Dose-response Relationships of Doxacurium Chloride in Humans during Anesthesia with Nitrous Oxide and Fentanyl, Enflurane, Isoflurane, or Halothane

In a two-part study, the dose-response relationships of doxacurium chloride (BW A938U) were evaluated during general anesthesia maintained with commonly used anesthetic techniques. In part 1, cumulative dose-response methodology was used to establish the ED95 of doxacurium in 36 patients receiving 70% nitrous oxide and fentanyl, or 50% nitrous oxide and either 1.26% enflurane, 0.84% isoflurane, or 0.57% halothane anesthesia. Mechanomyographic response to train-of-four stimulation was used to monitor neuromuscular blockade. The peak effect of doxacurium following each 5 micrograms/kg incremental dose was noted and a log-probit dose-response curve was constructed for each individual patient. The median ED50s were 11 micrograms/kg, 6 micrograms/kg, 8 micrograms/kg, and 8 micrograms/kg for patients receiving fentanyl, enflurane, isoflurane, or halothane anesthesia, respectively. The median ED95s were 24 micrograms/kg, 14 micrograms/kg, 16 micrograms/kg, and 19 micrograms/kg for patients receiving fentanyl, enflurane, isoflurane, and halothane anesthesia, respectively. In part 2, 72 additional patients received a rapid single injection of the ED95 (n = 36) or 2 X ED95 (n = 36) of doxacurium appropriate for the administered anesthetic as estimated from part one of the study. Peak effects of the ED95 given as single injections correlated well with the results in part 1.(ABSTRACT TRUNCATED AT 250 WORDS)