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羟氯喹/阿奇霉素联合治疗住院 SARS-CoV-2 下呼吸道感染患者时 QT 间期延长。

QT Interval Prolongation Under Hydroxychloroquine/Azithromycin Association for Inpatients With SARS-CoV-2 Lower Respiratory Tract Infection.

机构信息

Cardiology Department, Pasteur University Hospital, Nice, France.

Cardiology Department, Clinique la Casamance, Aubagne, France.

出版信息

Clin Pharmacol Ther. 2020 Nov;108(5):1090-1097. doi: 10.1002/cpt.1968. Epub 2020 Jul 20.

Abstract

Association between Hydroxychloroquine (HCQ) and Azithromycin (AZT) is under evaluation for patients with lower respiratory tract infection (LRTI) caused by the Severe Acute Respiratory Syndrome (SARS-CoV-2). Both drugs have a known torsadogenic potential, but sparse data are available concerning QT prolongation induced by this association. Our objective was to assess for COVID-19 LRTI variations of QT interval under HCQ/AZT in patients hospitalized, and to compare manual versus automated QT measurements. Before therapy initiation, a baseline 12 lead-ECG was electronically sent to our cardiology department for automated and manual QT analysis (Bazett and Fridericia's correction), repeated 2 days after initiation. According to our institutional protocol (Pasteur University Hospital), HCQ/AZT was initiated only if baseline QTc ≤ 480ms and potassium level> 4.0 mmol/L. From March 24 to April 20 2020, 73 patients were included (mean age 62 ± 14 years, male 67%). Two patients out of 73 (2.7%) were not eligible for drug initiation (QTc ≥ 500 ms). Baseline average automated QTc was 415 ± 29 ms and lengthened to 438 ± 40 ms after 48 hours of combined therapy. The treatment had to be stopped because of significant QTc prolongation in two out of 71 patients (2.8%). No drug-induced life-threatening arrhythmia, nor death was observed. Automated QTc measurements revealed accurate in comparison with manual QTc measurements. In this specific population of inpatients with COVID-19 LRTI, HCQ/AZT could not be initiated or had to be interrupted in less than 6% of the cases.

摘要

羟氯喹(HCQ)和阿奇霉素(AZT)联合用于治疗由严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2)引起的下呼吸道感染(LRTI)。这两种药物都有已知的致扭转型潜力,但关于这种联合用药引起的 QT 延长的数据很少。我们的目的是评估 COVID-19 LRTI 患者在接受 HCQ/AZT 治疗前后 QT 间期的变化,并比较手动和自动 QT 测量。在开始治疗前,将基线 12 导联心电图通过电子方式发送到我们的心脏病科,进行自动和手动 QT 分析(Bazett 和 Fridericia 校正),在开始治疗后 2 天重复。根据我们的机构方案(巴斯德大学医院),只有在基线 QTc≤480ms 且钾水平>4.0mmol/L 的情况下,才开始使用 HCQ/AZT。从 2020 年 3 月 24 日至 4 月 20 日,共纳入 73 例患者(平均年龄 62±14 岁,男性 67%)。由于有 2 例患者(2.7%)不符合药物起始标准(QTc≥500ms),因此未开始使用该药物。基线时自动测量的平均 QTc 为 415±29ms,联合治疗 48 小时后延长至 438±40ms。有 2 例患者(2.8%)因 QTc 显著延长而停止治疗。未观察到药物引起的危及生命的心律失常或死亡。与手动 QTc 测量相比,自动 QTc 测量更准确。在这组特定的 COVID-19 LRTI 住院患者中,不到 6%的患者无法开始或不得不中断 HCQ/AZT 的治疗。

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