RETRACTED: Postoperative modulation of central nervous system prostaglandin E2 by cyclooxygenase inhibitors after vascular surgery (Retracted Article)

Background: The clinical availability of injectable cyclooxygenase inhibitors allows examination of the importance of cyclooxygenase 1 and 2 after surgery. The authors hypothesize that spinal prostaglandin E-2 increases with lower extremity vascular surgery and that spinal prostaglandin E-2 decreases with intravenous postsurgical administration of either a mixed cyclooxygenase 1/2 inhibitor (ketorolac) or a cyclooxygenase 2 selective inhibitor (parecoxib). Methods: Thirty patients undergoing elective lower extremity revascularization under continuous spinal anesthesia had cerebrospinal fluid obtained at baseline and then up to 6 h after the start of surgery. Four hours after surgical incision, patients were randomized to receive intravenous parecoxib 40 mg, ketorolac 30 mg, or preservative-free normal saline. Patients were administered intravenous fentanyl in the postanesthesia care unit and acetaminophen/oxycodone on the surgical ward to control pain. Results: Cerebrospinal fluid prostaglandin E-2 concentrations were increased during and after surgery. After surgery, intravenous parecoxib 40 mg rapidly decreased cerebrospinal fluid prostagtandin E-2, and intravenous ketorolac 30 mg also reduced cerebrospinal fluid prostaglandin E-2 compared with placebo, but not as much as parecoxib. Postanesthesia care unit pain scores were reduced in the two drug groups compared with placebo, and surgical ward pain scores were also decreased for both drug groups, especially with parecoxib. No patient receiving parecoxib required postoperative intravenous fentanyl. Acetaminophen/oxycodone consumption was reduced in both drug groups compared with placebo, more so with parecoxib. Conclusions: Cerebrospinal fluid prostaglandin E-2 is elevated in patients after lower extremity vascular surgery. Postsurgical intravenous administration of the cyclooxygenase 1/2 inhibitor ketorolac, and especially the cyclooxygenase 2 inhibitor parecoxib, reduces cerebrospinal fluid prostaglandin E, concentration and postoperative pain.