Effects of topical ketorolac tromethamine on tear parameters, meibography, goblet cell density, and conjunctival oxidative stress in healthy dogs.

OBJECTIVES: The objective of the study was to evaluate whether a twice-daily instillation of 0.45% preservative-free ketorolac tromethamine (FKT) or 0.4% benzalkonium chloride-preserved ketorolac tromethamine (BACKT), every 12 h for 30 days may affect tear film parameters and the meibography in healthy dogs. Additionally, we assessed whether the same treatments irritated the ocular surface, affected goblet cell density (GCD), and the levels of oxidative stress biomarkers (OSB) in the conjunctiva of the same dogs. PROCEDURES: Experimental and masked comparison study. In 11 healthy dogs baseline values of the lipid layer thickness, tear meniscus height, non-invasive tear breakup time (NI-TFBT), and the meibomian gland (MG) loss were assessed by OSAvet®. For each dog, one eye received 40 µL of BACKT, while the other received 40 µL FKT, every 12 h for 30 consecutive days. Tear parameters and meibography were repeated 15, 30, and 60 days post-treatments. Conjunctival hyperemia and blepharospasm were monitored at the same time points. At baseline and Day 30, a conjunctival biopsy was collected for GCD and OSB determination. RESULTS: Conjunctival hyperemia and blepharospasm were not observed. At Day 15, the MG loss increased only in FKT-treated eyes (p < .001). On Day 30, both treatment groups showed increased MG loss, shortened NI-TFBT, and reduced GCD and catalase (p < .05). At Day 30, BACKT-treated eyes showed lower levels of superoxide dismutase (SOD) (p = .006) and higher levels of malondialdehyde (MDA) (p = .02). Differences between treatments were not observed for any parameter at any time point (p > .05). 60 days after treatment, OSAvet® parameters tended to return to values assessed at baseline; however, significant differences remained for MG loss (p < .05). CONCLUSIONS: Twice-daily instillation of KT, containing or not BAC, for 30 consecutive days shortened NI-TFBT, decreased GCD, and increased the MG loss in healthy dogs. KT should be used with caution when prescribed for long periods, particularly in patients with tear film abnormalities. However, future controlled studies using KT, BAC, and other topical NSAIDs are indicated to further support this finding.

Ketorolac tromethamine pretreatment suppresses sufentanil-induced cough during general anesthesia induction: a prospective randomized controlled trial.

BACKGROUND: To observe the effect of pretreatment with ketorolac tromethamine on sufentanil-induced cough in general anesthesia patients. METHODS: A total of 102 patients were screened, and 90 patients were scheduled for elective surgery under general anesthesia. The 90 patients were randomly divided into two groups: the control group (C group) and the observation group (KT group). Five minutes before anesthesia induction, the observation group was given ketorolac tromethamine 0.5 mg/kg intravenously within 3 s, while the control group was given the same amount of normal saline intravenously. All patients were given a sufentanil bolus of 0.5 µg/kg (within 3 s) intravenously. One minute later, propofol 2.5 mg/kg and vecuronium 0.15 mg/kg were injected intravenously, and endotracheal intubation was guided by laryngoscopy. The number of coughs that occurred within 1 min after sufentanil injection was recorded. The mean arterial pressure (MAP), heart rate (HR) and pulse oxygen saturation (SpO2) were recorded at T0 (immediately before pretreatment), T1 (5 min after pretreatment), T2 (before intubation), T3 (1 min after intubation) and T4 (5 min after intubation). The incidence of adverse reactions, including nausea and vomiting, dizziness, drowsiness, delay of recovery, restlessness in the recovery period, respiratory depression and postoperative incision pain, was analyzed. RESULTS: Within 1 min after sufentanil injection, the incidence and severity of cough in the KT group was significantly lower than that in the C group (P <  0.05). At T0, T1, T2, T3 and T4, there were no significant differences in MAP, HR and SpO2 between the two groups (P >  0.05). There was no significant difference in the dosage of sufentanil, propofol, remifentanil and vecuronium, the incidence of nausea and vomiting, the delay of recovery, dizziness, drowsiness or respiratory depression between the two groups (P >  0.05). However, the incidence of restlessness and the number of patients with VAS scores > 3 in the KT group were significantly lower than those in the C group (P <  0.05). CONCLUSION: Pretreatment with intravenous ketorolac tromethamine can significantly reduce the incidence of sufentanil-induced cough during induction of general anesthesia, which can also significantly reduce postoperative incision pain and restlessness during the recovery period. TRIAL REGISTRATION: Chinese Clinical Trial Registry (registration number# ChiCTR2000030287 ; date of registration: 27/02/2020).

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.

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.

In vitro anti-LPS dose determination of ketorolac tromethamine and in vivo safety of repeated dosing in healthy horses.

Flunixin meglumine (FM) is a commonly used Nonsteroidal anti-inflammatory drug (NSAID) in horses, but clinical efficacy is often unsatisfactory. Ketorolac tromethamine (KT) demonstrates superior efficacy compared to other NSAIDs in humans, but its anti-inflammatory effects have not been investigated in the horse. Safety of repeated dosing of KT has not been evaluated. The first objective was to conduct a dose determination study to verify that a previously described dosage of KT would inhibit Lipopolysaccharide (LPS)-induced eicosanoid production in vitro, and to compare KT effects of this inhibition to those of FM. Then, a randomized crossover study was performed using nine healthy horses to evaluate plasma concentrations of KT and FM following IV administration. Administered dosages of KT and FM were 0.5 mg/kg and 1.1 mg/kg, respectively. Safety following six repeated doses of KT was assessed. Ketorolac tromethamine and FM suppressed LPS-induced Thromboxane B2 (TXB2 ) and Prostaglandin E2 (PGE2 ) production in vitro for up to 12 hr. Intravenous administration produced plasma concentrations of KT and FM similar to previous reports. No adverse effects were observed. A KT dosage of 0.5 mg/kg IV inhibited LPS-induced eicosanoids in vitro, and repeated dosing for up to 3 days appears safe in healthy horses. Investigation of in vivo anti-inflammatory and analgesic effects of KT is warranted.

Nanodispersion-loaded mucoadhesive polymeric inserts for prolonged treatment of post-operative ocular inflammation.

Mucoadhesive polymeric films incorporated with ketorolac tromethamine-loaded nanodispersion aiming the sustained delivery of the drug to the cornea have been developed and characterised for the treatment of post-operative ocular inflammation. Nanodispersions were prepared by ionic gelation method with various concentrations of chitosan and sodium tripolyphosphate. The developed nanodispersions were analysed for morphology, particle size, dispersion homogeneity, zeta potential, entrapment efficiency and drug release. The nanodispersion that showed the smallest particle size and the highest entrapment efficiency was incorporated in optimised HPMC E15 and Eudragit RL100/HPMC K4m films. The formulation with optimum physicomechanical properties was selected to study its ex vivo transcorneal permeation through freshly excised bovine cornea in comparison with the nanodispersion and the marketed eye drops (Acular®). The polymeric ocular film showed greater permeation than aqueous eye drops. Moreover, the ocular film revealed a prolonged anti-inflammatory effect compared to eye drops when applied to inflamed rabbit's eyes.

Pharmacokinetics of ketorolac tromethamine in horses after intravenous, intramuscular, and oral single-dose administration.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are an integral component of equine analgesia, yet currently available NSAIDs are both limited in their analgesic efficacy and have adverse effects. The NSAID ketorolac tromethamine (KT) is widely used in humans as a potent morphine-sparing analgesic drug but has not been fully evaluated in horses. The purpose of this study was to determine the pharmacokinetic profile of KT in horses after intravenous (i.v.), intramuscular (i.m.), and oral (p.o.) administration. Nine healthy adult horses received a single 0.5-mg/kg dose of KT via each route of administration. Plasma was collected up to 48 h postadministration and analyzed for KT concentration using HPLC/MS/MS. Noncompartmental analysis of i.v. dosage indicated a mean plasma clearance of 8.4 (mL/min)/kg and an estimated mean volume of distribution at steady-state of 0.77 L/kg. Noncompartmental analysis of i.v., i.m., and p.o. dosages indicated mean residence times of 2.0, 2.6, and 7.1 h, respectively. The drug was rapidly absorbed after i.m. and p.o. administration, and mean bioavailability was 71% and 57% for i.m. and p.o. administration, respectively. Adverse effects were not observed after i.v., i.m., and p.o. administration. More studies are needed to evaluate the analgesic and anti-inflammatory properties of KT in horses.

Long term outcome after lichtenstein hernia repair using general, locoregional or local anaesthesia.

BACKGROUND: Chronic pain or discomfort after hernia surgery is nowadays a more challenging concern than recurrence. This study aimed to evaluate the long-term impact of local anaesthetic repair (LA) on pain, discomfort, paraesthesia and functional outcome after Lichtenstein hernia repair as compared to locoregional (LRA) and general anaesthesia (GA). METHODS: patients with primary or recurrent inguinal hernia underwent Lichtenstein repair with a polypropylene mesh. All patients with a follow-up of at least three years were sent a detailed questionnaire and offered an outpatient visit. Kaplan-Meier estimates and Cox proportional hazard regressions were used to analyse the relationship between time to event variables and explanatory variables including anaesthesia type. RESULTS: Between 1994 and 2006, in two cohorts, 330 patients answered the questionnaire: 100 under GA, 35 under LRA, and 195 under LA. This represented a response rate of 95, 94, and 98% respectively. Compared to GA and LRA, LA resulted in less long term pain, discomfort and paraesthesia. Moreover, resumption of social and professional activities was faster after LA. Recurrence rates were 1, 0, and 0.5% respectively. CONCLUSIONS: After Lichtenstein inguinal hernia repair, LA results in beneficial effects beyond the immediate postoperative period.

Ketorolac tromethamine - routes and clinical implications.

Opioids have long been used for analgesic purposes for a wide range of procedures. However, the binding of these drugs to opiate receptors has created various challenges to the clinician due to unfavorable side effect profiles and the potential for tolerance and abuse. In 1989, ketorolac became an approved nonsteroidal inflammatory drug (NSAID) for injectable use as an analgesic. Over the last 20 years, numerous studies have been conducted involving ketorolac. These studies have provided additional information about various routes of administration and their effect on the efficacy and the side effect profile of ketorolac. Moreover, ketorolac has been compared with several widely used analgesics. This review evaluates both the potential benefits and potential drawbacks of ketorolac generally, and specifically discusses routes of administration, including their advantages and disadvantages when compared to several traditional analgesics in both inpatient and outpatient settings.

Neurotrophic Keratopathy after wide retinal endolaser and postoperative Ketorolac eye drops: A case series.

PURPOSE: We report a series of 5 cases, happened in a period of 5 months, who developed neurotrophic keratopathy (NK) following pars plana vitrectomy (PPV) and retinal endolaser for rhegmatogenous retinal detachment (RRD). In our several decennary experience of surgical center predominantly based on vitreoretinal surgery, we had rare cases of postoperative NK. These recent cases of post-surgical NK happened contextually to our change of postoperative non-steroidal anti-inflammatory drugs (NSAIDs) drops, based on Ketorolac Tromethamine 0.5% eye drops. CASES PRESENTATION: Five patients with a mean age of 61 ± 7.3 years were treated with one or more PPV with intraoperative peripheral endolaser for RRD. Nobody had previous herpetic keratitis, systemic disease like diabetes mellitus or other predisposing factors for NK. In the postoperative period, all patients received Ketorolac Tromethamine 0.5% eye drops for a mean period of 54 ± 25 days. During follow-up visits they developed NK and they were successfully treated with suspension of Ketorolac eye drops, application of therapeutic contact lens or amniotic membrane patch and topical lubricant therapy. CONCLUSIONS: Postoperative Ketorolac eye drops, in patients who underwent PPV with endolaser, may reduce the corneal sensitivity, predispose to epithelial disruption and NK development. Studies are needed to explore the effect of NSAIDs on corneal sensitivity reduction in patient who will undergo PPV and extensive endolaser.

The impact of pregnancy on urinary ketorolac metabolites after single intravenous bolus.

Compared to female volunteers or postpartum, ketorolac clearance is higher at delivery. To explore the alterations that explain this higher clearance, urinary ketorolac metabolites collected at delivery (n = 40) were compared to female volunteers (unpaired, n = 8) or postpartum (paired, n = 8) following intravenous administration of 30 mg ketorolac tromethamine. A mean 38 (SD 9) % of the ketorolac dose was retrieved in 8-h urine collections. This was based on mean portions of 56 (20), 10 (14) and 33 (12) % for free ketorolac, ketorolac-glucuronide and p-hydroxy-ketorolac, respectively. The mean ketorolac-glucuronide portion at delivery (5 %) was lower compared to female volunteers (21 %) or postpartum (21 %) (p = 0.003 and p = 0.002, respectively). Similarly, there was a difference in mean portion of free urinary ketorolac at delivery when compared to healthy female volunteers (60-45 %, p = 0.046). Using paired statistics, the mean portion of total urinary ketorolac was lower (62-73 %, p = 0.015) while the portion retrieved as p-hydroxy-ketorolac was significantly higher at delivery compared to postpartum (38-28 %, p = 0.031). The differences in urine metabolites suggest that the increased ketorolac clearance at delivery is in part explained by increased metabolic clearance to p-hydroxy-ketorolac, reflecting increased oxidation activity.

Intranasal ketorolac tromethamine (SPRIX(R)) containing 6% of lidocaine (ROX-828) for acute treatment of migraine: safety and efficacy data from a phase II clinical trial.

OBJECTIVE: Ketorolac is a non-triptan, non-opioid, mixed cyclooxygenase (COX)1/2-inhibitor for short-term management of moderate-to-severe acute pain. This trial evaluated an intranasal formulation of ketorolac tromethamine (SPRIX®) containing 6% lidocaine (ROX-828) for the acute treatment of migraine with and without aura as defined by the International Headache Society. METHODS: Patients were randomly assigned 1:1 to self-treat with intranasal ROX-828 (31.5 mg ketorolac tromethamine/200 µL, containing 6% of lidocaine) or placebo (with 6% lidocaine) within four hours of a new migraine attack rated ≥ moderate in pain intensity. Assessments included headache intensity and associated migraine symptoms (nausea, vomiting, phonophobia, photophobia) measured at baseline and at regular intervals through 48 hours post-dosing, and global impression of efficacy (seven-point scale) measured at two hours. RESULTS: Randomized patients who had a migraine attack (N = 140) were evaluable (ROX-828, N = 68; placebo, N = 72). Patients receiving ROX-828 showed a significant (p < 0.05) improvement in pain relief at all time points except 0.5 and 24 hours compared with those who received placebo. More patients achieved pain-free status with ROX-828 than with placebo at 1.5, 3, 4, 24 and 48 hours (p < 0.05); significance at the two-hour time point, which was the primary endpoint, was not met. Patients' global impression of efficacy showed statistically significantly better results for patients receiving ROX-828 than for those receiving placebo. Associated migraine symptoms were significantly improved (p < 0.05) with ROX-828 relative to placebo at several time points throughout the observation period. The most frequently reported adverse events in both groups were associated with nasal discomfort. CONCLUSION: Self-administered intranasal ROX-828 was well tolerated. While the primary endpoint was not met, the results provide preliminary evidence that ROX-828 improves migraine pain.

The pharmacokinetics of ketorolac after single postoperative intranasal administration in adolescent patients.

BACKGROUND: Ketorolac tromethamine (ketorolac) administration reduces postoperative opioid requirements. The pharmacokinetic characteristics of intranasal ketorolac tromethamine in children have not been characterized. Our objective of this study was to determine the pharmacokinetics of a single intranasal dose of ketorolac in adolescent patients. METHODS: Twenty surgical patients, ages 12 to 17 years, were enrolled. After surgery, subjects received intranasal ketorolac 15 mg (weight ≤50 kg) or 30 mg (weight >50 kg) using a proprietary administration system. Blood samples were obtained for ketorolac assay at baseline (within 15 minutes before the dose) and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours after the dose. A population analysis was undertaken using nonlinear mixed-effects models. Parameter estimates were standardized to a 70-kg person. RESULTS: The intranasal dosing in adolescents was well tolerated with minimal adverse effects. A 1-compartment model with first-order absorption and elimination was satisfactory to describe time-concentration profiles. Population parameter estimates (between subject variability) were clearance (CL/F) 2.05 L/h (60.5%), volume of distribution (V/F) 15.2 L (32.4%), absorption half-life (t(1/2)abs) 0.173 hour (25.0%). Time to peak concentration (Tmax) was 52 minutes (SD 6 minutes). CONCLUSION: Administration of ketorolac by the intranasal route resulted in a rapid increase in plasma concentration and may be a useful therapeutic alternative to IV injection in adolescents because plasma concentrations attained with the device are likely to be analgesic (investigational new drug no. 62,829).

Pharmacokinetic comparison of ketorolac after intracameral, intravitreal, and suprachoroidal administration in rabbits.

PURPOSE: To investigate the concentrations and pharmacokinetics of ketorolac in the rabbits by three different routes of administrations: a single intracameral, intravitreal, and suprachoroidal injection. METHODS: Fifty-four New Zealand white rabbits received ketorolac (250 µg/0.05 mL) in one eye by a single intracameral injection (group A, n = 18), single intravitreal injection (group B, n = 18), and single suprachoroidal injection (group C, n = 18). Drug concentrations in the vitreous, retina-choroid (RC), and plasma were determined by the methods of high-performance liquid chromatography at 0.5, 1, 2, 4, 8, and 24 hours after injection. The concentrations in the opposite eyes were also investigated. RESULTS: The mean maximum concentrations (Cmax) of ketorolac in the vitreous and RC were 0.378 ± 0.19 µg/mL and 3.15 ± 0.49 µg/g (at 0.5 hours), respectively, in group A; 156.2 ± 20.74 µg/mL (at 0.5 hours) and 208.0 ± 21.67 µg/g (at 1 hours), respectively, in group B; and 0.873 ± 0.34 µg/mL and 56.71 ± 22.64 µg/g (at 0.5 hours), respectively, in group C. In the RC, the area under the curve (AUC0-t) in group B (866.1 ± 52.67 µg/g·h) was higher (P < 0.01) than that in group C (77.10 ± 25.90 µg/g·h). The elimination half-life (t1/2) in group B (3.09 hours) was longer (P < 0.01) than that in group C (1.19 hours). In the control eyes, a drug level below 2 µg/g was detected in the RC in group C. Plasma concentrations were below 0.4 µg/mL in all 3 groups. Ketorolac was detectable in the RC till 24 hours after the intravitreal injection and 8 hours after the suprachoroidal injection. CONCLUSION: Intravitreal injection of ketorolac produced higher intraocular drug concentrations for a longer period compared with the other two routes. Suprachoroidal injection of ketorolac could reach an effective drug level in the RC with short half-lives and low drug levels in the vitreous. The plasma drug concentrations were low by all three routes.

Paracetamol and ketorolac pharmacokinetics and metabolism at delivery and during postpartum.

During pregnancy, changes in renal elimination, body composition and metabolic activity occur. Since these important alterations in physiology also affect drug disposition, pregnancy warrants a focused approach. Despite these differences, even commonly administered drugs have not undergone pharmacokinetic evaluation in pregnant women or at delivery. This is also true for analgesics routinely administered by anesthesiologists during pregnancy or at delivery, like intravenous (i.v.) paracetamol or ketorolac. We report on our observations on i.v. paracetamol and ketorolac disposition following cesarean delivery to illustrate the feasibility of such focused studies and the impact of pregnancy on drug disposition. The clinical relevance of these observations are subsequently discussed, and some future research directions are suggested.

SPRIX (ketorolac tromethamine) nasal spray: a novel nonopioid alternative for managing moderate to moderately severe dental pain.

In summary, SPRIX is a nonopioid alternative for the management of moderate to moderately severe pain. SPRIX offers dentists, physicians, and patients a new non-opioid option to control acute moderate to moderately severe pain in situations in which use of an IM or IV access is not feasible or not wanted. SPRIX is a valuable treatment option for patients with nausea or vomiting, those unable to take oral medications, and those unable to tolerate the side effects of opioids. In ambulatory acute pain settings, use of SPRIX will allow patients who need to remain alert to receive effective pain control. Currently, there are no nonopioid alternatives for the treatment of moderate to moderately severe pain other than ketorolac. In patients with more severe pain states, the combination of opioids and SPRIX provides unique advantages in maximizing analgesia while minimizing the unwanted adverse effects of both classes of drugs (referred to as multimodal or "balanced analgesia").

Comparison of multi-drug injection versus placebo after hallux valgus surgery.

BACKGROUND: Hallux valgus surgery is followed by a significant amount of postoperative pain. Local multi-drug injection can be an option for pain control, but few clinical studies exist. METHODS: Between May 2008 and July 2009, 30 consecutive patients (60 feet) received simultaneous bilateral proximal osteotomies for the correction of hallux valgus deformities. Each patient received local infiltration of the test solution made with ropivacaine, morphine, ketorolac, and epinephrine on one foot and same amount of normal saline on the other foot. The test side and the control side were randomly selected and both the patient and the surgeon remained blinded until the end of the data collection. RESULTS: The multi-drug injection resulted in significantly less pain at 4 hours after the operation through the night of the first postoperative day. The difference in visual analogue scale (VAS) between the two sides was most significant at 8 hours after the operation, and then gradually decreased through the first and second postoperative day. Mean satisfaction VAS was significantly higher on the injection side (8.2+/-0.9) compared to the control side (6.2+/-1.9, p<0.0001). CONCLUSION: Local multi-drug injection was easy to perform and safe and effective in reducing pain and enhancing patient satisfaction after hallux valgus surgery.

Effect of salts on gelation and drug release profiles of methylcellulose-based ophthalmic thermo-reversible in situ gels.

The poor bioavailability and therapeutic response exhibited by conventional ophthalmic solutions may be overcome by the use of thermo-reversible in situ gel. The purpose of this study was to examine the influence of different salts on the gelation, rheology and drug release of in situ gel based on methylcellulose. The gel temperature of 1% w/v methylcellulose (MC) was 60?C. It was found that 5?7% w/v sodium chloride (NaCl), 8?9% w/v potassium chloride (KCl), or 5% w/v sodium bicarbonate (NaHCO(3)) was capable of decreasing the gel temperature below physiological temperature, i.e. 37?C. Rheological studies indicated a large increase in viscosity at 37?C with the addition of salts in MC solutions. The duration of drug release from MC solution was 1.5?h. The significant observation was that the duration of drug release increased from 1.5?h to 3?5?h from salted MC solutions depending on the concentration and the type of salt. So, it can be concluded that the salted MC solutions were a better alternative than the MC solution to enhance the ocular bioavailability of the drug.

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.

Use of Acular LS in the pain management of keratoconus: a pilot study.

PURPOSE: The purpose of this pilot study was to determine the efficacy of ketorolac tromethamine 0.4% for pain management in conjunction with rigid gas permeable contact lenses in keratoconus. Any potential side effects and complications of this application were examined. METHODS: A total of 12 current keratoconus patients who were presently experiencing discomfort or pain associated with their rigid gas permeables for keratoconus and/or who were contact lens-intolerant were identified from the existing patient population at the SUNY University Optometric Center. Symptomatic subjects were identified through positive feedback to a study Inclusion Questionnaire mailed to their homes. Subjects were treated on the basis of each eye separately in a modified monocular trial that spanned 5 weeks. After establishing that all inclusion and exclusion criteria were met, subjects were instructed to first use an unlabeled bottle of artificial tear solution (placebo) for 2 weeks, and then an unmarked bottle of ketorolac tromethamine 0.4% for 2 weeks in the designated eye. One drop was instilled twice a day, and the eye not assigned to take the drops served as the control. Subjects were monitored through weekly follow-up visits and repeated Keratoconus Symptom and Severity Questionnaires. RESULTS: Responses from the Keratoconus Symptom and Severity Questionnaire were analyzed using a 2-factor Repeated Measures Analysis of Variance. Among the small subject subset, there was no statistically significant predilection for the ketorolac tromethamine 0.4% in managing the discomfort and pain associated with keratoconus. The artificial tear solution appeared to be equally effective in improving comfort. CONCLUSIONS: There was no conclusive result as to the efficacy of the ketorolac tromethamine 0.4% vs. the artificial tear solution in the pain management of keratoconus. This could be attributed to a number of physiological and situational factors, as well as small sample size.