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循環器薬大量投与時のマネージメント

著者: 森田英晃 大阪医科薬科大学 循環器内科

監修: 今井靖 自治医科大学 薬理学講座臨床薬理学部門・内科学講座循環器内科学部門

著者校正/監修レビュー済:2021/06/23
参考ガイドライン:
  1. 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2010;122:S829–S861
  1. 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2015;132:S315–S367
  1. Experts Consensus Recommendations for the Management of Calcium Channel Blocker Poisoning in Adults. Crit Care Med. 2017 Mar;45(3):e306-e315.
  1. Treatment for beta-blocker poisoning: a systematic review. Clin Toxicol (Phila). 2020 Apr 20;1-41.
  1. 日本中毒学会急性中毒の標準治療

概要・推奨   

  1. 本稿に関してはAHAによる心肺蘇生と救急心血管治療のためのガイドラインからの情報を中心に記載した。薬物中毒症例におけるRCTは困難であり、レビュー、エキスパートコンセンサス、症例からの勧告であり、エビデンスレベルは低いものとなっている。
  1. 2015年に改定されたAmerican Heart Association(AHA)による心肺蘇生ガイドラインで、標準的な蘇生処置が奏功しないその他の薬物中毒を呈する患者に対し、静注用脂肪乳剤を投与することは妥当としてよいと記載された[1]
  1. 中毒症状の有無に関わらず、入院のうえ厳重なモニター管理を行う。中毒症状を認めれば、心機能評価の上、集中治療室での血行動態管理を行う。
  1. 十分な気道確保を行ったのち、消化管除染として、活性炭投与を行う。胃洗浄・腸洗浄はルーチン処置としては推奨されない。催吐、下剤は行わない[2][3][4][5]
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲 覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご 契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
森田英晃 : 特に申告事項無し[2021年]
監修:今井靖 : 講演料(第一三共株式会社)[2021年]

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 原因不明の低血圧、徐脈では、急性薬物中毒の可能性を考慮する。
  1. 可能な限り、患者本人、患者家族、救急隊より服用した薬剤の種類、摂取量、摂取時間などを情報収集する。
  1. 消化管除染として、吸収阻害のため活性炭投与を考慮する。薬物服用から1時間以内であれば、十分な気道確保の上、合併症に注意し胃洗浄が有効なことがある。
  1. 薬物の意図的な大量摂取の場合には、精神科医師へのコンサルトを行う。

これより先の閲覧には個人契約のトライアルまたはお申込みが必要です。

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文献 

著者: Robert W Neumar, Michael Shuster, Clifton W Callaway, Lana M Gent, Dianne L Atkins, Farhan Bhanji, Steven C Brooks, Allan R de Caen, Michael W Donnino, Jose Maria E Ferrer, Monica E Kleinman, Steven L Kronick, Eric J Lavonas, Mark S Link, Mary E Mancini, Laurie J Morrison, Robert E O'Connor, Ricardo A Samson, Steven M Schexnayder, Eunice M Singletary, Elizabeth H Sinz, Andrew H Travers, Myra H Wyckoff, Mary Fran Hazinski
雑誌名: Circulation. 2015 Nov 3;132(18 Suppl 2):S315-67. doi: 10.1161/CIR.0000000000000252.
Abstract/Text
PMID 26472989  Circulation. 2015 Nov 3;132(18 Suppl 2):S315-67. doi: 1・・・
著者: B E Benson, K Hoppu, W G Troutman, R Bedry, A Erdman, J Höjer, B Mégarbane, R Thanacoody, E M Caravati, American Academy of Clinical Toxicology, European Association of Poisons Centres and Clinical Toxicologists
雑誌名: Clin Toxicol (Phila). 2013 Mar;51(3):140-6. doi: 10.3109/15563650.2013.770154. Epub 2013 Feb 18.
Abstract/Text CONTEXT: The first update of the 1997 gastric lavage position paper was published by the American Academy of Clinical Toxicology and the European Association of Poisons Centres and Clinical Toxicologists in 2004. This second update summarizes the 2004 content and reviews new data.
METHODS: A systematic review of the literature from January 2003 to March 2011 yielded few studies directly addressing the utility of gastric lavage in the treatment of poisoned patients.
RESULTS: Sixty-nine new papers were reviewed. Recent publications continue to show that gastric lavage may be associated with serious complications. A few clinical studies have recently been published showing beneficial outcomes, however, all have significant methodological flaws.
CONCLUSIONS: At present there is no evidence showing that gastric lavage should be used routinely in the management of poisonings. Further, the evidence supporting gastric lavage as a beneficial treatment in special situations is weak, as is the evidence to exclude benefit in all cases. Gastric lavage should not be performed routinely, if at all, for the treatment of poisoned patients. In the rare instances in which gastric lavage is indicated, it should only be performed by individuals with proper training and expertise.

PMID 23418938  Clin Toxicol (Phila). 2013 Mar;51(3):140-6. doi: 10.310・・・
著者: P A Chyka, D Seger, E P Krenzelok, J A Vale, American Academy of Clinical Toxicology, European Association of Poisons Centres and Clinical Toxicologists
雑誌名: Clin Toxicol (Phila). 2005;43(2):61-87. doi: 10.1081/clt-200051867.
Abstract/Text Single-dose activated charcoal therapy involves the oral administration or instillation by nasogastric tube of an aqueous preparation of activated charcoal after the ingestion of a poison. Volunteer studies demonstrate that the effectiveness of activated charcoal decreases with time. Data using at least 50 g of activated charcoal, showed a mean reduction in absorption of 47.3%, 40.07%, 16.5% and 21.13%, when activated charcoal was administered at 30 minutes, 60 minutes, 120 minutes and 180 minutes, respectively, after dosing. There are no satisfactorily designed clinical studies assessing benefit from single-dose activated charcoal to guide the use of this therapy. Single-dose activated charcoal should not be administered routinely in the management of poisoned patients. Based on volunteer studies, the administration of activated charcoal may be considered if a patient has ingested a potentially toxic amount of a poison (which is known to be adsorbed to charcoal) up to one hour previously. Although volunteer studies demonstrate that the reduction of drug absorption decreases to values of questionable clinical importance when charcoal is administered at times greater than one hour, the potential for benefit after one hour cannot be excluded. There is no evidence that the administration of activated charcoal improves clinical outcome. Unless a patient has an intact or protected airway, the administration of charcoal is contraindicated. A review of the literature since the preparation of the 1997 Single-dose Activated Charcoal Position Statement revealed no new evidence that would require a revision of the conclusions of the Statement.

PMID 15822758  Clin Toxicol (Phila). 2005;43(2):61-87. doi: 10.1081/cl・・・
著者:
雑誌名: J Toxicol Clin Toxicol. 1999;37(6):731-51. doi: 10.1081/clt-100102451.
Abstract/Text In preparing this Position Statement, all relevant scientific literature was identified and reviewed critically by acknowledged experts using agreed criteria. Well-conducted clinical and experimental studies were given precedence over anecdotal case reports and abstracts were not usually considered. A draft Position Statement was then produced and subjected to detailed peer review by an international group of clinical toxicologists chosen by the American Academy of Clinical Toxicology and the European Association of Poisons Centres and Clinical Toxicologists. The Position Statement went through multiple drafts before being approved by the Boards of the two societies. The Position Statement includes a summary statement for ease of use and is supported by detailed documentation which describes the scientific evidence on which the Statement is based. Although many studies in animals and volunteers have demonstrated that multiple-dose activated charcoal increases drug elimination significantly, this therapy has not yet been shown in a controlled study in poisoned patients to reduce morbidity and mortality. Further studies are required to establish its role and the optimal dosage regimen of charcoal to be administered. Based on experimental and clinical studies, multiple-dose activated charcoal should be considered only if a patient has ingested a life-threatening amount of carbamazepine, dapsone, phenobarbital, quinine, or theophylline. With all of these drugs there are data to confirm enhanced elimination, though no controlled studies have demonstrated clinical benefit. Although volunteer studies have demonstrated that multiple-dose activated charcoal increases the elimination of amitriptyline, dextropropoxyphene, digitoxin, digoxin, disopyramide, nadolol, phenylbutazone, phenytoin, piroxicam, and sotalol, there are insufficient clinical data to support or exclude the use of this therapy. The use of multiple-dose charcoal in salicylate poisoning is controversial. One animal study and 2 of 4 volunteer studies did not demonstrate increased salicylate clearance with multiple-dose charcoal therapy. Data in poisoned patients are insufficient presently to recommend the use of multiple-dose charcoal therapy for salicylate poisoning. Multiple-dose activated charcoal did not increase the elimination of astemizole, chlorpropamide, doxepin, imipramine, meprobamate, methotrexate, phenytoin, sodium valproate, tobramycin, and vancomycin in experimental and/or clinical studies. Unless a patient has an intact or protected airway, the administration of multiple-dose activated charcoal is contraindicated. It should not be used in the presence of an intestinal obstruction. The need for concurrent administration of cathartics remains unproven and is not recommended. In particular, cathartics should not be administered to young children because of the propensity of laxatives to cause fluid and electrolyte imbalance. In conclusion, based on experimental and clinical studies, multiple-dose activated charcoal should be considered only if a patient has ingested a life-threatening amount of carbamazepine, dapsone, phenobarbital, quinine, or theophylline.

PMID 10584586  J Toxicol Clin Toxicol. 1999;37(6):731-51. doi: 10.1081・・・
著者: Ruben Thanacoody, E Martin Caravati, Bill Troutman, Jonas Höjer, Blaine Benson, Kalle Hoppu, Andrew Erdman, Regis Bedry, Bruno Mégarbane
雑誌名: Clin Toxicol (Phila). 2015 Jan;53(1):5-12. doi: 10.3109/15563650.2014.989326. Epub 2014 Dec 16.
Abstract/Text CONTEXT: A position paper on the use of whole bowel irrigation (WBI) was first published in 1997 by the American Academy of Clinical Toxicology (AACT) and the European Association of Poisons Centres and Clinical Toxicologists (EAPCCT) and updated in 2004. The aims of this paper are to briefly summarize the content of the 2004 Position Paper and to present any new data and recommendations.
METHODS: A systematic review of the literature from January 2003 to February 28, 2013 was conducted using multiple online databases for articles concerning WBI for gastrointestinal decontamination. An evidence table was created for applicable articles. The authors produced the initial draft that was reviewed by AACT and EAPCCT.
RESULTS: The literature search produced 60 articles with the possibility of applicable human data. Based mainly on volunteer studies, WBI can be considered for potentially toxic ingestions of sustained-release or enteric-coated drugs particularly for those patients presenting later than 2 h after drug ingestion when activated charcoal is less effective. WBI can be considered for patients who have ingested substantial amounts of iron, lithium, or potassium as the morbidity is high and there is a lack of other potentially effective options for gastrointestinal decontamination. WBI can be considered for removal of ingested packets of illicit drugs in "body packers." However, controlled data documenting improvement in clinical outcome after WBI are lacking. WBI is contraindicated in patients with bowel obstruction, perforation, or ileus, and in patients with hemodynamic instability or compromised unprotected airways. WBI should be used cautiously in debilitated patients and in patients with medical conditions that might be further compromised by its use. The concurrent administration of activated charcoal and WBI might decrease the effectiveness of the charcoal. The clinical relevance of this interaction is uncertain.
CONCLUSION: WBI can facilitate removal of select toxicants from the gastrointestinal tract in some patients, but there is no convincing evidence from clinical studies that it improves the outcome of poisoned patients. There is no new evidence that would require a major revision of the conclusions of the 2004 position statement.

PMID 25511637  Clin Toxicol (Phila). 2015 Jan;53(1):5-12. doi: 10.3109・・・
著者: Sophie Gosselin, Lotte C G Hoegberg, Robert S Hoffman, Andis Graudins, Christine M Stork, Simon H L Thomas, Samuel J Stellpflug, Bryan D Hayes, Michael Levine, Martin Morris, Andrea Nesbitt-Miller, Alexis F Turgeon, Benoit Bailey, Diane P Calello, Ryan Chuang, Theodore C Bania, Bruno Mégarbane, Ashish Bhalla, Valéry Lavergne
雑誌名: Clin Toxicol (Phila). 2016 Dec;54(10):899-923. doi: 10.1080/15563650.2016.1214275. Epub 2016 Sep 8.
Abstract/Text BACKGROUND: Although intravenous lipid emulsion (ILE) was first used to treat life-threatening local anesthetic (LA) toxicity, its use has expanded to include both non-local anesthetic (non-LA) poisoning and less severe manifestations of toxicity. A collaborative workgroup appraised the literature and provides evidence-based recommendations for the use of ILE in poisoning.
METHODS: Following a systematic review of the literature, data were summarized in four publications: LA and non-LA poisoning efficacy, adverse effects, and analytical interferences. Twenty-two toxins or toxin categories and three clinical situations were selected for voting. Voting statements were proposed using a predetermined format. A two-round modified Delphi method was used to reach consensus on the voting statements. Disagreement was quantified using RAND/UCLA Appropriateness Method.
RESULTS: For the management of cardiac arrest, we recommend using ILE with bupivacaine toxicity, while our recommendations are neutral regarding its use for all other toxins. For the management of life-threatening toxicity, (1) as first line therapy, we suggest not to use ILE with toxicity from amitriptyline, non-lipid soluble beta receptor antagonists, bupropion, calcium channel blockers, cocaine, diphenhydramine, lamotrigine, malathion but are neutral for other toxins, (2) as part of treatment modalities, we suggest using ILE in bupivacaine toxicity if other therapies fail, but are neutral for other toxins, (3) if other therapies fail, we recommend ILE for bupivacaine toxicity and we suggest using ILE for toxicity due to other LAs, amitriptyline, and bupropion, but our recommendations are neutral for all other toxins. In the treatment of non-life-threatening toxicity, recommendations are variable according to the balance of expected risks and benefits for each toxin. For LA-toxicity we suggest the use of Intralipid® 20% as it is the formulation the most often reported. There is no evidence to support a recommendation for the best formulation of ILE for non-LAs. The voting panel is neutral regarding ILE dosing and infusion duration due to insufficient data for non-LAs. All recommendations were based on very low quality of evidence.
CONCLUSION: Clinical recommendations regarding the use of ILE in poisoning were only possible in a small number of scenarios and were based mainly on very low quality of evidence, balance of expected risks and benefits, adverse effects, laboratory interferences as well as related costs and resources. The workgroup emphasizes that dose-finding and controlled studies reflecting human poisoning scenarios are required to advance knowledge of limitations, indications, adverse effects, effectiveness, and best regimen for ILE treatment.

PMID 27608281  Clin Toxicol (Phila). 2016 Dec;54(10):899-923. doi: 10.・・・
著者: Sophie Gosselin, Martin Morris, Andrea Miller-Nesbitt, Robert S Hoffman, Bryan D Hayes, Alexis F Turgeon, Brian M Gilfix, Ami M Grunbaum, Theodore C Bania, Simon H L Thomas, José A Morais, Andis Graudins, Benoit Bailey, Bruno Mégarbane, Diane P Calello, Michael Levine, Samuel J Stellpflug, Lotte C G Hoegberg, Ryan Chuang, Christine Stork, Ashish Bhalla, Carol J Rollins, Valéry Lavergne, AACT Lipid Emulsion Therapy workgroup
雑誌名: Clin Toxicol (Phila). 2015 Jul;53(6):557-64. doi: 10.3109/15563650.2015.1052498. Epub 2015 Jun 10.
Abstract/Text Intravenous lipid emulsion (ILE) therapy is a novel treatment that was discovered in the last decade. Despite unclear understanding of its mechanisms of action, numerous and diverse publications attested to its clinical use. However, current evidence supporting its use is unclear and recommendations are inconsistent. To assist clinicians in decision-making, the American Academy of Clinical Toxicology created a workgroup composed of international experts from various clinical specialties, which includes representatives of major clinical toxicology associations. Rigorous methodology using the Appraisal of Guidelines for Research and Evaluation or AGREE II instrument was developed to provide a framework for the systematic reviews for this project and to formulate evidence-based recommendations on the use of ILE in poisoning. Systematic reviews on the efficacy of ILE in local anesthetic toxicity and non-local anesthetic poisonings as well as adverse effects of ILE are planned. A comprehensive review of lipid analytical interferences and a survey of ILE costs will be developed. The evidence will be appraised using the GRADE system. A thorough and transparent process for consensus statements will be performed to provide recommendations, using a modified Delphi method with two rounds of voting. This process will allow for the production of useful practice recommendations for this therapy.

PMID 26059735  Clin Toxicol (Phila). 2015 Jul;53(6):557-64. doi: 10.31・・・
著者: Bryan D Hayes, Sophie Gosselin, Diane P Calello, Nicholas Nacca, Carol J Rollins, Daniel Abourbih, Martin Morris, Andrea Nesbitt-Miller, José A Morais, Valéry Lavergne, Lipid Emulsion Workgroup
雑誌名: Clin Toxicol (Phila). 2016 Jun;54(5):365-404. doi: 10.3109/15563650.2016.1151528. Epub 2016 Apr 1.
Abstract/Text BACKGROUND: Intravenous lipid emulsions (ILEs) were initially developed to provide parenteral nutrition. In recent years, ILE has emerged as a treatment for poisoning by local anesthetics and various other drugs. The dosing regimen for the clinical toxicology indications differs significantly from those used for parenteral nutrition. The evidence on the efficacy of ILE to reverse acute toxicity of diverse substances consists mainly of case reports and animal experiments. Adverse events to ILE are important to consider when clinicians need to make a risk/benefit analysis for this therapy.
METHODS: Multiple publication databases were searched to identify reports of adverse effects associated with acute ILE administration for either treatment of acute poisoning or parenteral nutrition. Articles were selected based on pre-defined criteria to reflect acute use of ILE. Experimental studies and reports of adverse effects as a complication of long-term therapy exceeding 14 days were excluded.
RESULTS: The search identified 789 full-text articles, of which 114 met the study criteria. 27 were animal studies, and 87 were human studies. The adverse effects associated with acute ILE administration included acute kidney injury, cardiac arrest, ventilation perfusion mismatch, acute lung injury, venous thromboembolism, hypersensitivity, fat embolism, fat overload syndrome, pancreatitis, extracorporeal circulation machine circuit obstruction, allergic reaction, and increased susceptibility to infection.
CONCLUSION: The emerging use of ILE administration in clinical toxicology warrants careful attention to its potential adverse effects. The dosing regimen and context of administration leading to the adverse events documented in this review are not generalizable to all clinical toxicology scenarios. Adverse effects seem to be proportional to the rate of infusion as well as total dose received. Further safety studies in humans and reporting of adverse events associated with ILE administration at the doses advocated in current clinical toxicology literature are needed.

PMID 27035513  Clin Toxicol (Phila). 2016 Jun;54(5):365-404. doi: 10.3・・・
著者: Michael Levine, Robert S Hoffman, Valéry Lavergne, Christine M Stork, Andis Graudins, Ryan Chuang, Samuel J Stellpflug, Martin Morris, Andrea Miller-Nesbitt, Sophie Gosselin, Lipid Emulsion Workgroup
雑誌名: Clin Toxicol (Phila). 2016 Mar;54(3):194-221. doi: 10.3109/15563650.2015.1126286. Epub 2016 Feb 6.
Abstract/Text BACKGROUND: The use of intravenous lipid emulsion (ILE) therapy for the treatment of lipophilic drug toxicity is increasing. Despite this, the evidence for its effect in non-local anesthetic toxicity remains sparse. Furthermore, many case reports describe ILE use for substances in which no clear efficacy data exists. The American Academy of Clinical Toxicology established a lipid emulsion workgroup. The aim of this group is to review the available evidence regarding the effect of ILE in non-LA drug poisoning and develop consensus-based recommendations on the use of this therapy.
METHODS: A systematic review of the literature was performed to capture articles through 15 December 2014. Relevant articles were determined based upon a predefined methodology. Articles involving pre-treatment experiments, pharmacokinetic studies not involving toxicity, and studies not addressing antidotal use of ILE met pre-defined exclusion criteria. Agreement of at least two members of the subgroup was required before an article could be excluded.
RESULTS: The final analysis included 203 articles: 141 for humans and 62 for animals. These include 40 animal experiments and 22 case reports involving animal toxicity. There were three human randomized control trials (RCT): one RCT examined ILE in TCA overdose, one RCT examined ILE in various overdoses, and one study examined ILE in reversal of sedation after therapeutic administration of inhaled anesthesia. One observational study examined ILE in glyphosate overdose. In addition, 137 human case reports or case series were identified. Intravenous lipid emulsion therapy was used in the management of overdose with 65 unique substances.
CONCLUSIONS: Despite the use of ILE for multiple substances in the treatment of patients with poisoning and overdose, the effect of ILE in various non-local anesthetic poisonings is heterogenous, and the quality of evidence remains low to very low.

PMID 26852931  Clin Toxicol (Phila). 2016 Mar;54(3):194-221. doi: 10.3・・・
著者: Joe-Anthony Rotella, Shaun L Greene, Zeff Koutsogiannis, Andis Graudins, Yit Hung Leang, Kelvin Kuan, Helen Baxter, Elyssia Bourke, Anselm Wong
雑誌名: Clin Toxicol (Phila). 2020 Oct;58(10):943-983. doi: 10.1080/15563650.2020.1752918. Epub 2020 Apr 20.
Abstract/Text Introduction: Beta-adrenoreceptor antagonist (beta-blocker) poisoning is a common overdose which can lead to significant morbidity and mortality.Objective: To evaluate the effects of treatments for beta-adrenoreceptor antagonist poisoning.Methods: Searches were conducted across MEDLINE (1946-26 November 2019, Ovid); Embase (1974-26 November 2019, Ovid); and the Cochrane Central Register of Controlled Trials (CENTRAL, to 26 November 2019) utilising a combination of subject headings and free text. The search strategy identified 15, 553 citations. Two reviewers screened titles and abstracts prior to selecting 141 articles (Kappa on articles included = 0.982, 95% CI 0.980-0.985). Primary outcomes included mortality and improvement in haemodynamic parameters (e.g., heart rate, blood pressure or a composite measure able to quantitate a haemodynamic response).Results: The risk of bias was high for all interventions.Gastric decontamination: Fifteen case reports described the administration of activated charcoal and five detailed the use of gastric lavage. As there was concurrent utilisation of multiple interventions, it was difficult to draw definitive conclusions regarding the relative contribution of these interventions to mortality or survival.Catecholamines, inotropes and vasopressors: The use of catecholamines in treating beta-blocker toxicity was reported in 16 case reports, 3 case series and 2 animal studies. These agents most likely provided a survival benefit and improved haemodynamics.Atropine: Multiple intravenous boluses of atropine were associated with improvement in heart rate and blood pressure in one case report.Calcium: Intravenous calcium was associated with an improvement in haemodynamics in three out of six case reports but in association with multiple other therapies as well as in two animal studies.High-dose insulin euglycaemic therapy: The use of this therapy was associated with mortality benefit in 10 case series. Two case reports showed clear haemodynamic improvement in a timeframe consistent with insulin administration (bolus then continuous infusion). Maintenance dosing ranged from 1 to 10 units/kg/h of insulin. However, it is unclear whether high-dose insulin euglycaemic therapy improved haemodynamic response above catecholamines and other inotropic agents in humans. Hypoglycaemia and hypokalemia were commonly observed adverse effects.Glucagon: Glucagon was associated with minor improvements in haemodynamics through an increase in heart rate in two cases series, nine case reports and five animal studies.Methylthioninium chloride (methylene blue): Four case reports reported an association with improvement in haemodynamics following administration of methylene blue but in the setting of co-ingestion with amlodipine.Intravenous lipid emulsion therapy: There was variable response to intravenous lipid emulsion therapy reported in 10 case series, 5 animal studies and 21 case reports.Lignocaine: There were four case reports showing variable response to lignocaine in arrhythmias secondary to beta-blocker toxicity.Other treatments: Fructose diphosphate, levosimendan and amrinone did not provide a mortality or significant haemodynamic benefit in three animal studies and nine case reports. .Veno-arterial extracorporeal membrane oxygenation: Veno-arterial extracorporeal membrane oxygenation was associated with improved survival in patients with severe cardiogenic shock or cardiac arrest in an observational study and four cases series.Dialysis: The evidence of four case reports suggest haemodialysis may assist in the management of massive overdose of specific water-soluble beta-blockers (e.g., atenolol) by improving elimination; however, a survival or haemodynamic benefit was not established.Pacing: One case series and a single case report showed the utility of temporary overdrive cardiac pacing to prevent arrhythmias in sotalol toxicity.Conclusions: Catecholamines, vasopressors, high-dose insulin euglycaemic therapy and veno-arterial extracorporeal membrane oxygenation were associated with reduced mortality. However, it must be acknowledged that multiple treatments were often given simultaneously. Haemodynamic improvements in blood pressure and cardiac output were seen with the use of catecholamines, vasopressin and high-dose insulin euglycaemic therapy. Evidence for treatment recommendations is almost entirely drawn from very low- to low-quality studies and subject to bias. However, it is reasonable to have a graduated response to cardiovascular instability beginning with intravenous fluids, commencement of a single or a combination of catecholamine inotropes and vasopressors depending upon the type of haemodynamic compromise (bradycardia, left ventricular dysfunction, vasodilation). High-dose insulin euglycaemic therapy can be introduced as an adjunctive inotrope and lastly, more invasive methods such as veno-arterial extracorporeal membrane oxygenation should be considered in cases unresponsive to other therapies.

PMID 32310006  Clin Toxicol (Phila). 2020 Oct;58(10):943-983. doi: 10.・・・
著者: Benoit Bailey
雑誌名: J Toxicol Clin Toxicol. 2003;41(5):595-602.
Abstract/Text BACKGROUND: Glucagon is usually accepted as part of the standard treatment in the management of patients with beta-blocker and calcium channel blocker overdoses.
METHODS: A systematic review was done in order to evaluate the evidence supporting glucagon use in beta-blocker and calcium channel blocker overdoses. Studies evaluating glucagon for those uses were identified using the Cochrane Database of Systematic Reviews, the Cochrane Controlled Trials Register, MedLine, ToxLine, and EMBASE searches, as well as reviewing medical toxicology textbooks and references of identified articles. Only controlled studies of human or animal studies were included, the latter only when it was an in vivo model of acute poisoning. The quality of the included studies was assessed.
RESULTS: The search found no study in humans but identified 30 in animals. In the five studies of animal models of beta-blocker overdose included, glucagon appeared to consistently increase the heart rate at least transiently but appeared to have no effect on mean arterial pressure even though it possibly increased cardiac output. Its effect on the survival rate in animal models of beta-blocker overdose was unclear. In the six studies of animal models of calcium channel blocker overdose included, glucagon appeared to increase heart rate and cardiac output and reverse second and third degree AV blocks, all at least transiently. There appeared to be no effect of glucagon on mean arterial pressure although it did increase in one model. Glucagon appeared to have no effect on survival rate. The included studies for both overdoses were not blinded, had limited numbers of animals, and some had inadequate glucagon regime.
CONCLUSION: The evidence supporting the use of glucagon in the management of patients with beta-blocker and calcium channel blocker overdoses is limited to animal studies.

PMID 14514004  J Toxicol Clin Toxicol. 2003;41(5):595-602.
著者: C Bismuth, M Gaultier, F Conso, M L Efthymiou
雑誌名: Clin Toxicol. 1973;6(2):153-62. doi: 10.3109/15563657308990513.
Abstract/Text
PMID 4715199  Clin Toxicol. 1973;6(2):153-62. doi: 10.3109/1556365730・・・
著者: Salim Satar, Ahmet Sebe, Akkan Avci, Hasan Yesilagac, Yuksel Gokel
雑誌名: Hum Exp Toxicol. 2005 Jun;24(6):337-9. doi: 10.1191/0960327105ht531oa.
Abstract/Text Experience with overdosage and toxicity with the alpha-adrenoreceptor antagonists remains very limited in the literature. In this paper, the second case in the literature with doxazosin overdosage is reported. Supportive treatment was given to the patient and the patient was discharged 48 hours after admission to the emergency department.

PMID 16004202  Hum Exp Toxicol. 2005 Jun;24(6):337-9. doi: 10.1191/096・・・
著者: Cory Anderson, Timothy Lynch, Ronish Gupta, Rodrick K Lim
雑誌名: J Emerg Med. 2018 Dec;55(6):e141-e145. doi: 10.1016/j.jemermed.2018.09.015. Epub 2018 Oct 2.
Abstract/Text BACKGROUND: Pediatric exposure to prazosin is unusual because it is most commonly indicated for the treatment of hypertension. Prazosin's increase in popularity as a treatment for posttraumatic stress disorder makes it important for emergency physicians to be aware of how to manage potential toxic ingestion because of prazosin overdose.
CASE REPORT: A 16-year-old, 76-kg female presented after ingesting 110 mg of prazosin, 209.3 g of acetaminophen, and 55 g of naproxen. She was admitted to the pediatric intensive care unit for rapidly deteriorating hypotension (lowest blood pressure 47/19 mm Hg) refractory to aggressive fluid resuscitation and infusions of epinephrine and norepinephrine each at 0.5 mcg/kg/min. Stabilization of blood pressure was eventually achieved, and associated with use of a vasopressin infusion of 0.004 units/kg/min. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Because of the increasing exposure of children to prazosin, clinicians should be aware of the pharmacology behind alpha-1 antagonist overdose and consider treatment options, such as vasopressin, when hypotension is resistant to standard fluid and catecholamine therapy.

Copyright © 2018 Elsevier Inc. All rights reserved.
PMID 30287134  J Emerg Med. 2018 Dec;55(6):e141-e145. doi: 10.1016/j.j・・・
著者: C Lucas, G A Christie, W S Waring
雑誌名: Emerg Med J. 2006 Nov;23(11):854-7. doi: 10.1136/emj.2006.038836.
Abstract/Text BACKGROUND: Angiotensin converting enzyme (ACE)-inhibitor overdose may result in severe hypotension. Existing data do not adequately deal with the likely onset of haemodynamic effects, which has implications for the appropriate duration of monitoring in the acute-care setting. Therefore, the relationship between the interval after an ACE-inhibitor overdose and onset of hypotension was examined.
METHODS: A retrospective case review of patients who attended our institution after an ACE-inhibitor overdose between 1 January 2000 and 31 December 2005 was carried out. Data collected were heart rate, blood pressure, electrolytes, electrocardiogram variables, and interval between ingestion and lowest recorded blood pressure.
RESULTS: 33 patients (24 men) who presented after an ACE-inhibitor overdose were identified. Median (interquartile range (IQR)) age was 49 (42-56) years, and stated quantity ingested was 20 (7-42) times the defined daily dose. The median (IQR) interval between ACE-inhibitor ingestion and lowest recorded systolic blood pressure was 4.5 (3.8-5.5) h, diastolic blood pressure was 3.8 (3.3-6.5) h and mean blood pressure was 4.2 (3.5-5.5) h. Heart rate did not increase substantially in response.
CONCLUSION: The lowest blood pressure was recorded within a short interval after an ACE-inhibitor overdose, irrespective of therapeutic intervention. Patients in whom hypotension has not occurred within 6 h of ingestion can be considered for discharge.

PMID 17057137  Emerg Med J. 2006 Nov;23(11):854-7. doi: 10.1136/emj.20・・・
著者: T Jackson, C Corke, J Agar
雑誌名: Lancet. 1993 Mar 13;341(8846):703. doi: 10.1016/0140-6736(93)90479-z.
Abstract/Text
PMID 8095618  Lancet. 1993 Mar 13;341(8846):703. doi: 10.1016/0140-67・・・
著者: Martine Robert, David De Bels, Martin Chaumont, Patrick M Honoré, Philippe Gottignies
雑誌名: Am J Emerg Med. 2019 Jun;37(6):1217.e1-1217.e2. doi: 10.1016/j.ajem.2019.03.046. Epub 2019 Mar 28.
Abstract/Text We report here the case of a patient with perindopril intoxication inducing severe bradycardia together with a profound hypotension. Initiation of a naloxone infusion completely resolved those symptoms. As a consequence, we could recommend as a first step the use of naloxone in order to prevent the use of more invasive therapeutic tools.

Copyright © 2019 Elsevier Inc. All rights reserved.
PMID 30952604  Am J Emerg Med. 2019 Jun;37(6):1217.e1-1217.e2. doi: 10・・・
著者: Silas W Smith, Kathy L Ferguson, Robert S Hoffman, Lewis S Nelson, Howard A Greller
雑誌名: Clin Toxicol (Phila). 2008 Jun;46(5):470-4. doi: 10.1080/15563650701779695.
Abstract/Text INTRODUCTION: Compared to other calcium channel blockers (CCBs), overdose with dihydropyridine CCBs are considered relatively benign due to their vascular selectivity. Although not a sustained-release preparation, amlodipine's prolonged duration of effect is concerning following overdose. In addition, angiotensin II receptor blocker blunting of vasoconstrictive and sympathetic compensatory responses could exacerbate calcium channel blocker toxicity. We describe severe toxicity associated with an overdose of amlodipine and valsartan.
CASE REPORT: A 75-year-old woman presented to the ED 45 minutes after a witnessed suicidal ingestion of a "handful" of amlodipine and valsartan tablets. Hypotension, which appeared two hours after ingestion, was refractory to crystalloids and colloids, calcium gluconate, epinephrine, norepinephrine, phenylephrine, and vasopressin infusions. High-dose insulin euglycemia (HIE) therapy, and treatment with glucagon and naloxone were successful in improving her hemodynamic status. In this combined overdose, right heart catheterization demonstrated both negative inotropic effects and decreased systemic vascular resistance.
CONCLUSION: Co-ingestion of amlodipine with valsartan produced profound toxicity. Early institution of HIE therapy may be beneficial to reverse these effects.

PMID 18568804  Clin Toxicol (Phila). 2008 Jun;46(5):470-4. doi: 10.108・・・
著者: Rebecca E Bruccoleri, Michele M Burns
雑誌名: J Med Toxicol. 2016 Mar;12(1):121-9. doi: 10.1007/s13181-015-0483-y.
Abstract/Text Sodium bicarbonate is a well-known antidote for tricyclic antidepressant (TCA) poisoning. It has been used for over half a century to treat toxin-induced sodium channel blockade as evidenced by QRS widening on the electrocardiogram (ECG). The purpose of this review is to describe the literature regarding electrophysiological mechanisms and clinical use of this antidote after poisoning by tricyclic antidepressants and other agents. This article will also address the literature supporting an increased serum sodium concentration, alkalemia, or the combination of both as the responsible mechanism(s) for sodium bicarbonate's antidotal properties. While sodium bicarbonate has been used as a treatment for cardiac sodium channel blockade for multiple other agents including citalopram, cocaine, flecainide, diphenhydramine, propoxyphene, and lamotrigine, it has uncertain efficacy with bupropion, propranolol, and taxine-containing plants.

PMID 26159649  J Med Toxicol. 2016 Mar;12(1):121-9. doi: 10.1007/s1318・・・
著者: D Tzivoni, S Banai, C Schuger, J Benhorin, A Keren, S Gottlieb, S Stern
雑誌名: Circulation. 1988 Feb;77(2):392-7.
Abstract/Text Twelve consecutive patients who developed torsade de pointes (polymorphous ventricular tachycardia with marked QT prolongation, TdP) over a 4 year period were treated with intravenous injections of magnesium sulfate. In nine of the patients a single bolus of 2 g completely abolished the TdP within 1 to 5 min, and in three others complete abolition of the TdP was achieved after a second bolus was given 5 to 15 min later. Nine of the patients also received continuous infusion of MgSO4 (3 to 20 mg/min) for 7 to 48 hr until the QT interval was below 0.50 sec. In nine of the 12 patients the TdP was induced by antiarrhythmic agents. The QT interval preceding TdP ranged from 0.54 to 0.72 sec. After the MgSO4 bolus, which prevented the recurrence of TdP, no significant changes were observed in the QT interval. There were no side effects of this treatment. In eight of the 12 patients potassium levels before the TdP were below 3.5 meq/liter; magnesium levels were available in eight patients before TdP, and were normal in all. Five additional patients with polymorphous ventricular tachycardia but normal QT intervals (non-TdP patients) received two to three boluses of MgSO4. This treatment was ineffective in all, but they responded to conventional antiarrhythmic therapy. Thus, MgSO4 is a very effective and safe treatment for TdP, and its application is rapid and simple. Its use is therefore recommended as the first line of therapy for TdP.

PMID 3338130  Circulation. 1988 Feb;77(2):392-7.
著者: Akshay Gupta, Andrew T Lawrence, Kousik Krishnan, Clifford J Kavinsky, Richard G Trohman
雑誌名: Am Heart J. 2007 Jun;153(6):891-9. doi: 10.1016/j.ahj.2007.01.040.
Abstract/Text Drug-induced long QT syndrome is characterized by a prolonged corrected QT interval (QTc) and increased risk of a polymorphic ventricular tachycardia known as torsade de pointes (TdP). We review mechanisms, predispositions, culprit agents, and management of this potentially fatal phenomenon. Virtually all drugs that prolong QTc block the rapid component of the delayed rectifier current (I(kr)). Some drugs prolong QTc in a dose-dependent manner, others do so at any dose. Most patients that develop drug-induced TdP have underlying risk factors. Female sex is the most common. Implicated drugs include class 1A and III antiarrhythmics, macrolide antibiotics, pentamidine, antimalarials, antipsychotics, arsenic trioxide, and methadone. Treatment for TdP includes immediate defibrillation for hemodynamic instability and intravenous magnesium sulfate. Potassium levels should be maintained in the high normal range, and all QT prolonging agents must be promptly discontinued.

PMID 17540188  Am Heart J. 2007 Jun;153(6):891-9. doi: 10.1016/j.ahj.2・・・
著者: Emily Brumfield, Kenneth R L Bernard, Christopher Kabrhel
雑誌名: Am J Emerg Med. 2015 Dec;33(12):1840.e3-5. doi: 10.1016/j.ajem.2015.04.012. Epub 2015 Apr 12.
Abstract/Text Flecainide is a Class Ic antiarrythmic agent associated with adverse events due to its pro-arrythmic effects. We report the case of a 33-year-old female presenting in cardiac arrest after a flecainide overdose treated with intravenous fat emulsion (IFE), sodium bicarbonate (NaHCO₃), and extracorporeal membrane oxygenation (ECMO). This case reviews the pathophysiology and management of flecainide toxicity including novel strategies of IFE and ECMO.

PMID 25921969  Am J Emerg Med. 2015 Dec;33(12):1840.e3-5. doi: 10.1016・・・
著者: J Evers, U Büttner-Belz
雑誌名: J Toxicol Clin Toxicol. 1995;33(2):157-9. doi: 10.3109/15563659509000466.
Abstract/Text A case of lorcainide poisoning with fatal outcome is reported. A young girl of 15 ingested, without high lethality of intent, 2500 mg lorcainide, an antiarrhythmic agent. Bradycardia, shock, coma, and cerebral convulsions rapidly occurred. Despite immediate resuscitative measures with high doses of catecholamines and hypertonic sodium bicarbonate the patient died three hours later. The course of lorcainide poisoning was similar to that of other class Ic antiarrhythmic agents.

PMID 7897755  J Toxicol Clin Toxicol. 1995;33(2):157-9. doi: 10.3109/・・・
著者: L S Nelson, R S Hoffman
雑誌名: J Toxicol Clin Toxicol. 1994;32(6):731-6. doi: 10.3109/15563659409017980.
Abstract/Text Few cases of mexiletine overdose have been reported in the literature. The available case reports have invariably noted significant hemodynamic or electrocardiographic abnormalities. A 41-year-old woman, on mexiletine for arrhythmia control, ingested up to 90 of her 200 mg mexiletine tablets in a suicide attempt. She presented to the emergency department awake with a normal blood pressure and pulse. Shortly afterwards, the patient had a generalized motor seizure, which responded after 40 minutes to intravenous diazepam 100 mg, phenobarbital 1 g and pyridoxine 5 g. Recurrent status epilepticus at one hour required an additional 40 mg of diazepam and a loading dose of pentobarbital. During the entire episode, her electrocardiogram remained normal. The patient's mexiletine level was 20 micrograms/mL (therapeutic 1-2 micrograms/mL) and the patient's urine screen was negative for cocaine. Mexiletine is a group Ib antidysrhythmic agent with electrophysiologic effects similar to lidocaine. Mexiletine has a little first pass hepatic metabolism and a large volume of distribution along with a high lipid solubility, and prolonged central nervous system toxicity may be expected. As with lidocaine, the toxic deaths from mexiletine have resulted from hypotension and bradycardia. The patient reported had a significant mexiletine overdose which resulted in convulsive status epilepticus, but was devoid of hemodynamic or electrocardiographic abnormalities.

PMID 7966531  J Toxicol Clin Toxicol. 1994;32(6):731-6. doi: 10.3109/・・・
著者: C Köppel, U Oberdisse, G Heinemeyer
雑誌名: J Toxicol Clin Toxicol. 1990;28(4):433-44. doi: 10.3109/15563659009038586.
Abstract/Text 120 cases of class IC antiarrhythmic overdose, including propafenone, flecainide, ajmaline and prajmaline overdose, were evaluated with respect to clinical course, therapy and outcome. Whereas drug overdose in general has an overall mortality of less than 1%, intoxication with antiarrhythmic drugs of class IC was associated with a mean mortality of 22.5%. Nausea, which occurred within the first 30 minutes after ingestion, was the earliest symptom. Spontaneous vomiting probably led to self-detoxication in about half the patients. Cardiac symptoms including bradycardia and, less frequently, tachyrhythmia occurred after about 30 minutes to 2 hours. Therapeutic measures included administration of activated charcoal, gastric lavage and a saline laxative, catecholamines, and in some patients, hypertonic sodium bicarbonate, insertion of a transvenous pacemaker and hemoperfusion. Fatal outcome was mainly due to cardiac conduction disturbances progressing to electromechanical dissociation or asystolia. Resuscitation, which had to be performed in 29 patients, was successful in only two of them. No correlation was found between fatal outcome, the type of antiarrhythmic, and ingested dose. Since a specific treatment is not available and resuscitive procedures including sodium bicarbonate and insertion of a pacemaker are of limited therapeutic value, early diagnosis and primary detoxification are most important for prevention of fatal outcome.

PMID 2176700  J Toxicol Clin Toxicol. 1990;28(4):433-44. doi: 10.3109・・・
著者: F Alderfliegel, M Leeman, P Demaeyer, R J Kahn
雑誌名: Intensive Care Med. 1993;19(1):57-8. doi: 10.1007/BF01709280.
Abstract/Text Sotalol overdose has special features because this beta-blocker has the potential to lengthen the Q-T interval and to initiate severe arrhythmias such as ventricular tachycardia or fibrillation. We describe the case of a 70-year-old woman who ingested 6.72 g sotalol with suicide attempt. Despite administration of activated charcoal, glucagon, atropine and isoprenaline, two episodes of asystole occurred, requiring cardiopulmonary resuscitation. Further treatment included ventricular pacing and dopamine. The patient recovered without neurologic nor cardiac sequelae.

PMID 8440801  Intensive Care Med. 1993;19(1):57-8. doi: 10.1007/BF017・・・
著者: Tetsuhiro Takei, Hiroko Fukushima, Junji Hatakeyama, Michiko Fujisawa, Toshitaka Ito
雑誌名: Clin Toxicol (Phila). 2011 Dec;49(10):944-5. doi: 10.3109/15563650.2011.629201. Epub 2011 Nov 9.
Abstract/Text
PMID 22070560  Clin Toxicol (Phila). 2011 Dec;49(10):944-5. doi: 10.31・・・

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