The retinal pigment epithelial (RPE) cell monolayer forms the outer blood-retinal barrier and has a crucial role in ocular pharmacokinetics. Although several RPE cell models are available, there have been no systematic comparisons of their barrier properties with respect to drug permeability. We compared the barrier properties of RPE secondary cell lines (ARPE19, and ARPE19mel) and both primary (hfRPE) and stem-cell derived RPE (hESC-RPE) cells by investigating the permeability of nine drugs (aztreonam, ciprofloxacin, dexamethasone, fluconazole, ganciclovir, ketorolac, methotrexate, voriconazole, and quinidine) across cell monolayers. ARPE19, ARPE19mel, and hfRPE cells displayed a narrow Papp value range, with relatively high permeation rates (5.2-26 × 10-6 cm/s). In contrast, hESC-RPE cells efficiently restricted the drug flux, and displayed even lower Papp values than those reported for bovine RPE-choroid, with the range of 0.4-32 cm-6/s. Therefore, ARPE19, ARPE19mel, and hfRPE cells failed to form a tight barrier, whereas hESC-RPE cells restricted the drug flux to a similar extent as bovine RPE-choroid. Therefore, hESC-RPE cells are valuable tools in ocular drug discovery.

Prior to 2020, pain management in the Washtenaw/Livingston County Medical Control Authority (W/L MCA) Emergency Medical Service (EMS) system in Southeast Michigan was limited to morphine, fentanyl, ketorolac, and acetaminophen. Based on the increasing evidence describing its safety and efficacy, ketamine was added to local protocols for pain management. This study aimed to evaluate differences in pain management and adverse effects of ketamine and opioid administration. Data from pediatric patients who received ketamine or an opioid in the W/L MCA EMS system from October 2019 to March 2021 were analyzed. The primary outcome was the difference in pain score, and the secondary outcome was adverse effects observed after analgesic administration. The decrease in pain scores was greater among ketamine patients (mean: 5.2) compared to opioid patients (mean: 2.9), p < 0.001. The prevalence of adverse effects was higher among patients in the ketamine group (28.6%) compared to patients in the opioid group (2.4%, p < 0.001). Of 14 patients who received ketamine, one 17-year-old male experienced mild anxiety (7.1%), two teenage females experienced mild dissociation (14.3%), and one 20-year-old female experienced mild nausea (7.1%). Overall, ketamine is a safe and effective option compared to opioids for pediatric patients experiencing moderate to severe prehospital pain.

Opioid minimization in the acute postoperative phase is timely in the era of the opioid epidemic. The authors hypothesize that patients with facial trauma receiving multimodal, narcotic-minimizing pain management in the perioperative period will consume fewer morphine milligram equivalents (MMEs) while maintaining adequate pain control compared with a traditional analgesia protocol. An IRB-approved pilot study evaluating isolated facial trauma patients compared 10 consecutive prospective patients of a narcotic-minimizing pain protocol beginning in August 2020 with a retrospective, chart-reviewed cohort of 10 consecutive patients before protocol implementation. The protocol was comprised of multimodal nonopioid pharmacotherapy given preoperatively (acetaminophen, celecoxib, and pregabalin). Postoperatively, patients received intravenous (IV) ketorolac, scheduled acetaminophen, ibuprofen, and gabapentin. Oxycodone was reserved for severe uncontrolled pain. The control group had no standardized protocol, though opioids were ad libitum. Consumed MMEs and verbal Numeric Rating Scale (vNRS) pain scores (0-10) were prospectively tracked and compared with retrospective data. Descriptive and inferential statistics were run. At all recorded postoperative intervals, narcotic-minimizing subjects consumed significantly fewer MMEs than controls [0-8 h, 21.5 versus 63.5 (P = 0.002); 8-16 h, 4.9 versus 20.6 (P = 0.02); 16-24 h, 3.3 versus 13.9 (P = 0.03); total 29.5 versus 98.0 (P = 0.003)]. At all recorded postoperative intervals, narcotic-minimizing subjects reported less pain (vNRS) than controls (0-8 h, 7.7 versus 8.1; 8-16 h, 4.4 versus 8.0; 16-24 h 4.3 versus 6.9); significance was achieved at the 8 to 16-hour time point (P = 0.006). A multimodal, opioid-sparing analgesia protocol significantly reduces opioid use in perioperative facial trauma management without sacrificing satisfactory pain control for patients.

This study aimed to develop ketorolac microparticles stabilized by hyaluronic acid based on poly(lactide-co-glycolide) (PLGA), poly(lactide) (PLA), and their blend for further application in osteoarthritis. The polymer blend may provide tailored drug release and improved physicochemical characteristics. The microparticles were prepared by water-in-oil-in-water (w/o/w) double emulsion solvent evaporation using two emulsification techniques, probe sonication (PS) and high-speed stirring (HSS), to obtain the microparticles in different size ranges. The results revealed that the polymer composition and emulsification technique influenced the ketorolac microparticle characteristics. The PS technique provided significantly at least 20 times smaller average size (1.3-2.2 µm) and broader size distribution (1.5-8.5) than HSS (45.5-67.4 µm and 1.0-1.4, respectively). The encapsulation efficiency was influenced by the polymer composition and the emulsification technique, especially in the PLA microparticles. The DSC and XRD results suggested that the drug was compatible with and molecularly dissolved in the polymer matrix. Furthermore, most of the drug molecules existed in an amorphous form, and some in any crystalline form. All of the microparticles had biphasic drug release composed of the burst release within the first 2 h and the sustained release over 35 days. The obtained microparticles showed promise for further use in the treatment of osteoarthritis.

Our objective was to determine whether (-)-Epicatechin administered alone or simultaneously with topical Ketorolac decreased the relative expression of GFAP and modulated the response of Nrf2 in a mouse model with induced hyperglycemia. We found that GFAP and Nrf2 decreased in the groups that received treatments alone or simultaneous during 8 weeks; even when the effect on the Nrf2 was not pronounced, it showed a higher concentration when GFAP decreased. Our results suggest a protective effect of Ketorolac and (-) - Epicatechin, which seem to limit the preclinical retinal damage caused by inflammation in hyperglycemia.

A 58-year-old male who underwent cataract extraction with combined intraocular lens and Hydrus® Microstent (Ivantis Inc, Irvine, CA, US) implantation 2 years ago in the right eye (OD) due to advanced glaucoma presented with blurry vision in right eye (OD) for 3 months. The visual acuity was 20/60 and slit-lamp examination indicated mild anterior chamber inflammation with unexposed, functioning tube shunt superotemporally in OD. Optical coherence tomography demonstrated cystoid macular edema (CME) with subretinal fluid. Fluorescein angiography demonstrated petaloid pattern leakage of CME. Gonioscopy revealed a kinked appearance of a Hydrus® Microstent protruding into the anterior chamber and causing iris chafing. Topical ketorolac tromethamine and prednisolone acetate were started. At the 2nd month of follow-up, the anterior chamber was quiet, and the CME resolved completely. Protruded kinked Hydrus® Microstent may lead to acute iridocyclitis and CME through iris chafing, which may be responsive to topical anti-inflammatory drops.

In older individuals, minor trauma may cause potentially fatal intracranial subdural hematoma (SDH). Rarely, these patients present with only low back and radicular pain as gravity redistributes the SDH to the lumbar spine. A 69-year-old male presented to a chiropractor with a 10-day history of acute on chronic low back pain, which radiated into his lower extremities bilaterally, involving weakness and difficulty walking, and a ground-level fall onto his elbows 16 days prior. He had visited his primary care provider, orthopedist, and traditional Chinese medicine practitioner, received oral analgesics and three ketorolac injections, and had lumbar radiographs, followed by acupuncture, cupping, and spinal manipulation without lasting relief. Considering the patient's concerning presentation, the chiropractor ordered lumbar magnetic resonance imaging (MRI) on the first visit, revealing findings suggestive of late subacute lumbar SDH, and recommended urgent brain MRI and neurosurgical referral. The patient went to an orthopedic surgeon at a nearby hospital, becoming disoriented upon presentation, prompting admission. Brain MRI confirmed bilateral chronic intracranial SDH, prompting emergency hematoma evacuation via burr hole craniostomy. The patient's gait rapidly improved, and the pain subsided over the following two weeks. This case highlights an older male identified as having spinal SDH by a chiropractor, leading to referral and surgery for concurrent life-threatening intracranial SDH. Clinicians should be aware that spinal SDH may stem from asymptomatic intracranial SDH and should be suspicious of SDH in older individuals after a fall, signs of which warrant emergency referral for MRI and surgical evaluation.

Eye drops represent 90% of all currently used ophthalmic treatments. Only 0.02% of therapeutic molecules contained in eye drops reach the eye anterior chamber despite their high concentration. The tear film efficiently protects the cornea, reducing access to the target. Thereby, the increase in the drug bioavailability and efficiency must come from the mucoadhesion optimization of the drug delivery system. The gold nanoparticles, used as a drug delivery system in this study, already showcased ultrastable and mucoadhesive properties. The goal was to study the gold nanoparticles' ability to release two specific ophthalmic drugs, flurbiprofen and ketorolac. The parameters of interest were those involving the loading conditions, the gold nanoparticles properties, and the release experimental conditions. The drug release was measured using an in vitro model based on dialysis bags coupled with UV-visible spectroscopy. Gold nanoparticles showed an ability to release different molecules, whether hydrophobic or hydrophilic, in passive or active drug release environments. Based on these preliminary results, gold nanoparticles could represent a promising drug delivery system for ketorolac and flurbiprofen when topically applied through eye drops.

This study is to compare ibuprofen and ketorolac for children with trauma-related acute pain. We conducted a multicentre randomized, double-blind, controlled trial in the Paediatric Emergency Department setting. We enrolled patients aged 8 to 17 who accessed the emergency department for pain related to a limb trauma that occurred in the previous 48 h. At the admission, patients were classified based on numeric rating scale-11 (NRS-11) in moderate (NRS 4-6) and severe (NRS 7-10) pain groups. Each patient was randomized to receive either ibuprofen (10 mg/kg) or ketorolac (0.5 mg/kg) and the placebo of the not given drug in a double dummies design. NRS-11 was asked every 30 min until 2 h after drug and placebo administration. The primary outcome was NRS-11 reduction at 60 min. Among 125 patients with severe pain, NRS-11 reduction after 60 min from drug administration was 2.0 (IQR 1.0-4.0) for ibuprofen and 1.0 (IQR 1.0-3.0) for ketorolac (p = 0.36). Ibuprofen was significantly better, considering secondary outcomes, at 90 min with a lower median of NRS-11 (p 0.008), more patients with NRS-11 less than 4 (p 0.01) and a reduction of pain score of more than 3 NRS-11 points (p 0.01). Among 87 patients with moderate pain, the NRS-11 reduction after 60 min from drug administration was 1.63 (± 1.8) for ibuprofen and 1.8 (± 1.6) for ketorolac, with no statistically significant difference.Conclusions: Oral ibuprofen and ketorolac are similarly effective in children and adolescents with acute traumatic musculoskeletal pain.Trial registration: ClinicalTrial.gov registration number: NCT04133623.

Uterine fibroid embolization (UFE) procedures performed from 2013 to 2019 were reviewed. Seventy-two patients were treated with a standard protocol consisting of sedation, ketorolac, ondansetron, and overnight parenteral analgesics and antiemetics. Ninety-six patients were treated with a new protocol, which added transdermal scopolamine, lorazepam, and intravenous acetaminophen. Outpatient uterine fibroid embolization (OP-UFE) not requiring hospitalization was successful in 81.4% and 2.7% of patients treated with the new and old protocols, respectively (odds ratio [OR], 141.4; P < .0001). Procedural fentanyl doses were lower with the new protocol than with the old one (mean, 148 vs 186 mcg; P = .0016). In the new protocol subset, patients were 1.01 times more likely to fail OP-UFE for every microgram increase in procedural fentanyl (OR, 0.99, P = .009), and those presenting with pain were less likely to succeed with OP-UFE than those with bleeding or bulk symptoms (OR, 0.31, P = .04). In conclusion, decreasing the opioid dose while increasing the antiemetic and nonopioid analgesic medications improves the chances of same day discharge after UFE.

Laparoscopic cholecystectomy (LC), unlike laparotomy, is an invasive surgical procedure, and some patients report mild to moderate pain after surgery. Transversus abdominis plane (TAP) block has been shown to be an appropriate method for postoperative analgesia in patients undergoing abdominal surgery. However, there have been few studies on the efficacy of TAP block after LC surgery, with unclear information on the optimal dose, long-term effects, and clinical significance, and the analgesic efficacy of various procedures, hence the need for this review. Five electronic databases (PubMed, Academic Search Premier, Web of Science, CINAHL, and Cochrane Library) were searched for eligible studies published from inception to the present. Post-mean and standard deviation values for pain assessed were extracted, and mean changes per group were calculated. Clinical significance was determined using the distribution-based approach. Four different local anesthetics (Bupivacaine, Ropivacaine, Lidocaine, and Levobupivacaine) were used at varying concentrations from 0.2% to 0.375%. Ten different drug solutions (i.e., esmolol, Dexamethasone, Magnesium Sulfate, Ketorolac, Oxycodone, Epinephrine, Sufentanil, Tropisetron, normal saline, and Dexmedetomidine) were used as adjuvants. The optimal dose of local anesthetics for LC could be 20 mL with 0.4 mL/kg for port infiltration. Various TAP procedures such as ultrasound-guided transversus abdominis plane (US-TAP) block and other strategies have been shown to be used for pain management in LC; however, TAP blockade procedures were reported to be the most effective method for analgesia compared with general anesthesia and port infiltration. Instead of 0.25% Bupivacaine, 1% Pethidine could be used for the TAP block procedures. Multimodal analgesia could be another strategy for pain management. Analgesia with TAP blockade decreases opioid consumption significantly and provides effective analgesia. Further studies should identify the long-term effects of different TAP block procedures.

Total knee arthroplasty (TKA) is the final treatment option for patients with advanced knee osteoarthritis (OA). Unfortunately, TKA surgery is accompanied by acute postoperative pain that is more severe than arthroplasty performed in other joints. Elucidating the molecular mechanisms specific to post-TKA pain necessitates an animal model that replicates clinical TKA procedures, induces acute postoperative pain, and leads to complete functional recovery. Here, we present a new preclinical TKA model in rats and report on functional and behavioral outcomes indicative of pain, analgesic efficacy, serum cytokine levels, and dorsal root ganglia (DRG) transcriptomes during the acute postoperative period. Following TKA, rats exhibited marked deficits in weight bearing that persisted for 28 days. Home cage locomotion, rearing, and gait were similarly impacted and recovered by day 14. Cytokine levels were elevated on postoperative days one and/or two. Treatment with morphine, ketorolac, or their combination improved weight bearing while gabapentin lacked efficacy. When TKA was performed in rats with OA, similar functional deficits and comparable recovery time courses were observed. Analysis of DRG transcriptomes revealed upregulation of transcripts linked to multiple molecular pathways including inflammation, MAPK signaling, and cytokine signaling and production. In summary, we developed a clinically relevant rat TKA model characterized by resolution of pain and functional recovery within five weeks and with pain-associated behavioral deficits that are partially alleviated by clinically administered analgesics, mirroring the postoperative experience of TKA patients.

A novel approach for the separation of ketorolac enantiomers by capillary electrophoresis is presented. A cationic β-cyclodextrin derivative based on imidazole was synthesized and used as a chiral selector in the background electrolyte. The influence of pH and ionic strength of background electrolyte, as well as cationic β-cyclodextrin derivative concentration on the resolution of ketorolac enantiomers, was investigated. The highest value of the resolution for ketorolac enantiomers was 1.46 when the background electrolyte consisted of 25 mM NaH2 PO4 (pH 6.4) with 1 mM 1-butyl-3-β-cyclodextrinimidazolium tosylate. Additionally, the possibilities of cationic derivatives for the separation of ketoprofen enantiomers were shown (peak resolution 1.06). The two-step preconcentration mode was developed to reduce the limit of detection of individual enantiomers. The proposed approach was successfully applied to determine ketorolac enantiomers in tablet "Ketorol express" and human plasma. The calibration range of ketorolac enantiomers for plasma samples was 0.25-2.50 μg/ml with coefficients of determination ≥ 0.99. The relative standard deviation both of the peak area and migration time was less than 15%, as well as the accuracy ranged from 90.1% to 110.2% for both analytes. The limits of detection were 44 and 55 ng/ml for R- and S-ketorolac. The quantity of ketorolac in plasma was verified with high-performance liquid chromatography.

Acute pain after surgery can cause harmful effects. There are many ways to treat pain after surgery. Bier block technique is also a type of intravenous regional anesthesia that is suitable for short and minor surgeries of the arm, wrist, and fingers, so this study aims to compare the analgesic effect of Ketorolac in intravenous injection and when the lidocaine is added to Bier block. In surgery, traumatic injuries to the upper limbs. This study was a clinical trial, randomized and double-blind. The target population was candidates for upper limb orthopedic surgery. The patients selected based on the entry and exit criteria were randomly assigned to one of the 3 study groups. The intensity of pain, the amount of morphine consumed through the intravenous PCA pump, the incidence of side effects of morphine and ketorolac, as well as the overall patient satisfaction regarding the anesthesia method and pain control were compared between the groups. Data analysis, both descriptive and analytical, was done using SPSS statistical software version 21. The three studied groups were identical and had no differences in terms of quantitative and qualitative demographic variables. The median tourniquet closing time is different between the control group and the intravenous ketorolac and topical ketorolac groups with P=0.002 and P=0.001, respectively. There was no significant difference between the three groups in terms of the time of the first request to receive painkillers after deflating the tourniquet, but the amount of morphine received between the groups was significantly different (P=0.02). Comparison of pain intensity based on NRS, considering Taking the measurement repetition times indicated the significance of the effect of pain intensity between the groups (P=0.001). In terms of overall satisfaction with the quality of analgesia and anesthesia method, no significant difference was observed between the three study groups. In terms of the occurrence of complications related to the use of ketorolac, no complications were observed in any of the groups receiving this drug. In general, by conducting this study, it can be said that the administration of Ketorolac reduces the intensity of postoperative pain in the recovery room and transfer to the inpatient ward, and reduces the amount of morphine received by patients, but the time of the first request for pain relief by the patient It does not significantly delay and does not affect the overall satisfaction of patients with the quality of analgesia during and after the operation and their satisfaction with the anesthesia method they received.