Systemic absortion and adverse effects of topical ocular use of ketorolac tromethamine and sodium diclofenac in New Zealand rabbits for 90 days / Absorção sistêmica e efeitos adversos do uso tópico ocular por 90 dias de cetorolaco de trometamina e diclofenacode sódio em coelhos da raça Nova Zelândia

The effect of the systemic absorption of 0.1% diclofenac sodium (DS) eyedrop was compared to that of 0.5% ketorolac tromethamine (KT) in female New Zealand white rabbits treated on both eyes three times a day for 90 days. The rabbits were divided in three groups of six animals (n= 18): KT group, DS group, and control (Co) group, in which saline (0.9% NaCl) solution was instilled. Water and food consumption were measured daily, clinical examination was performed weekly, and blood samples were collected every 30 days for laboratory examination. The plasma was analyzed for the presence of KT and DS by solid-phase extraction (SPE) associated with mass spectrometry (MS). Systemic absorption of these drugs was confirmed by SPE-MS, allowing their separation and identification in the plasma. At the end of the treatment, the animals were euthanized and necropsied, and no macroscopic or microscopic changes were found. This observation confirmed the laboratory results, which were within normal reference standards for the species. According to the results obtained, it can be concluded that treatment with eyedrops containing KT and DS for 90 days in healthy rabbits does not cause adverse systemic effects.(AU)

Comparou-se o efeito da absorção sistêmica do colírio de diclofenaco de sódio 0,1% (DS) em relação ao de cetorolaco de trometamina 0,5% (CT) em coelhas da raça Nova Zelândia, tratadas nos dois olhos, três vezes ao dia, por 90 dias. As coelhas foram separadas em três grupos de seis animais (n=18): grupo CT, grupo DS e grupo controle (Co), no qual foi instilada solução fisiológica (NaCl 0,9%). Os consumos de água e ração foram mensurados diariamente, os exames clínicos foram realizados semanalmente e o sangue foi coletado a cada 30 dias para realização de exames laboratoriais. O plasma foi analisado para detectar a presença de CT e DS por extração em fase sólida (SPE) associada à espectrometria de massas (MS). A absorção sistêmica desses fármacos foi confirmada por SPE-MS, permitindo sua separação e identificação no plasma. Ao final do tratamento, os animais foram eutanasiados e necropsiados, e não foram encontradas alterações macroscópicas ou microscópicas. Essa observação confirmou os resultados laboratoriais, que estavam dentro dos padrões de referência para a espécie. De acordo com os resultados obtidos, pode-se concluir que o tratamento com colírio contendo KT e DS, por 90 dias, em coelhos saudáveis, não causa efeitos adversos sistêmicos.(AU)

Liposomes as potential carriers for ketorolac ophthalmic delivery: formulation and stability issues / Liposomes as potential carriers for ketorolac ophthalmic delivery: formulation and stability issues

ABSTRACT Drug delivery to treat ocular disorders locally is a challenging endeavor. Traditional ocular dosage form - eye drops - exhibits poor availability, consequently inefficient therapeutic response. The objective of the study was to formulate and characterize a ketorolac tromethamine ocular system with a prolonged release pattern based on liposomes as a vesicular carrier and to design once daily liquid preparation realizing the thermal in situ gelation principle. Liposomes were prepared by film hydration method. The influence of cholesterol concentration, pH and volume of hydration medium, and type and concentration of charging imparting agents were studied. Liposomes were characterized via, morphological examination, vesicular size, and encapsulation efficiency, and in vitro release performance, moreover its stability was assessed. The results obtained highlighted that liposomes showed a closed vesicular multi-lamellar structure. Ketorolac was successfully encapsulated within the liposomal structure in a cholesterol and charge inducing agent concentration-dependent behaviour. The dispersion of liposomes within thermosensitive Poloxamer in situ gel was able to retard the release of the drug by diffusion providing a controlled prolonged delivery. The liposomal formulations were physically stable for six months. Ketorolac tromethamine in situ liposomal gel representing an efficient alternative in terms of ocular retention and patient compliance when compared with conventional eye drops.

Dor em urgência odontológica: uso de anti-inflamatórios, corticoides e analgésicos em casos de pulpite aguda irreversível / Pain in dental emergency: anti inflammatory use, steroids and painkillers in cases of irreversible acute pulpitis

O objetivo deste estudo foi avaliar o uso do cetorolaco de trometamina 10mg sublingual 30 minutos antes do procedimento de biopulpectomia em pacientes com pulpite irreversível com relação à dor antes do procedimento e nas 48 horas subsequentes, a quantidade de medicação consumida no pós-operatório e tempo esperado para sua utilização. Também foi avaliada a influência da anestesia intrapulpar, o uso da automedicação analgésica antes da procura pelo atendimento e diferença entre gêneros sobre os níveis de dor pré e pós-operatória. Propôs-se avaliar também a necessidade da presença do antibiótico na medicação intracanal, comparando o Otosporin® com hidrocortisona. Participaram da pesquisa 608 pacientes que procuraram o Setor de Urgência Odontológica da Faculdade de Odontologia de Bauru ou o Setor Odontológico do Pronto Socorro Central da Prefeitura Municipal de Bauru, sendo que 34 completaram de forma adequada o protocolo previsto. Foram divididos em 4 grupos que receberam cetorolaco ou placebo como medicação pré-operatória e Otosporin® ou hidrocortisona como medicação intracanal. Foram anotados os valores de intensidade de dor, em uma escala visual analógica, antes da medicação pré-operatória, antes do atendimento, após o atendimento, 1, 2, 4, 12, 24, 48 horas após e quando houve necessidade de medicação pós-operatória para alívio da dor. Também foi anotado se o paciente havia se automedicado e qual a droga utilizada, se houve necessidade de anestesia intrapulpar, a quantidade de medicação consumida pelo paciente no pós-operatório e o tempo esperado para seu consumo. Dos resultados observou-se que os pacientes que receberam cetorolaco como medicação pré-operatória tiveram uma redução significativa da dor em 30 minutos, quando comparado ao placebo. Foi observado que o tempo necessário para a ingestão de medicamentos pós-operatórios não demonstrou diferença significativa entre os grupos, assim como na quantidade de medicação ingerida. O tempo decorrido entre a primeira e a última dose de medicação pós-operatória também não demonstrou diferença estatística. Com relação a anestesia intrapulpar, 78% dos pacientes necessitaram desta técnica, mas devido ao pequeno tamanho da amostra obtida, não foi possível correlacionar o seu uso com a utilização da medicação pós-operatória. Para os pacientes que se automedicaram previamente, não houve diferença significativa em relação à dor inicial. Quando os gêneros foram comparados, não foi possível observar uma diferença estatística significante entre eles com relação aos parâmetros estudados. Também foram descritos no trabalho os motivos de não inclusão dos 574 pacientes que foram abordados durante a realização deste estudo. Com base nos resultados, conclui-se que o cetorolaco diminuiu expressivamente o nível de dor durante a espera pelo atendimento, porém com relação ao tempo esperado pelo paciente para tomar a primeira dose de medicação pós-operatória, a última dose, a quantidade de comprimidos e a frequência de ingestão não demonstrou a mesma diferença. Também não houve diferença no nível de dor inicial entre os pacientes que se automedicaram e os que não fizeram uso dessa prática. Devido ao pequeno número da amostra, não foi possível encontrar uma correlação entre o uso da técnica anestésica intrapulpar e medicação pós-operatória, sugerindo mais estudos futuros.(AU)

The aim of this study was to evaluate the use of ketorolac tromethamine (10mg sublingual taken 30 minutes before pulpectomy in patients with irreversible pulpitis) in pain reduction immediately before the procedure and the 48 subsequent hours, postoperative consumption of analgesic drugs and time for its use. The influence of intrapulpal anesthesia, the use of analgesic self-medication prior to the demand for care and gender difference on the levels of pre- and postoperative pain was also evaluated. It was also proposed assess the need for antibiotic presence in the intracanal medicament, comparing Otosporin® with hydrocortisone. A total of 608 patients who presented to Dental Urgency Sector from Dental School of Bauru (USP) or Emergency Dental Sector from Bauru City Hall were invited to participate, and 34 completed properly planned protocol. They were distributed in 4 groups that received either ketorolac or placebo as preoperative medication and Otosporin® or hydrocortisone as intracanal medication. The rates of pain intensity were recorded by means of a visual analogue scale before pretreatment medication, immediately before the appointment, 1, 2, 4, 12, 24, 48 hours after the appointment, and when there was taken post medication for postoperative pain relief. It was also recorded if the patient had self medicated and which the drug used and, if there was need intrapulpal anesthesia, amount of ketorolac and rescue medication (paracetamol 750mg) consumed by the patient postoperative time and the waitng time for consumption. The results showed that patients receiving Ketorolac as preoperative medication had a significant reduction of pain in 30 minutes compared to placebo. It was observed that the time required for the intake of postoperative drug showed no significant difference between groups, as well as the amount of medication intake. The time elapsed between the first and last dose of postoperative medication also showed no statistical difference. Concerning intrapulpal anesthesia, 78% of patients required for this technique, but because of the small sample size obtained it was impossible to correlate their use with the use of postoperative medication. For patients who practiced self medication previously, there was no significant difference with respect to initial pain. When genders were compared, it was not possible to observe a statistically significant difference between them regarding the parameters studied. Were also described in the study the reasons of non-inclusion of 574 patients that were addressed during this study. Based on the results, it is concluded that ketorolac significantly decreased the level of pain during the waiting time, but with respect to the time length for the patient to take the first dose of postoperative medication, the last dose, the number of tablets and taken frequency did not show the same difference. There was no difference in the initial level of pain among patients who practiced self medication and those who did not use this practice. Due to the small sample size, it was not possible to find a correlation between the use of the anesthetic technique intrapulpal and postoperative medication, suggesting more future studies.(AU)

Artificial tears alone versus 0.45% ketorolac tromethamine with artificial tears for the treatment of acute viral conjunctivitis / Lágrima artificial versus cetorolaco de trometamina 0,45% associado à lagrima artificial no tratamento da conjuntivite viral aguda

Purpose: To evaluate the effects of preservativefree 0.45% ketorolac tromethamine and artificial tears (carboxymethylcellulose) compared with those of preservativefree artificial tears alone on the symptoms and signs of acute viral conjunctivitis. Methods: This was a randomized, doublemasked clinical trial that included 50 patients who were diagnosed with acute viral conjunctivitis and distributed into two groups (Group 0: artificial tears and Group 1: 0.45% ketorolac tromethamine + carboxymethylcellulose). The patients were instructed to use the medication 4 times daily. Signs (conjunctival hyperemia, chemosis, follicles, and secretion) and symptoms (general ocular discomfort, itching, foreign body sensation, tearing, redness, and swelling of the eyelids) were scored at baseline and on the third and seventh days of treatment using a standardized questionnaire and slitlamp anterior segment examination. Results: Both groups showed an improvement in the signs and symptoms of conjunctivitis in their follow-up visits. There was no significant difference in symptom and sign scores between Group 0 and Group 1 in the study visits (p>0.05). The frequency of side effects during treatment was similar between groups (p>0.05). Conclusions: Our findings indicate that 0.45% ketorolac tromethamine was not superior to the use of artificial tears in relieving the signs and symptoms of viral conjunctivitis. .

Objetivo: Avaliar o efeito do colírio de cetorolaco de trometamina 0,45% associado à carboximetilcelulose sem conservante em comparação ao uso isolado de lágrimas artificiais sem conservantes nos sinais e sintomas da conjuntivite viral aguda. Métodos: Ensaio clínico duplo-mascarado randomizado incluindo 50 pacientes com diagnóstico de conjuntivite viral aguda, distribuídos em dois grupos (Grupo 0: lágrimas artificiais e Grupo 1: cetorolaco 0,45% + carboximetilcelulose). Os pacientes foram orientados a utilizar a medicação quatro vezes ao dia. Sinais (hiperemia conjuntival, quemose, folículos e secreção) e sintomas (desconforto ocular geral, prurido, sensação de corpo estranho, lacrimejamento, vermelhidão e inchaço de pálpebras) foram avaliados na consulta inicial, no terceiro e no sétimo dia de tratamento utilizando um questionário padronizado e biomicroscopia de segmento anterior. Resultados: Ambos os grupos apresentaram melhora dos sinais e sintomas de conjuntivite nas visitas de reavaliação. Não foi observado diferença estatística na mudança dos escores dos sinais e sintomas entre o Grupo 0 e o Grupo 1 durante as visitas do estudo (p>0.05). A frequência de efeitos colaterais durante o tratamento foi similar entre os dois grupos (p>0.05). Conclusão: O uso do cetorolaco de trometamina 0,45% não se mostrou superior ao uso isolado de lágrimas artificiais no alívio dos sinais e sintomas da conjuntivite viral. .

Estimation of paracetamol present in a physical mixture containing ketorolac tromethamine solid dispersion with different polymers

Co-administration of combination of paracetamol with non-steroidal anti-inflammatory drugs showed synergistic effects leading to validation of clinical use of this combination in the treatment of majority of pain conditions. Controlled release drug delivery systems based on ketorolac tromethamine solid dispersion with Eudragit RS100, Eudragit RL100, and ethyl cellulose as polymers in a ratio of [1:3] drug:polymer with paracetamol in a physical mixture form were prepared in order to make use of the synergistic effect of this combination. An accurate simple and precise method was developed for simultaneous determination of ketorolac and paracetamol in the proposed solid dispersion preparation; a derivative spectrophotometric method was utilized. The method is based on measuring the first derivative amplitudes [1]D at 338 and 249 for ketorolac and paracetamol in 0.1 N HCl using 0.1 N HCl as a blank with linearity ranges of 2-10 micro g.ml[-1] and mean percent recovery not less than 99% and S.D not more than 0.03. Similarly, the first derivative values of absorbance [1]D at 304nm and 233 nm were measured for ketorolac and paracetamol respectively in phosphate buffer pH 7.4 using phosphate buffer pH 7.4 as a blank with concentration ranges of 2-10 and 3-10 micro g.ml[-1] for ketorolac and paracetamol respectively. The in-vitro drug release studies were performed for both drugs at different pH values. About 25% of ketorolac tromethamine combined with over 90% paracetamol were released at pH 1.2 whereas over 85% of ketorolac and 99% paracetamol were released at pH 7.4 all over the experimental time period. The obtained results can explain the synergistic effect of the proposed combination as well as the decreased gastrotoxic effects of ketorolac

Effect of preoperative use of topical prednisolone acetate, ketorolac tromethamine, nepafenac and placebo, on the maintenance of intraoperative mydriasis during cataract surgery: A randomized trial.

Purpose: To compare the effects of preoperative use of topical anti-inflammatory prednisolone acetate, ketorolac tromethamine, nepafenac and placebo, on the maintenance of intraoperative mydriasis during cataract surgery. Design: Randomized clinical trial. Materials and Methods: This single-center, masked, randomized clinical study comprised 140 patients scheduled for cataract surgery. Patients (35 in each group) were randomized to receive placebo, prednisolone acetate, ketorolac tromethamine 0.4% or nepafenac. These eye drops were administered three times daily for the two days prior to surgery. The pupillary diameters were measured by the surgeon using a compass prior to the corneal section and at the end of surgery. The primary outcome was the number of patients with pupil ≥ 6mm at the end of the surgery; the secondary outcome was the number of patients with pupil ≥ 6mm at the beginning of the surgery. Results: All the patients achieved pupil ≥ 6mm at the beginning of the surgery. The number of patients in the prednisolone (29/35), nepafenac (31/35) and ketorolac (30/35) groups with pupil ≥ 6mm was greater than in the placebo group in the maintenance of intraoperative mydriasis (19/35 – P =0.003). There was no statistical difference among the prednisolone, nepafenac and ketorolac groups in the maintenance of intraoperative mydriasis (P =.791). There were no complications during surgery or related to the preoperative use of the eye drops. Conclusion: Preoperative use of ketorolac, prednisolone and nepafenac was effective in maintaining intraoperative mydriasis when compared with placebo.

Evaluation of ketorolac tromethamine as anti-inflammatory drug for topical applications in treatment of knee osteoarthritis

The non-steroidal anti-inflmmatory drugs [NSAIDs] are used as a classic treatment for painful rheumatic disorders of the knee such as osteoarthritis and rheumatoid arthritis. Ketorolac tromethamine [KT] is considered as a member of NSAIDs. It is a non-selective cycloxygenase COX inhibitor that is used in treatment of musculoskeletal and joint disorders. Because KT appears to be associated with a higher incidence of adverse effects mainly irritation to the stomach, change in kidney and liver functions, its use is restricted for the treatment of patients for whom other NSAIDs have been ineffective. The main problems associated with the frequent administration of KT could be overcome by alternative routes of administration. This could be achieved by avoiding the contact between the drug and the stomach through formulating the drug in topical formulations and this was the aim of this work. Seventy osteoarthritis patients were selected and were classified into three groups, KT group [24 patients], piroxicam group [23 patients] and placebo group [23 patients]. Efficacy assessments were done by using the Western Ontario and McMasters Individual Osteoarthritis Index [WOMAC-OA] and the WOMAC Composite Index [WOMAC-CI] for pain, stiffness, and physical functions. Tolerability assessments were done by recording any adverse effects at each visit. All adverse effects or unexpected events were recorded in the case record forms. During the study, 8 patients were lost to follow up 2 from piroxicam group, 3 from KT group and 3 from placebo group. The obtained results indicated that, there was no significant difference in efficacy between KT gel and piroxicam gel [p>0.05] in treatment symptoms of osteoarthritis patients. While there was significant difference between either KT gel or piroxicam gel and placebo gel [p<0.05]. No adverse effects were recorded in all groups within the duration of study except two patients in of KT group and one patient in placebo group showed mild skin irritation [erythema]. The clinical evaluation revealed that, therapy with topical KT in carbopol 934 gel was successful to a great extent and produced high efficacy and safety in improving patients symptoms of osteoarthritis of the knee

Controle da dor pós-operatória em odontologia com cetorolaco de trometamol / Control of postoperative pain in dentistry with ketorolac of trometamol

O controle da dor e da inflamação pós-operatória são constantes preocupações dos cirurgiões, bem como o bem-estar do paciente após o ato cirúrgico, esses fatores estão intimamente ligados ao sucesso dos procedimentos e técnicas aplicadas. O cetorolaco é um anti-inflamatório não esteroidal (AINE) não seletivo, que age indistintamente sobre as cicloxigenases 1 e 2 e está indicado no tratamento da dor pós-operatória ou processos dolorosos de intensidade moderada a grave. Esta revisão de literatura se propôs a elucidar os efeitos analgésicos e anti-inflamatórios do cetorolaco de trometamol aplicado tanto de forma preventiva quanto pre-emptiva no tratamento da dor, bem como suas reações adversas, apresentando vantagens e desvantagens deste fármaco. Diante da revisão de literatura abordada, os autores concluíram que: a analgesia pre-emptiva deve ser feita sempre que possível; o cetorolaco de trometamol apresenta maior eficácia analgésica que os opióides, porém, deve ser usado em curto prazo, pelo risco de desenvolver doenças gastrointestinais, além do cuidado da sua indicação que segue as recomendações comuns a todos os AINES empregados em odontologia.

The pain control and postoperatory inflammation are constant concerns of surgeons, as well as the welfare of the patient after surgery, these factors are closely linked to the success of the procedures and techniques. Ketorolac is a non steroid anti-inflammatory drug (NSAID) non-selective, which acts indiscriminately on cyclooxygenase 1 and 2 and is indicated for the treatment of postoperative pain or painful processes of moderate to severe intensity. This literature review aimed to elucidate the analgesic and anti- inflammatory ketorolac trometamol applied as a preventive and preemptive treatment of pain and its adverse reactions, presenting advantages and disadvantages of this drug. Given the literature review addressed, the authors concluded that: preemptive analgesia should be performed whenever possible; ketorolac trometamol shows greater efficacy than opioids, however, should be used in short term, at risk of developing gastrointestinal diseases, beyond the care of his statement following the recommendations common to all NSAIDs used in dentistry.

Preemptive Analgesic Effect of Topical NSAIDS in Postoperative Pain Relief after LASEK

PURPOSE: To assess the preemptive analgesic effect of topical NSAIDs (0.5% ketorolac tromethamine, Acular) as postoperative pain relief in patients undergoing LASEK. METHODS: A prospective, randomized, placebo-controlled, paired eye study was performed. Patients undergoing LASEK were randomized to receive 0.5% ketorolac in one eye and 0.3% ofloxacin (placebo) in the contralateral eye at 30 minutes, 20 minutes, or ten minutes prior to LASEK. Pain was assessed using a visual analog scale of 0 to 10 in each eye 6, 12, 24, 36, 48 and 72 hours after surgery. Patients were also asked to assess the levels of glare, tearing and irritation using a visual analog scale from 0 to 10. RESULTS: A total of 62 eyes from 31 patients were enrolled in the present study. The mean postoperative pain score in the NSAID group was significantly lower than that in the placebo group at postoperative hours 6 (2.35 versus 4.97), 12 (2.52 versus 5.16), and 24 (3.84 versus 4.94) (p 0.05). Patients reported significantly less tearing and irritation in the NSAID-administered eye compared to those in the placebo eye after LASEK (p < 0.05). CONCLUSIONS: Preemptive administration of topical NSAIDs before LASEK was effective in reducing acute postoperative pain. Preemptive analgesia with topical NSAIDs may be a valuable treatment option for controlling postoperative pain following ocular surgery.

Injeção intravítrea de cetorolaco de trometamina em pacientes com edema macular diabético refratário à fotocoagulacão retiniana / Intravitreal injection of ketorolac tromethamine in patients with diabetic macular edema refractory to retinal photocoagulation

OBJETIVO: Avaliar o efeito em curto prazo da injeção intravítrea de cetorolaco de trometamina (500 µg/0,1ml) em pacientes com edema macular diabético refratário à fotocoagulação retiniana. MÉTODOS: Estudo prospectivo. Foram selecionados 20 pacientes com edema macular diabético refratário à fotocoagulação retiniana em ambos os olhos e apresentando acuidade visual (ETDRS) entre 20/50 e 20/200. Foi injetado em um olho de cada paciente, pela via intravítrea, 500 µg em 0,1 ml de cetorolaco de trometamina, sem conservante. O olho contralateral serviu de controle. Exames oftalmológicos, que incluíram a acuidade visual (ETDRS) com melhor correção, a aferição da pressão intraocular e a tomografia de coerência óptica, foram realizados em 3 etapas: antes da aplicação, após uma semana e, posteriormente após um mês do tratamento. RESULTADOS: Houve diferença estatisticamente significativa na acuidade visual (ETDRS) ao longo do tempo, havendo uma melhora na visão do olho tratado (p=0,039) quando comparado com o olho contralateral. Não foram encontradas diferenças estatisticamente significativas na avaliação da pressão intraocular (p=0,99), espessura foveal (p=0,86) e volume macular total (p=0,23) no decorrer do período. CONCLUSÃO: Pacientes com edema macular diabético refratário à fotocoagulação apresentaram melhora da acuidade visual ao longo de um mês com diferença estatisticamente significativa quando comparados com o olho controle. Não foram encontradas diferenças estatisticamente significativas na pressão intraocular, espessura foveolar e volume macular total entre os olhos tratados e os olhos controle.

PURPOSE: To evaluate the effect of a single dose of intravitreous injection of ketorolac tromethamine (500 µg/0.1 ml) in patients with diabetic macular edema refractory to retinal photocoagulation. METHODS: Prospective study. Twenty patients with bilateral diabetic macular edema and ETDRS best-corrected visual acuity between 20/50 and 20/200 were selected. Patients who had other ocular diseases or previous eye surgery were excluded. Preservative-free ketorolac tromethamine was injected intravitreally (500 µg in 0.1 ml) in 20 eyes; fellow eyes served as controls. Ophthalmic examinations included ETDRS best-corrected visual acuity, measurement of intraocular pressure and optical coherence tomography. The examinations were performed preoperatively, 1 week and 1 month postoperatively. RESULTS: A statistically significant increase in visual acuity over time in the treated eye compared with the fellow eye was noted (p=0.039). There were no statistically significant differences in the assessment of intraocular pressure (p=0.99), foveal thickness (p=0.86) and macular volume (p=0.23) during the period. CONCLUSION: Patients with diabetic macular edema refractory to photocoagulation showed improvement in visual acuity over a one month period with a statistically significant difference when compared with the control eye. There were no statistically significant differences in intraocular pressure, foveolar thickness and macular volume between the treated and control eyes.

Comparison of ketorolac tromethamine and prednisolone acetate in preventing surgically induced miosis during cataract surgery

The aim of this study was to compare the efficacy and safety of topical prednisolone acetate 1% and topical ketorolac tromethamine 0.5% in the maintenance of pupillary mydriasis during cataract surgery. Fifty patients were enrolled in this prospective, partially masked and randomised study. They were assigned to receive topical treatment with either prednisolone acetate [n=25] or ketorolac tromethamine [n=25], starting 24 hours before cataract extraction [either routine extracapsular cataract extraction or phacoemulsification]. One drop of the study medication was instilled every 6 hours for a total of 4 drops. No epinephrine was used in the intraoperative irrigation solution. Pupil diameter was measured three different times during surgery. To ensure participant safety, biomicroscopy, ophthalmoscopy, intraocular pressure, adverse events and visual acuity were also monitored. The mean pupil diameter change from the time of the pre-incision until after cortical irrigation and aspiration and lens implantation was significantly less with ketorolac than with prednisolone [P=0.003]. Consequently, mean pupil diameter after cortical irrigation and aspiration and lens implantation was significantly greater with ketorolac than with prednisolone [P<0.0001]. No significant differences between groups were observed in the pupil diameter before the first incision [P=0.244], nor after administration of a miotic agent [P=0.505]. Safety variables were comparable and no drug-related adverse events were reported. Ketorolac tromethamine 0.5% and prednisolone acetate 1% solutions were equally well tolerated without related adverse events, but ketorolac was better in preventing surgically induced miosis

Preparation, characterization and in-vitro release of controlled release ketorolac tromethamine cellulose acetate butyrate microspheres

The purpose of this study was to prepare and characterize controlled release ketorolac tromethamine microspheres. To achieve this goal, cellulose acetate butyrate microspheres loaded by ketorolac tromethamine were prepared by the emulsion solvent evaporation method. The prepared ketorolac tromethamine microspheres were evaluated for their production yields, particle size distribution, morphology, drug content and drug release characteristics. Thermal Gravimetric Analysis [TGA] were performed on the drug polymer systems in order to shed a light on the possibility of solid state changes of ketorolac tromethamine with CAB. A Box-Behnken design was selected for formulating ketorolac tromethamine microspheres with revolution per minute [X1], drug-polymer ratio [X2] and span 80 percent [X3] as independent variables. Three levels of the independent variables were used which equal to-1, 0 and +1 for the above design. The values of the corresponding variables were 500, 700 and 900 rpm for the machine speed; 1:1, 1:2 and 1:3 for drug-polymer ratio; 1%, 1.5% and 2% [w/w] for span 80 percent

Formulation and evaluation of novel mucoadhesive ketorolac tromethamine liquid suppository

Ketorolac tromethamine (KT) loaded mucoadhesive liquid suppository was prepared as a site-specific mucoadhesive rectal dosage form. Poloxamer mixture formed of 21P407 and 9P188 were used as liquid suppository base. In-vitro release rate of KT from liquid suppository was studied and compared to that from conventional suppository. The safety of the prepared suppository on GIT was conducted; hepatotoxicity of KT after 5 days of administration of liquid suppository was evaluated histologically and biochemically. The levels of liver enzymes alanine aminotransferase (ALT); aspartate amino transferase (AST); alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) were used as the biochemical markers of liver damage. The results obtained revealed that the addition of KT increased the gelation temperature of poloxamer gel and reduced the gel strength and the mucoadhesive force. The study of the release rate of KT from liquid suppository was significantly higher than from conventional suppositories. Histological pictures of the GI tissues indicated no pathological damage after 5 days of rectal administration compared to oral administration. Also; it was revealed that no hepato-cellular damage occurred after administration of liquid suppository; unlike oral administration; which produced certain hepato-toxicity. The administration of KT liquid suppository did not significantly increase the basic levels of ALT and AST when compared to the control. On the other hand; the administration of KT oral solution in a dose of 10 mg/kg body weight/day for 5 days significantly increased serum ALT and AST levels; thus; KT liquid suppository in poloxamer gel was a convenient; safe and effective rectal dosage form for administration with lower hepato-toxic effect

Usefulness of Modified Intravenous Analgesia: Initial Experience in Uterine Artery Embolization for Leiomyomata

PURPOSE: We wanted to evaluate the usefulness of modified intravenous analgesia for the management of pain during uterine artery embolization for leiomyomata. MATERIALS AND METHODS: Between April 2004 and July 2004, 15 patients with symptomatic fibroids underwent uterine artery embolization and pain management. Except the three patients for whom the Visual Analogue Scale (VAS) score was not obtained, twelve patients were included in this study. For pain management, epidural PCA (Patient Controlled Analgesia) was used in two patients, intravenous PCA was used in two patients and modified intravenous analgesia injection was used in eight patients. For all the patients, we used the 2.8 Fr coaxial microcatheter and 500-710 μm PVA particles for the embolic materials. The protocol of the modified intravenous analgesia injection was as follow, 1) prior to femoral artery puncture, 30 mg of ketorolac tromethamine (Tarasyn) was injected via an intravenous route. 2) At the time that the one side uterine artery embolization was finished, normal saline mixed 150 mg meperidine (Demerol) was administered through the side port of the intravenous line that was used for hydration. 3) Additional ketorolac tromethamine 30 mg was injected after 6 hour. The VAS score and side effects were then checked. After 12 hours, the VAS score was rechecked. If the VAS score was above 4, this was considered as failure of pain management. The VAS scores, complications and side effects for the modified intravenous analgesia injection were compared with that of IV PCA and epidural PCA. RESULTS: The average VAS score of the modified intravenous analgesia injection, intravenous PCA and epidural PCA was 1.4, 1 and 0, respectively; the number of additional intramuscular injections of analgesia was 0.5, 0.5 and 0, respectively. All the patients who underwent epidural PCA had back pain at the puncture site and 1 patient who underwent modified intravenous analgesia injection experienced mild dyspnea, but they easily recovered with such conservative treatment as an oxygen supply. No serious side effects or complications developed from the modified intravenous analgesia injection. CONCLUSION: Modified intravenous analgesia injection is well tolerated for the pain management of uterine fibroid embolization and it is a relatively inexpensive, safe method as used in our radiologic practice.

Patient-Controlled Analgesia Using Accufuser-plus kit(R) after Arthroscopic Rotator CuffRepair: Subacromial Catheter vs Intravenous Injection / 대한정형외과학회잡지

PURPOSE: To compare the efficacy of a patient-controlled subacromial with intravenous analgesia following arthroscopic rotator cuff repair. MATERIALS AND METHODS: In this prospective study, 40 cases of arthroscopic rotator cuff repair who received patient-controlled analgesia by Accufuser-plus kit(R) were analyzed. There were 21 men and 19 women with a mean age of 54 years (range, 33 to 73). The patients were divided into two groups, one (20 cases in each) receiving subacromial infusion with 0.5% bupivacaine and the other receiving an intravenous infusion with fentanyl and ketorolac tromethamine. A visual analog scale (VAS) was used to record the patient's level of pain every 12 hours until the first 72 hours after surgery, and for 48 hours after the patient-controlled analgesia was stopped. RESULTS: The mean preoperative VAS during motion was 6.8 in the subacromial infusion group and 5.8 in the intravenous infusion group. The immediate postoperative VAS was 7.6 and 7.4. The subacromial infusion showed significantly better results than the intravenous infusion in 24 hours, 48 hours at rest and 48 hours during motion. After the patient-controlled analgesia was stopped, the VAS increased for the first 12 hours but decreased thereafter. Acromioplasty did not affect the results and the number of supplemental analgesic injections during patient-controlled analgesia was similar in the two groups. Three cases in the intravenous infusion group gave up the patient-controlled analgesia due to transient hypotension, nausea and vomiting. CONCLUSION: Patient-controlled analgesia using Accufuser-plus kit(R) after an arthroscopic rotator cuff repair showed that a subacromial infusion is a faster and more effective method of decreasing the level of postoperative pain than an intravenous infusion with less complications.

Investigação experimental da utilidade da medicação no pós-operatório em cirurgia refrativa / Experimental investigation of postoperative use of medication in refractive surgery

OBJETIVO: Isolar microrganismo em microceratótomo, induzir ceratite infecciosa avaliando a resposta terapêutica. MÉTODOS: Foram realizadas coletas consecutivas de material a partir do microceratótomo usado rotineiramente para cirurgia refrativa em olhos humanos durante um período de 8 dias. Preparou-se uma diluição segundo a escala de MacFarland para inocular na córnea de cobaias. Utilizaram-se oito animais, injetou-se 10 µl no estroma corneano de ambos os olhos. No olho direito não se instilou medicamento (grupo 1) e no olho esquerdo instilou-se ciprofloxacina 0,3 por cento associado a dexametasona a 0,1 por cento e trometamina de cetorolac de 4 em 4 horas por 24 horas (grupo 2). Após este período as cobaias foram sacrificadas e as córneas divididas, sendo uma metade enviada para análise microbiológica e outra para histopatologia. RESULTADOS: No grupo sem tratamento, todas as 8 amostras foram positivas, ao passo que no grupo tratado, 3 desenvolveram cultura positiva para Staphylococcus aureus (p=0,0128). A avaliação histopatológica de polimorfonucleares e monomorfonucleares no estroma mostrou que eram menos numerosos no grupo tratado (grupo 2), com p=0,0203 e p=0,0051, respectivamente. CONCLUSAO: Este estudo portanto sugere que o uso de antibiótico de amplo espectro associado a antiinflamatório tem efeito significativo na diminuição do processo inflamatório e infeccioso em possível contaminação intra-estromal após cirurgia refrativa.

Initial Experience of Retroperitoneal Laparoscopic Nephroureterectomy for Upper Urinary Tract Transitional Cell Carcinoma / 대한비뇨기과학회지

PURPOSE: We report our experience of retroperitoneal laparoscopic nephroureterectomy (RLNUx) in 10 consecutive patients with an upper tract transitional cell carcinoma, and compare the results to those of a contemporary group of patients who underwent an open nephroureterectomy (ONUx). MATERIALS AND METHODS: The records of 10 and 17 patients who underwent RLNUx and ONUx, respectively, for an upper urinary tract transitional cell carcinoma between February 1988 and February 2004, were reviewed. RESULTS: The RLNUx, for the upper urinary tract transitional cell carcinoma, was successfully performed in all patients. Patients who underwent RLNUx had significantly less blood loss (308 versus 626.4cc, p=0.002) and consumption of ketorolac tromethamine for postoperative pain control (128.5 versus 215mg, p=0.001). However, there were no significant differences between the RLNUx and ONUx regarding the mean operative time (250 versus 222.6 minutes, p=0.081), interval to resuming oral intake (1.7 versus 1.8 days, p=0.530) and hospital stay (9.3 versus 9.8 days, p=0.300). Atelectasis and postoperative bleeding occurred in 1 RLNUx patient and atelectasis occurred in 3 ONUx patients. During average follow-ups of 19 and 25.9 months, for the RLNUx and ONUx, respectively, 1 and 2 patients had lymph node metastasis. Two patients with concomitant bladder tumors who had undergone transurethral resection at the time of the RLNUx, and two who had undergone ONUx had recurrent transitional cell carcinoma of the bladder. CONCLUSIONS: Based on our experience, we believe that RLNUx is a feasible treatment option for patients with an upper tract transitional cell carcinoma. However, long-term follow-up is necessary to confirm the efficacy for patients with transitional cell carcinomas of the renal pelvis and ureter.

Topical cyclosporine 0.5 per cent and preservative-free ketorolac tromethamine 0.5 per cent in vernal keratoconjunctivitis.

A prospective, randomized cross-over study was conducted in patients with vernal keratoconjunctivitis, successfully treated with cyclosporine, to evaluate the efficacy of cyclosporine 0.5 per cent compared with preservative-free ketorolac tromethamine 0.5 per cent. Patients received topical cyclosporine in both eyes along with an assessment of the severity of their conjunctivitis. In cyclosporine-treated patients, medication was discontinued 1 week before evaluation, then the medication was started for I month, and washed out 1 week before the other drug was started. Symptoms of itching, foreign body sensation, tearing, photophobia, discharge, burning, conjunctival injection, chemosis, giant papilla, keratopathy and intraocular pressure were evaluated weekly. There was a statistically significant decrease in all symptoms of cyclosporine-treated eyes at day 7, 14 and 30 and all signs at day 21 and 30. In ketorolac-treated eyes, there was a significant difference in itching, foreign body sensation, photophobia, tearing, mucous discharge, all symptoms, chemosis, giant papillae and conjunctival injection at day 7, and overall symptoms at day 14. Compared to cyclosporine-treated eyes at day 7, kotorolac-treated eyes had significantly fewer symptoms. Topical cyclosporine 0.5 per cent reduces symptoms and signs slower than preservative-free ketorolac tromethamine 0.5 per cent.

Estudo comparativo da eficácia do uso de prednisolona e cetorolaco de trometamina tópicos após cirurgia de estrabismo / Comparison of the efficacy of topical prednisolone and ketorolac tromethamine after strabismus surgery

OBJETIVO: Avaliar os resultados do uso de antiinflamatório näo hormonal (AINH) no controle da inflamaçäo no pós-operatório de estrabismo, comparando-se com corticóide tópico. MÉTODOS: Selecionaram-se exclusivamente pacientes submetidos a recuo-ressecçäo em um só olho. Os dois grupos de pacientes usaram o mesmo antibiótico, sendo que para um grupo foi prescrito prednisolona 0,12 por cento e para o outro cetorolaco de trometamina. Eles foram avaliados quanto a hiperemia, edema, conforto e variaçäo da pressäo intra-ocular, até o 21º dia de pós-operatório. RESULTADOS: Foram 27 pacientes, sendo 15 no grupo de AINH e 12 no de corticóide. Com relaçäo a edema, conforto e PIO näo houve variaçäo entre os grupos. Porém, no grupo com AINH houve 5 (33,3 por cento) casos de hiperemia conjuntival de ++/4 no 21º dia de pós-operatório e três (20 por cento) de granuloma. Entre os pacientes com corticóide só se observou 1 (8,3 por cento) caso de hiperemia de ++/4 ao término do tratamento e nenhum de granuloma. CONCLUSÄO: Para cirurgias de recuo-ressecçäo, procedimentos que parecem induzir maior resposta inflamatória, o uso de AINH näo é aconselhável

Comparison of topical prednisolone acetate, ketorolac tromethamine and fluorometholone acetate in reducing inflammation after phacoemulsification.

AIMS: To compare the efficacy and ocular adverse effects of topical prednisolone acetate, ketorolac tromethamine, and fluorometholone acetate in reducing inflammation after phacoemulsification. METHOD: One hundred and twenty eyes were enrolled in a prospective, investigator-masked, randomized controlled trial. Each drug was prescribed 4 times a day for 28 days. The following data were recorded weekly: visual acuity, intraocular pressure, slit lamp biomicroscopy, grading of cells and flare in the anterior chamber, and ocular symptoms. RESULTS: The number of eyes with a minimal amount of cells in the anterior chamber in the ketorolac group was less than the prednisolone group on day 7 (11:20, p = 0.008) and day 14 (23:31, p = 0.015), and than fluorometholone group on day 7 (11:21, p = 0.011). Intraocular pressure in the prednisolone group was higher than the ketorolac group on day 21 (14.6:12.2 mmHg, p = 0.016). One eye in the prednisolone group had intraocular pressure of 32 mmHg. Burning sensation was reported frequently in the ketorolac group. CONCLUSION: All 3 drugs were effective in reducing post-operative inflammation. The efficacy of prednisolone acetate and fluorometholone acetate was comparable. Ketorolac tromethamine showed less efficacy than corticosteroids, however, it did not induce ocular hypertension.