In Reply:—
The “black box” warning regarding the use of droperidol for antiemetic prophylaxis issued by Food and Drug Administration (FDA) on December 5, 2001, has created tremendous controversy within the anesthesia community. Many anesthesiologists, myself included, believe that the action taken by the FDA was inappropriate because of its basis on limited and scientifically suspect data. 1This action was thus unwarranted and potentially detrimental to patient care. Many practitioners continue to use low-dose droperidol as a first-line agent for preventing postoperative nausea and vomiting (PONV). Others in our profession have suggested that the FDA warning regarding the use of droperidol should be taken seriously and that practitioners should reconsider the risk/benefit ratio of even low-dose droperidol for managing PONV. 2Regardless of which position (if either) is correct, the position taken by the FDA has had an undeniable effect. As Drs. Bailey and White note, many clinicians have stopped using droperidol, even in very low doses, because of the perceived medicolegal implications of continued use. My own informal polling also indicates that droperidol has even been removed from many hospital formularies out of the same medicolegal concerns.
Unfortunately, strength of personal convictions may have little to do with scientific fact. Evidence-based medicine continues to be the goal of all thoughtful clinicians. Nevertheless, much of the practice of medicine in general, and anesthesiology in particular, must of necessity be based on experience and judgment, because conclusive scientific data may simply not exist. This does not, however, imply that we should not continually question the premises on which our clinical practice is based. Consequently, I am amazed to think that Drs. Bailey and White would believe my editorial “will make some anesthesia providers less comfortable about using this cost-effective antiemetic drug in the future.” I believe it is highly unlikely that thoughtful and conscientious practitioners will be unduly swayed by a balanced presentation.
I stand by my assertion that the risk of serious adverse events (SAEs) associated with the use of low-dose droperidol remains unquantified. Just as important, the risk of SAEs associated with the use of all other antiemetics is also unknown. Similarly, the risk of SAEs from PONV has not been quantified, despite our tacit belief that certain frequently cited complications can occur. To restate this important point: neither the risk of SAEs from low-dose droperidol administration nor from PONV is known. Does this in any way imply that we should not attempt to manage PONV in a responsible fashion? Of course not! Virtually every drug and every therapeutic intervention that can be undertaken in the practice of medicine in general or the specialty of anesthesiology in particular carries some risk. Our duty is to balance the risk with the benefit. Clearly, there are rational strategies for both preventing and treating PONV. Most of these strategies, at least in my opinion, involve the use of low-dose droperidol. To once again restate the obvious, droperidol has a nearly unparalleled safety record coupled with undeniable efficacy. It is a cost-efficient therapeutic option for preventing PONV. The frequency with which this drug has been administered virtually guarantees that some “association” with adverse events will occur. As I pointed out in the editorial, an association of adverse events with drug administration cannot be used to prove cause and effect. So what then is the “point?” The disservice that the FDA's black box warning does is to imply that alternate therapeutic options for managing PONV are somehow “safer” than droperidol. There are not only no data to support this position, but there are also no theoretical reasons to believe that it is so.
The variety of reaction by the anesthesia community to the black box warning on the use of droperidol calls attention to an extremely important philosophical point. It is frequently tempting to confuse the strength of one's beliefs with the weight of scientific evidence. What we believe may not coincide completely with what we know to be true. For instance, it is an incontrovertible fact that a certain percentage of patients undergoing anesthesia and surgery will experience PONV. Nearly as incontrovertible is the fact that low-dose droperidol will prevent a certain percentage of patients from experiencing these symptoms when compared to patients who received no prophylactic therapy. The data on the safety of droperidol is much less conclusive for several reasons. First, how safe is safe? What is an acceptable incidence of adverse effects? Of SAEs up to and including death? Many of us strongly believe that droperidol is in fact “safe” based on the incomplete data that are available. Although it is correct that we can estimate the number of doses of droperidol administered per year, 3the true incidence of SAEs remains unknown. Retrospective data analysis and voluntary reporting, particularly when event frequency is low, are not likely to yield conclusive results. Could prospective data collection provide the answer? The answer is, of course, yes, though as Drs. Bailey and White note, the task would be daunting and might be neither practical nor economically feasible. And even if the exact incidence of adverse effects could be determined, what would be an acceptable death rate for the use of low-dose droperidol?
My personal opinion is that I know droperidol works and I believe that it is safe. As a clinician, educator, and scientist I still am compelled to ask the difficult questions while knowing full well that the answers may be impossible to obtain. Unquestioning adherence to dogma does a disservice to our profession. Questioning accepted practice does not mean abandoning that practice; rather, it means maintaining an open mind and a willingness to change as new information becomes available.
