急性中毒
ENGLISH ABSTRACT
成人氨氯地平中毒剂量与休克程度相关性研究
李辉
张华
付源伟
郭治国
马青变
作者及单位信息
·
DOI: 10.3760/cma.j.issn.1671-0282.2025.03.012
A correlation study between drug dose and shock severity in adults with amlodipine poisoning
Li Hui
Zhang Hua
Fu Yuanwei
Guo Zhiguo
Ma Qingbian
Authors Info & Affiliations
Li Hui
Emergency Department, Peking University Third Hospital, Beijing 100191, China
Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing 100191, China
Zhang Hua
Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing 100191, China
Fu Yuanwei
Emergency Department, Peking University Third Hospital, Beijing 100191, China
Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing 100191, China
Guo Zhiguo
Emergency Department, Peking University Third Hospital, Beijing 100191, China
Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing 100191, China
Ma Qingbian
Emergency Department, Peking University Third Hospital, Beijing 100191, China
Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing 100191, China
·
DOI: 10.3760/cma.j.issn.1671-0282.2025.03.012
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摘要

目的通过分析氨氯地平中毒合并休克患者临床资料,分析剂量与休克严重程度的关系。

方法选取2018年1月1日至2022年12月31日因氨氯地平中毒并发休克在北京大学第三医院急诊科救治的成年患者并检索1997—2022年公开发表的氨氯地平中毒文献中合并休克的成年患者,分为非难治性休克组和难治性休克组,对两组间的数据进行统计学分析。

结果共纳入80例患者,其中非难治性休克的患者37例,难治性休克43例,两组间性别( P=0.037)、服药剂量差异有统计学意义( P=0.001)。将性别、年龄、剂量、是否混合中毒进行二元Logistic回归分析,结果显示剂量是休克严重程度的独立影响因素( OR=1.43,95% CI: 1.12~1.84, P=0.005)。亚组分析将仅服用氨氯地平未同服其他药物而中毒的非难治性休克和难治性休克的两组患者进行比较,两组间服药剂量同样差异有统计学意义( P=0.003)。用受试者工作曲线对中毒剂量和难治性休克进行分析,曲线下面积AUC为0.723 (95% CI: 0.613~0.833),最佳界值剂量为347.5 mg(敏感度0.651、特异度0.784)。敏感性分析(不包括混合中毒病例)得出的AUC较高,为0.795 (95% CI:0.634~0.956),最佳界值剂量为350 mg(敏感度0.867,特异度0.737)。服药剂量和难治性休克发生率的剂量反应关系表显示,随着剂量的增大,发生难治性休克的比例也随之增加。

结论在因超量服用氨氯地平引起中毒的成人患者中,药物剂量与休克的严重程度相关,当剂量大于347.5 mg时要高度警惕难治性休克的发生,给予更多临床关注,调配更多医疗资源。

心血管药物;钙通道阻滞剂;氨氯地平;中毒;剂量;休克;难治性休克;剂量反应关系
ABSTRACT

ObjectiveThis study aimed to investigate the correlation between the ingested dose of amlodipine and the severity of shock in affected patients by analyzing clinical data from documented cases.

MethodsThis study respectively included adult patients treated for amlodipine poisoning-induced shock at the emergency department of Peking University Third Hospital between January 2018 and December 2022. Additionally, cases reported in the literature from January 1997 to December 2022 were also included. Patients were categorized into two groups: non-refractory shock and refractory shock. Statistical analysis was conducted on the data between the two groups.

ResultsThis study included a total of 80 patients, with 37 experiencing non-refractory shock patients and 43 presenting with refractory shock patients. Significant differences were observed between the two groups in terms of sex distribution ( P=0.037) and the ingested amlodipine dose ( P=0.001). Through binary logistic regression analysis, the amlodipine dose was identified as an independent predictor of shock severity ( OR=1.43, 95% CI: 1.12-1.84, P=0.005). A subgroup analysis was performed on patients who were poisoned by ingesting amlodipine alone, further confirming the significant dose difference ( P=0.003) between the non-refractory shock and refractory shock categories. The area under the receiver operating characteristic curve (AUC) for predicting refractory shock in patients with amlodipine poisoning was 0.723 (95% CI: 0.613-0.833). The optimal cutoff dose for predicting refractory shock was 347.5 mg, with a sensitivity of 0.651 and a specificity of 0.784. Sensitivity analyses, excluding cases of mixed poisoning, yielded a higher AUC of 0.795 (95% CI: 0.634-0.956), with a slightly adjusted cutoff dose of 350 mg, a sensitivity of 0.867, and a specificity of 0.737. The dose-response relationship table between medication dosage and incidence of refractory shock shows that as the dosage increases, the proportion of refractory shock also increases.

ConclusionsIn adult patients with amlodipine poisoning, the severity of shock was correlated with the ingested dose of the drug. When the ingested amlodipine dose exceeds 347.5 mg, it is crucial to be cautious of the development of refractory shock.

Cardiovascular drugs;Calcium channel blockers;Amlodipine;Poisoning;Dose;Shock;Refractory shock;Dose-response relationship
Ma Qingbian, Email: mocdef.6ab21naibgniqam;
Guo Zhiguo, Email: mocdef.3ab61tcivelppa
引用本文

李辉,张华,付源伟,等. 成人氨氯地平中毒剂量与休克程度相关性研究[J]. 中华急诊医学杂志,2025,34(03):359-368.

DOI:10.3760/cma.j.issn.1671-0282.2025.03.012

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心血管药物中毒已经成为全球性的公共卫生问题 [ 1 ]。钙通道阻滞剂(calcium channel blockers,CCBs)是一种临床常用的心血管药物,主要应用于治疗高血压,还可用于治疗冠状动脉性疾病和心律失常。CCBs临床需要量大且容易获得,近年来已成为导致中毒的常见心血管药物类型。不仅如此,严重的CCBs中毒导致死亡的占比正在逐年增加,2019年美国中毒控制中心报道因中毒导致死亡的病例中CCBs中毒占4.62% [ 2 ],而2020年报道比例已增至6.4% [ 3 ]。其造成死亡的病理生理基础是难以纠正的休克、循环系统的崩溃和致命的心脏骤停。
根据最新的国际专家共识,成人CCBs中毒的一线治疗包括补液、静脉钙剂、血管活性药物(去甲肾上腺素、肾上腺素或多巴酚丁胺)、大剂量胰岛素和阿托品。在难治性休克、围心脏骤停期和心脏骤停时,可使用静脉脂肪乳、起搏器或静脉-动脉体外膜肺氧合(veno-arterial extracorporeal membrane oxygenation, VA-ECMO) [ 4 ],其核心的治疗理念在于纠正休克或循环衰竭。
氨氯地平是最常见的二氢吡啶类CCBs,过去十年应用氨氯地平治疗高血压的患者增加了3倍 [ 5 ]。在钙通道阻滞剂中,氨氯地平是报道最多的导致急性中毒的CCBs药物,也是造成死亡最多的CCBs药物 [ 3 ]。目前有关氨氯地平中毒的临床研究较少,且多为个案报道,更未见氨氯地平中毒剂量与临床结果之间的相关性研究,为此在本研究中笔者回顾分析了因氨氯地平中毒并发休克而在北京大学第三医院急诊科救治的成年患者的病例资料并检索了已发表的氨氯地平中毒各类病例报道和临床研究,试图发现服药剂量与临床严重程度的关系,特别是与休克严重程度的相关关系,为预测和评估此类中毒的严重程度提供参考。
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备注信息
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马青变,Email: mocdef.6ab21naibgniqam
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郭治国,Email: mocdef.3ab61tcivelppa
C

李辉:论文撰写;张华:统计学分析;付源伟:数据收集及整理;郭治国、马青变:指导并审阅论文

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国家临床重点专科建设项目(2022)专项资金 (301-2305)
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