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钙通道阻滞剂中毒患者接受大剂量胰岛素治疗后的血管扩张:氨氯地平与非二氢吡啶类药物的比较。

Vasodilation in patients with calcium channel blocker poisoning treated with high-dose insulin: a comparison of amlodipine versus non-dihydropyridines.

机构信息

Minnesota Poison Control System, Department of Pharmacy, Hennepin Healthcare, Minneapolis, MN, USA.

Department of Emergency Medicine, Hennepin Healthcare, Minneapolis, MN, USA.

出版信息

Clin Toxicol (Phila). 2022 Nov;60(11):1205-1213. doi: 10.1080/15563650.2022.2131565. Epub 2022 Oct 25.

Abstract

High dose insulin (HDI), an inotrope and vasodilator, is a standard therapy for calcium channel blocker (CCB) poisoning. HDI causes vasodilation by stimulating endothelial nitric oxide synthase (eNOS). Most literature supporting HDI for CCB poisoning involves verapamil toxicity; however, amlodipine now causes more CCB poisonings. Unlike other CCBs, amlodipine stimulates eNOS and may cause synergistic vasodilation with HDI. The purpose of this study was to determine if amlodipine-poisoned patients treated with HDI had more evidence of vasodilation than similarly treated patients with non-dihydropyridine (non-DHP) poisoning. This was a retrospective study from a single poison center. Cases were identified via the generic code "Calcium Antagonists" in which the therapy "High Dose Insulin/Glucose" was "performed, whether or not recommended" from 2019-2021. Evidence of vasodilation was assessed via maximum number of vasopressor infusions per case, vasopressor doses, and use of rescue methylene blue to treat refractory vasoplegia. Thirty-three patients were enrolled: 18 poisoned with amlodipine, 15 with non-DHPs (verapamil  = 10, diltiazem  = 5). The median number of maximum concomitant vasopressors in the amlodipine group was 3 (IQR: 2-5; range 0-6) and 2 in the non-DHP group (IQR: 1-3; range 0-5;  = 0.04); median difference in maximum concomitant vasopressors between groups was 1 (95% confidence interval: 0-2). Median maximum epinephrine dosing was higher in the amlodipine group (0.31 mcg/kg/min) compared to non-DHPs (0.09 mcg/kg/min;  = 0.03). Use of rescue methylene blue was more common in the amlodipine group (7/18 [39%]) than in the non-DHP group (0;  = 0.009). Amlodipine poisoned patients treated with HDI required more vasopressors, higher doses of epinephrine, and more often received rescue methylene blue than similarly treated patients with verapamil or diltiazem poisoning. These differences suggest amlodipine-poisoned patients had more evidence of vasodilation. Further study is warranted to determine if synergistic vasodilation occurs when HDI is used to treat amlodipine poisoning.

摘要

高剂量胰岛素(HDI)作为一种正性肌力药和血管扩张剂,是钙通道阻滞剂(CCB)中毒的标准治疗方法。HDI 通过刺激内皮型一氧化氮合酶(eNOS)来引起血管扩张。大多数支持 HDI 治疗 CCB 中毒的文献都涉及维拉帕米毒性;然而,氨氯地平现在导致更多的 CCB 中毒。与其他 CCB 不同,氨氯地平刺激 eNOS,并且可能与 HDI 产生协同血管扩张作用。本研究的目的是确定用 HDI 治疗的氨氯地平中毒患者是否比用同样方法治疗的非二氢吡啶(非-DHP)中毒患者有更多的血管扩张证据。这是一项来自单一中毒中心的回顾性研究。通过治疗“高剂量胰岛素/葡萄糖”是否“进行,无论是否推荐”,从 2019 年至 2021 年,使用通用代码“钙拮抗剂”来确定病例。通过每个病例的最大血管加压素输注次数、血管加压素剂量以及使用救援亚甲蓝治疗难治性血管扩张来评估血管扩张的证据。共纳入 33 例患者:18 例氨氯地平中毒,15 例非-DHP 中毒(维拉帕米 10 例,地尔硫卓 5 例)。氨氯地平组的最大同时血管加压素中位数为 3(IQR:2-5;范围 0-6),非-DHP 组为 2(IQR:1-3;范围 0-5;  = 0.04);两组之间最大同时血管加压素的中位数差异为 1(95%置信区间:0-2)。与非-DHP 组(0.09 mcg/kg/min;  = 0.03)相比,氨氯地平组的最大肾上腺素剂量更高(0.31 mcg/kg/min)。氨氯地平组使用救援亚甲蓝更为常见(18 例中的 7 例[39%])而非-DHP 组(0 例;  = 0.009)。用 HDI 治疗的氨氯地平中毒患者需要更多的血管加压剂、更高剂量的肾上腺素,并且更常接受救援亚甲蓝治疗,而用维拉帕米或地尔硫卓治疗的类似患者则不然。这些差异表明氨氯地平中毒患者有更多的血管扩张证据。需要进一步研究以确定当使用 HDI 治疗氨氯地平中毒时是否会发生协同血管扩张。

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