QTc prolongation and valproate toxicity

To the Editor:

We thank Ray and Skellett for highlighting the need for cardiac monitoring in patients presenting with valproic acid overdose.¹ Of note, they remarked on prolonged QTc in relation to high serum concentration of valproic acid that corrected as serum concentrations normalized. To our knowledge, a relationship between valproic acid overdose and QTc prolongation was previously reported, and the authors suggested that this effect might be due to valproic acid action on sodium channels.²

However, it is also reported that severe valproic acid overdose, that is, in concentrations usually above 450 mg/L, can lead to hypocalcemia.^3,4 Unfortunately, the authors Ray and Skellett did not report a serum calcium concentration for their case. We wonder whether the prolonged QTc observed might have been related to the underlying hypocalcemia. If the calcium concentrations were normal, other hypotheses could be formulated, such as reduced inward rectifying potassium currents in cardiac myocytes. Further studies on the electrophysiologic properties of valproic acid would help answer this question.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.