A DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL OF TRANSDERMAL FENTANYL AFTER ABDOMINAL HYSTERECTOMY - ANALGESIC, RESPIRATORY, AND PHARMACOKINETICEFFECTS

Background: A randomized, double-blind, placebo-controlled trial was c onducted to assess the analgesic, pharmacokinetic, and clinical respir atory effects of 72-h application of two transdermal fentanyl (TTSF) p atch sizes in patients undergoing abdominal hysterectomy. Methods: TTS F patches releasing 50 mu g/h (TTSF-50) or 75 mu g/h (TTSF-75) fentany l or placebo patches were applied to 120 women 2 h before abdominal hy sterectomy under general anesthesia. Postoperatively, all patients had access to supplemental morphine using patient-controlled analgesia pu mps. Each patient was attended continuously by a research nurse for 8 h on the night before surgery and for 84 h after patch application. Th e following data were collected: visual analog scale pain scores, supp lementary analgesia, fentanyl plasma concentration (4-h intervals), co ntinuous hemoglobin saturation (pulse oximetry), respiratory pattern ( continuous respiratory inductive plethysmography), and adverse effects (nausea, vomiting, pruritus). Data analysis included analysis of vari ance, Kruskal-Wallis, and chi-squared. P < 0.05 was considered signifi cant. Results: There were no demographic differences among groups. Vis ual analog scale pain scores were significantly lower for the TTSF-75 group, and supplemental morphine was significantly decreased in the TT SF-75 group in the postanesthesia care unit and for both the TTSF-50 a nd the TTSF-75 group for 8-48 h postoperatively. Between 5 and 36 h, t he TTSF groups had significantly increased abnormal respiratory patter n including apneic episodes (tidal volume of less than 100 mi for more than 15 s) and episodes of slow respiratory rate (less than 8 breaths /min persisting for more than 5 min) and significantly increased requi rement for oxygen supplementation. Nine patients in the TTSF groups we re withdrawn because of severe respiratory depression compared to none in the placebo group. No significant between-group differences were p resent in the incidence of nausea, vomiting, or pruritus. Although fen tanyl plasma concentration was higher in the TTSF-75 group than in the TTSF-50 group, the differences were not significant. Fentanyl plasma concentration decreased significantly 48 h after patch application. Co nclusions: Application of TTSF patches 2 h preoperatively is associate d with moderate supplementary opioid requirements for analgesia in the early postoperative period and ongoing opioid supplementation for at least 72 h. Although good analgesia is the result of this combination therapy, it is associated with a high incidence of respiratory depress ion requiring intensive monitoring, oxygen supplementation, removal of the TTSF patches in approximately 11% of the patients, and opioid rev ersal with naloxone in approximately 8% of the patients.