thromboxane-b2 and Pain--Postoperative

Based on a PubMed search of the literature using the terms parecoxib, platelets, thromboxane, bleeding, and platelet aggregation, the effects of parecoxib on platelet function have not fully been established under clinical conditions.. The aim of this study was to determine platelet aggregation, thromboxane B(2) (TxB(2)) formation, and plasma concentrations with the use of parecoxib in postoperative pain management.. This double-blind, randomized, parallel-group trial was conducted at the University Hospital for Orthopedic Surgery, Friedrichsheim, Frankfurt, Germany. Male and female patients aged 18 to 55 years and scheduled to undergo routine partial meniscectomy (or a similar arthroscopic procedure) were eligible. All patients received dose-adjusted enoxaparin before surgery and parecoxib 40 mg BID or dipyrone 1000 mg QID. Blood samples were drawn before first injection (predose) and at 0.5, 2, and 6 hours after injection. Platelet aggregation (expressed as percentage of the maximal light transmittance [A(max)]) was induced with arachidonic acid (A(max)AA) and collagen (A(max)CO). TxB(2) formation was determined using enzyme-linked immunosorbent assay.. This study included 26 patients. In both treatment groups, 8 males and 5 females, all white, were enrolled. In the dipyrone group, the mean age was 48 years (range, 32-61 years) and the mean weight was 85 kg (range, 63-122 kg); in the parecoxib group, the mean age was 47 years (range, 31-61 years) and the mean weight was 81 kg (range, 57-100 kg). Median (interquartile range [IQR]) predose values for A(max)AA were 76% (65%-83%) in the parecoxib group and 87% (80%-89%) in the dipyrone group. At 0.5 hour after injection, A(max)AA was 52% (5%-77%) with parecoxib and 8% (0%-11%) with dipyrone (P=0.004). At 2 hours after injection, A(max)AA was 78% (72%-80%) in the parecoxib group versus 7% (5%-11%) in the dipyrone group (P<0.001). At 6 hours after study drug administration, no treatment differences were found. For A(max)CO, no statistically significant differences were found. Consistent with the stronger inhibition of aggregation, patients who received dipyrone had lower TxB(2) formation values. Six hours after parecoxib administration, mean TxB(2) formation was significantly enhanced compared with predose values (132 ng/mL [IQR, 62-228 ng/mL] vs 185 ng/mL [IQR, 135-239 ng/mL]; P=0.05).. Platelet aggregation and TxB(2) formation were significantly lower for 6 hours in dipyronetreated patients compared with parecoxib-treated patients. In contrast, TxB(2) formation was increased with parecoxib 6 hours after administration compared with pretreatment values. In this small study, parecoxib did not affect platelet aggregation in a population of patients undergoing routine partial meniscectomy (or a similar arthroscopic procedure) under clinical conditions.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthroscopy; Child; Cyclooxygenase Inhibitors; Dipyrone; Double-Blind Method; Drug Therapy, Combination; Enoxaparin; Enzyme-Linked Immunosorbent Assay; Female; Humans; Isoxazoles; Male; Middle Aged; Pain, Postoperative; Platelet Aggregation; Thromboxane B2

Paracetamol is often given as an adjunctive analgesic to reduce opioid-related adverse effects but its optimal dose is unknown. We studied the analgesic effect and safety of a single 3-g intravenous (i.v.) dose of paracetamol in adults.. One hundred and seven patients undergoing tonsillectomy under local anaesthesia were randomly allocated to receive i.v. 3 g of paracetamol, 75 mg of diclofenac or placebo prior to surgery. The consumption of post-operative morphine using a patient-controlled analgesia-device was quantified for 6 h. Platelet aggregation and the concentrations of paracetamol, liver aminotransferases, glutathione transferase alpha 1-1 (GSTA1-1) and thromboxane B(2) were measured.. During the first hours after surgery, both paracetamol and diclofenac reduced (P < 0.05) the consumption of morphine but had no effect thereafter. The values for the 6-h cumulative consumption of morphine in patients given paracetamol (18.7 +/- 13.8 mg), diclofenac (16.1 +/- 9.9 mg) and placebo (22.0 +/- 12.1 mg) did not differ. Paracetamol had no effect on platelet aggregation, which was impaired only by diclofenac in response to arachidonic acid (P < 0.005). Both paracetamol (P < 0.01) and diclofenac (P < 0.005) inhibited the release of thromboxane B(2) at 1 h but they did not affect serum aminotransferase and GSTA1-1 levels. One patient given paracetamol displayed a transient increase in GSTA1-1 and liver aminotransferases.. During the initial hours after tonsillectomy, the administration of 3 g of i.v. paracetamol and 75 mg of diclofenac reduced the consumption of morphine. Both drugs also reduced the release of thromboxane B(2) from activated platelets but only diclofenac had a negative effect on platelet aggregation. In sensitive individuals, large doses of paracetamol may disturb the hepatocellular integrity. We do not recommend the use of i.v. doses of paracetamol higher than 1 g.

Topics: Acetaminophen; Adult; Analgesics, Non-Narcotic; Anesthesia, Local; Anti-Inflammatory Agents, Non-Steroidal; Diclofenac; Dose-Response Relationship, Drug; Double-Blind Method; Female; Glutathione Transferase; Humans; Liver; Male; Pain Measurement; Pain, Postoperative; Platelet Aggregation; Prospective Studies; Statistics, Nonparametric; Thromboxane B2; Time Factors; Tonsillectomy

The therapeutic effects of glucocorticoids are generally attributed to suppression of multiple signaling pathways involved in the inflammatory response leading to decreased levels of inflammatory mediators at the site of injury. This study evaluated the in vivo relationship between levels of prostanoids at the site of tissue injury and analgesia after dexamethasone administration in a clinical model of tissue injury.. Subjects were administered dexamethasone 4 mg or placebo 12 hours and 1 hour before the removal of 2 mandibular third molars. A microdialysis probe was implanted at each surgical site for measurement of immunoreactive prostaglandin E2 (PGE(2)) or immunoreactive thromboxane B(2) (TxB(2)), and pain was measured concurrently. Subjects received either ketorolac 30 mg intravenously or placebo at pain onset.. PGE(2) was detectable in the first postoperative sample, decreased over the next hour and then increased coincident with the onset of postoperative pain. Administration of dexamethasone suppressed PGE(2) levels in samples collected at pain onset in comparison to placebo and significantly suppressed TxB(2) at the surgical site but without any effect on pain report. Subsequent administration of ketorolac significantly reduced pain while decreasing both PGE(2) and TxB(2) levels at the surgical site.. The lack of an analgesic effect for dexamethasone while reducing both PGE(2) and TxB(2) at the site of injury in comparison to ketorolac analgesia accompanied by greater reductions in levels of these prostanoids suggests that glucocorticoids at this dose do not suppress PGE(2) release sufficiently to attenuate peripheral sensitization of nociceptors after tissue injury.

Topics: Adult; Analgesia; Analysis of Variance; Anti-Inflammatory Agents, Non-Steroidal; Dexamethasone; Dinoprostone; Double-Blind Method; Female; Humans; Ketorolac; Male; Mandible; Molar, Third; Pain Measurement; Pain, Postoperative; Postoperative Care; Preoperative Care; Prospective Studies; Thromboxane B2; Tooth Extraction; Tooth, Impacted

Prostanoids formed by cyclooxygenase play an important role in pain and the induction of inflammation. It is generally believed that COX-1 is constitutively expressed, whereas COX-2 is primarily inducible during inflammation. This study examined the in vivo selectivity of celecoxib, a COX-2 inhibitor, and evaluated whether estimates of selectivity that are based on in vitro and ex vivo analyses are reliable indicators of in vivo selectivity.. Subjects (103 outpatients undergoing surgical removal of two impacted mandibular third molars) received either 200 mg celecoxib, 600 mg ibuprofen, or placebo 8 hours before surgery and a second dose 1 hour before surgery. After surgery, microdialysis probes were placed in the surgical sites for collection of inflammatory transudate. Samples were collected every 20 minutes and pain intensity was estimated concurrently with a visual analog scale and a categorical rating scale for up to 4 hours after surgery.. A significant analgesic effect (P <.01, compared with placebo) was shown for both drugs, with the efficacy of celecoxib being intermediate between ibuprofen and placebo. A similar relationship was observed for the suppression of prostaglandin E(2) (a product of both isoforms) at time points consistent with COX-2 expression (P <.001). Ibuprofen consistently suppressed thromboxane B(2) (a product of COX-1) levels at all time points (P <.05), whereas the effect of celecoxib did not differ from that of placebo.. The suppression of products of COX-2 coincident with pain suppression and the absence of COX-1 inhibition suggest that celecoxib is a relatively selective COX-2 inhibitor in vivo.

Topics: Adult; Celecoxib; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Dinoprostone; Double-Blind Method; Enzyme-Linked Immunosorbent Assay; Female; Humans; Ibuprofen; Isoenzymes; Male; Membrane Proteins; Microdialysis; Molar, Third; Oral Surgical Procedures; Pain Measurement; Pain, Postoperative; Prostaglandin-Endoperoxide Synthases; Pyrazoles; Substrate Specificity; Sulfonamides; Thromboxane B2; Tooth Extraction