Randomized controlled study on the use of multiple-dose activated charcoal in patients with supratherapeutic phenytoin levels

To the Editor:

In the article by Skinner et al.,¹ a prospective randomized control study was performed to compare management of patients with supratherapeutic phenytoin levels by either observation alone or with multi-dose activated charcoal (MDAC).

The authors state in their statistical power analysis that 19 patients would be needed in order for the data to have validity. However, only 15 patients completed the study. Further, the study excluded critically ill patients, whose participation would have allowed the evaluation of MDAC for supratherapeutic phenytoin levels in patients who need treatment the most. It is likely that a retroactive consent would have allowed their inclusion. Additionally, since study included only male patients with chronic overuse the data obtained cannot be widely extrapolated. Allowing more time to collect data or inclusion of another hospital into the study may have broadened the study and improved its external validity.

Furthermore, the study's control and experimental groups had dissimilar initial phenytoin concentrations. The authors correctly commented that this is a potential confounder. The two outliers in the control group that had concentrations of 47.6 mg/L and 45.6 mg/L, respectively (in Table 1 and Fig. 2), maintained a high phenytoin level for greater than 100 hours. This exceeds the time listed in ‘The Time to Study Completion’ column of Table 1. These two results skew the data and merit further discussion. These results could explain the lack of statistical significance between the study's subgroups of greater than or less than 40 mg/L at initial concentration. Removing these two outliers reveals very little difference between the control and experimental groups as a whole, leading one to question the efficacy of MDAC in patients with phenytoin overdose.

Lastly, the major question that arises from the study is: what is the utility and safety in reducing phenytoin concentrations? Phenytoin toxicity rarely leads to permanent neurological damage and drastically lowering levels may be detrimental to the patient, raising the risk for seizure and complicating redosing.

In conclusion, we commend the authors’ efforts in investigating the management of phenytoin toxicity. However, it is not yet clear that MDAC is safe, or necessary, in the management of patients with phenytoin toxicity.