The Pharmacodynamic Interaction between Remifentanil and Propofol.

M.J. Mertens, M.D., J. Vuyk, M.D., E. Olofsen, M.Sc., Frank H. M. Engbers, M.D., A.G.L. Burm, M.Sc..

Dept of Anaesthesiology, Leiden University Medical Center, Leiden, The Netherlands.

Background and Goal of Study. We studied the effect of propofol (PROP) on the remifentanil (REM) requirements for suppression of responses to lower abdominal surgery.

Materials and Methods. With ethics committee approval and informed consent, 30 ASA 1-2 unpremedicated female patients, aged 18-65 yr, scheduled for lower abdominal surgery, were randomly assigned to receive a target controlled infusion of PROP with target concentrations (Ct) of 2, 4, or 6 mg/ml. In the presence of a constant Ct of PROP the Ct of REM was changed in response to signs of inadequate anaesthesia.¹ Arterial blood samples for the determination of REM and PROP concentrations were collected after blood/effect site equilibration when patients did or did not respond to surgical stimuli. The REM concentrations associated with a 50% probability of no response to lower abdominal surgery (EC₅₀), determined in each patient by logistic regression, were related to the corresponding mean PROP concentrations by nonlinear regression analysis exploring both the possibility of an additive and non-additive interaction.

Results and Discussions. The REM-EC₅₀ versus mean PROP concentrations were best fitted with a non-additive model (R²: 0.43) suggesting that the interaction is synergistic (Fig). With mean PROP concentrations increasing from 1.5 to 10 mg/ml, the REM-EC₅₀ for suppression of responses to lower abdominal surgery decreased from 9.0 to 0 ng/ml.

Conclusions. PROP decreases REM requirements for lower abdominal surgery in female patients in a synergistic manner. With PROP concentrations exceeding 9 mg/ml, REM requirements are close to zero.

References.

1. Vuyk J, Lim T, Engbers FH, et al. Anesthesiology 1995;83:8-22.