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

Background: Sufficient propofol or fentanyl doses necessary to prevent the response to skin incision do not necessarily attenuate hemodynami c responses during surgery. The goal of this study was to characterize the pharmacodynamic interaction between propofol and fentanyl with re spect to the suppression of somatic or hemodynamic responses after thr ee stimuli: skin incision, peritoneum incision, and abdominal wall ret raction. 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 gr oups that received predetermined concentrations of fentanyl (from 0 to 9 ng/ml). Each patient was administered different target concentratio ns of propofol. Somatic and hemodynamic responses were measured before and after each of three different stimulations: skin incision (si), p eritoneum incision (pi), and abdominal wall retraction (ret). The prop ofol plasma concentrations at which 50% of the patients did not respon d to each type of stimulation (Cp50si, Cp50pi, and Cp50ret) were calcu lated by fitting the Loewe synergistic model. Results: For propofol al one, Cp50si, Cp50pi, and Cp50ret were 12.9, 17.1, and 19.4 mu g/ml, re spectively, increasing the fentanyl concentration markedly reduced pro pofol Cp50si, Cp50pi, and Cp50ret for somatic response, indicating the potential synergistic interaction of both drugs. During the prestimul ation period, fentanyl did not decrease systolic blood pressure; howev er, propofol specifically decreased systolic blood pressure. Both drug s had a synergistic drug interaction on the systolic blood pressure in crease after various surgical stimulations. Fentanyl and propofol conc entrations that suppressed both the 50% probability of somatic respons e and the 50% probability of moderate hemodynamic change defined by th e 15% systolic blood pressure increase over the prestimulation value w ere 3.6 ng/ml and 2.5 mu g/ml for skin incision, 8.4 ng/ml and 1.6 mu g/ml for peritoneum incision, and 5.9 ng/ml and 5.1 mu g/ml for wall r etraction, 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 dep ending on the type of surgical stimuli.