In Reply:-We thank Drs. Donati and Plaud for pointing out the error in Figure 2in our published study. [1] Unfortunately, this calculation error not only escaped our attention, but also the attention of the reviewers. However, this error does not change our conclusions. The isobolographic analysis still demonstrates a synergistic interaction with respect to the neuromuscular blocking activity of the rocuronium and cisatracurium combination (Figure 1). The experimentally determined ED50(and 95% confidence interval) for the combination was 36.8 (35–38)[micro sign]g/kg for rocuronium and 8.7 (8.3–9.1)[micro sign]g/kg for cisatracurium. The theoretic additive ED50(and 95% confidence interval) was 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. The confidence intervals of these points do not overlap, and the results of a Student t test for potency ratio were significant (P < 0.001), indicating synergism. The fractional (algebraic) analysis of this interaction still demonstrates synergism (Table 1).
Figure 1. First-twitch ED50isobologram for the interaction of rocuronium and cisatracurium. The dashed line connecting the single-drug ED (50) points is the theoretical additive line, and the point on this line is the theoretical additive ED50point (95% confidence interval). The experimentally determined ED50dose (95% confidence interval) of the rocuronium-cisatracurium combination decreased significantly (P < 0.001) below the corresponding theoretical additive point, indicating synergistic interaction.
Figure 1. First-twitch ED50isobologram for the interaction of rocuronium and cisatracurium. The dashed line connecting the single-drug ED (50) points is the theoretical additive line, and the point on this line is the theoretical additive ED50point (95% confidence interval). The experimentally determined ED50dose (95% confidence interval) of the rocuronium-cisatracurium combination decreased significantly (P < 0.001) below the corresponding theoretical additive point, indicating synergistic interaction.
Table 1. ED50Values and 95% CI for Rocuronium and Cisatracurium Administered Alone and in Combination in a Fixed-dose Ratio
Mohamed Naguib, M.B., B.Ch., M.S.C., F.F.A.R.C.S.I., M.D.
Professor of Anesthesiology; Department of Anaesthesiology; King Khalid University Hospital; Riyadh, Saudi Arabia;naguib01@ksu.edu.sa
(Accepted for publication March 31, 1999.)
