Ketorolac In Treatment Research Articles

A randomized controlled trial of ketorolac for prevention of headache related to electroconvulsive therapy

Background and Purpose: Headache is one of the most common side effects of electroconvulsive therapy (ECT), with a reported prevalence as high as 45%. Typical pharmacologic measures include aspirin, acetaminophen, or nonsteroidal anti-inflammatory medications. Among the latter, ketorolac may be especially advantageous in that it can be administered intravenously right before a treatment. The primary aim of this study was to measure the efficacy of intravenous ketorolac administration for the prevention of post-ECT headache at the first treatment session. Methods: Sixteen patients were assigned to the control group, while eight patients were assigned to the ketorolac treatment group (8 males, 16 females; mean age ± standard deviation = 46 ± 13.5 years). Statistical analysis consisted of a one-way analysis of variance using the two-sample test. We utilized a post-ECT headache severity scale from zero (no headache) to 3 (severe headache). Results:The mean score for the control group was 1.3 (±1.1), while the mean score for the ketorolac treatment group was 1.2 (±1.1), p = 0.86 (not significant). Conclusions: Ketorolac administration does not decrease the incidence of post ECT headache at the first treatment session. It is possible that ketorolac may be effective at subsequent treatments for patients with particularly bothersome headaches after the first treatment. Implications: Ketorolac should not be routinely used at the first treatment session to prevent headache associated with ECT.

Abstract 910: Selective inhibition of Rac1 and Cdc42 in ovarian cancer using the R-enantiomer of ketorolac

Abstract Ovarian cancer is the 5th leading cause of cancer death for women in the United States and is frequently diagnosed at late stage with multiple secondary metastases. Ras-homologous (Rho) family GTPases contribute to metastatic dissemination through regulation of actin reorganization, cell motility, cell-cell and cell-extracellular matrix adhesion. Rho GTPases are altered in a number of human cancers and our work provides the first evidence for dysregulation of Rac1 and Cdc42 in ovarian cancer. These findings suggest that Rac1 and Cdc42 inhibitors represent potential therapeutics for ovarian cancer. Using high throughput screening we identified the R-enantiomers of ketorolac and naproxen as novel inhibitors of Rac1 and Cdc42. Although it has been noted that R-enantiomers of nonsteroidal anti-inflammatory drugs are poor inhibitors of cyclooxygenase (COX) activity, little is known about the pharmacologic activities or targets of the R-enantiomers. The objective of this study was to investigate the effects of R-ketorolac on ovarian cancer. The effects of racemic, R- and S-ketorolac were investigated using SKOV3ip ovarian cancer cells. The compounds NSC23766 and MLS0000693334 were used as positive controls for Rac1 and Cdc42 respectively. An in vitro G-LISA assay indicated R-ketorolac, and not S-ketorolac, inhibits Rac1 and Cdc42 activity. In cells, R-Ketorolac, not S-ketorolac, inhibits cell:cell adhesion and cell migration. An intra-peritoneal xenograft model of tumor implantation was used to determine the effects of drugs in vivo. Racemic ketorolac decreased the number of implanted tumors by 70%. To elucidate the mechanism of GTPase inhibition by R-ketorolac, a targeted microarray analysis was performed. Preliminary results show an alteration to the gene expression profile of human cytoskeletal regulators in response to ketorolac treatment. These effects may be due to inhibition of Rac1 and Cdc42 directly or through upstream or downstream inhibition. This analysis also provides biomarkers that can be used to analyze tumor tissues from primary patients and animal studies. Together, these findings indicate that R-ketorolac is a novel inhibitor of Rac1 and/or Cdc42, and inhibit cellular processes necessary for ovarian cancer metastasis. The mechanism behind ketorolac inhibition will require further investigation. In the future, this drug may offer benefit to ovarian cancer patients through inhibition of these GTPase targets Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 910. doi:1538-7445.AM2012-910

Activating transcription factor 4, a mediator of the integrated stress response, is increased in the dorsal root ganglia following painful facet joint distraction

Chronic neck pain is one of the most common musculoskeletal disorders in the US. Although biomechanical and clinical studies have implicated the facet joint as a primary source of neck pain, specific cellular mechanisms still remain speculative. The purpose of this study was to investigate whether a mediator (activating transcription factor; 4ATF4) of the integrated stress response (ISR) is involved in facet-mediated pain. Holtzman rats underwent C6/C7 facet joint loading that produces either painful (n=16) or nonpainful (n=8) responses. A sham group (n=9) was also included as surgical controls. Behavioral sensitivity was measured and the C6 dorsal root ganglia (DRGs) were harvested on day 7 to evaluate the total and neuronal ATF4 expression. In separate groups, an intra-articular ketorolac injection was administered either immediately (D0 ketorolac) or 1 day (D1 ketorolac) after painful facet joint loading. Allodynia was measured at days 1 and 7 after injury to assess the effects on behavioral responses. ATF4 and BiP (an indicator of ISR activation) were separately quantified at day 7. Facet joint loading sufficient to elicit behavioral hypersensitivity produced a threefold increase in total and neuronal ATF4 expression in the DRG. After ketorolac treatment at the time of injury, ATF4 expression was significantly (P<0.01) reduced despite not producing any attenuation of behavioral responses. Interestingly, ketorolac treatment at day 1 significantly (P<0.001) alleviated behavioral sensitivity at day 7, but did not modify ATF4 expression. BiP expression was unchanged after either intervention time. Results suggest that ATF4-dependent activation of the ISR does not directly contribute to persistent pain, but it may sensitize neurons responsible for pain initiation. These behavioral and immunohistochemical findings imply that facet-mediated pain may be sustained through other pathways of the ISR.

Critical appraisal of ophthalmic ketorolac in treatment of pain and inflammation following cataract surgery

Background:The purpose of this review was to provide a critical appraisal of the literature supporting the efficacy of ophthalmic ketorolac (Acuvail®) in the treatment of pain and inflammation after cataract surgery.Methods:Literature search and expert opinion of the authors.Results:Recent studies indicate greater intraocular drug levels in the anterior chamber and iris-ciliary body after topical application of Acuvail in comparison with older formulations of ketorolac. A large randomized, multicenter, placebo-controlled study demonstrated significantly less inflammation and pain after cataract surgery using Acuvail.Conclusion:Acuvail appears to be effective in reducing post-cataract surgery pain and inflammation.

Kinin B1Receptors Contributes to Acute Pain following Minor Surgery in Humans

BackgroundKinins play an important role in regulation of pain and hyperalgesia after tissue injury and inflammation by activating two types of G-protein-coupled receptors, the kinin B1 and B2 receptors. It is generally accepted that the B2 receptor is constitutively expressed, whereas the B1 receptor is induced in response to inflammation. However, little is known about the regulatory effects of kinin receptors on the onset of acute inflammation and inflammatory pain in humans. The present study investigated the changes in gene expression of kinin receptors and the levels of their endogenous ligands at an early time point following tissue injury and their relation to clinical pain, as well as the effect of COX-inhibition on their expression levels.ResultsTissue injury resulted in a significant up-regulation in the gene expression of B1 and B2 receptors at 3 hours post-surgery, the onset of acute inflammatory pain. Interestingly, the up-regulation in the gene expression of B1 and B2 receptors was positively correlated to pain intensity only after ketorolac treatment, signifying an interaction between prostaglandins and kinins in the inflammatory pain process. Further, the gene expression of both B1 and B2 receptors were correlated. Following tissue injury, B1 ligands des-Arg9-BK and des-Arg10-KD were significantly lower at the third hour compared to the first 2 hours in both the placebo and the ketorolac treatment groups but did not differ significantly between groups. Tissue injury also resulted in the down-regulation of TRPV1 gene expression at 3 hours post-surgery with no significant effect by ketorolac treatment. Interestingly, the change in gene expression of TRPV1 was correlated to the change in gene expression of B1 receptor but not B2 receptor.ConclusionsThese results provide evidence at the transcriptional level in a clinical model of tissue injury that up-regulation of kinin receptors are involved in the development of the early phase of inflammation and inflammatory pain. The up-regulation of B1 receptors may contribute to acute inflammatory pain through TRPV1 activation.

Upregulation of IL-6, IL-8 and CCL2 gene expression after acute inflammation: Correlation to clinical pain

Tissue injury initiates a cascade of inflammatory mediators and hyperalgesic substances including prostaglandins, cytokines and chemokines. Using microarray and qRT-PCR gene expression analyses, the present study evaluated changes in gene expression of a cascade of cytokines following acute inflammation and the correlation between the changes in the gene expression level and pain intensity in the oral surgery model of tissue injury and acute pain. Tissue injury resulted in a significant upregulation in the gene expression of interleukin-6 (IL-6; 63.3-fold), IL-8 (8.1-fold), chemokine (C-C motif) ligand 2 (CCL2; 8.9-fold), chemokine (C-X-C motif) ligand 1 (CXCL1; 30.5-fold), chemokine (C-X-C motif) ligand 2 (CXCL2; 26-fold) and annexin A1 (ANXA1; 12-fold). The upregulation of IL-6 gene expression was significantly correlated to the upregulation of IL-8, CCL2, CXCL1 and CXCL2 gene expression. Interestingly, the tissue injury-induced upregulation of IL-6, IL-8 and CCL2 gene expression, was positively correlated to pain intensity at 3 h post-surgery, the onset of acute inflammatory pain. However, ketorolac treatment did not have a significant effect on the gene expression of IL-6, IL-8, CCL2, CXCL2 and ANXA1 at the same time point of acute inflammation. These results demonstrate that the upregulation of IL-6, IL-8 and CCL2 gene expression contributes to the development of acute inflammation and inflammatory pain. The lack of effect of ketorolac on the expression of these gene products may be related to the ceiling analgesic effects of non-steroidal anti-inflammatory drugs.

Selective and Nonselective Cyclooxygenase-2 Inhibitors and Experimental Fracture-Healing

Background: Cyclooxygenase-2-specific anti-inflammatory drugs (coxibs) and nonspecific nonsteroidal anti-inflammatory drugs have been shown to inhibit experimental fracture-healing. The present study tested the hypothesis that these effects are reversible after short-term treatment. Methods: With use of a standard model of fracture-healing, identical ED50 dosages of either a nonsteroidal anti-inflammatory drug (ketorolac), a coxib (valdecoxib), or vehicle (control) were orally administered to rats for either seven or twenty-one days and fracture-healing was assessed with biomechanical, histological, and biochemical analyses. Results: When healing was assessed at twenty-one days, the seven-day treatment produced only a trend for a higher rate of nonunion in valdecoxib and ketorolac-treated animals as compared with controls. No differences were observed at thirty-five days. The twenty-one-day treatment produced significantly more nonunions in valdecoxib-treated animals as compared with either ketorolac-treated or control animals (p < 0.05), but these differences disappeared by thirty-five days. The dose-specific inhibition of these drugs on prostaglandin E2 levels and the reversibility of the effects after drug withdrawal were assessed in fracture calluses and showed that ketorolac treatment led to twofold to threefold lower levels of prostaglandin E2 than did valdecoxib. Withdrawal of either drug after six days led to a twofold rebound in these levels by fourteen days. Histological analysis showed delayed remodeling of calcified cartilage and reduced bone formation in association with valdecoxib treatment. Conclusions: Cyclooxygenase-2-specific drugs inhibit fracture-healing more than nonspecific nonsteroidal anti-inflammatory drugs, and the magnitude of the effect is related to the duration of treatment. However, after the discontinuation of treatment, prostaglandin E2 levels are gradually restored and the regain of strength returns to levels similar to control. Clinical Relevance: While animal studies have suggested that both nonsteroidal anti-inflammatory drugs and coxibs inhibit bone repair, there have been no clinical reports with Level-1 evidence to support these findings. Because most patients discontinue these medications when pain has subsided, it is important to determine whether the inhibitory effects are reversible. The present animal study confirms that inhibition of cyclooxygenase 2 impairs fracture-healing and that the effects are dependent on both the dose and duration of treatment. However, the reduced prostaglandin levels in callus rebound with drug withdrawal, and the impairment in the mechanical integrity of the healing fractures is reversed after short-term treatment.

Selective and Nonselective Cyclooxygenase-2 Inhibitors and Experimental Fracture-Healing

Cyclooxygenase-2-specific anti-inflammatory drugs (coxibs) and nonspecific nonsteroidal anti-inflammatory drugs have been shown to inhibit experimental fracture-healing. The present study tested the hypothesis that these effects are reversible after short-term treatment. With use of a standard model of fracture-healing, identical ED50 dosages of either a nonsteroidal anti-inflammatory drug (ketorolac), a coxib (valdecoxib), or vehicle (control) were orally administered to rats for either seven or twenty-one days and fracture-healing was assessed with biomechanical, histological, and biochemical analyses. When healing was assessed at twenty-one days, the seven-day treatment produced only a trend for a higher rate of nonunion in valdecoxib and ketorolac-treated animals as compared with controls. No differences were observed at thirty-five days. The twenty-one-day treatment produced significantly more nonunions in valdecoxib-treated animals as compared with either ketorolac-treated or control animals (p < 0.05), but these differences disappeared by thirty-five days. The dose-specific inhibition of these drugs on prostaglandin E2 levels and the reversibility of the effects after drug withdrawal were assessed in fracture calluses and showed that ketorolac treatment led to twofold to threefold lower levels of prostaglandin E2 than did valdecoxib. Withdrawal of either drug after six days led to a twofold rebound in these levels by fourteen days. Histological analysis showed delayed remodeling of calcified cartilage and reduced bone formation in association with valdecoxib treatment. Cyclooxygenase-2-specific drugs inhibit fracture-healing more than nonspecific nonsteroidal anti-inflammatory drugs, and the magnitude of the effect is related to the duration of treatment. However, after the discontinuation of treatment, prostaglandin E2 levels are gradually restored and the regain of strength returns to levels similar to control.

Ketorolac prevents recurrent withdrawal induced hyperalgesia but does not inhibit tolerance to spinal morphine in the rat

Chronic use of opioid is associated with pro-nociceptive phenomena such as hyperalgesia or tolerance. The interaction between opioid and non-steroidal anti-inflammatory drugs (NSAIDs) with respect to opioid-associated hyperalgesia and tolerance remains largely unknown. This study examines the effect of subcutaneous or intrathecal administration of ketorolac, an NSAID, on recurrent withdrawal induced hyperalgesia and tolerance to spinal morphine in rats. Animals were infused with morphine intrathecally, and daily subcutaneous naloxone was used for recurrent withdrawal purpose. We observed that escape latencies on hot box were decreased in animals subjected to withdrawal, and this decrease was reversed by subcutaneous ketorolac pretreatment. In addition, we observed that recurrent withdrawal did not significantly affect the magnitude of spinal morphine tolerance. Compared to controls, all morphine infused animals showed similar changes in their dose responses to spinal morphine, effective dose 50 values and tolerance ratios; and these changes were not affected by the ketorolac given subcutaneously. The effect of ketorolac on tolerance was further examined by directly delivering ketorolac to the spinal cord, and again we observed similar changes in the daily latency, percentage of area under the curve and percentage of maximal possible effects among groups infused with morphine, regardless of intrathecal ketorolac treatment. Together, our results demonstrate that recurrent withdrawal is associated with hyperalgesia but this has no effect on the tolerance development; ketorolac protects against recurrent withdrawal induced hyperalgesia without significantly altering spinal morphine tolerance.

Nonsteroidal Antiinflammatory Drugs Suppress Pain-Related Behaviors, but Not Referred Hyperalgesia of Visceral Pain in Mice

Visceral pain is characterized by spontaneous pain and referred hyperalgesia. After inducing visceral pain in mice using intracolonic mustard oil administration, we examined the effects of various nonsteroidal antiinflammatory drugs (NSAIDs) on pain-related behavior and on Evans blue dye extravasation. Animals were given one of the following: saline, ethanol, dimethylsulfoxide (DMSO), morphine, ketoprofen, ketorolac, or DFU (a cyclooxygenase-2 inhibitor). After drug treatment, mice underwent intracolonic administration of 50 microL 1.5% mustard oil. Spontaneous pain-related responses were assessed for the next 20 min. The frequency of withdrawal responses to the application of von Frey hairs to the abdomen, foot, and tail was determined. After completion of the behavioral tests, Evans blue was injected into the animals via the tail vein. Two hours later, the colon was removed postmortem and Evans blue content was measured. Spontaneous pain behaviors were significantly less in animals administered 3 and 10 mg/kg morphine, 50 mg/kg ketorolac, 100 mg/kg ketoprofen, and 20 mg/kg DFU (P < 0.05). Response frequencies to the application of von Frey hairs were lower in mice administered 3 and 10 mg/kg morphine (P < 0.05) but were not affected by ketorolac, ketoprofen, or DFU treatment. Colonic Evans blue content was smaller in mice given 100 mg/kg ketoprofen and 20 mg/kg DFU (P < 0.05). We concluded that NSAIDs reduced pain behavior and inflammation but had little effect on referred hyperalgesia.

Valutazione farmacoeconomica dell’uso di tramadolo vs ketorolac nella gestione del dolore postoperatorio

This article represents the first evaluation that compares the economic consequences of managing postsurgical pain with tramadol or ketorolac in the Italian setting. The economic evaluation was based on 5 clinical trials that directly compared the efficacy and tolerability of tramadol and ketorolac treatments in different settings and that contained drug consumption data. Since the review of these data confirmed that their efficacy is comparable (tramadol showed a quicker onset of the analgesic action, which was not considered for the purposes of the economic evaluation), it was chosen to conduct a cost minimization analysis. The calculations were made considering two different drug acquisition costs: the hypothetical price for the hospital, computed by discounting 50% off the retail price, and the mean price really paid by hospitals according to the IHS. The analyses showed that, when the discounted price is applied, tramadol induces costs that are similar to those induced by ketorolac in 2/3 of the cases and lower in the remaining 1/3. Considering the mean price paid by hospitals, tramadol results economically more advantageous than ketorolac in all considered settings. In conclusion, ketorolac and tramadol are two effective and tolerable drugs in the management of post-surgical pain, although they differ in the adverse event pattern and in the rapidity of their action. In the Italian setting, tramadol appears to be economically more efficient, due to lesser consumption and lower drug acquisition costs.

Inhibition of prostaglandin synthesis during polystyrene microsphere-induced pulmonary embolism in the rat.

Our objective was to test the effect of inhibition of thromboxane synthase versus inhibition of cyclooxygenase (COX)-1/2 on pulmonary gas exchange and heart function during simulated pulmonary embolism (PE) in the rat. PE was induced in rats via intrajugular injection of polystyrene microspheres (25 micro m). Rats were randomized to one of three posttreatments: 1) placebo (saline), 2) thromboxane synthase inhibition (furegrelate sodium), or 3) COX-1/2 inhibition (ketorolac tromethamine). Control rats received no PE. Compared with controls, placebo rats had increased thromboxane B(2) (TxB(2)) in bronchoalveolar lavage fluid and increased urinary dinor TxB(2). Furegrelate and ketorolac treatments reduced TxB(2) and dinor TxB(2) to control levels or lower. Both treatments significantly decreased the alveolar dead space fraction, but neither treatment altered arterial oxygenation compared with placebo. Ketorolac increased in vivo mean arterial pressure and ex vivo left ventricular pressure (LVP) and right ventricular pressure (RVP). Furegrelate improved RVP but not LVP. Experimental PE increased lung and systemic production of TxB(2). Inhibition at the COX-1/2 enzyme was equally as effective as inhibition of thromboxane synthase at reducing alveolar dead space and improving heart function after PE.

Tissue adhesive to treat 2-site corneal melting associated with topical ketorolac use

We report a case of a 78-year-old man presenting with 2 discrete areas of sterile corneal melting associated with chronic use of topical ketorolac after uneventful clear corneal phacoemulsification. He was treated successfully with tissue adhesive application. Patients receiving chronic topical ketorolac treatment, especially those with ocular surface abnormalities, can present with severe complications such as corneal melting.

A randomized, placebo controlled, trial of preoperative sustained release Betamethasone plus non-controlled intraoperative Ketorolac or Fentanyl on pain after diagnostic laparoscopy or laparoscopic tubal ligation [ISRCTN52633712

BackgroundGynecological laparoscopic surgery procedures are often complicated by postoperative pain resulting in an unpleasant experience for the patient, delayed discharge, and increased cost. Glucocorticosteroids have been suggested to reduce the severity and incidence of postoperative pain.MethodsThis study examines the efficacy of a sustained release betamethasone preparation to reduce postoperative pain and the requirement for pain relief drugs after either diagnostic laparoscopy or tubal ligation. Patients were recruited, as presenting, after obtaining informed consent. Prior to surgery, patients were randomly selected by a computer generated table to receive either pharmacy-coded betamethasone (12 mg IM Celestone™) or an optically identical placebo injection of Intralipid™ and isotonic saline mixture. The effect of non-controlled prophylactic intraoperative treatment with either fentanyl or ketorolac per surgeon's orders was also noted in this study. Blood samples taken at recovery and at discharge times were extracted and analyzed for circulating betamethasone. Visual analog scale data on pain was gathered at six post-recovery time points in a triple blind fashion and statistically compared. The postoperative requirement for pain relief drugs was also examined.ResultsAlthough the injection achieved a sustained therapeutic concentration, no beneficial effect of IM betamethasone on postoperative pain or reduction in pain relief drugs was observed during the postoperative period. Indeed, the mean combined pain scores during the 2 hour postoperative period, adjusted for postoperative opioids as the major confounding factor, were higher approaching statistical significance (P = 0.056) in the treatment group. Higher pain scores were also observed for the tubal ligation patients relative to diagnostic laparoscopy. Intraoperative fentanyl treatment did not significantly lower the average pain score during the 2 hour postoperative period. Intraoperative ketorolac treatment significantly lowered (P = 0.027) pain scores and reduced the postoperative requirement for additional pain relief drugs.ConclusionsThere was a lack of efficacy of preoperative sustained release betamethasone in reducing postoperative pain despite maintaining a therapeutic concentration during the postoperative period. Intraoperative Ketorolac did afford some short-term pain relief in the postoperative period and reduced the need for additional pain relief drugs.

Efficacy of Nasal Sumatriptan vs Intravenous Ketorolac in Treatment of Acute Migraine

Efficacy of Nasal Sumatriptan vs Intravenous Ketorolac in Treatment of Acute Migraine

Minimising the adverse effects of ketorolac.

Gastrointestinal bleeding and perforation, platelet inhibition with altered haemostasis, and renal impairment are among the list of adverse effects associated with the administration of ketorolac. The incidence of serious adverse events has declined since dosage guidelines were revised. Most of the published literature suggests that the overall risk of gastrointestinal or operative site bleeding related to ketorolac therapy is only slightly higher than with opioids. The risk for adverse events, however, increases with high doses, with prolonged therapy (>5 days) or in vulnerable patients (e.g. the elderly). Acute renal failure has been reported after ketorolac treatment but is usually reversible after discontinuation of the drug. As with other nonsteroidal anti-inflammatory drugs (NSAIDs), ketorolac may trigger allergic or hypersensitivity reactions. Careful patient selection is essential if use of ketorolac is considered. Contraindications to ketorolac use include a history of, or current risk of, gastrointestinal bleeding, risk of renal failure, compromised haemostasis, hypersensitivity to aspirin (acetylsalicylic acid) or other NSAIDs, labour, delivery and nursing. Ketorolac should be prescribed at the lowest dosage necessary to control pain; the duration of therapy should also be limited to as few days as possible. Practitioners should be familiar with, and follow, label warnings and dosage guidelines.

Ketorolac treatment of pseudophakic cystoid macular edema identified more than 24 months after cataract extraction

Objective To evaluate whether ketorolac ophthalmic drops prescribed four times a day can be associated with improved visual acuity and prompt resolution of edema for patients with pseudophakic cystoid macular edema identified more than 24 months after cataract surgery. Design Prospective, nonrandomized, comparative (subject self-controlled) trial. Participants The records of nine patients who had pseudophakic cystoid macular edema more than 24 months after cataract surgery at the time treatment commenced were identified at the Wilmer Retinal Vascular Center from September 1, 1996, through March 1, 1997. Main outcome measures Best-corrected visual acuities measured on a retroilluminated Bailey-Lovie chart approximately every 3 months, contact lens biomicroscopy, and fluorescein angiography following ketorolac. Intervention Commercially available ketorolac ophthalmic drops 0.5% were prescribed for the affected eye four times a day for at least 3 months and continued until edema resolved. Results Ten eyes of nine patients were identified more than 24 months after cataract extraction (median, 59 months). Seven eyes (70%) improved (mean, +3.2 lines; range, +1 to +13 lines), including six by 2 or more lines 3 months after treatment initiation. Two eyes (20%) were unchanged, and one eye (10%) was 1 line worse. All seven eyes that improved 1 line or more had some or complete angiographic resolution of fluorescein dye leakage. In these seven eyes, ketorolac was discontinued when dye leakage completely resolved or failed to continue to improve on periodic 3-month follow-up examinations. In all seven eyes, recurrence of edema was noted within 3 months after ketorolac was stopped. Conclusions Chronic pseudophakic cystoid macular edema identified more than 24 months after cataract surgery can improve with topical ketorolac but probably requires persistent use.

Immunomodulation with interleukin-10 and interleukin-4 compared with ketorolac tromethamine for prevention of postoperative adhesions in a murine model

Objective: To assess the effects of two macrophage down-regulating cytokines (interleukin [IL]-10 and IL-4) and the nonsteroidal anti-inflammatory drug ketorolac tromethamine on postoperative adhesion formation. Design: Randomized controlled trial. Setting: Research center vivarium. Animal(s): Six-week-old Swiss Webster mice. Intervention(s): One hundred eighty animals were randomized to serve as nonsurgical controls or to undergo a standardized adhesion-inducing procedure. Subsequently, animals were randomized to nine different treatment groups to receive no injections, phosphate-buffered saline (PBS) only, IL-10, IL-4, ketorolac, IL-10 plus IL-4, IL-10 plus ketorolac, IL-4 plus ketorolac, or all three agents. Main Outcome Measure: Adhesion scores on postoperative day 10. Result(s): Postoperative adhesion scores were significantly reduced in all groups of animals treated with IL-10 or ketorolac. Animals treated with IL-4 showed a nonsignificant trend toward reduction of adhesions. There were significantly more animals with adhesion scores of ≤3 in the IL-10 and ketorolac treatment groups than in the control groups receiving no treatment or PBS only. Conclusion(s): Although treatment with IL-10 and ketorolac did not completely prevent adhesion formation, treatment with these drugs did lead to a significant reduction in adhesion formation. Adhesions also tended to be thin and filmy rather than thick and vascular. Addition of IL-4 did not augment these effects.

The effects of chronic ketorolac tromethamine (toradol) on wound healing.

Intramuscular ketorolac is a commonly used nonsteroidal anti-inflammatory (NSAI) agent for analgesia in surgical patients. Increasing numbers of surgical patients are chronically taking some form of an NSAI drug. We examined the effects of "chronic" intramuscular ketorolac on the healing of a closed linear surgical wound in the rat. Wistar rats were pretreated with 4 mg per kilogram per day ketorolac intramuscularly prior to receiving dorsal incisional wounds. The ketorolac treatment was continued and after 2 weeks the wounds were excised and separated with a tensiometer to measure mechanical properties. Breaking strength was directly measured, tensile strength was calculated, and collagen concentrations at the wound site were determined. A significant decrease in the mean breaking strength was seen in the ketorolac-treated animals when compared to controls. The ketorolac-treated animals had a mean tensile strength less than the controls, although this difference did not reach statistical significance. The mean collagen concentration of the ketorolac-treated wounds was significantly less than the untreated wounds. Use of ketorolac for just 1 week prior to surgery in rats produced a significant decrease in the breaking strength of their wounds. With the increasing use of ketorolac in surgical patients as well as the increasing use of oral NSAI drugs, more study of this effect is warranted.

The effect of ketorolac on recovery after outpatient gynecologic laparoscopy

Opioids, although effective postoperative analgesics, are associated with undesirable side effects. To determine whether nonopioid medication would reduce the amount required for postoperative analgesia, the efficacy of ketorolac, an injectable nonsteroidal anti-inflammatory drug, was studied in ambulatory patients undergoing gynecologic laparoscopy. Patients were randomized to a treatment group (n = 49) or control group (n = 50), then studied using a prospective double-masked design. Intraoperatively, the ketorolac treatment group received a 60-mg intramuscular injection of ketorolac; the control group received an injection of placebo (0.9% sodium chloride). Anesthetic management, postoperative pain, and the management of nausea were standardized in the two groups. Postoperative pain was treated with incremental doses of fentanyl 25 μg intravenously. Nausea and vomiting were treated with droperidol or prochlorperazine. Pain and nausea assessments were done every 30 minutes in the post-anesthesia care unit (PACU), at discharge, and at 24 hours after discharge. Postoperatively, for the first hour in the PACU, visual analog scale pain scores, as well as verbal pain scores, were statistically significantly lower in the ketorolac treatment group. Similarly, the severity of pain was twofold less in the ketorolac treatment group than in the control group. Less fentanyl was required in the ketorolac group (26 ± 20 μg, mean ± SD) compared with the control group (56 ± 32 μg, mean ± SD). However, there were no significant differences between the two groups with respect to postoperative sedation or nausea, although the incidence of vomiting requiring treatment was higher in the control group. There was high overall satisfaction of patients in both groups. In conclusion, intraoperative administration of ketorolac resulted in fewer patients awakening in pain and in a decreased need for opioid analgesic in the postoperative period. Ketorolac is an effective alternative to opioids for the control of postoperative pain in patients undergoing gynecologic laparoscopy.