Postoperative modulation of central nervous system prostaglandin E2 by cyclooxygenase inhibitors after vascular surgery

• Published in: Anesthesiology (Philadelphia) 2006-03, Vol.104 (3), p.411-416
• Main Authors: Reuben, Scott S, Buvanendran, Asokumar, Kroin, Jeffrey S, Steinberg, Robert B
• Format: Article
• Language: English
• Subjects: Aged; Central Nervous System - metabolism; Cyclooxygenase Inhibitors - pharmacology; Cyclooxygenase Inhibitors - therapeutic use; Dinoprostone - biosynthesis; Dinoprostone - cerebrospinal fluid; Female; Humans; Lower Extremity - surgery; Male; Middle Aged; Pain, Postoperative - drug therapy; Postoperative Nausea and Vomiting - prevention & control; Vascular Surgical Procedures
• ISSN: 0003-3022
• DOI: 10.1097/00000542-200603000-00006

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 E2 increases with lower extremity vascular surgery and that spinal prostaglandin E2 decreases with intravenous postsurgical administration of either a mixed cyclooxygenase 1/2 inhibitor (ketorolac) or a cyclooxygenase 2 selective inhibitor (parecoxib). 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. Cerebrospinal fluid prostaglandin E2 concentrations were increased during and after surgery. After surgery, intravenous parecoxib 40 mg rapidly decreased cerebrospinal fluid prostaglandin E2, and intravenous ketorolac 30 mg also reduced cerebrospinal fluid prostaglandin E2 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. Cerebrospinal fluid prostaglandin E2 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 E2 concentration and postoperative pain.