BACKGROUND: A randomized, double-blind, placebo-controlled trial was conducted to assess the analgesic, pharmacokinetic, and clinical respiratory effects of 72-h application of two transdermal fentanyl (TTSF) patch sizes in patients undergoing abdominal hysterectomy. METHODS:TTSF patches releasing 50 micrograms/h (TTSF-50) or 75 micrograms/h (TTSF-75) fentanyl or placebo patches were applied to 120 women 2 h before abdominal hysterectomy under general anesthesia. Postoperatively, all patients had access to supplemental morphine using patient-controlled analgesia pumps. Each patient was attended continuously by a research nurse for 8 h on the night before surgery and for 84 h after patch application. The following data were collected: visual analog scale pain scores, supplementary analgesia, fentanyl plasma concentration (4-h intervals), continuous hemoglobin saturation (pulse oximetry), respiratory pattern (continuous respiratory inductive plethysmography), and adverse effects (nausea, vomiting, pruritus). Data analysis included analysis of variance, Kruskal-Wallis, and chi-squared. P < 0.05 was considered significant. RESULTS: There were no demographic differences among groups. Visual analog scale pain scores were significantly lower for the TTSF-75 group, and supplemental morphine was significantly decreased in the TTSF-75 group in the postanesthesia care unit and for both the TTSF-50 and the TTSF-75 group for 8-48 h postoperatively. Between 5 and 36 h, the TTSF groups had significantly increased abnormal respiratory pattern including apneic episodes (tidal volume of less than 100 ml 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 requirement for oxygen supplementation. Nine patients in the TTSF groups were withdrawn because of severe respiratory depression compared to none in the placebo group. No significant between-group differences were present in the incidence of nausea, vomiting, or pruritus. Although fentanyl 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. CONCLUSIONS: Application of TTSF patches 2 h preoperatively is associated 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 depression requiring intensive monitoring oxygen supplementation, removal of the TTSF patches in approximately 11% of the patients and opioid reversal with naloxone in approximately 8% of the patients.
RCT Entities:
BACKGROUND: A randomized, double-blind, placebo-controlled trial was conducted to assess the analgesic, pharmacokinetic, and clinical respiratory effects of 72-h application of two transdermal fentanyl (TTSF) patch sizes in patients undergoing abdominal hysterectomy. METHODS:TTSF patches releasing 50 micrograms/h (TTSF-50) or 75 micrograms/h (TTSF-75) fentanyl or placebo patches were applied to 120 women 2 h before abdominal hysterectomy under general anesthesia. Postoperatively, all patients had access to supplemental morphine using patient-controlled analgesia pumps. Each patient was attended continuously by a research nurse for 8 h on the night before surgery and for 84 h after patch application. The following data were collected: visual analog scale pain scores, supplementary analgesia, fentanyl plasma concentration (4-h intervals), continuous hemoglobin saturation (pulse oximetry), respiratory pattern (continuous respiratory inductive plethysmography), and adverse effects (nausea, vomiting, pruritus). Data analysis included analysis of variance, Kruskal-Wallis, and chi-squared. P < 0.05 was considered significant. RESULTS: There were no demographic differences among groups. Visual analog scale pain scores were significantly lower for the TTSF-75 group, and supplemental morphine was significantly decreased in the TTSF-75 group in the postanesthesia care unit and for both the TTSF-50 and the TTSF-75 group for 8-48 h postoperatively. Between 5 and 36 h, the TTSF groups had significantly increased abnormal respiratory pattern including apneic episodes (tidal volume of less than 100 ml 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 requirement for oxygen supplementation. Nine patients in the TTSF groups were withdrawn because of severe respiratory depression compared to none in the placebo group. No significant between-group differences were present in the incidence of nausea, vomiting, or pruritus. Although fentanyl 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. CONCLUSIONS: Application of TTSF patches 2 h preoperatively is associated 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 depression requiring intensive monitoring oxygen supplementation, removal of the TTSF patches in approximately 11% of the patients and opioid reversal with naloxone in approximately 8% of the patients.