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1
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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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2
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Alshaya OA, Alhamed A, Althewaibi S, Fetyani L, Alshehri S, Alnashmi F, Alharbi S, Alrashed M, Alqifari SF, Alshaya AI. Calcium Channel Blocker Toxicity: A Practical Approach. J Multidiscip Healthc 2022; 15:1851-1862. [PMID: 36065348 PMCID: PMC9440664 DOI: 10.2147/jmdh.s374887] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Accepted: 08/17/2022] [Indexed: 11/30/2022] Open
Abstract
Calcium channel blockers (CCBs) are widely prescribed medications for various clinical indications in adults and children. They are available in both immediate and long-acting formulations and are generally classified into dihydropyridines and nondihydropyridines, with nondihydropyridines having more cardioselectivity. CCB toxicity is common given the widespread use which leads to serious adverse clinical outcomes, especially in children. Severe CCB toxicities may present with life-threatening bradycardia, hypotension, hyperglycemia, and renal insufficiency. Dihydropyridine toxicity, however, may present with reflex tachycardia instead of bradycardia. Initial patient evaluation and assessment are crucial to identify the severity of CCB toxicity and design the best management strategy. There are different strategies to overcome CCB toxicity that requires precise dosing and close monitoring in various patient populations. These strategies may include large volumes of IV fluids, calcium salts, high insulin euglycemia therapy (HIET), and vasopressors. We hereby summarize the evidence behind the management of CCB toxicity and present a practical guide for clinicians to overcome this common drug toxicity.
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Affiliation(s)
- Omar A Alshaya
- Department of Pharmacy Practice, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
- Department of Pharmaceutical Care, Ministry of National Guard-Health Affairs, Riyadh, Saudi Arabia
- King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
- Correspondence: Omar A Alshaya, Department of Pharmacy Practice, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, P.O. Box 3660, Riyadh, 11481, Saudi Arabia, Email
| | - Arwa Alhamed
- King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
- College of Nursing, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Sara Althewaibi
- Department of Pharmacy Practice, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Lolwa Fetyani
- Department of Pharmacy Practice, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Shaden Alshehri
- Department of Pharmacy Practice, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Fai Alnashmi
- Department of Pharmacy Practice, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Shmeylan Alharbi
- Department of Pharmacy Practice, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
- Department of Pharmaceutical Care, Ministry of National Guard-Health Affairs, Riyadh, Saudi Arabia
- King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
| | - Mohammed Alrashed
- Department of Pharmacy Practice, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
- Department of Pharmaceutical Care, Ministry of National Guard-Health Affairs, Riyadh, Saudi Arabia
- King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
- Pharmacy Department, Northwest Medical Center, Tucson, AZ, USA
| | - Saleh F Alqifari
- Department of Pharmacy Practice, College of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia
| | - Abdulrahman I Alshaya
- Department of Pharmacy Practice, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
- Department of Pharmaceutical Care, Ministry of National Guard-Health Affairs, Riyadh, Saudi Arabia
- King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
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3
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Havan M, Kendirli T, Özcan S, Doğan MT, Yiğit AO, Uçar T. A successful treatment with intravenous lipid emulsion therapy in a child with verapamil poisoning. Turk J Emerg Med 2021; 21:217-220. [PMID: 34849436 PMCID: PMC8593422 DOI: 10.4103/2452-2473.329626] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Revised: 05/16/2021] [Accepted: 05/17/2021] [Indexed: 11/18/2022] Open
Abstract
In recent years, intravenous lipid emulsion therapy (ILE) was used for lipophilic drug intoxications, and successful results were obtained. In the literature, there is a small number of reported cases about verapamil intoxication and ILE therapy in the pediatric age group. We used ILE therapy in a 14-year-old girl with verapamil intoxication in the 2nd h of the pediatric intensive care unit stay, before using traditional treatments such as glucagon and hyperinsulinemic euglycemia. She had resistant bradycardia and hypotension which was unresponsive to inotropic agents and a successful result was obtained after using ILE treatment. We believe our report may contribute to the early use of ILE therapy for toxicity with calcium channel blockers such as verapamil in pediatric patients.
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Affiliation(s)
- Merve Havan
- Department of Pediatric Intensive Care, School of Medicine, Ankara University, Ankara, Turkey
| | - Tanıl Kendirli
- Department of Pediatric Intensive Care, School of Medicine, Ankara University, Ankara, Turkey
| | - Serhan Özcan
- Department of Pediatric Intensive Care, School of Medicine, Ankara University, Ankara, Turkey
| | - Melih Timuçin Doğan
- Department of Pediatric Cardiology, School of Medicine, Ankara University, Ankara, Turkey
| | - Ahmet Onur Yiğit
- Department of Pediatric Intensive Care, School of Medicine, Ankara University, Ankara, Turkey
| | - Tayfun Uçar
- Department of Pediatric Cardiology, School of Medicine, Ankara University, Ankara, Turkey
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4
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Ghosh S, Cotta KB, Hande AA, Fernandes M, Mehra S. PNA-mediated efflux inhibition as a therapeutic strategy towards overcoming drug resistance in Mycobacterium smegmatis. Microb Pathog 2021; 151:104737. [PMID: 33453316 DOI: 10.1016/j.micpath.2021.104737] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Revised: 01/06/2021] [Accepted: 01/07/2021] [Indexed: 11/27/2022]
Abstract
The emergence of antibiotic-resistant strains of Mycobacterium tuberculosis and the decelerating development of new and effective antibiotics has impaired the treatment of tuberculosis (TB). Efflux pump inhibitors (EPIs) have the potential to improve the efficacy of existing anti-TB drugs although with toxicity limitations. Peptide nucleic acids (PNAs), oligonucleotide mimics, by virtue of their high nucleic acid binding specificity have the capability to overcome this drawback. We, therefore, investigated the efflux pump inhibitory properties of a PNA designed against an efflux pump of Mycobacterium smegmatis. LfrA, an efflux pump found in M. smegmatis, is majorly involved in conferring innate drug resistance to this strain and, therefore, was selected as a target for gene silencing via PNA. qRT-PCR and EtBr assays confirmed the EPI activity of the anti-lfrA PNA. On testing the effect of the anti-lfrA PNA on the bactericidal activity of a fluoroquinolone, norfloxacin, we observed that 5 μM of anti-lfrA PNA in combination with norfloxacin led to an enhanced killing of up to 2.5 log-fold against wild-type and a lab-generated multidrug resistant strain, exemplifying its potential in countering resistance. Improved efficacy was also observed against intra-macrophage mycobacteria, where the drug-PNA combination enhanced bacterial clearance by 1.3 log-fold. Further, no toxicity was observed with PNA concentrations up to 4 times higher than the efficacious anti-lfrA PNA concentration. Thus, PNA, as an adjuvant, presents a novel and viable approach to rejuvenate anti-TB therapeutics.
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Affiliation(s)
| | - Karishma Berta Cotta
- Centre for Research in Nanotechnology and Science, IIT Bombay, Powai, Mumbai, India
| | - Aniket A Hande
- Université de Pau et des Pays de l'Adour E2S UPPA, CNRS, IPREM, Pau, France
| | - Moneesha Fernandes
- Organic Chemistry Division, CSIR-National Chemical Laboratory, Pune, India
| | - Sarika Mehra
- WRCB, IIT Bombay, Powai, Mumbai, Maharashtra, India; Department of Chemical Engineering, Indian Institute of Technology Bombay, Powai, Mumbai, India.
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An X, Mei Y, Sun H, Zhang J. Detoxification effects of long-chain versus a mixture of medium- and long-chain triglyceride-based fat emulsion on propafenone poisoning. ACTA ACUST UNITED AC 2020; 53:e9491. [PMID: 32520203 PMCID: PMC7296737 DOI: 10.1590/1414-431x20209491] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2019] [Accepted: 03/27/2020] [Indexed: 11/22/2022]
Abstract
In the present study, we aimed to compare the detoxifying effects of two fat
emulsions containing either long-chain triglyceride or a mixture of medium-chain
and long-chain triglycerides in the propafenone-poisoned rat model. Rats were
randomly divided into 3 groups according to the fat emulsions used: long-chain
triglyceride-based fat emulsion (LL) group; medium-chain and long-chain
triglyceride-based fat emulsion (ML) group; normal saline (NS) group.
Propafenone was continuously pumped (velocity=70 mg/kg per h) until the mean
blood pressure dropped to 50% of basal level. Then, LL/ML fat emulsions or NS
was intravenously infused instantly with a loading-dose (1.5 mL/kg) and a
maintenance dose (0.25 mL/kg per min) for 1 h. Subsequently, the propafenone was
added to plasma (3.5 μg/mL) in vitro, mixed with three doses of
LL or ML (1, 2, or 4%). Finally, after centrifugation, the concentration of
propafenone was measured. Rats treated with LL exhibited accelerated recovery,
characterized by higher blood pressure and heart rate. Rats in both the LL and
ML groups demonstrated decreased propafenone in plasma (time-points: 15, 25, and
60 min). However, rats that received LL showed lower propafenone in myocardial
tissue at the end of detoxification treatment. Rats in the ML group had the
lowest value of pH, the minimum content of HCO3-, and the highest production of lactic acid at the end. In the
in vitro experiments, propafenone decreased more
dramatically in the LL group compared to the ML group. Long-chain triglyceride
fat emulsion had a better effect on treating propafenone poisoning in rats.
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Affiliation(s)
- Xusheng An
- Department of Emergency Medicine, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu, China.,Department of Critical Care Medicine, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huaian, Jiangsu, China
| | - Yong Mei
- Department of Emergency Medicine, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu, China
| | - Hao Sun
- Department of Emergency Medicine, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu, China
| | - Jinsong Zhang
- Department of Emergency Medicine, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu, China
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Paneta M, Waring WS. Literature review of the evidence regarding intravenous lipid administration in drug-induced cardiotoxicity. Expert Rev Clin Pharmacol 2019; 12:591-602. [PMID: 31106655 DOI: 10.1080/17512433.2019.1621163] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
Introduction: Intravenous lipid emulsion (ILE) administration is capable of reversing the acute cardiac and neurological toxicity caused by local anesthetic agents. In recent years, ILE has also been explored as a potential antidote for cardiotoxicity caused by non-anesthetic agents too. Areas covered: The potential mechanisms, safety, and efficacy of this approach are considered. Data were sought from published reports listed in PubMed and EMBASE, and abstracts of meetings of the North American Congress of Clinical Toxicology and European Association of Poisons Centres and Clinical Toxicologists. There were reports involving 298 patients where ILE has been administered for severe drug toxicity. Clinical improvement was observed in 57 of 59 patients with local anesthetic toxicity (96.6%); there were 239 patients where toxicity was due to non-anesthetic agents, and ILE apparently improved clinical outcome in 215 (72.1%). Expert opinion: Response rates were similar between ILE treated toxicity caused by lipid soluble and non-lipid soluble drugs. Potential adverse effects of ILE include interference with laboratory assays, acute pancreatitis, and adult respiratory distress syndrome, although the rate of occurrence is difficult to ascertain.
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Affiliation(s)
- Maria Paneta
- a Acute Medical Unit , York Teaching Hospital NHS Foundation Trust , York , UK
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Ok SH, Lee SH, Kim JY, Kim HJ, Bae SI, Hwang Y, Tak S, Sohn JT. Lipid emulsion inhibits the vasodilation induced by a toxic dose of amlodipine in isolated rat aortae. Int J Med Sci 2019; 16:1621-1630. [PMID: 31839750 PMCID: PMC6909803 DOI: 10.7150/ijms.38502] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2019] [Accepted: 10/29/2019] [Indexed: 12/17/2022] Open
Abstract
The goal of this study was to examine the effect of lipid emulsion on the vasodilation induced in isolated endothelium-denuded rat aortae by a toxic dose of amlodipine. We examined the effects of lipid emulsion and verapamil on amlodipine-induced vasodilation. We also examined the effects of a mixture of lipid emulsion and amlodipine, as well as the centrifuged aqueous extract (CAE) obtained by ultracentrifuging such a mixture and then removing the upper lipid layer, on amlodipine-induced vasodilation. The effect of lipid emulsion on the amlodipine concentration was examined. Lipid emulsion attenuated amlodipine-induced vasodilation in isolated aortae. Both CAE and lipid emulsion containing amlodipine inhibited amlodipine-induced vasodilation. However, there was no significant difference in amlodipine-induced vasodilation between aortae treated with CAE and those treated with lipid emulsion containing amlodipine. Verapamil inhibited amlodipine-induced vasodilation. Lipid emulsion decreased the concentration of amlodipine. Lipid emulsion attenuated the vasodilation induced by a toxic amlodipine dose in NaF-precontracted aortae. The data show that lipid emulsion inhibited the vasodilation induced by a toxic amlodipine dose in isolated rat aortae by reducing the concentration of amlodipine. Amlodipine-induced vasodilation seems to be mediated mainly by blockade of L-type calcium channels and partially by inhibition of the Rho-kinase pathway.
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Affiliation(s)
- Seong-Ho Ok
- Department of Anesthesiology and Pain Medicine, Gyeongsang National University Changwon Hospital, Changwon, 51427, Republic of Korea.,Institute of Health Sciences, Gyeongsang National University, Jinju-si, 52727, Republic of Korea
| | - Soo Hee Lee
- Department of Anesthesiology and Pain Medicine, Gyeongsang National University College of Medicine, Gyeongsang National University Hospital, 15 Jinju-daero 816 beon-gil, Jinju-si, Gyeongsangnam-do, 52727, Republic of Korea
| | - Ji-Yoon Kim
- Department of Anesthesiology and Pain Medicine, Gyeongsang National University Hospital, 15 Jinju-daero 816 beon-gil, Jinju-si, Gyeongsangnam-do, 52727, Republic of Korea
| | - Hyun-Jin Kim
- Division of Applied Life Sciences (BK21 plus), Gyeongsang National University, Gyeongsang, Republic of Korea.,Department of Food Science & Technology, Institute of Agriculture and Life Science, Gyeongsang National University, Gyeongsang, Republic of Korea
| | - Sung Il Bae
- Department of Anesthesiology and Pain Medicine, Gyeongsang National University Hospital, 15 Jinju-daero 816 beon-gil, Jinju-si, Gyeongsangnam-do, 52727, Republic of Korea
| | - Yeran Hwang
- Department of Anesthesiology and Pain Medicine, Gyeongsang National University Hospital, 15 Jinju-daero 816 beon-gil, Jinju-si, Gyeongsangnam-do, 52727, Republic of Korea
| | - Seongyeong Tak
- Department of Anesthesiology and Pain Medicine, Gyeongsang National University Hospital, 15 Jinju-daero 816 beon-gil, Jinju-si, Gyeongsangnam-do, 52727, Republic of Korea
| | - Ju-Tae Sohn
- Department of Anesthesiology and Pain Medicine, Gyeongsang National University College of Medicine, Gyeongsang National University Hospital, 15 Jinju-daero 816 beon-gil, Jinju-si, Gyeongsangnam-do, 52727, Republic of Korea.,Institute of Health Sciences, Gyeongsang National University, Jinju-si, 52727, Republic of Korea
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8
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Fadhlillah F, Patil S. Pharmacological and mechanical management of calcium channel blocker toxicity. BMJ Case Rep 2018; 2018:bcr-2018-225324. [PMID: 30150339 PMCID: PMC6119390 DOI: 10.1136/bcr-2018-225324] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/11/2018] [Indexed: 11/04/2022] Open
Abstract
Cardiovascular instability associated with calcium channel blocker toxicity comprises a small percentage of overdose presentations, yet they are associated with a high mortality rate. We detail the management of a 64-year-old man who took an intentional overdose of 840 mg nimodipine. We include the treatment he received and highlight the scarcity of evidence behind the use of gastric decontamination, calcium, glucagon, intravenous lipid emulsion, high-dose insulin therapy, sodium bicarbonate, vasopressors and methylene blue in calcium channel blocker toxicity. Additionally, the article explores the use of electrical pacing and venoarterial extracorporeal membrane oxygenation (VA-ECMO). Following successful weaning of VA-ECMO, the patient was successfully extubated but remained neurologically impaired due to hypoxic-ischaemic brain injury, critical care polyneuropathy and renal failure requiring dialysis. He has cerebral performance category 3; he has mild cognitive impairment but able to perform some activities of daily living independently and communicate his thoughts and needs. He requires no respiratory or cardiovascular support.
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Affiliation(s)
- Fiqry Fadhlillah
- Emergency Department, Chelsea and Westminster Hospital NHS Foundation Trust, London, UK
| | - Shashank Patil
- Emergency Department, Chelsea and Westminster Hospital NHS Foundation Trust, London, UK
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Ok SH, Choi MH, Shin IW, Lee SH, Kang S, Oh J, Han JY, Sohn JT. Lipid Emulsion Inhibits Apoptosis Induced by a Toxic Dose of Verapamil via the Delta-Opioid Receptor in H9c2 Rat Cardiomyoblasts. Cardiovasc Toxicol 2018; 17:344-354. [PMID: 27990618 DOI: 10.1007/s12012-016-9392-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
The goals of this study were to investigate the effects of lipid emulsion (LE) on apoptosis induced by a toxic dose of verapamil in H9c2 cells and to elucidate the associated cellular mechanism. The effects of LE alone and combined with an inhibitor on the decreases in cell counts and viability induced by verapamil and diltiazem were examined using the MTT assay. The effects of verapamil alone, combined LE and verapamil treatment, and combined inhibitor, LE and verapamil treatment on cleaved caspase-3, caspase-8 and Bax expression, were examined using Western blotting. The effects of verapamil alone and combined with LE on the number of TUNEL-positive H9c2 cells were also examined. LE attenuated the decreases in cell counts and viability induced by verapamil and diltiazem. However, the magnitude of the LE-mediated attenuation of decreased cell viability was enhanced by verapamil compared with diltiazem treatment. Naloxone, naltrindole hydrochloride, LY294002 and MK-2206 inhibited the LE-mediated attenuation of increased cleaved caspase-3 and caspase-8 expression induced by verapamil. LE attenuated the increase in the number of TUNEL-positive cell induced by verapamil. These results suggest that LE attenuates apoptosis induced by verapamil via activation of the delta-opioid receptor, phosphoinositide 3-kinase and Akt.
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Affiliation(s)
- Seong-Ho Ok
- Department of Anesthesiology and Pain Medicine, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital, 79 Gangnam-ro, Jinju-si, 52727, Republic of Korea
| | - Mun Hwan Choi
- Department of Anesthesiology and Pain Medicine, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital, 79 Gangnam-ro, Jinju-si, 52727, Republic of Korea
| | - Il-Woo Shin
- Department of Anesthesiology and Pain Medicine, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital, 79 Gangnam-ro, Jinju-si, 52727, Republic of Korea
| | - Soo Hee Lee
- Department of Anesthesiology, Gyeongsang National University Hospital, Jinju-si, 52727, Republic of Korea
| | - Sebin Kang
- Department of Anesthesiology, Gyeongsang National University Hospital, Jinju-si, 52727, Republic of Korea
| | - Jiah Oh
- Department of Anesthesiology, Gyeongsang National University Hospital, Jinju-si, 52727, Republic of Korea
| | - Jeong Yeol Han
- Department of Anesthesiology and Pain Medicine, Gyeongsang National University Changwon Hospital, Changwon, Republic of Korea
| | - Ju-Tae Sohn
- Department of Anesthesiology and Pain Medicine, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital, 79 Gangnam-ro, Jinju-si, 52727, Republic of Korea. .,Institutes of Health Sciences, Gyeongsang National University, Jinju-si, Republic of Korea.
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10
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Abstract
OBJECTIVE Overdoses with cardio-depressive medications can result in toxin-induced cardiogenic shock (TICS), a life-threatening condition characterized by severe hypotension and ineffective tissue perfusion. Vasopressors are often employed in the treatment of shock to increase heart rate and blood pressure. We sought to conduct a systematic review of the literature to evaluate the effectiveness of vasopressors in improving hemodynamic function and survival in the treatment of TICS. DATA SOURCES We searched PubMed, EMBASE, TOXLINE, and International Pharmaceutical Abstracts. STUDY SELECTION We included studies evaluating the use of vasopressors in humans or animals with TICS. We limited human study types to randomized controlled trials, clinical trials, observational studies, and case reports. DATA EXTRACTION Our search yielded 913 citations and 144 of these met our inclusion criteria. 130 were human case reports and 14 were animal studies. DATA SYNTHESIS Human case report data showed vasopressors were ineffective more often than they were partially or fully effective. In the majority of animal studies, vasopressor treatment failed to improve hemodynamic parameters and resulted in decreased survival. CONCLUSIONS Human case reports and controlled animal experiments lead to different conclusions about vasopressors in TICS. Most animal studies indicate that vasopressors impair hemodynamic function and increase mortality. In contrast, human case reports suggest that vasopressors are often ineffective but not necessarily harmful.
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Affiliation(s)
- Cassandra A Skoog
- a College of Pharmacy, University of Minnesota , Minneapolis , MN , USA
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11
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A cohort study of unstable overdose patients treated with intravenous lipid emulsion therapy. CAN J EMERG MED 2016; 19:256-264. [DOI: 10.1017/cem.2016.396] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
AbstractObjectivesIntravenous lipid emulsion (ILE) has been used increasingly over the last decade for a range of drug overdoses. Although the use of ILE in local anesthetic toxicity (LAST) is well established, the hemodynamic effectiveness of ILE in non-LAST poisonings is still unclear. Thus, the primary objective of this study was to examine a cohort of poisoned patients in whom ILE was administered.MethodsConsecutive patients were identified by calls to a regional poison center from May 1, 2012 to May 30, 2014. Patients were enrolled if they ingested a drug, developed hemodynamic instability, failed conventional treatment, and received ILE therapy. Data were collected by medical record review. The primary outcome was the change in mean arterial pressure (MAP) in the first hour after ILE administration. Secondary outcomes included survival, length of stay, and the effect of drug class on patient outcome.ResultsThirty-six patients were enrolled. Agents ingested included calcium channel blockers and beta blockers (10/36, 27.8%), tricyclic antidepressants (5/36, 13.9%), bupropion (3/36, 8.3%), and antiepileptic agents (1/36, 2.8%). Seventeen patients (47.2%) ingested multiple agents. Twenty-five patients survived (69.0%). Overall, MAP increased by 13.79 mm Hg (95% CI 1.43–26.15); this did not meet oura prioridefinition of clinical significance.ConclusionsOur study did not find a clinically important improvement in MAP after ILE administration. Until future research is done to more definitively study its efficacy, ILE should remain a potential treatment option for hemodynamically unstable overdose patients only after conventional therapy has failed.
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12
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O’Connor J, Wilson SS. Intravenous Lipid Emulsion for Management of Systemic Toxic Effects of Drugs. AACN Adv Crit Care 2016; 27:394-404. [DOI: 10.4037/aacnacc2016570] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022]
Abstract
The incidence of toxic effects of drugs leading to emergency department visits has increased in the United States in the past several years. Most of these patients can be adequately managed by supportive care alone. However, pharmacological antidotes may be necessary, particularly in patients with hemodynamic instability. In severe cases refractory to conventional antidote therapy, rescue therapy with intravenous lipid emulsion (ILE) may be necessary. Traditionally, ILE has been used as an antidote of choice in treating toxic effects of local anesthetics. But data continue to emerge on the successful use of ILE to treat overdoses of drugs other than local anesthetics, particularly lipophilic medications. The recommended ILE dose is a 1.5 mL/kg bolus followed by infusion of 15 mL/kg per hour, with repeat dosing permissible for continued hemodynamic instability. Use of ILE should be considered early as a rescue therapy in the settings of lipophilic medication overdoses when cardiovascular compromise or cardiac arrest is present.
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Affiliation(s)
- Jaclyn O’Connor
- Jaclyn O’Connor is Clinical Pharmacy Specialist, Emergency Medicine, Department of Pharmacy Services, Martin Memorial Hospital, Stuart, Florida. Suprat Saely Wilson is Pharmacy Coordinator, Emergency Medicine Services, Detroit Receiving Hospital, Department of Pharmacy, 1B-UHC, 4201 St Antoine Blvd, Detroit, MI 48201
| | - Suprat Saely Wilson
- Jaclyn O’Connor is Clinical Pharmacy Specialist, Emergency Medicine, Department of Pharmacy Services, Martin Memorial Hospital, Stuart, Florida. Suprat Saely Wilson is Pharmacy Coordinator, Emergency Medicine Services, Detroit Receiving Hospital, Department of Pharmacy, 1B-UHC, 4201 St Antoine Blvd, Detroit, MI 48201
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14
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Murphy CM, Williams C, Quinn ME, Nicholson B, Shoe T, Beuhler MC, Kerns WP. Pilot Trial of Intravenous Lipid Emulsion Treatment for Severe Nifedipine-Induced Shock. J Med Toxicol 2016; 12:380-385. [PMID: 27501853 DOI: 10.1007/s13181-016-0572-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2016] [Revised: 07/02/2016] [Accepted: 07/06/2016] [Indexed: 11/24/2022] Open
Abstract
Animal studies and human case reports show promise in using lipid rescue to treat refractory calcium channel antagonist toxicity. However, the majority of research and clinical experience has focused on non-dihydropyridine agents. Thus, we sought to investigate the value of lipid emulsion (ILE) therapy for dihydropyridine-induced shock. This IACUC-approved study utilized seven swine that were sedated with alpha-chloralose, mechanically ventilated, and instrumented for drug delivery and hemodynamic measures. After stabilization and basal measures, nifedipine (0.01875 mg/kg/min) was infused until imminent cardiac arrest (seizure, end tidal CO2 < 10 mmHg, bradydysrhythmia, or pulseless electrical activity). Animals then received a 7 mL/kg bolus of 20% lipid emulsion via central catheter. Lipid circulation was visually confirmed by the presence of fat in peripheral arterial blood. Hemodynamics were continuously monitored until 10 min after lipid bolus. Surviving animals were euthanized. Pre- and post-lipid treatment parameters were analyzed using the Wilxocon signed rank test (p <0.05 significant). Nifedipine toxicity was characterized by vasodilatory hypotension, impaired vascular contractility, and tachycardia with terminal bradycardia. The median time to imminent cardiac arrest from start of nifedipine infusion was 218 min. Lipid treatment did not improve hemodynamics or restore circulation in any animal. There was no benefit from lipid rescue in this model of nifedipine toxicity. Further study of ILE for dihydropyridine toxicity is warranted but initial animal model results are not promising.
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Affiliation(s)
- Christine M Murphy
- Department of Emergency Medicine, Division of Medical Toxicology, Carolinas Medical Center, Charlotte, NC, USA.
| | - Cliff Williams
- Department of Emergency Medicine, Division of Research, Carolinas Medical Center, Charlotte, NC, USA
| | - Michael E Quinn
- Department of Comparative Medicine, Carolinas Medical Center, Charlotte, NC, USA
| | - Brian Nicholson
- Department of Comparative Medicine, Carolinas Medical Center, Charlotte, NC, USA
| | - Thomas Shoe
- United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, MD, USA
| | | | - William P Kerns
- Department of Emergency Medicine, Division of Medical Toxicology, Carolinas Medical Center, Charlotte, NC, USA
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15
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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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Insulin Signaling in Bupivacaine-induced Cardiac Toxicity: Sensitization during Recovery and Potentiation by Lipid Emulsion. Anesthesiology 2016; 124:428-42. [PMID: 26646023 DOI: 10.1097/aln.0000000000000974] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND The impact of local anesthetics on the regulation of glucose homeostasis by protein kinase B (Akt) and 5'-adenosine monophosphate-activated protein kinase (AMPK) is unclear but important because of the implications for both local anesthetic toxicity and its reversal by IV lipid emulsion (ILE). METHODS Sprague-Dawley rats received 10 mg/kg bupivacaine over 20 s followed by nothing or 10 ml/kg ILE (or ILE without bupivacaine). At key time points, heart and kidney were excised. Glycogen content and phosphorylation levels of Akt, p70 s6 kinase, s6, insulin receptor substrate-1, glycogen synthase kinase-3β, AMPK, acetyl-CoA carboxylase, and tuberous sclerosis 2 were quantified. Three animals received Wortmannin to irreversibly inhibit phosphoinositide-3-kinase (Pi3k) signaling. Isolated heart studies were conducted with bupivacaine and LY294002-a reversible Pi3K inhibitor. RESULTS Bupivacaine cardiotoxicity rapidly dephosphorylated Akt at S473 to 63 ± 5% of baseline and phosphorylated AMPK to 151 ± 19%. AMPK activation inhibited targets downstream of mammalian target of rapamycin complex 1 via tuberous sclerosis 2. Feedback dephosphorylation of IRS1 to 31 ± 8% of baseline sensitized Akt signaling in hearts resulting in hyperphosphorylation of Akt at T308 and glycogen synthase kinase-3β to 390 ± 64% and 293 ± 50% of baseline, respectively. Glycogen accumulated to 142 ± 7% of baseline. Irreversible inhibition of Pi3k upstream of Akt exacerbated bupivacaine cardiotoxicity, whereas pretreating with a reversible inhibitor delayed the onset of toxicity. ILE rapidly phosphorylated Akt at S473 and T308 to 150 ± 23% and 167 ± 10% of baseline, respectively, but did not interfere with AMPK or targets of mammalian target of rapamycin complex 1. CONCLUSION Glucose handling by Akt and AMPK is integral to recovery from bupivacaine cardiotoxicity and modulation of these pathways by ILE contributes to lipid resuscitation.
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17
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Xanthos T, Psichalakis N, Russell D, Papalois A, Koutsovasilis A, Athanasopoulos D, Gkiokas G, Chalkias A, Iacovidou N. Intralipid™ administration attenuates the hypotensive effects of acute intravenous amiodarone overdose in a swine model. Am J Emerg Med 2016; 34:1389-93. [PMID: 27131633 DOI: 10.1016/j.ajem.2016.04.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2016] [Revised: 03/31/2016] [Accepted: 04/01/2016] [Indexed: 10/22/2022] Open
Abstract
PURPOSE To investigate whether a lipid emulsion could counteract the hypotensive effects of amiodarone overdose after an acute intravenous administration and improve 4 h survival in an established model of swine cardiovascular research. METHODS Twenty pigs were intubated and instrumented to measure aortic pressures and central venous pressures (CVP). After allowing the animals to stabilize for 60 minutes, amiodarone overdose (1 mg/kg/min) was initiated for a maximum of 20 minutes. Afterwards, the animals were randomized into 2 groups. Group A (n = 10) received 0.9% Normal Saline (NS) and Group B (n = 10) received 20% Intralipid® (ILE). A bolus dose of 2 ml/kg in over 2 min time was initially administered in both groups followed by a 45 min infusion (0.2 ml/kg/min) of either NS or ILE. RESULTS All animals survived the overdose and all animals survived the monitoring period of 4 hours. Systolic aortic pressure (SpthAorta) (6.90 vs 14.10 mmHg, P = .006) and mean arterial pressure (MAP) (6.10 vs 14.90 mmHg, P = .001) were higher in the ILE group 2 min after the bolus ILE infusion. This difference was maintained for 15 min after ILE infusion for both SpthAorta (7.85 vs 13.15 mmHg, P = .044) and MAP (7.85 vs 13.15 mmHg, P = .042). Animals that received ILE had higher CVP (11.6 vs 15.7 mmHg, P = .046), an effect which was attenuated 2 and 4 hours post administration. Animals receiving ILE were more acidotic (7.21 vs 7.38, P = .048) in the monitoring period compared to animals receiving NS. CONCLUSIONS Intralipid attenuated the hypotensive effects of amiodarone toxicity for a period of 15 minutes compared to animals receiving NS.
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Affiliation(s)
- Theodoros Xanthos
- European University Cyprus, School of Medicine, Nicosia, Cyprus; Hellenic Society of Cardiopulmonary Resuscitation, Athens, Greece
| | | | | | | | | | | | - Georgios Gkiokas
- National and Kapodistrian University of Athens, Medical School, Aretaieion University Hospital, 2nd Department of Surgery
| | - Athanasios Chalkias
- Hellenic Society of Cardiopulmonary Resuscitation, Athens, Greece; National and Kapodistrian University of Athens, Medical School, Postgraduate Study Program (MSc) "Cardiopulmonary Resuscitation", Athens, Greece.
| | - Nicoletta Iacovidou
- Hellenic Society of Cardiopulmonary Resuscitation, Athens, Greece; National and Kapodistrian University of Athens, Medical School, Postgraduate Study Program (MSc) "Cardiopulmonary Resuscitation", Athens, Greece
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18
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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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19
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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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20
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Graudins A, Lee HM, Druda D. Calcium channel antagonist and beta-blocker overdose: antidotes and adjunct therapies. Br J Clin Pharmacol 2015; 81:453-61. [PMID: 26344579 DOI: 10.1111/bcp.12763] [Citation(s) in RCA: 76] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2015] [Revised: 08/25/2015] [Accepted: 08/26/2015] [Indexed: 12/26/2022] Open
Abstract
Management of cardiovascular instability resulting from calcium channel antagonist (CCB) or beta-adrenergic receptor antagonist (BB) poisoning follows similar principles. Significant myocardial depression, bradycardia and hypotension result in both cases. CCBs can also produce vasodilatory shock. Additionally, CCBs, such as verapamil and diltiazem, are commonly ingested in sustained-release formulations. This can also be the case for some BBs. Peak toxicity can be delayed by several hours. Provision of early gastrointestinal decontamination with activated charcoal and whole-bowel irrigation might mitigate this. Treatment of shock requires a multimodal approach to inotropic therapy that can be guided by echocardiographic or invasive haemodynamic assessment of myocardial function. High-dose insulin euglycaemia is commonly recommended as a first-line treatment in these poisonings, to improve myocardial contractility, and should be instituted early when myocardial dysfunction is suspected. Catecholamine infusions are complementary to this therapy for both inotropic and chronotropic support. Catecholamine vasopressors and vasopressin are used in the treatment of vasodilatory shock. Optimizing serum calcium concentration can confer some benefit to improving myocardial function and vascular tone after CCB poisoning. High-dose glucagon infusions have provided moderate chronotropic and inotropic benefits in BB poisoning. Phosphodiesterase inhibitors and levosimendan have positive inotropic effects but also produce peripheral vasodilation, which can limit blood pressure improvement. In cases of severe cardiogenic shock and/or cardiac arrest post-poisoning, extracorporeal cardiac assist devices have resulted in successful recovery. Other treatments used in refractory hypotension include intravenous lipid emulsion for lipophilic CCB and BB poisoning and methylene blue for refractory vasodilatory shock.
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Affiliation(s)
- Andis Graudins
- Monash Health Clinical Toxicology and Addiction Medicine Service, Monash Health, Dandenong Hospital, David Street, Dandenong, VIC, 3175, Australia.,Monash Emergency Program, Monash Health, Dandenong Hospital, David Street, Dandenong, VIC, 3175, Australia.,School of Clinical Sciences at Monash Health, Faculty of Medicine, Nursing and Health Sciences, Monash University, Monash Medical Centre, Clayton, VIC, 3168, Australia
| | - Hwee Min Lee
- Monash Health Clinical Toxicology and Addiction Medicine Service, Monash Health, Dandenong Hospital, David Street, Dandenong, VIC, 3175, Australia.,Monash Emergency Program, Monash Health, Dandenong Hospital, David Street, Dandenong, VIC, 3175, Australia.,School of Clinical Sciences at Monash Health, Faculty of Medicine, Nursing and Health Sciences, Monash University, Monash Medical Centre, Clayton, VIC, 3168, Australia
| | - Dino Druda
- Monash Health Clinical Toxicology and Addiction Medicine Service, Monash Health, Dandenong Hospital, David Street, Dandenong, VIC, 3175, Australia.,Monash Emergency Program, Monash Health, Dandenong Hospital, David Street, Dandenong, VIC, 3175, Australia
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21
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Fettiplace MR, Weinberg G. Past, Present, and Future of Lipid Resuscitation Therapy. JPEN J Parenter Enteral Nutr 2015; 39:72S-83S. [DOI: 10.1177/0148607115595979] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2015] [Accepted: 06/22/2015] [Indexed: 01/18/2023]
Affiliation(s)
- Michael R. Fettiplace
- Department of Anesthesiology, University of Illinois College of Medicine, Chicago, Illinois
- Research & Development Service, Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois
- Neuroscience Program, University of Illinois at Chicago, Chicago, Illinois
| | - Guy Weinberg
- Department of Anesthesiology, University of Illinois College of Medicine, Chicago, Illinois
- Research & Development Service, Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois
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22
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23
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Cao D, Heard K, Foran M, Koyfman A. Intravenous Lipid Emulsion in the Emergency Department: A Systematic Review of Recent Literature. J Emerg Med 2015; 48:387-97. [DOI: 10.1016/j.jemermed.2014.10.009] [Citation(s) in RCA: 69] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2014] [Revised: 10/01/2014] [Accepted: 10/12/2014] [Indexed: 10/24/2022]
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St-Onge M, Dubé PA, Gosselin S, Guimont C, Godwin J, Archambault PM, Chauny JM, Frenette AJ, Darveau M, Le Sage N, Poitras J, Provencher J, Juurlink DN, Blais R. Treatment for calcium channel blocker poisoning: a systematic review. Clin Toxicol (Phila) 2014; 52:926-44. [PMID: 25283255 PMCID: PMC4245158 DOI: 10.3109/15563650.2014.965827] [Citation(s) in RCA: 104] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2013] [Accepted: 09/10/2014] [Indexed: 11/25/2022]
Abstract
CONTEXT Calcium channel blocker poisoning is a common and sometimes life-threatening ingestion. OBJECTIVE To evaluate the reported effects of treatments for calcium channel blocker poisoning. The primary outcomes of interest were mortality and hemodynamic parameters. The secondary outcomes included length of stay in hospital, length of stay in intensive care unit, duration of vasopressor use, functional outcomes, and serum calcium channel blocker concentrations. METHODS Medline/Ovid, PubMed, EMBASE, Cochrane Library, TOXLINE, International pharmaceutical abstracts, Google Scholar, and the gray literature up to December 31, 2013 were searched without time restriction to identify all types of studies that examined effects of various treatments for calcium channel blocker poisoning for the outcomes of interest. The search strategy included the following Keywords: [calcium channel blockers OR calcium channel antagonist OR calcium channel blocking agent OR (amlodipine or bencyclane or bepridil or cinnarizine or felodipine or fendiline or flunarizine or gallopamil or isradipine or lidoflazine or mibefradil or nicardipine or nifedipine or nimodipine or nisoldipine or nitrendipine or prenylamine or verapamil or diltiazem)] AND [overdose OR medication errors OR poisoning OR intoxication OR toxicity OR adverse effect]. Two reviewers independently selected studies and a group of reviewers abstracted all relevant data using a pilot-tested form. A second group analyzed the risk of bias and overall quality using the STROBE (STrengthening the Reporting of OBservational studies in Epidemiology) checklist and the Thomas tool for observational studies, the Institute of Health Economics tool for Quality of Case Series, the ARRIVE (Animal Research: Reporting In Vivo Experiments) guidelines, and the modified NRCNA (National Research Council for the National Academies) list for animal studies. Qualitative synthesis was used to summarize the evidence. Of 15,577 citations identified in the initial search, 216 were selected for analysis, including 117 case reports. The kappa on the quality analysis tools was greater than 0.80 for all study types. RESULTS The only observational study in humans examined high-dose insulin and extracorporeal life support. The risk of bias across studies was high for all interventions and moderate to high for extracorporeal life support. High-dose insulin. High-dose insulin (bolus of 1 unit/kg followed by an infusion of 0.5-2.0 units/kg/h) was associated with improved hemodynamic parameters and lower mortality, at the risks of hypoglycemia and hypokalemia (low quality of evidence). Extracorporeal life support. Extracorporeal life support was associated with improved survival in patients with severe shock or cardiac arrest at the cost of limb ischemia, thrombosis, and bleeding (low quality of evidence). Calcium, dopamine, and norepinephrine. These agents improved hemodynamic parameters and survival without documented severe side effects (very low quality of evidence). 4-Aminopyridine. Use of 4-aminopyridine was associated with improved hemodynamic parameters and survival in animal studies, at the risk of seizures. Lipid emulsion therapy. Lipid emulsion was associated with improved hemodynamic parameters and survival in animal models of intravenous verapamil poisoning, but not in models of oral verapamil poisoning. Other studies. Studies on decontamination, atropine, glucagon, pacemakers, levosimendan, and plasma exchange reported variable results, and the methodologies used limit their interpretation. No trial was documented in humans poisoned with calcium channel blockers for Bay K8644, CGP 28932, digoxin, cyclodextrin, liposomes, bicarbonate, carnitine, fructose 1,6-diphosphate, PK 11195, or triiodothyronine. Case reports were only found for charcoal hemoperfusion, dialysis, intra-aortic balloon pump, Impella device and methylene blue. CONCLUSIONS The treatment for calcium channel blocker poisoning is supported by low-quality evidence drawn from a heterogeneous and heavily biased literature. High-dose insulin and extracorporeal life support were the interventions supported by the strongest evidence, although the evidence is of low quality.
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Affiliation(s)
- M St-Onge
- Ontario and Manitoba Poison Centre , Toronto, ON , Canada
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Martin C, Gonzalez H, Ruiz S, Ribes D, Franchitto N, Minville V. Acute respiratory distress syndrome following verapamil overdose treated with intravenous lipid emulsion: A rare life-threatening complication. ACTA ACUST UNITED AC 2014; 33:e101-2. [DOI: 10.1016/j.annfar.2014.05.013] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [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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27
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Successful resuscitation of a patient with continuous venovenous hemodiafiltration following intoxication from verapamil and trandolapril. Kaohsiung J Med Sci 2014; 30:321-2. [DOI: 10.1016/j.kjms.2013.04.008] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2013] [Accepted: 04/25/2013] [Indexed: 11/19/2022] Open
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28
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Garrett R, Kaura V, Kathawaroo S. Intravenous lipid emulsion therapy – The fat of the land. TRENDS IN ANAESTHESIA AND CRITICAL CARE 2013. [DOI: 10.1016/j.tacc.2013.04.001] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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29
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Bologa C, Lionte C, Coman A, Sorodoc L. Lipid emulsion therapy in cardiodepressive syndrome after diltiazem overdose—case report. Am J Emerg Med 2013; 31:1154.e3-4. [DOI: 10.1016/j.ajem.2013.03.010] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2013] [Accepted: 03/06/2013] [Indexed: 11/27/2022] Open
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Ozbilgin S, Ozbilgin M, Kucukoztas B, Kamaci G, Unek T, Yurtlu BS, Güneli ME, Hanci V, Gunerli A. Evaluation of the effectiveness of sugammadex for verapamil intoxication. Basic Clin Pharmacol Toxicol 2013; 113:280-5. [PMID: 23724791 DOI: 10.1111/bcpt.12089] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2013] [Accepted: 05/15/2013] [Indexed: 12/17/2022]
Abstract
Previous studies have shown that medications from the cyclodextrin family bind to verapamil. The aim of our study was to determine whether sugammadex could bind to verapamil and prevent the cardiovascular toxicity of that drug. Twenty-eight sedated Wistar rats were infused with verapamil at 37.5 mg/kg/h. Five minutes after the start of infusion, the animals were treated with a bolus of either 16 mg/kg, 100 mg/kg or 1000 mg/kg sugammadex. The control group was treated with an infusion without sugammadex. The heart rate and respiratory rate were monitored, and an electrocardiogram was recorded. The primary end-point was the time to asystole. The verapamil infusion continued until the animals arrested. The asystole time for the S16 group was significantly longer compared to those for the control and S1000 groups (p < 0.05). The asystole time for the S1000 group was significantly shorter than those for all of the other groups (p < 0.05). Reflecting these data, there was a near doubling of the mean lethal dose of verapamil from 13.57 mg/kg (S.D. ±8.1) in the saline-treated rats to 22.42 mg/kg (S.D. ±9.9) in the sugammadex 16 group (p < 0.05). However, for the sugammadex 1000 group, the mean lethal dose was found to be 6.28 ± 1.11 mg/kg. This dose is significantly lower than those for all of the other groups (p < 0.05). We found that treatment with 16 mg/kg sugammadex delayed verapamil cardiotoxicity in rats. However, 1000 mg/kg sugammadex accelerated verapamil cardiotoxicity in rats. Further studies must be conducted to investigate the interaction between verapamil and sugammadex.
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Affiliation(s)
- Sule Ozbilgin
- Department of Anesthesiology and Reanimation, School of Medicine, Dokuz Eylul University, Izmir, Turkey
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Perza MN, Schneider LA, Rosini JM. Suspected Tricyclic Antidepressant Overdose Successfully Treated With Lipids. J Emerg Nurs 2013; 39:296-8. [DOI: 10.1016/j.jen.2013.01.010] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
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Waring WS. Intravenous lipid administration for drug-induced toxicity: a critical review of the existing data. Expert Rev Clin Pharmacol 2013; 5:437-44. [PMID: 22943123 DOI: 10.1586/ecp.12.27] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Following the discovery that administration of intravenous lipid emulsion (ILE) may reverse the cardiac and neurological toxicity of certain local anesthetic agents, ILE's potential role has recently been explored in the setting of toxicity attributed to a variety of different drugs. The potential mechanisms, safety and efficacy of this approach are considered in this review. Data are reviewed from 76 published reports involving ILE administration for severe drug toxicity, including 55 where toxicity was due to nonanesthetic agents. ILE was reported to exert a positive therapeutic effect in only a proportion of the reported cases, with greatest evidence of efficacy concerning local anesthetic agents. Administration has typically involved bolus administration followed by continuous maintenance infusion, and a number of different mechanisms are proposed, from preferential partitioning of the drug from cardiac tissue to the circulating lipid fraction and direct inotropic effects related to carnitine pathways and fatty acid oxidative metabolism. No major adverse effects have been encountered, but too few data exist to adequately address the safety profile of ILE.
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Affiliation(s)
- W Stephen Waring
- Acute Medical Unit, York Teaching Hospital NHS Foundation Trust, York, UK.
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33
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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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Toxic bradycardias in the critically ill poisoned patient. Emerg Med Int 2012; 2012:852051. [PMID: 22545217 PMCID: PMC3321542 DOI: 10.1155/2012/852051] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2011] [Revised: 11/15/2011] [Accepted: 01/18/2012] [Indexed: 11/17/2022] Open
Abstract
Cardiovascular drugs are a common cause of poisoning, and toxic bradycardias can be refractory to standard ACLS protocols. It is important to consider appropriate antidotes and adjunctive therapies in the care of the poisoned patient in order to maximize outcomes. While rigorous studies are lacking in regards to treatment of toxic bradycardias, there are small studies and case reports to help guide clinicians' choices in caring for the poisoned patient. Antidotes, pressor support, and extracorporeal therapy are some of the treatment options for the care of these patients. It is important to make informed therapeutic decisions with an understanding of the available evidence, and consultation with a toxicologist and/or regional Poison Control Center should be considered early in the course of treatment.
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