A direct search procedure to optimize combinations of epidural bupivacaine, fentanyl and clonidine for postoperative analgesia

Background The authors applied an optimization model (direct search) to fin d the optimal combination of bupivacaine dose, fentanyl dose, clonidine dos e, and infusion rate for continuous postoperative epidural analgesia. Methods: One hundred ninety patients undergoing 48-h thoracic epidural anal gesia after major abdominal surgery were studied Combinations of the variab les of bupivacaine dose, fentanyl dose, clonidine dose, and infusion rate w ere investigated to optimize the analgesic effect (monitored by verbal desc riptor pain score) under restrictions dictated by the incidence and severit y of side effects. Six combinations were empirically chosen and investigate d. Then a stepwise optimization model was applied to determine subsequent c ombinations until no decrease in the pain score after three consecutive ste ps was obtained. Results: Twenty combinations were analyzed. The optimization procedure led to a reduction in the incidence of side effects and in the mean pain scores . The three best combinations of bupivacaine dose (mg/h), fentanyl dose (mu g/h), clonidine dose (mu g/h), and infusion rate (ml/h) were: 9-21-5-7, 8- 30-0-9, and 13-25-0-9, respectively. Conclusions: Given the variables investigated, the aforementioned combinati ons may be the optimal ones to provide postoperative analgesia after major abdominal surgery. Using the direct search method, the enormous number of p ossible combinations of a therapeutic strategy can be reduced to a small nu mber of potentially useful ones. This is accomplished using a scientific ra ther than an arbitrary procedure.