Dyloject, a novel injectable diclofenac formulation, offers greater safety and efficacy than voltarol for postoperative dental pain

BACKGROUND AND OBJECTIVES: Voltarol for injection (a diclofenac sodium formulation employing polyethylene glycol and benzyl alcohol [PG-BA] as excipients) is marketed in Europe but not in North America. A suspension, PG-BA diclofenac sodium, requires preparation for each patient and slow IV infusion to minimize venous irritation. Dyloject, a novel diclofenac formulation, employs hydroxypropyl beta-cyclodextrin (HPbetaCD) to solubilize diclofenac in a small volume. We compared the efficacy and safety of an IV HPbetaCD diclofenac sodium bolus, a 30-minute PG-BA diclofenac sodium infusion, and placebo in post-molar extraction pain. METHODS: A total of 155 adult patients were randomized to receive HPbetaCD diclofenac sodium 75 mg, PG-BA diclofenac sodium 75 mg, or placebo. Primary endpoints were superiority of HPbetaCD diclofenac sodium to placebo and noninferiority of HPbetaCD diclofenac sodium to PG-BA diclofenac sodium with respect to total pain relief over 4 hours (TOTPAR4) on a 0 to 100-mm visual analog scale (VAS). Secondary endpoints included categorical TOTPAR4, VAS and categorical TOTPAR up to 8 hours, other measures of pain intensity and relief, patient global evaluation, and time to rescue medication. RESULTS: HPbetaCD diclofenac sodium had efficacy superior to both placebo and PG-BA diclofenac sodium. At 15 minutes, more patients given HPbetaCD diclofenac sodium than PG-BA diclofenac sodium reported 30% reduction in pain intensity (52% vs. 21%, P = .0022). Both diclofenac products had a 6-hour duration of effect and were well tolerated. Patient global evaluations of HPbetaCD diclofenac sodium were high, superior to placebo, and similar to PG-BA diclofenac sodium. The adverse event (AE) incidence was similar for HPbetaCD diclofenac sodium and PG-BA diclofenac sodium, except that in the current trial and in integrated safety results from the present and prior studies, phlebitis was more common with PG-BA diclofenac sodium. No cardiac or renal AEs or gastrointestinal bleeding were reported or observed. CONCLUSIONS: IV bolus HPbetaCD diclofenac sodium produced analgesia more quickly than, and with equal duration as, the 30-minute PG-BA diclofenac sodium infusion. Pooled data on thrombophlebitis from the present investigation and our prior studies of the novel formulation indicate this adverse effect is less frequent and less severe with HPbetaCD diclofenac sodium than with PG-BA diclofenac sodium.     

Methylprednisolone intravenously 1 day after surgery has sustained analgesic and opioid-sparing effects

BACKGROUND: In previous studies on glucocorticoids for postoperative pain, the test drug has been given perioperatively, usually before measurement of baseline pain. In order to evaluate the time course and magnitude of the analgesic effect of a glucocorticoid in well-established postoperative pain, we compared methylprednisolone with ketorolac and placebo, after assessment of baseline pain on the first postoperative day. METHODS: This was a double-blind, single dose, randomized, parallel comparison of intravenous (i.v.) methylprednisolone 125 mg, ketorolac 30 mg as an active control, and placebo in 75 patients with moderate to severe pain 1 day after orthopaedic surgery. Outcome variables were pain intensity (0-100 VAS), pain relief (0-4 PAR) and rescue opioid consumption. RESULTS: Methylprednisolone was not significantly different from ketorolac and gave significantly lower pain intensity from 1 h (0-6 h, P < 0.02), and more pain relief 2-6 h after test drugs (P < 0.05) compared with placebo. After 24 h, pain intensity was lower in both active drug groups compared with placebo (methylprednisolone, P < 0.0001; ketorolac, P < 0.007). Number needed to treat (NNT) calculated from patients having more than at least 50% of maximum obtainable total pain relief during the first 6 h (>50%maxTOTPAR(6 h)) was 3.6 for methylprednisolone and 3.1 for ketorolac. Number needed to treat calculated from the percentage reporting at least 50% pain relief for at least 4 h (>50%PAR(4 h)) was 2.8 for both groups. Opioid consumption was significantly reduced for 72 h after methylprednisolone compared with ketorolac (P < 0.02) and placebo (P < 0.003). CONCLUSION: Methylprednisolone 125 mg i.v. 1 day after surgery gave similar early reduction of pain as i.v. ketorolac 30 mg. Less pain than placebo 24 h after methylprednisolone, and lower opioid consumption for 72 h compared with ketorolac and placebo indicate sustained analgesic effects of methylprednisolone.     

Platelet function following administration of a novel formulation of intravenous diclofenac sodium versus active comparators: a randomized, single dose, crossover study in healthy male volunteers

Study ObjectiveTo assess platelet function and safety following single-dose administration of a novel formulation of intravenous (IV) diclofenac sodium (Dyloject) 37.5 mg versus oral diclofenac 50 mg, IV ketorolac 30 mg, and oral acetylsalicylic acid (ASA) 325 mg.DesignOpen-label, randomized, single-dose, 4-treatment crossover study.SettingClinical research unit.Patients30 healthy, ASA physical status I adult men.InterventionsSubjects were randomized to one of 6 treatment sequences that included 4 single-dose treatments. Study drug administration occurred on Days 1, 3, 5, and 7.MeasurementsPlatelet count, closure time as measured by platelet function analyzer (PFA-100), prothrombin time (PT), activated partial thromboplastin time (aPTT), and plasma concentrations of the study drugs were obtained over 24 hours after each treatment. The primary endpoint was the area under the curve for PFA collagen-epinephrine (CEPI) closure time difference from 0-6 hours post-drug administration (AUC_0-6h). Secondary endpoints included the maximum change from baseline in PFA CEPI closure time.Main ResultsAUC_0-6h (mean ± SD) for CEPI closure time difference was significantly smaller after IV diclofenac 37.5 mg (249 ± 216 sec.hrs) than after ketorolac [and ASA (950 ± 287 sec.hrs and 834 ± 237 sec.hrs, respectively); P ≤ 0.0001 for both] but not after the oral diclofenac control (286 ± 265 sec.hrs; P = 0.40). Similarly, the maximum change from baseline in PFA CEPI closure time was lower after IV diclofenac than after ketorolac or ASA across all time intervals examined. There were no significant changes in PT or aPTT at any time point with any treatment. There was a low frequency of adverse events.ConclusionsAcetylsalicylic acid and ketorolac both substantially disrupted platelet function in contrast to IV diclofenac 37.5 mg or oral diclofenac 50 mg control. Diclofenac, with its balanced COX-1 and COX-2 inhibitory profile, may pose less risk of postoperative bleeding than nonsteroidal antiinflammatory drugs (NSAIDs) such as ketorolac and ASA, which predominantly inhibit COX-1.     

Ketoprofen, diclofenac or ketorolac for pain after tonsillectomy in adults?

We have compared the analgesic and opioid sparing effect of three i.v. non-steroidal anti-inflammatory drugs with placebo in a randomized, double-blind, placebo-controlled study in 80 adult patients after elective tonsillectomy. A standard anaesthetic was used. After induction of anaesthesia, patients received ketoprofen 100 mg, diclofenac 75 mg or ketorolac 30 mg by i.v. infusion over 30 min. Patients in the placebo group received saline. Ketoprofen and diclofenac infusions were repeated after 12 h and ketorolac infusion at 6 h and 12 h. Oxycodone was used as rescue analgesic. Patients in the ketoprofen group requested 32% less opioid and patients in the diclofenac and ketorolac groups 42% less opioid than those in the placebo group (P < 0.05). There were one, two and six patients in the placebo, diclofenac and ketorolac groups, respectively, but none in the ketoprofen group, who did not request opioid analgesia during the study (P < 0.05, ketorolac vs placebo and ketoprofen). Visual analogue pain scores were similar in all groups. Visual analogue satisfaction scores were significantly higher in the diclofenac group compared with the placebo group. The incidence of nausea was 44-54%. There were no differences in the incidence of other adverse reactions. We conclude that all three non-steroidal anti-inflammatory drugs were superior to placebo after tonsillectomy.      

Analgesic efficacy of diclofenac in combination with morphine and paracetamol after mastectomy and immediate breast reconstruction

BACKGROUND: Breast cancer treatment with mastectomy and immediate breast reconstruction (IBR) is associated with intense pain in the primary post-operative period. The present prospective, placebo-controlled and double-blind study aimed to evaluate the analgesic efficacy of diclofenac, a non-steroid anti-inflammatory drug (NSAID), in combination with paracetamol and opioids. This was done by 64-h assessment of post-operative pain intensity, opioid consumption, blood loss, nausea and tiredness. METHODS: Fifty women selected for mastectomy and IBR with submuscular implants with or without axillary lymph node dissection (ALND) were randomized to receive diclofenac 50 mg x 3 or placebo rectally in addition to oral paracetamol and intravenous opioids delivered using a patient-controlled analgesia (PCA) technique. RESULTS: During the first 20 h post-surgery, patients who received diclofenac experienced significantly less pain when resting than those who received placebo. When moving, a non-significant estimated difference in pain in favour of diclofenac was also noted. Opioid consumption during the first 6 h post-operatively was 34% less with diclofenac than with placebo. Means (SD) were 16.9 (10.3) mg and 25.6 (10.2) mg, respectively (P = 0.007). After 64 h, the difference was no longer statistically significant. Post-operative bleeding was significantly higher with diclofenac than with placebo (P < 0.01). Nausea and tiredness did not differ between the groups. CONCLUSIONS: The addition of NSAID to paracetamol and opioid-PCA reduced opioid consumption and improved pain relief during the first 20 h at rest but was not convincingly effective during mobilization. Post-operative blood loss was higher with diclofenac.     

Comparison of the opioid-sparing efficacy of diclofenac and ketoprofen for 3 days after knee arthroplasty

BACKGROUND: Comparative postoperative non-steroidal anti-inflammatory drug (NSAID) studies in orthopedic patients have usually been restricted in time to the first postoperative day. The opioid-sparing effect of NSAIDs may be beneficial postoperatively as long as pain otherwise restricts ambulation and rehabilitation. We therefore compared the analgesic efficacy of the maximum recommended doses of diclofenac and ketoprofen for 3 days after knee arthroplasty. METHODS: We studied 64 knee arthroplasty patients, operated on under spinal anesthesia. In a randomized, double-blind and placebo-controlled fashion, the patients received either i.v. diclofenac 75 mg (n = 24), ketoprofen 100 mg (n = 24) or saline (n = 16) in the recovery room, followed by oral diclofenac 150 mg/day, ketoprofen 300 mg/day or placebo, respectively, for 3 days, supplemented by patient-controlled analgesia (PCA) with i.v. oxycodone. RESULTS: The mean consumption of oxycodone during the first, second and third study days was 45.3, 22.3 and 15.2 mg in the diclofenac group, 43.5, 37.5 and 21.8 mg in the ketoprofen group, and 61.2, 45.9 and 36.1 mg, respectively, in the placebo group. Oxycodone consumption was significantly lower (P < 0.05) in the ketoprofen group than in the placebo group in the postoperative period 13-24 h and 61-72 h. Diclofenac was superior to placebo in the postoperative period 25-48 h (P < 0.01), 49-60 h (P < 0.05) and to ketoprofen at 49-60 h (P < 0.05). During administration of diclofenac on days 1-3 and ketoprofen on day 2, the mean pain scores (VAS) were lower than in the placebo group (P < 0.05). Six patients had difficulties in operating the PCA device. There were no differences in blood loss. CONCLUSION: We conclude that in the first day after knee arthroplasty (13-24 h), ketoprofen exerted an opioid-sparing effect. After day 1 (25-60 h), with the doses used, diclofenac proved to be better than placebo, whereas ketoprofen was not.     

Tramadol/acetaminophen tablets in the treatment of postsurgical orthopedic pain

Tramadol/acetaminophen (APAP) combination tablets were shown effective and safe for postsurgical orthopedic pain in a 6-day, multicenter, randomized, double-blind, active- and placebo-controlled study. Of 305 intent-to-treat (ITT) postsurgical patients, 153 patients undergoing arthroscopy who had at least moderate pain were randomized to receive either tramadol 37.5 mg/APAP 325 mg (mean, 4.3 tablets), or codeine 30 mg/APAP 300 mg (mean, 4.6 tablets), or placebo. Tramadol/APAP was superior to placebo for the following outcome variables: total pain relief (TOTPAR, P = .013), sum of pain intensity differences (SPID, P = .049), sum of total pain relief and sum of pain intensity differences (SPRID, P = .018), and average daily pain relief (P = .031). Similar incidence of adverse events for tramadol/APAP and codeine/APAP was found, except for constipation (0% vs 10.9%) and vomiting (8.2% vs 16.4%).     

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.     

Analgesic efficacy of parenteral paracetamol (propacetamol) and diclofenac in post-operative orthopaedic pain

BACKGROUND: Propacetamol is an injectable pro-drug of paracetamol (acetaminophen) with analgesic and antipyretic activities, especially used in the post-operative period. The aim of this study was to assess the analgesic efficacy and safety of intravenous paracetamol, administered as propacetamol, in comparison with placebo and intramuscular diclofenac in patients with post-operative pain. METHODS: This was a randomized, double-blind, double-dummy study. One hundred and twenty patients with moderate to severe pain following total hip arthroplasty received either two administrations of propacetamol 2 g intravenously, 5 h apart (n = 40), one single administration of diclofenac 75 mg intramuscularly (n = 40) or placebo (n = 40). Efficacy measures were assessed before each drug administration, for the 5 h following each study treatment administration and for the total study duration of 10 h. Safety was assessed by reporting adverse events and changes in vital signs, electrocardiogram (ECG) and biochemical investigations before and 24 h after dosing. RESULTS: Both active treatments were effective and statistically superior to placebo over the whole study period, as indicated by the total pain relief score. No significant differences were found between propacetamol and diclofenac for any measures of analgesic activity. Only minor and common adverse events were reported, with no overall differences between the groups. CONCLUSION: Both active treatments were superior to placebo, and the overall efficacy of two intravenous infusions of propacetamol 2 g (equivalent to 1 g of paracetamol), 5 h apart, was not statistically different from that provided by a single intramuscular injection of diclofenac 75 mg over the first 5 h post-dose and over the total 10-h study period. The safety was good.     

I.v. diclofenac and ketorolac for pain after thoracoscopic surgery

We studied intensity of pain, cumulative morphine consumption, ventilatory and renal function, and haemostasis in patients undergoing video-assisted thoracoscopic surgery and receiving a 2-day i.v. infusion of diclofenac, ketorolac or saline. Plasma concentrations of the two NSAID were also measured. The study was randomized, double- blind and placebo-controlled, with 10 patients in each group. Patients experienced mainly moderate pain. Mean consumption of i.v. morphine during the first day after operation was 57 (SEM 11) mg in the placebo group. Diclofenac and ketorolac were equally effective in reducing total morphine consumption (61% and 52%, respectively). Adverse events were similar and minor. Greater variability in plasma concentrations of ketorolac were detected compared with diclofenac.      

Methylprednisolone and ketorolac rapidly reduce hyperalgesia around a skin burn injury and increase pressure pain thresholds

BACKGROUND: Glucocorticoids and non-steroidal anti-inflammatory drugs (NSAIDs) decrease acute postoperative pain and hyperalgesia. The objectives of this study were to investigate the effects of methylprednisolone and ketorolac on hyperalgesia around a skin burn injury and on pressure pain thresholds. METHODS: In a double-blind, placebo-controlled, randomized trial with cross-over design, methylprednisolone 125 mg, ketorolac 60 mg or placebo was administered intravenously in 12 male volunteers on three separate days at least 4 days apart. Primary and secondary hyperalgesia were produced by a first-degree burn injury on abdominal skin 45 min before injection of the test medicines. The area of secondary mechanical hyperalgesia outside the site of injury was measured. Pressure pain stimuli were applied on the base of a fingernail, increasing until the pressure pain detection threshold (PPDT) and pressure pain tolerance threshold (PPTT) were reached. RESULTS: Compared with placebo, the active drugs reduced the area of secondary hyperalgesia (methylprednisolone, P < 0.001; ketorolac, P < 0.01). Ketorolac but not methylprednisolone increased PPDT compared with placebo (P < 0.05). Both active drugs increased PPTT compared with placebo (methylprednisolone, P < 0.01; ketorolac, P < 0.001). Ketorolac increased PPTT more than methylprednisolone (P < 0.05). CONCLUSIONS: Methylprednisolone and ketorolac increased PPTT attenuated secondary hyperalgesia around a skin burn injury. PPTT increased after both methylprednisolone and ketorolac. The present study demonstrates analgesic and anti-hyperalgesic properties of a glucocorticoid and a non-selective NSAID that have not been demonstrated previously in human subjects.     

Combination tramadol plus acetaminophen for postsurgical pain

BACKGROUND: This multicenter, randomized, double-blind, active- and placebo-controlled trial evaluated tramadol plus acetaminophen (APAP) for orthopedic (n = 153) and abdominal (n = 152) postsurgical pain. METHODS: Patients with moderate pain or greater were randomized to an initial two tablets of 37.5 mg tramadol plus 325 mg APAP (n = 98), codeine 30 mg plus APAP 300 mg (n = 109), or placebo (n = 98); thereafter, they received 1 to 2 tablets every 4 to 6 hours as needed for pain for 6 days. Outcome measures were pain relief and pain intensity, total pain relief, sum of pain intensity differences, and sum of pain relief and pain intensity differences during 4 hours and the daily averages. RESULTS: Tramadol plus APAP was superior to placebo for total pain relief, sum of pain intensity differences, and sum of pain relief and pain intensity differences (P < or =0.015); tramadol plus APAP and codeine plus APAP did not separate (P > or=0.281). For average daily pain relief, average daily pain intensity, and overall medication assessment, tramadol plus APAP was superior to placebo (P < or =0.038); codeine plus APAP did not separate from placebo (P > or =0.125). Discontinuation because of adverse events occurred in 8.2% of tramadol plus APAP, 10.1% of codeine plus APAP, and 3.0% of placebo patients. Except for constipation (4.1% tramadol plus APAP vs 10.1% codeine plus APAP) and vomiting (9.2% vs 14.7%, respectively), adverse events were similar for active treatments. CONCLUSIONS: Tramadol plus APAP (mean dose 4.4 tablets) was effective and well tolerated for postsurgical pain and showed better tolerability than did codeine plus APAP.     

Ketorolac and indomethacin are equally efficacious for the relief of minor postoperative pain

Injectable ketorolac is an effective analgesic in ambulatory surgery patients. However, no studies have compared ketorolac with other NSAIDs in this setting. The analgesic efficacy of intramuscular ketorolac, rectal indomethacin and placebo was compared in healthy women undergoing gynaecological or breast surgery as outpatients. Ninety patients received 30 mg im ketorolac, 100 mg pr indomethacin or placebo in a prospective, randomized, double-blind manner. A standardized anaesthetic protocol was followed. Patients graded their pain on a 10 cm visual analogue scale in the recovery room, twice in the surgical day care unit and during the car ride home. The patients’ postoperative fentanyl requirements, time to recovery milestones, and side effects were recorded. The placebo group received more fentanyl in the PACU but did not achieve the same pain relief as either of the NSAID-treated group (ketorolac 44 ± 53 μg, indomethacin 39 ± 55 μg, placebo 87 ± 100 μg, P < 0.05). Patients who received an NSAID had less pain at 15 and 90 min (P < 0.05). The PACU stay was longer for the placebo group (ketorolac 50 ± 13 min, indomethacin 49 ± 12 min, placebo 62 ± 35 min, P < 0.05). Time to ambulation was also longer in the placebo group (ketorolac 117 ± 25 min, indomethacin 121 ± 49 min, placebo 140 ± 51 min, P < 0.05). However, no differences were observed between the two NSAIDS. Side effects were similar in all groups. We conclude that im ketorolac and pr indomethacin are equally effective analgesics in this group of patients.     

Effects of diclofenac and intra-articular morphine/bupivacaine on postarthroscopic pain control

BACKGROUND: This study was undertaken to compare analgesic effects and requirements for supplemental analgesic therapy after knee arthroscopy in patients given intraarticular morphine/bupivacaine, diclofenac i.m., or both compared with placebo. METHOD: In a randomised, double-blind controlled trial 40 patients were divided into four groups. Patients received 25 ml of 0.25% bupivacaine and 2 mg of morphine intraarticularly in group I, 75 mg of diclofenac i.m. in group III, the combination of 75 mg of diclofenac i.m. and 25 ml of 0.25% bupivacaine and 2 mg of morphine intraarticularly in group II, and placebo in group IV. Postoperative analgesia was provided with fentanyl in the recovery room and acetaminophen was given for subsequent pain relief. RESULTS: In the postoperative period, VAS scores for pain were highest in the placebo group, whereas they were lowest in the combination group. VAS scores were significantly lower in group I and II than group IV at the postoperative 2nd hour (p < 0.05). VAS score was significantly lower in group II than groups III and IV at the postoperative 3rd hour (p < 0.01). VAS scores were significantly lower in group I, II and III than group IV at the postoperative 6th hour (p < 0.05). Fentanyl consumption was significantly lower in group II than group IV (p < 0.05). Acetaminophen consumption in groups II and III were significantly lower than group IV (p < 0.05). CONCLUSION: The combination of diclofenac i.m. and intraarticular morphine/bupivacaine appears to be the most beneficial analgesic combination due to its lower VAS scores and supplemental analgesic requirements in the postoperative period.     

Multicentre evaluation of the adenosine agonist GR79236X in patients with dental pain after third molar extraction

Background: Adenosine is analgesic in humans, and the selective adenosineA1 receptor agonist GR79236X has significant anti-nociceptiveactivity in an animal pain model of inflammatory pain. Methods: Seventy-nine patients with moderate pain after third molar extractionunder general anaesthesia were randomized to receive a 15 mindouble-blind infusion containing either GR79236X 4 µgkg ^–1, GR79236X 10 µg kg ^–1, diclofenac 50mg, or saline placebo. Rescue analgesia was promptly availableto all patients. Results: Meaningful pain relief (mild or no pain) was attained by 9 (47%)patients in the placebo group, 12 (63%) patients in the GR792364 µg kg ^–1 group, 10 (48%) patients in the 10 µgkg ^–1 group, and 16 (80%) patients in the diclofenac 50mg group. Neither dose of GR79236 produced a significant improvementover placebo, but diclofenac was superior to both placebo (P= 0.036) and GR79236 10 µg kg ^–1 (P = 0.034). Mediantimes to rescue or additional analgesia were 62, 100, 60, and363 min for patients receiving placebo, GR79236 4 µg kg^–1, 10 µg kg ^–1, and diclofenac 50 mg, respectively(diclofenac significantly longer than placebo, P = 0.002 log-ranktest). Pain control was poor in the placebo group and in bothGR79236 groups, with between 79 and 86% of patients having goodpain control (i.e. mild or no pain) for <20% of the timecompared with only 30% of patients who received diclofenac. Conclusion: We found no evidence of efficacy of GR79236 compared with placebo,but the active control diclofenac was effective. It is possiblethat a higher dose of GR79236 might have been effective or thati.v. administration of this drug does not achieve appropriateconcentrations in the brain or peripheral nerves.     

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 相似文献   

Double-blind, randomized, placebo-controlled trial comparing rofecoxib with dexketoprofen trometamol in surgical dentistry

Background. Rofecoxib, a selective cyclooxygenase-2 inhibitor,and dexketoprofen trometamol, a single isomer non-steroidalanti-inflammatory drug (NSAID), are available for the treatmentof acute pain. Both are claimed to have fewer adverse effectsthan traditional NSAIDs. We have compared them in a clinicalsetting. Methods. We performed a double-blind randomized controlled trialinvolving 120 patients undergoing surgical removal of a singlemandibular third molar at the Edinburgh Dental Institute. Thosewho developed moderate pain within 4 h of the procedure wereallocated to one of three groups: rofecoxib 50 mg (Group RO,n=37); dexketoprofen trometamol 25 mg (Group DE, n=42); or placebo(Group PL, n=41). Participants monitored pain intensity andpain relief for 24 h using visual analogue scales (VAS)and verbal rating scales (VRS). The summed, time-weighted painrelief score to 8 h derived from the VRS (TOTPAR 8) was usedas the primary outcome variable. Results. No significant difference was demonstrated betweenGroups RO and DE using TOTPAR 8 as the primary outcome variable.Both drugs were significantly different compared with placebo.Rescue analgesia during the trial period was required by only15 out of 37 subjects in Group RO, but 35 out of 42 subjectsin Group DE. The median times to use of rescue medication were150 (Group PL), 398 (Group DE) and 1440 min (Group RO). Bothdrugs were well tolerated and adverse events reported were mildto moderate in severity. Conclusions. Rofecoxib and dexketoprofen trometamol are effectivetreatments for acute pain using a dental pain model and arewell tolerated. Rofecoxib has a longer duration of action asa single dose and gave adequate analgesia for over half of thatstudy group; patients in the dexketoprofen trometamol groupneeded more rescue analgesia. Br J Anaesth 2004; 92: 675–80     

Intravenous ketorolac vs diclofenac for analgesia after maxillofacial surgery

Purpose

To compare the efficacy of the nonsteroidal antiinflammatory drugs (NSAID), ketorolac and diclofenac in prevention of pain after maxillofacial surgery.

Methods

Sixty ASA I– II patients (30 in each group) received randomly, and double blindly either ketorolac 0.4 mg · kg^{? 1} or diclofenac 1.0 mg · kg^{? 1} iv after general anaesthesia induction, before surgical incision. In the ketorolac group, the same dose was repeated iv three times at six hour intervals. The diclofenac group patients received diclofenac 1.0 mg μ kg^{? 1} after 12 hr iv. Rescue analgesic medication consisting of oxycodone 0.03 mg · kg^{? 1} iv, was administered by a patient controlled analgesia apparatus.

Results

Two patients in the ketorolac and three patients in the diclofenac group did not need oxycodone during the study period. On average, 12 and 11 doses of oxycodone were needed in the ketorolac and the diclofenac groups, respectively (NS). Sideeffects were similar in both groups. All patients except one were satisfied with the pain therapy.

Conclusion

Parenteral ketorolac (0.4 mg · kg^{? 1} four times in 24 hr) and diclofenac (1 mg · kg^{? 1} twice in 24 hr) were similar, but insufficient alone, for analgesia after maxillofacial surgery.     

Preoperative ketorolac administration has no preemptive analgesic effect for minor orthopaedic surgery

The utility of preoperative ketorolac administration to reduce the intensity and duration of postoperative pain was compared with placebo in a randomized double-blind design of 60 ASA 1–2 patients scheduled for minor orthopaedic surgery. No opioids nor local anaesthetic blocks were used during surgery. The patients received either 30 mg ketorolac IV before surgery followed by a placebo injection after surgery or the reverse. Postoperative pain intensity was assessed repeatedly for 6 h using a visual analogue scale. No differences in pain intensity were observed between the two groups except for the initial 15-min postoperative assesments in the ketorolac group. The time to first rescue morphine administration and the total morphine consumption during the 6-h observation period were similar. It is concluded that the preoperative administration of ketorolac did not provide a significant preemptive analgesic benefit with regard to postoperative pain relief and opioid dose-sparing effect.     

Single-dose ketorolac and pethidine in acute postoperative pain: systematic review with meta-analysis

For a systematic review of postoperative analgesic efficacy and adverse effects of single doses, injected or oral, of pethidine and ketorolac compared with placebo, we sought published randomized studies in moderate to severe postoperative pain. Information on summed pain intensity or pain relief outcomes over 4-6 h was extracted and converted to dichotomous information to produce the number of patients with at least 50% pain relief. This was used to calculate the relative benefit and number-needed-to-treat (NNT) for one patient to achieve at least 50% pain relief. Minor and major adverse effect data were extracted and summarized. For pethidine 100 mg i.m., eight randomized, controlled studies met the inclusion criteria, with 203 patients given pethidine and 161 placebo. The NNT to produce at least 50% pain relief was 2.9 (95% confidence interval 2.3-3.9). At this dose, pethidine produced significantly more drowsiness and dizziness than placebo, with numbers-needed-to-harm (NNH) of 2.9 (2.2-4.4) and 7.2 (4.8-14), respectively. For ketorolac, 14 reports met the inclusion criteria (six i.m. and eight oral). Most i.m. information (176 patients) was available for the 30 mg dose, which had an NNT of 3.4 (2.5-4.9). Most oral information was available for the 10 mg dose, which had an NNT of 2.6 (2.3-3.1). Oral ketorolac 10 mg was consistently at least as effective as ketorolac 30 mg i.m. Only with oral ketorolac 10 mg were there significantly more adverse effects than with placebo, with an NNH for any adverse effect of 7.3 (4.7-17).