Analgesic efficacy of rofecoxib compared with codeine/acetaminophen using a model of acute dental pain.

OBJECTIVE: To determine analgesic efficacy of a single oral dose of rofecoxib 50 mg compared with acetaminophen/codeine 600/60 mg, we conducted a double-blind, randomized, placebo- and active-comparator-controlled, parallel-group study. STUDY DESIGN: Patients (N = 390) experiencing moderate or severe pain postextraction of 2 or more third molars, with at least 1 mandibular impaction, were randomized to placebo (n = 30), rofecoxib (n = 180), or codeine/acetaminophen 60/600 mg (n = 180). Time to confirmed perceptible pain relief, and patient evaluations of pain intensity, pain relief, and global assessments were recorded. RESULTS: For total pain relief over 6 hours (primary end point), rofecoxib was superior to codeine/acetaminophen (15.5 vs 10.7; P < .001). Rofecoxib was statistically significantly superior to codeine/acetaminophen with respect to TOPAR4, patient global assessment, peak pain relief, and duration of analgesic effect. Median onset of analgesia was similar for both drugs. The codeine/acetaminophen group had more patients with 1 or more adverse events. CONCLUSION: Rofecoxib provided superior analgesic efficacy compared with codeine/acetaminophen with fewer gastrointestinal and nervous system adverse events.     

Effective treatment of laparoscopic cholecystectomy pain with intravenous followed by oral COX-2 specific inhibitor

In this multicenter, double-blinded, randomized, placebo-controlled study we evaluated the analgesic and opioid-sparing efficacy of a preoperative dose of i.v. parecoxib followed by oral valdecoxib in treating pain associated with elective laparoscopic cholecystectomy. Patients were randomized to receive a single i.v. dose of parecoxib 40 mg (n = 134) or placebo (n = 129) 30-45 min before induction of anesthesia. Six to 12 h after the i.v. dose, the parecoxib group received a single oral dose of valdecoxib 40 mg, followed by valdecoxib 40 mg qd on postoperative days 1-4, then 40 mg qd prn days 5-7. The placebo i.v. group received oral placebo on an identical schedule. All patients were allowed supplemental i.v. fentanyl as needed during the first 4 h postoperatively (T0-240 min) followed by hydrocodone 5 mg/acetaminophen 500 mg (Vicodin(R); 1-2 tablets orally every 4-6 h as needed). Patients taking parecoxib used 21% less fentanyl than those receiving placebo (P = 0.011). The mean area under the curve of pain intensity (PI) scores over time from T0-240 min was 55.2 for parecoxib and 61.2 for placebo (P = 0.083). At T180 and T240 min, mean PI score was 7.0 and 7.6 points lower in the parecoxib group, respectively (P < 0.02). Fewer patients on valdecoxib required supplemental analgesics (P < 0.05) after discharge. At T240 min and at day 7, Patient's and Physician's/Nurse's Global Evaluations were significantly better in the parecoxib/valdecoxib group (P < 0.05). Incidences of adverse events, adverse events causing withdrawal, and serious adverse events were less for parecoxib/valdecoxib than for placebo. The authors conclude that preoperative parecoxib is a valuable opioid-sparing adjunct to the standard of care for treating pain after laparoscopic cholecystectomy, and subsequent treatment with oral valdecoxib extends this clinical benefit. IMPLICATIONS: Parecoxib 40 mg i.v., 30-45 min preoperatively followed by oral valdecoxib 40 mg qd reduced opioid requirements and provided superior pain relief as well as improved patient global evaluation after laparoscopic cholecystectomy.     

Preoperative oral rofecoxib does not decrease postoperative pain or morphine consumption in patients after radical prostatectomy: a prospective, randomized, double-blinded, placebo-controlled trial

STUDY OBJECTIVES: To evaluate the analgesic efficacy of the rofecoxib po before radical prostatectomy. DESIGN: Prospective, randomized, double-blinded, placebo-controlled trial. SETTING: Teaching hospital. PATIENTS: Anesthetic management was standardized. Patients received either a 50-mg rofecoxib capsule or a placebo capsule po 1 hour before induction of anesthesia. MEASUREMENTS AND MAIN RESULTS: Patient-generated 10-cm visual analog scale (VAS) scores for pain were assessed at 1, 2, 4, 6, 8, and 24 hours after surgery. Morphine consumption was recorded from a patient-controlled analgesia device at the same time. A patient-generated overall pain relief score was obtained at 24 hours after surgery. We were unable to detect any differences between study groups with respect to postoperative morphine consumption, VAS score, or overall pain relief score. CONCLUSIONS: When rofecoxib is used po in maximum recommended doses before surgery, it does not provide significant analgesia that results in reduction in pain scores or analgesic requirements for patients after radical prostatectomy.     

A systematic review of COX-2 inhibitors compared with traditional NSAIDs, or different COX-2 inhibitors for post-operative pain

BACKGROUND: We have reviewed the analgesic efficacy of cyclooxygenase-2 (COX-2) inhibitors compared with traditional non-steroidal anti-inflammatory drugs (NSAIDs), different COX-2 inhibitors, and placebo in post-operative pain. METHODS: Randomized controlled trials were evaluated. Outcome measures were pain scores and demand for supplementary analgesia 0-24 h after surgery. RESULTS: Thirty-three studies were included in which four COX-2 inhibitors, rofecoxib 50 mg, celecoxib 200 and 400 mg, parecoxib 20, 40 and 80 mg, and valdecoxib 10, 20, 40, 80 mg were evaluated. Ten of these studies included 18 comparisons of rofecoxib, celecoxib, or parecoxib with NSAIDs. Rofecoxib 50 mg and parecoxib 40 mg provided analgesic efficacy comparable to that of the NSAIDs in the comparisons, and with a longer duration of action after dental surgery but possibly not after major procedures. Celecoxib 200 mg and parecoxib 20 mg provided less effective pain relief. Four studies included five comparisons of rofecoxib 50 mg with celecoxib 200 and 400 mg. Rofecoxib 50 mg provided superior analgesic effect compared with celecoxib 200 mg. Data on celecoxib 400 mg were too sparse for firm conclusions. Thirty-three studies included 62 comparisons of the four COX-2 inhibitors with placebo and the COX-2 inhibitors significantly decreased post-operative pain. CONCLUSION: Rofecoxib 50 mg and parecoxib 40 mg have an equipotent analgesic efficacy relative to traditional NSAIDs in post-operative pain after minor and major surgical procedures, and after dental surgery these COX-2 inhibitors have a longer duration of action. Besides, rofecoxib 50 mg provides superior analgesic effect compared with celecoxib 200 mg.     

Propacetamol versus ketorolac for treatment of acute postoperative pain after total hip or knee replacement

We assessed the analgesic efficacy of IV propacetamol and ketorolac in a double-blinded, placebo-controlled study involving patients undergoing total hip or knee replacement procedures. On the first morning after major joint replacement surgery, 164 patients experiencing moderate-to-severe pain were randomly assigned to receive an IV infusion of propacetamol (2 g), ketorolac (15 or 30 mg), or placebo (saline). Patient-controlled analgesia with morphine was made available as a "rescue" analgesic on patient's request during the 6-h postdosing evaluation period. The median time to onset of analgesia with propacetamol (8 [95% confidence interval 6,10] min) was shorter than ketorolac 15 mg (14 [7,16] min), and placebo (16 [8; not estimable] min) although the differences did not reach statistical significance. However, compared with ketorolac 30 mg, propacetamol had a shorter duration of analgesia (3.5 [2;5.4] vs 6 [3.3; not estimable] h). Analysis of pain intensity and pain relief scores demonstrated that propacetamol produced a significantly greater improvement in pain relief than saline from 45 min until 5 h after the injection. Propacetamol was not significantly different from ketorolac 15 mg and 30 mg with respect to the main analgesic efficacy variables during the 6-h assessment period. The most frequently reported adverse event with propacetamol was injection site pain (28% vs 19% for ketorolac 15 mg, 29% for ketorolac 30 mg, and 10% for placebo, respectively). In conclusion, propacetamol (2 g IV) possesses a similar analgesic efficacy to ketorolac (15 or 30 mg IV) after total hip or knee replacement surgery.     

The preemptive analgesic effect of rofecoxib after ambulatory arthroscopic knee surgery.

Nonsteroidal antiinflammatory drugs (NSAIDs) provide effective postoperative analgesia after arthroscopic knee surgery. Some investigators have suggested that the preemptive administration of NSAIDs may reduce postoperative analgesic requirements and hypersensitivity. We evaluated the analgesic effect of administering rofecoxib either before or after surgical incision in patients undergoing arthroscopic knee surgery under local anesthesia. Sixty patients undergoing arthroscopic meniscectomy were randomized into three groups. All patients received intraarticular bupivacaine 0.25% pre- and postsurgery together with IV sedation using midazolam and propofol. The Preincisional group received a single 50 mg dose of rofecoxib 1 h before surgery, the Postincisional group received rofecoxib 50 mg after the completion of surgery, and the Placebo group received a placebo tablet before surgery. Pain scores, the time to first opioid use, and 24-h analgesic use were recorded. Analgesic duration, defined as the time from completion of surgery until first opioid use, was significantly longer in those patients receiving pre- (803 +/- 536 min) versus postincisional (461 +/- 344 min) rofecoxib or placebo (318 +/- 108 min). The 24 h acetaminophen/oxycodone use was less in the Preincisional group (1.5 +/- 0.6 pills) versus the Postincisional group (3.3 +/- 1.3 pills) or the Placebo group (5.5 +/- 1.6 pills). Pain scores with movement were lower in the Preincisional group at all postoperative time intervals. We conclude that rofecoxib provides effective postoperative analgesia for arthroscopic meniscectomy. Further, the administration of rofecoxib 50 mg before surgery provides a longer duration of postoperative analgesia, less 24 h opioid use, and lower incidental pain scores compared with administering the drug after the completion of surgery. IMPLICATIONS: The administration of rofecoxib 50 mg before arthroscopic knee surgery provides a longer duration of analgesia, less 24-h opioid use, and lower pain scores than administering the drug after the completion of surgery.     

A single preoperative oral dose of valdecoxib,a new cyclooxygenase-2 specific inhibitor,relieves post-oral surgery or bunionectomy pain

BACKGROUND: The trend toward day-case surgery, with discharge on oral medication, has highlighted the need for effective and safe analgesics that facilitate a rapid recovery and discharge time. This study evaluated the analgesic efficacy, dose dependency, duration of action, and safety of the cyclooxygenase-2 specific inhibitor, valdecoxib, administered before oral or orthopedic surgery. METHODS: Eligible healthy adult patients were scheduled to undergo either extraction of two impacted third molar teeth (n = 284) or bunionectomy surgery (n = 223) with local anesthesia in two randomized, double-blind, placebo-controlled studies conducted at three centers in the United States. Patients received a single, preoperatively administered oral dose of placebo or 10 (oral surgery only), 20, 40, or 80 mg valdecoxib. Analgesic efficacy was assessed postoperatively, over a 24-h treatment period, or until the patient required rescue medication. Efficacy measures included time to rescue medication, proportion of patients requiring such rescue, pain intensity, and the Patient's Global Evaluation of Study Medication. RESULTS: In both studies, all doses of valdecoxib produced analgesia with a duration (time to rescue analgesia) and magnitude (Pain Intensity, Patient's Global Evaluation) significantly greater than placebo. A dose-dependent effect was observed up to 40 mg valdecoxib, with an 80-mg dose providing no additional analgesic benefit. In both models, all doses of valdecoxib were well tolerated, with no clinically significant treatment-related gastrointestinal, renal, or platelet-derived adverse events, and no evidence of a dose-related increase in adverse events. CONCLUSIONS: Preoperative orally administered valdecoxib provides well-tolerated and effective analgesia for mild to moderate postoperative pain.     

术前口服罗非昔布对双膝关节置换术后疼痛和全身炎性反应的影响

目的探讨术前环氧化酶2抑制剂罗非昔布是否能增强双膝关节置换术后吗啡的镇痛作用,及其对术后全身炎性反应的影响.方法 30例因关节炎需行双膝关节置换手术患者,通过抓阄方法随机分为罗非昔布加硬膜外镇痛组(RE组)和硬膜外镇痛组(E组),每组15例.RE组在术晨口服罗非昔布25 mg,其余同E组.所有患者均以异氟醚、硬膜外0.75%布比卡因复合维持麻醉.术毕连接患者自控镇痛泵 (1.2 mg/ml布比卡因加0.1 mg/ml吗啡加0.02 mg/ml氟哌利多)镇痛72 h.分别在术前、术毕、及术后2、6、12、24、48 h时抽取股静脉血,检测白细胞总数及分类,以及炎性细胞因子白介素6、8、10和肿瘤坏死因子-α.术后24、48、72 h各进行疼痛评分,记录比较每日吗啡用量、镇痛满意度、镇痛期间副作用以及术中出血量和术后关节引流量.结果复合罗非昔布可明显降低术后24 h静息、48 h静息和活动时疼痛评分.RE组提高术后24 h镇痛满意度为100%,高于E组60%(χ2＝6.71,P<0.01).RE组术后24 h平均吗啡消耗量为6.8 mg明显低于E组8.1 mg,(t=-2.71,P<0.05).RE组血白细胞和嗜中性粒细胞数在12 h和24 h明显低于E组.RE组血浆白介素6含量在术后48 h,白介素8含量在术后24 h明显低于E组.RE组术毕、术后6 h、12 h肿瘤坏死因子-α明显低于E组(t值分别为-2.4、-2.25、-2.41,P值均<0.05).结论术前口服罗非昔布可明显改善双膝置换术后疼痛,增加镇痛满意度,减轻全身炎性反应,减少吗啡用量.     

A randomized, placebo-controlled study of rofecoxib with paracetamol in early post-tonsillectomy pain in adults

BACKGROUND AND OBJECTIVE: Effective and early treatment of postoperative pain and nausea have become pivotal for the early discharge of patients after tonsillectomy. Opioid-based analgesia is standard practice but the use of non-steroidal anti-inflammatory drugs is discouraged due to their platelet inhibiting properties. The cyclo-oxygenase-2 selective non-steroidal anti-inflammatory drugs are effective analgesics and do not affect platelet function. We hypothesized that premedication with cyclo-oxygenase-2 selective non-steroidal anti-inflammatory drug in addition to paracetamol would provide effective analgesia and decrease opioid consumption during early recovery from tonsillectomy. METHODS: In a randomized, placebo-controlled study of adult tonsillectomy patients (n=40) one group (R-group; n=20) was premedicated with paracetamol 1.5 g and rofecoxib 50 mg and a control group (P-group; n=20) was premedicated with paracetamol 1.5 g and placebo. Morphine was used as rescue medication. Postoperative (24 h) pain scores (0--10), morphine consumption as well as intraoperative blood loss were recorded. RESULTS: We found no overall difference in pain scores between the groups but significantly more patients in the placebo group had pain scores >5 within the first 8 h. The rofecoxib group consumed less morphine during the first 12 h. A lower intraoperative blood loss was observed in the rofecoxib group. CONCLUSION: Our results suggest an early although clinically minor analgesic benefit of the addition of a cyclo-oxygenase-2 selective non-steroidal anti-inflammatory drug to paracetamol as premedication for adult tonsillectomy.     

Intravenous acetaminophen (paracetamol): comparable analgesic efficacy, but better local safety than its prodrug, propacetamol, for postoperative pain after third molar surgery

We compared an acetaminophen (paracetamol) 1 g (n = 51) formulation for infusion with propacetamol 2 g (n = 51) and placebo (n = 50) in a randomized, controlled, double-blind, parallel group trial in patients with moderate-to-severe pain after third molar surgery. Treatment efficacy was assessed in house for 6 h after starting the 15-min infusion. Significant effects versus placebo (P < 0.01) were obtained with both active treatments on pain relief, pain intensity difference on a 100-mm visual analog scale, and on a categorical scale (except for propacetamol at 6 h). No significant differences were noted between active groups except at 1 h. Six-hour weighted sums of primary assessments showed significantly better efficacy than placebo (P < 0.0001) and no difference between active treatments. Median stopwatch time to onset of pain relief for active treatment was 6-8 min after infusion start. Active treatments showed comparable efficacy with a significantly longer duration of analgesia and better patients' global evaluation compared with placebo. The incidence of patients reporting local pain at the infusion site was significantly less frequent after IV acetaminophen or placebo (0%) in comparison with propacetamol (49%). In conclusion, acetaminophen 1 g and propacetamol 2 g were superior to placebo regarding analgesic efficacy, with a more frequent incidence of local pain at the infusion site for propacetamol.     

Doubtful effect of continuous intraarticular analgesia after total knee arthroplasty

Background and purpose — Local infiltration analgesia (LIA) is well established for effective postoperative pain relief in total knee arthroplasty (TKA). To prolong the effect of LIA, infusion pumps with local intraarticular analgesia can be used. We evaluated the effect of such an infusion pump for the first 48 h postoperatively regarding pain, knee function, length of stay (LOS) in hospital, and complications.

Patients and methods — 200 patients received peroperative LIA and a continuous intraarticular elastomeric infusion pump set at 2 mL/h. The patients were randomized either to ropivacaine (7.5 mg/mL) or to NaCl (9 mg/mL) in the pump. Visual analog scale (VAS) pain (0–100 mm), analgesic consumption, side effects of medicine, range of motion (ROM), leg-raising ability, LOS, and complications during the first 3 months were recorded.

Results — On the first postoperative day, the ropivacaine group had lower VAS pain (33 vs. 40 at 12 noon and 36 vs. 43 at 8 p.m.; p = 0.02 and 0.03, respectively), but after that all recorded variables were similar between the groups. During the first 3 months, the ropivacaine group had a greater number of superficial and deep surgical wound infections (11 patients vs. 2 patients, p = 0.02). There were no other statistically significant differences between the groups.

Interpretation — Continuous intraarticular analgesia (CIAA) with ropivacaine after TKA has no relevant clinical effect on VAS pain and does not affect LOS, analgesic consumption, ROM, or leg-raising ability. There may, however, be a higher risk of wound-healing complications including deep infections.     

A double-blind prospective comparison of rofecoxib vs ketorolac in reducing postoperative pain after arthroscopic knee surgery

STUDY OBJECTIVE: The aim of this study was to compare the analgesic efficacy of premedication with rofecoxib vs intravenous (IV) ketorolac in reducing postoperative pain after arthroscopic knee surgery. STUDY DESIGN: This is a prospective, randomized, double-blinded study. SETTING: This study was set at a university hospital. SUBJECTS: The subjects include 54 patients with American Society of Anesthesiologists physical statuses I, II, and III undergoing knee arthroscopy. INTERVENTIONS: Group 1 received 50 mg oral rofecoxib preoperatively with IV placebo injection, which was administered 20 minutes before the end of the operation. Group 2 received a preoperative placebo and 30 mg IV ketorolac 20 minutes before the end of surgery. MEASUREMENTS: The primary outcome measure was the proportion of patients reporting pain in the postoperative anesthesia care unit, 6 hours and 24 hours after discharge. Additional end points included the use of 5:325 mg oxycodone-acetaminophen (O/A) tablets, pain scores, patient's satisfaction survey, and comparison of side effects. Data were analyzed using independent samples t tests for continuous variables or chi2 tests for categorical variables. P < .05 was considered significant. RESULTS: The 2 groups were comparable with regard to patient characteristics, intraoperative medication use, and duration of surgery. There was no difference either in pain scores or O/A use in the postoperative anesthesia care unit. At 24 hours after discharge, significantly more patients in the ketorolac group (91%) reported pain than the rofecoxib group (63%) (P = .02). Sixty-one percent of patients in the ketorolac group used O/A during the first 24 hours vs 38% in the rofecoxib group. The difference, however, was not statistically significant. CONCLUSION: Preoperative rofecoxib is as effective as ketorolac for the treatment of pain after knee arthroscopy. Higher frequency of pain reporting at 24 hours by patients in ketorolac group is explained by the longer analgesic effect of rofecoxib. Future studies should directly compare gastrointestinal injury of these drugs, as well as cost-effectiveness of rofecoxib vs ketorolac.     

Forty-eight hours of postoperative pain relief after total hip arthroplasty with a novel, extended-release epidural morphine formulation

BACKGROUND: Epidural morphine has proven analgesic efficacy in the postoperative period and is widely used. This study evaluated the efficacy of extended-release epidural morphine (EREM; DepoDur; Endo Pharmaceuticals Inc., Chadds Ford, PA; SkyePharma, Inc., San Diego, CA) in providing pain relief for 48 h after surgery. METHODS: Patients (n = 200) scheduled to undergo total hip arthroplasty were randomized to receive a single dose of 15, 20, or 25 mg EREM or placebo. After surgery and after asking for pain medication, patients had access to intravenous patient-controlled analgesia fentanyl for breakthrough pain as needed. Postoperative intravenous patient-controlled analgesia fentanyl use, time to first postoperative fentanyl use, pain intensity at rest and with activity, patient and surgeon ratings of pain control, and adverse events were recorded. RESULTS: All EREM dosages reduced the mean (+/- SD) fentanyl use versus placebo (510 +/- 708 vs. 2,091 +/- 1,803 microg; P < 0.0001) and delayed the median time to first dose of fentanyl (21.3 vs. 3.6 h; P < 0.0001). All EREM groups had significantly improved pain control at rest through 48 h postdose (area under the curve [0-48 h]) compared with placebo (P < 0.0005). More EREM-treated patients rated their pain control as good or very good compared with placebo (at 24 h: 90 vs. 65%, P < 0.0001; at 48 h: 83 vs. 67%, P < 0.05). No supplemental analgesia was needed in 25% of EREM-treated patients and 2% of placebo-treated patients at 48 h (P < 0.05). The safety profile of EREM was consistent with that of other epidurally administered opioid analgesics. CONCLUSIONS: EREM provided significant postoperative pain relief over a 48-h period after hip surgery, without the need for indwelling epidural catheters.     

Efficacy and Safety of Intravenous Parecoxib Sodium in Relieving Acute Postoperative Pain following Gynecologic Laparotomy Surgery

Background: This study tested the hypothesis that an injectable cyclooxygenase (COX)-2-specific inhibitor will be at least as effective and well tolerated as a COX-nonspecific conventional nonsteroidal antiinflammatory drug (NSAID) by comparing the analgesic efficacy and tolerability of one intravenous dose of parecoxib sodium, an injectable prodrug of the novel COX-2-specific inhibitor, valdecoxib, with ketorolac and placebo in postoperative laparotomy surgery patients. Intravenous morphine, 4 mg, was studied as a positive analgesic control.

Methods: In this multicenter, double-blinded, placebo-controlled study, women experiencing moderate-to-severe pain on the first day after abdominal hysterectomy or myomectomy received one intravenous dose of parecoxib sodium, 20 or 40 mg, ketorolac, 30 mg, morphine, 4 mg, or placebo. Analgesic efficacy and tolerability were evaluated for 24 h postdose or until patients, whose pain was not adequately controlled, opted to receive rescue analgesia.

Results: Two hundred two patients were enrolled. All treatment groups had comparable demographics and baseline pain status. All active treatments had an equally rapid time to onset of analgesia (10-23 min). Overall, each parecoxib sodium dose and ketorolac were significantly superior to morphine and placebo for most measures of analgesic efficacy at most time points, including a significantly longer (two- to threefold) time to rescue analgesia (P <= 0.05). All treatments were well tolerated.     

The specific cox-2 inhibitor valdecoxib provides effective analgesia after inguinal hernia surgery

OBJECTIVE: To compare 3 oral analgesic doses--valdecoxib 20 mg, valdecoxib 40 mg and controlled-release diclofenac 75 mg--to placebo in the treatment of pain after inguinal herniorrhaphy. METHOD: An international multicenter double-blind placebo-controlled trial comparing parallel groups receiving oral valdecoxib 20 or 40 mg, controlled-release diclofenac 75 mg, or placebo every 12 hours over a period of 36 hours. The study enrolled 269 patients undergoing inguinal herniorrhaphy with spinal anesthesia. Pain intensity difference, the sum pain intensity difference, need for rescue medication, and overall patient satisfaction were compared. RESULTS: Valdecoxib 40 mg and controlled-release diclofenac 75 mg take every 12 hours provided similar analgesia that was significantly more efficacious than placebo as shown by the sum pain intensity difference at 12 hours. Both treatments decreased pain intensity in comparison with baseline throughout the study. Differences were significant in comparison with placebo at 8-10 hours through 24 hours of administration of the first dose. No significant differences between valdecoxib 20 mg and placebo were observed. The percentage of patients needing rescue medication was significantly lower in the valdecoxib 40 mg group (30% in that group vs. 52% for placebo), and that difference was not seen for any of the other groups. All treatments were well tolerated. CONCLUSIONS: Valdecoxib 40 mg and diclofenac 75 mg provided similar quality of analgesia for treating pain after inguinal herniorrhaphy.     

Efficacy of single-dose and multidose rofecoxib in the treatment of post-orthopedic surgery pain

To determine the efficacy of rofecoxib in post-orthopedic surgery pain, we conducted a double-blind, randomized, placebo- and active-comparator-controlled, parallel-group trial. Two hundred eighteen patients enrolled. Day 1 patients received placebo, rofecoxib 50 mg, or naproxen sodium 550 mg. Days 2 through 5, the placebo and naproxen sodium groups received placebo, and the rofecoxib group received rofecoxib 25 or 50 mg. Rofecoxib 50 mg was superior to placebo (P < .05) and similar to naproxen sodium for all single-dose measures of pain relief. Days 2 through 5, the rofecoxib 50 mg group used less supplemental narcotic analgesia (P = .005) and reported less pain on global evaluations (P = .041) when compared with the placebo group; the efficacy of rofecoxib 25 mg fell between that of placebo and rofecoxib 50 mg for these endpoints (P < or = .267). Rofecoxib 50 mg once daily effectively treated post-orthopedic surgery pain.     

A Single Preoperative Oral Dose of Valdecoxib, a New Cyclooxygenase-2 Specific Inhibitor, Relieves Post-Oral Surgery or Bunionectomy Pain

Background: The trend toward day-case surgery, with discharge on oral medication, has highlighted the need for effective and safe analgesics that facilitate a rapid recovery and discharge time. This study evaluated the analgesic efficacy, dose dependency, duration of action, and safety of the cyclooxygenase-2 specific inhibitor, valdecoxib, administered before oral or orthopedic surgery.

Methods: Eligible healthy adult patients were scheduled to undergo either extraction of two impacted third molar teeth (n = 284) or bunionectomy surgery (n = 223) with local anesthesia in two randomized, double-blind, placebo-controlled studies conducted at three centers in the United States. Patients received a single, preoperatively administered oral dose of placebo or 10 (oral surgery only), 20, 40, or 80 mg valdecoxib. Analgesic efficacy was assessed postoperatively, over a 24-h treatment period, or until the patient required rescue medication. Efficacy measures included time to rescue medication, proportion of patients requiring such rescue, pain intensity, and the Patient's Global Evaluation of Study Medication.

Results: In both studies, all doses of valdecoxib produced analgesia with a duration (time to rescue analgesia) and magnitude (Pain Intensity, Patient's Global Evaluation) significantly greater than placebo. A dose-dependent effect was observed up to 40 mg valdecoxib, with an 80-mg dose providing no additional analgesic benefit. In both models, all doses of valdecoxib were well tolerated, with no clinically significant treatment-related gastrointestinal, renal, or platelet-derived adverse events, and no evidence of a dose-related increase in adverse events.     

Does perioperative administration of rofecoxib improve analgesia after spine, breast and orthopaedic surgery?

BACKGROUND AND OBJECTIVE: Data on the effectiveness of cyclooxygenase 2 inhibitors in postoperative pain therapy vary widely. We tested in a prospective, placebo-controlled, randomized, double-blind trial the hypotheses that perioperative (i.e. preoperative and postoperative) administration of the cyclooxygenase 2 inhibitor rofecoxib decreases pain scores and morphine consumption after spine, breast and orthopaedic surgery. METHODS: Five hundred and forty patients scheduled for spine, breast or orthopaedic surgery were randomly assigned to receive in combination with postoperative morphine via patient controlled analgesia pump for 4 days either rofecoxib 50 mg administered perioperatively, rofecoxib 50 mg administered only postoperatively, or placebo. Primary outcome criteria were pain score at rest (numeric rating scale 0-4) and morphine consumption. RESULTS: Perioperative rofecoxib significantly decreased pain score 0 (0-1) vs. 1 (0-2) (median (interquartile range)), and morphine consumption 18 (6-33) vs. 22.5 (12-38) compared with placebo. In contrast, rofecoxib when administered only postoperatively did not significantly improve analgesic effects or side-effects at time of assessment of the main criteria (24 h after skin closure), but during the follow-up period at 48 h and 72 h after skin closure pain scores and morphine consumption were improved compared to placebo. The analgesic effects of rofecoxib were independent from the type of surgery. CONCLUSIONS: Perioperative administration of the cyclooxygenase 2 inhibitor rofecoxib decreases pain scores and morphine consumption after orthopaedic, breast and spine surgery. However, the benefit of preoperative administration of the cyclooxygenase 2 inhibitor seems to be only moderate, suggesting that early postoperative administration may be a useful alternative approach. There is no evidence that the type of surgery influences analgesic effects of cyclooxygenase 2 inhibitors.     

Analgesic effects of rofecoxib in ear-nose-throat surgery

In this study we evaluated the analgesic efficacy and the opioid-sparing effect of rofecoxib in ear-nose-throat surgery patients. Patients undergoing nasal septal or sinus surgery were randomized to receive either oral placebo or rofecoxib 50 mg 1 h before surgery. All patients received propofol 0.8 mg/kg, fentanyl 1 microg/kg, and local anesthesia at the operative site. Sedation was maintained by a continuous infusion of propofol adjusted to maintain sedation at a 2-3 level on the Ramsey scale. Additional fentanyl 0.5-1 microg/kg was administered at the patient's request or if the verbal rating scale score was >4. Patient sedation and pain scores were obtained at 5, 15, 30 45, and 60 min during surgery and 30 min and 2, 4, 6, 12, and 24 h after completion of the procedure. During the postoperative period, diclofenac 75 mg IM was administered for analgesia at the patient's request or if the visual analog scale (VAS) rating for pain was more than 4. VAS pain scores, intraoperative fentanyl, and postoperative diclofenac requirements were significantly smaller in the rofecoxib group compared with the placebo group (P < 0.001). The times to first analgesic request were also significantly less in the rofecoxib group. We conclude that the preoperative administration of oral rofecoxib provided a significant analgesic benefit and decreased the need for opioids in patients undergoing nasal septal and nasal sinus surgery. IMPLICATIONS: The aim of this study was to evaluate the analgesic efficacy and opioid-sparing effect of rofecoxib, a new selective cyclooxygenase-2 inhibitor drug, in ear-nose-throat surgery patients. Preoperative administration of oral rofecoxib provided a significant analgesic benefit and decreased the need for opioids in patients undergoing nasal septal and nasal sinus surgery.     

Prospective national survey on alternatives to obstetrical peridural analgesia

OBJECTIVE: To assess the type of an alternative technique for epidural analgesia for pain relief during labour, the reason of its choice and its efficiency. STUDY DESIGN: A one-year prospective survey in 34 french hospitals. MATERIAL AND METHODS: A questionnaire was filled for each request for a non-epidural technique during labour. The data recorded the reason for this non-epidural method, the technique used, the repeated visual analog scale (VAS) pain scores before (T0) and during the treatment (T30, T60 T120,...), the maternal and foetal side effects of the method, and the maternal satisfaction. RESULTS: 177 questionnaires were studied among the 270 collected. The lack of VAS measurements was the main reason for excluding questionnaires. Refusing the epidural by the obstetric patient was the most frequent reason for requesting a non-epidural method (39%). Five non-epidural methods were identified: nalbuphine (NAL, n = 75), sufentanil by patient-controlled analgesia (SUF, n = 44), nitrous oxide/oxygen inhalation (N2O, n = 22), pethidine (PET, n = 19), and spinal analgesia (SA, n = 17). The choice of the method was dependant on the prescribe (midwife or anaesthetist) and of the cervical dilation. The SA group exhibited the most pain relief compared to the other groups during the treatment. No difference in pain relief was noted between the 4 groups (SUF, NAL, PET, N2O). Only in the PET group did the VAS pain score remain unchanged at T30. There were 25 maternal side effects, with a significant maternal sedation in the NAL group, and pruritus in the SA group. There were 6 respiratory depressions in infants, unrelated with the analgesic method. Maternal satisfaction was higher in the SA, SUF and N2O groups than in the PET and NAL groups. Factors explaining lack of analgesic effect (i.e. no decrease in VAS pain score more than 10 mm during the treatment) were the use of pethidine, the VAS pain score at T0 and the induced labour. CONCLUSION: Epidural and spinal analgesia are the most efficient methods for pain relief during labour. The analgesic effect of non-regional methods during labour is minimal, associated with some maternal side effects. Due to its lack of analgesic effect, pethidine should be avoided in this indication.