To the Editor:-The article by Ebert et al. [1]describing an absence of renal injury in volunteers anesthetized with 1.25 minimum alveolar concentration sevoflurane for 8 h raises several issues. First, in a recent letter [2]a colleague of Dr. Ebert's questions the clinical relevance of a study by Eger et al. [3]nearly identical to this study and further comments that “it is alarming that Eger et al. [3]would design and conduct a research protocol that maximized the likelihood that sevoflurane administration would result in human renal injury and that this protocol received approval from the human research review committee.” Are we to infer that the concern expressed in the cited letter no longer exists, and, if not, what in fact were the volunteers and the human research committee evaluating the merits of this study [1]told about the real possibility of renal damage?
Second, the results of this apparently well-done study are substantially different than those of the previous and apparently equally well-done study. [3]More specifically, Eger et al. [3]found evidence of worrisome, albeit transient, renal function changes in volunteers breathing 1.25 minimum alveolar concentration sevoflurane for 8 h, whereas Ebert et al. [1]found little or no renal impairment in volunteers after the same exposure to sevoflurane. It may be that this difference is caused by the greater concentration of compound A reached in subjects in the study by Eger et al. [3]than in those of Ebert et al. [1]Unfortunately, as Ebert et al. 1 state, “an explanation for the divergence of compound A concentrations … is not apparent.”
However, in my opinion, what is more important is that these studies and their divergent results may represent an example of the potential problems related to close, prolonged, and repeated relationships between investigators and pharmaceutical companies. Dr. Eger's studies are and have long been supported by Ohmeda (the manufacturer of desflurane, the anesthetic for which the clinical pharmacology has been principally defined by Eger and his colleagues), whereas the studies of Ebert et al. [1]are and have long been supported by Abbott (the manufacturer of sevoflurane). This in turn recalls my concern expressed several years ago [4]in response to additional apparently well-done studies from Dr. Eger's lab [5,6]that demonstrate the potential for renal damage in laboratory animals after exposure to sevoflurane. At that time, I suggested that it might “have been more appropriate… for the sponsor (Ohmeda) to have engaged alternative investigators to conduct these studies.” I reiterate my concern that investigators (in this case, both Eger et al. [3]and Ebert et al. [1]) may be too strongly linked (emotionally, economically, and scientifically) to one drug, device, technique, or company and that the independence necessary for truly valid, important, and clinically relevant studies might be compromised, if ever so slightly, in subtle and, in many cases, unknown ways. The current situation vis a vis Ebert and Abbott and Eger and Ohmeda reminds me of knights on a field of battle jousting in the names of their respective patrons. Perhaps it is time for Sir Edmond and Sir Thomas to collaborate on a joint study using an agreed-on protocol and a respected, but independent, analytical laboratory that cared little about the data other than as accurate results.
Lawrence J. Saidman, M.D.
Department of Anesthesia; Stanford University School of Medicine; Stanford, California;Isaidman@leland.stanford.edu
(Accepted for publication August 14, 1998.)
