Postoperative Morphine Use and Hyperalgesia Are Reduced by Preoperative but Not Intraoperative Epidural Analgesia: Implications for Preemptive Analgesia and the Prevention of Central Sensitization

Background: The aim of this study was to evaluate the postoperative morphine-sparing effects and reduction in pain and secondary mechanical hyperalgesia after preincisional or postincisional epidural administration of a local anesthetic and an opioid compared with a sham epidural control.

Methods: Patients undergoing major gynecologic surgery by laparotomy were randomly assigned to three groups and studied in a double-blinded manner. Group 1 received epidural lidocaine and fentanyl before incision and epidural saline 40 min after incision. Group 2 received epidural saline before incision and epidural lidocaine and fentanyl 40 min after incision. Group 3 received a sham epidural control (with saline injected into a catheter taped to the back) before and 40 min after incision. All patients underwent surgery with general anesthesia.

Results: One hundred forty-one patients completed the study (group 1, n = 45; group 2, n = 49; group 3, n = 47). Cumulative patient-controlled analgesia morphine consumption at 48 h was significantly lower (P = 0.04) in group 1 (89.8 ± 43.3 mg) than group 3 (112.5 ± 71.5 mg) but not group 2 (95.4 ± 60.2 mg), although the hourly rate of morphine consumption between 24 and 48 h after surgery was significantly lower (P < 0.0009) in group 1 (1.25 ± 0.02 mg/h) than group 2 (1.41 ± 0.02 mg/h). Twenty-four hours after surgery, the visual analog scale pain score on movement was significantly less intense (P = 0.005) in group 1 (4.9 ± 2.2 cm) than group 3 (6.0 ± 2.6 cm) but not group 2 (5.3 ± 2.5 cm), and the von Frey pain threshold near the wound was significantly higher (P = 0.03) in group 1 (6.4 ± 0.6 log mg) than in group 3 (6.1 ± 0.8 log mg) but not group 2 (6.2 ± 0.7 log mg).

Conclusions: Preincisional administration of epidural lidocaine and fentanyl was associated with a significantly lower rate of morphine use, lower cumulative morphine consumption, and reduced hyperalgesia compared with a sham epidural condition. These results highlight the importance of including a standard treatment control group to avoid the problems of interpretation that arise when two-group studies of preemptive analgesia (preincisional vs. postsurgery) fail to find the anticipated effects.