The Pharmacodynamic Interaction between Propofol and Fentanyl with Respect to the Suppression of Somatic or Hemodynamic Responses to Skin Incision, Peritoneum Incision, and Abdominal Wall Retraction

Abstract

Background Sufficient propofol or fentanyl doses necessary to prevent the response to skin incision do not necessarily attenuate hemodynamic responses during surgery. The goal of this study was to characterize the pharmacodynamic interaction between propofol and fentanyl with respect to the suppression of somatic or hemodynamic responses after three stimuli: skin incision, peritoneum incision, and abdominal wall retraction. Methods Propofol and fentanyl were administered via computer-assisted continuous infusion to provide equilibration between plasma-blood and biophase concentrations. Patients were randomized to nine groups that received predetermined concentrations of fentanyl (from 0 to 9 ng/ml). Each patient was administered different target concentrations of propofol. Somatic and hemodynamic responses were measured before and after each of three different stimulations: skin incision (si), peritoneum incision (pi), and abdominal wall retraction (ret). The propofol plasma concentrations at which 50% of the patients did not respond to each type of stimulation (Cp50si, Cp50pi, and Cp50ret) were calculated by fitting the Loewe synergistic model. Results For propofol alone, Cp50si, Cp50pi, and Cp50ret were 12.9, 17.1, and 19.4 microg/ml, respectively. Increasing the fentanyl concentration markedly reduced propofol Cp50si, Cp50pi, and Cp50ret for somatic response, indicating the potential synergistic interaction of both drugs. During the prestimulation period, fentanyl did not decrease systolic blood pressure; however, propofol specifically decreased systolic blood pressure. Both drugs had a synergistic drug interaction on the systolic blood pressure increase after various surgical stimulations. Fentanyl and propofol concentrations that suppressed both the 50% probability of somatic response and the 50% probability of moderate hemodynamic change defined by the 15% systolic blood pressure increase over the prestimulation value were 3.6 ng/ml and 2.5 microg/ml for skin incision, 8.4 ng/ml and 1.6 microg/ml for peritoneum incision, and 5.9 ng/ml and 5.1 microg/ml for wall retraction, respectively. Conclusions The anesthesia requirements for stimuli that are more intense than skin incision should be considered during abdominal surgery. Somatic and hemodynamic responses varied depending on the type of surgical stimuli.