In Reply:-We are grateful for comments regarding the execution of our protocol. The goal of that study was to examine the efficacy and safety of remifentanil in neuroanesthetic practice. The study was designed when factors such as cumulative effects of long-term remifentanil infusions (which would occur during complex craniotomies) were unknown. We generally agree with the characterization of our results with one exception. Remifentanil-treated patients required postoperative analgesia earlier than did those receiving fentanyl, but incidence of postoperative analgesic requirement did not differ between groups.
New drugs have been and will continue to be introduced into the practice of anesthesia. Specific examination of the pharmacokinetic and pharmacodynamic properties of any new drug should be obtained in patient populations having unique anesthetic requirements. All anesthetics carry risk. Therefore, interpretation of the effects of a new drug should be made in the context of properties of established agents. This explains our choice of fentanyl-based anesthesia as the comparator group.
Remifentanil proved to be efficacious during neuroanesthesia (a fact unknown before the execution of this protocol). Outcome, to the extent that it was measured, was generally similar for the two opioids. The only logical conclusion is that remifentanil (when administered appropriately) can be substituted for fentanyl with an apparently similar efficacy and safety profile in this patient population. A Phase IV trial examining a far larger population of neurosurgical patients is being conducted to confirm this with respect to relative frequency of adverse events.
Numerous factors other than safety are involved in the decision to select one agent over another. Such factors include cost, convenience, reliability, tradition, and familiarity with the agent. Those factors were not examined in our trial because of practical limitations (e.g., difficulty in quantifying those end-points) and because we believed those factors to be of secondary importance during an initial investigation. In reality, the final verdict regarding appropriate use of a compound does not occur during highly structured clinical trials but rather during routine use by regular anesthesiologists who weigh the above factors and actually make the selection. We hope that we have contributed a scientific basis to that process.
John Guy, M.D.
Department of Anesthesiology; Duke University Medical Center; Durham, North Carolina 27710
Bradley J. Hindman, M.D.
Department of Anesthesia; University of Iowa College of Iowa City, Iowa 52242
William L. Young, M.D.
Department of Anesthesiology; College of Physicians and Surgeons; Columbia University; New York, New York 10032
David S. Warner, M.D.
Department of Anesthesiology; Duke University Medical Center; Box 3094; Durham, North Carolina 27710
(Accepted for publication August 6, 1997.)
The editorial review for these letters was conducted by Lawrence J. Saidman, M.D.