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Re: Response to Page et al

Dear Editor

We read with interest the letter by Page et al and acknowledge some important points.

1. The heart rate-corrected QT interval (QTc) is the traditional method of assessing the duration of repolarization. However, the QTc maybe misleadingly prolonged when QRS duration is 120 ms, because increased QRS duration (QRSd) contributes to QT interval prolongation. The rate- corrected JT interval (JTc) is a more accurate measurement of ventricular repolarization, and therefore may be a more sensitive means of assessing abnormalities. In these circumstances, using our case as an example, the JTc is a more specific measurement of ventricular repolarization than the QTc by eliminating QRS duration variability.

2. However, it must be stated that the pharmacological effects of Dolasetron in the setting of an overdose are still incompletely understood. It is possible that the cardiotoxicity may not only involve sodium channel blockade leading to intraventricular conduction delay and prolonged JTc but may also involve QTc prolongation secondary to repolarisation changes associated with potassium channel blockade. I think it is important that Dolasetron should be administered with caution in patients who have or may develop prolongation of cardiac conduction intervals, particularly QTc. These include patients with hypokalemia or hypomagnesemia, patients taking diuretics with potential for inducing electrolyte abnormalities, patients with congenital QT syndrome, patients taking anti-arrhythmic drugs or other drugs which lead to QT prolongation, and cumulative high dose anthracycline therapy.

Yours sincerely

Send letter to journal:
Re: Dolasetron and QT Interval

Dear Editor

We read with interest the case report by Rochford et al. However, we are concerned that the title associates dolasetron overdose with a prolonged QTc despite electrocardiogram (ECG) and clinical features that are more consistent with sodium channel blockade and QRS widening.

1.The ECG presented in the figure demonstrates the characteristic features of sodium channel blockade with a markedly widened QRS complex and a rightward shift of the terminal 40 msec of the frontal plane QRS complex vector (1). The apparent prolongation of the QT interval (QTc 611msec) in this type of cardiac toxicity is secondary to widening of the QRS, not as a result of prolonged repolarisation associated with potassium channel blockade, which is more appropriately measured in this situation by examining the JT interval. The JT interval is an independent measure of repolarisation that is not affected by QRS widening (2,3). The JT interval is this case is normal (320msec).

2.The authors report the use of sodium bicarbonate (400 mmol in total) over a 2 hour and subsequent 10 hour period aiming for a pH of 7.45 with normalisation of the QTc interval over a 12 hour period. Traditional management of sodium channel blockade has encouraged the use of sodium bicarbonate over a much shorter time period aiming to produce a rapid change in blood pH (4). The end-point for treatment is a narrowing of the QRS complex on the ECG and not changes in either the QT or QTc. It is probable that the QRS widening would have normalised much quicker with more aggressive use of sodium bicarbonate.

It is likely that more cases of dolasetron poisoning will occur so it is important to clearly define its cardiac toxicity. The authors provide good evidence that it cause sodium channel blockade in overdose and not QT prolongation associated with potassium channel blockade. Treatment of a widened QRS should be undertaken with boluses of sodium bicarbonate.

1. Harrigan RA, Brady WJ. ECG abnormalities in tricyclic antidepressant ingestion. Am J Emerg Med 1999;17(4):387-393.

2. Salim MA, Case CL, Gillette PC. The JT interval as a depolarization independent measure of repolarization: lessons from catheter ablation of the Wolff-Parkinson-White syndrome. Pacing Clin Electrophysiol. 1995;18:2158–2162.

3. Spodick DH. Reduction of QT-interval imprecision and variance by measuring the JT interval. Am J Cardiol. 1992;70:628–629.

4. Hoffman JR, Votey SR, Bayer M et al. Effect of Hypertonic Sodium Bicarbonate in the treatment of Moderate-to-Severe Cyclic Antidepressant Overdose. Am J Emerg Med. 1993;11:336-441.

Colin Page - Clinical Toxicology Fellow

Geoffrey Isbister - Clinical Toxicologist