Preparation of polycaprolactone and polymethacrylate nanofibers for controlled ocular delivery of ketorolac tromethamine: Pharmacokinetic study in Rabbit's Eye.

Ophthalmitis is an inflammation of the eye triggered by various conditions including diseases, allergy, trauma, or surgery. Management of this condition usually includes administration of topical anti-inflammatory eye drops such as nonsteroidal anti-inflammatory drugs. To overcome the challenges of conventional eye drops such as frequent administration and low intraocular bioavailability, nanofibrous inserts of Ketorolac tromethamine (KET) were developed in this study. Polycaprolactone and polymethacrylate containing KET were electrospun to prepare biocompatible and biodegradable nanofibers. The inserts were studied for morphology, drug-polymer interaction, physicochemical properties, cell viability, in vitro drug release study and pharmacokinetic study in rabbit's eye. Uniform nanofibers with mean diameters < 350 nm were developed. Suitable mechanical properties with tensile strength up to 2.8 MPa indicated high strength and flexibility of inserts. Nanofibers exhibited controlled drug release for up to 140 h at a concentration more than 50 µg/ml in tears without causing any damage or irritation to the eye. Formulations indicated enhanced pharmacokinetics with 6- to 8-times higher Area Under the Curve (AUC0-144) compared to KET eye drop. Acceptable cell viability confirmed the safety of inserts. Due to the fact that this preservative-free polymer insert can obtain therapeutic concentration in the tear film without fluctuation, it can be a suitable alternative for the treatment of intraocular inflammations with less complications, easier use, and even higher intraocular penetration.

The effect of topical ketorolac tromethamine on macular thickening after phacoemulsification in diabetic patients.

BACKGROUND: To determine the effect of ketorolac tromethamine 0.5% in preventing post-phacoemulsification macular thickening. This randomized clinical trial. patients randomized 1:1 to receive either topical ketorolac three times a day or a placebo. METHODS: A total of 101 eyes of 101 diabetic patients who were scheduled for phacoemulsification and had normal macular contour and thickness enrolled consecutively. The topical ketorolac and placebo were prescribed on the day before surgery and continued up to 4 weeks after surgery. Patients with proliferative diabetic retinopathy, a history of intravitreal injection in less than three months, a history of macular photocoagulation in less than 6 months, and any other concomitant ocular pathologies were excluded. Central macular thickness (CMT) and best corrected visual acuity (BCVA) was recorded in the follow-ups of 6, 12, and 24 weeks after the surgery and compared with the controls. RESULTS: 49 eyes in the case group and 52 eyes in the control group were analyzed. Mean BCVA was significantly improved in both groups at all follow-ups (P < 0.001 for all). There was no statistically significant difference regarding the BCVA in different time points except week 12 (P = 0.028) among the study group. In the case and control groups, CMT was increased at all follow-ups (P < 0.05). There was no statistically significant difference when comparing the two groups regarding the mean of CMT at any time point postoperatively (P > 0.05 for all). CONCLUSION: Based on our findings, topical ketorolac tromethamine 0.5% is not effective in the prevention of post-phacoemulsification macular thickening in diabetic patients. TRAIL REGISTRATION: The study protocol was registered into www. CLINICALTRIAL: gov with the RCT registration number NCT03551808. (2018/06/11 ) CLINICAL TRIAL REGISTRATION NUMBER: NCT03551808.

Platelet lysate and tendon healing: comparative analysis of autologous frozen-thawed PRP and ketorolac tromethamine in the treatment of patients with rotator cuff tendinopathy.

Platelet-rich blood derivatives are being nowadays increasingly used in the treatment of tendon-related pathologies as a rich source of growth factors. We sought to ascertain if local application of platelet lysate (PL) to augment rotator cuff repair ameliorates patient outcomes compared to ketorolac tromethamine treated group. A total of forty patients, with clinical diagnosis of Rotator Cuff Tendinopathy were randomized to receive sub acromial injections of PL every week for a total of 3 injections and two injection of ketorolac tromethamine once every two weeks. Subjective assessments included VAS, SPADI and shoulder range of motion were assessed at baseline and at 1 and 6 months after injection. Taking both control and PL groups, it was vividly seen that the outcomes were identical at the initial state, as well as the short-term one; whereas, when considering the 6-month period, there is a seemingly remarkable superiority in PL group in all parameters.

Effect of ketorolac tromethamine combined with dezocine prior administration on hemodynamics and postoperative analgesia in patients undergoing laparoscopic hernia repair.

OBJECTIVE: To observe the effect of Ketorolac tromethamine combined with dezocine prior administration on hemodynamics and postoperative sedation in patients undergoing laparoscopic hernia repair. METHODS: 100 male patients aged 60 to 80 years old, a line to elective laparoscopic inguinal hernia repair, were randomly divided into four groups: control group (Group A) and dezocine group (Group B), ketorolac tromethamine group (Group C), ketorolac tromethamine combined with dezocine group (Group D). Patients were administrated with 0.1 mg/kg dezocine in Group B, 0.5 mg/kg ketorolac in Group C, 0.1 mg/kg dezocine, and 0.5 mg/kg ketorolac in Group D, and with an equal dose of normal saline in group A. The heart rate (HR) and mean arterial pressure (MAP) of patients in 4 groups were recorded at each time point as follows, T0 (enter the operating room), T1 (before skin resection), 10 min after pneumoperitoneum (T2), mesh placement (T3), and laryngeal mask extraction (T4). Operation time, awakening time (time from drug withdrawal to consciousness recovery), the dosage of propofol, sufentanil, remifentanil, and intraoperative vasoactive drug dosage were recorded to compare. Visual analog scale score and sedation Ramsay score were evaluated 1, 6, 12, and 24 hours after extubation. RESULTS: There was no significant difference in operation time, anesthesia recovery time, sufentanil dosage, and vasoactive drugs among all groups. The amount of propofol in Group B and D was less than that in Group A and C (P < .05), and there was no difference between Group B and D, A and C (P > .05). The amount of remifentanil in Group B, C, and D was less than that in Group A (P < .05), and Group D was less than B and C (P < .05). After extubation, HR and MAP were significantly higher than before (P < .05). Compared with T0, HR and MAP increased in each group at T4, but MAP and HR in Group D increased the least (P < .05). There were significant differences between Group B, C, D, and A, MAP and HR fluctuated little during extubation (P < .05), but there was a significant difference between Group D and B, C (P < .05). Visual analog scale scores of Group B, C, and D were lower than those of A at 1, 6, and 12 hours after surgery (P < .05), and there was a significant difference between Group D, and B, C (P < .05). Ramsay scores in Group B and D were higher than those in A and C at 1 and 6 hours after the operation (P < .05). There was no difference in the incidence of adverse reactions among groups. CONCLUSION: The prophylactic use of ketorolac tromethamine and dezocine before laparoscopic inguinal hernia repair can reduce hemodynamic disorder during anesthesia recovery, increase postoperative sedative and analgesic effects.

Toradol to Reduce Ureteroscopy Symptoms Trial (TRUST).

OBJECTIVE: To assess the use of intraoperative IV ketorolac (Toradol) on the peri-operative total morphine milligram equivalent (MME) requirements of patients undergoing ureteroscopy for nephrolithiasis. METHODS: Patients undergoing ambulatory ureteroscopy for nephrolithiasis were randomized to receive ketorolac at time of anesthesia induction. Patients and surgeons were blinded to treatment. Intraoperative, postoperative and combined MME were calculated. Multivariable regression was used to identify independent predictors of MME requirement. Complications were recorded. RESULTS: A total of 94 patients were analyzed following randomization. There were 46 patients in the treatment arm and 48 patients in the control arm. There were no statistically significant differences in gender, age, BMI, operative length or baseline pain medication use between groups (P >.05). Patients in the treatment arm required lower intraoperative MME when compared to the control arm (17.1 vs 24, P< .01). There were no statistically significant differences in the postoperative MME requirements between groups. The combined peri-operative MME was lower in the treatment arm compared to the control arm (22.2 vs 30.4, P< .02). Ketorolac use was an independent predictor of lower MME use on multivariable analysis (beta coefficient -5.1, P< .01). There was no statistically significant difference with regards to complication numbers between the treatment arms. CONCLUSION: Ketorolac during ureteroscopy is associated with a 37% reduction in narcotic requirement and is an independent predictor of decreased peri-operative narcotic needs. These findings show that intra-operative use of ketorolac effectively reduces narcotic requirements and should be considered independently or as part of a multimodal pain control protocol, unless otherwise contraindicated.

Intravenous Ketorolac Infusion for Intractable Pleuritic Pain Secondary to Metastatic Epithelioid Hemangioendothelioma.

Background: Epithelioid hemangioendothelioma (EHE) patients can experience severe pain. Nonsteroidal anti-inflammatory drugs, including ketorolac tromethamine, can effectively treat cancer-related pain, provide an opioid-sparing effect, and may be particularly effective for EHE pain. There are limited data describing prolonged (>5 days) continuous intravenous (IV) ketorolac infusion for cancer-related pain and no data on its use in EHE. Case Description: A 67-year-old woman with metastatic hepatic EHE suffered from chronic intractable pleuritic pain unresponsive to trials of nonopioid, opioid, adjuvant medications, and nonpharmacological interventions. In the hospital, continuous IV ketorolac infusion at 3.8 mg/hour (91.2 mg/day) effectively managed pain. With thorough monitoring, the patient was discharged on continuous IV ketorolac infusion at 3 mg/hour (72 mg/day). Infusion continued for 79 days without clinical or laboratory evidence of ketorolac toxicity. Conclusion: Ketorolac tromethamine as a long-term infusion is a potentially viable analgesic for patients with intractable EHE-related pain unresponsive to standard therapies.

Pre-Emptive Topical Ketorolac Tromethamine 0.5% for Panretinal Photocoagulation.

Purpose: To evaluate the efficacy of topical ketorolac tromethamine 0.5% given pre-emptively a day before, for alleviating pain in patients undergoing panretinal photocoagulation (PRP) treatment. Methods: A controlled single-blinded study was conducted on 33 patients with diabetic retinopathy (DR; severe nonproliferative DR, proliferative DR, or advanced diabetic eye disease) who required PRP treatment in both eyes simultaneously. Each eye of the patients was randomly assigned for ketorolac tromethamine 0.5% eyedrop or placebo. Both eyedrop bottles were randomly labeled. Eyedrops were self-administered by the patients, 4 times a day before the procedure (at 6 am, 12 noon, 6 pm, and 12 midnight) and every 15 min for 1 h (4 times) before the laser. Each patient was subjected to PRP using a Visulas 532s Zeiss device set to spot size 200 µm, time 0.10 s, and ∼600 burns in each eye. The pain score was evaluated immediately after treatment in each eye independently with Scott's visual analog scale (VAS) and the McGill Pain Questionnaire (MPQ). Results: VAS pain score in ketorolac-treated eyes (median 3.0, interquatile range [IQR] ±2.5) was lower than in placebo-treated eyes (median 5.0, IQR ±3.0). Total Pain Rate Index score from MPQ was lower in ketorolac-treated eyes (median 3.0, IQR ±3.0) than in placebo-treated eyes (median 3.0, IQR ±2.5). Both pain score differences are statistically significant with P ˂ 0.05. Conclusion: Topical ketorolac tromethamine 0.5% given pre-emptively a day before is effective in alleviating pain in patients undergoing PRP treatment.

Comparison of intravenous ketorolac at three doses for treating renal colic in the emergency department: A noninferiority randomized controlled trial.

BACKGROUND: Ketorolac tromethamine is a nonsteroidal anti-inflammatory drug (NSAID) that is extensively used for the management of renal colic in the emergency department (ED). It has been proposed that ketorolac is used at doses above its analgesic ceiling with no more advantages and increased risk of adverse effects. In this study, we compared the analgesic effects of three doses of intravenous ketorolac in patients with renal colic. METHODS: This noninferiority, randomized, double-blind clinical trial evaluated the analgesic efficacy of three doses of intravenous ketorolac (10, 20, and 30 mg) in adult patients presenting to the ED with renal colic. Exclusion criteria consisted of age > 65 years, active peptic ulcer disease, acute gastrointestinal hemorrhage, renal or hepatic insufficiency, NSAID hypersensitivity, pregnancy or breastfeeding, unstable vital signs, and patients who had received analgesics in the past 24 hours. Pain was recorded every 15 minutes from baseline up to 60 minutes, and the primary outcome was pain reduction at 30 minutes. If patients still required additional pain medications at 30 minutes, they would receive 0.1 mg/kg intravenous morphine sulfate as a rescue analgesic. RESULTS: A total of 165 subjects enrolled in this study, 55 in each group. The median visual analog scale score in 30 minutes was improved from 90 at baseline to 40 among subjects who were randomized to 30-mg group. This improvement was 40 and 50 mm in 20- and 10-mg ketorolac treatment arms, respectively, with no significant difference between the three doses (p < 0.05). Secondary outcomes showed similar rescue analgesic administration and adverse effects. There was no serious adverse event. CONCLUSION: Ketorolac at 10-, 20-, and 30-mg doses can produce similar analgesic efficacy in renal colic.

DDX3 modulates cisplatin resistance in OSCC through ALKBH5-mediated m6A-demethylation of FOXM1 and NANOG.

Platinum based drugs alone or in combination with 5FU and docetaxel are common regimen chemotherapeutics for the treatment of advanced OSCC. Chemoresistance is one of the major factors of treatment failure in OSCC. Human RNA helicase DDX3 plays an important role in cell proliferation, invasion, and metastasis in several neoplasms. The potential role of DDX3 in chemoresistance is yet to be explored. Enhanced cancer stem cells (CSCs) population significantly contributes to chemoresistance and recurrence. A recent study showed that m6A RNA regulates self-renewal and tumorigenesis property in cancer. In this study we found genetic (shRNA) or pharmacological (ketorolac salt) inhibition of DDX3 reduced CSC population by suppressing the expression of FOXM1 and NANOG. We also found that m6A demethylase ALKBH5 is directly regulated by DDX3 which leads to decreased m6A methylation in FOXM1 and NANOG nascent transcript that contribute to chemoresistance. Here, we found DDX3 expression was upregulated in both cisplatin-resistant OSCC lines and chemoresistant tumors when compared with their respective sensitive counterparts. In a patient-derived cell xenograft model of chemoresistant OSCC, ketorolac salt restores cisplatin-mediated cell death and facilitates a significant reduction of tumor burdens. Our work uncovers a critical function of DDX3 and provides a new role in m6 demethylation of RNA. A combination regimen of ketorolac salt with cisplatin deserves further clinical investigation in advanced OSCC.

Multimodal opioid-sparing postoperative pain regimen compared with the standard postoperative pain regimen in vaginal pelvic reconstructive surgery: a multicenter randomized controlled trial.

BACKGROUND: Postoperative pain control after urogynecological surgery has traditionally been opioid centered with frequent narcotic administration. Few studies have addressed optimal pain control strategies for vaginal pelvic reconstructive surgery that limit opioid use. OBJECTIVE: The objective of the study was to determine whether, ice packs, Tylenol, and Toradol, a novel opioid-sparing multimodal postoperative pain regimen has improved pain control compared with the standard postoperative pain regimen in patients undergoing inpatient vaginal pelvic reconstructive surgery. STUDY DESIGN: This was a multicenter randomized controlled trial of women undergoing vaginal pelvic reconstructive surgery. Patients were randomized to the ice packs, Tylenol, and Toradol postoperative pain regimen or the standard regimen. The ice packs, Tylenol, and Toradol regimen consists of around-the-clock ice packs, around-the-clock oral acetaminophen, around-the-clock intravenous ketorolac, and intravenous hydromorphone for breakthrough pain. The standard regimen consists of as-needed ibuprofen, as-needed acetaminophen/oxycodone, and intravenous hydromorphone for breakthrough pain. The primary outcome was postoperative day 1 pain evaluated the morning after surgery using a visual analog scale. Secondary outcomes included the validated Quality of Recovery Questionnaire, satisfaction scores, inpatient narcotic consumption, outpatient pain medication consumption, and visual analog scale scores at other time intervals. In all, 27 patients in each arm were required to detect a mean difference of 25 mm on a 100 mm visual analog scale (90% power). RESULTS: Thirty patients were randomized to ice packs, Tylenol, and Toradol and 33 to the standard therapy. Patient and surgical demographics were similar. The median morning visual analog scale pain score was lower in the ice packs, Tylenol, and Toradol group (20 mm vs 40 mm, P = .03). Numerical median pain scores were lower at the 96 hour phone call in the ice packs, Tylenol, and Toradol group (2 vs 3, P = .04). Patients randomized to the ICE-T regimen received fewer narcotics (expressed in oral morphine equivalents) from the postanesthesia care unit exit to discharge (2.9 vs 20.4, P < .001) and received fewer narcotics during the entire hospitalization (55.7 vs 91.2, P < .001). At 96 hour follow up, patients in the ice packs, Tylenol, and Toradol group used 4.9 ketorolac tablets compared with 4.6 oxycodone/acetaminophen tablets in the standard group (P = .81); however, ice packs, Tylenol, and Toradol patients required more acetaminophen than ibuprofen by patients in the standard arm (10.7 vs 6.2 tablets, P = .012). There were no differences in Quality of Recovery Questionnaire or satisfaction scores either in the morning after surgery or at 96 hour follow up. CONCLUSION: The ice packs, Tylenol, and Toradol multimodal pain regimen offers improved pain control the morning after surgery and 96 hours postoperatively compared with the standard regimen with no differences in patient satisfaction and quality of recovery. Ice packs, Tylenol, and Toradol can significantly limit postoperative inpatient narcotic use and eliminate outpatient narcotic use in patients undergoing vaginal pelvic reconstructive surgery.

Current and emerging pharmaceutical interventions for myopia.

Myopia is a major cause of visual impairment. Its prevalence is growing steadily, especially in East Asia. Despite the immense disease and economic burden, there are currently no Food and Drug Administration-approved drugs for myopia. This review aims to summarise pharmaceutical interventions of myopia at clinical and preclinical stages in the last decade and discuss challenges for preclinical myopia drugs to progress to clinical trials. Atropine and oral 7-methylxanthine are shown to reduce myopia progression in human studies. The former has been extensively studied and is arguably the most successful medication. However, it has side effects and trials on low-dose atropine are ongoing. Other pharmaceutical agents being investigated at a clinical trial level include ketorolac tromethamine, oral riboflavin and BHVI2 (an experimental drug). Since the pathophysiology of myopia is not fully elucidated, numerous drugs have been tested at the preclinical stage and can be broadly categorised based on the proposed mechanisms of myopisation, namely antimuscarinic, dopaminergic, anti-inflammatory and more. However, several agents were injected intravitreally or subconjunctivally, hindering their progress to human trials. Furthermore, with atropine being the most successful medication available, future preclinical interventions should be studied in combination with atropine to optimise the treatment of myopia.

Natamycin niosomes as a promising ocular nanosized delivery system with ketorolac tromethamine for dual effects for treatment of candida rabbit keratitis; in vitro/in vivo and histopathological studies.

OBJECTIVES: This study was aimed to develop dual-purpose natamycin (NAT)-loaded niosomes in ketorolac tromethamine (KT) gels topical ocular drug delivery system to improve the clinical efficacy of natamycin through enhancing its penetration through corneal tissue and reducing inflammation associated with Fungal keratitis (FK). SIGNIFICANCE: Nanosized carrier systems, as niosomes would provide great potential for improving NAT ocular bioavailability.NAT niosomal dispersion formulae were prepared and then incorporated in 0.5%KT gels using different mucoadhesive viscosifying polymers. METHODS: Niosomes were prepared using the reverse-phase evaporation technique. In vitro experimental, and in vivo clinical evaluations for these formulations were done for assessment of their safety and efficacy for treatment of Candida Keratitis in Rabbits. In vitro release study was carried out by the dialysis method. In vivo and histopathological studies were performed on albino rabbits. RESULTS: NAT niosomes exhibited high entrapment efficiency percentage (E.E%) up to96.43% and particle size diameter ranging from 181.75 ± 0.64 to 498.95 ± 0.64 nm, with negatively charged zeta potential (ZP). NAT niosomal dispersion exhibited prolonged in vitro drug release (40.96-77.49% over 24h). NAT-loaded niosomes/0.5%KT gel formulae revealed retardation in vitro release, compared to marketed-product (NATACYN®) and NAT-loaded niosomes up to57.32% (F8). In vivo experimental studies showed the superiority for F8 in treatment of candida keratitis and better results on corneal infiltration and hypopyon level. These results were consistent with histopathological examination in comparison with F5 and combined marketed products (NATACYN® and Ketoroline®). CONCLUSIONS: This study showed that F8 has the best results from all pharmaceutical in vitro evaluations and a better cure percent in experimental application and enhancing the prolonged delivery of NAT and penetrating the cornea tissues.

The Determination and Clinical Significance of Prostaglandin E2 in Blood and Urine of Patients with Renal Colic.

BACKGROUND: This study explores the role of prostaglandin E2 (PGE2) in the etiology of urolithiasis in acute renal colic by analyzing the PGE2 levels in blood and urine throughout the clinical course of renal colic. METHODS: From June 2015 to November 2017, a total of 60 patients with acute renal colic were enrolled in the study. Blood and urine samples were taken before and after administration of drug to inhibit prostaglandin synthesis; further blood and urine samples were obtained from the patients 2 weeks after their recovery. The concentration of PGE2 in blood and urine samples was determined by using a Human Prostaglandin E2 ELISA Kit. RESULTS: The mean concentration of PGE2 was 420 ± 50.3 ng/L in blood and 600 ± 70.1 ng/L in urine when the patients had renal colic. After drug therapy, these concentrations fell to 300 ± 40.4 ng/L in blood and 500 ± 54.5 ng/L in urine. After 2 weeks the PGE2 concentration was 220 ± 47.5 ng/L and 300 ± 50.2 ng/L in blood and urine, respectively. Compared with PGE2 levels after medication, these concentrations were significantly higher during acute renal colic (p < 0.05). CONCLUSIONS: The synthesis and release of PGE2 increase at the onset of renal colic, suggesting that PGE2 plays an important role in acute renal colic. Administration of a prostaglandin synthesis inhibitor is a reliable way to treat renal colic.

Evolving Treatment Patterns of NFL Players by Orthopaedic Team Physicians Over the Past Decade, 2008-2016.

BACKGROUND: Previous studies have analyzed the treatment patterns used to manage injuries in National Football League (NFL) players. HYPOTHESIS: Treatment patterns for injuries in NFL players will have changed over the study period. STUDY DESIGN: Descriptive epidemiology study. LEVEL OF EVIDENCE: Level 5. METHODS: The head orthopaedic team physicians for all 32 NFL teams were asked to complete a survey containing questions regarding experience as team physician, medical coverage of the team, and treatment preferences for some of the most common injuries occurring in football players. Responses from the current survey were compared with responses from the same survey sent to NFL team physicians in 2008. RESULTS: Responses were received from 31 (31/32, 97%) NFL team physicians in 2008 and 29 (29/32, 91%) NFL team physicians between April 2016 and May 2017. The proportion of physicians preferring patellar tendon autograft in anterior cruciate ligament (ACL) reconstruction increased from 87% in 2008 to 97% in 2016 ( P = 0.054). In 2008, 49% of physicians allowed return to contact after ACL reconstruction at 6 months or less as compared with only 14% of physicians in 2016 ( P = 0.033). In 2008, 93% of physicians used Toradol injections prior to a game to help with nagging injuries. Toradol injection utilization decreased to 48% of physicians in 2016 ( P < 0.001). Seventy-nine percent of physicians would administer 5 or more Toradol injections prior to a game in 2008, as compared with 28% of physicians in 2016 ( P < 0.0001). CONCLUSION: Orthopaedic physicians have changed their injury treatment preferences for professional football players. In particular, physicians have become more cautious with allowing players to return to play after ACL reconstruction and with the use of pregame Toradol injections. CLINICAL RELEVANCE: Expert opinions can help guide treatment decisions and lead to better care of all athletes.

Cost-effectiveness of intravenous acetaminophen and ketorolac in adolescents undergoing idiopathic scoliosis surgery.

BACKGROUND: Enhanced recovery after surgery protocols increasingly use multimodal analgesia after major surgeries with intravenous acetaminophen and ketorolac, despite no documented cost-effectiveness of these strategies. AIMS: The goal of this prospective cohort study was to model cost-effectiveness of adding acetaminophen or acetaminophen + ketorolac to opioids for postoperative outcomes in children having scoliosis surgery. METHODS: Of 106 postsurgical children, 36 received only opioids, 26 received intravenous acetaminophen, and 44 received acetaminophen + ketorolac as analgesia adjuncts. Costs were calculated in 2015 US $. Decision analytic model was constructed with Decision Maker® software. Base-case and sensitivity analyses were performed with effectiveness defined as avoidance of opioid adverse effects. RESULTS: The groups were comparable demographically. Compared with opioids-only strategy, subjects in the intravenous acetaminophen + ketorolac strategy consumed less opioids (P = .002; difference in mean morphine consumption on postoperative days 1 and 2 was -0.44 mg/kg (95% CI -0.72 to -0.16); tolerated meals earlier (P < .001; RR 0.250 (0.112-0.556)) and had less constipation (P < .001; RR 0.226 (0.094-0.546)). Base-case analysis showed that of the 3 strategies, use of opioids alone is both most costly and least effective, opioids + intravenous acetaminophen is intermediate in both cost and effectiveness; and opioids + intravenous acetaminophen and ketorolac is the least expensive and most effective strategy. The addition of intravenous acetaminophen with or without ketorolac to an opioid-only strategy saves $510-$947 per patient undergoing spine surgery and decreases opioid side effects. CONCLUSION: Intravenous acetaminophen with or without ketorolac reduced opioid consumption, opioid-related adverse effects, length of stay, and thereby cost of care following idiopathic scoliosis in adolescents compared with opioids-alone postoperative analgesia strategy.

The Evolving Treatment Patterns of NCAA Division I Football Players by Orthopaedic Team Physicians Over the Past Decade, 2008-2016.

BACKGROUND: Previous studies have analyzed the treatment patterns used to manage injuries in National Collegiate Athletic Association (NCAA) Division I football players. HYPOTHESIS: Treatment patterns used to manage injuries in NCAA Division I football players will have changed over the study period. STUDY DESIGN: Descriptive epidemiology study. LEVEL OF EVIDENCE: Level 5. METHODS: The head orthopaedic team physicians for all 128 NCAA Division I football teams were asked to complete a survey containing questions regarding experience as team physician, medical coverage of the team, reimbursement issues, and treatment preferences for some of the most common injuries occurring in football players. Responses from the current survey were compared with responses from the same survey sent to NCAA Division I team physicians in 2008. RESULTS: Responses were received from 111 (111/119, 93%) NCAA Division I orthopaedic team physicians in 2008 and 115 (115/128, 90%) orthopaedic team physicians between April 2016 and April 2017. The proportion of team physicians who prefer a patellar tendon autograft for primary anterior cruciate ligament reconstruction (ACLR) increased from 67% in 2008 to 83% in 2016 ( P < 0.001). The proportion of team physicians who perform anterior shoulder stabilization arthroscopically increased from 69% in 2008 to 93% in 2016 ( P < 0.0001). Of team physicians who perform surgery for grade III posterior cruciate ligament (PCL) injuries, the proportion who use the arthroscopic single-bundle technique increased from 49% in 2008 to 83% in 2016 ( P < 0.0001). The proportion of team physicians who use Toradol injections prior to a game to help with nagging injuries decreased from 62% in 2008 to 26% in 2016 ( P < 0.0001). CONCLUSION: Orthopaedic physicians changed their injury treatment preferences for NCAA Division I football players over the study period. In particular, physicians have changed their preferred techniques for ACLR, anterior shoulder stabilization, and PCL reconstruction. Physicians have also become more conservative with pregame Toradol injections. CLINICAL RELEVANCE: These opinions may help guide treatment decisions and lead to better care of all athletes.

The R-Enantiomer of Ketorolac Delays Mammary Tumor Development in Mouse Mammary Tumor Virus-Polyoma Middle T Antigen (MMTV-PyMT) Mice.

Epidemiologic studies report improved breast cancer survival in women who receive ketorolac (Toradol) for postoperative pain relief compared with other analgesic agents. Ketorolac is a racemic drug. The S-enantiomer inhibits cyclooxygenases; R-ketorolac is a selective inhibitor of the small GTPases Ras-related C3 botulinum toxin substrate 1 (Rac1) and cell division control protein 42 (Cdc42), which are signaling molecules up-regulated during breast cancer progression and metastasis. The goal of this study was to determine whether R-ketorolac altered breast cancer development in the mouse mammary tumor virus-polyoma middle T-antigen model. Mice were administered ketorolac orally at 1 mg/kg twice daily to approximate the typical human dose. Mammary glands were analyzed for tumor number and immunohistochemical markers of proliferation and differentiation. R-ketorolac treatment significantly reduced mammary epithelial proliferation, based on Ki67 staining, and suppressed tumor development. Proliferative mammary epithelium from R-ketorolac-treated mice displayed greater differentiation, based on significantly higher total E-cadherin and decreased keratin 5 staining than epithelium of placebo-treated mice. No differences were detected in estrogen receptor, progesterone receptor, ß-catenin, or vimentin expression between placebo and R-ketorolac treatment groups. These findings indicate that R-ketorolac treatment slows tumor progression in an aggressive model of breast cancer. R-ketorolac may thus represent a novel therapeutic approach for breast cancer prevention or treatment based on its pharmacologic activity as a Rac1 and Cdc42 inhibitor.

The Interaction of Intramuscular Ketorolac (Toradol) and Concussion in a Rat Model.

The purpose of this study was to examine the interaction of a single dose of Toradol and head impact in an in vivo rat model for sport-related concussion using a validated rat concussion model. Thirty-five Sprague-Dawley rats were placed into one of four groups: (1) Control, (2) Impact Only, (3) Toradol Only, (4) Impact and Toradol. Animals in the impact groups were subjected to a single head impact. Animals in the Toradol group received a single intramuscular injection of Toradol prior to impact. We examined magnetic resonance imaging, serum S100-B and cognitive function using a Morris Water Maze. In the control group, latency decreased significantly from day 0 (74.9 s) to 24 h (57.4 s) after anesthesia. There was no statistically significant difference between time zero and 24 h after impact in the Impact only or Impact and Toradol group. Our findings indicate that there were no differences between cognitive ability, MRI findings or S100B in rats that were administered a single dose of Toradol and subjected to a single impact and rats that were subjected to a single impact only. In both impact groups there were transient changes in cognitive ability as measured by the Morris Water Maze.

Randomized Controlled Trial Comparing the Effects of 2 Analgesic Drug Protocols in Patients who Received 5 Dental Implants.

PURPOSE: This randomized controlled trial compares postoperative pain and swelling after placing dental implants in patients treated with nonsteroidal anti-inflammatory drugs (NSAIDs) versus NSAIDs and corticosteroids. MATERIALS AND METHODS: Thirty patients received 5 dental implants each in the interforaminal region of the mandible. All patients were treated with ketorolac tromethamine 10 mg, 2 tablets daily for 2 days and amoxicillin 500 mg, 3 tablets daily for 7 days starting 24 hours before surgery. Experimental patients received an im injection of betamethasone 2 mL within 10 hours after surgery. Pain perception, intraoral inflammation (InIn), and extraoral inflammation (ExIn) data were collected 3, 7, and 14 days after surgery. Patients filled out a pain visual analog scale. InIn and ExIn were recorded by observing the existence of 7 signs. RESULTS: One patient was excluded from control group. Pain perception, InIn, and ExIn were not different between groups at each time point. However, these variables were different from the previous time point within each group. CONCLUSION: This study suggests that there is no difference in managing postoperative pain and swelling with betamethasone versus betamethasone and ketorolac.

Comparison of the anti-inflammatory effect of dexamethasone and ketorolac in the extractions of third molars.

This double-blind, split-mouth, and randomized study was aimed to compare the efficacy of dexamethasone and ketorolac tromethamine, through the evaluation of pain, edema, and limitation of mouth opening. Thirty-four individuals aged 18-26 years, having bilateral mandibular third molars, in a similar position, were selected. Two different surgical procedures were performed on the same individual by the single surgeon. For an extraction, the individual received 1 capsule of 10 mg ketorolac tromethamine 1 h before surgery and every 8 h for 2 days. For the extraction of the contralateral side, the individual received 1 capsule of 8 mg dexamethasone 1 h before surgery and 1 placebo capsule every 8 h for 2 days. Sodium metamizol, 500 mg, was given as rescue medication in postoperative. Pain was assessed by the Visual Box Scale-11 points (BS-11) at 24 h postoperative. Edema (metric measurement) and the maximum mouth opening (interincisal) were recorded in the pre-operative, 24 h, 48 h, 72 h and 7 days postoperatively. The results showed that both therapeutic treatments used were effective in the postoperative, and there were no statistically significant differences between the groups for the pain and edema variables. However, for the limitation of mouth opening, 24 h and 7 days postoperatively, the dexamethasone group had a lower limitation of mouth opening, behaving better than the ketorolac for this variable in these periods. Due also to the higher margin of safety, the use of dexamethasone as a single dose becomes a more suitable alternative for use in routine surgical extractions of third molars.