High-Risk QT-Prolonging Medications

Sanjay highlights methadone, ondansetron, macrolides, fluoroquinolones, and antipsychotics as culprits.

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🧭 REBEL Rundown

📌 Key Points

- 🫀 Prolonged QTc raises risk of torsades de pointes
- ⏱️ Correct for heart rate: QTc > 440 ms (men) or > 460 ms (women); > 500 ms = high TdP risk.
- 💊 Common culprits: Methadone, ondansetron, macrolides, fluoroquinolones, antipsychotics.
- 🧪 Prevention: Check & replete K, Mg, Ca and avoid QT-prolonging meds when possible.
- 🚑 If TdP develops: Defibrillate + IV magnesium and stop offending agents.

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📝 Introduction

The QT interval is a vital part of ECG interpretation, reflecting the heart’s electrical recovery after each beat. When prolonged, it can set the stage for torsades de pointes. Understanding how to measure and correct the QT interval, identify high-risk medications, and act quickly when TdP occurs is essential for every clinician. This guide walks you through the physiology, interpretation, common causes, and emergency management of QTc prolongation to keep your patients safe.

🤔 Definition and Physiology

QT evaluation is a fundamental component of EKG analysis. The QT interval reflects the time from ventricular depolarization and contraction through ventricular repolarization and relaxation.
Clinically, QT prolongation increases the risk of torsades de pointes (TdP) – a form of polymorphic ventricular tachycardia (a non-perfusing rhythm) that is classically described as a pattern of “twisting points” or alternating amplitudes. This occurs when a premature ventricular contraction leads to an R on T phenomenon during the repolarization period.
The differential for QT prolongation is long and varied: congenital long QT, electrolyte disturbances (hypoK, hypoMg, hypoCa), hypothermia, myocardial ischemia, and increased intracranial pressure. Moreover, a whole host of xenobiotics can prolong the QT interval: methadone, anti-microbials, anti-emetics, anti-psychotics, and anti-dysrhythmics.

🧮 ECG Interpretation

The QT interval must be interpreted in conjunction with the patient’s heart rate. The QT interval with shorten in the context tachycardia and length in the context of bradycardia. In other words, tachycardia is protective when evaluating the patient with prolonged QT.
With that in mind, many EKG machines will calculate a corrected QT interval or QTc. The QTc is a standardized way to account for variations in heart rate so clinicians are able to compared QT intervals at different heart rates over time and thus calculate risk.
Generally, a QTc is considered prolonged if greater than 440ms in males or 460ms in females. Once the QTc > 500msec, the risk of TdP increases 2-3 fold.¹
A variety of different correction formulas exist: Bazett, Fridericia, Hodges, Framingham, Rautaharju.
Manually, the QT interval should be measured from the beginning of the QRS complex to the end of the T wave – and thus should be measured in leads where all portions can be visualized, most frequently lead II or V5/V6. Ideally, the QT interval should be average over 3 or more beats.² To determine the end of the T wave, a tangent line should be drawn through the maximum slope of the T wave – the point at which this line crosses the isoelectric line is the end of the T wave.³

💊 Commonly Used QTc Prolonging Medications

Methadone: particularly concerning because not only does it inherently prolong QT but also induces a bradycardia
Antiemetics: Ondansetron
Macrolides: azithromycin, erythromycin, clarithromycin
Fluroquinolones: ciprofloxacin, levofloxacin
Antipsychotics: Haloperidol, Olanzapine

️ Management

Prevention is key!
- Assess electrolytes (Mg, Ca, K) and replete as needed
- Telemetry Monitoring
If patient happens to fall into TdP, initiate ACLS with immediate defibrillation and magnesium.
Withdrawal of offending agents.

📚 References

Drew BJ, Ackerman MJ, Funk M, Gibler WB, Kligfield P, Menon V, Philippides GJ, Roden DM, Zareba W. Prevention of torsade de pointes in hospital settings: a scientific statement from the American Heart Association and the American College of Cardiology Foundation. Circulation. 2010 Mar;121(8):1047-1060.
Postema PG and Wilde AAM. The measurement of the QT interval. Curr Cardiol Rev. 2014 Aug;10(3): 287-294.
https://litfl.com/qt-interval-ecg-library/

Post Peer Reviewed By: Marco Propersi, DO (Twitter/X: @Marco_propersi), and Mark Ramzy, DO (X: @MRamzyDO)