The need for opioid in the postoperative analgesia of dogs undergoing hemilaminectomy due to intervertebral disc extrusion

ABSTRACT: The aim of this study was to evaluate the postoperative analgesic effect of protocols with and without the opioid methadone in dogs with intervertebral disc extrusion undergoing decompressive surgery. Sixteen paraplegic dogs with preserved nociception underwent hemilaminectomy/disc fenestration and were randomly assigned to two groups. The analgesic protocol consisted of methadone, meloxicam and dipyrone in Group I (G1), and meloxicam and dipyrone in Group II (G2). The animals were blindly assessed by two observers, using the visual analogue scale (VAS) and the short-form Glasgow Composite Measure Pain Scale (CMPS-SF). Assessments occurred every 2 hours during first 24 hours post-surgery, and every 4 hours afterwards. There was no statistical difference among groups regarding pain scores or analgesic rescues. Both analgesic protocols provided analgesia in the initial 48 hours postoperatively, demonstrating that opioids are not necessary in the postoperative period of dogs undergoing hemilaminectomy and disc fenestration.

RESUMO: O objetivo deste estudo foi avaliar a analgesia pós-operatória de protocolos com e sem o opioide metadona em cães com extrusão de disco intervertebral submetidos à descompressão cirúrgica. Dezesseis cães paraplégicos com presença de nocicepção foram submetidos à hemilaminectomia/fenestração de disco e distribuídos aleatoriamente em dois grupos. No Grupo I (G1), o protocolo analgésico consistiu em metadona, meloxicam e dipirona e, no Grupo II (G2), por meloxicam e dipirona. Os pacientes foram avaliados de maneira cega por dois avaliadores, com base na escala visual analógica (EVA) e na escala simplificada composta de dor de Glasgow (CMPS-SF). As avaliações ocorreram a cada 2 horas durante as primeiras 24 horas de pós-operatório e, por mais 24 horas, a cada 4 horas. Não houve diferença estatística entre os grupos avaliados em relação à escores de dor e nem a necessidade de resgate analgésico. Ambos os protocolos promoveram analgesia nas 48 horas iniciais de pós-operatório, demonstrando não haver a necessidade do uso de opioide em cães submetidos à hemilaminectomia e fenestração de disco.

The need for opioid in the postoperative analgesia of dogs undergoing hemilaminectomy due to intervertebral disc extrusion / A necessidade de opioide na analgesia pós-operatória de cães submetidos à hemilaminectomia devido à extrusão do disco intervertebral

The aim of this study was to evaluate the postoperative analgesic effect of protocols with and without the opioid methadone in dogs with intervertebral disc extrusion undergoing decompressive surgery. Sixteen paraplegic dogs with preserved nociception underwent hemilaminectomy/disc fenestration and were randomly assigned to two groups. The analgesic protocol consisted of methadone, meloxicam and dipyrone in Group I (G1), and meloxicam and dipyrone in Group II (G2). The animals were blindly assessed by two observers, using the visual analogue scale (VAS) and the short-form Glasgow Composite Measure Pain Scale (CMPS-SF). Assessments occurred every 2 hours during first 24 hours post-surgery, and every 4 hours afterwards. There was no statistical difference among groups regarding pain scores or analgesic rescues. Both analgesic protocols provided analgesia in the initial 48 hours postoperatively, demonstrating that opioids are not necessary in the postoperative period of dogs undergoing hemilaminectomy and disc fenestration.(AU)

O objetivo deste estudo foi avaliar a analgesia pós-operatória de protocolos com e sem o opioide metadona em cães com extrusão de disco intervertebral submetidos à descompressão cirúrgica. Dezesseis cães paraplégicos com presença de nocicepção foram submetidos à hemilaminectomia/fenestração de disco e distribuídos aleatoriamente em dois grupos. No Grupo I (G1), o protocolo analgésico consistiu em metadona, meloxicam e dipirona e, no Grupo II (G2), por meloxicam e dipirona. Os pacientes foram avaliados de maneira cega por dois avaliadores, com base na escala visual analógica (EVA) e na escala simplificada composta de dor de Glasgow (CMPS-SF). As avaliações ocorreram a cada 2 horas durante as primeiras 24 horas de pós-operatório e, por mais 24 horas, a cada 4 horas. Não houve diferença estatística entre os grupos avaliados em relação à escores de dor e nem a necessidade de resgate analgésico. Ambos os protocolos promoveram analgesia nas 48 horas iniciais de pós-operatório, demonstrando não haver a necessidade do uso de opioide em cães submetidos à hemilaminectomia e fenestração de disco.(AU)

Efectividad de la indometacina vs analgésico habitual en el tratamiento del dolor posthisterectomía / Effectiveness of using indomethacin vs usual analgesic in the management of postoperative pain in hysterectomy

Resumen: OBJETIVO: Determinar la efectividad de la indometacina, por vía rectal, en el tratamiento del dolor posthisterectomía versus paracetamol o metamizol administrados por vía intravenosa. MATERIALES Y MÉTODOS: Estudio experimental, comparativo y prospectivo llevado a cabo en el Hospital Central del Estado de Chihuahua entre noviembre y diciembre de 2019. Criterios de inclusión: pacientes histerectomizadas, con expediente clínico completo y de cualquier edad. Criterios de exclusión: pacientes con alteraciones en el umbral del dolor, inconsistencias en el expediente, histerectomía total no ginecológica. Criterios de eliminación: pacientes con limitantes en la información que no permitieron relacionar la variable dependiente con la independiente. El seguimiento del dolor referido se efectuó con la escala análoga del dolor y valoraciones a las 12 y 24 horas posteriores a la cirugía. RESULTADOS: Se reunieron 141 pacientes, que se dividieron en tres grupos. Grupo 1: metamizol intravenoso e indometacina por vía rectal (n = 24). Grupo 2: paracetamol intravenoso e indometacina por vía rectal (n = 19). Grupo 3: paracetamol y metamizol intravenosos (n = 98). La mayoría de las pacientes de los grupos 1 y 2 reportaron, a las 24 h, una escala visual análoga menor de 3 vs las del grupo 3. Diez de 98 pacientes requirieron tratamiento en el servicio de Anestesiología. CONCLUSIÓN: La administración de indometacina por vía rectal a pacientes histerectomizadas demostró menor dolor que con metamizol y paracetamol, y evolución clínica y alta hospitalaria más temprana.

Abstract: OBJECTIVE: To determine the effectiveness of indomethacin in the treatment of post-hysterectomy pain versus paracetamol or metamizole administered intravenously. MATERIALS AND METHODS: Experimental, comparative and prospective study at the Central Hospital of the State of Chihuahua, period November to December 2019, patients undergoing hysterectomy with complete clinical record, any age. Patients with alterations in the pain threshold, inconsistencies in the file, total non-gynecological hysterectomy were excluded, patients with information limitations were eliminated, which did not allow to relate the dependent variable, with the independent one. RESULTS: 141 patients were collected, which were divided into three groups. Group 1: intravenous metamizole and indomethacin rectally (n = 24). Group 2: intravenous paracetamol and indomethacin rectally (n = 19). Group 3: intravenous paracetamol and metamizole (n = 98). Most of the patients in groups 1 and 2 reported, at 24 hours, a visual analog scale of less than 3 vs those of group 3. Ten of 98 patients required treatment in the Anesthesiology service. CONCLUSION: The administration of indomethacin rectally in postoperative patients of hysterectomy has been shown to reduce pain more effectively than conventional analgesics such as metamizole and paracetamol, relating to clinical evolution and early hospital discharge.

Síndrome de Nicolau. Manejo conservador. Caso clínico / Nicolau syndrome, Conservative management: Clinical case

Introducción: el síndrome de Nicolau, embolia cutis o dermatitis livedoide, es una reacción adversa poco frecuente a la administración de inyección intramuscular, subcutánea o intraarticular de medicamentos, inicia con dolor intenso y eritema que evoluciona a lesión livedoide que se torna hemorrágica, progresa a necrosis isquémica de piel y tejidos más profundos. Caso clínico: niño de 7 meses de edad, luego de inyección intramuscular de metamizol sódico presenta llanto continuo, seguido de lesión purpúrica afectando espalda, glúteo, muslo y pierna derechos, evolucionando hasta cicatrización total en 18 semanas. Conclusión: el síndrome de Nicolau, condición iatrogénica por inyección de múltiples medicamentos, produce lesión necrótica en área de irrigación de vasos afectados. El conocimiento de este síndrome facilitaría su prevención, al igual que su diagnóstico y manejo tempranos

Introduction: Nicolau syndrome, embolism cutis or livedoid dermatitis, is a rare adverse reaction to the administration of intramuscular, subcutaneous or intra-articular injection of drugs, begins with intense pain and erythema that progresses to a livedoid lesion that becomes hemorrhagic, progresses to ischemic necrosis of skin and deeper tissues. Clinical case: A 7-month-old boy, after intramuscular injection of sodium metamizole, presented continuous crying followed by a purpuric lesion affecting the right back, gluteus, thigh and leg, evolving to total healing in 18 weeks. Conclusion: Nicolau Syndrome, iatrogenic condition by injection of multiple drugs, produces necrotic lesion in irrigated area of affected vessels. The knowledge of this syndrome would facilitate its prevention, as well as its early diagnosis and management.

Respondiendo a la interrogante: ¿el metamizol es o no un antiinflamatorio no esteroideo? / Answering the question: is metamizole a non-steroidal anti-inflammatory or not?

Resumen: El objetivo de este artículo es determinar la importancia del metamizol como analgésico en México, al conocer la frecuencia de su uso y los mecanismos de acción y así clasificar adecuadamente al medicamento dentro de la farmacopea de analgésicos. Pocos fármacos generan discusión sobre su filiación, pero el metamizol, desde que salió al mercado en 1922 hasta el día de hoy, se mantiene sin definirse claramente. Comúnmente cuando se busca una clasificación de los antiinflamatorios no esteroideos (AINE), se clasifica al metamizol dentro de los mismos como derivados de la pirazolona. Se debe comenzar entonces con los aspectos farmacológicos para relacionar las semejanzas y diferencias con otros AINEs y poder sacar conclusiones adecuadas. Aun así, el medicamento es de los más utilizados por los médicos en los hospitales de segundo y tercer nivel (82%), aunque la mayoría no sabe en realidad cuál es su mecanismo de acción (91%), por ello, la importancia de conocer el mecanismo de acción de este fármaco.

Abstract: The aim of this article is to know the importance of metamizol as analgesic in Mexico, knowing the frequency of their use and the mechanisms of action and to adequately classify the drug in the pharmacopoeia of painkillers. Few drugs generate discussion about their parentage but metamizol from that hits the market in 1922 until today, it has no clearly defined. Commonly when NSAIDs rated seeks to metamizol is classified within the same as pyrazolone derivatives. We then start with the pharmacological aspects and later to know the similarities and differences with other NSAIDs and can draw appropriate conclusions. Even so, the medicine is one of the most used by physicians in second and third level hospitals (82%), although most do not really know what their mechanism of action is (91%), so the importance of knowing the mechanism of action of this drug.

Identificación de reacciones adversas por dipirona en pacientes de un hospital de tercer nivel / Identification of adverse drug reactions in patients treated with dipyrone in a third level hospital

Resumen Introducción: la dipirona es un antipirético, analgésico y antiespasmódico, posicionado como una de las primeras opciones en el manejo del dolor. El objetivo de esta investigación fue establecer la incidencia de efectos adversos relacionados al uso de dipirona en pacientes internados en un hospital de tercer nivel en la ciudad de Pereira -Risaralda durante 2016. Métodos: estudio descriptivo que incluyó pacientes con cualquier efecto adverso relacionado con el uso de dipirona. Se utilizó la clasificación de reacciones adversas de Rawlins y Thompson. La relación de causalidad se calculó con la escala de Naranjo. Resultados: se evaluaron 59 pacientes con reacciones adversas por el uso de dipirona, con una edad media de 44,4 ± 21,6 años y el 52,5 % eran mujeres. La mayoría de las reacciones se presentaron en el servicio de cirugía (52,5 %). La indicación más frecuente para su uso fue traumatismo (39 %), seguida de algún procedimiento quirúrgico (25,4 %). La reacción reapareció en 28,8 % de los casos tras una nueva administración de dipirona en la misma hospitalización. Se presentó un caso de granulocitopenia. La incidencia de reacciones adversas fue 1,4 por cada 1 000 pacientes. Conclusión: las reacciones adversas relacionadas con el uso de dipirona son un hallazgo poco frecuente a pesar del amplio uso del medicamento. La toxicidad hematológica se debe tener en cuenta a la hora de prescribir dipirona. Se deben mejorar los protocolos de seguridad del paciente con el fin de disminuir las posibles reacciones adversas relacionados con la administración de medicamentos.

Abstract Background. Dipyrone is an antipyretic, analgesic and antispasmodic, positioned as one of the first options in pain management. The aim was to establish the incidence of adverse effects related to the use of dipyrone in patients hospitalized in a third level hospital in the city of Pereira- Colombia during 2016. Methods: A descriptive study that included patients with any adverse effect related to the use of dipyrone. The classification of adverse reactions of Rawlins and Thompson was used. The causal relationship was calculated with Naranjo scale. Results: A total of 59 patients were evaluated for adverse reactions with the use of dipyrone, with a mean age of 44.36 ± 21.6 years and 52.5% were women. The reactions occurred mainly in surgical patients (52.5%). The most frequent indication for its use was trauma in 39 % of cases, followed by some surgical procedure (25.4%). In 28.8% of the cases, the event reappeared after a new administration of dipyrone during the same hospitalization. A case of granulocytopenia was presented. The incidence of adverse events with dipyrone was 1.4 per 1000 patients. Conclusion: Adverse reactions related to the use of dipyrone are a rare finding despite the wide use of the drug. Hematological toxicity should be considered when prescribing dipyrone. Patient safety protocols should be improved in order to reduce possible adverse events related to the administration of medications.

Descripción y cuantificación de riesgos atribuidos a analgésicos antiinflamatorios no esteroides no selectivos consumidos por la población mexicana / Description and quantification of risks attributed to non-selective non-steroidal anti-inflammatory drugs consumed by Mexican population

Resumen OBJETIVO Analizar las reacciones adversas a medicamentos asociadas con la administración de antiinflamatorios no esteroides (AINEs) no selectivos reportadas al Centro Nacional de Farmacovigilancia durante el periodo 2011-2014. MATERIAL Y MÉTODO Estudio en el que para el análisis descriptivo se utilizó la base de datos del Centro Nacional de Farmacovigilancia 2011-2014 que contiene las reacciones adversas a medicamentos asociadas con la administración de analgésicos provenientes de los diferentes integrantes del Programa Permanente de Farmacovigilancia, que se agruparon de acuerdo con edad y sexo del paciente, procedencia de la reacción adversa a medicamentos, principio activo sospechoso, gravedad y causalidad de la reacción. RESULTADOS 4553 reacciones adversas a medicamentos se asociaron con la administración de un AINE (3.9%). El metamizol fue el más reportado con 21.1% del total de reacciones adversas registradas para este grupo de medicamentos. CONCLUSIONES El metamizol fue el medicamento con más reacciones adversas a medicamentos reportadas. Las reacciones dermatológicas de importancia (necrólisis epidérmica tóxica, síndrome de Stevens-Johnson y síndrome de Lyell) se manifestaron mayormente con nimesulida.

Abstract OBJECTIVE To analyze drug-adverse reactions related to the administration of non-selective non-steroidal anti-inflammatory drugs (NSAIDS) reported to the National Pharmacovigilance Center from 2011 to 2014. MATERIAL AND METHOD A study was done in which for the descriptive analysis was used the database of the National Pharmacovigilance Center 2011-2014 containing the drug-adverse reactions related to the administration of analgesic drugs coming from the different members of the Permanent Program of Pharmacovigilance, that were grouped according to: age and sex of patient, proceeding of the drug-adverse reaction, suspect active principle, severity and causality of reaction. RESULTS 4553 drug-adverse reactions were related to the administration of an NSAID (3.9%). Metamizol was the most reported with 21.1% of the total of adverse reaction registered for this group of drugs. CONCLUSIONS Metamizol was the drug with more drug-adverse reactions reported. The dermatological reactions of importance (toxic epidermal necrolysis, Stevens-Johnson syndrome and Lyell syndrome) were higher reported with nimesulide.

Cardiac complications in a metamizole-induced type I Kounis syndrome / Complicações cardíacas em síndrome de Kounis tipo I induzida por metamizol

ABSTRACT Kounis syndrome is defined as the coincidental occurrence of allergic reaction and acute coronary syndrome secondary to vasospasm. Anti-inflammatory drugs are included as one of the multiple causes. Current data available about this syndrome come from case reports. We present the case of a patient who suffered Kounis syndrome with cardiogenic shock and asystole after intravenous infusion of Metamizole, and in which no lesions were observed in coronariography.

RESUMO A síndrome de Kounis é definida como a ocorrência concomitante de reação alérgica e síndrome coronariana aguda secundária ao vasoespasmo. Os medicamentos anti-inflamatórios estão incluídos como uma das múltiplas causas. Os dados atuais disponíveis sobre essa síndrome são provenientes de relatos de caso. Relatamos o caso de um paciente que apresentou síndrome de Kounis com choque cardiogênico e assistolia após infusão intravenosa de metamizol e no qual não foram observadas lesões na coronariografia.

Eficacia y seguridad metamizol - tramadol en comparación metamizol - ketorolaco para manejo del dolor postoperatorio en colecistectomía laparoscópica / Metamizol efficacy and safety - metamizol tramadol in comparison -ketorolac for postoperative pain management in laparoscopic cholecystectomy

La Asociación Internacional para el Estudio del Dolor (IASP) define el dolor como una experiencia sensorial y emocional desagradable con daño tisular actual o potencial descrito en términos de dicho daño. El objetivo del presente estudio fue analizar la eficacia y seguridad de la combinación de metamizol - tramadol en comparación con el metamizol - ketorolaco en el manejo del dolor postoperatorio de colecistectomía laparoscópica del Hospital Obrero N° 2. Se realizó un estudio analítico, longitudinal, ensayo clínico aleatorizado. El análisis de los datos fue no paramétrico: las variables ordinales y nominales con tablas de frecuencia; variables continuas y discretas con medidas de posición, Escala Visual Analgésica (EVA) prueba de hipótesis U de Mann-Whitney mediante el programa SPSS® versión 22.5 para Windows. Los resultados mostraron que es eficaz y seguro la utilización de la asociación de esquema 1 (metamizol - tramadol) en comparación al esquema 2 (metamizol - ketorolaco) debido a que la EVA del dolor es significativa (p < 0,05) prueba de U de Mann-Whitney.Además, ambos esquemas de tratamiento tienen una conformidad analgésica satisfactoria. Sin embargo, tienen efectos adversos similares en ambos esquemas de tratamiento. Por lo tanto se acepta la hipótesis alternativa.

The International Association for the Study of Pain (IASP) defines pain as an unpleasant sensory and emotional experience with actual or potential tissue damage described in terms of such damage. The objetive of this study was to analyze the efficacy and safety of the combination of metamizol - tramadol compared to metamizol - ketorolac in postoperative pain management in laparoscopic cholecystectomy Hospital Obrero No. 2. An analytical, longitudinal study, clinical trial randomized.The analysis was nonparametric data: ordinal and nominal variables with frequency tables; continuous and discrete variables with position measurements,Visual Analgesic Scale (EVA) hypothesis test U Mann-Whitney through the program SPSS® version 22.5 for Windows. The results showed that it is effective and safe use of the association scheme 1 (metamizol - tramadol) compared to scheme 2 (metamizol - ketorolac) EVA because the pain is significant (p <0.05) U test Mann-Whitney. In addition, both schemes have a satisfactory analgesic treatment compliance. However, they have similar adverse effects in both treatment regimens. Therefore the alternative hypothesis is accepted.

Analgésicos en el paciente hospitalizado: Revisión de tema / Analgesics in hospitalized patients: Topic review

El dolor como experiencia subjetiva es de alta incidencia en el paciente adulto hospitalizado, por tal motivo el uso de analgésicos en estos pacientes tiene gran impacto en la evolución clínica y en la calidad de la estancia hospitalaria. Entre las opciones terapéuticas para el manejo del dolor se encuentran antiinflamatorios no esteroideos (AINEs), opioides, paracetamol, metamizol; los cuales se pueden administrar en diferentes formas farmacéuticas, que se adaptan a las condiciones de cada uno de los pacientes. Actualmente, el uso de opioides está siendo reevaluado, así como las técnicas de administración, entre las que se destacan la analgesia controlada por el paciente y la analgesia intervencionista (analgesia epidural, bloqueo de nervios periféricos y la infiltración local). El éxito de la terapia analgésica no solo consiste en el adecuado uso de los analgésicos, sino también en las estrategias usadas para objetivar el dolor; esto se consigue por medio de la aplicación de escalas para cuantificar el dolor, de las cuales se destacan la escala visual análoga, la escala verbal numérica y la de valoración verbal.

Pain as a subjective experience is high incidence in the adult hospitalized patient, so the use of analgesics in these patients has a high impact on their medical developments and their comfort during their hospital stay. Among the therapeutic options for pain management there are Non-Steroidal Anti- Inflammatory drugs (NSAIDs), Opioids, Paracetamol and Metamizol. Each has different pharmaceutical dosage forms to adjust to the condition of each patient. Currently the use of Opioids is being re-evaluated as well as the management techniques like patient-controlled analgesia and interventionist analgesia(epidural analgesia, peripheral nerve blocks and local infiltration). The success of analgesic therapy consists of the appropriate use of analgesics and in the strategies used to objectify the pain; this can be achieved with the implementation of scales to quantify the pain like the visual analogous scale, numeric verbal scale and the verbal assessment.

Bloqueo de la fascia iliaca frente al metamizol para analgesia preoperatoria en pacientes con fractura de cadera / Blocking of the iliac fascia compared to metamizol for preoperative analgesia in patients with hip fracture

Se efectuó un estudio de intervención terapéutica en 134 adultos mayores con fractura de cadera, operados en el Hospital Universitario "Dr. Ambrosio Grillo Portuondo" de Santiago de Cuba, desde noviembre del 2009 hasta igual periodo del 2012, a fin de evaluar el uso del bloqueo de la fascia iliaca frente al metamizol para el alivio del dolor agudo en el periodo preoperatorio. Se conformaron 2 grupos de estudio, ambos con 67 integrantes; a uno se le realizó el bloqueo con bupivacaína al 0,25 % y al otro se le administró metamizol intramuscular. Se utilizó la escala analógica visual para evaluar el alivio del dolor en reposo y al movimiento. Predominó el sexo femenino (64,2 %) y los pacientes de 81-90 años (38,8 %). A los 60 minutos de usar el bloqueo de la fascia iliaca se obtuvo mejoría evidente en los afectados, lo cual demostró su efectividad respecto al metamizol, tanto en posición de reposo como en movimiento.

A study of therapeutic intervention in 134 aged adults with hip fracture, operated in "Dr. Ambrosio Grillo Portuondo" University Hospital in Santiago de Cuba was carried out from November, 2009 to same period of 2012, in order to evaluate the use of the blocking of the iliac fascia compared to metamizol for the relief of the acute pain in the preoperative period. Two study groups were formed, both with 67 members; blocking with 0.25 % bupivacaína was carried out in one of them, and intramuscular metamizol was administered in the other one. The visual analogical scale was used to evaluate the relief of pain during rest and when there was movement. Female sex (64.2 %) and the 81-90 age group patients (38.8 %) prevailed. After 60 minutes of using the blockade of the iliac fascia, an evident improvement was obtained in the affected patients, demonstrating its effectiveness regarding metamizol, either during rest as during movement.

Comparative study of the pharmacopeial quality and dissolution profiles of generic and other drug forms of sodium metamizole (dipyrone) sold in Brazil / Comparação entre a qualidade farmacopéica e perfis de dissolução de medicamentos genéricos e similares de metamizol sódico (dipirona) comercializados no Brasil

In Brazil, in order for a pharmaceutical company to register a drug form as generic or ?similar? with the Brazilian food and drug agency (Anvisa), it must be proved bioequivalent to its innovatory branded form (reference drug). This requires comparative trials, carried out in conformity with official compendia (Brazilian Pharmacopeia or another officially recognized code). Additionally, according to the Anvisa resolution RDC 31/2010, the dissolution profile of the drug must be tested and compared with that of the branded reference, as a benchmark of quality. The aim of this study was to assess the quality of 500 mg sodium metamizole (dipyrone) tablets produced by seven different laboratories in Brazil: three generic drugs (G1, G2, G3), three (branded) similar drugs (S1, S2, S3) and their reference branded product (Novalgina®, Sanofi-Aventis, drug R). All tests were carried out by methods specified in the Brazilian Pharmacopeia 4th edition (Farmacopeia Brasileira IV). The following tests were performed: uniformity of mass, friability, disintegration time, hardness, assay, uniformity of dosage units, salicylic acid limit assay, dissolution and identification. The dissolution profile was also recorded, as recommended in RDC 31/2010. Whereas every sample was approved in all the Farmacopeia Brasileira IV tests, the results in the dissolution profile test showed that four of the test drugs (G1, G2, S1 and S2) were not pharmaceutically equivalent to drug R. Thus, only drugs G3 and S3 showed dissolution profiles similar to that of drug R and the other four drugs could not be considered equivalent to it and were not approved.

No Brasil, para que uma indústria farmacêutica registre um produto como genérico ou similar, o medicamento deve ser bioequivalente a seu medicamento de referência. Isto requer a realização de estudos comparativos, seguindo um compêndio oficial (Farmacopeia Brasileira ou outra reconhecida oficialmente). Além disso, de acordo com a RDC 31/2010, também deve ser realizado o estudo do perfil de dissolução em relação ao seu medicamento de referência. Este estudo teve como objetivo avaliar a qualidade de comprimidos de metamizol sódico (ou dipirona) com teor de 500mg produzidos por sete diferentes laboratórios brasileiros: três medicamentos genéricos (G1, G2, G3), três similares (S1, S2, S3) e o medicamento de referência (Novalgina®, Sanofi-Aventis, R). Todos os testes seguiram os métodos descritos na Farmacopeia Brasileira IV. Os seguintes ensaios foram realizados: uniformidade de massa, friabilidade, tempo de desintegração, dureza, doseamento, uniformidade de doses unitárias, ensaio limite de ácido salicílico e identificação. O perfil de dissolução foi realizado como recomendado pela RDC 31/2010. Apesar das amostras terem sido aprovadas em todos os ensaios farmacopéicos, os resultados do perfil de dissolução indicaram que quatro medicamentos (G1, G2, S1 e S2) não são equivalentes farmacêuticos de R. Apenas G3 e S3 mostraram perfis similares a R. Assim, quatro medicamentos foram reprovados.

Bloqueo 3 en 1 para analgesia en pacientes con fractura de cadera / Three-in-one block for analgesia in patients with hip fracture

Se realizó una intervención terapéutica en 81 adultos mayores con fractura de cadera, operados de urgencia en el Hospital Clinicoquirúrgico Docente Dr Ambrosio Grillo Portuondo de Santiago de Cuba, de enero del 2008 a igual mes del 2009, con vistas a determinar la efectividad del bloqueo 3 en 1 para aliviar el dolor en el período preoperatorio. Los pacientes fueron asignados aleatoriamente a 2 grupos de tratamiento: el de estudio (n=39), a cuyos integrantes se les aplicó el bloqueo 3 en 1 con bupivacaina a 0,5 por ciento, y el de control (n=42), al cual se le trató con metamizol por vía intramuscular (600 mg cada 8 horas). Utilizando una escala analógica visual, se midió el dolor al inicio del tratamiento, pasados 30 y 60 minutos, y cada 4 horas hasta completar 12. Se obtuvo un predominio del grupo etario de 60-79 años (51,2 por ciento) y el sexo femenino (58,0 por ciento), así como una disminución de la dolencia en el estado de reposo con el uso de ambos procedimientos terapéuticos. Igualmente, se logró alivio adecuado del dolor en los que recibieron bloqueo 3 en 1, de los cuales solo 5,1 por ciento requirió analgesia de rescate, de modo que esta técnica resultó efectiva para alcanzar el resultado deseado.

A therapeutic intervention was conducted in 81 older adults with hip fracture, who underwent emergency operation in Dr Ambrosio Grillo Portuondo Teaching Clinical Surgical Hospital of Santiago de Cuba, from January 2008 to January 2009 in order to determine the effectiveness of the 3-in-1 block for pain relief in the preoperative period. Patients were randomly assigned to two treatment groups: study group (n=39) in whom 3-in-1 block with 0.5 percent bupivacaine was administered, and control group (n=42), which was treated intramuscularly with metamizole (600 mg every 8 hours). Using a visual analogical scale pain was measured at the beginning of the treatment, after 30 and 60 minutes, and every 4 hours to complete 12. A prevalence of 60-79 (51.2 percent ) age group and female sex (58.0 percent ) was found, as well as a reduction of the disease at rest with both therapeutic procedures. Also, adequate pain relief was achieved in those that received 3-in-1 block, of them only 5.1% required rescue analgesia, so that this technique was effective to achieve the desired effect.

Comparación de ketorolaco sublingual contra metamizol endovenoso en el manejo del dolor posoperatorio en cirugía de corta estancia / Comparison of sublingual ketorolac vs. IV metamizole in the management of pain after same-day surgery

Introducción: El dolor posquirúrgico es uno de los retos más importantes en cirugía, los estudios comparativos con ketorolaco en pacientes con cirugía de corta estancia se han restringido generalmente a la administración intravenosa. Por lo tanto, comparamos la eficacia analgésica de ketorolaco sublingual y metamizol en cirugía de corta estancia. Material y métodos: Ensayo clínico controlado ciego simple; los pacientes recibieron 30 mg de ketorolaco sublingual o 1 g de metamizol endovenoso, cada ocho horas, durante las primeras 24 horas posoperatorio. Se evaluó dolor con la escala análoga visual (EVA). También fueron evaluados los efectos colaterales. Para el análisis estadístico se utilizó t de dos colas o U de Mann-Whitney y la prueba exacta de Fisher o χ2, además del cálculo de reducción de riesgo absoluto, razón de momios (OR), intervalo de confianza a 95 %, reducción del riesgo relativo y número necesario a tratar. Resultados: El consumo de analgésico suplementario fue mayor en el grupo de metamizol pero sin diferencia significativa (p = 0.286). Durante el estudio, la EVA promedio fue menor para ketorolaco que para metamizol, sobre todo a las ocho horas de posoperatorio, pero sin diferencia estadística (p = 0.06). La reducción del riesgo absoluto para cuadros de dolor severo fue de casi 5 % (OR = 1.78). No hubo diferencia en la presentación de efectos adversos (p = 0.642). Conclusiones: Tanto ketorolaco como metamizol demostraron un efecto comparable y pueden ser utilizados con seguridad.

BACKGROUND: Therapeutic pain is one of the most important outcome measures in surgery. Comparative studies investigating ketorolac efficiency in ambulatory surgery have generally been restricted to IV administration. We compared analgesic effectiveness of sublingual ketorolac and metamizole in short stay surgery. METHODS: This was a randomized single-blind clinical trial. All patients received either a three-dose (30 mg) of sublingual ketorolac or 1 g of IV metamizole, respectively. We evaluated pain with a visual/analog scale (VAS). Side effects were also recorded. Statistical analysis included t-test or Mann-Whitney U test and Fisher exact test or chi(2). Absolute risk reduction (ARR), odds ratio (OR), confidence interval (CI), relative risk ratio (RRR) and numbers needed to treat (NNT) were also evaluated. RESULTS: Rescue doses of analgesics were greater in patients receiving metamizole although the difference was not significant (p = 0.286). Mean VAS score was lower in the ketorolac group at 8 h after surgery, with no statistical difference (p = 0.06). ARR for severe pain score was almost 5% (OR = 1.78). Adverse effects did not show differences between groups (p = 0.642). CONCLUSIONS: Ketorolac and metamizole have comparable effects and can be safely used in ambulatory settings.

Lysine clonixinate versus dipyrone (metamizole) for the acute treatment of severe migraine attacks: a single-blind, randomized study / Clonixinato de lisina versus dipirona (metamizol) para o tratamento agudo de uma crise intensa de enxaqueca: estudo monocego e randomizado

BACKGROUND AND OBJECTIVE: Nonsteroidal anti-inflammatory drugs (NSAID) are effective to treat migraine attacks. Lysine clonixinate (LC) and dipyrone (metamizol) have been proven effective to treat acute migraine. The aim of this study was to evaluate the efficacy and tolerability of the intravenous formulations of LC and dipyrone in the treatment of severe migraine attacks. METHOD: Thirty patients (28 women, 2 men), aged 18 to 48 years with migraine according the International Headache Society (IHS) (2004) were studied. The patients were randomized into 2 groups when presenting to an emergency department with a severe migraine attack. The study was single-blind. Headache intensity, nausea, photophobia and side effects were evaluated at 0, 30, 60 and 90 minutes after the drug administration. Rectal indomethacin as rescue medication (RM) was available after 2 hours and its use compared between groups. RESULTS: All patients completed the study. At 30 minutes, 0 percent of the dipyrone group 13 percent of the LC group were pain free (p=0.46). At 60 and 90 minutes, 2 (13 percent) and 5 (33 percent) patients from the dipyrone group and 11 (73 percent) and 13 (86.7 percent) patients from the LC group were pain free (p<0.001). At 60 minutes, significantly more patients from the LC group were nausea-free (p<0.001). Regarding photophobia, there were no differences between groups at 60 minutes (p=0.11). The use of RM at 2 hours did not differ among groups (p=0.50). Pain in the site of the injection was reported by more patients of the LC group compared to the dipyrone group (p<0.0001). CONCLUSION: LC is significantly superior to dipyrone in treating severe migraine attacks. LC promotes significantly more burning at the site of the injection.

CONTEXTO E OBJETIVO: Antiinflamatórios não esteroidais (AINE) são eficazes no tratamento de crises de enxaqueca. O objetivo deste estudo foi comparar a eficácia e a tolerabilidade das apresentações injetáveis do clonixinato de lisina (CL) e da dipirona no tratamento de crises intensas de enxaqueca. MÉTODO: Trinta pacientes (28 mulheres, 2 homens), com idades entre 18 e 48 anos e enxaqueca de acordo com a Classificação Internacional de Cefaléias (2004) foram estudados. Os pacientes foram randomizados em 2 grupos ao se apresentarem em uma unidade de emergência, com uma crise intensa de enxaqueca. O desenho do estudo foi monocego. A intensidade da cefaléia, a presença de náusea e fotofobia e os efeitos colaterais foram avaliados e comparados na administração das drogas e após 30, 60 e 90 minutos. Indometacina retal foi disponibilizada como droga de resgate (DR) e seu uso comparado entre os grupos. RESULTADOS: Todos os pacientes completaram o estudo. Após 30 minutos, 0 por cento do grupo da dipirona e 13 por cento do CL encontravam-se sem cefaléia (p=0,46). Após 60 e 90 minutos, 2 (13 por cento) e 5 (33 por cento) do grupo da dipirona e 11 (73 por cento) e 13 (86,7 por cento) do grupo do CL encontravam-se sem cefaléia (p<0,001). Após 60 minutos, o CL foi mais eficaz que a dipirona em eliminar a náusea (p<0,001), mas não houve diferença quanto à melhora da fotofobia entre os grupos (p=0,11). Não houve diferenças entre os grupos que utilizaram DR (p=0,50). Dor no local da injeção foi apresentada por mais pacientes que usaram CL comparados aos da dipirona (p<0,001). CONCLUSÃO: O CL é significativamente superior a dipirona no tratamento de uma crise intensa de enxaqueca, mas resulta em mais queimação no local da injeção.