Valproate toxicity in a child

To the Editor:

We thank [the correspondents] for their enquiry into potential mechanisms of QTc prolongation in our reported case of valproate overdose. In our original report we had speculated that the electrophysiological effects of valproate may be mediated through sodium channels, based on previous reports.¹ However, we accept that other mechanisms may be responsible.

The serum calcium in our child at presentation to their local hospital was 2.44 mmol/L with 47 g/L of albumin. This corresponded with an ionized calcium of 1.28 mEq/l on a blood gas. The ionized calcium dropped to 0.98 mEq/L when checked by the intensive care retrieval team 4 h later. This was corrected with calcium gluconate. On admission to the ICU the serum calcium was 1.98 mmol/L, corresponding with an ionized calcium of 1.05 mEq/L. This dropped slightly to a minimum of 0.94 mEq/L with haemofiltration, but was again corrected with calcium gluconate. All subsequent ionized calcium values were above 1 mEq/L, and the serum calcium was 2.09 mmol/L the following day.

We have also been asked about the heart rates when the QTc was noted to be prolonged. At presentation to her local hospital our child had a heart rate of 130–150/min, with a QTc in the normal range (320 ms). After admission to the ICU her QTc was noted to be prolonged at 500 ms with a heart rate between 110 and 120/min. At this point, she was sedated with morphine (20 μg/kg/h) and midazolam (2 μg/kg/min) infusions. The QTc normalized the following day after the valproate had been cleared to 400 ms, with a heart rate of 100–110/min. Although both morphine and midazolam infusions had been stopped, it was unlikely that the drugs had been fully cleared.

We accept that hypocalcaemia secondary to valproate may have been a cause for our child's prolonged QTc, although this had been corrected promptly on detection. We also accept the need for further investigation into the electrophysiological effects of valproate, although this should not detract from its use as an anti-convulsant. However, as we have previously suggested, in the context of a valproate overdose, cardiac monitoring is necessary.