Department of Hospital Pharmacy, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Department of Paediatric Surgery, Erasmus MC Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Pharmacol Res Perspect. 2021 Dec;9(6):e00865. doi: 10.1002/prp2.865.
QTc interval prolongation is an adverse effect associated with the use of fluoroquinolones and macrolides. Ciprofloxacin and erythromycin are both frequently prescribed QTc-prolonging drugs in critically ill patients. Critically ill patients may be more vulnerable to developing QTc prolongation, as several risk factors can be present at the same time. Therefore, it is important to know the QTc-prolonging potential of these drugs in the intensive care unit (ICU) population. The aim of this study was to assess the dynamics of the QTc interval over a 24-hour dose interval during intravenous ciprofloxacin and low-dose erythromycin treatment. Therefore, an observational study was performed in ICU patients (≥18 years) receiving ciprofloxacin 400 mg t.i.d. or erythromycin 100 mg b.i.d. intravenously. Continuous ECG data were collected from 2 h before to 24 h after the first administration. QT-analyses were performed using high-end holter software. The effect was determined with a two-sample t-test for clustered data on all QTc values. A linear mixed model by maximum likelihood was applied, for which QTc values were assessed for the available time intervals and therapy. No evident effect over time on therapy with ciprofloxacin and erythromycin was observed on QTc time. There was no significant difference (p = 0.22) in QTc values between the ciprofloxacin group (mean 393 ms) and ciprofloxacin control group (mean 386 ms). The erythromycin group (mean 405 ms) and erythromycin control group (mean 404 ms) neither showed a significant difference (p = 0.80). In 0.6% of the registrations (1.138 out of 198.270 samples) the duration of the QTc interval was longer than 500 ms. The index groups showed slightly more recorded QTc intervals over 500 ms. To conclude, this study could not identify differences in the QTc interval between the treatments analyzed.
QTc 间期延长是与氟喹诺酮类和大环内酯类药物使用相关的一种不良反应。环丙沙星和红霉素都是重症患者常用的延长 QTc 药物。重症患者可能更容易发生 QTc 延长，因为同时可能存在多种危险因素。因此，了解这些药物在重症监护病房（ICU）人群中的延长 QTc 潜力非常重要。本研究旨在评估静脉滴注环丙沙星和小剂量红霉素治疗期间 24 小时剂量间隔内 QTc 间期的变化。因此，在接受静脉滴注环丙沙星 400mg tid 或红霉素 100mg bid 的 ICU 患者中进行了一项观察性研究（≥18 岁）。从首次给药前 2 小时到给药后 24 小时连续采集心电图数据。使用高端动态心电图软件进行 QT 分析。使用两样本 t 检验对所有 QTc 值进行聚类数据分析，以确定影响。应用最大似然法的线性混合模型，对可获得的时间间隔和治疗进行 QTc 值评估。在 QTc 时间上，没有观察到环丙沙星和红霉素治疗的时间依赖性影响。环丙沙星组（平均 393ms）与环丙沙星对照组（平均 386ms）的 QTc 值无显著差异（p=0.22）。红霉素组（平均 405ms）和红霉素对照组（平均 404ms）也无显著差异（p=0.80）。在 0.6%的记录（198.270 个样本中的 1.138 个）中，QTc 间期的持续时间超过 500ms。指数组记录的超过 500ms 的 QTc 间期略多。总之，本研究未能确定分析的治疗方法之间 QTc 间期的差异。
