Manejo del estado epiléptico en niños: encuesta en hospitales pediátricos de la Ciudad Autónoma de Buenos Aires / Management of status epilepticus in childhood: a survey conducted at pediatric hospitals in the City of Buenos Aires

Introducción. El estado epiléptico constituye la emergencia neurológica más frecuente. Si bien la mortalidad en niños es baja, su morbilidad puede superar el 20 %. Objetivo. Conocer las pautas de manejo del estado epiléptico referidas por médicos pediatras que atienden esta patología en forma habitual. Población y métodos. Estudio descriptivo, transversal, basado en una encuesta a médicos de tres hospitales pediátricos monovalentes de gestión pública de la Ciudad Autónoma de Buenos Aires. Resultados. Se administraron 292 encuestas (la tasa de respuesta completa alcanzó el 86 %); el 77 % se administró a pediatras y el 16 %, a especialistas en cuidados intensivos. Un 47 % de los participantes refiere indicar la primera benzodiacepina en el tiempo correcto; el 56 % utilizar diazepam intrarrectal en ausencia de un acceso intravenoso; el 95 % elige lorazepam como benzodiacepina inicial en caso de contar con acceso intravenoso; el 58 % refiere iniciar la etapa de fármacos de segunda línea en tiempo adecuado; el 84 % opta por fenitoína como fármaco inicial de segunda línea, un 33 % no cronometra el tiempo durante el tratamiento. La adherencia global a las recomendaciones internacionales fue del 17 %. Conclusiones. Nuestro estudio advierte una baja adherencia referida de los pediatras a las guías internacionales, en particular en las decisiones tiempo-dependientes. También se observó mayor heterogeneidad en las conductas terapéuticas a medida que se avanza en el algoritmo de tratamiento.

Introduction. Status epilepticus is the most common neurological emergency. Although mortality in children is low, morbidity may exceed 20%. Objective. To evaluate the management of status epilepticus by pediatricians who usually treat this condition. Population and methods. Descriptive, cross-sectional study based on a survey administered to physicians from 3 pediatric hospitals in the City of Buenos Aires. Results. A total of 292 surveys were administered (complete response rate as high as 86%); 77% were administered to pediatricians and 16% to intensive care specialists. Forty-seven percent of the participants reported that they administer the first dose of a benzodiazepine within the correct timeframe; 56% use intrarectal diazepam when intravenous access is not available; 95% choose lorazepam as the initial benzodiazepine if an intravenous access is available; 58% initiate the administration of a second-line drug within the correct timeframe; 84% administer phenytoin as the first-choice, second-line drug; and 33% do not measure treatment time. Overall adherence to international recommendations was 17%. Conclusions. Our study highlights poor adherence of pediatricians to international guidelines, particularly in time-dependent decisions. Greater heterogeneity was observed in treatment approaches as the treatment algorithm progressed.

Eficácia do topiramato como terapia adicional em pacientes com estado epiléptico refratário: uma breve revisão sistemática / Efficacy of topiramate as an add-on therapy in patients with refractory status epilepticus: a short systematic review

RESUMO Objetivo: Identificar evidências atuais sobre topiramato para o estado de mal epiléptico refratário. Métodos: Foi revisada a literatura para investigar a eficácia do topiramato no tratamento de estado de mal epiléptico refratário. Os termos de busca utilizados foram: "status epilepticus", "refractory", "treatment" e "topiramate". Não se empregaram restrições. Resultados: A busca identificou 487 artigos que descreviam o uso de topiramato para tratamento de estado de mal epiléptico refratário e seus resultados. Relatos de caso, revisões e experimentos em animais foram excluídos. Após exclusão de duplicatas e aplicação dos critérios de inclusão e exclusão, restaram nove estudos. Realizaram-se análises descritivas e qualitativas, com os seguintes resultados: as taxas de resposta, definidas como término de crises até 72 horas após administração de topiramato, variaram entre 27% e 100%. A mortalidade variou de 5,9% a 68%. Desfechos funcionais positivos, definidos como alta hospitalar, volta à funcionalidade basal ou reabilitação, foram documentados por sete estudos, e as taxas variaram entre 4% e 55%. A maioria dos estudos reportou apenas efeitos colaterais leves ou ausentes. Conclusão: Topiramato foi efetivo em abortar estado de mal epiléptico refratário, apresentando baixa mortalidade e boa tolerabilidade. Portanto, topiramato poderia ser uma boa opção como terceira linha para estado de mal epiléptico refratário, porém mais estudos são necessários.

ABSTRACT Objective: To identify current evidence on the use of topiramate for refractory status epilepticus. Methods: We reviewed the literature to investigate the efficacy of topiramate in the treatment of refractory status epilepticus. The search terms used were "status epilepticus", "refractory", "treatment" and "topiramate". No restrictions were used. Results: The search yielded 487 articles that reported using topiramate as a treatment for refractory status epilepticus and its outcomes. Case reports, review articles, and animal experiments were excluded. After excluding duplicates and applying inclusion and exclusion criteria, nine studies were included for analyses. Descriptive and qualitative analyses were performed, and the results were as follows: response rates (defined as termination in-hospital until 72 hours after the administration of topiramate) varied from 27% to 100%. The mortality rate varied from 5.9% to 68%. Positive functional long-term outcomes, defined as discharge, back to baseline or rehabilitation, were documented by seven studies, and the rates ranged between 4% and 55%. Most studies reported no or mild adverse effects. Conclusion: Topiramate was effective in terminating refractory status epilepticus, presented relatively low mortality and was well tolerated. Therefore, topiramate could be a good option as a third-line therapy for refractory status epilepticus, but further studies are necessary.

Effect of gap junction blockers on hippocampal ripple energy expression in rats with status epilepticus / 中国当代儿科杂志

OBJECTIVES@#To study the effect of gap junction blockers, quinine (QUIN) and carbenoxolone (CBX), on hippocampal ripple energy expression in rats with status epilepticus (SE).@*METHODS@#A total of 24 rats were randomly divided into four groups: model, QUIN, valproic acid (VPA), and CBX (@*RESULTS@#Ripple expression was observed in the hippocampal CA1, CA3, and dentate gyrus regions of normal rats. After 10 minutes of PILO injection, all groups had a gradual increase in mean ripple energy expression compared with 1 day before modeling, with the highest expression level before chloral hydrate injection in the model, VPA and CBX groups (@*CONCLUSIONS@#The change in ripple energy can be used as a quantitative indicator for early warning of seizures, while it cannot predict seizures in the interictal period. Gap junction blockers can reduce ripple energy during seizures.

Efficacy and safety of levetiracetam versus phenytoin as second-line drugs for the treatment of children with convulsive status epilepticus: a Meta analysis / 中国当代儿科杂志

OBJECTIVE@#To systematically evaluate the efficacy and safety of levetiracetam (LEV) versus phenytoin (PHT) as second-line drugs for the treatment of convulsive status epilepticus (CSE) in children.@*METHODS@#English and Chinese electronic databases were searched for the randomized controlled trials comparing the efficacy and safety of LEV and PHT as second-line drugs for the treatment of childhood CSE. RevMan 5.3 software was used for data analysis.@*RESULTS@#Seven studies with 1 434 children were included. The Meta analysis showed that compared with the PHT group, the LEV group achieved a significantly higher control rate of CSE (@*CONCLUSIONS@#LEV has a better clinical effect than PHT in the treatment of children with CSE and does not increase the incidence rate of adverse events.

Uso de tarjetas de medicación en el manejo de estado epiléptico en un servicio de emergencias. Mejoras en prescripción, preparación y administración de drogas / Use of medication cards in the management of statu epilepticus at an emergency department. Improvements in drug prescription, preparation and administration

Introducción: Los errores de medicación (EM) causan una elevada morbimortalidad y generan costos innecesarios. El servicio de emergencias (SE) presenta un mayor riesgo de EM que otras áreas. El desarrollo de una herramienta que estandarice el uso de fármacos podría mejorar la seguridad y el proceso de medicación. Objetivos: Evaluar las mejoras en el proceso de medicación mediante el uso de tablas de medicación (TM) durante la atención del estado epiléptico (EE). Materiales y métodos: Se realizó un estudio de tipo antes y después no controlado. La intervención fue el desarrollo e implementación de TM. Se relevó in situ la prescripción, preparación y administración de fármacos incluidos en las TM durante segunda quincena de Octubre y mes de Noviembre 2016, previo a la implementación de la herramienta, y en el mismo período de 2017, luego de la inducción e implementación de las tablas. Se registraron los EM y se categorizaron de acuerdo a la etapa del proceso en que ocurrieron. Resultados: En el período pre-intervención se realizaron 14 registros, 86% (12) tenía al menos un error; 57% (8) errores en la etapa de prescripción, 57% (8) en la de preparación y 21% (3) en la de administración. En el período post-intervención se realizaron 17 registros, 12% (2) tenía por lo menos un EM. No se registraron errores en la fase de prescripción, hubo 12% (2) de errores de preparación y 6% (1) de administración. Conclusión: La implementación de las TM para la estandarización del uso de fármacos en EE resultó una medida muy positiva, mejorando la seguridad en el proceso de medicación (AU)

Introduction: Medication errors (ME) are associated with high morbidity mortality and lead to unnecessary costs. The risk of ME is higher at the emergency department (ED) than in other areas. Developing a tool that standardizes drug use may improve safety and medication processes. Objectives: To evaluate improvements in the medication process by using medication cards (MCs) during status epilepticus (SE) care. Materials and methods: An uncontrolled before-and-after study was conducted. The intervention was the development and implementation of MCs. The in situ prescription, preparation, and administration of drugs included in the MCs was recorded during the second half of October and November 2016, prior to the implementation of the tool, and in the same period of 2017, after the introduction and implementation of the MCs. ME were recorded and categorized according to the stage of the process in which they occurred. Results: In the pre-intervention period 14 episodes were recorded; in 86% (12) at least one error occurred; 57% (8) were ME in the prescription stage, 57% (8) were ME in the preparation stage, and 21% (3) were ME in the administration stage. In the post-intervention period 17 errors were recorded, in 12% (2) at least one ME occurred. No errors were recorded in the prescription stage, 12% (2) were preparation errors, and 6% (1) administration errors. Conclusion: The implementation of MCs for the standardization of medications used in the RU was successful, improving safety in the medication process (AU)

Estado epiléptico refractario en UCIP. Experiencia en un hospital de la Provincia de Buenos Aires / Refractory status epilepticus in the PICU. Experience at a hospital in the Province of Buenos Aires

Introducción: El estado epiléptico (EE) es la emergencia neurológica más frecuente en pediatría. Los pacientes que no responden al tratamiento estándar con dosis adecuadas de benzodiacepinas seguido de una droga antiepiléptica aceptable son definidos como Estado epiléptico Refractario (ER). Objetivo: caracterizar la población de niños con EE que ingresan a UCIP y determinar qué factores son predictores de refractariedad en esta población. Métodos: Estudio de casos y controles, retrospectivo. Población: niños con EE internados en UCIP desde Febrero 2015 a Febrero 2017. Casos: Estado epiléptico Refractario (ER). Controles: Estado epiléptico No Refractario (ENR). Se calculó el Odds Ratio (OR) individual para las distintas variables en Med Calc. Resultados: Se internaron 35 pacientes de los cuales 12 fueron casos y 23 controles. Hubo fiebre en 77% de los pacientes. En el total de niños estudiados hubo 11% con antecedente de convulsión febril, 11% con antecedente de epilepsia y 9% con antecedente de malformación del SNC. Los niños con antecedente de convulsión febril tuvieron 2,5 veces mayor riesgo de ER (OR: 2,58; IC 95%: 1,17-5,68). Los niños con EE que tenían antecedentes de enfermedad neurológica previa presentaron riesgo de ER 2,6 veces mayor que el grupo control (OR 2,60; IC 95%: 1,24-5,42). Discusión: Dado el aumento en la mortalidad de los pacientes con ER sería importante disponer de más herramientas para predecir este desenlace e iniciar tratamiento oportuno. Resultaría útil entrenar a los padres de niños con antecedente de convulsión febril en la aplicación de medicación antiepiléptica prehospitalaria, esto podría prevenir la farmacorresistencia, el daño neurológico y las complicaciones que acarrea el ingreso a UCIP. (AU)

Introduction: Status epilepticus (SE) is the most common neurologic emergency in children. Patients that do not respond to standard treatment with adequate doses of benzodiazepines followed by an acceptable antiepileptic drug are defined as having refractory status epilepticus (RSE). Objective: To characterize the population of children with SE admitted to the PICU and to determine predictive factors for refractoriness in this population. Methods: A retrospective case-control study was conducted. Population: Children with SE admitted to the PICU between February 2015 and February 2017. Cases: Refractory status pilepticus (RSE). Controls: Non-refractory status epilepticus (NRSE). Individual Odds Ratio (OR) was calculated for different variables using Med Calc. Results: 35 patients were admitted of whom 12 were cases and 23 controls. Overall, 77% of the patients had fever. Of all the children, 11% had a history of febrile seizures, 11% had history of epilepsy and 9% had a CNS malformation. Children with a history of febrile seizures had a 2.5-fold higher risk of developing RSE (OR: 2.58; 95% CI: 1.17-5.68). Children with SE that had a history of neurologic disease had a 2.6-fold higher risk of developing RSE than controls (OR 2.60; 95% CI: 1.24-5.42). Discussion: Given the increased mortality in children with RSE, availability of tools to predict this outcome in order to initiate early treatment is important. It would be useful to train the parents of children with a history of febrile seizures in the prehospital administration of antiepileptic drugs as this may prevent pharmaco-resistance, neurologic damage, and complication related to PICU admission (AU)

Nuevos fármacos antiepilépticos / New antiepileptic drugs

Los fármacos antiepilépticos constituyen el tratamiento inicial en pacientes con epilepsia. Los antIepilépticos producidos después del año 2000 se conocen como fármacos de tercera generación. Estas drogas ofrecen nuevos mecanismos de acción y una farmacocinética más favorable, minimizando efectos adversos o interacciones medicamentosas. Las drogas de amplio espectro como brivaracetam y clobazam son una buena opción en casos de crisis generalizadas y poseen un grado de tolerabilidad muy aceptable. Los nuevos antiepilépticos bloqueadores de canales de sodio, como lacosamida y eslicarbazepina tienen un perfil de efectos adversos más favorable que los bloqueadores de sodio de primera o segunda generación. Estos nuevos medicamentos pueden utilizarse en pacientes con epilepsia de difícil control. Cannabidiol y fenfluramina son muy útiles en el tratamiento del síndrome de Dravet o Lennox Gastaut. La Alopregnenolona y ganaxolona demuestran buena eficacia en casos de estado epiléptico y podrían en el futuro cercano tener un papel importante en este escenario clínico.

Antiepileptic drugs are the first treatment option in patients with epilepsy. Drugs developed after 2000 are known as third generation antiepileptic drugs. These medications offer new mechanisms of action and favorable pharmacokinetics, decreasing the occurrence of side effects and drug-drug interactions. Broad spectrum antiepileptic drugs, such as brivaracetam and clobazam are good choices for generalized tonic colonic seizures and are well tolerated.New sodium channel blockers such as lacosamide and eslicarbazepine, have a more "benign" side effect profile than the first or second generation of sodium channel blockers. These new drugs are useful therapies in patients with epilepsy of difficult control. Cannabidiol and fenfluramine are useful in the treatment of Dravet or Lennox Gastaut syndrome. Allopregnenolona and ganaxolone showed good efficacy in status epilepticus and could play an important future role in this clinical scenario.

Estado de mal epiléptico / Status epilepticus

El estado de mal epiléptico (EME) es la emergencia más frecuente en la neuropediatría. Es el resultado de un fallo en los mecanismos responsables de terminar la convulsión o de la iniciación de mecanismos que provocan una convulsión anormalmente prolongada. Esta definición se relaciona con el momento de iniciar el tratamiento. En general, el primer punto de tiempo o t1, es el momento cuando el tratamiento debería comenzarse, que es a los 5 minutos para las convulsiones tónico-clónicas generalizadas y a los 10 minutos para las focales con o sin compromiso de la conciencia. El segundo punto de tiempo o t2 marca el momento en el cual el daño neuronal o de las redes neuronales puede comenzar e indica que el EME debería ser controlado, que para los casos de mal tónico-clónico generalizados debe ser de 30 minutos. Todos los protocolos de tratamiento diferencian estadios en donde se utilizan diferentes fármacos: temprano o 1, establecido o 2, refractario o 3, súper-refractario o 4; y enfatizan el rápido reconocimiento y tratamiento de la actividad epiléptica persistente en cada estadio con el objetivo de reducir la morbimortalidad y las secuelas a largo plazo (después de t2).

Status epilepticus (SE) is one of the most common neurologic emergencies in pediatrics. It is a condition resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms, which leads to abnormally, prolonged seizures. This definition provides a good guidance, when emergency treatment must be considered. In general, time point t1 is the time when treatment should be started, which is at 5 minutes for generalized tonic-clonic seizures, and at 10 min for focal seizures with or without impairment of consciousness. Time-point t2 marks the time at which neuronal damage or self-perpetuating alteration of neuronal networks may begin and indicates that SE should be controlled latest by that time; 30 min in case of generalized tonic-clonic seizures. All treatment protocols recognize a staged approach to treatment with different drugs used in early (stage I), established (stage II), refractory (stage III) and super-refractory SE (stage IV); and emphasize prompt recognition and treatment of persisting seizure activity at each stage aiming to reduce morbidity, mortality, and long-term consequences of status epilepticus (beyond t2).

Síndrome por Infusión de propofol en un caso de estatus epiléptico refractario / Propofol infusion syndrome in a refractory epileptic status case

INTRODUCCIÓN: El síndrome por infusión de propofol (SIP) es una reacción adversa poco frecuente, pero potencialmente letal descrita por la utilización de dicho fármaco en infusión intravenosa (IV) continua. El diagnóstico se basa en la combinación de acidosis metabólica, rabdomiolisis, hiperkalemia, hepatomegalia, insuficiencia renal, hiperlipidemia, arritmias e insuficiencia cardiaca rápida mente progresiva. OBJETIVO: Presentación de un caso clínico de SIP y revisión de literatura. CASO CLÍNICO: Paciente femenino de 6 años de edad con antecedentes de epilepsia secundaria a extensa alteración del desarrollo cortical hemisférico derecho. Presentó estatus epiléptico refractario que requirió ingreso a Unidad de Cuidados Intensivos para soporte vital y tratamiento, el que incluyó como terapia de tercera línea infusión intravenosa continua de propofol en dosis progresivas hasta alcanzar una tasa 10 mg/kg/h. Cursó con compromiso hemodinámico y a las 24 h de iniciado el tratamiento se observó alza de la creatinifosfokinasa (CK), acidosis metabólica y lactacidemia elevada, y luego de descartar otras causas se planteó el diagnóstico de SIP por lo que se suspendió la droga, logrando estabilización hemodinámica a las 24 h. DISCUSIÓN: El diagnóstico de SIP es complejo, se debe considerar en pacientes que estén recibiendo el fármaco y presenten acidosis metabólica o insuficiencia cardiaca. Los factores que más influyen en la mortalidad son la dosis acumulativa de la droga, la presencia de fiebre y lesión encéfalo craneana. En el caso descrito la paciente recibió una dosis mayor a 4 mg/ kg/h que es la dosis máxima recomendada y respondió favorablemente luego de 12 h después de la suspensión del fármaco.

INTRODUCTION: Propofol Infusion Syndrome (PRIS) is a rare but potentially lethal adverse reaction secondary to the continuous intravenous infusion of this drug. The diagnosis is based on the com bination of metabolic acidosis, rhabdomyolysis, hyperkalemia, hepatomegaly, renal failure, hyperli pidemia, arrhythmias, and rapidly progressive heart failure. OBJECTIVE: To report a case of PRIS and literature review. CLINICAL CASE: A 6-year-old female patient with history of epilepsy secondary to large malformation of cortical development of the right hemisphere. The patient presented a refractory status epilepticus that required admission to the Intensive Care Unit for life support and treatment, which included continuous intravenous infusion of propofol at 10 mg/kg/h. She developed hemo dynamic instability, and after 24 h of treatment an increase of creatine phosphokinase (CPK) levels, metabolic acidosis and elevated lactacidemia were observed. After ruling out other causes, PRIS was diagnosed; therefore, the drug was suspended, achieving hemodynamic stabilization after 24 hours. DISCUSSION: The diagnosis of PRIS is complex and should be considered in patients who are receiving this drug and present metabolic acidosis or heart failure. The factors that most influence mortality are the cumulative dose of the drug, the presence of fever, and cranial brain injury. In the case described, the patient received a dose higher than 4 mg/kg/h, which is the maximum recommended dose, and responded favorably 12 hours after stopping the drug.

Pacientes con crisis convulsivas en una unidad de cuidados intensivos pediátrico en un hospital de referencia de la ciudad de Cartagena, Colombia / Patients with seizures in a pediatric intensive care unit in a referral hospital in the city of Cartagena, Colombia

Introducción. Las crisis convulsivas son la urgencia neurológica más frecuente en pediatría, llegando a ser una urgencia vital, sobre todo cuando se presentan status convulsivos que ameritan vigilancia en unidad de cuidados intensivos pediátricos (UCIP). Materiales y métodos. La población de estudio fue un total de 60 pacientes menores de 18 años hospitalizados en UCIP en un hospital ubicado en Cartagena-Colombia. La data resultante se le calculó estadísticos univariados de tendencia central y proporciones, como tablas de frecuencia univariada y bivariadas. Resultados. Se obtuvo una población de 60 pacientes en edad pediátrica, con edad promedio de 3.85 años, teniendo antecedente de epilepsia el 64.81% y el 23,33% parálisis cerebral, la comorbilidad con mayor frecuencia fue la infección meníngea con un 25.71%. Los pacientes con antecedentes de epilepsia el medicamento más utilizado ambulatoriamente fue el ácido valproico con 48.33%, seguidamente de levetiracetam 26.67% y carbamazepina 13.33%. Dentro de la población estudiada el 83.33% presento status convulsivos, siendo la crisis tónico clónica generalizada el tipo de crisis más frecuentemente descrita con un porcentaje del 88%, los medicamentos anticonvulsivantes más utilizados para yugular crisis, se encontró el midazolam con un 98.33%. El 95% salió vivo de la institución y un 5% falleció. Conclusiones. Las principales causas de status epiléptico se encuentran la lesión cerebral aguda, convulsiones febriles atípicas, epilepsia y enfermedades degenerativas, lo que concuerda con lo descrito en la literatura, los medicamentos anticonvulsivantes más utilizados en UCIP son el midazolam en primera estancia y el ácido valproico en segunda estancia.

Introduction. Seizures are the most frequent neurological urgency in pediatrics, becoming a vital urgency, especially when there are convulsive states that merit surveillance in a pediatric intensive care unit (PICU). Materials and methods. The study population was a total of 60 patients under the age of 18 hospitalized in PICU in a hospital located in Cartagena-Colombia. The resulting data were calculated univariate statistics of central tendency and proportions, such as univariate and bivariate frequency tables. Results. A population of 60 pediatric patients with a mean age of 3.85 years was obtained, having a history of epilepsy in 64.81% and 23.33% in cerebral palsy. The most common comorbidity was meningeal infection with 25.71%. Patients with a history of epilepsy, the most widely used outpatient medication was valproic acid with 48.33%, followed by levetiracetam 26.67% and carbamazepine 13.33%. Within the study population, 83.33% presented convulsive status, with the generalized clonic tonic crisis being the most frequently described type of crisis with a percentage of 88%, the most used anticonvulsant drugs for jugular crisis, midazolam was found with 98.33%. 95% left the institution alive and 5% died. Conclusions. The main causes of epileptic status are acute brain injury, atypical febrile seizures, epilepsy and degenerative diseases, which is consistent with what has been described in the literature, the most used anticonvulsant medications in PICU are midazolam in the first stay and valproic acid In second stay.

Management protocols for status epilepticus in the pediatric emergency room: systematic review article / Protocolos de manejo de estado de mal epiléptico no pronto socorro pediátrico: análise sistemática

Abstract Objective: This systematic review of national or regional guidelines published in English aimed to better understand variance in pre-hospital and emergency department treatment of status epilepticus. Sources: Systematic search of national or regional guidelines (January 2000 to February 2017) contained within PubMed and Google Scholar databases, and article reference lists. The search keywords were status epilepticus, prolonged seizure, treatment, and guideline. Summary of findings: 356 articles were retrieved and 13 were selected according to the inclusion criteria. In all six pre-hospital guidelines, the preferred route of medication administration was to use alternatives to the intravenous route: all recommended buccal and intranasal midazolam; three also recommended intramuscular midazolam, and five recommended using rectal diazepam. All 11 emergency department guidelines described three phases in therapy. Intravenous medication, by phase, was indicated as such: initial phase - ten/11 guidelines recommended lorazepam, and eight/11 recommended diazepam; second phase - most (ten/11) guidelines recommended phenytoin, but other options were phenobarbital (nine/11), valproic acid (six/11), and either fosphenytoin or levetiracetam (each four/11); third phase - four/11 guidelines included the choice of repeating second phase therapy, whereas the other guidelines recommended using a variety of intravenous anesthetic agents (thiopental, midazolam, propofol, and pentobarbital). Conclusions: All of the guidelines share a similar framework for management of status epilepticus. The choice in route of administration and drug type varied across guidelines. Hence, the adoption of a particular guideline should take account of local practice options in health service delivery.

Resumo Objetivo: Esta análise sistemática de diretrizes nacionais ou regionais publicadas em inglês tem como objetivo entender melhor a diferença no tratamento do estado de mal epiléptico pré-hospitalar e no departamento de emergência. Fontes: Pesquisa sistemática de diretrizes nacionais ou regionais (janeiro de 2000 a fevereiro de 2017) contidas nas bases de dados do Pubmed e do Google Acadêmico e listas de referência de artigos. As palavras-chave da busca foram estado de mal epiléptico, convulsão prolongada, tratamento e diretriz. Resumo dos achados: Foram identificados 356 artigos e 13 foram selecionados de acordo com os critérios de inclusão. Em todas as seis diretrizes pré-hospitalares, o caminho preferencial de administração da medicação foi usar opções à via intravenosa: todas recomendaram midazolam bucal e intranasal; três também recomendaram midazolam intramuscular; e cinco recomendaram usar o diazepam via retal. Todas as 11 diretrizes de departamento de emergência descreveram três fases na terapia. No que diz respeito à medicação intravenosa, por fase, temos: fase inicial - 10/11 diretrizes recomendaram lorazepam e 8/11 recomendaram diazepam; segunda fase - a maioria (10/11) das diretrizes recomendou fenitoína, porém outras opções foram fenobarbital (9/11), ácido valproico (6/11) e fosfenitoína ou levetiracetam (individualmente, 4/11); terceira fase - 4/11 diretrizes incluíram a opção de repetir a terapia da segunda fase, ao passo que as outras diretrizes recomendaram usar diversos agentes anestésicos intravenosos (tiopental, midazolam, propofol e pentobarbital). Conclusões: Todas as diretrizes compartilham uma estrutura semelhante para manejo do estado de mal epiléptico. A escolha da via de administração e do tipo de medicamento variou em todas as diretrizes. Assim, a adoção de uma diretriz específica deve levar em consideração as opções da prática local na prestação de serviços de saúde.

Revisión del estado epiléptico convulsivo pediátrico y su manejo antiepiléptico / Management of pediatric status epilepticus

Pediatric Status Epilepticus (SE) is an emergency situation with high morbidity and mortality that requires early and aggressive management. The minimum time criterion to define SE was reduced from 30 to 5 minutes, defined as continuous seizure activity or rapidly recurrent seizures without resumption of consciousness for more than 5 minutes. This definition considers that seizures that persist for > 5 minutes are likely to do so for more than 30 min. Those that persist for more than 30 minutes are more difficult to treat. Refractory SE is the condition that extends beyond 60-120 minutes and requires anesthetic management. Super-refractory SE is the state of no response to anesthetic management or relapse during withdrawal of these drugs. The aim of this review is to provide and update on convulsive SE concepts, pathophysiology, etiology, available antiepileptic treatment and propose a rational management scheme. A literature search of articles published between January 1993 and January 2013, focused on pediatric population was performed. The evidence about management in children is limited, mostly corresponds to case series of patients grouped by diagnosis, mainly adults. These publications show treatment alternatives such as immunotherapy, ketogenic diet, surgery and hypothermia. A 35% mortality, 26% of neurological sequelae and 35% of recovery to baseline condition is described on patient’s evolution.

Uso de ketamina en el estatus epiléptico superrefractario en pediatría: reporte de un caso / Ketamine use in the super refractory status epilepticus in pediatrics: a case report

INTRODUCCIÓN: El estatus epiléptico superrefractario se define como convulsiones de 24 horas o más posterior al uso de anestésicos generales. Se presenta el siguiente caso con el fin de discutir el uso de anticonvulsivantes y la importancia del manejo multidisciplinario. PRESENTACIÓN DEL CASO: Escolar masculino de 8 años con antecedentes mórbidos de epilepsiades de los 2 meses en tratamiento con ácido valproico, lamotrigina y clobazam por recurrencia de crisis hipotónicas. Se hospitaliza por crisis atónicas frecuentes y compromiso de conciencia, se inicia levetiracetam y se retira lamotrigina. Electroencefalograma (EEG) muestra actividad epileptiforme muy frecuente sin variación ingresándose a unidad cuidados intensivos para administración de metilprednisolona por 5 días y manejo del estatus epiléptico superrefractario con midazolam en infusión continúa. Nuevo EEG severamente patológico compatible con status epiléptico eléctrico generalizado por lo que se induce coma barbitúrico con diferentes esquemas de tiopental y ketamina con persistencia del patrón de estallido supresión. Tras lo cual se modifica esquema a propofol y topiramato manteniendo antiepilépticos de base. A los 2 días de uso, se suspende propofol por mala respuesta, tras lo cual presenta 2 crisis convulsivas iniciándose fenobarbital. Evoluciona deforma favorable, sin crisis epilépticas clínicas, por lo que se decide alta con ácido valproico, levetiracetam, fenobarbital y topiramato. DISCUSIÓN: La tórpida evolución del caso expuesto y la necesidad de múltiples esquemas farmacológicos dejan en evidencia la necesidad de disponer y conocer el modo de uso de un amplio arsenal de fármacos anticonvulsivantes

INTRODUCTION: Super-refractory status epilepticus is defined as a 24 hours or more lasting seizure after the use of anaesthetics. The following case is shown in order to discuss the use of anticonvulsants and the importance of multidisciplinary management. CASE REPORT: 8 year old male with morbid history of epilepsy since 2 months old treated with valproic acid, lamotrigine and clobazam for recurrent hypotonic crisis. Is hospitalized for frequent atonicseizures and impaired consciousness, levetiracetam is initiated and lamotrigine removed. Electroencephalogram (EEG) shows persistent very frequent epileptiform activity. Patient is admitted to the intensive care unit for administration of methylprednisolone for 5 days and management with continuous infusion of midazolam for the super-refractory status epilepticus. New severely abnormal EEG compatible with generalized electrical status epilepticus deciding to induce a barbiturate coma with different schemes of ketamine and thiopental. Because of persistent suppression burst patter whereupon scheme is changed to propofol and topiramte maintaining chronic antiepileptic. After 2 days of use, propofol is suspended for poor response, after which the patient presents 2 seizures beginning the use of phenobarbital. He evolved favourably, without clinical seizures, so it is decided hospital discharge with valproic acid, levetiracetam, phenobarbital and topiramate. DISCUSSION: The torpid case exposed and the lack for multiple drug regimens are evidence of the need of having a wide arsenal of anticonvulsant drugs and how to use them

Evaluation of the efficacy of sodium valproate in convulsive status epilepticus following to ıschemic stroke / Avaliação da eficácia do valproato de sódio no status epilepticus convulsivo devido ao acidente vascular cerebral isquêmico

Objective : Convulsive status epilepticus (CSE) is very rarely observed after ischaemic stroke. Sodium valproate (SV) is one of the agents used in the treatment of CSE, but its role still controversial, and its degree of efficacy in treating CSE that develops following stroke is unclear. Method : We evaluated 19 patients who were treated with intravenous (IV) SV (20 mg/kg, 2 mg/kg/h-12h) after diazepam. Patients’ modified Rankin scores (mRS), SE types, and changes in biochemical parameters after treatment were assessed. Results : CSE was successfully treated in 12 (63.15%) patients. Side effects such as hypotension and allergic reactions were observed in two patients. Refractory SE development was observed in 5 (29.4%) patients with high mRS (˃ 3). No significant deterioration in patients’ laboratory evaluations, conducted before and after status, was observed. Conclusion : SV may be safe and effective in the treatment of CSE observed after ischaemic stroke, especially in patients with low mRS. .

Objetivo : Status epilepticus convulsivo (SEC) é muito raramente observado após acidente vascular cerebral isquêmico. Valproato de sódio (VS) é um dos agentes utilizados no tratamento do SEC, mas seu papel ainda é controverso e seu grau de eficácia não é claro no SEC pós acidente vascular. Método Avaliamos 19 pacientes que foram tratados com AV endovenoso (EV) (20 mg/kg, 2 mg/kg/h-12h) após diazepam. Valores da escala modificada de Rankin (mRS) dos pacientes, tipos de SE e mudanças nos parâmetros bioquímicos foram avaliados. Resultados SEC foi tratado com sucesso em 12 pacientes (63,15%). Efeitos colaterais como hipotensão e reações alérgicas foram observados em dois pacientes. Desenvolvimento de SE refratário foi observado em cinco pacientes (29,4%) com altos valores de mRS (˃ 3). Não houve deterioração significativa nas avaliações laboratoriais dos pacientes feitas antes ou depois do status. Conclusão AV pode ser eficaz no tratamento do SEC observado após acidente vascular cerebral isquêmico, especialmente nos pacientes com baixo mRS. .

Indomethacin can downregulate the levels of inflammatory mediators in the hippocampus of rats submitted to pilocarpine-induced status epilepticus

OBJECTIVE: Refractory status epilepticus is one of the most life-threatening neurological emergencies and is characterized by high morbidity and mortality. Additionally, the use of anti-inflammatory drugs during this period is very controversial. Thus, this study has been designed to analyze the effect of a low dose of indomethacin (a COX inhibitor) on the expression of inflammatory molecules. METHOD: The hippocampus of rats submitted to pilocarpine-induced long-lasting status epilepticus was analyzed to determine the expression of inflammatory molecules with RT-PCR and immunohistochemistry. RESULTS: Compared with controls, reduced levels of the kinin B2 receptors IL1β and TNFα were found in the hippocampus of rats submitted to long-lasting status epilepticus and treated with indomethacin. CONCLUSIONS: These data show that low doses of indomethacin could be employed to minimize inflammation during long-lasting status epilepticus. .

Higher mortality rate is associated with advanced age and periodic lateralized epileptiform discharges in patients with refractory status epilepticus / Alta taxa de mortalidade está associada com idade avançada e descargas periódicas lateralizadas em pacientes com estado de mal epiléptico refratário

To evaluate clinical data, electroencephalogram, etiology, classification, treatment, morbidity, and mortality in acute refractory status epilepticus. Fifteen patients, mean age of 41.3 years-old, six males, with refractory status epilepticus, were retrospectively studied. All of them were followed by serial electroencephalogram or continuous electroencephalographic monitoring. The most common comorbidity was hypertension. Seven (46.7%) patients were diagnosed with previous symptomatic focal epilepsy. More than one etiology was identified in 40.0% of the cases. Status epilepticus partial complex was the most common (n=14, 93.3%), and discrete seizures were the most observed initial ictal pattern. Continuous intravenous midazolam was used in nine (60.0%) patients and continuous thiopental in three (20.0%). Nine (60.0%) participants died, one (6.6%) had neurological sequelae, and five (33.3%) presented no neurological sequelae. Higher mortality rate was associated with advanced age and periodic lateralized epileptiform discharges. Midazolam proved to be a safe drug. The refractory status epilepticus is related to high mortality. .

Avaliar os dados clínicos, o eletroencefalograma, a etiologia, a classificação, o tratamento, a morbidade e a mortalidade do estado de mal epiléptico. Quinze pacientes, idade média de 41,3 anos, seis masculinos, foram avaliados retrospectivamente. Todos eles foram acompanhados por eletroencefalogramas seriados ou monitoração eletrencefalográfica contínua. A comorbidade mais comum foi hipertensão arterial. Sete (46,7%) pacientes tinham epilepsia focal sintomática prévia. Mais de uma etiologia foi identificada em 40,0% dos casos. O estado de mal epiléptico parcial complexo foi o mais frequente (n=14; 93,3%) e discrete seizures foram os padrões ictal inicial mais observados. Midazolam contínuo foi usado em nove (60,0%) pacientes e tiopental contínuo em três (20,0%). Nove (60,0%) participantes morreram, um (6,6%) teve sequelas neurológicas e cinco (33,3%) não apresentaram sequelas. Alta taxa de mortalidade foi associada com idade avançada e com a presença de descargas periódicas epileptiformes lateralizadas. Midazolam provou ser uma droga segura. Estado de mal epiléptico refratário está associado à alta mortalidade. .

Tratamiento del estado epiléptico refractario con topiramato oral / Treatment of refractory status epilepticus with topiramate: report of three cases

Refractory status epilepticus is a catastrophic illness of the central nervous system, with a mortality rate that reaches 50 percent. We report three patients admitted with refractory status epilepticus: a 24 year-old male that discontinued antiepileptic medications, a 46 year-old male with a focal epilepsy secondary to an encephalitis that discontinued medications due to gastrointestinal problems and a 59 year-old male with an ischemic encephalopathy AH were treated with topiramate, delivered through a nasogastric tube with a good response.

Isoniazid Toxicity Presenting As Status Epilepticus and Severe Metabolic Acidosis.

Isoniazid (INH) is an integral component of treatment of tuberculosis. An acute overdose is potentially fatal and is characterized by the clinical triad of repetitive seizures unresponsive to the usual anticonvulsants, metabolic acidosis with a high anion gap and coma. The diagnosis of INH overdose should be considered in any patient who presents to emergency medical services (EMS) with the triad. We report a patient presenting with multiple generalised tonic clonic (GTC) convulsions with severe metabolic acidosis as a manifestation of INH toxicity. ©