QT interval in Toxicology

Introduction

The QT interval is measured from the initiation of the QRS complex to the end of the T wave and largely represents ventricular repolarisation. Prolongation of the QT interval is important clinically as it is associated with life threatening Torsades de Pointes (TdP). QT Prolongation can be due to congenital or acquired causes. Of the acquired causes, drugs are a common culprit – with the usual mechanism being blockade of the inward rectifying potassium channel.

Risk Assessment

In the poisoned patient, you should consider QT prolongation in any exposure to a QT prolonging agent. Drugs associated with QT prolongation and TdP are listed below,1 (this list is not exhaustive):

table

QT prolongation without a history of exposure to a QT prolonging drug should prompt consideration for congenital QT prolongation, or regular treatment with a QT prolonging agent such as methadone. A previous ECG is helpful in these cases.

ecg1

QT prolongation following 820mg escitalopram OD

Measuring the QT & plotting on the nomogram

The best approach to measuring the QT is to measure the QT interval in multiple leads and take the median value1. Be mindful that computer generated QT calculations are unreliable and should not be used.

Plot the QT on the QT nomogram to determine risk of TdP. Values above the line are at risk of TdP and warrant closer observation.

qt-nomogram

The QT nomogram has a sensitivity of 97% and specificity of 99% for predicting TdP following toxicological ingestions and has been found to be more accurate in predicting TdP than using Bazett’s QTc of 440ms or 500ms.1

screen-shot-2016-10-07-at-2-52-40-pm

For the above example the measured QT in leads I, II aVF, V2, V4, V6 are 320, 340, 320, 300, 340 and 320 respectively. This gives a median QT of 320ms. Note the computer generated QT is longer at 360ms, correcting with Bazett’s formula to 485 – which would be considered prolonged. However plotting this on the nomogram shows a level which is well below the risk line. Bazett’s QTc overcorrects in tachycardia and undercorrects for slow heart rates and should not used in toxicology patients to determine overall risk of TdP.

screen-shot-2016-10-07-at-2-52-23-pm

Management of prolonged QT

Observe patient in a monitored environment with continuous telemetry. Review ECGs q4h to follow progression.

Correct modifiable risk factors for TdP;

·      Hypoxia

·      Hypokalaemia             (aim for K+ > 4.5)

·      Hypomagnesaemia    (aim for Mg2+ > 1.0)

·      Hypocalcaemia:          (aim for iCa > 1.2)

Management of Torsades de Pointes

As above & give magnesium sulphate 10mmol (0.1mmol/kg paediatrics) over 10 min, repeat as required.

Electrical cardioversion may be required in prolonged cases – although most cases are self-terminating bursts. Consider overdrive pacing or lignocaine if refractory.

Disposition

All poisoned patients with a prolonged QT interval should be discussed with the toxicology unit. Most are suitable for admission to the Short Stay Unit as a monitored patient with continuous telemetry and frequent ECGs until the QT interval normalises.

Additional Information

  • The QT nomogram was developed based on a ‘cloud’ of QT-RR pairings of individuals over the course of 24h period.1 You can look at clouds of QT-HR pairings for separate drugs to determine whether they are associated with TdP. Of the 4 drug clouds below, only amisulpride is associated with prolonged QT and the potential development of TdP.

clouds

6       Further reading

References

  1. Isbister G and Page C. “Drug induced QT prolongation: the measurement and assessment of the QT interval in clinical practive. Brit J Clin Pharmacol 2012; 76(1):48-57
  2. Thomas S and Behr E. “Pharmacological treatment of acquired QT prolongation and torsades de pointes.” Br J Clin Pharmacol 2015; 81(3):420-7