Showing papers on "Ketorolac published in 2007"

Reduced hospital stay and narcotic consumption, and improved mobilization with local and intraarticular infiltration after hip arthroplasty: a randomized clinical trial of an intraarticular technique versus epidural infusion in 80 patients.

Abstract: Background Epidural analgesia gives excellent pain relief but is associated with substantial side effects. We compared wound infiltration combined with intraarticular injection of local anesthetics for pain relief after total hip arthroplasty (THA) with the well-established practice of epidural infusion.Methods 80 patients undergoing elective THA under spinal block were randomly assigned to receive either (1) continuous epidural infusion (group E) or (2) infiltration around the hip joint with a mixture of 100 mL ropivacaine 2 mg/mL, 1 mL ketorolac 30 mg/mL, and 1 mL epinephrine 0.5 mg/mL at the conclusion of surgery combined with one postoperative intraarticular injection of the same substances through an intraarticular catheter (group A).Results Narcotic consumption was significantly reduced in group A compared to group E (p = 0.004). Pain levels at rest and during mobilization were similar in both groups but significantly reduced in group A after cessation of treatment. Length of stay was reduced by 2 d...

Postoperative analgesia in total hip arthroplasty: A randomized double-blinded, placebo-controlled study on peroperative and postoperative ropivacaine, ketorolac, and adrenaline wound infiltration

Abstract: Background Comfort and lack of pain are important for optimal mobilization after hip replacement. We investigated the efficacy of double wound infiltration.Patients and methods 40 consecutive patients undergoing total hip replacement were randomized into two groups in this double-blinded study. They received wound infiltration at the end of surgery and through an intraarticular catheter 24 h postoperatively. The catheter was placed at the end of surgery. One group received solutions of ropivacaine, ketorolac, and adrenaline. Patients in the control group were injected with saline instead. The observation period was 6 weeks.Results The patients who received the analgesic solution had less pain up to 2 weeks postoperatively. They reached an earlier and lower pain minimum during the first days postoperatively, had lower use of analgesia up to day 4 postoperatively, and were more satisfied. Use of analgesic solution resulted in less joint stiffness and better function 1 week postoperatively.Interpretation Ope...

In vivo pharmacokinetics and in vitro pharmacodynamics of nepafenac, amfenac, ketorolac, and bromfenac

Abstract: Purpose To evaluate the aqueous humor concentrations and cyclooxygenase (COX) inhibitory activities of nepafenac, amfenac, ketorolac, and bromfenac after topical ocular administration of Nevanac (nepafenac 0.1%), Acular LS (ketorolac 0.4%), or Xibrom (bromfenac 0.09%). Setting Five private ophthalmology practices throughout the United States. Methods Patients requiring cataract extraction were randomized to 1 of 3 treatment groups: Nevanac, Acular LS, or Xibrom. Patients were administered 1 drop of the test drug 30, 60, 120, 180, or 240 minutes before cataract surgery. At the time of paracentesis, an aqueous humor sample was collected and later analyzed for drug concentration. In addition, COX-1 (homeostatic) and COX-2 (inducible) inhibitory activities of nepafenac, amfenac, ketorolac, and bromfenac were determined via the in vitro measurement of prostaglandin E2 (PGE2) inhibition. Results Seventy-five patients participated in the study. The prodrug nepafenac had the shortest time to peak concentration and the greatest peak aqueous humor concentration (Cmax). The Cmax of nepafenac was significantly higher than that of the other drugs (P Conclusion Nepafenac showed significantly greater ocular bioavailability and amfenac demonstrated greater potency at COX-2 inhibition than ketorolac or bromfenac.

Acetaminophen selectively suppresses peripheral prostaglandin E2 release and increases COX-2 gene expression in a clinical model of acute inflammation.

Abstract: Acetaminophen is widely used for pain management as an alternative to NSAIDs and selective COX-2 inhibitors, but its action at a molecular level is still unclear. We evaluated acetaminophen's effect on PG release and the expression patterns of genes related to PG production in a clinical model of tissue injury and acute inflammation. Subjects (119 outpatients) received either 1000 mg acetaminophen, 50 mg rofecoxib (a selective COX-2 inhibitor), 30 mg ketorolac (a dual COX-1/COX-2 inhibitor), or placebo before the surgical removal of two impacted mandibular third molars. Microdialysis was used to collect inflammatory transudate from the surgical site for measurement of PGE2 and TXB2 levels at the site of injury. Biopsies were collected to investigate the expression patterns of genes related to PG production at baseline prior to surgery and at 3 or 24 h following surgery. PGE2 release was suppressed by ketorolac, rofecoxib and acetaminophen compared to placebo at 3 h coincident with increased COX-2 gene expression in biopsies collected from the surgical site. TXB2 release was suppressed only by ketorolac. COX-2 gene expression remained elevated at 24 h with continued ketorolac and acetaminophen treatment. COX-1 gene expression was significantly down-regulated at 24 h by ketorolac, rofecoxib and acetaminophen. Acetaminophen suppression of PGE2 without inhibiting TXB2 release, when COX-2 gene expression is up-regulated, suggests that acetaminophen is a selective COX-2 inhibitor in vivo. The up-regulation of COX-2 gene and down-regulation of COX-1 gene expression suggests that acetaminophen may result in changes in COX-derived prostanoids with repeated doses.

Optimizing recovery after laparoscopic colon surgery (ORAL-CS): effect of intravenous ketorolac on length of hospital stay.

Abstract: The objective of this study was to determine if intravenous ketorolac can reduce ileus following laparoscopic colorectal surgery, thus shortening hospital stay. This was a prospective, randomized, double-blind, placebo-controlled, clinical trial of patients undergoing laparoscopic colorectal resection and receiving morphine patient controlled analgesia (PCA) and either intravenous ketorolac (group A) or placebo (group B), for 48 h after surgery. Daily assessments were made by a blinded assistant for level of pain control. Diet advancement and discharge were decided according to strictly defined criteria. From October 2002 to March 2005, 190 patients underwent laparoscopic colorectal surgery. Of this total, 84 patients were eligible for this study and 70 consented. Another 26 patients were excluded, leaving 22 patients in each group. Two patients who suffered anastomotic leaks in the early postoperative period were excluded from further analysis. Median length of stay for the entire study was 4.0 days, with significant correlation between milligrams of morphine consumed and time to first flatus (r = 0.422, p = 0.005), full diet (r = 0.522, p < 0.001), and discharge (r = 0.437, p = 0.004). There we no differences between groups in age, body mass index, or operating time. Patients in group A consumed less morphine (33 ± 31 mg versus 63 ± 41 mg, p = 0.011), and had less time to first flatus (median 2.0 days versus 3.0 days, p < 0.001) and full diet (median 2.5 days versus 3.0 days, p = 0.033). The reduction in length of stay was not significant (mean 3.6 days versus 4.5 days, median 4.0 days versus 4.0 days, p = 0.142). Pain control was superior in group A. Three patients required readmission for treatment of five anastomotic leaks (4 in group A versus 1 in group B, p = 0.15). Two of them underwent reoperation. Intravenous ketorolac was efficacious in improving pain control and reducing postoperative ileus when anastomotic leaks were excluded. This simple intervention shows promise in reducing hospital stay, although the outcome was not statistically significant. The high number of leaks is inconsistent with this group’s experience and is of concern.

Patient-Controlled Analgesia After Arthroscopic Rotator Cuff Repair Subacromial Catheter Versus Intravenous Injection

Abstract: Background: No study has compared pain control results between patient-controlled subacromial infusion and intravenous injection after arthroscopic shoulder surgery.Hypothesis: Subacromial infusion of analgesics are more effective in pain alleviation than intravenous injection.Study Design: Randomized controlled clinical trial; Level of evidence, 2.Methods: The authors prospectively analyzed 40 cases of arthroscopic rotator cuff repair that received patient-controlled anal-gesia. They divided the 40 cases into 2 groups: subacromial infusion group with 0.5% bupivacaine (group 1, 20 cases) and intravenous injection group with fentanyl and ketorolac tromethamine (group 2, 20 cases). The visual analog scale was used to record the patient’s level of pain every 12 hours until postoperative 72 hours and the following 48 hours after the suspension of patient-controlled analgesia.Results: The mean preoperative visual analog scale score during motions was 6.8 in group 1 and 5.8 in group 2. The immediate postoperati...

Pharmacokinetics and Safety of Ketorolac Following Single Intranasal and Intramuscular Administration in Healthy Volunteers

Abstract: Ketorolac was administered to 15 healthy volunteers in a phase 1, single-dose, crossover, randomized study. Subjects received open-label randomized 15- and 30-mg intramuscular (i.m.) ketorolac and blinded randomized 15- and 30-mg intranasal (i.n.) ketorolac. The i.n. ketorolac was well tolerated; the only nasal symptoms were some instances of mild irritation. The i.n. ketorolac was rapidly and well absorbed (median tmax, 0.50-0.75 hours), and the half-life was approximately 5 to 6 hours, values that were similar to those following i.m. administration. Relative bioavailability of i.n. compared to i.m. administration at the same doses was approximately 67% to 75%. Dose proportionality was noted between the 15- and 30-mg i.n. and i.m. dose levels. Thus, i.n. ketorolac offers a therapeutic alternative to i.m. administration and may provide benefits in the clinical setting.

Low-dose intrathecal morphine for postoperative analgesia in children.

Abstract: Background We evaluated the efficacy and safety profile of low-dose (4-5 mcg/kg) intrathecal morphine for postoperative pain management after various surgical procedures in children. Methods We reviewed the pain management service database and the medical records of patients who received low-dose intrathecal morphine for postoperative analgesia at The Children's Hospital of Philadelphia between October 2003 and March 2006. Patients had been prospectively followed for 24-48 h after the intrathecal morphine administration. Results The medical records of 187 patients were examined. The mean age was 5.6 +/- 5.1 yr (median 4.0, interquartile range [IQR] 1.0-10.0). The median maximum pain score during the first 24 h in patients evaluated by the FLACC score and in those evaluated by the numeric verbal rating scale, was 0 (IQR 0-3) and 0 (IQR 0-4), respectively. The mean time to first rescue opioid was 22.4 +/- 16.9 h (range: 0-48 h, 95% CI: 19.9-24.8 h). During the first 24 h after surgery, 70 patients (37%) did not receive any opioids (oral or IV). Of the 117 patients who received opioids, 59 (50%) were managed with oxycodone only. Pain was managed with ketorolac in 33% of patients, either alone (11%) or in combination with IV or oral opioids (22%). The incidence of nausea or vomiting, pruritus, and urinary retention was 32%, 37%, and 6% respectively. One patient had transient postdural puncture headache, while two patients received supplemental oxygen beyond the first 60 postoperative minutes to manage occasional episodes of hypoxemia. No severe respiratory depression requiring assisted ventilation or naloxone administration was observed. Conclusion We conclude that low-dose intrathecal morphine in the pediatric population can be a useful and safe adjunct for postoperative analgesia.

Analgesic and anti-inflammatory effectiveness of nepafenac 0.1% for cataract surgery.

Abstract: BACKGROUND To compare nepafenac 0.1% with placebo and ketorolac 0.5% for prevention and treatment of ocular pain and inflammation after cataract surgery. METHODS In a multi-center, randomized, placebo- and active-controlled, double-masked clinical trial, 227 patients with cataract were randomized to receive nepafenac 0.1%, ketorolac 0.5%, or placebo TID beginning 1 day pre-operatively and continuing for 21 days postoperatively. At each postoperative visit, cure rates and clinical success rates (

Analgesic and antiemetic effect of ketorolac vs. betamethasone or dexamethasone after ambulatory surgery.

Abstract: Background: Glucocorticoids are known to provide slower onset and more prolonged duration of analgesic effect than ketorolac. In the present study, we wanted to evaluate the effect over time from a single dose of either intravenous (i.v.) dexamethasone or an intramuscular (i.m.) depot formulation of betamethasone compared with i.v. ketorolac. Materials and methods: One hundred and seventy-nine patients admitted for mixed ambulatory surgery were included in the study. After induction of general i.v. anaesthesia, the patients were randomized to receive double-blindly either dexamethasone 4 mg i.v. (Group D) or betamethasone depot formulation 12 mg i.m. (Group B) or ketorolac 30 mg i.v. (Group K). Fentanyl was used for rescue analgesic medication in the post-operative care unit (PACU) and codeine with paracetamol after discharge, for a study period of 3 days. Results: There was significantly less post-operative pain in the ketorolac group during the stay in the unit (88% with minor or less pain in Group K vs. 74% and 67% in Groups D and B, respectively, P < 0.05), significantly less need for rescue medication (P < 0.05) and significantly less nausea or vomiting (12% in Group K vs. 30% in the other groups pooled, P < 0.05). The ketorolac patients were significantly faster for ready discharge, median 165 min vs. 192 min and 203 min in Groups D and B, respectively (P < 0.01). There were no differences between the groups in perceived pain, nausea, vomiting or rescue analgesic consumption in the 4- to 72-h period. Conclusion: Dexamethasone 4 mg or bethamethasone 12 mg did not provide prolonged post-operative analgesic effect compared with ketorolac 30 mg, which was superior for analgesia and antiemesis in the PACU.

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

Abstract: 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.

Double-masked comparison of ketorolac tromethamine 0.4% versus nepafenac sodium 0.1% for postoperative healing rates and pain control in eyes undergoing surface ablation.

Abstract: Purpose Determine the degree of postoperative pain and rate of healing in eyes treated with either ketorolac tromethamine 0.4% (Acular LS) or nepafenac sodium 0.1% (Nevanac) after flapless surface ablation [epi-laser in situ keratomileusis (LASIK)]. Methods Prospective, randomized, double-masked, paired-eye comparison. Patients undergoing flapless surface ablation were randomized to receive ketorolac in 1 eye and nepafenac in the other. Drops were instilled immediately after the surgical procedure, and patients continued to instill the masked drops 3 times daily for 5 days. Study follow-up visits were at days 1 and 5 postoperatively. Patients were queried by phone regarding their level of pain at 5 hours postoperatively and on days 2, 3, and 4. Outcome measures included postoperative pain levels including need for additional rescue medications, rate of healing, and adverse events. Results Although the original target population was 60 eyes of 30 patients, this study was halted after only 14 eyes of 7 patients because of concern for patient safety, because most patients in 1 arm developed haze. Eyes treated with nepafenac healed at a slower rate than eyes treated with ketorolac in 57% of patients. Mean time to healing was 5.7 +/- 1.1 days with ketorolac and 7.9 +/- 2.1 days with nepafenac (P = 0.066). Moreover, eyes treated with nepafenac exhibited statistically significant greater mean hazing scores at week 2 (P = 0.024) and month 1 (P = 0.039). Throughout the study, a greater percentage of nepafenac-treated eyes exhibited haze than did ketorolac-treated eyes. This difference was statistically significant at week 2 (P = 0.005) and month 1 (P = 0.039). Patients reported significantly more pain in nepafenac-treated eyes at day 3 when pain was at its peak (P = 0.046). Conclusions In patients undergoing epi-LASIK, a statistically significant trend postoperative toward increased corneal haze was seen with nepafenac compared with ketorolac. Nepafenac therapy resulted in a non-statistically significant trend toward delayed healing. The study was halted because of safety concerns.

Ketorolac tromethamine LS 0.4% versus nepafenac 0.1% in patients having cataract surgery. Prospective randomized double-masked clinical trial

Abstract: Purpose To compare the clinical, subjective, and objective outcomes of the use of 2 topical nonsteroidal antiinflammatory drugs—ketorolac tromethamine LS 0.4% (Acular) and nepafenac 0.1% (Nevanac)—in patients having cataract surgery. Setting Single-center private practice, Las Vegas, Nevada, USA. Methods One hundred eighty-three patients (193 eyes) with visually significant cataract were recruited for the study. Consenting patients were randomized to a standard regimen of Acular, gatifloxacin 0.3% (Zymar), and prednisolone acetate 1% (Pred Forte) (ketorolac group) or Nevanac, moxifloxacin hydrochloride 0.5% (Vigamox), and prednisolone acetate (Econopred) (nepafenac group). Analysis included subjective complaints (burning, itching, foreign-body sensation, pain level after surgery) and objective findings (visual function, degree of inflammation in the anterior segment, complications). Results The ketorolac group consisted of 94 patients (100 eyes) and the nepafenac group, 89 patients (93 eyes). The between-group differences in visual outcomes and anterior chamber inflammation were not statistically significant (mean P = .33). There was a higher incidence of posterior capsule opacification in the nepafenac group ( P = 0.019). Patient satisfaction, patient compliance, and postoperative pain control were statistically significantly better in the ketorolac group ( P = .022, P = .023, and P = .025, respectively). Conclusion Ketorolac tromethamine was statistically significantly better than nepafenac in terms of patient satisfaction, compliance, and postoperative pain control.

Postoperative ketorolac tromethamine use in infants aged 6-18 months: the effect on morphine usage, safety assessment, and stereo-specific pharmacokinetics.

Abstract: Background Nonsteroidal antiinflammatory drugs have been useful for treating postoperative pain in children. The only parenteral nonsteroidal antiinflammatory drug currently available in the United States is ketorolac tromethamine with cyclooxygenase-1 and cyclooxygenase-2 effects. Information on the pharmacokinetics of ketorolac in infants is sparse, making dosing difficult. Ketorolac is administered as a racemic mixture with the S(-) isomer responsible for the analgesic effect. In this study, we describe the population pharmacokinetics of ketorolac in a group of 25 infants and toddlers who received a single IV administration of racemic ketorolac and evaluate the potential influence of patient covariates on ketorolac disposition. Methods In this double-blind, placebo-controlled study, ketorolac pharmacokinetic, safety, and analgesic effects were studied in 37 infants and toddlers (aged 6-18 mo) postoperatively. On postoperative day 1, infants were randomized to receive placebo, 0.5, or 1 mg/kg ketorolac as a 10-min IV infusion. Blood samples were collected up to 12-h after dosing. The data were analyzed using noncompartmental and compartmental (nonlinear mixed-effects model) means. The patient covariates, including body weight, age, and surgical procedure, were analyzed in a stepwise fashion to identify their potential influence on ketorolac pharmacokinetics. Results The data were best described by a two-compartmental model. Inclusion of covariates did not significantly decrease the nonlinear mixed-effects model objective function values and between-subject variability in the pharmacokinetic parameters of nested models. The mean and standard error of the estimates of the R(+) isomer were central volume of distribution 1200 +/- 163 mL (coefficient of variation of interindividual variability, 13.6%), peripheral volume of distribution 828 +/- 108 mL (13.0%), clearance from the central compartment 7.52 +/- 0.7 mL/min (9.3%), and extrapolated elimination half-life 238 +/- 48 min. Those of the S(-) isomer were 2320 +/- 34 (14.6%), 224 +/- 193 mL (86.2%), 45.3 +/- 5.5 mL/min (12.1%), and 50 +/- 42 min respectively. Dosing simulations, using population pharmacokinetic parameters, showed no accumulation of S(-) ketorolac but steady increases in R(+) ketorolac. Safety assessment showed no adverse effects on renal or hepatic function tests, surgical drain output, or continuous oximetry between placebo and ketorolac groups. Cumulative morphine administration showed large interpatient variability and was not different between groups. Conclusion The stereo-isomer-specific clearance of ketorolac in infants and toddlers (aged 6-18 mo) shows rapid elimination of the analgesic S(-) isomer. No adverse effects on surgical drain output, oximetry measured saturations, renal or hepatic function tests were seen. Simulation of single dosing at 0.5 or 1 mg/kg every 4 or 6 h does not lead to accumulation of S(-) ketorolac, the analgesic isomer, but does result in increases in R(+) ketorolac. Shorter dose intervals may be needed in infants older than 6 mo.

Double-masked study of the effects of nepafenac 0.1% and ketorolac 0.4% on corneal epithelial wound healing and pain after photorefractive keratectomy.

Abstract: Two NSAIDs—nepafenac 0.1% and ketorolac tromethamine 0.4%—were compared in terms of their effects on corneal reepithelialization and pain after photorefractive keratectomy (PRK) in a randomized, double-masked, contralateral eye, multicenter study. A total of 40 healthy adult patients who were undergoing sequential bilateral PRK received nepafenac 0.1% and ketorolac 0.4% in contralateral eyes, 1 drop 3 times daily for 3 d after bandage contact lens insertion. Patients were assessed on postoperative days 1, 3, 4, 5, and 7. At each visit, patients provided a general rating of pain. Each patient also assessed the sensation of each eyedrop following instillation (after-drop pain, irritation, burning/stinging, and overall comfort). Starting on day 3, epithelial defect size was assessed. Mean epithelial defect size was similar between treatments at each postoperative visit (P > .05). The average time-to-healing was 4.18 d for nepafenac 0.1 % and 4.00 d for ketorolac 0.4% (P=.3134). No statistical difference was observed between nepafenac 0.1% and ketorolac 0.4% in mean postoperative pain scores (P > .05). On day 3, the nepafenac 0.1% group had significantly lower mean sensation scores than did the ketorolac 0.4% group for after-drop pain (P=.0090), irritation (P=.0007), and burning/ stinging (P=.0003). Mean overall comfort score was also significantly better for nepafenac 0.1% on day 3 (7.43 vs 6.41; P < .0001). Nepafenac 0.1% and ketorolac 0.4% provide postoperative pain relief after PRK surgery without associated adverse effects on corneal epithelial healing. Nepafenac 0.1 % treatment may offer greater comfort upon instillation in patients who have undergone PRK.

Effects of nonsteroidal ophthalmic drops on epithelial healing and pain in patients undergoing bilateral photorefractive keratectomy (PRK).

Abstract: The present study, which was designed as a prospective, double-masked, randomized, controlled, single-site study, was conducted to compare the effects of 3 approved ophthalmic nonsteroidal anti-inflammatory drugs—nepafenac ophthalmic suspension 01% (Nevanac®; Alcon Laboratories, Inc, Fort Worth, Tex), ketorolac tromethamine ophthalmic solution 04% (Acular LS®; Allergan, Irvine, Calif), and bromfenac 009% (Xibrom™; ISTA Pharmaceuticals, Irvine, Calif)—on corneal reepithelialization and postoperative pain control in patients undergoing photorefractive keratectomy In addition to nonsteroidal anti-inflammatory drugs, each patient received an antibiotic—moxifloxacin hydrochloride ophthalmic solution 05% (nepafenac group) or gatifloxacin ophthalmic solution 03% (ketorolac and bromfenac groups) All treatments were administered 3 times daily beginning 1 d preoperatively and continuing for 1 wk postoperatively; prednisolone acetate 10% was administered concurrently 4 times daily Bandage contact lenses were replaced at each postoperative visit for corneal staining and epithelial defect grading Self-evaluation of pain relief was recorded on postoperative days 1 and 3 with the use of a visual analog scale A total of 29 patients (58 eyes) were enrolled and underwent bilateral custom photorefractive keratectomy Mean time to reepithelialization was 550±159 d for the nepafenac 01% group, 562±123 d for the ketorolac 04% group, and 725±253 d for the bromfenac 009% group A significant difference was detected between nepafenac 01% and bromfenac 009% and between ketorolac 04% and bromfenac 009% (P< 05) Significant reductions in pain scores were observed with nepafenac 01% on day 1 (−113) and day 3 (−132), ketorolac 04% on day 3 (−088), and bromfenac 009% on day 3 (−083) No adverse events were reported Eyes treated with nepafenac 01% or ketorolac 04% achieved complete reepithelialization significantly faster than those treated with bromfenac 009% Daily contact lens removal and application of fluorescein may have delayed reepithelialization in the overall population; however, the effect would have been the same in all 3 groups Pain relief with nepafenac 01% was achieved sooner than with ketorolac 04% or bromfenac 009%

Comparative effects of the nonsteroidal anti-inflammatory drug nepafenac on corneal sensory nerve fibers responding to chemical irritation.

Abstract: Purpose To compare the corneal analgesic efficacy of the nonsteroidal anti-inflammatory drugs (NSAIDs) nepafenac, diclofenac, and ketorolac, and to evaluate the possibility that their inhibitory effects on corneal polymodal nociceptor fiber activity are partly mediated by a decrease in sodium currents. Methods Corneal sensory afferent units were recorded in the anesthetized cat. The response of thin myelinated polymodal nociceptor fibers to mechanical and acidic stimulation (98.5% CO(2)) was recorded before and at various times after topical application of the vehicle or of nepafenac 0.1% (Nevanac; Alcon Laboratories, Ltd., Fort Worth, TX), diclofenac 0.1% (Voltaren; Novartis, Basel, Switzerland), and ketorolac 0.4% (Acular LS; Allergan, Irvine, CA). Voltage-clamp recordings were performed in cultured trigeminal ganglion neurons. Results Nepafenac, diclofenac, and ketorolac reduced the mean frequency of the impulse response evoked by repeated CO(2) stimuli in polymodal nociceptor fibers. The progressive increase in ongoing activity, observed in vehicle-treated eyes after repeated acidic stimulation was also prevented. Nepafenac exhibited a more rapid and a slightly more pronounced effect on spontaneous and CO(2)-evoked activity than did diclofenac and ketorolac and did not affect the responsiveness of corneal mechanonociceptor or cold receptor fibers. In cultured mice trigeminal ganglion neurons, diclofenac significantly suppressed sodium currents, whereas nepafenac or its metabolite, amfenac, exhibited only minimal inhibitory effects. Conclusions The inhibition of polymodal nociceptor activity by nepafenac, a weak inhibitor of cyclooxygenase, is most likely due to its greater lipophilicity compared with diclofenac and ketorolac, leading to a rapid saturation of the corneal epithelium where nociceptor terminals are located. In contrast to diclofenac, nepafenac does not exhibit local anesthetic effects.

Bleeding risk with ketorolac after lumbar microdiscectomy.

Abstract: There is a need to improve postoperative analgesia to support the trend to shorter hospitalization after minimally invasive spine surgeries. Ketorolac Tromethamine has proven efficacy in decreasing postoperative pain but there is concern with postoperative epidural bleeding after spine procedures. We prospectively assessed the incidence of bleeding complications after microdiscectomy in patients treated with a single 30 mg intraoperative dose of Ketorolac subsequent to wound closure. Group 1 consisted of 44 patients, 24 women and 20 men with mean age of 35.7 years (20 to 68 y) treated with Ketorolac. Group 2 consisted of 45 patients, 28 men and 17 women with mean age 46.8 years (32 to 74 y), who underwent discectomy without Ketorolac. Postoperative bleeding complications were monitored along with pain levels and time to discharge. We detected no significant postoperative changes in coagulation parameters or bleeding from the surgical site in either group. Both group 1 and 2 had averaged preoperative visual analog scale scores for leg pain of 8. Group 1 had an average postoperative visual analog scale score of 2.6 compared with 4 for group 2 two hours after surgery. Single dose intravenous Ketorolac provided beneficial analgesia without significant increase in risk of bleeding after microdiscectomy, enabling us to consistently perform microdiscectomy as an ambulatory procedure. Meticulous hemostasis should be accomplished before closure. Prolonged postoperative use is a promising alternative to narcotics.

Preincisional subcutaneous infiltration of ketamine suppresses postoperative pain after circumcision surgery.

Abstract: Objective: N-methyl-D-aspartate and other glutamate receptors have been shown to present on the peripheral axons of primary afferents, and peripheral injection of N-methyl-D-aspartate-receptor antagonists can suppress hyperalgesia and allodynia. Thus, this study examined postoperative analgesic and adverse effects of local ketamine administered postoperatively. Methods: Ketamine (0.3%, 3mL) or saline was subcutaneously infiltrated before incision in a double-blind manner using a sample population of 40 patients undergoing circumcision surgery, equally and randomly assigned to 2 groups based on the treatment. The saline-infiltrated patients also received 9-mg intramuscular ketamine into the upper arm to control for any related systemic analgesic effects. The patients were followed up for 24 hours to determine postoperative analgesia and identify adverse effects. Results: In the ketamine-infiltrated patients, the time interval until first analgesic demand (166 vs. 80min) was longer and the incidence of pain-free status (pain score = 0) during movement (45% vs. 10%) and erection (40% vs. 0%) was significantly higher than for the saline-treated analogs (P < 0.05). The dose of ketorolac use and pain score during erection were significant lower in group ketamine patients. No significant differences were noted with respect to the incidence of adverse effects comparing the 2 groups. Discussion: We conclude that preincisional subcutaneous ketamine infiltration can suppress postoperative pain after the circumcision surgery.

Myth: parenteral ketorolac provides more effective analgesia than oral ibuprofen.

Abstract: Acute pain is an extremely common presenting symptom to the emergency department (ED), making it imperative that emergency physicians provide adequate, safe and cost-effective analgesia. Nonsteroidal anti-inflammatory drugs (NSAIDs) are often first-line treatments for moderate to severe pain. Physicians can choose between intramuscular (IM) or intravenous (IV) ketorolac and an oral NSAID. The mechanism of action (reversible inhibition of prostaglandin synthesis at the level of cyclooxygenase) is identical irrespective of the route the medication is given. Despite the similar pharmacodynamics, many physicians believe that parenteral ketorolac is more efficacious, despite a greater cost and a more invasive route of administration. To investigate this myth (i.e., that parenteral ketorolac provides greater analgesic effect than an oral NSAID), we conducted a review of the literature, with specific focus on ibuprofen as the prototypical — and least expensive — oral NSAID.

Anxiolysis and postoperative pain in patients undergoing spinal anesthesia for abdominal hysterectomy.

Abstract: AIM The relationship between pain and psychological factors is well known. The aim of the study was to evaluate the influence of lorazepam, given before total abdominal hysterectomy, on postoperative pain control. METHODS Sixty patients, enrolled in the study, were defined as either anxious or not anxious when the State/Trait Anxiety Inventory (STAI) score was =/>51 or =/< 50, respectively. The anxious patients were randomly assigned to receive oral lorazepam 0.035 mg/kg the night and 2 h before surgery (Group A), or placebo at the same time (Group B). The not anxious patients were assigned to receive oral lorazepam 0.035 mg/kg the night and 2 h before surgery (Group C), or placebo at the same time (Group D). Anesthesia was performed with subarachnoidal block. Ketorolac was used for postoperative pain. As rescue drug, tramadol was administered using a patient controlled analgesia (PCA) modality. Postoperative pain was assessed during the 24 h after surgery by tramadol consumption. RESULTS Tramadol consumption was significantly greater in Group B (216.3+/-58.9 mg) than in Groups A, C and D respectively (150.9+/-28.9 mg; 153.6+/-39.9 mg; 154.4+/-39.9 mg). Group B showed a significantly higher pain score compared to the other groups during the first 8 h. No difference in patient satisfaction with perioperative treatment was noted. CONCLUSION Preoperative lorazepam reduced perioperative anxiety. This could explain the better postoperative pain control in patients undergoing hysterectomy, a very stressful surgical procedure.

A review of the use of ketorolac tromethamine 0.4% in the treatment of post-surgical inflammation following cataract and refractive surgery.

Abstract: The non-steroidal anti-inflammatory drug (NSAID) ketorolac tromethamine 0.4% ophthalmic solution, a recent reformulation containing 20% less active ingredient that the original formulation, is indicated for the reduction of ocular pain and burning/stinging following corneal refractive surgery. Clinical studies have shown ketorolac tromethamine 0.4% to be as effective as ketorolac tromethamine 0.5% to control inflammation after cataract surgery including prevention of cystoid macular edema (CME). Its efficacy to inhibit miosis during cataract surgery as well as its role in the treatment of dry eye has been reported. The purpose of this paper is to review the use of ketorolac tromethamine 0.4% in the treatment of post-surgical inflammation following cataract and refractive surgery.

Ketorolac-dextran conjugates: synthesis, in vitro and in vivo evaluation.

Abstract: Ketorolac is a non-steroidal anti-inflammatory drug. Dextran conjugates of ketorolac (KD) were synthesized and characterized to improve ketorolac aqueous solubility and reduce gastrointestinal side effects. An N-acyl-imidazole derivative of ketorolac (KAI) was condensed with a model carrier polymer, dextran of different molecular masses (40000, 60000, 110000 and 200000). IR spectral data confirmed formation of ester bonding. Ketorolac contents were evaluated by UV-spectrophotometric analysis. The molecular mass was determined by measuring viscosity using the Mark-Howink-Sakurada equation. In vitro hydrolysis studies were performed in aqueous buffers (pH 1.2, 7.4, 9) and in 80% (V/V) human plasma (pH 7.4). At pH 9, a higher rate of ketorolac release from KD was observed as compared to aqueous buffer of pH 7.4 and 80% human plasma (pH 7.4), following first-order kinetics. In vivo biological screening in mice and rats indicated that conjugates retained analgesic and anti-inflammatory activities with significantly reduced ulcerogenicity compared to the parent drug.

Determination of Ketorolac Tromethamine in Human Eye Samples by HPLC with Photo Diode-Array Detection

Abstract: A sensitive and selective reversed-phase HPLC method for analysis of ketorolac in aqueous and vitreous humor from the human eye has been developed and validated. Chromatographic separation was achieved on a 250 mm × 4.6 mm i.d., 5-μm particle, C18 analytical column. Photo diode-array detection was performed at 314 nm. Response was a linear function of ketorolac concentration from 10 to 800 ng mL−1. The limits of detection (LOD) and quantification (LOQ) were 3.0 and 10 ng mL−1, respectively. Intra-day and inter-day bias were less than 2.05 and 2.28%, respectively, and intra-day and inter-day RSD were no higher than 3.60 and 5.80%, respectively. Fluid obtained from patients eyes’ after topical application of Acular eye drops before retina decolman surgery was analyzed by use of the method. The method enabled successful quantification of levels of ketorolac in aqueous and vitreous humor.