To the Editor:-In a recent study, Naguib et al. [1] reported dose-response data of rocuronium and cisatracurium administered alone or in combination. We would like to ask the authors to clarify an inconsistency between (1) the degree of potentiation as described in the Results section, Table 1, and Figure 2, and (2) the dose-response curves shown in Figure 1and maximum depression data presented in Table 3. The authors state that "The experimentally determined ED50(and 95% confidence interval) for the combinations was 7.1 (5.4–8.7)[micro sign]g/kg for rocuronium and 1.7 (1.3–2)[micro sign]g/kg for cisatracurium. The theoretical additive ED50was calculated to be 55.5 (53.3–57.7)[micro sign]g/kg for rocuronium and 13.1 (12.6–13.6)[micro sign]g/kg for cisatracurium." Figure 2in their article is entirely consistent with this statement, which implies that when administered together, rocuronium and cisatracurium would be eight times more potent than expected from pure additivity! However, the dose-response curves in Figure 1of their article indicate that the ED50of the combination is approximately 0.65 x ED50equivalents. Thus, one would expect the ED (50) of the combination to be 36 [micro sign]g/kg rocuronium plus 8.5 [micro sign]g/kg cisatracurium, that is, 0.65 times the expected values of 55.5 [micro sign]g/kg and 13.1 [micro sign]g/kg, respectively. Table 3is consistent with the calculations made from Figure 1, because the ED25of each drug (rocuronium 28 [micro sign]g/kg and cisatracurium 6.5 [micro sign]g/kg) yielded 32.3% block, whereas the ED50(56 [micro sign]g/kg and 13 [micro sign]g/kg, respectively) yielded 77% block. From these data it can be estimated that 50% blockade would be produced by intermediate doses between the ED25and the ED50of both drugs as previously mentioned, which represents approximately 36 [micro sign]g/kg rocuronium plus 8.5 [micro sign]g/kg cisatracurium. This estimate is several times greater than the doses of 7.1 (5.4–8.7)[micro sign]g/kg for rocuronium and 1.7 (1.3–2)[micro sign]g/kg for cisatracurium reported in the Results section. We believe that this is a rather important discrepancy that the authors must clarify.
Francois Donati, Ph.D., M.D., F.R.C.P.C.
Professor
Benoit Plaud, M.D.
Visiting Professor; Department of Anaesthesia; CHUM-Campus Hotel-Dieu and Universite de Montreal; Montreal, Quebec, Canada;donatif@medclin.umontreal.ca
(Accepted for publication March 31, 1999.)
