We read with interest the article by Ramsay and Luterman1and accompanying editorial2discussing the use of high-dose dexmedetomidine as a single-agent intravenous anesthetic. We have several concerns, both with the technique described and the journal’s editorial position.

As to the case series itself, we wonder what was the basis for the clinical choice to use doses of dexmedetomidine at more than 7 to 50 times the recommended dose range of 0.2–0.7 μg·kg−1·h−1as the sole anesthetic. Ebert et al.’s work with volunteers3was extremely limited and in no way established dexmedetomidine as a safe single-agent anesthetic. Indeed, doses of dexmedetomidine lower than those in the case series have been recently reported as “accidental overdose” and are accompanied by guidelines for the management of same.4Although Ramsay and Luterman’s cases imply that the doses were increased when the patients could not tolerate the procedures at lower dose levels, there is no mention of the initial anesthetic plan. Did the authors undertake the anesthetics with the expectation of using dexmedetomidine at massive, unstudied doses? Given the properties of dexmedetomidine at its usual clinical dose range, it is unlikely that patients would be able to tolerate the procedures described without either supplementation or rapid escalation to massive doses, as actually occurred. We find no convincing evidence in the literature to believe that their course of action could be chosen with confidence in its safety and efficacy. The intraoperative management of the cases is also unusual. We fail to understand their need to avoid the use of supplemental oxygen except when absolutely necessary. The argument regarding electrocautery is unconvincing. It is almost as if the decreased margin of safety is used as a demonstration of dexmedetomidine’s properties with respect to maintenance of ventilation. In the two cases that did not receive supplemental oxygen, were the patients subsequently placed on oxygen in the postanesthesia care unit? Finally, we question the assertion that recovery time in these patients was not significantly prolonged when compared with many conventional anesthetic techniques. A recovery time and postanesthesia care unit stay of 2 to 3 h is considered by many to be significantly prolonged and is not a desirable side effect.

We are therefore concerned that Anesthesiology tacitly endorses this anesthetic technique by calling it “another arrow for the clinician’s quiver” in the accompanying editorial. On the basis of Ebert et al.’s two volunteers and the three cases described by Ramsay and Luterman, are we to assume that this is now an acceptable practice? Certainly, we all daily administer many medications “off-label” in a safe and reasonable manner. There comes a point, however, when the off-label use of a drug crosses the line of “reasonable” and becomes a deviation from the standard of care. Until properly controlled, Institutional Review Board reviewed clinical studies (with appropriate informed patient consent) are conducted addressing safety and efficacy issues of the doses in question, it is premature to call single-agent intravenous dexmedetomidine “another arrow for the clinician’s quiver.” A case report or small series of cases should highlight an unusual occurrence, pathology, or unanticipated anesthetic intervention, rather than act as a proving ground for new anesthetic techniques. There is nothing in the article to suggest that the patients involved provided informed consent as to the unusual nature of the anesthetic. Similarly, it does not appear that an Institutional Review Board or hospital ethics committee was consulted regarding this “case series.” The practice of anesthesiology is neither a contest of skills nor a game of what one can get away with. The essence of the practice of anesthesiology is the planning and administration of the safest and most efficient anesthetic for a given individual patient using principles grounded in science and controlled clinical studies. An unusual technique that worked in three patients does not rise to this standard and sidesteps the checks and balances of ethical scientific investigation.

Finally, the lack of complete disclosure of conflicts of interest on Dr. Ebert’s part is disturbing. The attestation states, “Dr. Ebert is not supported by, nor maintains any financial interest in, any commercial activity that may be associated with the topic of this editorial.” This may be true only in the strictest and most limited interpretation of the statement, but ignores Dr. Ebert’s long and close association with Abbott Laboratories (Abbott Park, IL) and previous substantial financial support and honoraria. In fact, the study cited by Ebert in the editorial, examining high-dose dexmedetomidine in volunteers,3was itself supported by a grant from Abbott Laboratories. At best, this is disingenuous. The casual reader of the journal should be fully aware that an unproven anesthetic technique, utilizing an expensive drug manufactured by Hospira, Inc. (Lake Forest, IL), a wholly-owned spin-off company of Abbott Laboratories, is advocated by an Abbott-funded investigator and is trumpeted by editorial writers with a long history of close association and support from Abbott Laboratories. It is difficult to understand how one can consider this an objective review of scientific data.

* University of Mississippi School of Medicine, Jackson, Mississippi. gmychaskiw@anesthesia.umsmed.edu

Ramsay MAE, Luterman DL: Dexmedetomidine as a total intravenous anesthetic agent. Anesthesiology 2004; 101:787–90
Ebert T, Maze M: Dexmedetomidine: Another arrow for the clinician’s quiver. Anesthesiology 2004; 101:568–70
Ebert TJ, Hall JE, Barney JA, Ulrich TD, Colinco MD: The effects of increasing plasma concentrations of dexmedetomidine in humans. Anesthesiology 2000; 93:382–94
Jorden VS, Pousman RM, Sanford MM, Thorborg PA, Hutchens MP: Dexmedetomidine overdose in the perioperative setting. Ann Pharmacother 2004; 38:803–7