6-ketoprostaglandin-f1-alpha and Pain--Postoperative

Cyclooxygenase 2 inhibition has proven analgesic efficacy in a variety of surgical procedures. We postulated that perioperative cyclooxygenase 2 inhibition significantly reduces postoperative morphine requirements after major thoracic surgery and investigated the site of this potential analgesic effect.. Ninety-two patients participated in this single-center, double-blind, randomized, placebo-controlled, parallel-group trial. Patients between the ages of 18 and 80 yr undergoing a thoracotomy or median sternotomy were randomized to receive either nimesulide or placebo in combination with a standard analgesic regimen perioperatively. Nimesulide was administered orally the evening before surgery and at 12-h intervals for 5 days postoperatively. The primary efficacy variables were morphine consumption and pain scores for the first 48 h postoperatively. The secondary efficacy variable was the effect of nimesulide on cyclooxygenase activity in cerebrospinal fluid (CSF).. Pain scores at rest or with movement, and total morphine consumption for the first 48 h postoperatively, were not statistically different between the groups. The mean difference in total morphine consumption up to 48 h postoperatively between the nimesulide and placebo group was a 9.0 mg reduction (95% CI: -28.9 to 10.9 mg) (P = 0.37). Adjusted mean (se) CSF 6-keto-PGF1alpha (6-keto-PGF1alpha) concentrations increased by 54.7 (25.7) pg/mL from preoperatively to Day + 2 postoperatively in the placebo group, whereas adjusted mean (se) CSF 6-keto-PGF1alpha concentration decreased by 0.6 pg/mL (18.2 pg/mL) in the nimesulide group. These changes were not statistically different between the groups (P = 0.095).. Nimesulide, at a dose of 90 mg twice daily in combination with a standard analgesic regimen, does not influence pain scores, morphine requirements, or CSF prostaglandin levels after major thoracic surgery.

Topics: 6-Ketoprostaglandin F1 alpha; Administration, Oral; Aged; Analgesics, Opioid; Cyclooxygenase 2 Inhibitors; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Morphine; Pain Measurement; Pain, Postoperative; Prospective Studies; Prostaglandin-Endoperoxide Synthases; Sternum; Sulfonamides; Thoracotomy; Time Factors; Treatment Outcome

Prostaglandins (PGs) generated in the spinal cord may play a major role in pain perception. Consequently, the suppression of spinal cyclooxygenase (COX) and PG formation may contribute to the analgesic effect of nonsteroidal anti-inflammatory drugs (NSAIDs) in pain following surgery. Which isoform of COX is responsible for postsurgical pain and, consequently, should be targeted, is unclear.. Prospective randomized blinded study.. University teaching hospital.. Thirty patients undergoing thoracotomy for lobectomy were recruited.. Patients were randomized to receive the COX-2 selective inhibitor nimesulide, 100 mg orally twice daily, or ibuprofen (nonselective), 400 mg orally three times daily, in an open-label study. In addition, there was a randomized control group that received no NSAIDs. Cerebrospinal fluid (CSF) was analyzed for 6-keto-PGF(1)alpha, the principle metabolite of prostacyclin. COX-1 and COX-2 activity was determined by measuring serum thromboxane (TX) B(2) and endotoxin-induced PGE(2) generation in whole blood.. Pain perception was measured by visual analog scores, and blinded assessment of opioid analgesic requirements and expiratory peak flow measurements were performed.. At the doses used, nimesulide was selective for COX-2, while ibuprofen was nonselective based on serum TXB(2) levels. The mean (+/- SEM) levels of 6-keto-PGF(1)alpha in CSF increased following surgery from 32 +/- 4.9 to 127 +/- 29 pg/mL (p < 0.001), and this was suppressed by nimesulide (49 +/- 9.3 pg/mL; p = 0.0025) but not by ibuprofen (122 +/- 35 pg/mL). Pain scores (p < 0.001), morphine requirement (p = 0.0175), and the fall in peak expiratory flow rate (p < 0.001) were significantly lower in the nimesulide group.. Increases in spinal PG synthesis after thoracotomy are repressed by a selective COX-2 inhibitor. This suggests that the inducible COX-2 mediates central PG synthesis, which may be important in the generation of pain, as the use of nimesulide also resulted in significant decreases in postoperative pain perception.

Topics: 6-Ketoprostaglandin F1 alpha; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Humans; Ibuprofen; Isoenzymes; Pain, Postoperative; Perception; Pneumonectomy; Prospective Studies; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Spinal Cord; Sulfonamides; Thoracotomy

One hundred unpremedicated patients scheduled for outpatient restorative dentistry and/or oral surgery were given either 75 mg diclofenac sodium (prostaglandin synthesis inhibitor) or a saline placebo i.v. in a double-blind random fashion before induction of anaesthesia with methohexitone (2 mg/kg). Intubation was facilitated with suxamethonium (1.2 mg/kg) and anaesthesia was maintained with isoflurane in 50% nitrous oxide and oxygen using spontaneous respiration. Cuff pressure was continuously monitored and maintained at 10-25 mmHg. The mean duration of anaesthesia was 141 +/- 75 min in the diclofenac group and 150 +/- 73 min in the saline group. Diclofenac inhibited prostaglandin synthesis, as evident from serum thromboxane B2 and urinary 6-keto-prostaglandin F1 alpha data. There was no difference in recovery as assessed from the orientation time (14.2 +/- 5.7 min and 14.5 +/- 6.3 min for diclofenac and saline patients, respectively), perceptual speed and ability to walk along a straight line 30 and 60 min after anaesthesia. Emetic symptoms were equally common in both groups: an overall incidence of 32.6% and 36.7% for the diclofenac and saline patients, respectively. In the whole patient series women became nauseated and vomited more than men (P less than 0.01). Diclofenac reduced the incidence of pain in the throat or oral region 1 h after anaesthesia (P less than 0.05) and other symptoms 1-24 h postoperatively (P less than 0.01). Thus, preoperative intravenous diclofenac appears useful in ambulatory patients undergoing restorative dentistry and oral surgery under isoflurane anaesthesia.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Ambulatory Surgical Procedures; Anesthesia, Dental; Anesthesia, General; Diclofenac; Double-Blind Method; Epoprostenol; Female; Humans; Injections, Intravenous; Isoflurane; Male; Oral Hemorrhage; Pain, Postoperative; Random Allocation; Thromboxane A2