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Letter to the Editor

USE OF INTRAVENOUS ACETYLCYSTEINE We recently reviewed Dr. Cantrell’s paper describing an increased use of intravenous acetylcysteine after the approval and release of an intravenous (IV) acetylcysteine formulation in the United States. While we agree with their conclusion that the medication use patterns changed after the release of IV acetylcysteine, we believe that several points from their discussion warrant comment. First, the authors do not adequately discuss that patients treated in the post-IV approval period were much less likely to develop major outcomes (OR 5 0.3 vs pre-IV approval patients). This finding is briefly mentioned, but the discussion is minimal. Although we recognize that this result may not be related to the increased use of IV acetylcysteine, the authors should thoroughly discuss the possible reasons for this clinically important and statistically significant finding. Second, the statement that IV acetylcysteine has ‘‘a higher rate of serious adverse events’’ suggests that the difference in severe adverse events between the oral and intravenous route is clinically significant. In fact, the overall rate of adverse events is higher for patients treated with oral acetylcysteine than for patients treated with IV acetylcysteine. Although adverse events occur with IV acetylcysteine, almost all are managed by stopping the infusion and treating the patient with antihistamines. Third, the authors cite a high rate of medication errors associated with IV administration as evidence that IV administration is inferior to oral therapy. Even though the Hayes study cited describes a high incidence of medication errors, none of the reported errors were of clinical significance or resulted in an adverse event. Furthermore, almost half of the errors involved administration to patients who did not require treatment; it seems unlikely that this error is related to the route of administration alone. Finally, in the discussion the authors postulate several reasons for the increase in use of IV acetylcysteine after the release of the IV product. For example, the authors state that ‘‘high rate of use may be the perception that Acetadote is safer than the oral product given IV’’ and ‘‘the change in IV NAC usage and the subsequent disproportionate use of Acetadote without published rationale may be the result of effective promotional campaigns by the manufacturer of Acetadote or the mistaken assumption that newly approved products are always superior to existing products.’’ As this study did not attempt to measure the perception of safety or the effectiveness of the promotional campaign, these statements are speculation. A more thorough discussion of alternative causes for the increase in IV use (such as ease of administration, fewer doses to be delivered, patient preference, and lower need for antiemetics) would help generate a hypothesis for future studies that could identify the reasons IV acetylcysteine used is increasing.