiodide (which does not cross the blood-brain barrier), and by a selective δ- and κ-opioid receptor antagonists at a higher (10 mg/kg) dose. Successful LE rescue was not affected by highly selective µ-opioid receptor antagonists. δ-Opioid receptor antagonist (10 mg/kg) pretreatment also resulted in reduced phosphorylation level of cardiac glycogen synthase kinase-3β in rats that were not resuscitated by LE compared with control. CONCLUSIONS Our data highlight the involvement of peripheral δ- and κ-opioid receptors in the rescue action of LE.
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Collins S, Neubrander J, Vorst Z, Sheffield B. Lipid Emulsion in Treatment of Local Anesthetic Toxicity. J Perianesth Nurs 2015. [DOI: 10.1016/j.jopan.2014.03.011] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
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Peacock RE, Hosgood G, Swindells KL, Smart L. A randomized, controlled clinical trial of intravenous lipid emulsion as an adjunctive treatment for permethrin toxicosis in cats. J Vet Emerg Crit Care (San Antonio) 2015; 25:597-605. [PMID: 26088727 DOI: 10.1111/vec.12322] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2013] [Accepted: 03/22/2015] [Indexed: 11/30/2022]
Abstract
OBJECTIVE To assess for any clinical benefit of intravenous lipid emulsion (ILE) for permethrin toxicosis in cats by comparing the progression of clinical signs of cats before and after treatment with ILE to cats treated with a saline control. To accomplish this objective, a clinical staging system for cats with permethrin toxicosis was developed and validated. DESIGN Prospective, multicenter, randomized, controlled clinical trial. SETTING University veterinary teaching hospital and 12 private veterinary emergency hospitals. ANIMALS Thirty-four client-owned cats with permethrin toxicosis. INTERVENTIONS A clinical staging system was designed based on abnormalities found on physical examination of cats with permethrin toxicosis. The clinical staging system had 6 stages, ranging from Stage A for cats with no abnormalities to Stage F for cats with grand mal seizures. The system was validated for intraviewer and interviewer variability. Cats in the clinical trial were randomized to receive 15 mL/kg of either intravenous 0.9% saline (control) or 20% ILE over 60 minutes. For each cat, a clinical stage was recorded at set time points before and after the randomized treatment was administered. The distribution of clinical stage stratified over time was compared across treatment groups. MEASUREMENTS AND MAIN RESULTS The clinical staging system showed excellent repeatability (P = 1.0) and reliability (P = 1.0). In the clinical trial, there was a significant difference in the distribution of clinical stages over time (P < 0.001) and from presentation stage to Stage B (P = 0.006), with ILE-treated cats (n = 20) having lower clinical stages earlier than control cats (n = 14). There was no significant difference in signalment, body weight, or supportive treatment between the groups. CONCLUSIONS The clinical staging system was repeatable and reliable. Clinical stages of permethrin toxicosis in ILE-treated cats improved earlier compared to control cats, suggesting ILE may be a useful adjunctive therapy in the treatment of permethrin toxicosis in cats.
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Affiliation(s)
- Rachel E Peacock
- School of Veterinary and Life Sciences, Murdoch University, 90 South Street, Murdoch, 6150, Western Australia
| | - Giselle Hosgood
- School of Veterinary and Life Sciences, Murdoch University, 90 South Street, Murdoch, 6150, Western Australia
| | - Katrin L Swindells
- School of Veterinary and Life Sciences, Murdoch University, 90 South Street, Murdoch, 6150, Western Australia
| | - Lisa Smart
- School of Veterinary and Life Sciences, Murdoch University, 90 South Street, Murdoch, 6150, Western Australia
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Kang C, Kim DH, Kim SC, Lee SH, Jeong JH, Kang TS, Shin IW, Kim RB, Lee DH. The effects of intravenous lipid emulsion on prolongation of survival in a rat model of calcium channel blocker toxicity. Clin Toxicol (Phila) 2015; 53:540-4. [PMID: 25984591 DOI: 10.3109/15563650.2015.1045979] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
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.
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Affiliation(s)
- Changwoo Kang
- Department of Emergency Medicine, Gyeongsang National University School of Medicine , Jinju , Korea
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Haloperidol imprinted polymer: preparation, evaluation, and application for drug assay in brain tissue. Anal Bioanal Chem 2014; 406:7729-39. [DOI: 10.1007/s00216-014-8178-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2014] [Revised: 09/07/2014] [Accepted: 09/09/2014] [Indexed: 10/24/2022]
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Kruger CJ, Marwick PC, Levin AI. Lipid rescue: the use of lipid emulsions to treat local anaesthetic toxicity. SOUTHERN AFRICAN JOURNAL OF ANAESTHESIA AND ANALGESIA 2014. [DOI: 10.1080/22201173.2009.10872619] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
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Cave G, Harvey MG. Should we consider the infusion of lipid emulsion in the resuscitation of poisoned patients? CRITICAL CARE : THE OFFICIAL JOURNAL OF THE CRITICAL CARE FORUM 2014; 18:457. [PMID: 25673255 PMCID: PMC4331416 DOI: 10.1186/s13054-014-0457-5] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
The use of intravenous lipid emulsions (ILEs) as antidote in local anaesthetic systemic toxicity has gained widespread support following convincing data from animal models, and successful case reports in humans. Proposed beneficial mechanisms of action for ILEs include intravascular sequestration of intoxicant and subsequent enhanced redistribution to biologically inert tissues, augmentation of fatty acid utilisation for ATP synthesis in the context of metabolic poisoning, and direct cardiotonic and ion channel effects. The evidence base for use of ILEs in acute drug intoxication is evolving. The present evidence supports use of ILEs only in local anaesthetic systemic toxicity and in lipophilic cardiotoxin intoxication when there is an immediate threat to life, and other therapies have proven ineffective.
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Carreiro S, Blum J, Hack JB. Pretreatment With Intravenous Lipid Emulsion Reduces Mortality From Cocaine Toxicity in a Rat Model. Ann Emerg Med 2014; 64:32-7. [DOI: 10.1016/j.annemergmed.2013.11.017] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2013] [Revised: 11/11/2013] [Accepted: 11/22/2013] [Indexed: 10/25/2022]
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Abstract
Intravenous lipid emulsion (ILE) has been used widely for the treatment of poisoning due to local anesthetic agent and is increasingly reported as a therapy for other forms of poisoning. This article will review the proposed mechanisms of action for ILE in poisoning and the evidence from animal studies and human experience supporting the use of ILE for poisoning due to nonlocal anesthetic agents.
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Carreiro S, Blum J, Jay G, Hack JB. Intravenous lipid emulsion alters the hemodynamic response to epinephrine in a rat model. J Med Toxicol 2014; 9:220-5. [PMID: 23412937 DOI: 10.1007/s13181-013-0291-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Intravenous lipid emulsion (ILE) is an adjunctive antidote used in selected critically ill poisoned patients. These patients may also require administration of advanced cardiac life support (ACLS) drugs. Limited data is available to describe interactions of ILE with standard ACLS drugs, specifically epinephrine. Twenty rats with intra-arterial and intravenous access were sedated with isoflurane and split into ILE or normal saline (NS) pretreatment groups. All received epinephrine 15 μm/kg intravenously (IV). Continuous mean arterial pressure (MAP) and heart rate (HR) were monitored until both indices returned to baseline. Standardized t tests were used to compare peak MAP, time to peak MAP, maximum change in HR, time to maximum change in HR, and time to return to baseline MAP/HR. There was a significant difference (p = 0.023) in time to peak MAP in the ILE group (54 s, 95 % CI 44-64) versus the NS group (40 s, 95 % CI 32-48) and a significant difference (p = 0.004) in time to return to baseline MAP in ILE group (171 s, 95 % CI 148-194) versus NS group (130 s, 95 % CI 113-147). There were no significant differences in the peak change in MAP, peak change in HR, time to minimum HR, or time to return to baseline HR between groups. ILE-pretreated rats had a significant difference in MAP response to epinephrine; ILE delayed the peak effect and prolonged the duration of effect of epinephrine on MAP, but did not alter the peak increase in MAP or the HR response.
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Affiliation(s)
- Stephanie Carreiro
- Department of Emergency Medicine, The Alpert Medical School, Brown University, Providence, RI, USA,
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Harvey M, Cave G. Lipid rescue: does the sink hold water? And other controversies. Br J Anaesth 2014; 112:622-5. [DOI: 10.1093/bja/aeu010] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
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Fettiplace MR, Akpa BS, Ripper R, Zider B, Lang J, Rubinstein I, Weinberg G. Resuscitation with lipid emulsion: dose-dependent recovery from cardiac pharmacotoxicity requires a cardiotonic effect. Anesthesiology 2014; 120:915-25. [PMID: 24496123 PMCID: PMC4077021 DOI: 10.1097/aln.0000000000000142] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND Recent publications have questioned the validity of the "lipid sink" theory of lipid resuscitation while others have identified sink-independent effects and posed alternative mechanisms such as hemodilution. To address these issues, the authors tested the dose-dependent response to intravenous lipid emulsion during reversal of bupivacaine-induced cardiovascular toxicity in vivo. Subsequently, the authors modeled the relative contribution of volume resuscitation, drug sequestration, inotropy and combined drug sequestration, and inotropy to this response with the use of an in silico model. METHODS Rats were surgically prepared to monitor cardiovascular metrics and deliver drugs. After catheterization and instrumentation, animals received a nonlethal dose of bupivacaine to produce transient cardiovascular toxicity, then were randomized to receive one of the four treatments: 30% intravenous lipid emulsion, 20% intravenous lipid emulsion, intravenous saline, or no treatment (n = 7 per condition; 28 total animals). Recovery responses were compared with the predictions of a pharmacokinetic-pharmacodynamic model parameterized using previously published laboratory data. RESULTS Rats treated with lipid emulsions recovered faster than did rats treated with saline or no treatment. Intravenous lipid emulsion of 30% elicited the fastest hemodynamic recovery followed in order by 20% intravenous lipid emulsion, saline, and no treatment. An increase in arterial blood pressure underlay the recovery in both lipid emulsion-treated groups. Heart rates remained depressed in all four groups throughout the observation period. Model predictions mirrored the experimental recovery, and the model that combined volume, sequestration, and inotropy predicted in vivo results most accurately. CONCLUSION Intravenous lipid emulsion accelerates cardiovascular recovery from bupivacaine toxicity in a dose-dependent manner, which is driven by a cardiotonic response that complements the previously reported sequestration effect.
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Affiliation(s)
- Michael R Fettiplace
- From the Department of Anesthesiology, University of Illinois College of Medicine, Chicago, Illinois (M.R.F., R.R., and G.W.); Research and Development Service, Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois (M.R.F., R.R., I.R., and G.W.); University of Illinois College of Medicine, Chicago, Illinois (M.R.F. and B.Z.); Department of Chemical Engineering, University of Illinois at Chicago, Chicago, Illinois (B.S.A.); University of Illinois College of Medicine, Peoria, Illinois (J.L.); and Section of Pulmonary, Critical Care, Sleep, and Allergy Medicine, Department of Medicine, University of Illinois College of Medicine, Chicago, Illinois (I.R.)
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Moshiri M, Vahabzadeh M, Mohammadpour AH, Hosseinzadeh H. Evaluation of intravenous lipid emulsion on haloperidol-induced hypotension in rabbits. Toxicol Ind Health 2014; 32:945-52. [PMID: 24444695 DOI: 10.1177/0748233713518601] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
There are many reports on the effects of intravenous lipid emulsion (ILE) as an antidote in drug toxicity. Haloperidol (HAL) is a butyrophenone antipsychotic agent which is highly lipophilic. Hypotension is an important adverse effect of HAL administration and overdose. The aim of this study was to investigate the beneficial hemodynamic effects of ILE on acute HAL poisoning. We used six groups of five male rabbits. Two groups received aseptic distilled water intravenously followed by infusion of 18.6 ml/kg normal saline, as negative control group, or ILE 20% after 0.5 h. The third group received 18.6 ml/kg normal saline after HAL infusion (2.6 mg/kg). The other three groups received ILE 20% solution (6, 12, and 18.6 ml/kg) following HAL (2.6 mg/kg) administration. We measured blood pressure at 0, 0.5, 1, 2, 3, 4, 8, and 24 h after starting HAL administration, from left forelimb using a noninvasive method that was carried out automatically with a neonatal intensive care unit bedside monitor. ILE 20% at the dose of 18 ml/kg could return the reduced mean arterial pressure and diastolic blood pressure sooner than the other doses and normal saline. In conclusion, ILE could reverse HAL-induced hypotension same as the other lipophilic drugs. However, the clinical use of ILE for this purpose needs more evaluation to determine its exact indication and safety.
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Affiliation(s)
- Mohammad Moshiri
- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Islamic Republic of Iran
| | - Maryam Vahabzadeh
- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Islamic Republic of Iran
| | - Amir Hooshang Mohammadpour
- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Islamic Republic of Iran
| | - Hossein Hosseinzadeh
- Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Islamic Republic of Iran
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Abstract
OBJECTIVES Bolus infusion of lipid emulsion can reverse cardiac pharmacotoxicity caused by local anesthetics and other lipophilic drugs. The mechanisms of this effect are not completely elucidated. The authors test the hypothesis that lipid emulsion infusion exerts direct, positive inotropic effects. DESIGN Prospective, randomized animal study. SETTING University research laboratory. SUBJECTS Adult male Sprague-Dawley rats. INTERVENTIONS Rats anesthetized with isoflurane were given intravenous infusions (9 mL/kg over 1 min) of either 20% soybean oil-based emulsion or saline. MEASUREMENTS AND MAIN RESULTS Arterial pressure and aortic flow were measured continuously in intact animals. Lipid infusion increased aortic flow and arterial pressure faster and to a greater degree than did the same volume of saline infusion. Isolated rat hearts were studied using an isovolumetric, constant flow, nonrecirculating system. Left ventricular pressure was monitored. The infusion of lipid emulsion in the isolated heart dose-dependently increased rate pressure product, dP/dt, -dP/dt, and myocardial oxygen demand. CONCLUSIONS Lipid emulsion exerts rapid, positive inotropic and positive lusitropic effects in both intact animal and isolated heart models. We hypothesize that this inotropy and the resulting increase in tissue blood flow contribute to the phenomenon of lipid reversal of cardiac toxicity caused by drug overdose.
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Epstein SE, Hollingsworth SR. Ivermectin-induced blindness treated with intravenous lipid therapy in a dog. J Vet Emerg Crit Care (San Antonio) 2013; 23:58-62. [DOI: 10.1111/vec.12016] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2011] [Accepted: 11/25/2012] [Indexed: 11/28/2022]
Affiliation(s)
- Steven E. Epstein
- Department of Surgical and Radiological Sciences; School of Veterinary Medicine; University of California; Davis; CA
| | - Steven R. Hollingsworth
- Department of Surgical and Radiological Sciences; School of Veterinary Medicine; University of California; Davis; CA
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Kaplan A, Whelan M. The Use of IV Lipid Emulsion for Lipophilic Drug Toxicities. J Am Anim Hosp Assoc 2012; 48:221-7. [DOI: 10.5326/jaaha-ms-5761] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
IV lipid emulsion (ILE) therapy is emerging as a potential antidote for lipophilic drug toxicities in both human and veterinary medicine. ILE has already gained acceptance in human medicine as a treatment of local anesthetic systemic toxicity, but its mechanism of action, safety margins, and standardized dosing information remains undetermined at this time. Experimental and anecdotal use of ILE in the human and veterinary literature, theorized mechanisms of action, current dosing recommendations, potential adverse effects, and indications for use in human and veterinary emergency medicine are reviewed herein.
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Affiliation(s)
- Amy Kaplan
- Angell Animal Medical Center-Boston, Boston, MA
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Ozcan MS, Weinberg G. Intravenous Lipid Emulsion for the Treatment of Drug Toxicity. J Intensive Care Med 2012; 29:59-70. [DOI: 10.1177/0885066612445978] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Intravenous lipid emulsion (ILE) has emerged as a powerful antidote for the treatment of drug toxicity in the past decade. Initial efficacy of ILE was shown in the setting of local anesthetic systemic toxicity (LAST), but recent case reports suggest its consideration in a variety of other drug toxicities. In this review, we will summarize the experimental evidence as well as the clinical experience in using ILE as an antidote. Specifically, we will look at the evidence for using ILE in LAST as well as toxicity due to beta-blockers, calcium-channel blockers, and tricyclic antidepressants. We will also review the current dosing recommendations as well as potential side effects of ILE as an antidote.
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Affiliation(s)
- Mehmet S. Ozcan
- Department of Anesthesiology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
| | - Guy Weinberg
- Department of Anesthesiology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
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Clarke DL, Lee JA, Murphy LA, Reineke EL. Use of intravenous lipid emulsion to treat ivermectin toxicosis in a Border Collie. J Am Vet Med Assoc 2011; 239:1328-33. [DOI: 10.2460/javma.239.10.1328] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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French D, Smollin C, Ruan W, Wong A, Drasner K, Wu AHB. Partition constant and volume of distribution as predictors of clinical efficacy of lipid rescue for toxicological emergencies. Clin Toxicol (Phila) 2011; 49:801-9. [PMID: 21981684 DOI: 10.3109/15563650.2011.617308] [Citation(s) in RCA: 84] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
CONTEXT Lipid infusion is useful in reversing cardiac toxicity of local anesthetics, and recent reports indicate it may be useful in resuscitation from toxicity induced by a variety of other drugs. While the mechanism behind the utility of lipid rescue remains to be fully elucidated, the predominant effect appears to be creation of a "lipid sink". OBJECTIVE Determine whether the extraction of drugs by lipid, and hence the clinical efficacy of lipid rescue in toxicological emergencies can be predicted by specific drug properties. MATERIALS AND METHODS Each drug investigated was added individually to human drug-free serum. Intralipid® was added to this drug-containing serum, shaken and then incubated at 37°C. The lipid was removed by ultracentrifugation and the concentration of drug remaining in the serum was measured by high-pressure liquid chromatography. RESULTS In this in vitro model, the ability of lipid emulsion to bind a drug was largely dependent upon the drug's lipid partition constant. Additionally, using a multiple linear regression model, the prediction of binding could be improved by combining the lipid partition constant with the volume of distribution together accounting for approximately 88% of the variation in the decrease in serum drug concentration with the administration of lipid emulsion. CONCLUSIONS The lipid partition constant and volume of distribution can likely be used to predict the efficacy of lipid infusion in reversing the cardiac toxicity induced by anesthetics or other medications.
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Affiliation(s)
- Deborah French
- Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA 94107, USA.
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Fernandez AL, Lee JA, Rahilly L, Hovda L, Brutlag AG, Engebretsen K. The use of intravenous lipid emulsion as an antidote in veterinary toxicology. J Vet Emerg Crit Care (San Antonio) 2011; 21:309-20. [DOI: 10.1111/j.1476-4431.2011.00657.x] [Citation(s) in RCA: 86] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Cave G, Harvey M, Graudins A. Review article: Intravenous lipid emulsion as antidote: A summary of published human experience. Emerg Med Australas 2011; 23:123-41. [DOI: 10.1111/j.1742-6723.2011.01398.x] [Citation(s) in RCA: 86] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Les émulsions lipidiques dans le traitement des effets cardiotoxiques des médicaments lipophiles autres que les anesthésiques locaux: antidote ou traitement d’exception? ANNALES FRANCAISES DE MEDECINE D URGENCE 2011. [DOI: 10.1007/s13341-010-0004-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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Hiller DB, Di Gregorio G, Kelly K, Ripper R, Edelman L, Boumendjel R, Drasner K, Weinberg GL. Safety of high volume lipid emulsion infusion: a first approximation of LD50 in rats. Reg Anesth Pain Med 2011; 35:140-4. [PMID: 20301820 DOI: 10.1097/aap.0b013e3181c6f5aa] [Citation(s) in RCA: 54] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND Lipid infusion reverses systemic local anesthetic toxicity. The acceptable upper limit for lipid administration is unknown and has direct bearing on clinical management. We hypothesize that high volumes of lipid could have undesirable effects and sought to identify the dose required to kill 50% of the animals (LD(50)) of large volume lipid administration. METHODS Intravenous lines and electrocardiogram electrodes were placed in anesthetized, male Sprague-Dawley rats. Twenty percent lipid emulsion (20, 40, 60, or 80 mL/kg) or saline (60 or 80 mL/kg), were administered over 30 mins; lipid dosing was assigned by the Dixon "up-and-down" method. Rats were recovered and observed for 48 hrs then euthanized for histologic analysis of major organs. Three additional rats were administered 60 mL/kg lipid emulsion and euthanized at 1, 4, and 24 hrs to identify progression of organ damage. RESULTS The maximum likelihood estimate for LD(50) was 67.72 (SE, 10.69) mL/kg. Triglycerides were elevated immediately after infusion but returned to baseline by 48 hrs when laboratory abnormalities included elevated amylase, aspartate aminotransferase, and serum urea nitrogen for all lipid doses. Histologic diagnosis of myocardium, brain, pancreas, and kidneys was normal at all doses. Microscopic abnormalities in lung and liver were observed at 60 and 80 mL/kg; histopathology in the lung and liver was worse at 1 hr than at 4 and 24 hrs. CONCLUSIONS The LD(50) of rapid, high volume lipid infusion is an order of magnitude greater than doses typically used for lipid rescue in humans and supports the safety of lipid infusion at currently recommended doses for toxin-induced cardiac arrest. Lung and liver histopathology was observed at the highest infused volumes.
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Affiliation(s)
- David B Hiller
- Department of Anesthesiology, University of Illinois College of Medicine at Chicago, IL 60612, USA
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Jeng CL, Torrillo TM, Rosenblatt MA. Complications of peripheral nerve blocks. Br J Anaesth 2011; 105 Suppl 1:i97-107. [PMID: 21148659 DOI: 10.1093/bja/aeq273] [Citation(s) in RCA: 188] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Complications of peripheral nerve blocks are fortunately rare, but can be devastating for both the patient and the anaesthesiologist. This review will concentrate on current knowledge about peripheral nerve injury secondary to nerve blocks, complications from continuous peripheral nerve catheter techniques, and local anaesthetic systemic toxicity.
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Affiliation(s)
- C L Jeng
- Department of Anaesthesiology, Mount Sinai School of Medicine, New York, USA
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Toledo P. The role of lipid emulsion during advanced cardiac life support for local anesthetic toxicity. Int J Obstet Anesth 2011; 20:60-3. [DOI: 10.1016/j.ijoa.2010.09.005] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2010] [Accepted: 09/13/2010] [Indexed: 11/28/2022]
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Rothschild L, Bern S, Oswald S, Weinberg G. Intravenous lipid emulsion in clinical toxicology. Scand J Trauma Resusc Emerg Med 2010; 18:51. [PMID: 20923546 PMCID: PMC2958894 DOI: 10.1186/1757-7241-18-51] [Citation(s) in RCA: 114] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2010] [Accepted: 10/05/2010] [Indexed: 11/30/2022] Open
Abstract
Intravenous lipid emulsion is an established, effective treatment for local anesthetic-induced cardiovascular collapse. The predominant theory for its mechanism of action is that by creating an expanded, intravascular lipid phase, equilibria are established that drive the offending drug from target tissues into the newly formed 'lipid sink'. Based on this hypothesis, lipid emulsion has been considered a candidate for generic reversal of toxicity caused by overdose of any lipophilic drug. Recent case reports of successful resuscitation suggest the efficacy of lipid emulsion infusion for treating non-local anesthetic overdoses across a wide spectrum of drugs: beta blockers, calcium channel blockers, parasiticides, herbicides and several varieties of psychotropic agents. Lipid emulsion therapy is gaining acceptance in emergency rooms and other critical care settings as a possible treatment for lipophilic drug toxicity. While protocols exist for administration of lipid emulsion in the setting of local anesthetic toxicity, no optimal regimen has been established for treatment of acute non-local anesthetic poisonings. Future studies will shape the evolving recommendations for lipid emulsion in the setting of non-local anesthetic drug overdose.
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Affiliation(s)
- Leelach Rothschild
- Department of Anesthesiology, University of Illinois at Chicago, UIC Medical Center, Chicago, Illinois, USA.
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Uncles DR, Willers J, Sable N, Finn SDH. Gift of the glob goes global. Anaesthesia 2010; 65:209-10. [DOI: 10.1111/j.1365-2044.2009.06214.x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Abstract
PURPOSE OF REVIEW Laboratory studies and clinical reports have led to the acceptance of lipid emulsion as an effective treatment of local anesthetic-induced cardiac arrest. This review discusses subsequent clinical reports, relevant laboratory studies and topics for further research. RECENT FINDINGS Case reports have confirmed the efficacy of lipid resuscitation for local anesthetic systemic toxicity. Furthermore, lipid emulsion has been used with apparent success early in the spectrum of local anesthetic systemic toxicity to preempt cardiac arrest. The role of lipid emulsion has expanded to treatment of cardiac toxicity due to other lipophilic drugs. This appears to have an acceptable safety profile, although elevated amylase has been reported. Laboratory investigations in animals suggest that concomitant hypoxemia hinders resuscitation attempts, and that epinephrine and vasopressin are more likely to be associated with poor outcomes than lipid. SUMMARY Lipid emulsion infusion appears to be an effective treatment for cardiac toxicity induced by lipophilic medications. Given the difficulties of performing clinical trials, further laboratory investigation and clinical correlation are needed to better define its role in resuscitation.
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Cave G, Harvey M. Intravenous lipid emulsion as antidote beyond local anesthetic toxicity: a systematic review. Acad Emerg Med 2009; 16:815-24. [PMID: 19845549 DOI: 10.1111/j.1553-2712.2009.00499.x] [Citation(s) in RCA: 164] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
OBJECTIVES The objective was to asses the efficacy of lipid emulsion as antidotal therapy outside the accepted setting of local anesthetic toxicity. METHODS Literature was accessed through PubMed, OVID (1966-February 2009), and EMBASE (1947-February 2009) using the search terms "intravenous" AND ["fat emulsion" OR "lipid emulsion" OR "Intralipid"] AND ["toxicity" OR "resuscitation" OR "rescue" OR "arrest" OR "antidote"]. Additional author and conference publication searches were undertaken. Publications describing the use of lipid emulsion as antidotal treatment in animals or humans were included. RESULTS Fourteen animal studies, one human study, and four case reports were identified. In animal models, intravenous lipid emulsion (ILE) has resulted in amelioration of toxicity associated with cyclic antidepressants, verapamil, propranolol, and thiopentone. Administration in human cases has resulted in successful resuscitation from combined bupropion/lamotrigine-induced cardiac arrest, reversal of sertraline/quetiapine-induced coma, and amelioration of verapamil- and beta blocker-induced shock. CONCLUSIONS Management of overdose with highly lipophilic cardiotoxic medications should proceed in accord with established antidotal guidelines and early poisons center consultation. Data from animal experiments and human cases are limited, but suggestive that ILE may be helpful in potentially lethal cardiotoxicity or developed cardiac arrest attributable to such agents. Use of lipid emulsion as antidote remains a nascent field warranting further preclinical study and systematic reporting of human cases of use.
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Picard J, Harrop-Griffiths W. A commentary on the effect of lipid emulsions on pathology tests. Anaesthesia 2009; 64:1035-6. [PMID: 19686505 DOI: 10.1111/j.1365-2044.2009.06049_2.x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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