Guest post : Ian Whyte, Professor of Clinical Pharmacology at Calvary Mater Newcastle and University of Newcastle

Case report (Knorr et al 2008 Ciprofloxacin-induced Q-T interval prolongation)

16-year-old boy was admitted for the treatment of an acute flare of Crohn’s disease and a perirectal abscess. The patient was started on ciprofloxacin 400 mg IV twice daily and metronidazole. Within 48 hours the patient became bradycardic. The ECG showed a mildly prolonged Q-T interval (corrected Q-T interval, 486 msec) with heart rate of 42 beats/min. Antimicrobial therapy was changed. The patient’s Q-T interval normalized within seven days of ciprofloxacin discontinuation. The patient had no further cardiac anomalies detected.

Key points

• Drugs including antimicrobials can cause prolongation of the QT interval, alone or in combination, potentially leading to fatal arrhythmias such as torsades des pointes
• When prescribing drugs that prolong the QT interval, the balance of benefit versus harm should always be considered
• Readouts from automated ECG machines are unreliable. The QT interval should be measured manually
• Changes in heart rate influence the absolute QT interval. Heart rate correction formulae are inaccurate, particularly for fast and slow heart rates
• The QT nomogram, a plot of QT interval versus heart rate, can be used as a risk assessment tool to detect an abnormal QT interval

The QT interval is the duration between the start of the Q wave and the end of the T wave on an ECG.

Most drugs known to cause QT prolongation block the rapid component of the delayed rectifier potassium channel. Delayed ventricular repolarisation will lead to early after-depolarisations, which can result in re-entrant pathways or focal activity and torsades des pointes.

Antimicrobials of concern include (crediblemeds.org):  (see also this AIMED recent posting concerning comparative mortality risks)

• Moxifloxacin> ciprofloxacin, gatifloxacin, levofloxacin,
• Azithromycin, erythromycin > clarithromycin
• Fluconazole, voriconazole
• Pentamidine
• Chloroquine, halofantrine

Measuring the QT interval is problematic. Standard ECG machines can be unreliable and taking the automated reading from the ECG machine in clinical practice may be inaccurate, particularly in patients with a long QT.

A simple manual method is:

• Obtain ECG
  • Measure the QT interval length manually in 6 leads, usually:
    • 3 limb leads: I, II and aVF
    • 3 chest leads: V2, V4 and V6
  • Measure the absolute QT interval from the start of the Q wave until the T wave returns to baseline. On a standard ECG at 25 mm per second this is best done by counting the number of small squares; 5 small squares = 200 milliseconds and 8 small squares = 320 milliseconds
  • Do not use the ECG automated readout for QTor QTc
• Calculate the median QT (the middle number of all 6 measured QT intervals when arranged in numerical order)
  • If there are 2 middle numbers e.g., position 3 and 4, then the average of these 2 measurements is the median
• Determine the heart rate from the automated ECG readout
• Plot the QT-HR pair on the QT nomogram
  • If the QT-HR pair is above the line on the nomogram it is a prolonged QT and there is an increased risk of torsades des pointes

References

This post is a shortened copy of Isbister GK (reference 1) with some minor edits and the addition of some drugs from reference 3.

1. Isbister GK. Risk assessment of drug-induced QT prolongation. Aust Prescr. 2015 Feb;38(1):20–4 [Free PMC article]
2. Isbister GK, Page CB. Drug induced QT prolongation: the measurement and assessment of the QT interval in clinical practice. Br J Clin Pharmacol. 2013 Jul;76(1):48–57 [Free PMC Article]
3. Woosley, RL and Romero, KA, www.Crediblemeds.org, QTdrugs List, Accession Date 15/12/2015, AZCERT, Inc. 1822 Innovation Park Dr., Oro Valley, AZ 85755