We are grateful for the thoughtful criticism expressed by Casserly et al of our article regarding the potential risk of midodrine use in surgical patients. We further appreciate the fact that the apparent point of their letter converges well with the intended message of our article. That is, midodrine is a potentially dangerous drug in surgical patients, especially when the operation will require the use of a vasoconstrictor such as epinephrine. If possible, the drug should be withheld perioperatively when use of such vasoactive agents is anticipated. The additional details that have been provided regarding the pharmacokinetics of the drug and the suggested duration of its withholding preoperatively are welcome additions to our comments.

As stated in our article, we agree with Casserly et al that our patient’s hyperdynamic reaction cannot be attributed to midodrine administration alone. Our speculative assertion was that midodrine may have been acting in concert with epinephrine’s well-known adrenergic effects in a patient with autonomic dysfunction, where hypertension while supine is known to occur in the absence of any pharmacologic therapy. We restate that our patient’s reaction was likely a combination of these elements and that it may have been avoided by preoperatively discontinuing midodrine.

The authors correctly point out that the articles by Low et al and Jankovic et al cite an incidence of supine hypertension of less than 10% with midodrine use. We quoted an incidence in the literature of 25% to 75% in our article. Our reference citation for these numbers should have additionally borne the reader to the article in our bibliography by Chaimberg et al that cites this range in their review. The Physicians’ Desk Reference states that supine hypertension occurs in 22% of patients taking a 10-mg dose and 45% of patients taking a 20-mg dose. Hurst et al reported an incidence of supine hypertension with midodrine use of 75%, although this was a small series. A more recent review by Pathak et al reported that the overall incidence of adverse drug reactions, including supine hypertension, exceeds 80% in patients taking midodrine. These authors suggested that adverse events from antihypotensive agents such as midodrine are likely to have been underestimated and have recommended a reevaluation of their safety.

In sum, although midodrine’s efficacy is well established in the treatment of orthostatic hypotension, there are adverse effects that have the potential to cause serious harm to some surgical patients. Our article was intended to alert surgeons with little experience with prescribing this drug that withholding it perioperatively may enhance patient safety. To this end, we are grateful to Casserly et al for reinforcing our message.