Quantifying the effect of enflurane on atracurium infusion requirements

The present study was designed to evaluate the interaction between atracurium and enflurane in 40 adult surgical patients using closed-loop feedback control of infusions of atracurium. Anaesthesia was induced with thiopentone and fentanyl and intubation was facilitated with atracurium 0.5 mg· kg^?1 lean body mass. During the first 90 min, anaesthesia was maintained with nitrous oxide in oxygen (2:1) and fentanyl. For the following 90 min the patients were randomly assigned to receive enflurane at different end-tidal concentrations: Group I, control, fentanyl-nitrous oxide anaesthesia; Group II, enflurane 0.3%-nitrous oxide; Group III, enflurane 0.6%-nitrous oxide; Group IV, enflurane 0.9%-nitrous oxide. The possible interaction of atracurium with enflurane was quantified by determining the asymptotic steady-state rate of infusion (I_ss) of atracurium necessary to produce a constant 90% neuromuscular block. This was accomplished by applying nonlinear curve fitting to data on the cumulative dose requirements. Every patient served as his/her own control and the changes in the infusion rates were determined individually. Patient characteristics and controller performance, i.e., the ability of the controller to maintain the neuromuscular blockade constant at the setpoint, did not differ among groups. In Group II I_ss decreased from 0.33 ± 0.12 to 0.26 ± 0.08 mg· kg^?1· hr^?1 (P < 0.01), in Group III from 0.32 ± to 0.12 to 0.24 ± 0.08 mg· kg^?1· hr^?1 (P < 0.001) and in Group IV from 0.29 ± 0.09 to 0.21 ± 0.09 mg· kg^?1 · hr^?1 (P < 0.001). In the control group atracurium requirements remained unchanged throughout the study. Enflurane reduces atracurium requirements in a dose-dependent manner. During enflurane anaesthesia the rate of atracurium infusion should be reduced but because of interindividual differences the monitoring of the neuromuscular function is important to ensure the appropriate level of neuromuscular block.