Isbister Geoffrey K, Friberg Lena E, Duffull Stephen B
Tropical Toxinology Unit, Menzies School of Health Research, Charles Darwin University, Darwin, Australia.
Intensive Care Med. 2006 Jul;32(7):1060-5. doi: 10.1007/s00134-006-0183-9. Epub 2006 May 10.
To develop guidelines for the management of QT prolongation after citalopram overdose, including decontamination with single-dose activated charcoal (SDAC) and cardiac monitoring.
Simulation study using a previously developed pharmacokinetic-pharmacodynamic (PKPD) model which predicted the time-course of QT prolongation and the effect of citalopram dose and use of SDAC on QT prolongation.
The previously developed PKPD model was used to address the following in patients following citalopram overdose: (1) Above what dose should patients be decontaminated? (2) Above what dose should patients have cardiac monitoring? (3) For what period of time should patients be monitored? The primary outcome was QT,RR combinations above an abnormal threshold as a surrogate predictor of torsades de pointes. Simulations were performed using MATLAB for an overdose patient with typical demographics: 30-year-old female with a heart rate of 79 bpm taking citalopram therapeutically. The simulations showed: (1) There was significant benefit associated with the administration of SDAC to patients following citalopram overdose ingesting >600 mg; (2) With citalopram overdoses >1,000mg it was advisable to give SDAC and cardiac monitor the patient; (3) The risk of developing future abnormal QT,RR combinations was less than 1% in patients with normal QT,RR combinations up to 13 h post-dose, so the minimum monitoring time for citalopram overdoses >1,000mg should be 13h. Recommended dose levels for intervention should be lowered in older patients and patients with tachycardia, while men are less sensitive to QT prolongation.
Guidelines for the management of QT prolongation after citalopram overdose were developed. We believe the model will help clinicians to decide which patients to decontaminate and monitor.
制定西酞普兰过量后QT间期延长管理指南，包括使用单剂量活性炭（SDAC）进行洗胃及心脏监测。
使用先前开发的药代动力学-药效学（PKPD）模型进行模拟研究，该模型可预测QT间期延长的时间进程以及西酞普兰剂量和SDAC使用对QT间期延长的影响。
先前开发的PKPD模型用于解决西酞普兰过量患者的以下问题：（1）患者超过何种剂量时应进行洗胃？（2）患者超过何种剂量时应进行心脏监测？（3）应对患者监测多长时间？主要结局是QT、RR组合超过异常阈值，作为尖端扭转型室速的替代预测指标。使用MATLAB对一名具有典型人口统计学特征的过量患者进行模拟：30岁女性，治疗期间服用西酞普兰，心率为79次/分钟。模拟结果显示：（1）西酞普兰过量摄入>600mg的患者服用SDAC有显著益处；（2）西酞普兰过量>1000mg时，建议给予SDAC并对患者进行心脏监测；（3）给药后13小时内QT、RR组合正常的患者发生未来异常QT、RR组合的风险小于1%，因此西酞普兰过量>1000mg的患者的最短监测时间应为13小时。老年患者和心动过速患者的推荐干预剂量水平应降低，而男性对QT间期延长的敏感性较低。
制定了西酞普兰过量后QT间期延长的管理指南。我们认为该模型将有助于临床医生决定对哪些患者进行洗胃和监测。
