Cost effectiveness analysis of intravenous ketorolac and morphine for treating pain after limb injury: double blind randomised controlled trial.
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OBJECTIVES: To investigate the cost effectiveness of intravenous ketorolac compared with intravenous morphine in relieving pain after blunt limb injury in an accident and emergency department. DESIGN: Double blind, randomised, controlled study and cost consequences analysis. SETTING: Emergency department of a university hospital in the New Territories of Hong Kong. PARTICIPANTS: 148 adult patients with painful isolated limb injuries (limb injuries without other injuries). MAIN OUTCOME MEASURES: Primary outcome measure was a cost consequences analysis comparing the use of ketorolac with morphine; secondary outcome measures were pain relief at rest and with limb movement, adverse events, patients' satisfaction, and time spent in the emergency department. RESULTS: No difference was found in the median time taken to achieve pain relief at rest between the group receiving ketorolac and the group receiving morphine, but with movement the median reduction in pain score in the ketorolac group was 1.09 per hour (95% confidence interval 1.05 to 2.02) compared with 0.87 (0.84 to 1.06) in the morphine group (P=0.003). The odds of experiencing adverse events was 144.2 (41.5 to 501.6) times more likely with morphine than with ketorolac. The median time from the initial delivery of analgesia to the participant leaving the department was 20 (4.0 to 39.0) minutes shorter in the ketorolac group than in the morphine group (P=0.02). The mean cost per person was $HK44 ( pound4; $5.6) in the ketorolac group and $HK229 in the morphine group (P<0.0001). The median score for patients' satisfaction was 6.0 for ketorolac and 5.0 for morphine (P<0.0001). CONCLUSION: Intravenous ketorolac is a more cost effective analgesic than intravenous morphine in the management of isolated limb injury in an emergency department in Hong Kong, and its use may be considered as the dominant strategy. (+info)
Antinociceptive effects of delta-opioid agonists in Rhesus monkeys: effects on chemically induced thermal hypersensitivity.
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The effects of SNC80 and other structurally related delta-opioid receptor agonists were assessed under conditions of chemically induced hypersensitivity to thermal stimuli in four rhesus monkeys. The shaved tail of each monkey was exposed to warm water (38, 42, 46, and 50 degrees C), and the tail-withdrawal latency from each temperature was recorded. The effects of drugs on the temperature that produced a 10-s tail-withdrawal latency (the T(10) value) were examined. Capsaicin (0.01-0.32 mg) injected into the tail of monkeys dose dependently decreased the T(10), indicating that capsaicin increased sensitivity to thermal stimuli. A dose of 0.1 mg of capsaicin decreased the T(10) from 48.0 to 42.1 degrees C (a -5.9 degrees C change) 15 min after injection. SNC80 (1.0-10.0 mg/kg s.c.) dose dependently blocked the capsaicin-induced decrease in the T(10), and 10.0 mg/kg SNC80 fully blocked the effects of capsaicin. The delta-selective antagonist naltrindole (0.1-1.0 mg/kg) dose dependently antagonized the effects of SNC80, whereas a mu-selective dose of the opioid antagonist quadazocine (0.1 mg/kg) did not. Two other delta-selective agonists, SNC162 (1.0-10.0 mg/kg) and SNC243A (1.0-10.0 mg/kg), also dose dependently blocked capsaicin-induced thermal hypersensitivity. In contrast, neither SNC67 (10.0 mg/kg), which is the (-)-enantiomer of SNC80, nor the nonsteroidal anti-inflammatory drug (NSAID) ketorolac (1.0-10.0 mg/kg) modified the effects of capsaicin. SNC80 was also effective in reversing thermal hypersensitivity induced by prostaglandin E(2) (0.0158 mg) and Freund's complete adjuvant (10% concentration). These findings suggest that delta-agonists have antinociceptive effects in primates under conditions of chemically induced thermal hypersensitivity and might be effective under a broader range of conditions than clinically available NSAIDs. (+info)
Incidence of postoperative posterior capsular opacification following treatment with diclofenac 0.1% and ketorolac 0.5% ophthalmic solutions: 3-year randomized, double-masked, prospective clinical investigation.
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PURPOSE: Laboratory studies in experimental animals suggest that use of nonsteroidal anti-inflammatory drugs decreases the incidence of posterior capsular opacification (PCO) following cataract surgery. Recently the incidence of PCO following cataract surgery and intraocular lens implantation was reported to be no different following postoperative treatment with diclofenac sodium 0.1% (Voltaren, Ciba Vision) or with dexamethasone 0.1% (Maxidex, Alcon). We studied the incidence of PCO in patients following treatment with diclofenac 0.1% and ketorolac tromethamine 0.5% (Acular, Allergan) ophthalmic solutions 3 years after cataract surgery and implantation of a foldable silicone intraocular lens. METHODS: A total of 120 patients underwent phacoemulsification and implantation of a foldable silicone intracular lens. Patients were treated with either diclofenac 0.1% ophthalmic solution or 0.5% ketorolac ophthalmic solution 4 times daily for 30 days in a double-masked, randomized fashion during the postoperative period. Patients were examined 3 years following surgery by a masked observer who determined which patients received YAG capsulotomies and graded any existing PCO. RESULTS: Each treatment group had 12% YAG capsulotomies 3 years following surgery. Although PCO was present more often with diclofenac treatment (25/62) than with ketorolac treatment (16/58), this difference is not statistically significant (P = .142). Patients tolerated both treatments well without a difference in toxic effects or tolerability. CONCLUSIONS: This study did not demonstrate a difference in the ability of diclofenac or ketorolac ophthalmic solutions to prevent PCO following cataract extraction and implantation of an intraocular lens. Both treatment regimens were equally well tolerated. (+info)
Preemptive analgesic effects of ketorolac in ankle fracture surgery.
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BACKGROUND: Preemptive analgesia has been difficult to show in human experiments. If ketorolac has preemptive effects, then there may be an advantage to administering it at the beginning of surgery despite the potential for increased blood loss. METHODS: The authors performed a randomized, double-blind, controlled trial of 48 patients scheduled for ankle fracture surgery in a county trauma hospital. Anesthesia management was standardized and included adequate opioid analgesia (5 microg/kg fentanyl and 0.1 mg/kg morphine). Intravenous 30 mg ketorolac was administered to 23 patients before tourniquet inflation and to 25 patients after tourniquet inflation. Visual analog scale pain scores, morphine patient-controlled analgesia consumption, nausea-vomiting, and postoperative bleeding were measured. RESULTS: The 23 patients given ketorolac before tourniquet inflation had no increase in pain postoperatively compared with their preoperative baseline (P = 0.280). The 25 patients who received ketorolac minutes later after tourniquet inflation had significant increases in their postoperative pain compared with their preoperative baseline (P = 0.00116). This effect was short-lived, and by 6 h the pain score in this group was not significantly more than it was preoperatively. Intergroup comparison showed a lower visual analog scale score at 2 (P = 0.0203) and 4 h (P = 0.00549) in the preemptive group and lower nausea scores at hour 6 (P = 0.00704). There was no difference in patient-controlled analgesia consumption between groups. CONCLUSIONS: Intravenous 30 mg ketorolac appears to have preemptive analgesic effects in patients undergoing ankle fracture repair. Ketorolac administered before tourniquet inflation prevents postoperative pain being perceived as more intense than preoperative pain. (+info)
Therapeutic uses of non-steroidal anti-inflammatory drugs in dentistry.
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The non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used classes of drugs for the management of acute and chronic pain in dentistry. Their therapeutic efficacy and toxicity are well-documented and provide evidence that NSAIDs generally provide an acceptable therapeutic ratio of pain relief with fewer adverse effects than the opioid-mild analgesic combination drugs that they have largely replaced for most dental applications. The great many studies done with the oral surgery model of acute pain indicate that a single dose of an NSAID is more effective than combinations of aspirin or acetaminophen plus an opioid, with fewer side-effects, thus making it preferable for ambulatory patients. The combination of an NSAID with an opioid generally results in marginal analgesic activity but with an increased incidence of side-effects, which limits its use to patients in whom the NSAID alone results in inadequate analgesia. The selective COX-2 inhibitors hold promise for clinical efficacy with less toxicity from chronic administration and may prove advantageous for the relief of chronic orofacial pain. The use of repeated doses of NSAIDs for chronic orofacial pain should be re-evaluated in light of a lack of documented efficacy and the potential for serious gastrointestinal and renal toxicity with repeated dosing. (+info)
Ketorolac, diclofenac, and ketoprofen are equally safe for pain relief after major surgery.
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BACKGROUND: Ketorolac is approved for the relief of postoperative pain but concerns have been raised over a possible risk of serious adverse effects and death. Two regulatory reviews in Europe on the safety of ketorolac found the data were inconclusive and lacked comparison with other non-steroidal anti-inflammatory drugs. The aim of this study was to compare the risk of serious adverse effects with ketorolac vs diclofenac or ketoprofen in adult patients after elective major surgery. METHODS: This prospective, randomized multicentre trial evaluated the risks of death, increased surgical site bleeding, gastrointestinal bleeding, acute renal failure, and allergic reactions, with ketorolac vs diclofenac or ketoprofen administered according to their approved parenteral and oral dose and duration of treatment. Patients were followed for 30 days after surgery. RESULTS: A total of 11,245 patients completed the trial at 49 European hospitals. Of these, 5634 patients received ketorolac and 5611 patients received one of the comparators. 155 patients (1.38%) had a serious adverse outcome, with 19 deaths (0. 17%), 117 patients with surgical site bleeding (1.04%), 12 patients with allergic reactions (0.12%), 10 patients with acute renal failure (0.09%), and four patients with gastrointestinal bleeding (0.04%). There were no differences between ketorolac and ketoprofen or diclofenac. Postoperative anticoagulants increased the risk of surgical site bleeding equally with ketorolac (odds ratio=2.65, 95% CI=1.51-4.67) and the comparators (odds ratio=3.58, 95% CI=1.93-6.70). Other risk factors for serious adverse outcomes were age, ASA score, and some types of surgery (plastic/ear, nose and throat, gynaecology, and urology). CONCLUSION: We conclude that ketorolac is as safe as ketoprofen and diclofenac for the treatment of pain after major surgery. (+info)
Role of prostanoids in regulation of the renin-angiotensin-aldosterone system by salt intake.
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We investigated the effect of cyclooxygenase (COX) activity on the regulation of the renin-angiotensin-aldosterone system by salt intake. Therefore, Sprague-Dawley rats were subjected to different salt diets [0.02, 0.6, and 8% NaCl (wt/wt)] and treated with the selective COX-2 inhibitor rofecoxib (10 mg x kg body wt(-1) x day(-1)) or with ketorolac at a dose selective for COX-1 inhibition (2 mg x kg body wt(-1) x day(-1)) for 3, 7, 14, and 21 days. Rofecoxib and ketorolac caused a similar reduction of renocortical PGE2 formation with a low-salt diet. Rofecoxib did not change plasma renin activity or renocortical renin mRNA abundance with any of the diets but clearly lowered plasma aldosterone concentration. In contrast, ketorolac delayed the increase in plasma renin activity and of renin mRNA in response to low salt intake but did not change plasma aldosterone concentration. Prolonged treatment with rofecoxib but not with ketorolac caused an upregulation of COX-2 expression while COX-1 mRNA abundance remained unchanged. These findings suggest that COX-1-derived, but not COX-2-derived, prostanoids are of relevance for the regulation of the renin system by salt intake. (+info)
Efficacy and safety of intravenous parecoxib sodium in relieving acute postoperative pain following gynecologic laparotomy surgery.
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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 +info)